1,192 Matching Annotations
  1. Sep 2016
    1. An increased role for inherited factors in autism families with shared ancestry was also suggested by a low rate of de novo CNVs

      The low rate of de novo copy number variant suggests that abnormalities in autistic patients' genomes comes from defective genes that were already present in the parents, rather than healthy genes that mutated before or shortly after fertilization.

    2. A second >300 kbp, linked, homozygous deletion (again not present in >2000 individuals other than this family) is closest to PCDH10 on 4q28 (Fig. 2 and table S5), which encodes a cadherin superfamily protein essential for normal forebrain axon outgrowth

      A second big deletion was identified on the chromosome. This codes for a protein that allows for neuron, and more specifically axon, growth.

    3. The deletion completely removes c3orf58, which encodes an uncharacterized protein with a signal peptide that localizes to the Golgi (28). Moreover, the deletion is near the 5′ region of NHE9, such that only 60 to 85 kbp upstream of the transcription initiation site is spared

      This deletion completely removes a protein-coding gene called c3orf58, and a large section of possible regulatory regions of another gene called NHE9. SK

      The authors focused on one pedigree in this paragraph: the family of patient AU-3101. A first deletion removes an entire gene, coding for a protein present in the Golgi Apparatus, as well an upstream region of the gene coding for NHE9, an ion exchanger.

    4. we were surprised to see that several consanguineous pedigrees showed large, rare, inherited homozygous deletions within linked regions, some of which are very likely causative mutations (Figs. 1 and 2 and table S5). Such deletions were present in 5 of 78 consanguineous pedigrees (6.4%) and ranged in size from 18 thousand base pairs (kbp) to > 880 kbp

      The authors noticed that in some cases, there were deletions of certain long sequences present on both chromosomes of the affected individuals. These huge deletions could cause symptoms of autism in certain cases.

    5. nonoverlapping between families, consistent with genetic heterogeneity,

      The abnormalities in autistic patient's chromosomes were not shared between families. This suggests that autism can have many different genetic origins.

    6. the M/F ratio of affected individuals was typical, at 4.8:1 (115 males: 24 females). However, in consanguineous, multiplex pedigrees, the M/F ratio was 2.6:1 (34 males: 13 females) (fig. S1), compared to 7.4:1 (81 males: 11 females) for the other categories of families (i.e., nonconsanguineous and consanguineous simplex)

      The authors observed that the proportion of women affected doubles in consanguineous multiplex compared to the whole HMCA and is almost tripled compared to simplex families.

    7. Our finding that deletions of genes regulated by neuronal activity or regions potentially involved in regulation of gene expression in autism suggests that defects in activity-dependent gene expression may be a cause of cognitive deficits in patients with autism.

      The authors found that large deletions of genes that are regulated by neuronal activity were associated with autism symptoms. This is an interesting finding, because autism symptoms often develop later in development.

    1. Overall, this study reveals that the electric eel has evolved a precise remote control mechanism for prey capture, one that takes advantage of an organisms’ own nervous system.

      This study revealed that Eels, through the process of evolution and survival for the fittest, have developed a very efficient system of prey detection and capture. The Eel's electrical powers work much like the way a TV remote control does. Using electrical pulses Eels turn off their prey's nervous system the same way a remote control turns off a tv screen. This happens because the electric pulses take advantage of the mechanism through which the Prey's nervous system works by hacking into it and telling it to freeze.

    2. This result indicates that fish are immobilized by massive, involuntary muscle contraction.

      The eel's electric shock contracts the fish's muscles, which paralyses it.

    3. These findings indicate that fish motor neuron activation is required to induce tetanus in prey

      The eel's shock affects the nervous system (motor neurons) of the fish.

    1. Although our findings show that NIH grants are not awarded purely for previous work or elite affiliations and that reviewers contribute valuable insights about the quality of applications, mistakes and biases may still detract from the quality of funding decisions.

      Summing up all results we can say that previous work or elite affiliations do not "close the door" for new ideas in research.

    1. These results reveal a new evolutionary scenario where hairs, feathers, and scales of extant species are homologous structures inherited, with modification, from their shared reptilian ancestor’s skin appendages already characterized by an anatomical placode and associated signaling molecules.

      The authors have found that the placode and the placode's signalling molecules are highly conserved - meaning it is found across many species.

      This study shows that the placode is responsible for the formation of many different structures in the various species, such as feathers, scales and hair.

    2. homozygous for a codominant mutation

      Homozygous means that they have two copies of the exact same gene.

      Co-dominant means that two different genes that are present in the same individual will both be expressed and blended together.

      In this case, the gene which causes a scaleless mutant must have two copies of the mutant gene. If there is one copy, there will be partial formation of scales.

    3. similar phenotypes in other vertebrates because of impairments of the EDA receptor (EDAR; a member of the TNF family) (18) or its ligand EDA, indicating a conserved role of this pathway in reptiles as well

      Similar disease symptoms can be observed in other animals with a mutation in the same gene.

    4. Scaleless dragons show an irregular skin surface with the initiation of some dermoepidermal undulations of the skin (Fig. 3G), indicating that this phenomenon does not fully require the presence of anatomical placodes.

      Even though the mutant does not have scales as a result of a non functional protein, it still shows the beginnings of a pattern for scales.

      This means that there are other elements that are not part of the anatomical placode which contribute to the formation of scales

    1. Pharmacotherapies that increase hippocampal BDNF may prove to be efficacious treatments for fear disorders characterized by extinction impairments

      One of the goals of fear learning research is to be able to improve therapies for people suffering from fear and anxiety disorders.

      The fear extinction process is impaired in many of these patients, so identifying molecular targets may aid in drug development.

    2. it is possible that BDNF treatment may lead to partial reversal of conditioning-induced changes

      Changes that occur following fear conditioning, such as a reduction in hippocampal BDNF, may be corrected by BDNF treatment.

    3. Because BDNF facilitates NMDA receptor currents (11, 12), exogenously applied BDNF may simulate extinction by inducing bursting in the IL mPFC

      The effects that infused BDNF has on extinction are mediated by NMDA receptors in the IL mPFC.

      Activation of these receptors may stimulate neurons in this region, and this could explain why infusion of BDNF results in reduced freezing even when the animals do not go through extinction training.

    4. Our results provide further support for the importance of this pathway in extinction and extend these findings by identifying BDNF as a key molecular mediator

      This research furthers our understanding of fear learning by describing extinction using both a systems level approach (hippocampus to IL-mPFC pathway) and a molecular mechanism (BDNF-mediated NMDA activation).

    5. We were able to pharmacologically induce extinction with a single infusion of BDNF into the hippocampal-infralimbic pathway, a key projection for extinction memory

      When infused into the hippocampus, BDNF can induce extinction in the absence of extinction training.

      This suggests that activation of this pathway is a key component of the fear extinction process.

    6. which suggests that the IL mPFC is the primary site of action for hippocampal BDNF

      Blocking BDNF activity in the IL mPFC inhibits the effects of BDNF infused into the hippocampus.

    7. BDNF infused into the hippocampus reduced fear, as measured by both freezing [main effect of drug F2,21 = 4.715, P = 0.020, post hoc P = 0.013 comparing SAL(IL) + SAL(Hipp) to SAL(IL) + BDNF(Hipp)] (Fig. 3C) and conditioned suppression of food seeking (fig. S4)

      The fact that BDNF infusion into the hippocampus results in similar fear reduction to infusion into the IL mPFC supports the hypothesis that the hippocampus supplies BDNF to the IL mPFC.

    8. NMDA receptors are necessary for BDNF-induced reductions in fear

      The role of NMDA receptors in fear acquisition has been previously established.

      By showing that rats receiving an NMDA antagonist do not respond to BDNF, the authors show that these receptors are also required for BDNF-induced fear reduction.

    9. indicating that BDNF left the original fear memory intact

      Based on the fact that unsignaled footshocks can reinstate freezing after extinction, the authors conclude that BDNF does not degrade the original memory.

    10. The lack of effect on conditioning and open-field anxiety suggests that BDNF infusions did not decrease amygdala activity nonspecifically

      When testing the behavioral effects of a treatment, it is important to rule out nonspecific interaction with other regions of the brain that may similarly affect behavior through an alternative route.

      The amygdala is known to be involved in fear acquisition, so if the BDNF was nonspecifically acting on the amygdala it would be apparent during conditioning or open-field anxiety testing.

