1,107 Matching Annotations
  1. Nov 2019
    1. Thus, although introduced birds are critical for seed dispersal in the ecosystem, they are primarily dispersing introduced plants (only 6.7% of interactions involved native plants).

      The authors concluded that the majority of plants and animals involved in the seed dispersion networks of O'ahu are introduced species, and that the majority of seeds being dispersed by these birds are from introduced plant species.

    1. we have observed these effects against unmanipulated, wild-type tumors

      Anti-CTLA-4 treatment can be used for the normal tumors that a patient's immune system may get exposed to. It is not necessary to first extract tumor cells and modify them for the immune system to be able to recognize them. This makes it a very powerful treatment.

    2. CTLA-4 blockade might sustain proliferation of activated T cells by removing inhibitory signals that would normally terminate the response

      Another proposed mechanism of the effectiveness of CTLA-4 blockade is given. This mechanism could work in tandem with the previous one. Anti-CTLA-4 treatment may be allowing activated T cells to divide and grow for a longer period of time, so that there is a larger number of them circulating in the body and available to respond to the cancerous cells.

    3. removal of inhibitory signals may lower the overall threshold of T cell activation and allow normally unreactive T cells to become activated

      The authors propose that the effectiveness of CTLA-4 blockade may arise from lowering the number or concentration of antigens that T cells expect to be exposed to before they become fully activated. That is, anti-CTLA-4 may be allowing T cells to become more sensitive.

    4. rapidly growing tumors, whereas 7 of 10 mice treated with anti-CTLA-4 were tumor-free by day 25 after injection

      Similar trends were observed in this experiment. Mice left untreated grew tumors rapidly, while the majority of those treated with anti-CTLA-4 remained tumor-free.

    5. only two mice treated with anti-CTLA-4 had tumors by day 30, and one additional mouse developed a tumor around day 40

      By treating the mice with anti-CTLA-4, the authors were able to prevent tumor growth in two mice, and delay it considerably in the other three.

    6. measurable, rapidly growing tumors within 7 days

      Those mice that were not treated grew tumors in the first week of the experiment.

    1. The He isotopic signatures released from the sparse fluid inclusions vary from 0.7 to 49.9 R/Ra (Figs. 1 and 2).

      This observation indicates that the R/Ra ratio measured from the sparse fluid inclusions cover a very wide range of values. Higher values indicate that the relative abundance of helium-3 to helium-4 to that in air is very high (almost 50 times). When the values are this high, there is a good chance of detection of elevated helium-3 isotope, thereby confirming the fact that these fluid inclusions are coming from a very ancient reservoir located deep inside the Earth.

    2. This observation requires that the high-3He/4He source has higher He abundances than reservoirs with low 3He/4He ratios and thus supports the presence of a primordial 3He plume.

      Any increase in the helium-3 isotope abundance provides strong evidence of the location and age of the chemical reservoirs explored in this study. Helium-3 isotope formation dates back to the beginning of Earth and any recent formation of the isotope on Earth's surface has been ruled out due to its tendency to get lost in the space. Thus the the authors are confident that this spike in helium-3 is coming from very ancient reservoir deep inside the Earth.

    3. The He isotopic data for fluid inclusions in superdeep diamonds presented here resolve this issue by showing direct evidence that the high-3He/4He source must be present in the deep mantle, beneath a depth of 410 km.

      This is the main conclusion of this research work. The authors have shown evidence that the diamond fluid inclusions analyzed originate from the deep mantle region of the Earth, which is at least 410 km underneath Earth's surface.

    4. Our diamonds have physical features and properties that are consistent with other diamonds from Earth’s transition zone (410 to 660 km depth), including dislocations or diffuse growth zones (database S1) and no detectable nitrogen (N) or fully aggregated N defects (database S2) (24).

      There has been an ongoing debate about the exact location of the chemical reservoirs that lie deep within the planet Earth. Timmerman and colleagues have successfully narrowed down this location to Earth's transition zone, i.e., 410 to 660 km underneath Earth's surface. These conclusions are based on not only the relative abundance of helium-3 to helium-4 isotopes, but also on the physical similarities between the studied diamonds with already identified ones.

    5. The highest R/Ra value for our diamonds was from the Juina-5 kimberlite, and it coincides with the R/Ra of 49.8 from Baffin Island picrites (4), the highest observed in basalts.

      In the diamond fluid inclusions richest in helium-3, the helium-3 to helium-4 ratio is about 50 times to that of air. This considerably high isotope ratio confirms the fact that the real age of these fluid inclusions date back to the early days of Earth's formation.

    6. We removed the outer rim of the diamond to eliminate any 4He implantation [up to 30 μm from the diamond surface

      The primordial diamonds excavated by the scientists contained fluid inclusions consisting both helium-4 and helium-3 isotopes. The helium-4 isotopes are formed from radioactive decay of trace-elements and hence take a long time to form. While, the helium-3 isotopes exist inside Earth from the early days of formation and there has been no new generation of helium-3 isotope since then. Hence, removing the outer rim consisting of helium-4 isotopes from the diamonds narrows the search to helium-3 isotopes located in very ancient chemical reservoirs.

  2. Oct 2019
    1. delaying treatment appeared to be more effective

      Not only was delaying treatment effective, it was more effective than treating the mice on the same day that tumors are introduced.

    2. These results demonstrate that tumor rejection mediated by CTLA-4 blockade results in immunologic memory

      The mice described in this section rejected the tumors twice: the first time, they were being treated with anti-CTLA-4, and the second time, they were not. This means that their immune system was able to fight off the second tumor on its own, and much faster than mice which had not previously survived exposure to the tumor. These are hallmarks of immunologic memory, the same phenomenon that ensures you only get chicken pox once in your life!

    3. Only one of the previously immunized mice had a detectable tumor by day 14

      Most of the previously immunized mice did not develop tumors of detectable size; that is, their immune system was able to kill all the tumor cells almost as soon as they were introduced. Only one of the mice developed a detectable tumor, but the growth was very slow.

    4. control animals had progressively growing tumors by 14 days after injection, developed massive tumor burdens, and required euthanasia by day 35

      If mice were not previously exposed to the tumor cells along with a treatment, they did not fare very well.

    5. significant protection against a secondary challenge

      The mice which previously mounted an immune response with the help of anti-CTLA-4 were able to leverage a similar response toward this re-exposure. Remember that naive mice exposed to half this many tumor cells were not able to control the cancer's growth.

    6. Anti-CTLA-4 appeared to be less effective at a tumor dose of 1×1061×106<math xmlns="http://www.w3.org/1998/Math/MathML"><mn>1</mn><mo>×</mo><msup><mn>10</mn><mn>6</mn></msup></math> cells, where treatment resulted in significantly reduced tumor growth rates, but four of five mice developed progressively growing tumors

      The authors repeated the experiment with an even lower tumor burden of 1x10\(^6\) cells, and found that the effectiveness of treatment was reduced at this dose. They do not propose a reason for this. Perhaps you can think of one!

    7. Anti-CTLA-4 treatment had a dramatic effect on tumor growth

      The treated mice had much better outcomes than the untreated mice, which were euthanized after 35 days.

    8. completely rejected their tumors after a short period of limited growth

      The mice treated with antibodies against CTLA-4 completely recovered and were able to clear the tumors.

    9. developed progressively growing tumors and required euthanasia by 35 days after inoculation

      The mice which received these treatments could not control the growth of their tumors. They died 35 days after the tumors were injected.

    10. three of five mice treated with anti-CTLA-4 developed very small tumors, all of which regressed completely by day 17

      The third group of mice was treated with antibodies targeting CTLA-4. Those mice were able to clear the tumors faster, by day 17, if they developed tumors at all.

    11. All mice in the untreated and antiCD28-treated groups developed small tumors that grew progressively for 5 to 10 days and then ultimately regressed in 8 of the 10 mice by about day 23 after injection. The two small tumors that did not regress remained static for more than 90 days

      Two groups were injected with anti-CD28 or not treated. Most of the mice in these two groups cleared the tumors, but did so by day 23. Two of the mice did not completely clear the tumors but were able to keep them from growing further.

    12. raise the possibility that blockade of inhibitory signals delivered by CTLA-4-B7 interactions might augment T cell responses to tumor cells and enhance antitumor immunity

      The pieces of evidence outlined in this paragraph led the authors to conclude that blocking tumors from being able to engage CTLA-4 might result in T cells being better able to fight off tumors.

    13. resulted in immunity to a secondary exposure to tumor cells

      Administering antibodies against CTLA-4 also allows the mice to prevent establishment of tumors due to future exposure.

    14. resulted in the rejection of tumors, including preestablished tumors

      By preventing CTLA-4 from binding to its ligands, T cells can now be activated more potently. This allows them to kill cancer cells.

  3. Sep 2019
    1. reduced contact area that slide against the DLC surface, achieving an incommensurate contact

      With a combination of materials (graphene, nanodiamond particles, and DLC), the researchers were able to demonstrate the formation of nanoscrolls, which reduced the overall contact area between two sliding interfaces, leading to substantially decreased friction.

