Lifeboat Foundation

Hoping to improve on those earlier efforts, Matthew Daugherty, a biochemist at the University of California San Diego, and colleagues used sophisticated computer software to trace the evolution of hundreds of human genes by searching for similar sequences in hundreds of other species. Genes that seemed to have appeared first in vertebrates and had no predecessors in earlier animals were good candidates for having jumped across from bacteria, particularly if they had counterparts in modern microbes. Among the dozens of potentially alien genes, one “blew me away,” Daugherty recalls.

The gene, called IRBP (for interphotoreceptor retinoid-binding protein), was already known to be important for seeing. The protein it encodes resides in the space between the retina and the retinal pigment epithelium, a thin layer of cells overlying the retina. In the vertebrate eye, when light hits a light-sensitive photoreceptor in the retina, vitamin A complexes become kinked, setting off an electrical pulse that activates the optic nerve. IRBP then shifts these molecules to the epithelium to be unkinked. Finally, it shuttles the restored molecules back to the photoreceptor. “IRBP,” Zhu explains, “is essential for the vision of all vertebrates.”

Vertebrate IRBP most closely resembles a class of bacterial genes called pepsidases, whose proteins recycle other proteins. Since IRBP is found in all vertebrates but generally not in their closest invertebrate relatives, Daugherty and his colleagues propose that more than 500 million years ago microbes transferred a pepsidase gene into an ancestor of all living vertebrates. Once the gene was in place, the protein’s recycling function was lost and the gene duplicated itself twice, explaining why IRBP has four copies of the original pepsidase DNA. Even in its microbial forebears, this protein may have had some ability to bind to light-sensing molecules, Daugherty suggests. Other mutations then completed its transformation into a molecule that could escape from cells and serve as a shuttle.

Join us on Patreon! https://www.patreon.com/MichaelLustgartenPhD

Discount Links:
NAD+ Quantification: https://www.jinfiniti.com/intracellular-nad-test/
Use Code: ConquerAging At Checkout.

Continue reading “Telomere Length Is Associated With Dementia Risk” »

A group of molecular and chemical biologists at the University of California, San Diego, has found possible evidence of interdomain horizontal gene transfer leading to the development of the eye in vertebrates. In their study, reported in Proceedings of the National Academy of Sciences, Chinmay Kalluraya, Alexander Weitzel, Brian Tsu and Matthew Daugherty used the IQ-TREE software program to trace the evolutionary history of genes associated with vision.

Ever since scientists proved that humans, along with other animals, developed due to evolutionary processes, one problem has stood out—how could evolution possibly account for the development of something as complicated as the eyeball? Even Charles Darwin was said to be stumped by the question. In recent times, this seeming conundrum has been used by some groups as a means to discredit evolutionary theory altogether. In this new effort, the team in California sought to answer the question once and for all.

Their work began with the idea that vision in vertebrates may have got its start by using light-sensitive genes transferred from microbes. To find out if that might be the case, the team submitted likely human gene candidates to the IQ-TREE program to look for similar genetic sequences in other creatures, most specifically, microbes.

Background: Breast cancer is the most common form of cancer in women worldwide. Advances in the early diagnosis and treatment of cancer in the last decade have progressively decreased the cancer mortality rate, and in recent years, immunotherapy has emerged as a relevant tool against cancer. HER2+ and triple-negative breast cancers (TNBCs) are considered more immunogenic and suitable for this kind of treatment due to the higher rate of tumor-infiltrating lymphocytes (TILs) and programmed death ligand 1 (PD-L1) expression. In TNBC, genetic aberrations further favor immunogenicity due to more neo-antigens in cancer cells. Methods: This review summarizes the principal ongoing conventional and investigational immunotherapies in breast cancer. Particularly, immune checkpoint inhibitors (ICIs) and their use alone or combined with DNA damage repair inhibitors (DDRis) are described.

(Visit: http://www.uctv.tv/) Animal development is directed by a genetic toolkit shared by all animals — from fruit flies to frogs to human beings — rather than different animals having different genetic toolkits. UCLA Professor of Biological Chemistry Edward De Robertis explains that the field of evolutionary development (or Evo-Devo) seeks to understand how so many beautiful animal forms evolved through the use of the original genetic toolkit of the last common ancestor of all animals, urbilateria, which existed at least 560 million years ago. Recorded on 10.25.2016. Series: “UCLA Faculty Research Lectures” [12/2016] [Science] [Show ID: 31409].