    11. that BDNF reduced fear independent of extinction training

      The purpose of extinction training is to subject the animals to the tone enough times to allow them to form a new memory. They realize that the tone is not followed by a shock and therefore is not associated with a threat. This concept forms the basis of exposure therapy, which is used to treat humans with anxiety disorders by progressively re-exposing them to a traumatic memory while in a safe environment.

      In this experiment, the BDNF animals show reduced freezing prior to extinction training. This allows the authors to conclude that at least some of the effects that BDNF infusion has on fear expression occur regardless of whether the animals receive extinction training.

    12. which indicated that BDNF strengthened extinction memory

      Extinction memory is tested on the third day, when the animals are subjected to another round of tones without footshocks. If the animals freeze less in response to the tones, it means that they have successfully extinguished their perceived association between the conditioned stimulus (tone) and unconditioned stimulus (footshock).

      BDNF infusions reduced freezing relative to controls, indicating that the extinction memory in these animals was strengthened.

    1. In the current study, the free rat was not simply empathically sensitive to another rat’s distress but acted intentionally to liberate a trapped conspecific.

      The latency to door opening as well as the likelihood of door opening to free a trapped cagemate were used as readouts for empathy. Based on these criteria the authors conclude that rats are capable of feeling empathy and will act on those feelings.

    2. the present study shows pro-social behavior accomplished by the deliberate action of a rat. Moreover, this behavior occurred in the absence of training or social reward, and even when in competition with highly palatable food.

      Here is a nice summary video of the authors' work, narrated by one of the authors, Dr. Peggy Mason.


    3. Like rats in the trapped condition, rats needed several days (5.8 ± 2.1) to learn to open the chocolate restrainer, which is evidence that door-opening was neither easy nor instinctual.

      Rats took about 6 days to learn to open the chocolate containing restrainer. In the earlier experiment with the trapped cagemate, the rats took about 7 days to open the restrainer.

      The length of time it takes for the rats to master this door-opening maneuver indicates that this action took some effort and didn't come naturally.

    4. These results show that the value of freeing a trapped cagemate is on par with that of accessing chocolate chips.

      Once rats learned to open the door, they were just as likely to open the door to the chocolate-containing restrainer as to the restrainer holding their cagemate.

    5. Thus, rats opened the door of a cagemate-containing restrainer but not of an empty restrainer, indicating that the expectation of social contact is not necessary for eliciting pro-social behavior.

      The helper rats' motivation to set their trapped cagemates free does not depend on social contact with their freed cagemates.

      This is evidenced by the fact that helper rats freed their trapped cagemates even when there was no possibility of interaction after freeing.

    6. This demonstrates that individual trait differences may factor into the expression of pro-social behavior.

      Rats that showed bolder traits may be more likely to act to help their fellow rat. The second panel of figure S1 shows this. However, although a trend is there, it did not reach statistical significance. http://www.sciencemag.org/content/suppl/2011/12/07/334.6061.1427.DC1/Bartal.SOM.pdf

    7. Animals who became openers had lower approach latencies than nonopeners (P < 0.01, t test), suggesting that successful opening behavior correlates with boldness scores (fig. S1)

      The rats that displayed more boldness, (as measured by a shorter time to emerge from a half-opened cage) were the ones who freed their cagemates.


    8. female rats in the trapped condition opened the restrainer door at a shorter latency than males

      When their cagemate was trapped in the restrainer, female rats moved around the arena faster than males and also opened the door of their trapped cagemates quicker than males.

    9. These data suggest that trapped rats were indeed stressed

      The trapped rats emitted ultrasonic alarm calls, which is a measure of stress in rats.

    10. Thus, rats were motivated to move and act specifically in the presence of a trapped cagemate

      Rats in an arena with a trapped cagemate:

      A. moved more frequently around the arena

      B. moved faster around the arena

      C. spent a longer time in the arena center near the<br> restrainer

      D. moved more after the restrainer was opened and the previously confined rat was freed

      All these findings point toward the movement and activity of the free rat being linked to the presence of a rat in the restrainer.

  2. Aug 2016
    1. rats free their cagemate in order to end distress, either their own or that of the trapped rat, that is associated with the circumstances of the trapped cagemate.

      The authors rule out the alarm calls as an indicator of stress and the source for door opening.

      QUESTION: What other criteria could the trapped rat use to communicate its distress to the helper rat?

    2. demonstrating that door-opening was the expected outcome of a deliberate, goal-directed action.

      The amount of time the helper rat remained frozen after door opening significantly decreased by day 6.

      This suggests the helper rat expected the door to fall as a result of its action.

    3. suggesting that the liberation of a trapped cagemate

      The free rat moved around much more quickly after the door opening that freed the trapped rat. The authors interpret this increase in activity as an indication of the importance of the freeing event in the mind of the rescuing rat.

    1. Our work suggests that the majority of ivory in large seizures since 2006 was poached in just two key areas

      Since 2006, most ivory poaching occurred in just two key areas.

    2. All but one of the 28 large ivory seizures (96%) that we assigned were geographically concentrated in a total of four areas, and seizures made after 2007 were concentrated in just two areas

      Poaching activity is highest in a few key regions.

  3. Jul 2016
    1. We found that honeybees were deterred from drinking sucrose solutions containing caffeine at concentrations greater than 1 mM

      The authors offered sugar solutions containing increasing amounts of caffeine to honeybees. They found that the honeybees preferred not to drink the sugar solutions containing higher amounts of caffeine. At caffeine concentrations greater than 1 mM, the sugar solutions were too bitter for the honeybees.

      As shown in Figure 1, the amounts of caffeine in the nectar of the plants tested were lower than this amount, indicating that the honeybees would have had no problem drinking their nectar.

    1. Males carried only this single allele, as expected, whereas females in addition possessed a band corresponding to the size of the wild-type y locus (Fig. 2D, lane 4), which varied in intensity between individuals, indicating that females were mosaic for MCR conversion.

      From their PCR genotyping experiment, the authors confirmed that F1 male MCR flies only had DNA bands from the PCR reactions that amplify the MCR insertion. F1 females had bands in all reactions, indicating that some females had one wildtype copy of the y+ allele and one MCR target copy.

      From this result, the authors concluded that these females were mosaic.

    2. we are also keenly aware of the substantial risks associated with this highly invasive method

      Because their strategy is so efficient and powerful, many people are raising concerns about whether or not such a tool should be used. It is a hotly debated issue as to whether or not this strategy should be used for research on human tissues in the future.

      Additionally, can you imagine what the consequences would be if a research animal carrying an MCR mutation were to accidentally be released into the environment? Essentially 100% of the offspring of that animal would have that mutation, and it would propagate rapidly through the native population.

    3. These infrequent examples of imperfect y-MCR transmission indicate that although HDR is highly efficient at this locus in both somatic and germline lineages, the target occasionally evades conversion.

      Although the authors found a strikingly high frequency of entirely y- flies (indicating that the MCR had been successful), they saw a few rare cases in which the flies were only partially y-. This suggests that the CRISPR-Cas9 MCR strategy doesn't work 100% of the time. Sometimes, the CRISPR gRNA doesn't successfully direct the Cas9 protein to the target region of the DNA.

      Another potential explanation for the wild-type appearance of some flies is that the non-MCR allele was mutated in a way that made it impossible for the MCR allele to direct it's mutation.

    4. All but one of their F2 female progeny had a full-bodied y– phenotype

      Based on Mendelian inheritance rules, you would predict that a cross between a y- male and a wildtype female (as diagrammed in Figure 2A) would generate all brown progeny; females would inherit one recessive allele from their father and one wildtype allele from their mother, while males would inherit one widltype allele from their mother. But the authors found that nearly all of the female progeny were yellow!

      For this to happen, the mutated allele the females inherited from their father subsequently mutated the wildtype allele they obtained from their mother, giving them two copies of a mutated allele and a yellow color. This is further support that the mutagenic chain reaction was successful.

    1. Our results show that when measles was common, MV infections could have been implicated in as many as half of all childhood deaths from infectious disease, thus accounting for nearly all of the interannual fluctuations in childhood infectious disease deaths.

      When all conclusions are put together the authors found that the immune-amnesia resulting from measles virus infections could be indirectly responsible for up to half of all childhood deaths from infectious disease.

      The authors determined this using statistics and found that when all of the deaths associated with the measles immune-amnesia lasting for 2-3 years were removed, then the overall rate of non-measles infectious disease deaths was calculated to be only half the rate of deaths measured without 'controlling' for the effects of measles.

    1. One key insight from the data is that incapacitation alone—the mechanical reduction in free time during the summer—cannot explain the program’s success

      This study makes it clear that summer jobs do not reduce violent activity because jobs keep youth occupied.