    2. We found that the presence of defects greatly facilitates the adsorption of water from the ambient atmosphere (fig. S13). Water preferentially adsorbs and stabilizes defective sites, which further prevents the formation of scrolls

      There are some limitations for the present observed near-zero friction sliding. A relatively poor tribological performance is found in humid test environments. The water molecules present at the interface is found to prevent the scrolling of graphene layers. Moreover, the defects present on graphene sheets act as catalytic sites further hampering the near-zero friction sliding in a humid environment.

    3. We saw a dramatic reduction in friction, reaching the superlubric state

      The authors have designed and executed experiments to calculate the coefficient of friction. The combination of nanomaterials they used were found to be successful in achieving super-low friction values in a dry environment.

    4. The superlubricity is thus attributed to (i) reduction in the interfacial contact area (>65%) and (ii) incommensurability between DLC and graphene scrolls.

      The mismatch of the lattices at the sliding interfaces prevents interlocking of atoms, resulting in near-zero friction. In the present case, a perfectly incommensurate surface along with reduced contact area benefited from the graphene scroll formation and contributed to superlubricity.

    5. nanodiamonds can activate, guide, and stabilize the scrolling

      The mechanism of superlubricity in the present system is explained. Authors found that nanodiamonds play a key role in the scroll formation and hence in facilitating the near-zero friction state.

    1. This is almost 100 times faster than that reported for optogenetic stimulation of the AgRP neuron soma and 500 times faster than stimulation of AgRP-PVT axon terminals (19, 20). As soon as the laser was turned off, the mice stopped eating.

      The authors wanted to compare the latency of eating onset upon stimulation of ZI projections to the PVT versus that of agRP neurons, which are known to promote food intake in response to hunger.

      They found that mice start to eat much faster than mice did in previous reports where AgRP neurons were stimulated or when agRP projections to the PVT were stimulated.

    2. Stimulation of PSTh glutamatergic neuron terminals in the PVT inhibited food intake (Fig. 4L).

      PVT vGlut2 neurons decrease food intake. Therefore, stimulation of excitatory neurons upstream of them, i.e. the vGlut2 PSTh neurons, was also found to increase food intake.

    3. In spite of the light aversion, photostimulation of VGATZI-PVTterminals significantly increased the time mice spent on the illuminated side to 61% when high-fat food was available (Fig. 3D). Photostimulation increased high-fat food intake in bright light (Fig. 3E).

      Mice that received stimulation of ZI GABA terminals in the PVT spent more time in the light compartment in the presence of high-fat food even though mice usually avoid places that are brightly lit.

      This means that the stimulation of the ZI to PVT projection was able to overcome the aversive nature of the light.

    4. Although mice prefer sweet and high-fat foods when stimulation is off,

      Mice will avidly consume high-fat and sweet foods even when not hungry. This is because these foods are palatable, meaning that they are pleasurable or rewarding to eat and so will be consumed even when nutrition requirements are met.

    5. Ghrelin, a hormone that signals a reduced gut energy state (12), excited ZI GABA neurons and increased excitatory synaptic input onto these neurons (Fig. 1, K to M, and fig. S2).

      Ghrelin is produced in the stomach. Its synthesis is increased by food deprivation.

      Application of ghrelin to the brain slices containing ZI GABA neurons increases their activity in a way similar to food deprivation.

    6. Food deprivation lasting 24 hours increased ZI GABA neuron activity and excitatory neurotransmission to these neurons

      Recordings made in brain slices show that ZI GABA neurons fire more, i.e. are more active in food deprived mice. Further, inputs from other neurons that excite/activate ZI GABA neurons are increased.

      Therefore, increased ZI GABA neuron activity correlates with hunger.

      See this HHMI BioInteractive video that explains how information is transmitted between neurons: Molecular mechanism of synapse function.

    7. In control mice with tdTomato expression, consumption was only 4% of their 24-hour intake during the same period (Fig. 1E).

      Lack of food intake in a control animal that was injected with an AAV expressing only a fluorescent protein shows that the result seen in ChIEF-expressing mice was not due to non-specific effects of AAV injection or protein expression in the neurons.

  4. Aug 2019
    1. In aggregate, these results indicate that intestinal tumors can transport fructose directly from the intestinal lumen, where the fructose concentration is high after oral administration of HFCS.

      Summarizing findings from the experiments up till this point: 1) fructose often reaches the colon at high concentrations when passive transporters in the upper intestines are saturated. 2) tumors in the lower intestines and colon absorb fructose efficiently, as demonstrated by decreased fructose in the liver in tumor-bearing mice 3) colorectal tumors are able to absorb more fructose than healthy intestinal cells because they have more fructose transporters

    2. Further supporting our hypothesis, we found that GLUT5 was expressed at higher levels in APC−/−tumors as compared to IECs (fig. S5A), and in human colon tumors as compared to adjacent normal IECs

      Investigating tumor uptake of fructose further, the scientists looked at sugar uptake proteins in colorectal tumors of both mice and human tissues. They found that colorectal tumor cells expressed more of the passive fructose transporter than normal intestinal cells do.

    3. Furthermore, the amount of fructose reaching the liver and serum was reduced in tumor-bearing APC−/− mice compared to WT mice (Fig. 2A), implying that fructose is trapped by the tumors instead of being transported to the liver and blood

      The scientists also looked at how much fructose and was reaching the liver and blood to test metabolism of the sugar. They found that in tumor-bearing mice there was less fructose metabolized in the liver and less reached the blood. This suggests that the tumors consumed more of the fructose.

    4. we confirmed that APC−/− tumors efficiently transported both fructose and glucose following a bolus of HFCS (fig. S4B).

      After administering high fructose corn syrup with the labeled carbons on glucose and fructose to a mouse with colorectal tumors the scientists found that the tumor took up and metabolized both glucose and fructose.

    5. These results suggest that the chronic intake of modest amounts of HFCS in liquid form facilitates tumor growth in the setting of APC deficiency independent of obesity and the metabolic syndrome.

      Summarizing their results: In APC deficient mice (where colorectal tumors readily develop) consumption of even small amounts of high fructose corn syrup increases tumor growth.

    6. Although the total number of tumors was similar (fig. S3, A and B), HFCS treatment significantly increased the number of large adenomas (>3 mm in diameter) and high-grade tumors in the HFCS group compared to the Con group (Fig. 1, C to F, and fig. S3C).

      Results from experiment Part 2: Comparing mice fed with different amounts of high fructose corn syrup did not change the number of tumors formed. However, the size of the tumors, and the aggressiveness of the cancer differed between the mice fed a small amount of high fructose corn syrup and the control group with no high fructose corn syrup. This demonstrates that even a small amount of high fructose corn syrup is increasing tumor growth.

    7. Chronic treatment of HFCS using this strategy did not induce obesity or metabolic dysfunction in APC−/− mice (Fig. 1, A and B, and fig S2).

      Result from experiment Part 1: Mice given a small amount of high fructose corn syrup did not become obese (as intended) and they did not develop metabolic syndrome. This suggests that high fructose corn syrup itself is not causing metabolic syndrome, but rather obesity is causing these health complications.

    8. The consumption of HFCS in this manner led to obesity in both WT and APC−/− mice (fig. S1), and to metabolic dysfunction in WT mice (fig. S2) over an 8-week period.

      In response to consumption of high fructose corn syrup mice in both groups gained a lot of weight and began displaying symptoms of metabolic dysfunction (high blood pressure, abnormal cholesterol etc.). It was unclear as to whether high fructose corn syrup consumption or obesity led to the development of metabolic dysfunction so the authors went on to test this next.

    9. Notably, there was almost no labeling of downstream metabolites of F1P from 13C-fructose when unlabeled glucose was added to the medium (Fig. 2D and fig. S6A), suggesting that the presence of glucose saturates aldolase and prevents fructose from being cleaved into three carbon units in this time frame. Because KHK produces F1P much faster than aldolase cleaves it, F1P accumulates (fig. S6B). This results in an acute drop in cytosolic ATP in tumors from APC−/− mice that had received HFCS as compared to Con tumors following a bolus (and Fig. 2E).


    10. As expected, F1P was predominantly 13C-labeled at all six positions (M+6) in tumors treated with 13C-fructose or 13C-fructose + unlabeled glucose (47.1 and 67.1%, respectively), as assessed by the percentage of labeling (Fig. 2C); these findings confirm the activity and presence of KHK in the tumors.
    1. veratridine did not significantly alter TH-positive cell number, suggesting that depolarization increased TH per neuron rather than increasing the number of neurons.

      What could have been the cause of the increase in TH activity? The answers could be one of the two options: An increase in the number of TH-positive neurons in the sample or an increase in the amount of TH per neuron.

      In other words, is it an individual neuron's effect or a collective effort of all neurons in the sample? To address this, the authors decided to measure the number of TH-positive cells in the control and veratridine-treated cultures.

      The results show that the there is no difference in the number of neurons between both groups. Based on that, they concluded there is an increase in the amount of TH per neuron individually but not in the total number of TH-positive neurons.

