NIF did a similar analysis and came up with many of the same resources, although we did not distinguish between data deposition and data use.

Good statistic to know. Most used (or at least referenced) repositories.

A more effective strategy might have been to search for URL's because generally one is included for many of these repositories.

FIgShare also has a lot of traction, although I don't know what the status of FigShare was in 2011 in terms of use.

The NIF Registry (now SciCrunch Registry) data set would have been really helpful here, as it contains synonyms, variants and a list of URL's that point to the resource.

Again, it is disgraceful that even NIH does not have access to the full text of all articles for text mining purposes. I do believe that this is one of the central issues facing biomedicine moving forward and one that needs to be solved.

That number is lower than I would expect based on some estimates from Chalmers and others.

Actually, it was never non-data centric. We just had no opportunity to share and preserve the data for reuse.

Another good statistic to have

This is a good statistic to have handy.

Need to tell Karl and others of the task force about this.

But not Prov?

But do not address the anchoring of the annotation to the object.

Did you know about Russ Poldrack's My Connectome? I'm hoping he didn't use a contrast agent. I'm assuming not.

This is the same as Mom's tumor, I believe, although I don't know the PgR or HER2 status.

Even though we can't read the full article, this statement is encouraging.

"Induration: Localized hardening of soft tissue of the body. The area becomes firm, but not as hard as bone."

But very confusing the way this is phrased: so hypo fractionation is associated with slightly more skin induration. Don't care if it's significant, it's a very small effect.

Probably could use some explanation; does this mean localized vs spread?

Six months? The length of recovery needs to be considered when treating the elderly.

These references are not in the pdf

In this paper, the authors developed a new class of diblock copolymers that have a metal-containing hydrophobic block (PFS) and an organic hydrophilic block (P2VP): PFS = poly(ferrocenyldimethylsilane) and P2VP = poly(2-vinylpyridine). The authors of this publication discovered the ability to obtain spherical and cylindrical morphologies simply by using different alcohols. Having established the ability to obtain cylindrical micelles using the PFS-b-P2VP block copolymer system in isopropyl alcohol, the authors modified their approach in the current study to obtain supermicelles.

This paper established that Karstedt's catalysts ability to cross-link the double bonds in polyisoprene in the absences of silicon-containing molecules. Besides acquiring a variety of morphologies, the authors also investigated their ability to use Karstedt's catalyst to synthesize reversible polymer gel networks.

This reference investigates the development of 1D nano-structures through the use of cross-linked cylindrical micelles. This paper highlights possible applications for these 1D nanomaterials such as microfluidics.

This review paper describes the uses and progress made in the field of cross-linked micelles. Concepts covered include stabilization as well chemical modification and functionalization.

References: This paper describes the synthesis of semiconducting nanotubes through a process similar to CDSA by connecting dissimilar junctions, referred to as heterojuntions, to study the behaviors of photocarriers.

This paper describes the use of a biodegradable polymer in order to obtain a variety of micelle morphologies. A concept referred to as tethering density is used in this paper to explain unexpected morphologies.

This paper uses triblock copolymers to synthesize cylindrical and spherical micelles. By carefully controlling crystallization, the authors were able to control the micellar morphology in a highly selective fashion.

This paper utilizes CDSA to synthesize noncylindrical block co-micelles. The authors utilized plateletlike micelle and cylindrical micelles in order to form scarflike architectures using platelet-cylindrical and cylindrical-cylindrical connections.

This paper describes the discovery of CDSA. The authors draw a comparison to living polymerization and explain the phenomenon of epitaxial crystallization-induced co-micellization

This reference describes the synthesis of brush block and random copolymers. The polymers are referred to as a "brush" because pendant groups are dangling off the main chain. The brush polymers synthesized were amphiphilic and demonstrated self-assembly.

This paper describes the synthesis of amphiphilic Janus discs using a block terpolymer (three distinct blocks comprised of three distinct monomers). Two different size discs were made where, depending on size, the manner in which the hydrophobic side is "protected" from water can vary. The smaller discs are stabilized by the long hydrophilic polymer chains, protruding out of one side and shielding the hydrophobic side against water. The larger discs undergo aggregation as well as bending to again shield the hydrophobic side from the water by flipping over one part of the structure.

This reference is an example where triblock copolymers were photo-crosslinked to create Janus particles which were classified as "hamburger-like" micelles.

This review paper discusses a class of noncentrosymmetric nanoparticles referred to as the Janus particle. These particles are rather challenging to synthesize because two different chemistries are present on the surface of the particle.