      If this was true, then rates of violence would be expected to return to normal rates soon after the program ends.

      However, violent activity continues to drop during the 13 months after the summer jobs program ends.

    2. Other interventions that target these skills

      So if social-emotional learning is capable of reducing violence when it's not part of a summer jobs program, how can we understand why it did not provide even more of an influence in this study?

      The author suggests that even without the formality of social-emotional learning curriculum, these skills were still taught on the job, perhaps through the job mentors.

      Another idea the author presents is that the act of working helps youth develop better skills for handing conflict.

    3. There are, however, other possible reasons why this study finds larger effects than previous work.

      An important part of interpreting results from data is to consider what other possible explanations might exist. This study concludes that summer jobs have a significant effect on reducing violent crime arrests and that this effect could be attributable to the preventative nature of the program.

      Other explanations for why this summer jobs program might reduce violent activity include consideration of the mentorship provided in this program. Mentorship is unique to this program and has not been part of previous jobs programs.

      Another possible explanation might be how crime was measured. This study considered crimes by type. Previous studies have only measured crime as a generic category. Because of that kind of measurement, those studies might have been constrained in their ability to detect an effect.

    4. The current study demonstrates that when offered to youth still in school, an intervention need not be lengthy to change behavior; an 8-week summer jobs program reduces violence among an adolescent population living in some of the most violent neighborhoods in the country.

      The contribution of this study is to show how a relatively short jobs program can have a substantial and significant effect on youth violent crime behavior.

      Previous studies have focused on more long-term jobs programs that are very costly to implement. These previous studies have also been implemented in a remediating manner.

      This study, by contrast, operates in a preventative manner. It shows how short and preventative oriented jobs programs can have a significant effect on reducing rates of violent crime among young adults.

    5. During the following 13 months (excluding the program period), treatment reduces the number of violent-crime arrests by –0.035 (P = 0.03, control mean = 0.08).

      One of the hypotheses about why summer jobs can reduce violent activity (the "incapacitation effect) is youth lack the time or opportunity to engage in violence.

      If this was the case we would expect to see that arrest rates for violent crime would occur during and most immediately after the summer jobs program. The researcher tests this hypothesis and finds that the 13 months after the summer program has concluded have an effect on violence.

      This suggests that the incapacitation effect is not at work in this study.

    6. Instead, it appears that both groups of youth experienced very similar drops in violence

      This study is testing whether or not replacing some work hours with social-emotional learning has a different effect on violent behavior than the effect of only participating in a jobs program.

      The findings show that there is no statistically significant difference between the groups who only participated in the summer jobs program and those who participated in both the summer jobs program and the social-emotional learning.

  4. Jun 2016
    1. These cultures were reacted under live conditions with antibody to Prod 1, and ∼70% of the cells were specifically stained on their cell surface

      About 70% of the cells extracted from the limb blastema had Prod1 expressed on the cell surface. This is an interesting finding showing exactly how many cells would be under the influence of nAG in the living organism.

    2. skeletal muscle on its innervation (28) was not satisfied by substituting nAG

      Skeletal muscle, like limb regeneration itself, is dependent on a nerve being present. When the authors rescue the denervated limb with nAG they don't see normal muscle regeneration.

      They conclude that nAG alone is not sufficient to regenerate the muscle tissue. So although nAG can regenerate the limb structure, it does not necessarily create it exactly as in an innervated limb.

    3. This result also indicates that nAG did not rescue the denervated blastema by enhancing the rate of nerve regeneration

      This shows that nAG likely has no effect on the nerve itself, instead it has its effect by some other means. Not by simply making the nerve regenerate, which would go on to allow the limb regenerate.

    4. red fluorescent protein (RFP) was strongly expressed in about 30 to 50% of the mesenchymal cells in this region (Fig. 4A) and persisted for up to 3 weeks

      This was an important experiment to show. Focal point electroporation is by no means a 100% successful procedure. Some cells in that region will just simply not pick up the exogenous DNA.

      Here the authors conclude that 30%–50% of cells in the region appear to take in the plasmid DNA. This information can help "temper" our expectations when looking at future data in their paper that use this technique. This may help explain variable results.

      Furthermore, the authors show that expression of red fluorescent protein (RFP) lasts 3 weeks. This is important because this demonstrates that RFP is turned on for a long period of time and does not get shut off within minutes, hours, or days. If this were the case, one would expect much different results.

    5. nAG protein is expressed in the key niche tissues early in regeneration and that expression in both locations is abrogated by denervation.

      The authors showed that when the nerve was removed and the limb amputated, there was very little nAG present compared with the amputated limb with intact nerves.

      This correlation between the presence of the nerve versus nAG presence suggests that nAG may be a molecule necessary for limb regeneration. Further follow-up studies needed to be performed to help support this idea.

    6. Epitope-tagged versions of bacterially expressed nAG and Prod 1 were found to complex together in a standard pull-down assay

      The authors demonstrated that Prod1 and nAG do in fact bind to each other. This is a major conclusion of their paper and is an important first study.

      For the authors' background and follow-up experiments to make sense, these data needed to be shown first.

    7. wo secreted proteins were identified as positives from the screen and subsequent control experiments

      Using yeast two-hybrid screening the authors determine that there are two secreted proteins that could potentially bind to Prod1.

      Because the yeast two-hybrid screens can sometime give false positives, the authors followed up with experiments to confirm this in later panels of figure 1.

      What is the significance of finding a secreted protein that binds two Prod1? Remember, where exactly do we find Prod1 in the cell? Why would a cytoplasmic protein probably be a false positive?

    8. It is induced after amputation as axons regenerate along the nerve sheath, and then appears in the wound epidermis. The expression in both locations is abrogated by denervation. Most notably, the expression of this protein can rescue the denervated limb blastema and support regeneration to the digit stage.

      Many papers that are limited in word count, such as the ones in Science and Nature, often cut to the chase and state their major conclusions at the end of the introduction or background section. This acts as a "hook" for readers to look at the data supporting these claims.

    1. Although p53 mutations provide cells with a selective growth advantage, such mutations burden them with a significant checkpoint deficit; they cannot respond normally to DNA-damaging agents and enter mitosis and subsequently replicate their genomes in the presence of DNA damage

      This paper had important implications for cancer treatment. p53 is required to stop the cell cycle and allow cells to repair DNA damage. Many cancer cells have mutated versions of p53 that are unable to activate this cell cycle arrest. As a result, DNA damage that normally causes cells to arrest and fix the damage may be ignored in cancer cells.

      Therefore, if we treat a patient with DNA-damaging agents, their normal cells will stop dividing and repair the damage, but the cancer cells will keep going. DNA replication or cell division in the presence of major DNA damage can be lethal to the cell. So, in theory, the treatment selectively kills only cancer cells.

      Unfortunately, though, it is not that simple. In practice, such drugs have many effects on both normal cells and cancer cells, beyond the ones that impact the cell cycle.

    2. In contrast, neither p53 nor p21 appears to play a major role in the spindle checkpoint because p53−/− and p21−/− cells respond normally to microtubule disruption

      Another checkpoint in the cell cycle occurs during mitosis. This checkpoint prevents division until all chromosomes are correctly attached to the mitotic spindle, a network of microtubules that pull sister chromatids to opposite sides of the cell.

      When cells are treated with nocodazole, which prevents chromatid attachment, they arrest at the spindle checkpoint. The authors conclude that the two proteins do not play a role at this checkpoint, because cells that lack p53 or p21 still arrest when the attachment is disrupted by nocodazole.

    3. These results demonstrate that induced expression of p21 and p53 is essential to sustain the G2 checkpoint after DNA damage in human cells

      The authors have conclusively shown that p53 and p21 are important regulators at the G2-M checkpoint. Previously, these proteins were thought to only play an important regulatory role at the G1-S checkpoint.

    4. Again, the parental cells entered a sustained G2 arrest while a substantial fraction of both p21- and p53-deficient fibroblasts escaped G2 and entered mitosis

      The parental cells are those that did not have disrupted p53 or p21 genes. It was important that the authors used the same cell line as a control because different cell lines have different features that could influence the studied effect.

      This result supported the conclusion that p53 and p21 are important in preventing cells from entering mitosis in the presence of DNA damage.

    5. Thus, although G2 arrest was initiated after irradiation in all cells tested, this arrest was not sustained in the absence of functional p53 (Figs. 1 and 2E)

      The authors conclude that the absence of functional p53 allows cells to eventually enter mitosis (M phase) despite DNA damage. Although the authors observed a brief arrest in cells with mutant p53, the arrest was only temporary, and the cells eventually progressed to M phase.

