Subjects -> BIOLOGY (Total: 3174 journals)
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BIOLOGY (1491 journals)            First | 1 2 3 4 5 6 7 8 | Last

Showing 401 - 600 of 1720 Journals sorted alphabetically
Cryoletters     Full-text available via subscription   (Followers: 4)
Cuadernos de Neuropsicología     Open Access   (Followers: 1)
Current Applied Science and Technology     Open Access  
Current Bioinformatics     Hybrid Journal   (Followers: 13)
Current Biology     Full-text available via subscription   (Followers: 226)
Current Genomics     Hybrid Journal   (Followers: 8)
Current Landscape Ecology Reports     Hybrid Journal   (Followers: 2)
Current Medical Science     Hybrid Journal   (Followers: 1)
Current Molecular Medicine     Hybrid Journal   (Followers: 3)
Current Opinion in Cell Biology     Hybrid Journal   (Followers: 51)
Current Opinion in Molecular Therapeutics     Full-text available via subscription   (Followers: 8)
Current Opinion in Neurobiology     Hybrid Journal   (Followers: 32)
Current Opinion in Structural Biology     Hybrid Journal   (Followers: 26)
Current Opinion in Systems Biology     Hybrid Journal   (Followers: 2)
Current Pharmacogenomics and Personalized Medicine     Hybrid Journal   (Followers: 3)
Current Protein and Peptide Science     Hybrid Journal   (Followers: 8)
Current Proteomics     Hybrid Journal   (Followers: 4)
Current Protocols in Bioinformatics     Hybrid Journal   (Followers: 1)
Current Protocols in Cell Biology     Hybrid Journal  
Current Protocols in Molecular Biology     Hybrid Journal  
Current Protocols in Mouse Biology     Hybrid Journal  
Current Protocols in Neuroscience     Hybrid Journal  
Current Protocols in Plant Biology     Hybrid Journal   (Followers: 2)
Current Protocols in Protein Science     Hybrid Journal   (Followers: 1)
Current Protocols in Stem Cell Biology     Hybrid Journal  
Current Research in Bacteriology     Open Access   (Followers: 3)
Current Research in Biostatistics     Open Access   (Followers: 8)
Current Research in Chemical Biology     Open Access  
Current Research in Neurobiology     Open Access  
Current Research in Parasitology & Vector-Borne Diseases     Open Access  
Current Research in Structural Biology     Open Access  
Current Research in Translational Medicine     Full-text available via subscription   (Followers: 1)
Current Research in Virological Science     Open Access   (Followers: 2)
Current Science     Open Access   (Followers: 115)
Current Stem Cell Reports     Hybrid Journal   (Followers: 4)
Current Stem Cell Research & Therapy     Hybrid Journal   (Followers: 8)
Current Topics in Developmental Biology     Full-text available via subscription   (Followers: 3)
Current Topics in Membranes     Full-text available via subscription   (Followers: 1)
Cytotechnology     Hybrid Journal   (Followers: 11)
Database : The Journal of Biological Databases and Curation     Open Access   (Followers: 10)
Dendrochronologia     Hybrid Journal   (Followers: 1)
Developing World Bioethics     Hybrid Journal   (Followers: 6)
Developmental & Comparative Immunology     Hybrid Journal   (Followers: 5)
Developmental Biology     Hybrid Journal   (Followers: 26)
Developmental Cell     Full-text available via subscription   (Followers: 46)
Developmental Dynamics     Hybrid Journal   (Followers: 4)
Developmental Neurobiology     Hybrid Journal   (Followers: 6)
Dhaka University Journal of Biological Sciences     Open Access  
Diatom Research     Hybrid Journal   (Followers: 3)
Differentiation     Hybrid Journal  
Digital Biomarkers     Open Access   (Followers: 1)
Disease Models and Mechanisms     Open Access   (Followers: 1)
Diseases of Aquatic Organisms     Hybrid Journal  
DNA and Cell Biology     Hybrid Journal   (Followers: 9)
DNA Repair     Hybrid Journal   (Followers: 3)
DNA Research     Open Access   (Followers: 4)
Doklady Physics     Hybrid Journal   (Followers: 1)
Drug Discovery Today: Technologies     Full-text available via subscription   (Followers: 13)
Drug Resistance Updates     Hybrid Journal   (Followers: 3)
e-Jurnal Rekayasa dan Teknologi Budidaya Perairan     Open Access  
Ecocycles     Open Access   (Followers: 4)