    2. depolarizing concentrations of K+ reproduced the effect of veratridine, suggesting that depolarization per se increased TH activity

      Potassium (K+) is used as a depolarizing agent in this study. The depolarization using potassium is expected to behave similarly to the effects observed with veratridine as both the chemicals increase the influx of sodium channels.

      The authors show that, in the presence of potassium, there is approximately a 35% increase in TH activity as compared to their controls.

    3. this effect was blocked by tetrodotoxin

      Tetrodotoxin is a sodium channel blocker while veratridine does the opposite, it activates these channels causing an influx of sodium. Since these two drugs act in opposition to each other, we expect them to have no net effect in the cultures. And that’s what was observed in the cultures exposed to veratridine in the presence of tetrodotoxin (see TTX+Ver in Figure 4). There is no further effect in the TH activity as compared to their controls.

    4. Veratridine exposure significantly increased TH activity over cultures of the contralateral control locus

      Veratridine binds to the sodium channel binding site thereby increasing the flow of sodium ions into the cell. The authors have shown that, when the cultures are exposed to veratridine, there is approximately a 40% increase in the activity of tyrosine hydrolase (TH) compared to their controls. Controls are cultures that are not exposed to any drugs.

    5. In culture, the (now denervated) adult ganglia exhibited a tenfold rise in substance P, mimicking the increase in neonatal ganglia

      Explants from the superior cervical ganglia were obtained to address the question: Is there transmitter plasticity in mature neurons?

      Explants were obtained from rats of age six months and one year. A ten-fold increase was observed in the activity of substance P.

    1. The geographical annual and diurnal ranges of temperature would be partly smoothed away, if the quantity of carbonic acid was augmented. The reverse would be the case (at least to a latitude of 50° from the equator), if the carbonic acid diminished in amount.

      The model predicted that atmospheric CO2 levels influence the temperature contrast between the seasons and between night and day. Lower CO2 levels increase the temperature contrast. Higher CO2 levels decrease the contrast.

    2. the temperature in the arctic regions would rise about 8° to 9° C., if the carbonic acid increased to 2.5 or 3 times its present value.

      Based on observations of the geological record, scientists estimated that the temperature in arctic regions during the warm Tertiary Period was 8 to 9 C higher than now.

      Using the data generated by his model and summarized in Table VII, Arrhenius concluded that this temperature increase could have been caused by an atmospheric CO2 increase of 2.5 to 3 times current levels.

  5. Jul 2019
    1. functional-group protection and/or manipulation

      Functional group protection and deprotection increases the number of steps and auxiliary agents during synthesis and is not considered green. The methodology described in this research obeys one of the principles of green chemistry: "Unnecessary derivatization (use of blocking groups, protection/deprotection, temporary modification of physical/chemical processes) should be minimized or avoided if possible, because such steps require additional reagents and can generate waste."

    2. free alcohols and primary amines

      Free alcohols and primary amines are very reactive functional groups that are inert during this carbene transfer reaction.

    3. Synthetic methodologies such as carbene insertion into silanes can be rendered enantioselective using chiral transition metal complexes based on rhodium (11, 12), iridium (13), and copper (14, 15).

      Certain iridium catalytic systems show 97% ee while copper catalysts show 35% ee and rhodium has been shown to exhibit 77% ee.

    4. We thus chose Rmacyt c as the platform for evolving a carbon–silicon bond-forming enzyme.

      The wildtype protein chosen must exhibit some degree of activity for the desired reaction. When compared to hemin, hemin with bovine serum, a range of protein engineered cytochrome P450 and myoglobin variants, it was found that Rmacyt c showed 97% ee. This was chosen as the enzyme that would form the basis for directed evolution.

    5. Chemoselectivity

      With each mutation, the chemoselectivity of the enzyme is greatly enhanced. V75T M100D M103E favors the carbon-silicon bond 29 times more than the wild type. This is attributed to the improved binding and orientation of the silicon donor in the enzyme's active site.

    6. the triple mutant catalyzed the formation of 20 silicon-containing products,

      A generally applicable protocol, as a result of directed evolution, over a variety of substrates illustrates the synthetic utility of the mutant.

    1. We found that specialization, modularity, nestedness, and the simulated robustness in all scenarios to species loss of the O‘ahu networks overlapped with the range of values observed in other networks.

      The results from the simulated extinction, along with the measurement of network factors (modularity, nestedness, and specialization) were all similar between Ohau and other tropical or non-tropical locations.

  6. Jun 2019
    1. Thus, plant-animal networks appear to have distinct links (high interaction rewiring) even when the same species are present in both sites, irrespective of whether networks are dominated by native or introduced species

      The authors conclude that plant and animals at different sites across the island develop their own unique pattern of interactions, even if the sites populated mostly of native or novel species.

    2. Here we show that the interaction patterns recurrently identified in native-dominated networks also emerge in novel mutualistic networks composed of species with little or no shared evolutionary history. This result indicates that prolonged shared evolutionary history is not necessary for the emergence of complex network structure

      The authors concluded that species do not necessarily have to be evolutionary related to form a mutual relationship. This conclusion was based on their results demonstrating that introduced species on the island successfully formed beneficial interactions with native and other species that shared little phylogenetic similarities.

    3. Furthermore, partner sharing (how distinct species share resources) in SDNs on Oʻahu is structured in a complementary way among bird and plant species, giving rise to distinct modules in which certain birds and plants interact preferentially. The emergence of such structures indicates that these novel SDNs largely reproduce the well-known patterns exhibited in mutualistic networks (18) and that SDN structure is highly conserved, regardless of variation in plant and bird communities.

      The reason the introduced birds and plants integrate successfully into the ecosystem of O'ahu is because they follow the same strategies that the native plants and birds developed: creating beneficial relationships with specific species, and carefully sharing the resources of the island with other organisms.

    4. This high degree of similarity between novel and native-dominated networks suggests that the processes that structure interactions in such communities are largely independent of species identity and that ecological filtering occurs over relatively short (ecological) time, leading to functionally similar sets of players as compared with systems that have long evolutionary histories

      The authors concluded that novel species' interactions, developed over a relatively short period of time, still resemble much older interactions between native species.

    5. However, the lack of association between rewiring and examined factors indicates that birds and plants in the system are highly flexible and can switch partners, irrespective of abiotic conditions and the identity of species in the community.

      The authors found that neither abiotic (rainfall and elevation) nor biotic (invasive species) factors influenced the variations in plant and animal interactions measured from different sites with similar species populations.

    6. pecifically, interaction dissimilarity and the dissimilarity caused by species turnover were influenced by elevation and rainfall, but not by percent of introduced plant species (tables S6 to S9). This suggests that the environment indirectly influences interactions via effects on species distributions, including the distribution of introduced species.

      Results in the supplement section show that abiotic factors (rainfall and elevation) affected the composition of species found at a site, thereby creating different network interactions between sites.

    7. Surprisingly, only 53% of the interaction dissimilarity was due to differences in species composition among sites (βST = 0.30 ± 0.09), whereas 47% was because pairs of species that interacted in one site did not interact in another site where they co-occurred (βOS = 0.27 ± 0.07; fig. S4

      Referring to figure 3, the majority of dissimilarity across sites was due to linkage turnover, represented as the grey bars. This means that even though the sites shared similar species, the interactions were different.

    8. [interaction dissimilarity (βWN) = 0.57 ± 0.11, mean ± SE; n = 21 pairwise sites; Fig. 3 and table S5], indicating that, on average, only 43% of interactions were shared between sites despite the most common bird and plant species occurring at all sites (tables S2 and S3)

      The authors measured high levels of dissimilarity across various sites of the island, depicted as the black/gray bars in the graph of Figure 3

    9. We found that despite all interactions being novel and primarily involving introduced species, networks were structurally complex and notably similar between scales (local versus regional) and across sites.

      The authors concluded that overall, the complex network structures of island's ecosystem on both the local and regional scale remained the same, even though these networks were now infiltrated with invading plant and animal species.

    10. At the local scale, networks had low to intermediate connectance and, unlike the regional network, were not nested. Similar to the regional network, six of seven local networks were specialized and modular, presenting three or four modules (Fig. 2, fig. S3, and table S4)

      At individual sites, the authors again saw species mostly interact with only a subset of the total interactions available, with instances of specialized species interacting with birds/plants also found in networks of more generalized species.

    1. The gender gap in the learning of physics concepts was substantial in the control condition (d = 0.46) (F1,304 = 6.23, P = 0.01), indicating that men improved their FMCE scores more than women over the semester. In the affirmation condition, however, this gender learning gap entirely disappeared

      Values affirmation erased the gender gap in the Force and Motion Conceptual Evaluation.

      Women who did not affirm values did not increase their scores on the FMCE from the first test to the second test as much as men did. However, women who did values affirmations had score increases similar to men.

    2. among women with higher levels of stereotype endorsement, the end-of-semester FMCE scores were higher in the affirmation condition than in the control condition

      Values affirmation improved performance for women, especially those who endorsed the gender stereotype.