    6. These experiments suggested that p53 controls a G2checkpoint that prevents entry into mitosis after DNA damage

      Because the p53 mutant cells were progressing into mitosis when they shouldn't be, the researchers concluded that in cells with intact p53 genes, p53 must be responsible for preventing mitotic entry in the presence of DNA damage.

    1. Our results provide evidence that primitive myeloid precursors give rise to microglia residing in the adult CNS in the steady state

      Microglia observed in the adult brain under nonpathological conditions trace their origin to yolk sac macrophages.

    2. Altogether, these data suggest minimal, if any, contribution of definitive hematopoiesis to the development of adult microglia

      In contrast to previous reports that relied on bone marrow irradiation that created experimental artifacts, this study showed that the pool of brain microglia arises from the yolk sac macrophages and is not replenished by circulating blood cells in an adult organism.

    3. Altogether, these results suggest that Runx1+ progenitors migrate from the yolk sac into the brain through blood vessels between E8.5 and E9.5.

      The influx of yolk sac macrophages into the brain occurs between embryonic days 8.5 and 9.5.

    4. Brain-infiltrating cells appeared only when blood circulation developed

      This indicated that yolk sac progenitors infiltrate the brain via a developed and functional vascular network.

    5. In contrast, less than 3% of blood circulating and tissue macrophages—including dermal and lung macrophages, as well as circulating T cells, B cells, and granulocytes—were eYFP+ in these mice (Fig. 3E and figs. S8 and S9)

      This indicates that blood cells such as granulocytes and lymphocytes, as well as others tissue macrophages, do not arise from the same Runx1 yolk sac progenitors as microglia.

    6. The partial labeling of Runx1+ yolk sac cells is inherent to in vivo labeling techniques and likely results from the insufficient expression of MER-Cre-MER and limited availability of the ligand in target cells

      The partial labeling would explain about 60% of F4/80-positive cells not expressing YFP (Figure 3, panel A: brain rudiment).

    7. suggesting that microglia homeostasis was not perturbed in Runx1Cre/wt embryos

      This indicated that the obtained results could not be attributed to the confounding effect of the genetic model used by the authors.

    8. IL-34 in the regulation of microglial homeostasis and with the increased severity of the microglial phenotype in Csf-1r−/− compared with Csf-1op/op mice.

      Although microglia do not form in mice lacking a CSF-1 receptor, they are present in mice with a mutation in the CSF-1 gene that codes for the ligand.

      As it turns out, presence of another ligand IL-34 (cytokine interleukin 34) is sufficient to activate CSF-1R on microglial cells to compensate for the loss of CSF-1. In contrast, some tissue macrophages fail to form in mice with a mutated ligand.

    9. All together, these results suggest that the development of yolk sac macrophages and microglia, but not monocytes, is strongly dependent on CSF-1R

      CSF-1R is required for the development of yolk sac macrophages and microglia.

    10. Consistent with a requirement for CSF-1R expression, absence of CSF-1R greatly reduced the development of microglia (Fig. 2B and fig. S6A) and yolk sac macrophages (Fig. 2C and fig. S6B), whereas circulating monocytes were present in these mice (fig. S6, C and D)

      Both yolk sac macrophages and microglia depend on the presence of CSF-1R receptor on their surface for their differentiation. Absence of this receptor did not affect development of circulating monocytes.

      This suggests that CSF-1R expression is not essential for monocyte differentiation outside the central nervous system (CNS).

      However, it does not exclude the possibility that monocytes require CSF-1R after they enter the CNS and could serve as microglial precursors.

    11. The phenotype of microglial cells resembled that of yolk sac macrophages throughout embryonic development

      Similarity in phenotype between two cell types suggests they have common origin.

    1. opening new therapeutic strategies for treating age-related neurodegenerative conditions.

      The possibility of introducing systemic factors present in young blood to remodel vasculature and increase neurogenesis is an exciting prospect for many neurodegenerative disorders.

      Treatment with GDF11, along with other key factors, may be able to reverse numerous detrimental effects associated with the decline of neural activity.

    2. In conclusion, circulating factors, specifically including GDF11, have diverse positive effects in aging mice, including enhancing neurogenesis.

      GDF11, is a key systemic factor that contributes to neurogenesis and declines with increased age. However, exposing this circulating factor in old mice improves vascular remodeling and increases neural stem cell populations.

    3. Analysis of these brains excluded any detectable contribution of young circulating endothelial progenitors to the vascular remodeling in Het-O animals

      The young mice were transgenic for green fluorescent protein, so all the cells of the young mice were green. The authors didn't see any green blood vessels in the old mice, meaning that the endothelial progenitor cells didn't travel from the young mice to the old.

    4. These results suggest that Het-O mice have a higher olfactory discrimination than do the Iso-O mice

      Because heterochronic old (Het-O) mice and isochronic young mice indicated similar levels of high smell sensitivity in the olfaction assay, this indicates that Het-O mice have increased functional olfaction due to being exposed to young systemic factors.

    5. Collectively, these data demonstrate that youthful circulating factors can restore the self-renewal and differentiation potential of aged SVZ stem cells, and this effect can persist for some time after isolation from the mouse brain.

      Exposure of old mice to young systemic factors restores the neurogenic potential of neural stem cells and increases their ability to proliferate and differentiate into neurons in the olfactory bulb.

  5. May 2016
    1. This loss of mechanical performance is because most natural and engineered cellular solids with random porosity, particularly at relative densities less than 0.1%, exhibit a quadratic or stronger scaling relationship between Young’s modulus and density as well as between strength and density

      The elastic properties of cellular materials with random porosity degrade when the density decreases. This is because of a nonlinear relationship between strength and density.

      That is why, in this paper, the authors proposed materials with a linear relationship, which maintain mechanical performance for a broad range of densities.

    2. We have shown that these high mechanical efficiencies are possible across a range of constituent materials. Fabricating ordered lattice structures at these length scales brings them into the regime in which it becomes possible to design microstructured functional materials with superior bulk-scale properties.

      In this paper, the authors presented a new class of materials based on a specific microlattice.

      These materials exhibit interesting mechanical properties for a range of constituent materials and densities.

      That made them suitable for a wide range of applications.

    3. By contrast, our Ni-P stretch-dominated metallic lattice is not only much stiffer in the same density range, its specific stiffness stays nearly constant, measured as 1.8 × 106 m2/s2 and 2.1 × 106 m2/s2 at densities of 14 mg/cm3 and 40 mg/cm3, respectively.

      Unlike previously developed materials, the proposed new materials present a higher specific stiffness (stiffness per unit of mass density), which remains nearly constant.

    4. In the ultralow-density regime (relative density <0.1%), we observed markedly different compression behavior in hollow-tube ALD ceramic octet-truss microlattices relative to solid ceramic lattices at higher relative densities

      The elastic behavior of the materials, for the ultralow densities, depends on the fabrication process: Hollow-tube microlattices and solid ceramic lattices present different responses to a compression load.

      The marked difference is a result of nanoscale wall thickness in microscale hollow tubes as apposed to solid microscale struts in higher density samples.

    5. These octet-truss lattice materials are highly isotropic, so the scaling of stiffness with density does not vary with the orientation of the lattice

      The developed materials also present the valuable specificity of being isotropic.

    6. The stretch-dominated microlattices populate the highly desirable ultralight, ultrastiff space toward the upper left of the chart (17) and have stiffness-to-weight ratios that do not substantially degrade as density decreases by several orders of magnitude

      The structures created by the authors present two interesting properties: They are both ultralight and ultrastiff, and the stiffness-to-weight ratio is not strongly affected by the density.

    7. we observed typical viscoelastic behavior for the polymer microlattices with pronounced

      A viscoelastic behavior is an intermediate between a purely elastic behavior (like a spring) and a purely viscous behavior (like an absorber).

      Polymers are known to exhibit a viscoelastic behavior, and the authors actually observed this phenomenon in the microlattices they produced.

    8. We found that these materials exhibit ultrastiff properties across more than three orders of magnitude in density, regardless of the constituent material.

      The authors designed and characterized a new category of light structures presenting ultrastiff properties for a wide range of densities and for different materials.

    1. Interactions between neutrophils and platelets within the microvasculature of infarcted brains were inhibited by blocking PSGL-1 (Fig. 4E and fig. S19), and this correlated with significant reductions in infarct volumes when PSGL-1 was inhibited or in the absence of Mac-1 (Fig. 4F).

