ResearchPad - Biological Sciences https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Spermatozoa lacking Fertilization Influencing Membrane Protein (FIMP) fail to fuse with oocytes in mice]]> https://www.researchpad.co/product?articleinfo=N7e089ef3-cdb3-4902-9d09-74f164ea37a0

Significance

As the human body is composed of 60 trillion cells that originate from a fertilized egg, sperm–oocyte fusion is the initial event of our life. Few sperm–oocyte fusion factors have been unveiled to date, and only IZUMO1 has been identified as a sperm-specific fusion-mediating protein. Here, we identified the testis-specific 4930451I11Rik gene important for male fertility, playing a role in sperm–oocyte fusion during fertilization. Based on its functional role, we renamed this gene fertilization influencing membrane protein (Fimp). We discovered a factor responsible for sperm–oocyte fusion in mammals, and this knowledge could be used to develop in vitro and in vivo infertility treatments as well as male contraceptives.

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<![CDATA[The type IV pilin PilA couples surface attachment and cell-cycle initiation in Caulobacter crescentus]]> https://www.researchpad.co/product?articleinfo=Ndf4b9f7d-0eed-4a07-9f4a-91f96a480897

Significance

Pili are dynamic, long proteinaceous appendages found on the surface of many bacteria to promote adhesion. Here, we provide systems-level findings on a molecular signal transduction pathway that interlinks surface sensing with cell-cycle initiation. We propose that surface attachment induces depolymerization of pili filaments. The concomitant increase in pilin subunits within the inner membrane function as a stimulus to activate the second messenger cyclic di-GMP and trigger cell-cycle initiation. Furthermore, we show that the provision of a 17-amino acid synthetic peptide corresponding to the membrane portion of the pilin subunit mimics surface sensing, activates cell-cycle initiation, and inhibits surface attachment. Thus, synthetic peptide mimetics of pilin represent promising chemotypes to control biofilm formation and treat bacterial infections.

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<![CDATA[Impact of Xylella fastidiosa subspecies pauca in European olives]]> https://www.researchpad.co/product?articleinfo=N35024fc2-4751-4bfa-b381-3fd461109092

Significance

Xylella fastidiosa is one of the most dangerous plant-pathogenic bacteria worldwide. Regulatory measures were enacted in response to the detection of the subsp. pauca (Xfp) in Italian olives in 2013, but the current impact is nevertheless major. We developed a spatially explicit bio-economic model to compute potential future economic impact of the Xfp strain. Uncertainty on spread is accounted for by simulating different scenarios. The majority of orchards were found to be within climatically suitable territory. Even under slow disease spread and the ability to replant with resistant cultivars, projections of future economic impact in affected countries run in the billions of Euros. Our findings highlight the importance of minimizing disease spread and implementing adaptation measures in affected areas.

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<![CDATA[A multiproducer microbiome generates chemical diversity in the marine sponge Mycale hentscheli]]> https://www.researchpad.co/product?articleinfo=N09e84a7f-8bd9-43bc-ab75-8afaa59bc07e

Significance

Sponges, one of the oldest extant animal phyla, stand out among marine organisms as sources of structurally diverse bioactive natural products. Previous work on chemically rich sponges identified single “superproducer” symbionts in their microbiomes that generate the majority of the bioactive compounds known from their host. Here, we present a contrasting scenario for the New Zealand sponge Mycale hentscheli in which a multiproducer consortium is the basis of chemical diversity. Other than the known cocktail of cytotoxins, metagenomic and functional data support further chemical diversity originating from various uncultivated bacterial lineages. The results provide a rationale for distinct patterns of chemical variation observed within sponge species and reinforce uncultured microbes as promising source of compounds with therapeutic potential.

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<![CDATA[Vip1 is a kinase and pyrophosphatase switch that regulates inositol diphosphate signaling]]> https://www.researchpad.co/product?articleinfo=Nd04d9fc2-a864-4158-9156-bedee43244a3

Significance

Our studies demonstrate that Vip1 represents a rare class of bifunctional enzyme capable of synthesizing and destroying signaling molecules important for nutrient adaptation, cellular architecture, and organelle morphology. We find that Vip1 contains two tethered autonomous catalytic active sites, which modulate levels of 1-IP7 and 1,5-IP8 through 1-kinase and 1-pyrophosphatase domains. Each activity is critical for maintaining the highly dynamic anabolic and catabolic regulation of cellular pools of IP7 and IP8. That this occurs through a single gene product emphasizes that Vip1 is a key metabolic switch critical for cellular adaptation.