This paper utilized charged polymers as well as metal cations and a variety of solvents to kinetically trap unique micelle morphologies. The self-assembly systems were forced down a specific pathway in order to form morphologies that would not have typically occurred without assistance.

This paper was one of the first papers to establish the ability to form micelles of different morphologies (beyond just spherical) for systems using amphiphilic block copolymers

This optical microscope, commonly referred to as a light microscope, uses light to magnify images.

The resolution power of an optical microscope is smaller than that of a TEM.

Optical microscope images were taken to confirm/support the starlike supermicelles seen in the TEM (which were several micrometers in diameter). The authors stated since the supermicelles were approximately 3 micrometers in diameter, the optical microscope could resolve the starlike strucutres. However, if the supermicelles were much smaller than 3 micrometers then resolution using an optical microscope would not be possible.

The outside of a micelle.

The center of a micelle.

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.

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".

TEM is a microscopy technique where a beam of electrons passes through a thin-film sample. As the electrons interact with the sample, an image is produced. Samples that have atoms with high atomic numbers can produce darker images/provide better contrast.

The TEM samples were prepared on a carbon-coated grid. A drop of the micelle suspension was placed on the grid and then the excess solvent was removed using filter paper.

Using TEM the authors can verify they have achieved unidirectional growth. Additionally, they were able to see larger starlike micellar aggregates formed from the target noncentrosymmetric micelles.

This term is used to describe solutions that have limited to no transparency; cloudy, opaque.

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.

Connects to AP Chemistry Learning Standard 6: Any bond or intermolecular attraction that can be formed can be broken. These two processes are in dynamic competition, sensitive to initial conditions and external perturbations.

Found on page 71 of the AP Chemistry Course and Exam Description:

http://media.collegeboard.com/digitalServices/pdf/ap/ap-chemistry-course-and-exam-description.pdf

Figure 1B depicts the synthetic strategy used to make micelles seeds capable of unidirectional growth:

After the cross-linking step, a solvent is chosen to dissolve the middle block (PFS-b-PDMS) of the triblock co-micelle. By doing this, the remaining PI-B-PFS micelle blocks can be used as seeds for elongation from the non-crosslinked end.

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.

Figure 1A depicts the synthetic strategy used to make triblock co-micelles:

1) The first step was to make micelles with crystalline cores. They did this by making a suspension of poly (ferrocenyl dimethylsilane)-b-poly(dimethylsiloxane) in hexane at 60C°. The solution was allowed to age at room temperature. They then sonicated the suspension in order to break up the micelles into smaller micelle seeds.

2) The next step was to add a second block copolymer to give bidirectional growth to form a triblock co-micelle. This was performed using a solution of unimers in THF which was added to the micelle suspension and allowed to age in order to form a longer micelle.

3) Finally, the polyisoprene end of the block co-micelle is cross-linked to prevent further growth using Karstedt's catalyst.

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.

Karstedt's catalyst is a platinum compound capable of forming bonds between carbon and silicon atoms.

In a separate publication, ref. 31 (DOI: 10.1021/ja206370k), the authors discovered the catalyst's ability to cross-link the double bonds in polyisoprene in the absences of silicon-containing molecules.

In this paper, Karstedt's catalyst was used to prevent block elongation from one end of the exposed cylindrical core to achieve unidirectional growth.

Winnik and Manners et. al. used Karstedt's catalysts to cross-link polyisoprene in order to create micelles of varying morphologies. They were able to apply this technique for the development of noncentrosymmetric micelles.

The growth of one crystalline material on the surface of another crystalline.

In this case, the crystalline surface upon which epitaxial growth occurs is the exposed crystalline core of the cylindrical micelle. The exposed core can continue to elongate as more block copolymers are added to the solution.

Prior to this article, despite the usefulness of CDSA, many of the structures synthesized were centrosymmetric since growth can happen from both ends of the micelle core. This article presents the development of a method to overcome this limitation.

To read how semiconducting nanotubes can be used to potentially improve eyesight click here:

http://www.acs.org/content/acs/en/pressroom/presspacs/2014/acs-presspac-november-12-2014/artificial-retina-could-someday-help-restore-vision.html

After the discovery of CDSA, the synthetic strategy has been used with a range polymers including conducting, biocompatible, metal-containing, etc.

A solution that has evenly dispersed particles that are 1 nm to 1000 nm. The particles are in solution and do not settle out. An example of a colloidal dispersion is milk.

Maximum end-to-end distance of a linear polymer chain.