    3. men's exam scores were little affected by stereotype endorsement, regardless of condition

      Men's performance on exams was not affected by the degree to which they endorsed the gender stereotype.

    4. the values affirmation was particularly beneficial for women who tended to endorse the gender stereotype

      Values affirmation was more effective for women who believed more strongly that the gender stereotype (i.e., that men are better at physics than women) was true.

    5. suggesting that the reduced gender gap observed in this study is based more robustly on the affirmation’s positive impact on women than on its negative impact on men.

      Because women did better on all measures when they performed values affirmation, and men only performed worse according to one measure, it is likely that the reduction in the gender gap observed after the values affirmation intervention is due to women's scores improving rather than men's scores becoming worse. 

    6. affirmation negatively affected men’s exam scores

      Men who performed values affirmation did, on average, slightly worse on course exams than men who didn't perform values affirmation. However, this was not seen on all measures of success (for example, the effect was not seen on the FMCE score).

    7. more women earned B’s in the affirmation group than in the control group, whereas more women earned C’s in the control group than in the affirmation group

      Values affirmation resulted in a shift in the distribution of overall grades for women (but not men). In the values affirmation group, more women earned Bs (relative to Cs) than in the control group.

    8. The reduction in the gender gap remained evident on the final

      Values affirmation reduced the gender gap in final exam scores even though the intervention occurred several weeks before the final exam. This suggests that the effects may be relatively long-lasting.

    9. Course grades, based substantially (75%) on the exam scores, showed a similar pattern

      Values affirmation reduced the gender gap in overall course grades between men and women.

    10. the gender gap was significantly smaller in the affirmation condition than in the control condition

      The authors found that the values affirmation intervention reduced the gender gap between men and women on average exam score.

      In the control condition, men scored higher than women. However, in the values affirmation condition, there was no significant difference in scores between men and women.

    1. Axotomy of the petrosal neurons, separating the cell bodies from peripheral targets, resulted in a precipitous decline in TH catalytic activity and disappearance of TH immunoreactivity

      Cutting down the axons in the petrosal neurons causes a decrease in TH activity and immunoreactivity. However, there is a certain level of TH recovery after four weeks, which could be due to the regeneration or recovery of the severed axon.

    2. nicotinic receptor stimulation, with consequent depolarization or attendant transmembrane Na+ influx, or both, decrease substance P in mature sympathetic neurons, as in neonatal neurons

      With nicotinic receptor stimulation, the depolarization or the influx of sodium ions across the membrane causes a decrease in substance P in both mature and developing neurons.

    3. These observations suggest that membrane depolarization and associated transmembrane Na+ influx decrease [Leu]enkephalin in adult medulla

      Decrease in [leu]enkephalin in adrenal medulla is dependent on two related factors: Membrane depolarization and the sodium influx through the membranes.

    4. In contrast, 4-day adult explants revealed a marked increase in proenkephalin mRNA, which paralleled the rise in [Leu]enkephalin

      At four days, mRNA of proenkephalin showed a greater increase similar to the increase observed in [leu]enkephalin in medullary explants.

    5. Our observations suggested, consequently, that opiate peptidergic and catecholaminergic traits may be differentially regulated in the adult medulla.

      The results described in the previous two sentences suggest that each class of transmitters are regulated differently in the adult medulla.

    1. Similarly, the expression of FosB after cocaine administration was the same in mice exposed to nicotine 14 days earlier and in mice without previous nicotine exposure

      In contrast to the results we obtained with 7 days of nicotine treatment paired with cocaine, these animals did not show any change in the magnitude of LTP, no increase in locomotor activity of in FosB gene expression.

      This indicates that the priming effect of nicotine can occur only when the drugs are given in a close window and not otherwise.

    2. Theophylline-treated mice also showed a reduction in levels of acetylated histone H4

      A reduction in acetylated levels of histone H4 was observed

    3. The acetylated chromatin induced by nicotine exposure would then allow greater FosB gene expression in response to cocaine injection than FosB gene expression after cocaine alone.

      Figures 5 and 6 suggest that the nicotine inhibits HDAC activity, thereby causing global acetylation in the striatum and affecting gene expression.

      In response to cocaine, this acetylation is further enhanced, thus allowing a more significant response in gene expression.

    4. exhibited no increase in FosB mRNA expression in response to cocaine, although cocaine alone increased FosB expression by 176%

      FosB gene expression is also reduced in mice treated with theophylline and cocaine compared to theophylline alone.

    5. Both groups showed a comparable increase in LTP. However, the theophylline-treated mice exhibited an attenuated LTP reduction in response to cocaine treatment

      As expected, in LTP experiments, the mice treated with theophylline and cocaine injections showed a decrease in the magnitude of LTP compared to mice treated with theophylline alone.

    6. Similar to nicotine alone, SAHA alone did not cause a depression in LTP

      SAHA alone did not impair LTP just like nicotine did not impair LTP.

    7. SAHA pretreatment fully simulated nicotine pretreatment and induced a greater reduction in LTP in the core of the NAc than did cocaine alone

      Pretreatment with SAHA followed by cocaine caused a dramatic decrease in the magnitude of LTP response at 180 mins. These results suggest that nicotine does inhibit HDAC activity.

    8. we found that a single cocaine injection after local pretreatment with SAHA for 7 days resulted in 142% more FosB mRNA expression than without pretreatment with SAHA

      Further, when SAHA was infused into nuclear accumbens for 7 days followed by cocaine injection, the FosB expression levels and acetylation of histone residues in striatum increased than the pretreatment with SAHA.

    9. observed a 71% increase in FosB expression in the pretreated mice compared to mice treated with cocaine alone

      Similar to nicotine, SAHA increased the FosB expression levels by 71% and caused acetylation of histone residues in the striatum.

    10. there was a 28% reduction in HDAC of mice treated for 7 to 10 days with nicotine

      28% reduction in HDAC activity was measured in animals treated with nicotine, suggesting that the nicotine inhibits the HDAC activity, thereby decreasing deacetylase activity.

    11. 7 days of nicotine treatment (10 μg/ml) increased histone H3 and H4 acetylation by 32 and 61% in the whole striatum, compared with controls treated with water, much as it did at the FosB promoter

      Again, there was an increase in acetylation levels of H3 and H4 in the striatum.

      These results suggest that the nicotine increases the effect of cocaine on FosB expression by increasing the acetylated residues in FosB, thereby enhancing chromatin reorganization.

    12. We found that, after 7 days of nicotine treatment (10 μg/ml), acetylation of both histone H3 and histone H4 was increased by 34 and 39%, respectively

      Authors observed the acetylation of histone H3 and H4. It is shown that both H3 and H4 got acetylated after a single dose of cocaine injection and after nicotine pretreatment.

    13. The effects on FosB expression are unidirectional; nicotine primes the cocaine response, but cocaine does not prime the nicotine response

      This suggests that the nicotine precedes cocaine and not in the reverse order.

    14. We found that 7 days of cocaine treatment blunted rather than amplified the effect of nicotine on FosB expression in the striatum when compared to the response to nicotine alone.

      On the contrary, the increase in FosB expression we observed in nicotine pretreatment is entirely absent with the cocaine pretreated animals.

    15. Chronic nicotine administration produces changes in gene expression in the brain so that, after nicotine, the brain responds differently to cocaine with respect to long-term synaptic changes

      It could be that the nicotine causes a gene expression in animals. This primed response serves as a precursor for the brain to respond differently to cocaine to produce long term plasticity changes.

    16. As in the behavioral and physiological experiments, 24 hours of nicotine pretreatment produced quite different results from the 7-day treatment and did not lead to an increased FosB response to cocaine

      On the contrary, FosB expression was increased only in animals that received a cocaine injection after 7 days of nicotine treatment and not in 24 hours of treatment.

      This suggests that the long term nicotine effect is responsible for the changes in gene expression.

    17. we found that both 24 hours and 7 days of administration of nicotine (10 μg/mg) in the drinking water caused 50 and 61% increases in FosB expression

      Both 24 hours and 7 days of nicotine administration caused an increase in FosB expression by 50% and 61%.

    18. Treatment with cocaine alone for 7 days or cocaine treatment for 7 days followed by 24 hours of nicotine treatment did not alter LTP

      However, mice treated with cocaine show a 17% decrease in the observed LTP.

    19. The reduction started immediately after the high-frequency stimulation (HFS) and persisted for up to 180 min compared with cocaine alone

      In this experiment, the authors wanted to determine if the sequential drug use of cocaine can alter the cocaine-induced synaptic plasticity.

      After high-frequency stimulation (HFS), mice treated with nicotine alone or water exhibit LTP that lasts for 180 mins. Mice pretreated with nicotine combined with cocaine injection show a dramatic reduction (~40%) in the observed LTP.

      This suggests that the changes in LTP in nucleus accumbens is caused by pre-exposure of nicotine to the mouse.