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<![CDATA[Rcf2 revealed in cryo-EM structures of hypoxic isoforms of mature mitochondrial III-IV supercomplexes]]> https://www.researchpad.co/product?articleinfo=Na42cde90-4275-4a05-8e54-55745c7be6e3

Significance

As the terminal electron acceptor of our mitochondrial respiratory chains, complex IV drives and regulates oxidative phosphorylation, the process by which most of our ATP is produced. Complex IV forms supercomplexes (SCs) of different stoichiometries with other respiratory proteins, interacting via its subunits with tissue-specific or oxygen level-dependent expression isoforms, suggesting a link between SC assembly and metabolic/disease state. We investigated the effect of complex IV subunit isoform exchange in yeast using cryo-EM and biochemical assays and found no significant differences in overall SC formation, architecture, or catalytic activities. However, our structural work unexpectedly revealed the presence of a Hig1 protein which we propose is a stoichiometric subunit of complex IV, at least when within a SC with complex III.

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<![CDATA[JNK-dependent intestinal barrier failure disrupts host–microbe homeostasis during tumorigenesis]]> https://www.researchpad.co/product?articleinfo=N219ffc0c-4077-4705-967b-51b558fe4c80

Significance

The intestinal epithelium forms a tight barrier to the environment and is constantly regenerated. Precise control of barrier function and tissue renewal is important to maintain homeostasis. Using an inducible tumor model in the Drosophila intestine, this study shows that tumor progression disrupts the intestinal barrier and leads to commensal dysbiosis, thereby further fueling tumor growth. This reenforcing feedback loop can be interrupted by treatments with JNK inhibitor or antibiotics.

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<![CDATA[Seasonal changes in NRF2 antioxidant pathway regulates winter depression-like behavior]]> https://www.researchpad.co/product?articleinfo=N6decbb21-8f58-4d33-8d93-cdfa62ac2583

Significance

At high latitudes, about 10% of the population suffers from depression in winter. Although it has become a serious public health issue, its underlying mechanism remains unknown. Interestingly, animals also show depression-like behavior in winter, and small teleosts have emerged as powerful models for the study of complex brain disorders. Here, we show that medaka exhibit decreased sociability and increased anxiety-like behavior under winter-like conditions. Using metabolomic and transcriptomic analyses, we found changes in multiple signaling pathways involved in depression, including the NRF2 antioxidant pathway. Chemical genomics and targeted mutation of the NRF2 gene revealed that seasonal changes in the NRF2 pathway regulate winter depression-like behavior. This study provides insights into the understanding and treatment of seasonally regulated affective disorders.

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<![CDATA[Evolutionary history of modern Samoans]]> https://www.researchpad.co/product?articleinfo=N19b91982-6334-4a34-98a9-a55396e10281

Significance

There are multiple archaeological debates regarding early Samoan population history. Here, we add genetic data to this discussion, which supports an initial small population size at the founding of the Samoan islands. We also indicate a major demographic change approximately 1,000 y ago that mirrors the archaeological record. In addition, we demonstrate the utility of rare genetic variants in identifying sparse population structure. These genetic results help establish a detailed demographic model for the Samoan population, which will aid in future studies of Oceanic populations for both history and disease.

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<![CDATA[Infectious KoRV-related retroviruses circulating in Australian bats]]> https://www.researchpad.co/product?articleinfo=Na7bff1f4-2d91-4ce2-88e7-be52c4bf7672

Significance

Bats represent 20% of all mammalian species and are an important reservoir of viruses that infect humans and other mammals. Retroviruses, such as HIV, are among the most important zoonotic viruses infecting humans, although little is known about their circulation in bat populations. We report the first exogenous retrovirus described in bats, the Hervey pteropid gammaretrovirus (HPG), a reproduction-competent retrovirus within northeast Australia. Koala populations are currently in severe decline and at risk from koala retrovirus (KoRV), which is closely related to HPG and whose origins remain unclear. The identification of bats as a source of diverse infectious retroviruses related to KoRV implicates bats as a reservoir of KoRV-related viruses that potentially can be transmitted to other mammalian species.