Previous Work: During CDSA, the crystalline core of the micelle is partially "exposed" to the solvent. When unimers are added to the micelle solution, they are able to grow on existing micelle. However, if the chemical structure of the core prevents crystallization/is not a lattice match, then micelle growth will not happen. This technique has been widely used with a variety of materials such as diblock polymers and nanotubes to create unique self-assemblies.

In a block copolymer, a block which lacks crystallinity and has great freedom of rotation due to its flexible nature.

This technique was first introduced in 2007 by Winnik and Manners et. al. where they discovered a "living" form of micellization. The term "living" in this scenario is derived from the phase "living polymerization" where monomers form long chains by continuous addition to the reactive chain ends, without termination. In the same way, certain micelles specifically those that had crystalline cores exhibited the ability to elongate when additional block copolymers are added to the micelle solution.

A type of polymerization mechanism that uses strained cyclic olefins (alkene) as the monomer source to produce polymer chains.

A chemical compound that has a hydrophilic (water-loving) component and lipophilic (fat-loving) component.

A cross-link bonds together different polymer chains together at a specific site (i.e., double bonds, sulfur atoms) to form a larger polymer network.

Glossary: Molecules have different degrees of molecular symmetry. A molecule that is noncentrosymmetric will not contain an inversion center or a center of symmetry. An example of a molecule that is centrosymmetric is a benzene ring (C6H6) where the inversion center is the center of the ring.

Anisotropy is defined as having a directional dependence. In the case of shape, anisotropy it is referring to an object that is not spherical.

Connects to AP Chemistry Learning Standard:2.B

Forces of attraction between particles (including the noble gases and also different parts of some large molecules) are important in determining many macroscopic properties of a substance, including how the observable physical state changes with temperature

Found on page 27 of the AP Chemistry Course and Exam Description:

http://media.collegeboard.com/digitalServices/pdf/ap/ap-chemistry-course-and-exam-description.pdf

Particles of any shape that have at least one dimension less than 100 nm or less in size.

Connects to AP Chemistry Learning Standard:2.A.3: Solutions are homogeneous mixtures in which the physical properties are dependent on the concentration of the solute and the strengths of all interactions among the particles of the solutes and solvent:

Found on page 25 of the AP Chemistry Course and Exam Description:

http://media.collegeboard.com/digitalServices/pdf/ap/ap-chemistry-course-and-exam-description.pdf

The formation of complex structures from a bottom-up approach.

To read general information on nanotechnology click on the following link:

http://www.nano.gov/nanotech-101/what/definition

The following article is an interestng example of using nanotechnology to create jewelery:

http://www.nytimes.com/2014/11/18/style/international/jewelry-nanotechnology.html

From one direction or side.

A micelle is an aggregate comprised of amphiphilic molecules. A micelle will have a core (inside-lipophilic) and a corona (outside-hydrophilic).

The individual components that make up this aggregate are referred to as unimers.

Although most micelles are have hydrophobic cores and hydrophilic corona, these micelles don't fit this classification. The corona is PI (hydrophobic) and the core is PFS (also hydrophobic). Self-assembly is induced because hexane/decane are poor solvents for PFS but good for PI .

Molecular self-assembly is the process in which a disordered group of molecules occupy some organized arrangement without direction from an outside source.

A block copolymer is a polymer chain comprised of homopolymer subunits linked by a covalent bond.

For example:

Homopolymer (where A is the monomer unit) : A-A-A-A-A-A-A-A

Block copolymer (where A and B are monomer units): A-A-A-A-B-B-B-B

Unidirectional Growth ... the Road to Designer Micelles

As the field of nanotechnology continues to grow, the ability to carefully control nanoparticle size, shape, and composition still remains a challenge. Most nanoparticles exhibit a great deal of symmetry. The authors of this paper focused on developing a method to create block copolymer micelles that had very little symmetry (i.e., noncentrosymmetric). They were able to achieve their goal through unidirectional micelle growth. The authors later used this same strategy to synthesize a "supermicelle."

Assistant project scientists are specifically mentioned. See next annotation.

This implies that associate project scientists are not eligible, but I don't know why they don't just come out and say so.

Very clever. And, as the author implies, everything need not be seen through the lens of a Facebook user. There are still some of us out there who don't use Facebook (gasp!) and who prefer more in depth considerations of topics. But we now have more choices in how and where we wish to consume information.

This is a point that I usually make when discussing the scholarly communications ecosystem. There are many platforms available and they are not interchangeable; rather, each does well with a relatively small piece of the pie. For a scholar, the goal should be to present content in the platform that is best for the content. Pieces of it can be disseminated through other venues, but we have to move beyond our current 1-2 sizes fits all system.