Ecohydrology & Hydrobiology     Full-text available via subscription   (Followers: 4)
Ecología en Bolivia     Open Access  
Ecological Engineering     Hybrid Journal   (Followers: 4)
Ecological Questions     Open Access   (Followers: 5)
Ecological Solutions and Evidence     Open Access   (Followers: 1)
Ecology and Society     Open Access   (Followers: 50)
Ecology Letters     Hybrid Journal   (Followers: 245)
Economics & Human Biology     Hybrid Journal   (Followers: 1)
Ecoprint : An International Journal of Ecology     Open Access   (Followers: 4)
Ecoscience     Hybrid Journal   (Followers: 2)
Ecosystem Health and Sustainability     Open Access   (Followers: 1)
Ecosystems and People     Open Access   (Followers: 2)
Educational Technology Research and Development     Partially Free   (Followers: 45)
EDUSAINS     Open Access  
EFB Bioeconomy Journal     Open Access  
Egyptian Journal of Basic and Applied Sciences     Open Access  
Egyptian Journal of Biology     Open Access  
Egyptian Journal of Natural History     Open Access   (Followers: 1)
EJNMMI Research     Open Access  
Ekologia     Open Access  
el-Hayah     Open Access  
Electromagnetic Biology and Medicine     Hybrid Journal  
eLife     Open Access   (Followers: 95)
Embo Molecular Medicine     Open Access   (Followers: 10)
EMBO reports     Full-text available via subscription   (Followers: 23)
Emotion Review     Hybrid Journal   (Followers: 20)
Endangered Species Research     Open Access   (Followers: 6)
Endocrine Connections     Open Access   (Followers: 4)
Endothelium: Journal of Endothelial Cell Research     Full-text available via subscription   (Followers: 3)
Engineering & Technology     Hybrid Journal   (Followers: 22)
Engineering Economist, The     Hybrid Journal   (Followers: 4)
Engineering in Life Sciences     Hybrid Journal   (Followers: 3)
Engineering Optimization     Hybrid Journal   (Followers: 19)
Ensaios e Ciência : Ciências Biológicas, Agrárias e da Saúde     Open Access  
Environmental Biology of Fishes     Hybrid Journal   (Followers: 4)
Environmental DNA     Open Access  
Environmental Dynamics and Global Climate Change     Open Access   (Followers: 21)
Environmental Epigenetics     Open Access   (Followers: 2)
Environmental Microbiology     Hybrid Journal   (Followers: 27)
Environmental Microbiome     Open Access  
Environmental Science & Technology     Hybrid Journal   (Followers: 180)
Enzyme and Microbial Technology     Hybrid Journal   (Followers: 12)
Enzyme Research     Open Access   (Followers: 4)
Epidemiology & Infection     Open Access   (Followers: 23)
Epigenomes     Open Access  
EPMA Journal     Open Access  
Ethiopian Journal of Biological Sciences     Open Access   (Followers: 3)
Ethnobiology and Conservation     Open Access   (Followers: 3)
Ethnobiology Letters     Open Access  
Ethnobotany Research & Applications : a journal of plants, people and applied research     Open Access   (Followers: 2)
Ethnoscientia : Brazilian Journal of Ethnobiology and Ethnoecology     Open Access  
Ethology     Hybrid Journal   (Followers: 11)
Ethology Ecology & Evolution     Hybrid Journal   (Followers: 16)
EuPA Open Proteomics     Open Access   (Followers: 2)
EUREKA : Life Sciences     Open Access  
European Journal of Biological Research     Open Access   (Followers: 1)
European Journal of Biology     Open Access   (Followers: 1)
European Journal of Cell Biology     Hybrid Journal   (Followers: 6)
European Journal of Ecology     Open Access   (Followers: 1)
European Journal of Neuroscience     Hybrid Journal   (Followers: 36)
European Journal of Obstetrics & Gynecology and Reproductive Biology     Hybrid Journal   (Followers: 19)
European Journal of Obstetrics & Gynecology and Reproductive Biology : X     Open Access  
European Journal of Phycology     Hybrid Journal   (Followers: 4)
European Journal of Protistology     Hybrid Journal   (Followers: 5)
European Journal of Soil Biology     Hybrid Journal   (Followers: 3)
European Online Journal of Natural and Social Sciences     Open Access   (Followers: 4)
European Scientific Journal     Open Access   (Followers: 1)
Evidência - Ciência e Biotecnologia - Interdisciplinar     Open Access  
EvoDevo     Open Access   (Followers: 4)