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<![CDATA[Robust landscapes of ribosome dwell times and aminoacyl-tRNAs in response to nutrient stress in liver]]> https://www.researchpad.co/product?articleinfo=Nda03592f-cc78-44ee-ae52-ab18aa18c815

Significance

Protein synthesis is a fundamental and tightly controlled process which allows organisms to respond rapidly to external signals such as nutrient availability or stress conditions. While the initiation step is well studied, the determinants of translation elongation rate on mRNAs are poorly understood, particularly in mammals. Here we combined computational and molecular biology approaches to shed light on the determinants of translation elongation rates and their relationships with aminoacyl-tRNAs in livers of normally fed and fasted mice. We found that the ribosome dwell times in mouse liver depend on codon pairs, were robust to prolonged fasting, and can be explained to some extent by a combination of aminoacyl-tRNA level and codon usage/tRNA balance.

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<![CDATA[Dynamic coupling of whole-brain neuronal and neurotransmitter systems]]> https://www.researchpad.co/product?articleinfo=N82972317-7e5c-4699-b806-9f254f2b43e8

Significance

In a technical tour de force, we have created a framework demonstrating the underlying fundamental principles of bidirectional coupling of neuronal and neurotransmitter dynamical systems. Specifically, in the present study, we combined multimodal neuroimaging data to causally explain the functional effects of specific serotoninergic receptor (5-HT2AR) stimulation with psilocybin in healthy humans. Longer term, this could provide a better understanding of why psilocybin is showing considerable promise as a therapeutic intervention for neuropsychiatric disorders including depression, anxiety, and addiction.

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<![CDATA[Analysis of APOBEC-induced mutations in yeast strains with low levels of replicative DNA polymerases]]> https://www.researchpad.co/product?articleinfo=N2cf55f91-3913-4f73-bfad-eaa282412c81

Significance

Perturbations in DNA replication cause high levels of chromosome rearrangements and it has been suggested that DNA replication stress promotes oncogenesis. In this study, we show that low levels of the DNA polymerases involved in replication in the yeast Saccharomyces cerevisiae lead to greatly elevated levels of single-stranded DNA. We suggest that these single-stranded regions are fragile, generating the DNA breaks that initiate translocations and other types of chromosome rearrangements.

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<![CDATA[Noninvasive hippocampal blood−brain barrier opening in Alzheimer’s disease with focused ultrasound]]> https://www.researchpad.co/product?articleinfo=N45f31126-6340-488f-bf4d-7df2c4768529

The blood–brain barrier (BBB) presents a significant challenge for treating brain disorders. The hippocampus is a key target for novel therapeutics, playing an important role in Alzheimer’s disease (AD), epilepsy, and depression. Preclinical studies have shown that magnetic resonance (MR)-guided low-intensity focused ultrasound (FUS) can reversibly open the BBB and facilitate delivery of targeted brain therapeutics. We report initial clinical trial results evaluating the safety, feasibility, and reversibility of BBB opening with FUS treatment of the hippocampus and entorhinal cortex (EC) in patients with early AD. Six subjects tolerated a total of 17 FUS treatments with no adverse events and neither cognitive nor neurological worsening. Post-FUS contrast MRI revealed immediate and sizable hippocampal parenchymal enhancement indicating BBB opening, followed by BBB closure within 24 h. The average opening was 95% of the targeted FUS volume, which corresponds to 29% of the overall hippocampus volume. We demonstrate that FUS can safely, noninvasively, transiently, reproducibly, and focally mediate BBB opening in the hippocampus/EC in humans. This provides a unique translational opportunity to investigate therapeutic delivery in AD and other conditions.