A very limited definition of existence: "I view ads therefore I am"

This is the way I would like scholarly publishing to work as well.

Importazole is a small molecule inhibitor of the transport receptor importin-β. This inhibitor was identified by a screening assay developed by the authors of this paper.

This work reported the discovery of ciliobrevins, the first specific small-molecule antagonists of cytoplasmic dynein.

This paper reported the development of Tubastatin A, a potent and selective HDAC6 inhibitor.

This work suggested a novel ubiquitin-mediated signaling pathway, where the exposure of ubiquitin C termini within protein aggregates enables HDAC6 recognition and transport to the aggresome. The authors found that the ubiquitin-binding domain (ZnF-UBP) of HDAC6, instead of recognizing protein aggregates by binding directly to polyubiquitinated proteins, binds exclusively to the unanchored C-terminal diglycine motif of ubiquitin.

In this report, the authors showed that both HDAC domains are required for the intact deacetylase activity of HDAC-6.

In this study, the author generated HDAC6 knock out mice and investigated the in vivo functions of HDAC6 and the relevance of tubulin acetylation/deacetylation. they observed that HDAC6-deficient mice are viable and fertile and show hyperacetylated tubulin in most tissues.They concluded that mice survive well without HDAC6 and that tubulin hyperacetylation is not detrimental to normal mammalian development.


This work showed that when influenza virus ribonucleoproteins (vRNPs), devoid of M1, were introduced into the cytoplasm of cells by microinjection, they were found to be imported into the nucleus, and the RNA was transcribed. Their uptake into the nucleus was ATP-dependent, inhibited by antibodies to the nuclear pore complex, unaffected by the prior acidification of the vRNPs, and not inhibited by an anti-virurs, called amantadine. These experiments demonstrated that for productive infection, all the early stages of the viral entry pathway can be bypassed.

This study provides a powerful high-throughput platform to understand the host cell processes. The authors developed quantitative, imaging-based assays to dissect seven consecutive steps in the early phases of IAV infection in tissue culture cells.

This work investigated the cell fusion process of representatives of 3 families of enveloped viruses. it was discovered that hemagglutinin plays a role for the influenza in the low-pH-dependent membrane fusion activity. Low-pH-induced fusion is a widespread property of enveloped animal viruses and that it may play a role in the infective process.

The authors of this paper identified the ion channel activity of M2.

This work investigated the cell fusion process of representatives of 3 families of enveloped viruses. it was discovered that hemagglutinin plays a role for the influenza in the low-pH-dependent membrane fusion activity. Low-pH-induced fusion is a widespread property of enveloped animal viruses and that it may play a role in the infective process.

This work described the nuclear transport of influenza virus ribonucleoproteins (vRNPs). Viral matrix protein (M1) associates with newly assembled vRNPs in the nucleus and escorts them to the cytoplasm through the nuclear pores. In contrast, during entry of the virus into a new host cell, M1 protein dissociates from the RNPs, allowing them to enter the nucleus.

Possible Therapy? Find out what the author Dr. Yamauchi says in this regard.

http://www.futurity.org/flu-virus-capsid-789992/

Cytoskeleton is a network of fibers composed of proteins (microfilaments made of actin and microtubules made of tubulin) contained within a cell's cytoplasm.

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.

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.


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.

Because the host cell entry comprises multiple steps, the authors investigated which one was affected by the depletion of HDAC6. They noticed that HDAC6 has a function specifically during the uncoating and the vRNPs import.

Authors investigated the role of myosin 10 and 9, which belong to type II myosin, in IAV uncoating after plasma membrane fusion. They blocked separately the gene expression for both Myosin 9 and 10 and observed that uncoating was reduced only in myosin 10-depleted cells. Additionally, two different inhibitors of type II myosins inhibited the uncoating.

Often, when more than one technique is available for exploring an hypothesis (i.e. involvement of myosin in IAV uncoating), scientists use them all to confirm their observations. By getting rid of myosins, authors can understand how important it is in the uncoating. Two ways were used to do so: blockage of the expression of the corresponding genes and inhibition of myosins by using drugs.

CCSS.ELA-LITERACY.RST.11-12.8

http://www.corestandards.org/ELA-Literacy/RST/11-12/

Whenever an observation is not fully understood, scientists try to analyze the issue from different angles. Here, the authors observed that the inhibition of dynein wasn't sufficient for inhibiting the viral uncoating completely. Therefore, they deduced that other factors were implicated with uncoating and decided to explore this possibility.