    20. We found that the rate of cocaine dependence was the highest among cocaine users who initiated cocaine after having smoked cigarettes

      Similar to the results obtained from animals, the individuals who started using cocaine were also active smokers, i.e., they initiated cocaine after smoking.

    21. mice pretreated with nicotine showed a 78% further increase in preference for the cocaine-coupled chamber compared with mice treated only with cocaine, with no previous exposure to nicotine

      Mice pretreated with nicotine coupled with cocaine injections showed a further 78% increase in preference to cocaine-coupled chamber than cocaine-treated animals.

      This suggests that persistent treatment of nicotine for 7 days increases the locomotor activity and behavioral responses of the animals

    22. Cocaine alone increased place preference by 223% compared with saline control

      The experiment was performed to determine the behavioral response in the 4 groups of animals.

      Do these animals have a conditioned place preference or aversion to cocaine? If the place preference to cocaine exists, which group out of 4 show the most sensitization to the CPP?

      In the conditioned place preference test, mice pretreated with cocaine alone showed preference to the cocaine-coupled chamber by 223%.

    23. Mice treated with nicotine for 7 days followed by cocaine showed a significant enhancement of 98% in locomotor activity compared with mice treated with cocaine alone

      Mice treated with nicotine for 7 days, followed by cocaine for 4 days show a 98% increase in locomotor activity than the control mice

    24. Mice treated only with cocaine showed a 58% increase in locomotion (sensitization) compared with controls

      Mice treated with an injection of cocaine for 4 days show a 58% increase in locomotor activity than the control mice

    25. Mice treated with nicotine (50 μg/ml) showed the same levels of locomotion (that is, no increase in locomotion compared to day 1) as water controls.

      There is no difference in the distance traveled by the animals that were treated with nicotine in drinking water versus drinking water. (yellow vs. black bars, fig 1A).

    1. We propose that many of the ecological surprises that have confronted society over past centuries—pandemics, population collapses of species we value and eruptions of those we do not, major shifts in ecosystem states, and losses of diverse ecosystem services—were caused or facilitated by altered top-down forcing regimes associated with the loss of native apex consumers or the introduction of exotics.

      The disruption of many biological processes and natural ecosystem functions can be traced to the loss of predators shifting systems to a new state. Alternatively, introducing invasive exotic species that may outcompete native organisms, removing food sources of predators/herbivores, may cause ecosystem collapse via trophic cascade.

    2. Bottom-up forces are ubiquitous and fundamental, and they are necessary to account for the responses of ecosystems to perturbations, but they are not sufficient. Top-down forcing must be included in conceptual overviews if there is to be any real hope of understanding and managing the workings of nature

      Given the numerous instances of trophic cascades noted in the literature, and the critical impacts that top-down forcing can have as noted above, it is necessary for researchers to consider both bottom-up and top-down controls when looking at ecosystem function, change, and decline.

    3. Many practicing ecologists still view large animals in general, and apex consumers in particular, as ecological passengers riding atop the trophic pyramid but having little impact on the structure below.

      There has previously been lack of appreciation for the role that top-down forces can have within a system, often until those organisms are removed.

      The authors are calling for a change in the lens through which ecosystem ecologists view the role of these species. Specifically, that the working hypothesis of ecosystem ecologists should be that apex consumers play a fundamental role in any particular ecosystem's structure and stability until empirical research indicates otherwise.

    1. Based on retrograde rabies virus and anterograde AAV tracing, ZI axonal projections to the excitatory neurons of the PVT appear more robust than those from other known regions of the brain involved in food intake, suggesting the ZI is not a minor component

      More so than any region of the brain studied so far, ZI GABA neurons and their projections promote binge-like eating behavior.

    2. Bic attenuated photostimulation-evoked feeding (Fig. 2K). That Bic did not completely block photostimulation-evoked food intake could be a diffusion limitation of Bic after application, or ZI VGAT-Cre neurons may coexpress other neurotransmitters responsible for the remaining action.

      The authors found that blocking the function of the GABA receptor (GABA<sub>A</sub> receptor) in the PVT could blunt the increase in food intake mediated by stimulation of ZI terminals in the PVT. This suggests that GABA is an important neurotransmitter underlying this effect.

      The limitations of this approach include that the authors cannot control the spread of the GABA<sub>A</sub> receptor blocker or that other neurotransmitters might be involved.

  7. May 2019
    1. Brain slice electrophysiology confirmed that optogenetic activation of PSTh glutamatergic neuron terminals in the PVT evoked strong glutamate-mediated postsynaptic excitatory currents in PVT vGlut2-GFP neurons, suggesting a functional role for PSTh glutamate neurons in the synaptic excitation of PVT glutamate neurons

      The authors confirmed that stimulation of the PSTh terminals in the PVT was able to activate PVT neurons, i.e. induce excitatory activity in the PVT cells.

      This confirms the rabies tracing result and shows that the connection between the PSTh and the PVT is functional.

    2. In the absence of available food, optogenetic activation of the VGATZI-PVT pathway evoked a significant preference for the chamber associated with laser stimulation compared with the control chamber

      The mice preferred to spend more time in the compartment where they received stimulation of the ZI-PVT pathway. This suggests that stimulation of the neurons is pleasurable for the animal.

    3. ZI GABA neurons project to multiple brain regions, including the hypothalamus and midline thalamus (fig. S6). We therefore measured the relative contribution of stimulation of ZI somata with selective stimulation of ZI axons targeting the PVT. Stimulation of ZI VGAT cell bodies or VGATZI-PVT terminals in the PVT evoked similar levels of feeding

      This suggests that even though ZI GABA neurons project to other brain regions in addition to the PVT, the PVT projection appears to be the most important mediator of increased food intake.

      This is because ZI GABA cell body stimulation and stimulation of the projections to the PVT evoked similar degrees of food intake.

    4. In our monosynaptic retrograde tracing with Cre-dependent rabies virus, although less robust than the projection from the ZI, we found a substantial projection to PVT glutamate neurons from the parasubthalamic nucleus (PSTh) (Fig. 4I and fig. S11) (27, 28).

      Analysis of the inputs to PVH vGlut2 neurons showed that these neurons receive input from the parasubthalamic nucleus, a brain region with previously described roles in appetite.

    5. Food deprivation lasting 24 hours increased inhibitory synaptic neurotransmission to PVT glutamate neurons

      In food-deprived mice, PVT glutamate neurons receive more inhibitory inputs compared to fed mice. These may come from ZI inhibitory GABA neurons, which the authors demonstrated to have increased activity upon food deprivation.

    6. confirmed that PVT glutamate neurons receive strong and direct innervation from ZI neurons

      The authors confirm their anterograde tracing findings using retrograde tracing to show that ZI GABA neurons send projections to excitatory neurons in the PVT.

    7. VGAT-Cre mice with ChIEF expression, bilateral laser stimulation (20 Hz) in the ZI increased food intake

      When ZI GABA neurons are activated by delivering blue light into the brains of the mice, the mice eat a large amount of food.

    8. ChIEF-tdTomato was selectively expressed in ZI GABA neurons

      The optogenetic tool ChIEF-tdTomato was found to be expressed only the ZI GABA neurons.

    9. Satiety feedback signals can thus attenuate ZI-induced feeding.

      Signals from the body inform the brain that sufficient food has been eaten (satiety). These include release of hormones from the gut as well as stomach distention.

      The finding that ZI-stimulated mice will not eat indefinitely suggests that satiety feedback mechanisms are still intact.

    10. Photostimulation of ZI-PVT inhibitory axons evoked gnawing, but not eating, of nonnutritional wood sticks (fig. S5, A and B); photostimulation leading to food intake eliminated subsequent evoked stick gnawing. A priori wood gnawing had no effect on photostimulation-evoked food intake (fig. S5, C and D).

      The authors conclude that the food intake seen with ZI stimulation is not because the manipulation increases gnawing behavior directed at any object, but directs behavior towards edible sources of food.

    11. After the days of photostimulation were completed, mice showed a significantly reduced food intake compared with that of controls (Fig. 3H).

      The authors measured daily food intake for 15 days during the stimulation protocol. They then continued measuring daily food intake in the absence of stimulation.

      The mice likely reduced their food consumption when the stimulation protocol ceased due to satiety signals that normally prevent overeating in the absence of the manipulation of the ZI to PVT pathway.

    12. Ablation of ZI GABA neurons decreased long-term food intake and reduced body weight gain by 53% over 8 weeks (Fig. 3, J and K).

      When the ZI GABA neurons were killed, the mice could no long maintain their normal body weight and ate less food than control mice that had their ZI GABA neurons intact.

      This suggests that these cells are required for normal food intake and body weight maintenance.

    13. Ablation of PVT vGluT2 neurons substantially increased both food intake and body weight gain for an extended period (16-week study) (fig. S10, G and H).

      The increase in food intake and body weight gain with PVT neuron ablation shows that these cells are important for body weight maintenance.

      This finding is opposite to what was found when ZI GABA neurons were ablated, suggesting that PVT neurons are downstream of ZI GABA neurons and have an opposing effect on food intake and body weight.