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<![CDATA[Phosphoinositides regulate chloroplast processes]]> https://www.researchpad.co/product?articleinfo=N5fa10e02-9abc-41e9-b9de-ebc5a911aefd ]]> <![CDATA[Redefining the heterogeneity of peripheral nerve cells in health and autoimmunity]]> https://www.researchpad.co/product?articleinfo=Nf11306cd-b1fa-4dea-b8f8-c518a6d7fffd

Significance

We here present a transcriptional map of peripheral nerve cells in health and autoimmunity. Identified marker genes of nonmyelinating Schwann cells and nerve-associated fibroblasts will facilitate a better understanding of the complex cellular architecture of peripheral nerves. The two distinct populations of nerve-resident homeostatic myeloid cells suggest an unexpectedly unique and heterogeneous local immune repertoire in peripheral nerves with signs of heterogeneous ontogenetic origin. Complex changes of local cell–cell communication networks indicate autoimmune neuritis as a disease affecting “immune networks” rather than single cell types. The findings also suggest that immunological features are partially shared and conserved across different parts of the nervous system.

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<![CDATA[Viral zoonotic risk is homogenous among taxonomic orders of mammalian and avian reservoir hosts]]> https://www.researchpad.co/product?articleinfo=Na03c08b5-ea2f-46f5-a054-75e787634ae7

Significance

Identifying whether novel human viruses disproportionately originate from certain animal groups could inform risk-based allocations of research and surveillance effort. Whether such “special reservoirs” exist remains controversial. We show that the proportion of viruses that infect humans varies minimally across reservoir taxonomic orders. Instead, the number of human-infecting viruses increases proportionately to the total number of viruses maintained by each reservoir group, which is in turn explained by the number of animal species within each group. This supports a host-neutral explanation for observed variation in the number of zoonoses among animal groups, such that traits of animal orders are unlikely to produce viruses that disproportionately threaten humans. These findings refine strategies to identify high-risk viruses prior to their emergence.

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<![CDATA[Cavitation in soft matter]]> https://www.researchpad.co/product?articleinfo=Nd0a93384-098b-4855-abf9-29f74edc2c6d

Cavitation is the sudden, unstable expansion of a void or bubble within a liquid or solid subjected to a negative hydrostatic stress. Cavitation rheology is a field emerging from the development of a suite of materials characterization, damage quantification, and therapeutic techniques that exploit the physical principles of cavitation. Cavitation rheology is inherently complex and broad in scope with wide-ranging applications in the biology, chemistry, materials, and mechanics communities. This perspective aims to drive collaboration among these communities and guide discussion by defining a common core of high-priority goals while highlighting emerging opportunities in the field of cavitation rheology. A brief overview of the mechanics and dynamics of cavitation in soft matter is presented. This overview is followed by a discussion of the overarching goals of cavitation rheology and an overview of common experimental techniques. The larger unmet needs and challenges of cavitation in soft matter are then presented alongside specific opportunities for researchers from different disciplines to contribute to the field.

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<![CDATA[Pathogen manipulation of chloroplast function triggers a light-dependent immune recognition]]> https://www.researchpad.co/product?articleinfo=Nda9be7b8-5caf-4f1d-81e2-2b6bef726e32

Significance

Plant pathogens, such as Irish potato famine agent Phytophthora infestans, remain the most significant threats to global food security. Plant disease resistance is often conferred by nucleotide-binding leucine-rich repeat (NLR) proteins, intracellular immune sensors that recognize and eliminate pathogens. However, little is known about how pathogen-activated NLR immunity is influenced by environmental factors such as light. Here, we show that P. infestans manipulation of plant chloroplast function triggers a light-dependent immune response. Our results reveal that light-induced alternative promoter selection regulates plant immune recognition of a pathogen virulence factor by an agriculturally important NLR-type receptor protein.

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<![CDATA[A common coupling mechanism for A-type heme-copper oxidases from bacteria to mitochondria]]> https://www.researchpad.co/product?articleinfo=N3c240945-18cb-4c51-94cc-0f62213cf780

Significance

We present a comprehensive investigation of mitochondrial DNA-encoded variants of cytochrome c oxidase (CcO) that harbor mutations within their core catalytic subunit I, designed to interrogate the presently disputed functions of the three putative proton channels. We assess overall respiratory competence, specific CcO catalytic activity, and, most importantly, proton/electron (H+/e) stoichiometry from adenosine diphosphate to oxygen ratio measurements on preparations of intact mitochondria. We unequivocally show that yeast mitochondrial CcO uses the D-channel to translocate protons across its hydrophilic core, providing direct evidence in support of a common proton pumping mechanism across all members of the A-type heme-copper oxidase superfamily, independent of their bacterial or mitochondrial origin.

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