      These experiments conclude that even in the brain, interactions between neutrophils and platelets is mediated by PSGL-1.

    2. Deficiency in either receptor or inhibition of PSGL-1 also prevented hepatic damage during endotoxemia (Fig. 4D and fig. S15B). Consistent with previous reports (20, 21), we detected elevations in the plasma levels of neutrophil-derived extracellular traps (NETs) during ALI and sepsis. These elevations were completely blunted when platelets were depleted, by blocking PSGL-1, or in the absence of Mac-1 (fig. S17), suggesting that other forms of neutrophil activation can be triggered upon platelet interactions through PSGL-1.

      The authors examine other tissues to show that wherever they observe neutrophil-mediated inflammation it is regulated by PSGL-1. Also, functions of neutrophils (such as formation of extracellular traps that can bind pathogen) are also regulated by PSGL-1.

    3. interactions at the uropod critically contribute to vascular injury

      These experiments provided evidence that interactions of neutrophils with platelets occurs via PSGL-1 and in its absence, recruitment of neutrophils to tissue decreases, and thus inflammation induced because of neutrophils decreases.

    4. a model of endotoxemia

      The authors used another model of pathogenic inflammation. They injected a higher dose of LPS into the blood stream to induce endotoxemia (toxins in the blood). This can lead to sepsis because of drastic activation of the immune system.

    5. ALI-induced mice confirmed the findings

      The authors confirmed the results obtained earlier with TNF-a–induced inflammation was consistent even during pathogenic inflammation, such as ALI.

    6. orchestrating the appropriate distribution of adhesive and chemotactic receptors

      The authors reach this conclusion because the original localization of the chemotactic receptor (CXCR2) and adhesive receptor (MAC-1) is disturbed in PSGL-1–deficient mice.

    7. indicating that these receptors function along the same pathway

      Previously, the authors described that neutrophils from Mac-1–deficient mice and PSGL-1–deficient mice show reduced crawling.

      However, inhibiting PSGL-1 in Mac-1–deficient mice (these neutrophils are now deficient in both) did not result in an additive reduction in crawling. This might be possible if signaling through these receptors leads to the same pathway downstream.

    8. polarization of a signaling-competent PSGL-1 drives the intravascular migration of neutrophils.

      Without intact signaling through PSGL-1, neutrophils were unable to migrate into the blood vessels. The loss of signaling through PSGL-1, however, did not affect the polarization of neutrophils.

    9. Impaired polarization in these mutants compromised interactions between neutrophils and circulating platelets (fig. S8C), and neutrophils in these mice displayed severely impaired crawling kinetics

      Because of lack of Cdc-42, neutrophils were not able to interact with platelets and their crawling ability was affected.

    10. neutrophils recruited to inflamed vessels extend a PSGL-1–bearing microdomain into the vessel lumen that scans for activated platelets present in the bloodstream through P-selectin

      The authors were able to conclude that the interaction between neutrophils and platelets occurred because of recognition of PSGL-1 on neutrophils and P-selectin on platelets.

    11. As a consequence, the luminal space of inflamed venules was populated by multiple PSGL-1–bearing clusters suitably positioned to interact with circulating cells

      The PSGL-1–bearing end of the neutrophils were in a way poking through the blood vessel wall into the inside of the vessel (luminal space). This positioned the cells in an ideal way to interact with cells in circulations (flowing through the blood vessel).

    12. active structural dynamics within this region

      Rac GTPases are known to be involved in cell motility and cytoskeletal dynamics in a cells. Thus, regions where they observe Dock-2 fluorescence would suggest "active structural dynamics."

    13. uropod underwent continuous collisions with circulating platelets, a fraction of which established measurable interactions that were usually transient

      Through IVM the authors observed that the uropod of neutrophils was constantly bumping with the platelets and some of these collisions lasted long enough for them to measure.

    1. A greater proportion of female rats (6/6) than male rats (17/24) in the trapped condition became door-openers (P < 0.05, χ-square),

      ERRATUM: actually no difference between the sexes. See Volume 335 page 401

    2. In the trapped condition, the proportion of rats that opened the door increased (Fig. 2A), and the latency to door-opening decreased (Fig. 2B and movie S2) across sessions, which is evidence of learning.
    1. possibly by means of cyclic SWS-REM periods

      Throughout the night, sleepers experience many periods of slow-wave sleep and rapid-eye-movement sleep. The authors suggest that this cycle of SWS-REM-SWS-REM throughout the night may importantly contribute to consolidation (the transformation of memories to stable storage).

    2. We found that only SWS × REM sleep duration consistently predicted cueing-specific bias reduction at 1 week relative to baseline

      The authors found that the amount of time participants spent in slow-wave sleep and rapid-eye-movement sleep combined was related to how much less biased participants were one week after training.

      From this result the authors conclude that sleep in particular was necessary for the bias reduction to last.

    3. When compared with baseline (Fig. 1F), cued biases were weaker after 1 week [t(37) = 2.203, P = 0.034], whereas uncued biases were not [t(37) = 0.524,P = 0.603], although the interaction was not significant (F1,37 = 0.471, P = 0.497).

      The authors found that compared to initial bias scores, bias scores one week later for the cued counterbias training were significantly less biased than for the uncued counterbias training.

      From this result the authors conclude that without cueing, bias returned to pre-study levels while cueing the training during sleep resulted in a sustained bias reduction one week later.

    4. Implicit biases were measured again after 1 week, revealing that the differential bias reduction endured

      The authors found that 1 week after the counterbias training and nap, participants continued to show reduced bias for the training that was cued during sleep. The uncued training, however, showed a significant increase in bias over the week back to baseline-levels.

      From this result the authors conclude that cueing the counterbias training during sleep results in a lasting reduction in bias.

    5. the magnitude of which was associated with time in slow-wave and rapid-eye-movement sleep after training

      The more time participants spent in different kinds of sleep (i.e. slow-wave sleep and rapid-eye-movement sleep), the smaller their bias.

      This finding suggests that the type of sleep specifically affected the training rather than simply the passage of time or some other factor.

    1. plants secure pollinator fidelity and improve reproductive success

      That is, the plants use caffeinated nectar to make sure that pollinators keep returning back to them instead of going to other plants. This makes it more likely that their pollen and ovules will be used to produce new plants, and thus that their genes will be passed on to the next generation.

    2. Our data show that plant-produced alkaloids like caffeine have a role in addition to defense: They can pharmacologically manipulate a pollinator's behavior.

      Chemicals like caffeine have traditionally been recognized as defense mechanisms for plants; if a predator eats too much of that plant, they will overdose on the chemical and get ill or die. Thus, the chemical acts as a deterrent against predation.

      However, the authors of this study have now identified another role for caffeine, and maybe for other chemicals like it. These chemicals can change the behavior of their insect pollinators to the plants' advantage.

      In this case, caffeine helped the insects remember that plant, thus causing them to return to it and increase the chances that its pollen will be brought to female reproductive structures. This increases the plant's fitness by increasing the chances that its genes will be passed on to the next generation.

    3. by affecting a pollinator's memory, plants reap the reproductive benefits arising from enhanced pollinator fidelity

      That is, by helping pollinators remember that specific plant, it makes it more likely that the pollinator will return to it and transport its pollen to female reproductive structures. This helps the plant reproduce more often.

    4. they are more likely to visit flowers bearing the same scent signals

      As shown in Figure 2. Bees were more likely to remember an odor presented to them while they fed on sugar and caffeine than if they were fed sucrose alone.

    5. vegetative and seed tissues of Coffea

      That is, in the seeds, stems, leaves, etc. of the plant.

      Remember that in this study, the authors were only assessing the importance of nectar caffeine concentrations in altering honeybee behavior.

    6. This implies that pollinators drive selection toward concentrations of caffeine that are not repellent but still pharmacologically active.

      In other words, certain concentrations of caffeine help pollinators remember a plant's scent, and so the pollinators return to them. Those plants are therefore more likely to reproduce and generate many offspring with similar concentrations of caffeine in their nectar.

      However, other plants with very high or very low levels of caffeine are less likely to have pollinators return to them. High amounts of caffeine are bitter and repellant to bees, whereas low amounts aren't as effective at stimulating scent memory. As a result, those plants will be less successful at reproducing, and won't generate as many offspring with very high or very low concentrations of caffeine in their nectar.

      This means that over time, the population as a whole will have concentrations of caffeine in their nectar that are sufficient to have an effect on pollinator behavior, without being so high as to drive the pollinators away.