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


By depleting dynactin 2 via RNAi and inhibiting dynein via treatment with CilioD (dynein inhibitor), the authors found out that viral uncoating was reduced in A549 cells. Also, uncoating is decreased in MEFs expressing HDAC6 that lacks the dynein-binding domain.


Previous study demonstrated that HDAC6 has the capacity to bind both polyubiquitinated misfolded proteins and dynein motors, thereby acting to recruit misfolded protein cargo to dynein motors for transport to aggresomes.

Cells deficient in HDAC6 fail to clear misfolded protein aggregates from the cytoplasm, cannot form aggresomes properly, and are hypersensitive to the accumulation of misfolded proteins.

This experiment confirmed that HDAC6 associates with M1. Authors highlighted HDAC6 associated to M1-containing vacuoles by using indirect immunofluorescence, in which one antibody binds to the target protein (HDAC6 in this experiment) and a second antibody, bearing a fluorophore, binds to the first antibody.

Coimmunoprecipitation (Co-IP) is the immunoprecipitation of intact protein complexes. Co-IP works by selecting an antibody that targets a known protein that is believed to be a member of a larger complex of proteins. By targeting this known member with an antibody it may become possible to pull the entire protein complex out of solution and thereby identify unknown members of the complex.

Immunoprecipitation (IP) is the technique of precipitating a protein antigen out of solution using an antibody that specifically binds to that particular protein. This process can be used to isolate and concentrate a particular protein from a sample containing many thousands of different proteins.

Western blot is an analytical technique used to detect specific proteins in a sample of tissue homogenate or extract.

The authors verified that what observed by immunoblotting was ubiquitin by using the super-resolution microscopy technique.

The pull-down assay is an in vitro method used to determine a physical interaction between two or more proteins.

Triton X-100 is a detergent widely used to lyse cells to extract protein or organelles, or to permeabilize the membranes of living cells.

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.

This study reported the design and synthesis of a potent and selective HDAC6 inhibitor.

In a previous work, scientists investigated whether ubiquitin chain binding affects HDAC6 activity. To generate a ubiquitin-chain binding deficient mutant of HDAC6, they mutated several residues in the BUZ finger that were predicted to make contacts with ubiquitin. It was found that W1182A point mutation markedly disrupted the ability of HDAC6 to bind free ubiquitin chains.

In a previous work, scientists investigated whether ubiquitin chain binding affects HDAC6 activity. To generate a ubiquitin-chain binding deficient mutant of HDAC6, they mutated several residues in the BUZ finger that were predicted to make contacts with ubiquitin. It was found that W1182A point mutation markedly disrupted the ability of HDAC6 to bind free ubiquitin chains.

Point mutation is a technique in which a single base nucleotide is replaced with another nucleotide. As a result, the mutant protein has a different primary sequence with respect to the wild-type protein.

In this figure the authors showed the results obtained when they investigated HDAC6 role in IAV entry.

Panel A: The top part shows a cartoon of IAV entry that consists of multiple steps. The authors studied what step HDAC6 was critical during the virus host cell entry. Bottom part shows quantitative analysis graphs, each corresponding to the above step of IAV entry under investigation.

Panel A (endocytosis): The authors measured the amount of HA-stained spots per cell in wild type MEFs (WT MEF) compared to HADC5 Knock-out MEFs (HDAC6 KO). The third bar represents WT MEFs that were treated with dynasore (Dyn) in order to stop the endocytosis process. Depletion of HDAC6 did not influence the endocytosis step.

Panel A (HA-Acidification): In this step HDAC6 KO MEFS did not show any difference with respect to the wild type cells. It was concluded that HDAC6 does not influence this step of the virus infection.

Panel A (Fusion): fusion of capsid to endosome membrane is not affected by the lack of HDAC6 in knock-out MEF cells as shown in graph.

Panel A (Uncoating): Measuring the amount of cells with dispersed M1, the authors noticed that cells lacking HDAC6 dispersed less M1. This observation led to the conclusion that HDAC6 was fundamental for the uncoating process.

Panel A (vRNP import): Indeed, As vRNP import represents the step following uncoating, HDAC6 KO MEFs showed less NP-positive nuclei because the previous uncoating step was reduced.

In analyzing HA Acidification, Fusion, Uncoating and vRNP import, the authors used BafA1, which is a drug that is able to block uncoating, as a control for their experiment.

