/genes/ - Genes, their effects, factors

all right guys.

I don't know shit about genes

ENLIGHTEN ME

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A scientific team from the Scripps Research Institute (TSRI), the Veterans Affairs San Diego Healthcare System (VA), and University of California (UC) San Diego School of Medicine reports that increasing a crucial cholesterol-binding membrane protein in neurons within the brain can improve learning and memory in aged mice.

"This is a novel strategy for treating neurodegenerative diseases, and it underscores the importance of brain cholesterol," said Chitra Mandyam, Ph.D., associate professor at TSRI and co-first author of the study (“Neuron-targeted caveolin-1 improves molecular signaling, plasticity and behavior dependent on the hippocampus in adult and aged mice”) that appears online in Biological Psychiatry.

Senior author Brian Head, Ph.D., a research scientist with the VA and associate professor at UC San Diego, added, "By bringing back this protein, you're actually bringing cholesterol back to the cell membrane, which is very important for forming new synaptic contacts."

The research focuses on a specific membrane protein called caveolin-1 (Cav-1) and expands scientists' understanding of neuroplasticity, the ability of neural pathways to grow in response to new stimuli.

Previous work by Dr. Head's group at the VA and at UC San Diego had shown that raising Cav-1 levels supported healthy "rafts" of cholesterol involved in neuron growth and cell signaling. However, it wasn't clear if this new growth actually improved brain function or memory.

To find out, the researchers delivered Cav-1 directly into the hippocampus in adult and "aged" mice. The hippocampus is a structure thought to participate in formation of contextual memories, e.g., if one remembers a past picnic when later visiting a park.

In addition to improved neuron growth, treated mice demonstrated better retrieval of contextual memories, i.e., they froze in place, an indication of fear, when placed in a location where they'd once received small electric shocks.

Drs. Mandyam and Head believe that this type of gene therapy may be a pPost too long. Click here to view the full text.

Barley is an attractive vehicle for producing recombinant protein, since it is a readily transformable diploid crop species in which doubled haploids can be routinely generated. High amounts of protein are naturally accumulated in the grain, but optimal endosperm-specific promoters have yet to be perfected. Here, the oat GLOBULIN1 promoter was combined with the legumin B4 (LeB4) signal peptide and the endoplasmic reticulum (ER) retention signal (SE)KDEL. Transgenic barley grain accumulated up to 1.2 g/kg dry weight of recombinant protein (GFP), deposited in small roundish compartments assumed to be ER-derived protein bodies. The molecular farming potential of the system was tested by generating doubled haploid transgenic lines engineered to synthesize the anti-HIV-1 monoclonal antibody 2G12 with up to 160 μg recombinant protein per g grain. The recombinant protein was deposited at the periphery of protein bodies in the form of a mixture of various N-glycans (notably those lacking terminal N-acetylglucosamine residues), consistent with their vacuolar localization. Inspection of protein-A purified antibodies using surface plasmon resonance spectroscopy showed that their equilibrium and kinetic rate constants were comparable to those associated with recombinant 2G12 synthesized in Chinese hamster ovary cells.

In summary, the endosperm-specific expression system based on the oat GLO1 promoter in combination with the LeB4 signal peptide has been shown to be effective in barley, and is appropriate as a technology for producing recombinant protein in the barley grain. The test protein, an anti-HIV antibody, was produced in a functional and soluble form and accumulated within the periphery of the PSV, alongside the hordeins. Its level of accumulation exceeded those achieved in transgenic tobacco, maize and rice.

https://archive.is/Tku6X

Searching bacteria for an alternative to Cas9, the enzyme used in the CRIPSR system to cut DNA at a site specified by RNA guides, synthetic biologist Feng Zhang of the Broad Institute in Cambridge, Massachusetts, and his colleagues discovered a protein called Cpf1 in some bacteria that use CRISPR for viral defense. Taking a closer look at Cpf1 from 16 microbial species, the research team identified two that could cut human DNA, they reported last week (September 25) in Cell.

“It’s a noteworthy addition to the biology [of CRISPR] and a valuable addition to the tool box,” North Carolina State University molecular biologist Rodolphe Barrangou, who did not participate in the research, told Science.