      Thus, the pollinators have "driven selection" toward a specific range of nectar caffeine concentrations by specifically helping plants within that range produce more offspring than those outside it.

    1. However, individuals at conservative organizations expressed significantly less intense facial action in the muscles around the eyes that indicate genuine feelings of happiness [AU6; liberals M = 1.78, SD = 1.43; conservatives M = 1.50, SD = 1.38; t(455) = 2.14, d = 0.20, P = 0.033; controlling for gender and ethnicity: β = –0.09, P = 0.051]. We also found that the proportion of individuals displaying non-Duchenne smiles was significantly higher at conservative organizations (n = 41 of 217, or 18.89%) than at liberal organizations (n = 24 of 240, or 10.00%; χ2 = 7.39, P = 0.007; controlling for demographics: OR = 2.35, P = 0.003).

      Like in Study 2, conservatives, compared with liberals, were likely to display less intense activation of the muscles around the eyes (the orbicularis oculi muscle), indicating a less intense/genuine smile.

      Conservatives in this study were also more likely than liberals to not use those eye muscles at all (i.e., to display "insincere" or "non-Duchenne" smiles).

      In Study 2, if you remember, this difference in likelihood of displaying non-Duchenne smiles was not statistically significant.

    1. Understanding the controls on these pathways of DOC fate, and incorporating photochemical processing into models, will improve predictions of how the arctic C cycle will respond to and perhaps amplify

      Climate change could increase the importance of sunlight-driven degradation of dissolved organic carbon (DOC)—both by releasing carbon that has been frozen in soils for years and by increasing the amount of time with no ice on the water surface.

      If more DOC is processed into carbon dioxide, climate change could become more extreme.

    2. At present, our data show that for the entire Kuparuk basin 55% of the DOC processed in the water column of aquatic ecosystems is completely oxidized to CO2, and 45% is partially oxidized and transported downstream in the DOC pool

      To summarize, the authors found that 55% of organic carbon in arctic waters is broken down into carbon dioxide by either sunlight or microbes, while the other 45% is only partially broken down. (So it is still a form of dissolved organic carbon.)

    3. the fate of DOC varied consistently by water type. In small streams, DOC was mainly mineralized by sunlight to CO2, whereas in lakes the main fate of DOC was partial photo-oxidation (Table 1 and Fig. 2). Large rivers were intermediate between these end members, and photomineralization to CO2 was about equal to or less than partial photo-oxidation (Table 1 and Fig. 2). We suggest that this pattern is a result of light exposure history

      The authors found that dissolved organic carbon (DOC) degrades differently depending on the type of water it is in.

      The authors offer this possible explanation: When carbon dissolves out of the soil, it is most likely to enter a small stream first, then a larger river, then a lake.

      DOC is degraded by light most easily when it is "new" and has not been exposed to light before (e.g., if it was previously buried in the soil).

      DOC in small streams is "newest," so photodegradation is more important in small streams than in lakes or rivers.

    4. Results for the open-water period highlight the day-to-day variability in available UV radiation

      Variability in daily weather and the decrease in sunlight over the course of the summer had a large effect on the rate of sunlight-driven dissolved organic carbon degradation.

    5. which suggests that sunlight controls the fate of DOC in arctic surface waters.

      The amount of organic carbon broken down or partially broken down by sunlight was between three and 19 times larger than the amount broken down by bacteria when not exposed to sunlight.

      Based on this observation, the authors conclude that sunlight controls the break down of organic carbon in streams, lakes, and rivers.

      This is different from what scientists previously thought.

    1. Elevated loss due to storm damage is indicated for a few areas

      Hansen and colleagues verify the changes in forest cover that they saw in the Landsat images by exploring news on natural disturbances.

      In this case, they found that drastic and instantaneous reductions in forest cover in southern Sweden in 2005 and southwestern France in 2009 were caused by cyclones.

    2. Of all countries globally, Brazil exhibited the largest decline in annual forest loss

      Brazil has historically had high rates of deforestation (e.g., cutting down the Amazon rainforest for agriculture and logging), however Hansen and colleagues show that this rate is steadily decreasing. Read on to find out why!

      On the other side of things, Indonesia is steadily increasing the amount of forest that is cut down each year. Why might this be the case? Check out reference #23 for some potential explanations!

    3. A total of 2.3 million km2 of forest were lost

      How much is 2.3 million square kilometers of land? For perspective, Alaska is the largest state in the United States and it is 1.7 million square kilometers.

      Texas is the second largest state and it is 0.7 million square kilometers. Thus, imagine adding both Alaska and Texas together, and that is roughly how much forest was lost from 2000 to 2012.

      Now, how much forest was gained in that same time? If you add the area of Texas to Kentucky (0.1 million square kilometers and the 37th largest state), you roughly have 0.8 million square kilometers.

    4. Results are depicted in Fig. 1

      Hansen and colleagues use Landsat data to evaluate changes in forest cover from 2000 to 2012. How do they communicate this information? Are these maps informative? Why or why not?

    1. nAG has no role in specifying that identity but rather acts through Prod 1 to promote cell division

      The authors don't believe that nAG has any effect on specifying tissues. In other words, it does not tell a stem cell to become bone or neurons or skin.

      Instead, nAG has its effect simply by increasing the number of dividing cells.

    2. This evidence supports the view that nAG can rescue the denervated blastema by acting directly on blastemal cells to stimulate their proliferation and, therefore, that it mediates the nerve-dependent growth of the early regenerate.

      The evidence from this figure suggests that nAG is able to cause more blastemal cells to divide. The authors propose that this is how nAG works in the salamander.

      This gets at a possible mechanism for nAG's effect in the living organism and provides potential avenues for further study.

    1. The sulfate levels in the source and product waters are comparable in the 17 plants that do not use sulfate-containing coagulants

      In other words, when sulfate is not used as a coagulant, sulfate concentrations of the water coming into the treatment plants were similar to the sulfate concentrations of the water leaving the plants.

  6. Apr 2016
    1. The decline occurs largely after the 8-week intervention ends.

      By looking at the difference in violent behavior between youth who are involved in a summer jobs program and those who are not involved in a summer jobs program, this study finds that summer jobs do help reduce youth violence. Importantly, the reduction occurs after the summer jobs program ends.

    2. As such, the estimates here may considerably understate the number of violent crimes prevented (supplementary materials, section 2.9).

      Another consideration for the interpretation of these data is that analysis relies on arrest rates. Arrest rates only reflect a fraction of actual violent acts since many such acts are not reported and many do not result in an arrest.

    3. There is no treatment effect on days present (or other academic outcomes) during the following school year, with confidence intervals small enough to make changes in attendance an implausible cause of the drop in violence

      One of the possible explanations for why violent crime arrests drop consistently after the end of the jobs program is that time spent in school increases. Testing for this effect, however, shows that this is not likely.

    4. Although the study was not powered to detect heterogeneous treatment effects across subgroups, there is suggestive evidence that arrests fall more among youth at higher risk of violence

      Because of the way this study is designed, it is not possible to make the claim that arrest rates decline even more for youth who can be categorized as at higher risk for violent activity. However, findings from this study show that this might be likely. This would make for interesting future research.

    5. There are no significant changes in other types of arrests (39)

      Even though there was a reduction in the arrest rates for violent crimes, there are no statistically significant changes in the arrest rates for property, drug, or other kinds of crimes. This indicates that there is something unique about the relationship between the summer jobs program and violent crime.

    6. Violent-crime arrests among the treatment group decrease by 43% relative to the control group (0.0395 fewer arrests, or almost 4 fewer per 100 youth; P = 0.022).

      This is a significant finding of the study. When comparing violent crime arrests between the treatment group (summer jobs) and the control group (no summer jobs), there were 43% fewer arrests for the treatment group after they participated in this summer job program.

    1. results were robust to individual disease classes (table S1), with best-fit durations of immunomodulation predisposing to individual classes of infectious disease mortality lasting between 18 and 30 months (mean, 27 months; median, 24 months)

      Conclusion 4: When the analyses in this paper were repeated using non-measles deaths due to specific infectious diseases (i.e. pneumonia, bronchitis, diarrheal disease, etc...) the results were consistent with the primary analyses, which were performed by pooling all of the non-measles infectious disease death counts together.

    2. the corresponding prevalence of MV immunomodulation to the mortality data (SM 3), centered at a 28.3-month duration of measles-induced immunomodulation

      Conclusion 2 and 3: When the authors take into account that there is some extended duration to the measles induced immune-amnesia, they find that their math reveals an average 28.3 months duration. As explained above, this is because the prevalence of immune-amnesia had the strongest correlation with non-measles infectious disease mortality under the assumption that the immune-amnesia lasted for 28.3 months on average.