    14. photostimulation of ZI VGAT-ChIEF-tdTomato terminals in the PVT evoked GABA-mediated inhibitory currents in PVT vGlut2-GFP neurons (Fig. 2D).

      Stimulation of ZI GABA neuron projections (terminals) in the PVT with blue light led to inhibition of PVT excitatory neurons.

      This finding confirms the rabies tracing result and shows that the connection between ZI neurons and PVT neurons is inhibitory.

    1. The experimental proof of the colinearity of a gene and the polypeptide chain it produces may be confidently expected within the next year or so.

      Crick proposed that a gene was a linear sequence of nucleotides, where each gene encoded a single protein. However, this explanation is a bit too simplistic, especially for higher-level and multicellular organisms.

      In fact, we now know that colinearity is generally the exception, not the rule, in eukaryotic genomes.

      For more information, check out this piece in Nature Education: https://www.nature.com/scitable/topicpage/what-is-a-gene-colinearity-and-transcription-430

    2. That is, either (+ with + with +) or (- with - with -). Whereas a single + or a pair of them (+ with +) makes the gene completely inactive, a set of three, suitably chosen, has some activity.

      DNA with only one additional base generates a completely different protein than that of the original code. The same is true of DNA with two additional bases.

      However, when bases are added in triplets, the generated protein is identical to the native protein with one minor difference: an extra amino acid.

    3. The preliminary results presented so far disclose no clear difference, with respect to the code, between E. coli and mammals, and this is encouraging (10, 13).

      Since mammals and E. coli (a bacterium) are extremely different biological species, it is remarkable that their genes are comprised of identical genetic codes. Their similarity suggests the genetic code is not different per species, but universal across all living organisms.

    4. It is possible that some triplets may code more than one amino acid—that is, they may be ambiguous.

      While most amino acids are encoded by at least two codons (with the exception of methionine and tryptophan), the reverse is not true. Each codon specifies just one amino acid or stop signal. Thus, the genetic code is unambiguous.

    5. In general, more than one triplet codes each amino acid.

      In other words, the same amino acid is coded by more than one base triplet. For example, there are six different codon combinations to encode arginine. This property is now known as degeneracy.

    1. One of these regions (~525 kb in size) showed the strongest differentiation in all three contrasts. The region included four genes: high mobility AT-hook 2 (HMGA2), methionine sulfoxide reductase B3 (MSRB3), LEM domain-containing protein 3 (LEMD3), and WNT inhibitory factor 1 (WIF1).

      This index scan allowed the researchers to narrow down the region that showed the strongest differences between the large, medium, and small ground and tree finches.

    2. The results suggest that the phenotypic effects of these loci are small relative to the effect of the HMGA2 locus.

      The investigators were able to rule out the six other loci that may have been associated with beak size, body size, or beak shape.

    3. This SNP showed a highly significant association with beak size, a significant association with body size, and no association with beak shape among medium ground finches (Fig. 2E).

      Investigations within the HMGA2 gene showed that it did, in fact, show a high relationship with beak size.

      This seems to confirm the fact that HMGA2 played an important role in the evolutionary shift in beak size during the drought.

    4. Our results provide evidence of two loci with major effects on beak morphology across Darwin’s finches. ALX1, a transcription factor gene, has been associated with beak shape (15), and here we find that HMGA2 is associated with beak size.

      Coupled with the team's previous study that showed the ALX1 gene controlled beak shape, this study shows evidence that HMGA2 is associated with beak size.

      These findings show how scientific researcher builds upon itself to continue to not only answer questions, but to continue to ask questions.

    5. We have shown that the HMGA2 locus played a critical role in this character shift. The selection coefficient at the HMGA2locus (s = 0.59 ± 0.14) is comparable in magnitude to the selection differential on the phenotype and is higher than other examples of strong selection, such as loci associated with coat color in mice (s < 0.42) (25). The main implication of our findings is that a single locus facilitates rapid diversification.

      This single HMGA2 locus seems to allow for diversity among finch beak size. However, the exact mechanism for how HMGA2 controls beak size in finches is unknown.

      Would the findings of this study provide enough justification for further studies that would attempt to better understand that function of HMGA2?

    6. Thus, we conclude that the relationship between HMGA2 and fitness was mediated entirely by the effect of this locus on beak size or associated craniofacial bones or muscles; developmental research will be necessary to reveal the underlying mechanism for the association. There is no evidence of pleiotropic effects of the gene on other, unmeasured, traits affecting fitness (table S5).

      The HMGA2 gene is strongly associated with beak size. Beak size is the main factor that allowed some medium ground and tree finches to survive after a drought.

      Thus, the researchers provided a direct link between this particular gene and the fitness of finches.

    7. Segregation is mainly observed in species with intermediate size (medium ground and tree finches).

      In contrast to haplotypes present in large and small finches, the medium-sized finches tended to inherit the particular genes from both parents.

      This is what we may call heterozygous condition.

    8. revealed two major haplotype groups associated with size; 98% of small birds (body weight <16 g) clustered into one group and 82% of the large birds (body weight >17 g) clustered into the other (Fig. 1D). The split between the two haplotypes occurred before the divergence of warbler and nonwarbler finches at the base of the phylogeny (Fig. 1D), about 1 million years ago (Fig. 1C).

      Why was it important to not only construct a phylogenetic tree based on the entire genome sequences (Fig. 1C), but also construct one based on the HMGA2 region (Fig. 1D)?

      What do these two trees reveal about the differing sizes of finches?

    9. Genotypes associated with large beak size were at a strong selective disadvantage in medium ground finches (selection coefficient s = 0.59).

      After the drought, medium ground finches wither larger beaks were at a severe disadvantage because they could not compete for food with the large ground finch.

      When a genotype is shown to be disadvantaged, what happens to the genes in that gene pool? What happens to those disadvantaged individuals? What happens to the population as a whole?

    10. We discovered a genomic region containing the HMGA2 gene that varies systematically among Darwin’s finch species with different beak sizes.

      For the first time, researchers have been able to find a gene that controls beak size in Darwin's finches. Why is this finding such an important part of the story of these birds and how they evolved?

    1. Oʻahu’s SDN included 15 bird and 44 plant species connected by 112 distinct links (Fig. 1)

      The authors identified 44 different plant species and 25 different birds in O'ahu. Figure 1 depicts each bird (left column) and each plant (right column) as rectangles. The lines connecting a bird to a plant represents a seed dispersal event.

    1. in-class exam scores by approximately 61% and entirely eliminated the gap on the FCME

      Taking into account pre-existing differences in students' preparation for the class, values affirmation was highly effective in reducing or eliminating the gender gap.

    1. The transient nature of REPAIR-mediated edits will likely be useful for treating diseases caused by temporary changes in cell state, such as local inflammation, and could also be used to treat disease by modifying the function of proteins involved in disease-related signal transduction.

      Compared to DNA editing, RNA editing is temporary and can be reversed more easily. This means that RNA editing with REPAIR can be used not only to correct inherited mutations that cause disease, but disease-causing mutations that arise later in life. While DNA editing could treat a mutation that occurred later in life, the treatment would be permanent. RNA editing could treat something temporarily, so it could be used for temporary cell growth or inhibition of imflammation in response to an infection.

      The programmability of RNA and DNA editing by simple base pairing rules makes it much easier to develop than alternative therapies such as drug inhibitors that are targeted to specific enzymes. Finding an inhibitor that is specific enough without causing side effects is difficult. The REPAIR system is a potential solution to this precision problem.

    2. can target either the sense or antisense strand

      Cas9 (as the targeting unit of the DNA base editor) can be directed against the sense or antisense strand. The gRNA pairs with the strand, causing a short sequence of the opposite strand to be displaced. Then, the "free" fragment is accessible for the cytidine deaminase that acts on single-stranded DNA.

      This means that DNA base editors can be used to correct mutations in either strand. By contrast, RNA editors can only work with the mRNA which limits their editing ability two times.

      In contrast, REPAIR is not constrained by PAM, PFS, and other motifs, meaning it can act on a broader range of sequences (but can only act on transcripts).

    3. The lack of motif for ADAR editing, in contrast with previous literature, is likely due to the increased local concentration of REPAIR at the target site owing to dCas13b binding.

      Previously, it has been shown that the ADAR proteins prefer certain nucleotides at the 5' and 3' positions next to the target sequence (reference 21). However, this is not a strict preference, and some mutants are more strict than others.

      In addition, previous work has shown that when ADAR2 is site-specifically directed at a target, its local concentration is increased and less favorable reactions sometimes occur. 

    4. Deeper sequencing and novel inosine enrichment methods could further refine our understanding of REPAIR specificity in the future.

      In this work, the authors used next-generation sequencing to detect editing events. They compared the obtained sequences (reads) with the genomic sequence. If the genome contained A but the read had G at the same position, they considered that an editing event.

      However, this approach may overestimate the number of edits. First, the sequencing itself generates errors that can be mistakenly attributed to ADAR activity. Second, the gene may have many versions in a genome that differ at some positions, including A>G differences. This leads to some ambiguity in data interpretation.