Synaptic plasticity is a critical process that regulates neuronal activity by allowing neurons to adjust their synaptic strength in response to changes in activity. Despite the high proximity of excitatory glutamatergic and inhibitory GABAergic postsynaptic zones and their functional integration within dendritic regions, concurrent plasticity has historically been underassessed. Growing evidence for pathological disruptions in the excitation and inhibition (E/I) balance in neurological and neurodevelopmental disorders indicates the need for an improved, more “holistic” understanding of synaptic interplay. There continues to be a long-standing focus on the persistent strengthening of excitation (excitatory long-term potentiation; eLTP) and its role in learning and memory, although the importance of inhibitory long-term potentiation (iLTP) and depression (iLTD) has become increasingly apparent. Emerging evidence further points to a dynamic dialogue between excitatory and inhibitory synapses, but much remains to be understood regarding the mechanisms and extent of this exchange. In this mini-review, we explore the role calcium signaling and synaptic crosstalk play in regulating postsynaptic plasticity and neuronal excitability. We examine current knowledge on GABAergic and glutamatergic synapse responses to perturbances in activity, with a focus on postsynaptic plasticity induced by short-term pharmacological treatments which act to either enhance or reduce neuronal excitability via ionotropic receptor regulation in neuronal culture. To delve deeper into potential mechanisms of synaptic crosstalk, we discuss the influence of synaptic activity on key regulatory proteins, including kinases, phosphatases, and synaptic structural/scaffolding proteins. Finally, we briefly suggest avenues for future research to better understand the crosstalk between glutamatergic and GABAergic synapses.

Ligand-gated ion channel GABA type A receptors (GABA_ARs) mediate the majority of fast inhibition in the central nervous system, while glutamatergic AMPA receptors (AMPARs) and NMDA receptors (NMDARs) collectively mediate fast excitatory neurotransmission. NMDARs particularly play a unique role in synaptic plasticity due to high calcium permeability and voltage-dependent Mg²⁺ block typically relieved by AMPAR-mediated depolarization. Slow inhibition and excitation are generated by G protein-coupled, GABA type B (GABA_BRs) and metabotropic glutamate receptors (mGluRs), respectively. The concerted action of these receptors balances neuronal excitability. A close and coordinated spatial relationship between glutamatergic and GABAergic synapses on dendrites (Megías et al., 2001; Bleckert et al., 2013; Iascone et al., 2020), sometimes as near as on the same spine (Chen et al., 2012), facilitates synaptic input integration, dynamic calcium regulation, synaptic crosstalk, and coregulation.

Synaptic plasticity describes the ability of synapses to adapt their relative strength based on the overall level of activity or specific activity patterns, often by dynamic regulation of receptor-synaptic scaffold interactions or through trafficking. During development, it is heavily involved in dendritic growth, synaptogenesis, and the formation of neural circuits (reviewed in Akgül and McBain, 2016; Ismail et al., 2017; Jenks et al., 2021). In mature neurons, synaptic plasticity is responsible for synapse remodeling during experience. Genetic mutations or pathology leading to altered excitatory or inhibitory neurotransmission or impaired synaptogenesis typically result in deficits in synaptic plasticity, a common feature in neurodevelopmental and neurological disorders (Rudolph and Möhler, 2014; Mele et al., 2019), including autism (Hansel, 2019; Sohal and Rubenstein, 2019), down syndrome (Galdzicki et al., 2001; Schulz et al.

What is antibiotic resistance? What is the global clinical antibacterial pipeline? What is the global preclinical antibacterial pipeline? Institutions associated with preclinical drug development Preclinical projects Trends in the preclinical antibacterial pipeline References Further reading.

The global preclinical antibacterial pipeline refers to innovative antibacterial candidate drugs that are under development with the aim of effectively eliminating newly emerged and pre-existing priority pathogens.

Antibacterial medicines or antibiotics treat bacterial infections in humans, animals, and plants. However, bacteria may eventually develop resistance against antibiotics-mediated killing by acquiring genetic mutations. Although antibiotic resistance occurs naturally, misuse or overuse of antibiotics can significantly escalate the process.

Many cancer therapies do not produce the hoped-for results. A common reason for this is that the tumors develop resistance to the medications. This is the case, for example, with alpelisib, a drug that has been approved for use in Switzerland for the past few years as a treatment for advanced breast cancer.

A research group at the Department of Biomedicine of the University of Basel has now discovered that the loss of the neurofibromin 1 (NF1) gene leads to a reduced response to alpelisib. The researchers also found that the dietary supplement N-acetylcysteine restores the sensitivity of cancer cells to this treatment. The findings have been published in the journal Cell Reports Medicine on April 11.

At the moment, patients with advanced and metastatic breast cancer lack effective treatment options. The PI3K signaling pathway is often overactive in breast cancer due to mutations promoting tumor development. The approval of the PI3K inhibitor Alpelisib was therefore keenly anticipated.

The remarkable physicochemical properties of the natural nucleic acids, DNA and RNA, define modern biology at the molecular level and are widely believed to have been central to life’s origins. However, their ability to form repositories of information as well as functional structures such as ligands (aptamers) and catalysts (ribozymes/DNAzymes) is not unique. A range of nonnatural alternatives, collectively termed xeno nucleic acids (XNAs), are also capable of supporting genetic information storage and propagation as well as evolution. This gives rise to a new field of “synthetic genetics,” which seeks to expand the nucleic acid chemical toolbox for applications in both biotechnology and molecular medicine. In this review, we outline XNA polymerase and reverse transcriptase engineering as a key enabling technology and summarize the application of “synthetic genetics” to the development of aptamers, enzymes, and nanostructures.

Copyright © 2019 Cold Spring Harbor Laboratory Press; all rights reserved.