    3. These associations could reflect transient measles immune suppression.

      Conclusion 1 The authors observe a correlation in Europe and the United States between measles infections and overall mortality (death). These results meet their first hypothesis.

    1. leading edge of adherent neutrophils

      Blocking PSGL-1 did not affect the ability of neutrophils to adhere firmly to the blood vessels, but it affected the crawling.

      Thus, the authors take a guess that indirectly the PSGL-1 on the uropod, although not interacting with the endothelium, is somehow helping the neutrophils crawl.

    2. we observed numerous interactions of platelets

      The authors were able to see the neutrophils and platelets interacting with each other (in close proximity of these cells). Having labeled the CD62L with blue color, they were able to distinguish between the leading edge and the uropod.

  7. Mar 2016
    1. In summary, both genetic and molecular data reveal that the y-MCR element efficiently drives allelic conversion in somatic and germline lineages.

      Overall, the authors can conclude that their mutagenic chain reaction strategy is very efficient at driving mutations in both chromosomes simultaneously, creating a homozygous mutant.

    2. MCR technology should be applicable to different model systems and a broad array of situations, such as enabling mutant F1 screens in pioneer organisms, accelerating genetic manipulations and genome engineering, providing a potent gene drive system for delivery of transgenes in disease vector or pest populations, and potentially serving as a disease-specific delivery system for gene therapy strategies

      As the authors discuss, there are so many ways in which this MCR strategy could be used to speed up the creation of animal models for research or for potential therapeutic uses. It is certainly an exciting new tool for biomedical research and for clinical applications!

    3. From two independent F0 male (♂) × y+ female (♀) crosses and 7 F0♀ × y+♂ crosses, we recovered y– F1♀ progeny, which should not happen according to Mendelian inheritance of a recessive allele

      Among the F1 progeny (offspring from flies injected with the Mutagenic Chain Reaction construct mated to wildtype flies), the authors obtained females that were yellow (y-), meaning that they expressed two copies of the recessive yellow allele. This is not possible according to the Mendelian rules of inheritance, which predict that all females of this cross should be brown (they would inherit a y+ allele from the wildtype parent and since the y- allele is recessive, one is not sufficient to create the yellow color).

      The fact that the authors obtained yellow female flies means that their mutagenic chain reaction worked! The mutant allele these females inherited from the F0 parent subsequently mutated the wildtype allele they inherited from the wildtype parent, giving them two copies of the mutated allele.

    4. All had the precise expected HDR-driven insertion of the y-MCR element into the chromosomal y locus

      Their DNA sequencing experiment confirmed that all yellow flies from the F2 generation had insertion of the expected MCR construct, again confirming the success of the MCR targeting. The authors also DNA sequenced the y locus from flies that did not have the predicted yellow color. They found that these events likely resulted from failure of homology-directed repair to occur. Instead, it seems that the Cas9 cut the DNA, but non-homologous end joining occurred to repair the break, so the MCR construct could not be inserted.

      This YouTube video (starting at 3:18) describes the difference between homology-directed repair and non-homologous end-joining.


    1. The dominance of photochemical over biological C processing in the water column of arctic surface waters, relative to that of lower-latitude waters, is likely due to three reasons. First, the measured volumetric rates of dark bacterial respiration tend toward the low end of the range reported for fresh waters (17, 25–27), thereby elevating the relative importance of sunlight over bacteria in this study. Second, our apparent quantum yields were on the high end of the range measured in waters outside the Arctic (16, 28, 29)

      The amount of bacterial respiration measured by the authors was lower than in previous studies in other areas, and the reactivity of the dissolved organic carbon with sunlight was higher. Therefore, sunlight-driven degradation was more important in this study than in others that took place in other locations.

    2. compared to previous, similar measurements in relatively deep lakes of forested regions (14–17, 29), the shallow and unshaded surface waters in the Arctic essentially confine photoprocessing of DOC to a thin boundary layer that maximizes DOC exposure to sunlight and facilitates photochemical degradation (table S2 and fig. S3). Given these conditions, it is likely that photochemical DOC degradation is substantial in any shallow and unshaded inland surface water and plays an important role in freshwater carbon cycling.

      Because most of the surface water in the study area is shallow, and there is little shade, sunlight-driven dissolved organic carbon (DOC) degradation is more important than in deep lakes, streams, and forests. The authors suggest that photodegradation of DOC may also be important in other areas with shallow surface water and little shade.

    3. photochemical reactions accounted for 75% of the total of 6.11 Gg DOC-C year−1 processed in surface waters, of which 3.34 Gg C year−1 was released to the atmosphere as CO2 (~55% from photoreactions; Table 2).

      Final tally: Sunlight is responsible for 75% of dissolved organic carbon degradation and 55% of carbon dioxide production in the Kuparuk River basin.

    1. Intensive forestry practiced within subtropical forests resulted in the highest rates of forest change globally

      To clarify, subtropical forests changed the most in terms of gain and loss, yet when looking at all subtropical regions as a whole, there isn't a clear trend as there is for tropical forests.

      What might be causing these large changes in forest cover in the subtropics?

    2. The maps and statistics we present can be used as an initial reference for a number of countries lacking such data, as a spur to capacity building in the establishment of national-scale forest extent and change maps, and as a basis of comparison in evolving national monitoring methods.

      The authors' results and analyzed data are a great jumping off point for governments that want to better understand how their country's land is changing with time.

      These results can then be used to implement policies that manage or protect land where needed.

      To look at the maps of forest change data from Hansen and colleagues, click here.

    3. The tropics were the only climate domain to exhibit a trend, with forest loss increasing by 2101 square kilometers per year.

      When comparing across different climate domains (i.e., tropical, subtropical, temperate, or boreal), Hansen and colleagues found that only the tropics showed a clear change in the rate of forest loss during the time that they surveyed (2000–12).

      In this case, forests are decreasing rapidly in the tropics and in the next sentence we find out exactly where this decrease is taking place; mainly in Malaysia, Paraguay, Bolivia, Zambia, and Angola.

      Take a look at Google Maps to find the location of these countries.

    4. Subtropical forests experience extensive forestry land uses where forests are often treated as a crop and the presence of long-lived natural forests is comparatively rare (8). As a result, the highest proportional losses of forest cover and the lowest ratio of loss to gain (1.2 for >50% of tree cover) occurred in the subtropical climate domain.

      Many subtropical forests are treated like crops (e.g., corn, soybean). As such, the trees are cut down and harvested for timber and then replanted for the next harvest season.

      Thus, this climate domain experienced the most forest loss while also having the lowest ratio of loss to gain (because the trees that were harvested were subsequently replanted).

      To see an example of this, check out an article on forest landowners in Mississippi here.

    5. Russia has the most forest loss globally.

      Out of all countries, Russia lost the most forest cover from 2000 to 2012. Why do you think Russia has lost more forest cover than any other country?

      Look at this forest loss on this map (click on Forest Cover Loss 2000-2014).

    1. A bootstrapped mediation analysis revealed that, as hypothesized, self-deceptive enhancement fully mediated the ideology–life satisfaction association [indirect effect:b = 0.05, P < 0.001, 95% confidence interval (CI) = (0.03, 0.07)

      These results indicate that the relationship between political conservatism and life satisfaction can be statistically explained by self-deceptive enhancement.

      With this kind of mediation analysis, the effect is said to be significant when the 95% confidence interval (in this case, from 0.03 to 0.07) does not include zero within its range. See this website for some more information.

    2. Greater conservatism was associated with a small but significant decrease in positive affect word use (β = –0.16, P < 0.001). Conservatism was not significantly associated with the use of negative affect words, joviality-related words, or sadness-related words (Table 2).

      The results from this analysis indicate that, as political conservatism (according to voting record) increases, use of positive affect words decreases.

      There is no statistical relationship between political conservatism and use of negative affect words, joviality words, or sadness words.

      Critical thinking: Why do you think there was a relationship for positive affect, but not joviality?

    3. A key difference is that these previous accounts would predict happiness-related behavior to correspond with self-report evidence of greater conservative happiness. Our self-enhancement-based account explains this discrepancy.

      The authors point out that previous research would suggest that self-reported happiness should match behavioral indications of happiness; the fact that their studies show the opposite finding, they argue, can be explained through self-enhancement.