      To make up for these problems, several approaches have been suggested to detect inosine modification directly, including chemical modification and antibody-based enrichment. Post publication of this paper, newer techniques have been introduced that could be used for chemical modification.

    5. it is unlikely to do so in this case because Cas13b does not bind DNA efficiently and because REPAIR is cytoplasmically localized.

      ADAR activity on DNA-RNA heteroduplexes might be a problem for precise RNA editing by REPAIR. Fortunately, Cas13b predominantly binds RNA and the REPAIR system is sequestered from the DNA in the cytoplasm as a result of the nuclear export sequence (NES) fused to Cas13b.

    6. The overlap in off-targets between the targeting and nontargeting conditions and between REPAIRv1 and BoxB conditions suggests that ADAR2DD drives off-targets independent of dCas13 targeting

      In summary, the authors found two pieces of evidence supporting the hypothesis that the ADAR2 deaminase domain is the main source of off-targets:

      First, they found overlap between the off-target effects of REPAIRv1 under different targeting conditions and ADAR2(DD).

      Second, they saw overlap in the off-target effects between REPAIR and ADAR2(DD) in a completely different targeting system. This offers strong support that ADAR2 drives off-target effects regardless of the targeting module.

    7. Given the high number of overlapping off-targets between the targeting and nontargeting guide conditions, we reasoned that the off-targets may arise from ADARDD.

      The authors found a lot of overlap between the off-target effects they saw in the targeting and non-targeting conditions, meaning that the REPAIRv1 complex was modifying adenosines even when the gRNA did not guide it. This suggests that ADAR is increasing off-target editing effects independent of dCas13b.

    8. These results indicate that Cas13a and Cas13b display similar sequence constraints and sensitivities against mismatches.

      The researchers found that Cas13a and Cas13b had the same sequence requirements for successful target recognition and cleavage. Neither nuclease was affected by changes to the PFS sequence, but both of them functioned less well when there were changes in the middle of the target sequence.

      Another consequence of these findings is that, because changes to PFS sequences (which are at the edge of target sequences) don't affect Cas13 activity, off-target mRNA molecules that differ from the target only in PFS sequences might be mistakenly destroyed by Cas13.

      Fortunately, because of its length (more than 30-nt), the spacer is highly specific and binds unique sequences.

    9. found that PspCas13b had consistently increased levels of knockdown relative to LwaCas13a (average of 92.3% for PspCas13b versus 40.1% knockdown for LwaCas13a)

      As you can see on the figures 1C and 1D, the blue line corresponding to the PspCas13b nuclease goes far beyond the red line which corresponds to the LwaCas13a nuclease.

      The signal of the Gluc luciferase that resulted from the PspCas13b knockdown was around 10% for all gRNA molecules along the transcript. This means that the average knockdown efficiency was 90%. The signal of Gluc in the case with LwaCas13a was not as consistent, but on average dropped by about 40%.

    10. We selected the top five Cas13b orthologs and the top two Cas13a orthologs for further engineering

      Several Cas13a and b orthologs decreased Gluc luciferase signal in up to 10-30% of the control cells. Some Cas13b nucleases demonstrated even greater effectiveness than the previously characterized Cas13a from Leptotrichia wadei.

    1. which enables maximum regeneration with minimal temperature increase

      This means that the water desorption process is highly efficient, not requiring a large amount of energy from heat.

    2. By considering both the adsorption and desorption dynamics, a porosity of 0.7 was predicted to yield the largest quantity of water.

      The results of the simulations show that if the porosity is too low, the adsoprtion process becomes slower. In contrast, if the porosity is too high, more MOF is required to harvest the same amount of water but the process is slower. The simulations showed that the ideal porosity was 0.7.

    3. We also report a device based on this MOF that can harvest and deliver water (2.8 liters of water per kilogram of MOF per day at 20% RH) under a nonconcentrated solar flux less than 1 sun (1 kW m–2), requiring no additional power input for producing water at ambient temperature outdoors.

      In this study, the authors demonstrate that a MOF-based device can harvest water from the atmosphere at humidity and temperature conditions similar to a desert, without requiring any more energy than natural sunlight. Since this paper was published, the authors published another paper with the results of a devise test in the Arizona desert. In the "Related Content" tab, see their 2018 Nature Communications paper.

  8. Apr 2019
    1. Our experimental studies confirm that the stable superlubricity regime occurs over a wide range of test conditions; when the load was changed from 0.5 to 3 N, velocity was varied from 0.6 to 25 cm/s, temperature increased from 20°C to 50°C (fig. S15), and the substrate was changed to nickel or bare silicon (fig. S16).

      Superlubricity experiments at any sliding interface should follow certain local load and sliding velocity conditions. Thermal effects are also dominant in frictional energy dissipation during sliding. Authors have tested a wide range of experimental conditions and shown that their system exhibits stable superlubricity under the tested conditions.

    2. The tribological evolution of a single graphene patch at the nanoscale resembles that of a single asperity contact, whereas the mesoscopic behavior resembles a multiple asperity contact. The friction mechanism at the mesoscale for an ensemble of graphene patches is not different from nanoscale (single patch). The initial tribological state of the patches, as well as the configuration of the patches versus nanodiamonds, dictates the dynamics of scroll formation, which in turn affects the dynamical evolution of COF for the mesoscopic system

      The mechanism of friction reduction at the macroscale is found to be the same as that at the nanoscale. At the macroscale, nanoscrolls at different orientations are observed while an assembly of graphene patches at different initial configurations slide over the nanodiamonds. Over time, this reduced contact area leads to ultralow friction sliding at the large scale.

    1. changes in sea surface temperature may remain relatively small in this region

      Has this hypothesis been proven true since this paper was published in 2000?

      Use the National Oceanic and Atmospheric Administration's (NOAA) website to investigate changes in ocean temperatures since this study was published: https://www.nodc.noaa.gov/OC5/3M_HEAT_CONTENT/

    2. changes we observe in global ocean heat content may be related to the hemispheric and/or global modal variability of the atmosphere

      The Earth is an interconnected system where conditions in the atmosphere also affect what happens in the oceans. While the authors cannot say for sure that specific climate oscillations are driving the changes in ocean heat content, it is possible to say that changing climates are likely impacting ocean heat content.

    3. increase in ocean heat content preceded the observed warming of sea surface temperature

      The heat content of the atmosphere contributes to the warming of the ocean, so it would seem logical for the surface ocean to warm more quickly than the deep ocean (because the deep ocean is farther from the atmosphere).

      However, data suggests that the heat content of the deep ocean is increasing more quickly than the surface ocean. This further suggests that deep ocean circulation is transporting warmth from the surface to greater depths.

    4. our results support the findings of Hansenet al.

      Levitus et al. found a ∼2 × 10<sup>23</sup> joules warming between the mid-1950s and mid-1990s, which corresponds to a warming rate of 0.3 watts per meter squared.

      Thus, the ocean appears to be absorbing nearly half of the total heat that results from the warming of the Earth.

    5. warming in the western midlatitudes is due to nearly equal contributions by the 0- to 500- and 500- to 1000-m layers

      The western midlatitudes in this case represent the area between 30° - 45°N and 80° - 40°W. In this area the surface 300 m of the ocean has warmed by 1-2°C from the 1970s to the 1990s (Fig. 3A). This increase is even more extreme in the deeper ocean which has warmed by as much as 8°C (Fig. 3B).

      After examining the data in 500 m increments, Levitus and coauthors determined that most of this warming is occurring in the top 1000 m.

    6. There is a consistent warming signal in each ocean basin, although the signals are not monotonic.

      In each ocean basin, there have been periods when the heat content has increased and periods when the heat has decreased. However, the overall trend shown by the data is that every ocean basin on the planet has been warming over the last 50 years.

      Most of that warming has occurred after the 1950s and 1960s.

    7. Only the Atlantic exhibits a substantial contribution to these basin integrals below 1000-m depth.

      It is only in the North Atlantic that the ocean is being warmed at deeper depths. In the Pacific and Indian oceans, warming appears to only occur in the surface 1000m. 

    8. The cooling of the Labrador Sea is composed of nearly equal contributions of about 1.0 W m−2 from each 500-m-thick ocean layer down to 2500-m depth.

      The Labrador Sea is the region between Greenland and Canada around 60°N, 50°W that shows some of the most extreme cooling throughout the water column (Fig. 3B).

      Levitus et al. found that the cooling of the Labrador Sea has consistently declined by 1W/m<sup>2</sup> for every 500m in depth, extending all the way down to 2500 m.

    9. maximum heat storage for this basin occurs at depths exceeding 300 m

      The North Atlantic ocean absorbs a lot of heat, but where is that heat being stored?

      The heat that the ocean absorbs does not remain in the surface ocean, but is instead carried to deeper depths by deep ocean convection currents. From the 1970s to the 1990s, the deep water of the North Atlantic has gained more heat than the surface ocean has over the same period.

    10. demonstrates the opposite picture.