Important differences exist between Cpf1 and Cas9. Cas9 relies on two RNA molecules to specify the DNA to be cut, while Cpf1 only requires one, for instance. And the nature of the cut is also different: Cas9 cuts both DNA strands at the same location, while Cpf1 snips DNA such that there are short, single-stranded pieces on either side of the cut. “The sticky ends carry information that can direct the insertion of the DNA,” Zhang told Nature. “It makes the insertion much more controllable.”

The sticky ends could also improve the efficiency of CRISPR gene editing, as the blunt ends left by Cas9 cuts are often simply stuck back together, rather than incorporating new DNA. “Boosting the efficiency would be a big step for plant science,” Iowa State University plant biologist Bing Yang, who was not involved in the study, told Nature. “Right now, it is a major challenge.”

The new discovery could also hold financial value, as the Broad and the University of California, Berkeley, continue to duke it out over who first invented CRISPR editing tools such as Cas9. While the US Patent and Trademark Office considers intervening in the case, Cpf1 could sidestep the problem altogether. “The greatest value may be more in terms of the patent landscape than a scientific advancement,” the University of Minnesota’s Dan Voytas told MIT Technology Review.

https://archive.is/7caSb

Panoramix, a newly identified transcription repressor, takes the bounce out of jumping genes.

A paper published, October 15, in Science provides a greater understanding of how cells shut down these rogue jumping genes. Greg Hannon of the Cancer Research UK Cambridge Institute and his colleagues have identified a protein in fruit flies that appears to halt transposons before they begin to leap.

“This is a mountain of impressive work, a huge amount of data, [the result of which] is that we now understand something about how piRNAs are transcriptionally silencing their targets,” said molecular geneticist Keith Slotkin of Ohio State University who was not involved in the work. “We knew that this was happening, but the mechanism was all question marks and hand-waving.”

Piwi-interacting RNAs, or piRNAs, are short noncoding RNAs that, as their name implies, interact with a protein called Piwi—a highly conserved transposon-suppressing factor. To protect the host against damaging tranposon-induced mutations, Piwi-piRNA complexes both destroy transposon transcripts in the cytoplasm (post-transcriptional silencing) and block transposon transcription in the nucleus (transcriptional silencing). Essentially, the piRNA pathway “mops up the water” and “turns off the spigot,” explained human geneticist John Moran of the University of Michigan who also did not participate in the study. How the spigot is turned off, however, was largely a mystery.

In fact, with the exception of Piwi itself and a protein called Asterix—a nucleus-specific component of Piwi complexes—the machinery responsible for transcriptional silencing of transposons was unknown. To identify possible candidates, Hannon’s team scoured the results of their own and others’ genome-wide screens for piRNA pathway components in the fruit fly Drosophila melanogaster, finding one that seemed to fit the bill: the protein CG9754.

Suppression of CG9754 in fruit fly ovaries not only ramped up transposon transcription, but also erased the repressive epigenetic marks normally present at suppressed transposon loci—indicating that the protein was acting at the genetic loci rather than post transcriptionally.

The work was presented on 5 October at a meeting of the US National Academy of Sciences (NAS) in Washington DC on human gene editing. Geneticist George Church of Harvard Medical School in Boston, Massachusetts, announced that he and colleagues had used the CRISPR/Cas9 gene-editing technology to inactivate 62 porcine endogenous retroviruses (PERVs) in pig embryos. These viruses are embedded in all pigs’ genomes and cannot be treated or neutralized. It is feared that they could cause disease in human transplant recipients.

Church’s group also modified more than 20 genes in a separate set of pig embryos, including genes that encode proteins that sit on the surface of pig cells and are known to trigger a human immune response or cause blood clotting. Church declined to reveal the exact genes, however, because the work is as yet unpublished. Eventually, pigs intended for organ transplants would need both these modifications and the PERV deletions.

Preparing for implantation

“This is something I’ve been wanting to do for almost a decade,” Church says. A biotech company that he co-founded to produce pigs for organ transplantation, eGenesis in Boston, is now trying to make the process as cheap as possible.