Panel B is a graphical representation of the 2 deacetylase catalytic domains of HDAC6 and the zinc-finger ubiquitin binding domain that is close to the C-terminus of the enzyme.

Panel C HDAC6 (WTr) (light gray bar) was a line of HDAC6 KO MEFs able to express again HDAC6. HDAC6 (HDm) (blue bar) was a line of HDAC6 KO MEFs expressing HDAC6 mutated in its deacetylase domain. HDAC6 (ZnFm) (purple bar) was a line of HDAC6 KO MEFs expressing HDAC6 with a mutation in its zinc-finger domain. The authors evaluated the effect of these mutations on the uncoating capacity of IAV. Depletion of deacetylase activity of HDAC6 did not influence the uncoating. Instead, loss of zinc-finger ubiquitin binding domain was detrimental for the uncoating.

The two asterisks on top of the purple bar indicate that this result is statistically significant, that is a result that is caused by something other than mere random chance.

Panel D: life in technicolor!!! These experiments were performed using the confocal microscopy technique. Fluorescent dye molecules bind to specific parts of the cell, so that only those parts are visualized. Fluorescent dyes are chemical compounds that re-emit light upon light excitation (light absorption).<br> The following video, created by Northwest Missouri State University, explains the basics of confocal microscopy. https://www.youtube.com/watch?v=jUAvneBhDcQ

The authors observed that after 2.5 hours from infection, M1 is dispersed inside WT MEFs, indicating that uncoating has occurred. Instead, M1 is confined inside vacuoles when cells lack HDAC6 and the mutant cells in which HDAC6 lacks the Zinc-finger ubiquitin binding region, meaning that the uncoating hasn't occurred.

Zinc finger is any small, functional, independently folded protein domain that requires coordination of one or more zinc ions to stabilize its structure and is essential for DNA- or RNA-binding protein-protein interactions and membrane association. http://www.ncbi.nlm.nih.gov/pubmed/11179890

Following the observation that HDAC6 was implicated in the viral uncoating, next question that the authors asked was: knowing that HDAC6 has deacetylase activity domains as well as ubiquitin binding domain, what HDAC6 function is critical in the uncoating? To study these functions separately, the authors re-introduced WT HDAC6 or HDAC6 point mutated for etheir deacetylase or ubiquitin binding domain in HDAC6 knock-out MEFs

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

Authors ran a second experiment to confirm the involvement of HDAC6 after the fusion step. In this experiment, they bypassed the endocytosis process by means of pH change.

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

Because the host cell entry comprises multiple steps, the authors investigated which one was affected by the depletion of HDAC6. They noticed that HDAC6 has a function specifically during the uncoating and the vRNPs import.

Viral titer is a way to express concentration. It refers to the concentration of viruses in a sample.

IAV was introduced into the trachea of mice.

To determine whether HDAC6 was involved with virus infection, the author examined mutant cells in which HDAC6 expression was silenced. The author observed that when HDAC6 is absent, viral infection and concentration were reduced.

RNAi is a biological process in which RNA molecules inhibit gene expression, typically by causing the destruction of specific mRNA molecules. The final result is the depletion of specific target proteins.

Aggresomes are dynamic structures, formed of improperly folded proteins.

Ubiquitin is a small regulatory protein that has been found in almost all eukaryotic cells. Ubiquitin binds to proteins and labels them for destruction.

Tubulin is the protein that polymerizes into long chains or filaments that form microtubules, hollow fibers which serve as a skeletal system for living cells.

Connect to Learning Standards: http://www.nap.edu/openbook.php?record_id=13165&page=69

Progression for explanation. In a previous study, the authors observed that HDAC6 was required for viral infection. As a consequence, they continued to study the function of HDAC6 in deep detail.

In a previous work, the authors found the histone deacetylase 8 was required for centrosome cohesion and influenza A virus entry.

Hemagglutinin is a glycoprotein found on the surface of the influenza viruses. It is responsible for binding the virus to cells.

A conformational change is a change in the shape of a macromolecule, often induced by environmental factors.

Endosomes are membrane-bound vesicles, formed via a complex family of processes collectively known as endocytosis, and found in the cytoplasm of virtually every animal cell.

A host cell is a living cell invaded by or capable of being invaded by an infectious agent (as a bacterium or a virus).

The genome of influenza A viruses consists of eight segments of single-stranded, negative-sense RNA that are encapsidated as individual rod-shaped ribonucleoprotein complexes (RNPs). Each RNP contains a viral RNA, a viral polymerase and multiple copies of the viral nucleoprotein (NP).