      The deep ocean of the North Atlantic cooled between the period 1970-1974 and the period 1988-1992, two decades later. While higher latitudes show this cooling most strongly, the decline in deep water temperatures appears to have occurred through much of the North Atlantic.

    11. difference field for the two earlier periods shows that much of the North Atlantic was warming between these periods

      Overall, the deep water of the North Atlantic had higher temperatures during the period 1970-1974 than during a period two decades earlier, from 1955-1959.

    12. decadal variability of the upper ocean heat content in each basin is a significant percentage of the range of the annual cycle for each basin

      The change in heat content from one decade to the next is similar in scale to the shift in heat content that happens over the course of a year due to the change in seasons.

      That is, the range of temperature from the highs of summer to lows in winter is similar to the extent of change from one decade to the next.

    13. There is relatively little contribution to the climatological range of heat content from depths below 300 m.

      The deep ocean below 300m is disconnected from the atmosphere and appears to have little influence on climate.

    14. the two basins positively correlated

      While there are periods of increasing and decreasing heat content in the oceans, with swings happening roughly every two decades, the Pacific Ocean has seen an overall increase in temperature over time.

    15. temperature anomaly of 0.37°C

      In 1998, the North Atlantic ocean was 0.37°C (0.37°F) warmer than the 50-year average.

      Has this trend continued since Levitus et al. published this study in 2000?

      You can find the answer by examining ocean temperature data available from NASA: https://climate.nasa.gov/vital-signs/global-temperature/

    16. In each basin before the mid-1970s, temperatures were nearly all relatively cool, whereas after the mid-1970s these oceans are in a warm state.

      Levitus et al. found that, as time progresses, ocean temperatures increase. Thus, time and ocean temperature are positively correlated.

      Much of this ocean warming has occurred since the mid-1970s.

    1. Some early-life events that are generally thought to affect adult microbiota composition were not associated with microbiota composition variation in our study, including mode of birth [cesarean section (N = 36) or vaginal delivery (N = 1036)], place of birth [home (N = 207) or hospital (N = 899); increased diversity in home-born individuals, FDR>5% when controlling for age], and infant nutrition [breastfed (N = 537) or not breastfed (N = 359)]

      Their study suggests that early-life events, such as birth method or nutrition, do not have any significant correlations with the adult microbiome.

    2. the second bicluster, consisting of seven genera, including Bacteroides and Parabacteroides, comprised individuals with reduced microbiome diversity. Characterization of these individuals revealed a preference for white, low-fiber bread [bread being the major source of carbohydrates in an average Belgian diet (34)] and higher prevalence of recent amoxicillin treatment.

      The other subset of individuals was characterized by lower microbiome diversity, having only seven genera (compared to 15 genera in the first subset). These individuals showed a preference for white bread and were associated with recent antibiotic treatment.

    3. Moreover, correlations between RBC counts and Faecalibacterium abundances are in line with the known oxygen requirements of this genus

      They found that red blood cell counts were also associated with the relative abundance of Faecalibacterium. As oxygen transport is the most important function of red blood cells, this fits the oxygen requirements of this genus.

    4. 308 samples collected in Papua New Guinea (15), Peru (16), and Tanzania (17) reduced the size of the human core microbiota to 14 genera. Notably, Alistipes, Clostridium IV, Parabacteroides, and all Actinobacteria were excluded from the global core composition

      When data was collected from samples outside of Europe and the United States, the core microbiota (which is defined as a genus that is common to at least 95% of samples) decreased to 14 genera.

    5. core microbiota (i.e., the genera shared by 95% of samples) composed of 17 genera with a median core abundance (MA) of 72.20%

      They found that the core microbiota—defined by being shared by 95% of samples from the United Kingdom, United States, FGFP, and LLDeep data sets—was 17 genera. The median abundance of these genera was 72.20%.

    6. Combined, these data sets comprised a total richness of 664 genera (fig. S2A). Extrapolation estimated total western genus richness at 784 ± 40 (fig. S2B), suggesting that total western richness is still undersampled. Observing total richness would require sampling an estimated additional 40,739 individuals

      The overall microbiota richness of their samples accounted for 664 genera, but does not cover all 784 genera expected for the entire Western population. They calculate that in order to observe all 784 genera, they would need to sample over 40,000 more individuals.

    7. Sixty-nine clinical and questionnaire-based covariates were found associated to microbiota compositional variation with a 92% replication rate.

      The study found 69 dependent factors from clinical-based—that is, measurements taken by doctors—and questionnaire-based—that is, provided by the patients about their lifestyle—data. They found that for 92% of the factors that had a counterpart in an independent study (=LLDeep study), these factors were still significantly associated to variation in microbiome composition.

    1. having about equal amounts of uracil and cytosine in (presumably) random order, will increase the incorporation of the amino acids phenylalanine, serine,  leucine, and proline, and possibly threonine.

      As seen in the figure below, random triplet combinations of U and C are now known to encode for the amino acid residues Crick suspected.

  9. Mar 2019
    1. it can be established in only three generations

      The authors summarize all their evidence that homoploid hybrid speciation has occurred in the BigBird lineage. They note how unusual this example is because it occurs faster than expected.

    2. The key features of success of the new lineage are reproductive isolation based on learned song and morphology, transgressive segregation producing novel phenotypes, and the availability of underexploited food resources.

      Here, the authors list the main reasons that this hybrid lineage survived and reproduced rather than dying out or mating with members of the parental species.

    3. The low values probably represent low additive genetic variation because the traits are highly heritable in Geospizaspecies

      The authors conclude that their measurements, both genetic (inbreeding coefficient, admixture, average nucleotide diversity) and bill shape (length and depth) do show low levels of variation in the Big Bird population.

      They conclude that this is expected because the bill shape traits are highly determined by genes, and so low genetic diversity would lead to low physical diversity of certain traits, such as bill shape.

    4. the founder male (5110) was not a G. fortis x G. scandens hybrid as previously hypothesized (12), but a G. conirostris

      This conclusion of the authors is a reclassification of the founder male into a different species than previously thought, based on the genetic analysis.

    1. Our data, in implicating deep layer V neurons as sufficient targets in primary motor cortex, may help address these issues by informing the design of cortical interventions with regard to subdural rather than superficial extradural stimulation.

      Based upon the investigators results, they can extrapolate how their findings will impact future treatment of Parkinson's disease—not by implementing an optogenetic approach, but by targeting a different area in the pathological neural circuit that could prove more effective.

    2. M1 stimulation of this kind potently influenced neural activity in the STN

      By doing a separated-optrode experiment where an optrode was placed over M1 and a recording electrode placed in STN, the researchers were able to see a frequency dependent resolution of parkinsonian motor deficits.

    3. indeed, as expected from our light-scattering measurements and tissue geometry, we found that at least 0.7 mm3 of STN is recruited by light stimulation, which closely matched the actual volume of the STN

      Measuring the area of c-fos activated neurons upon light stimulation provided the authors with support for using an optrode to stimulate the STN since the area activated closely matched the true volume of the STN.

    4. the direct activation of local glial cells appeared not to be sufficient to treat parkinsonian symptoms, pointing to consideration of other circuit mechanisms.

      When blue light passed through the optrode to the STN, neuronal firing was inhibited by activating ChR2-expressing astrocytes. ChR2 allowed for the influx of calcium into astrocytes causing a release of glutamate and adenosine into the cellular environment. Adenosine would then bind to adenosine A1 receptors and inhibit neuronal firing. Even though they were able to inhibit firing, motor pathology was still unaffected by this intervention alluding to other circuit mechanisms.

    1. Fig. 4 Time series of 5-year running composites of heat content (1022 J) in the upper 3000 m for each major ocean basin

      This figure shows how ocean temperatures have changed in each ocean basin from 0 to 3000m in depth. Due to gaps in temperature data (especially in the 1950s), Levitus et al. used 5-year averages (composites) instead of looking at annual data (as in Figure 1).

      The authors found that there is an overall increase in temperatures within each ocean basin. This warming is not consistent, but instead has periods of lower temperatures and periods of higher temperatures.

      How does this figure differ from Figure 1 that only looks at 0 to 300m depths?

    2. Atlantic and Pacific Oceans have undergone a net warming since the 1950s and the Indian Ocean has warmed since the mid-1960s

      All of the world's oceans have been warming since at least the 1970's according to measurements by ships and research vessels.

      From the data available, it appears the Atlantic and Pacific started warming before the Indian Ocean, but this result could be due to the fewer number of data points collected in the Indian Ocean.

    3. global volume mean temperature increase for the 0- to 300-meter layer was 0.31°C

      While the whole ocean warmed 0.06 C between the 1950s and 1990s, Levitus et al. found that the surface ocean (the top 300 meters or 984 feet) warmed by 0.31 C.

    4. volume mean warming of 0.06°C

      All of the world's oceans combined - the Atlantic, the Pacific, the Indian - have warmed by 0.06°C overall between 1948 and 1998.

      But have the oceans all warmed equally, or have some basins or depths warmed more than others?