Evolution     Partially Free   (Followers: 129)
Evolution and Human Behavior     Hybrid Journal   (Followers: 22)
Evolution Letters     Open Access   (Followers: 8)
Evolutionary Applications     Open Access   (Followers: 6)
Evolutionary Bioinformatics     Open Access   (Followers: 12)
Evolutionary Biology     Hybrid Journal   (Followers: 25)
Evolutionary Computation     Hybrid Journal   (Followers: 11)
Evolutionary Systematics     Open Access   (Followers: 2)
EXCLI Journal : Experimental and Clinical Sciences     Open Access  
Experimental & Molecular Medicine     Open Access  
Experimental and Applied Acarology     Hybrid Journal   (Followers: 1)
Experimental Parasitology     Hybrid Journal   (Followers: 1)
Expert Opinion on Biological Therapy     Hybrid Journal   (Followers: 4)
Expert Opinion on Environmental Biology     Hybrid Journal  
Expert Review of Proteomics     Hybrid Journal   (Followers: 4)
ExRNA     Open Access  
Extreme Life, Biospeology & Astrobiology - International Journal of the Bioflux Society     Full-text available via subscription   (Followers: 4)
Extremophiles     Hybrid Journal   (Followers: 1)
F&S Science : Official journal of the American Society for Reproductive Medicine     Open Access  
Facta Universitatis, Series : Medicine and Biology     Open Access  
Familial Cancer     Hybrid Journal   (Followers: 2)
FASEB BioAdvances     Open Access  
Fauna Norvegica     Open Access  
Fauna of New Zealand     Open Access  
Febs Journal     Hybrid Journal   (Followers: 29)
Feddes Repertorium     Hybrid Journal  
Fems Yeast Research     Hybrid Journal   (Followers: 11)
FIGEMPA : Investigación y Desarrollo     Open Access   (Followers: 1)
Fire Ecology     Open Access   (Followers: 2)
Fish & Shellfish Immunology     Hybrid Journal   (Followers: 10)
Fish and Shellfish Immunology Reports     Open Access   (Followers: 1)
Fishes     Open Access  
Fitoterapia     Hybrid Journal   (Followers: 4)
Florea : Jurnal Biologi dan Pembelajarannya     Open Access  
Fly     Full-text available via subscription  
Folia Biologica     Free   (Followers: 1)
Folia Histochemica et Cytobiologica     Open Access  
Folia Microbiologica     Hybrid Journal   (Followers: 2)
Folia Primatologica     Full-text available via subscription   (Followers: 4)
Food and Bioproducts Processing     Hybrid Journal   (Followers: 3)
Food and Ecological Systems Modelling Journal     Open Access  
Food and Waterborne Parasitology     Open Access  
Food Webs     Hybrid Journal   (Followers: 1)
Forensic Genomics     Full-text available via subscription   (Followers: 2)
Forest Pathology     Hybrid Journal   (Followers: 1)
Forschung     Hybrid Journal   (Followers: 1)
Foundations of Physics     Hybrid Journal   (Followers: 40)
Free Radical Biology and Medicine     Hybrid Journal   (Followers: 6)
Free Radical Research     Hybrid Journal   (Followers: 2)
Freshwater Science     Full-text available via subscription   (Followers: 14)
Frontiers in Ecology and Evolution     Open Access   (Followers: 45)
Frontiers in Evolutionary Neuroscience     Open Access   (Followers: 7)
Frontiers in Life Science     Hybrid Journal   (Followers: 1)
Frontiers in Marine Science     Open Access   (Followers: 13)
Frontiers in Network Physiology     Open Access   (Followers: 2)
Frontiers in Neurogenesis     Open Access   (Followers: 2)
Frontiers in Neuroprosthetics     Open Access   (Followers: 6)
Frontiers of Biogeography     Open Access   (Followers: 4)
Frontiers of Biology     Hybrid Journal   (Followers: 2)
Frontiers of Environmental Science & Engineering     Hybrid Journal   (Followers: 3)
Frontiers of Medical and Biological Engineering     Hybrid Journal  
Functional & Integrative Genomics     Hybrid Journal   (Followers: 7)
Fundamental and Applied Limnology / Archiv für Hydrobiologie     Full-text available via subscription   (Followers: 3)
Fundamental Research     Open Access  
Fungal Biology     Hybrid Journal   (Followers: 6)
Fungal Biology and Biotechnology     Open Access   (Followers: 2)
Fungal Biology Reviews     Full-text available via subscription   (Followers: 9)
Fungal Diversity     Hybrid Journal   (Followers: 2)
Fungal Ecology     Hybrid Journal   (Followers: 6)
Fungal Genetics Reports     Open Access  