A supramolecular complex is a well-defined assembly of molecules held together by noncovalent bonds. While a supramolecular assembly can be simply composed of two molecules (e.g., a DNA double helix), it is more often used to denote larger complexes of molecules that form sphere-, rod-, or sheetlike species.

A capsid is the protein shell of a virus. The capsid encloses the genetic material of the virus.

Viral RNA with a base sequence complementary to that of mRNA; during replication it serves as a template for the transcription of viral complementary RNA. Negative-sense (3' to 5') viral RNA cannot be translated into protein directly. Instead, it must first be transcribed into a positive-sense RNA (5' to 3') which acts as an mRNA. Some viruses (influenza, for example) have negative-sense genomes and so must carry an RNA polymerase inside the virion.

http://www.nap.edu/openbook.php?record_id=13165&page=43

Science can contribute to meeting many of the major challenges that confront society today, such as preventing and treating disease.

Fighting the influenza A virus (IAV) still remains a great challenge, and there is a real and urgent need for developing new antiviral medicines. Until now, scientists did not know how the virus was able to release its viral genetic material, which is well protected inside a shell, the capsid. A group of scientists discovered that IAV uses the waste disposal system of the host cell for breaking apart the capsid. The presence of a protein, ubiquitin, on the surface of the capsid makes the host cell perceive the IAV as an aggregate of proteins to waste. Then, a histone deacetylase 6 (HDAC6)-dependent pathway, along with cellular transport factors such as dynein and myosin 10, come into play for disposing the virus. The final result is the opening of the capsid followed by the host cell infection. Understanding the molecular mechanisms underlying IAV infection could lead to advances in medicine. HDAC6, as well as other proteins, were suggested as potential targets for the development of new antiviral therapeutics.

Title: Mimicking a bundle of waste: Influenza A virus strategic attack.

Aye, there's the rub

Yes. If we added all the things that graduate students needed to learn to the curriculum, we wouldn't have to worry about careers at all, as they would be students for their entire careers.

Would be nice to be able to track down this reference, because this is a rather startling statistic. Although I suppose that in any highly competitive field, e.g., acting, sports, the percentages of those actually pursuing what they were trained for might be even lower?

This is an important point to keep in mind.

Coalescence is a merging of two units. For example, here the authors consider that Middle East or China are unlikely centers of dog origin because such a scenario would require that ancient wolves and dogs from these areas are united by a common ancestor.

A population bottleneck is the reduction of the population size, followed by an expansion, e.g. a small group leaves the first population and immigrates elsewhere.

This reduction often leads to the loss of genetic diversity in the population; it is called the founder effect.

Previously, the DNA analysis of the genome of prehistoric wolves and dogs support the idea of a two-step domestication process. The first one was the evolution of wolves through a mutually beneficial relationship with humans, sharing food and space. The second one was the active breeding of dogs by humans in order to select dogs which were adapted to the current needs (hunting, tracking, pet).

Furthermore, there are two main hypotheses to explain the first domestication step (http://www.americanscientist.org/issues/pub/early-canid-domestication-the-farm-fox-experiment):

1) “Self-domestication” by the wolves: Some wolves lived in the vicinity of the camps of the nomadic hunter-gatherers to eat the garbage left by the prehistoric people. Those that were less anxious thrived and continued to follow the humans, generation after generation, and gradually the first dogs emerged from this group.

2) The prehistoric people actively selected wolf pups and let only the most docile ones reproduce. After several generations, the first dogs emerged. This hypothesis has been being tested in Novosibirsk since 1959, where foxes are being bred for “tamability.”

This study is about animal domestication. It explains that the dog is the only animal domesticated before the advent of agriculture. It also discuss the limits of mtDNA analysis.

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.

This entire sentence should be selected, but when I try, I don't pop up an annotation box. It seems to be the first four words (gray wolf (Canis lupus) that is the problem. Encountered something similar below.

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.

Read more about this research in these two news articles: DNA Analysis Indicates Domesticated Dogs Originated In Europe

http://www.redorbit.com/news/science/1113004478/domestic-dogs-from-europe-dna-analysis-111513/#MkuDjF53wbrGoqcb.99http://www.redorbit.com/news/science/1113004478/domestic-dogs-from-europe-dna-analysis-111513/

DNA hint of European origin for dogs

http://www.bbc.com/news/science-environment-24946944

This technique allows the authors to determine the precise order of nucleotides within specific regions of a DNA sample.

high-throughout means that large volumes of DNA can be sequenced quickly.