Church released few details about how his team managed to remove so many pig genes. But he says that both sets of edited pig embryos are almost ready to implant into mother pigs. eGenesis has procured a facility at Harvard Medical School where the pigs will be implanted and raised in isolation from pathogens.

I'm doing hw but I just found this and will be hanging out alot. Im working this year data mining expression data from mouse cerebral cortex. Two groups, one trisomy and the other wt were used in the study, which was designed to see how expression of critters in learning environments is different between normal mice and retarded trisomy models who can't learn.

Later Summer 2015 Genetics Updates

The Right way to use Genetic Modification

Throughout history, people have relied on plants for medicines. Even modern drugmakers get about half their new drugs from plants. But that’s harder to do when plants are slow growing and endangered, as is the Himalayan mayapple (Podophyllum hexandrum). The short, leafy plant was the original source of podophyllotoxin, a cytotoxic compound that’s the starting point for an anticancer drug called Etoposide. The drug has been on the U.S. market since 1983 and is used to treat dozens of different cancers, from lymphoma to lung cancer. Today, podophyllotoxin is mainly harvested from the more common American mayapple. But this plant is also slow growing, producing only small quantities of the compound.

Mayapples churn out podophyllotoxin to defend against would-be munchers. To do so, the plants use a step-by-step approach to synthesize their chemical defense. But because the synthetic pathway of the compound had never been worked out, no one knew precisely which genes were involved in stitching together the molecule. What researchers did know was that podophyllotoxin isn’t always present in the plant. “It’s only when the leaf is wounded that the molecule is made,” says Elizabeth Sattely, a chemical engineer at Stanford University in Palo Alto, California, who led the current research effort.

Sattely and her graduate student Warren Lau reasoned that the podophyllotoxin-building proteins were likely themselves only made by the plant in response to an injury. So the pair made tiny punctures in the leaves of healthy Himalayan mayapples provided to them by a commercial nursery, testing them before and after to see which new proteins appeared around the damaged tissue. They discovered 31, which they categorized by probable function.

The pair then narrowed the likely candidates for enzymes in podophyllotoxin production by focusing on members of four classes known to carry out the right types of chemical reactions. They then spliced genes for each of these enzymes into bacteria known to infect Nicotiana benthamiana, a fast-growing relative of tobacco that serves as a sort of lab rat of plant biologists. The bacteria readily infect tobacco and insert their genes into the plant tissuPost too long. Click here to view the full text.

New Genes Are Expressed in the Early Developing Human Brain

>Previous analyses of the molecular evolution of the human brain did not find consistent evidence of rapid evolution in the protein-coding genes expressed in the adult human brain [8]–[9]. Faster evolution in the human lineage was not observed at the gene expression level either [2].

>However, we noticed that all these analyses were based on the adult brain, just one stage of brain development. It is thus understandable that they were inconclusive as to the understanding of the genetic basis for the evolution of how the brain develops.

>Our analyses revealed an unexpected pattern: the expression patterns and protein sequences of new genes appear to contribute to the early (fetal and infant) brain development of humans.

>This pattern supports the argument that genes formed by duplication and by de novo origination could escape pleiotropic constraints [42]. On the other hand, the enrichment of transcription factors in human young genes also suggests the important role of regulation in the development of the human brain [1],[4]–[6].

>Our results show that regulatory evolution can occur in both cis [5] and trans, in the protein sequence of transcription factors [32],[43], and in the creation of new transcription factors through gene duplication. From this aspect, fine-tuning of gene regulation by human-specific genes [44] might underlie many human-specific characteristics and behaviors.

>However, we also observed that young genes were associated with diverse functions, ranging from nuclear pore proteins to ribosomal proteins (Table 1).

>In fact, the striking correspondence of the origination times of the neocortex and PFC with the ages of new genes suggests the functional association of these young genes with the development of these expanding brain structures. Specifically, new genes began to be recruited into neocortex or PFC after their morphological origination (Figure 5B, 5C).

>The recruitment of young genes into the early developmental stages of neocortex, regardless of the various processes which created these genPost too long. Click here to view the full text.