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Similar Journals
Journal Cover
Disease Models and Mechanisms
Journal Prestige (SJR): 2.427
Citation Impact (citeScore): 4
Number of Followers: 1  

  This is an Open Access Journal Open Access journal
ISSN (Print) 1754-8403 - ISSN (Online) 1754-8411
Published by Company of Biologists, The Homepage  [5 journals]
  • Stool is a sensitive and noninvasive source of DNA for monitoring
           expansion in repeat expansion disease mouse models

    • Authors: Zhao X; McHugh C, Coffey SR, et al.
      Abstract: ABSTRACTRepeat expansion diseases are a large group of human genetic disorders caused by expansion of a specific short tandem repeat tract. Expansion in somatic cells affects age of onset and disease severity in some of these disorders. However, alleles in DNA derived from blood, a commonly used source of DNA, usually show much less expansion than disease-relevant cells in the central nervous system in both humans and mouse models. Here we examined the extent of expansion in different DNA sources from mouse models of the fragile X-related disorders, Huntington's disease, spinocerebellar ataxia type 1 and spinocerebellar ataxia type 2. We found that DNA isolated from stool is a much better indicator of somatic expansion than DNA from blood. As stool is a sensitive and noninvasive source of DNA, it can be useful for studies of factors affecting the risk of expansion, or the monitoring of treatments aimed at reducing expansion in preclinical trials, as it would allow expansions to be examined longitudinally in the same animal and allow significant changes in expansion to be observed much earlier than is possible with other DNA sources.
      PubDate: Fri, 13 May 2022 00:00:00 GMT
       
  • Osteoblast lineage Sod2 deficiency leads to an osteoporosis-like phenotype
           in mice

    • Authors: Schoppa AM; Chen X, Ramge J, et al.
      Abstract: ABSTRACTOsteoporosis is a systemic metabolic skeletal disease characterized by low bone mass and strength associated with fragility fractures. Oxidative stress, which results from elevated intracellular reactive oxygen species (ROS) and arises in the aging organism, is considered one of the critical factors contributing to osteoporosis. Mitochondrial (mt)ROS, as the superoxide anion (O2−) generated during mitochondrial respiration, are eliminated in the young organism by antioxidant defense mechanisms, including superoxide dismutase 2 (SOD2), the expression and activity of which are decreased in aging mesenchymal progenitor cells, accompanied by increased mtROS production. Using a mouse model of osteoblast lineage cells with Sod2 deficiency, we observed significant bone loss in trabecular and cortical bones accompanied by decreased osteoblast activity, increased adipocyte accumulation in the bone marrow and augmented osteoclast activity, suggestive of altered mesenchymal progenitor cell differentiation and osteoclastogenesis. Furthermore, osteoblast senescence was increased. To date, there are only a few studies suggesting a causal association between mtROS and cellular senescence in tissue in vivo. Targeting SOD2 to improve redox homeostasis could represent a potential therapeutic strategy for maintaining bone health during aging.
      PubDate: Fri, 13 May 2022 00:00:00 GMT
       