Stochasticity is randomness; in this context, the fact that several lineages mixed resulted in different offspring but each did not recapitulate all the characteristics of its ancestors.

In ref. 5, a genome-wide array of SNP between dogs and wolves suggest that dogs originate from Middle East.

However, ref. 6, the comparison between dog and wolf mitochondrial DNA suggests East Asia as the center of dog origin.

A phylogeny is the method to resolve the evolutionary history of a group of species. The relationship between these species can be inferred from various statistical analyses that estimate the genetic relatedness of each species to one another, depending on their differences either in DNA or protein material.

DNA located in the mitochondria. All animal mitochondrial genomes, with a few exceptions, contain the same 37 genes, making them useful as a model for genome evolution.

Specifically, the comparison of mitochondrial gene arrangements in animals has been critical to inferring ancient evolutionary relationships.

Phenotypic variation is the variability of all observable or measurable characteristics of the individual animals.

Phenotypic variation is the variability of all observable or measurable characteristics of the individual animals.

Check out a Science special issue on Dogs: http://www.sciencemag.org/site/extra/dogs/

Wolves were domesticated much earlier than thought. Researchers discovered that wolves were domesticated by European hunter-gatherers between 19,000 and 32,000 years ago. The analysis cannot, however, be used to determine the origin of the dog, argues a Danish DNA scientist.

http://sciencenordic.com/wolves-became-domesticated-dogs-much-earlier-thought

The authors collected the mtDNA sequences previously published by other teams in order to get more data to analyze and a larger diversity of samples.

This technique allows the authors to determine the precise order of nucleotides within specific regions of a DNA sample.

high-throughout means that large volumes of DNA can be sequenced quickly.

Some of the phenotypic adaptation can be observed, such as: shorter fangs and claws alteration of some brain areas.

By comparing the DNA of phenotypically domesticated canids and actual dogs and identifying the genes which are responsible of the domesticate phenotype, it is possible to understand which genes have been altered by domestication and when they have been altered.

In ref. 5, a genome-wide array of SNP between dogs and wolves suggest that dogs originate from Middle East.

However, ref. 6, the comparison between dog and wolf mitochondrial DNA suggests East Asia as the center of dog origin.

Commonly accepted.

Stochasticity is randomness; in this context, the fact that several lineages mixed resulted in different offspring but each did not recapitulate all the characteristics of its ancestors.

Phenotypic variation is the variability of all observable or measurable characteristics of the individual animals.

Molecular dating is a technique that allows biologists to determine the divergence time for two genes or for two species. It is based on the theory of the molecular clock stating that mutations accumulate in organisms at a stable speed.

Thus, if you compare genes or protein sequences in different species, you can, assuming you know the speed of variation for these sequences, estimate the age of the last common ancestor.

A phylogeny is the method to resolve the evolutionary history of a group of species. The relationship between these species can be inferred from various statistical analyses that estimate the genetic relatedness of each species to one another, depending on their differences either in DNA or protein material.

DNA located in the mitochondria. All animal mitochondrial genomes, with a few exceptions, contain the same 37 genes, making them useful as a model for genome evolution.

Specifically, the comparison of mitochondrial gene arrangements in animals has been critical to inferring ancient evolutionary relationships.

Hi Jeremy: Can you see this?

Really cute poem.

Think I've annotated this before, but sitting at a conference on Open Science where it was suggested that science used to be open. Not really!

We should consider adding this to the SciCrunch Registry, even though it is a commercial tool.

awkward phrasing.

See paper by Hu et al., published in 2000.

Add to SciCrunch Registry

Interesting, but perhaps ignores technology?

Paul Groth: Downside of teamwork = communication overhead.

Read this paper

In doing some research, I see that a paper was published in 1991 by Hayashi and colleagues on ubiquitin and esteem. They showed by immunoblot: "high-mol-wt ubiquitin conjugates (HMWUC) above 40 kDa increased, whereas free ubiquitin and ubiquitinated histone 2A decreased slightly after 4 h and 24 h of reperfusion", consistent with the findings of this study.

Dr. Hu is now at the University of Maryland.

Was this study ever published?

Around this time, it was becoming apparent that abnormal protein aggregates were a hallmark of neurodegenerative disease. I think this was one of the first studies to suggest that they were associated with ischemic cell death.

That makes me happy somehow; that there is preservation of something that gives people such happiness.

I am rather surprised, given the size of the neuroimaging literature, that this is the case.

Yes, I think this is a very important point. The clinician has to be receptive to an activated patient, but the clinician should invite activation from patients.