    4. Members of the liberal-leaning Democratic Party used a higher ratio of positive to negative affect words (M = 13.65:1) than members of the conservative-leaning Republican Party (M = 11.50:1), including a higher frequency of positive affect word usage in 17 of 18 years.

      Democrats tended to use one negative word for every 13.65 positive words. This negative word usage is less frequent than Republicans, who used one negative word for every 11.5 positive words.

    5. conservatism predicted significantly less intense facial action in the muscles around the eyes that indicate genuine happiness (AU6: β = –0.13, P = 0.031). The odds of displaying non-Duchenne smiles (i.e., action in AU12 but not AU6) were slightly higher for conservatives than for liberals, but this did not reach statistical significance [controlling for demographics: odds ratio (OR) = 1.04, P = 0.206].

      That is, the results indicate that although conservatives were not significantly more likely than liberals to not use the orbicularis oculi at all, conservatives were likely to display less muscle activation around the eyes, compared with liberals.

  8. Nov 2015
    1. Biases were reduced compared with baseline levels (Fig. 1B) [within-subject analysis of variance (ANOVA), F1,39= 15.453, P < 0.001, ηp2 = 0.284]. The mean IAT score was 0.559 at baseline and 0.335 at the prenap test

      The authors found a decrease in bias from the beginning of the study to just after the counterbias training.

      From this finding, the authors can conclude that their counterbias training had an immediate (before-nap) effect.

    2. This bias reduction did not differ as a function of bias type

      From this result the authors can conclude that the bias decrease after training was equally effective for both types of bias training (gender and race).

    3. IAT scores showed that participants held implicit social biases for both gender and race, with both scores significantly greater than zero [mean ± SEM, 0.559 ± 0.044; gender t(39) = 9.076, P < 0.001; race t(39) = 8.388, P < 0.001]

      At the beginning of the study, participants showed:

      1) a gender bias (preference for associating science words with male faces and art words with female faces)

      2) a race bias (preference for associating good words with White faces and bad words with Black faces)

  9. Oct 2015
    1. To facilitate this process, we bioinformatically generated ~190,000 specific gRNA-targetable sequences targeting ~40.5% exons of genes in the human genome

      The authors ran a computer simulation to see how much of the human genome could possibly be targeted using this system.

    2. These results demonstrate that this approach enables efficient integration of foreign DNA at endogenous loci in human cells

      The authors had previously inserted DNA into an artificially inserted target. Now they targeted a natural site.

    3. NHEJ-mediated deletions for T1 and T2 were centered around the target site positions,

      The deletions were not always exactly on target, but they tended to center around the target thus providing evidence that the process itself targets specific DNA sequences.

    4. these results confirm that RNA-guided genome targeting in human cells is simple to execute and induces robust HR across multiple target sites

      The authors demonstrated that the system can edit various different genes in the human genome.

    5. observed HR only upon simultaneous introduction of the repair donor, Cas9 protein, and gRNA

      This provides support for the authors' description of the mechanism for the system earlier described.

    6. resource of ~190 K unique gRNAs targeting ~40.5%

      The authors generated a database of about 190,000 guide RNAs which can potentially target about 40.5% of the human genome. This will be a resource for future experiments.

    7. is sequence-specific

      The authors had to show that the results follow the addition of specific components to the system. By demonstrating this, they support their explanation for what is happening on the microbiological level.

    8. relies on CRISPR components

      This is a microscopic process which cannot be directly observed, so it is important to show that the process really does rely on CRISPR components.

    1. Corresponding bias reductions were fortified in comparison with the social bias not externally reactivated during sleep

      The counterstereotype training whose sound was played during sleep was more effective (bias was more reduced) than the training whose sound was not played.

      This supports the authors' hypothesis!

    2. This differential bias reduction was not moderated by bias type

      The authors found that cueing reduced bias equally for both gender counterbias training and racial counterbias training.

      From this the authors can conclude that the type of training did not deferentially affect bias reduction.

    3. Bias change from prenap to postnap varied with cueing condition as predicted

      The authors found that for the counterbias training that was cued (the sound associated with it was played during the nap), the bias was smaller post-nap than pre-nap while for the training that was uncued (the sound wasn't played), the bias was no different post-nap than pre-nap.

      From this finding the authors can conclude that the cueing during the nap decreased post-nap bias.

    1. ght, Y. Watanabe, E. Howard, R. L. de Lima, S. Daack-Hirsch, A. Sander, D. M. McDonald-McGinn, E. H. Zackai, E. J. Lammer, A.


  10. Sep 2015
  11. Aug 2015
    1. This will allow access to a wide variety of well-defined non-centrosymmetric architectures with control of segment length and segment composition.

      Because the authors have demonstrated the ability to synthesize noncentrosymmetric structures through coronal cross-linking, they have set a foundation to expand the field of non-centrosymmetric nanostrctures when coupled with CDSA.

    2. As expected on the basis of the behavior of other amphiphilic systems of different sizes, the A-B-C amphiphilic block co-micelles assembled into star-shaped supermicelles.

      Upon synthesis of a triblock co-micelle comprised of three different types of unimers (all of which have a crystalline PFS core), the amphiphilic block co-micelle demonstrated the ability to self-assemble into a star-shaped "supermicelle".

    3. The non-centrosymmetric A-B block co-micelles were also found to be active in further CDSA

      The authors showed they were able to definitively deactivate the micelle ends from CDSA by employing coronal cross-linking. Figs. 3D, E, and F demonstrate the ability for elongation to occur from only the non-crosslinked end.

    4. co-micelles did not elongate, thus verifying that CDSA was inhibited after cross-linking

      In order to test if the authors had successfully blocked the active micelle ends, the authors took TEM images before and after unimers were added to the cross-linked micelle solution. As the TEM figure shows, Fig. 2D, upon unimer addition the average micelle length did not increase.

    5. We therefore concluded that the corona cross-linking strategy provides an efficient method of blocking micelle termini toward further participation in CDSA.

      The authors have previously presented the ability to cross-link micelles for increased micellar stability as well as for the synthesis of polymer gel networks (see references).

      In this paper, they used this prior knowledge to cross-link the micelle corona to prevent CDSA and limit elongation by deactivating the ends of the micelles.

  12. Jul 2015
    1. HDAC6 is recruited

      HDAC6 binds to the free ubiqiuitin associated with the capsid and, in turn, activates cytoskeletal molecules. The involvement of HDAC6 is crucial for the virus to undergo the uncoating and release the vRNPs into the cytosol.

    2. our results demonstrated that key components of the aggresome formation and disassembly machinery promote IAV uncoating

      By studying the correlation between HDAC6 and dynein/dynactin, the authors discovered that proteins belonging to the aggresome formation and disassembly machinery participate to the IAV uncoating step during the virus host cell entry.

    3. The results showed that inhibitors of dynein, myosin II, actin, and MT assembly all reduced uncoating significantly

While before authors explore the role of dynein, myosin II, microtubules and actin on IAV uncoating after plasma membrane fusion, another set of experiments were performed in order to study the effect of these proteins on IAV uncoating when the virus enters by endocytosis. Inhibition of dynein, myosin II, actin and microtubules resulted in reduction of uncoating.

    4. Thus, HDAC6 binding to dynein and dynactin promoted IAV uncoating

      Authors concluded that both dynactin 2 and dynein are essential for the viral uncoating step.

    5. Thus, the ZnF-UBP domain of HDAC6 was critical for IAV uncoating and infection, whereas the deacetylase activity was not.

      Authors established that HDAC6, through its ZnF-UBP domain but not its deacetylase activity domain, was essential for the uncoating step during the infectious process.

    6. HDAC6 was required after fusion

      HDAC6 plays an important role during IAV infection after the fusion of the virus capsid to the endosome membrane.

    7. It was apparent that HDAC6 played a role in the release of viral capsids from the cytosolic surface of endosomes, the dissociation of M1 from vRNPs, and the dispersion of capsid components in the cytosol.

      The authors drew the conclusion that HDAC6 was playing an important role in helping the viral uncoating.

    1. Our findings support the conclusion thatthe mitochondrial legacy of dogs derives fromwolves of European origin.

      The authors observe: I) The process of domestication began in Europe between 18,800 and 32,100 years ago;

      II) The population of proto-dog moved with human populations.

      Therefore, the authors concluded of the European origin of the modern dogs.

    2. ourresults imply that some of the earliest putative dogremains, such as the Goyet dog from Belgium (2)or Altai Mountain specimen from Russia

      Some domestication did not work, which is why we find traces of domesticated dogs that do not exist today.

      This is based on the mitochondrial DNA; the autosomal DNA has not been analyzed yet.