  • Temporal and spatially controlled APP transgene expression using
           Cre-dependent alleles

    • Authors: Koller EJ; Comstock M, Bean JC, et al.
      Abstract: ABSTRACTAlthough a large number of mouse models have been made to study Alzheimer's disease, only a handful allow experimental control over the location or timing of the protein being used to drive pathology. Other fields have used the Cre and the tamoxifen-inducible CreER driver lines to achieve precise spatial and temporal control over gene deletion and transgene expression, yet these tools have not been widely used in studies of neurodegeneration. Here, we describe two strategies for harnessing the wide range of Cre and CreER driver lines to control expression of disease-associated amyloid precursor protein (APP) in modeling Alzheimer's amyloid pathology. We show that CreER-based spatial and temporal control over APP expression can be achieved with existing lines by combining a Cre driver with a tetracycline-transactivator (tTA)-dependent APP responder using a Cre-to-tTA converter line. We then describe a new mouse line that places APP expression under direct control of Cre recombinase using an intervening lox-stop-lox cassette. Mating this allele with a CreER driver allows both spatial and temporal control over APP expression, and with it, amyloid onset.This article has an associated First Person interview with the first author of the paper.
      PubDate: Fri, 13 May 2022 00:00:00 GMT
       
  • Endometrial organoids derived from Mayer–Rokitansky–Küster–Hauser
           syndrome patients provide insights into disease-causing pathways

    • Authors: Brucker SY; Hentrich T, Schulze-Hentrich JM, et al.
      Abstract: ABSTRACTThe uterus is responsible for the nourishment and mechanical protection of the developing embryo and fetus and is an essential part in mammalian reproduction. Mayer–Rokitansky–Küster–Hauser (MRKH) syndrome is characterized by agenesis of the uterus and upper part of the vagina in females with normal ovarian function. Although heavily studied, the cause of the disease is still enigmatic. Current research in the field of MRKH mainly focuses on DNA-sequencing efforts and, so far, has been unable to decipher the nature and heterogeneity of the disease, thereby holding back scientific and clinical progress. Here, we developed long-term expandable organoid cultures from endometrium found in uterine rudiment horns of MRKH patients. Phenotypically, they share great similarity with healthy control organoids and are surprisingly fully hormone responsive. Transcriptome analyses, however, identified an array of dysregulated genes that point to potentially disease-causing pathways altered during the development of the female reproductive tract. We consider the endometrial organoid cultures to be a powerful research tool that promise to enable an array of studies into the pathogenic origins of MRKH syndrome and possible treatment opportunities to improve patient quality of life.
      PubDate: Tue, 10 May 2022 00:00:00 GMT
       
  • TOR signalling is required for host lipid metabolic remodelling and
           survival following enteric infection in Drosophila

    • Authors: Deshpande R; Lee B, Qiao Y, et al.
      Abstract: ABSTRACTWhen infected by enteric pathogenic bacteria, animals need to initiate local and whole-body defence strategies. Although most attention has focused on the role of innate immune anti-bacterial responses, less is known about how changes in host metabolism contribute to host defence. Using Drosophila as a model system, we identify induction of intestinal target-of-rapamycin (TOR) kinase signalling as a key adaptive metabolic response to enteric infection. We find that enteric infection induces both local and systemic induction of TOR independently of the Immune deficiency (IMD) innate immune pathway, and we see that TOR functions together with IMD signalling to promote infection survival. These protective effects of TOR signalling are associated with remodelling of host lipid metabolism. Thus, we see that TOR is required to limit excessive infection-mediated wasting of host lipid stores by promoting an increase in the levels of gut- and fat body-expressed lipid synthesis genes. Our data support a model in which induction of TOR represents a host tolerance response to counteract infection-mediated lipid wasting in order to promote survival.This article has an associated First Person interview with the first author of the paper.
      PubDate: Mon, 09 May 2022 00:00:00 GMT
       
  • Characterization of a novel zebrafish model of SPEG -related centronuclear
           myopathy

    • Authors: Espinosa KG; Geissah S, Groom L, et al.
      Abstract: ABSTRACTCentronuclear myopathy (CNM) is a congenital neuromuscular disorder caused by pathogenic variation in genes associated with membrane trafficking and excitation–contraction coupling (ECC). Bi-allelic autosomal-recessive mutations in striated muscle enriched protein kinase (SPEG) account for a subset of CNM patients. Previous research has been limited by the perinatal lethality of constitutive Speg knockout mice. Thus, the precise biological role of SPEG in developing skeletal muscle remains unknown. To address this issue, we generated zebrafish spega, spegb and spega;spegb (speg-DKO) mutant lines. We demonstrated that speg-DKO zebrafish faithfully recapitulate multiple phenotypes associated with CNM, including disruption of the ECC machinery, dysregulation of calcium homeostasis during ECC and impairment of muscle performance. Taking advantage of zebrafish models of multiple CNM genetic subtypes, we compared novel and known disease markers in speg-DKO with mtm1-KO and DNM2-S619L transgenic zebrafish. We observed Desmin accumulation common to all CNM subtypes, and Dnm2 upregulation in muscle of both speg-DKO and mtm1-KO zebrafish. In all, we establish a new model of SPEG-related CNM, and identify abnormalities in this model suitable for defining disease pathomechanisms and evaluating potential therapies.This article has an associated First Person interview with the joint first authors of the paper.
      PubDate: Mon, 09 May 2022 00:00:00 GMT
       
  • Inhibition of activin A receptor signalling attenuates age-related
           pathological cardiac remodelling

    • Authors: Clavere NG; Alqallaf A, Rostron KA, et al.
      Abstract: ABSTRACTIn the heart, ageing is associated with DNA damage, oxidative stress, fibrosis and activation of the activin signalling pathway, leading to cardiac dysfunction. The cardiac effects of activin signalling blockade in progeria are unknown. This study investigated the cardiac effects of progeria induced by attenuated levels of Ercc1, which is required for DNA excision and repair, and the impact of activin signalling blockade using a soluble activin receptor type IIB (sActRIIB). DNA damage and oxidative stress were significantly increased in Ercc1Δ/− hearts, but were reduced by sActRIIB treatment. sActRIIB treatment improved cardiac systolic function and induced cardiomyocyte hypertrophy in Ercc1Δ/− hearts. RNA-sequencing analysis showed that in Ercc1Δ/− hearts, there was an increase in pro-oxidant and a decrease in antioxidant gene expression, whereas sActRIIB treatment reversed this effect. Ercc1Δ/− hearts also expressed higher levels of anti-hypertrophic genes and decreased levels of pro-hypertrophic ones, which were also reversed by sActRIIB treatment. These results show for the first time that inhibition of activin A receptor signalling attenuates cardiac dysfunction, pathological tissue remodelling and gene expression in Ercc1-deficient mice and presents a potentially novel therapeutic target for heart diseases.
      PubDate: Mon, 09 May 2022 00:00:00 GMT
       
  • Long-term non-invasive drug treatments in adult zebrafish that lead to
           melanoma drug resistance

    • Authors: Lu Y; Patton E.
      Abstract: ABSTRACTZebrafish embryos are widely used for drug discovery, however, administering drugs to adult zebrafish is limited by current protocols that can cause stress. Here, we developed a drug formulation and administration method for adult zebrafish by producing food-based drug pellets that are consumed voluntarily. We applied this to zebrafish with BRAF-mutant melanoma, a model that has significantly advanced our understanding of melanoma progression, but not of drug resistance due to the limitations of current treatment methods. Zebrafish with melanomas responded to short-term, precise and daily dosing with drug pellets made with the BRAFV600E inhibitor, vemurafenib. On-target drug efficacy was determined by phospho-Erk staining. Continued drug treatment led to the emergence, for the first time in zebrafish, of acquired drug resistance and melanoma relapse, modelling the responses seen in melanoma patients. This method presents a controlled, non-invasive approach that permits long-term drug studies and can be widely applied to adult zebrafish models.
      PubDate: Mon, 09 May 2022 00:00:00 GMT
       
  • A genetic screen in Drosophila reveals the role of fucosylation in host
           susceptibility to Candida infection

    • Authors: Glittenberg MT; Kounatidis I, Atilano M, et al.
      Abstract: ABSTRACTCandida infections constitute a blind spot in global public health as very few new anti-fungal drugs are being developed. Genetic surveys of host susceptibilities to such infections using mammalian models have certain disadvantages in that obtaining results is time-consuming, owing to relatively long lifespans, and these results have low statistical resolution because sample sizes are usually small. Here, we report a targeted genetic screening of 5698 RNAi lines encompassing 4135 Drosophila genes with human homologues, several of which we identify as important for host survival after Candida albicans infection. These include genes in a variety of functional classes encompassing gene expression, intracellular signalling, metabolism and enzymatic regulation. Analysis of one of the screen hits, the infection-induced α-(1,3)-fucosylase FucTA, showed that N-glycan fucosylation has several targets among proteins involved in host defence, which provides multiple avenues of investigation for the mechanistic analysis of host survival to systemic C. albicans infection.
      PubDate: Mon, 09 May 2022 00:00:00 GMT
       
  • First person – Karla G. Espinosa and Salma Geissah

    • Abstract: ABSTRACTFirst Person is a series of interviews with the first authors of a selection of papers published in Disease Models & Mechanisms, helping early-career researchers promote themselves alongside their papers. Karla G. Espinosa and Salma Geissah are co-first authors on ‘ Characterization of a novel zebrafish model of SPEG-related centronuclear myopathy’, published in DMM. Karla completed the research described in this article while an MSc student in the lab of Dr James J. Dowling at the Hospital for Sick Children and University of Toronto, Toronto, ON, Canada, investigating the molecular mechanisms behind cardiac and skeletal muscle contraction. Salma is an MSc student in the lab of Dr James J. Dowling at the Hospital for Sick Children and University of Toronto, Toronto, ON, Canada, investigating the molecular biology of muscle disease, how muscles function and the dynamic processes involved.
      PubDate: Mon, 09 May 2022 00:00:00 GMT
       
  • First person – Rujuta Deshpande

    • Abstract: ABSTRACTFirst Person is a series of interviews with the first authors of a selection of papers published in Disease Models & Mechanisms, helping early-career researchers promote themselves alongside their papers. Rujuta Deshpande is first author on ‘ TOR signalling is required for host lipid metabolic remodelling and survival following enteric infection in Drosophila’, published in DMM. Rujuta conducted the research described in this article while a PhD student in Dr Savraj Grewal's lab at Clark H. Smith Brain Tumour Centre, Arnie Charbonneau Cancer Institute, and Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, Canada. She is now a Postdoctoral Associate in the lab of Dr Derek McKay at Calvin, Phoebe & Joan Snyder Institute for Chronic Diseases, Department of Physiology & Pharmacology, Cumming School of Medicine, University of Calgary, investigating the role of human interleukin (IL)4-activated macrophages in wound healing of the intestinal epithelium as a new treatment for inflammatory bowel diseases (IBD).
      PubDate: Mon, 09 May 2022 00:00:00 GMT
       
  • Rapid assessment of the temporal function and phenotypic reversibility of
           neurodevelopmental disorder risk genes in Caenorhabditis elegans

    • Authors: Kepler LD; McDiarmid TA, Rankin CH.
      Abstract: ABSTRACTRecent studies have indicated that some phenotypes caused by decreased function of select neurodevelopmental disorder (NDD) risk genes can be reversed by restoring gene function in adulthood. However, few of the hundreds of risk genes have been assessed for adult phenotypic reversibility. We developed a strategy to rapidly assess the temporal requirements and phenotypic reversibility of NDD risk gene orthologs using a conditional protein degradation system and machine-vision phenotypic profiling in Caenorhabditis elegans. We measured how degrading and re-expressing orthologs of EBF3, BRN3A and DYNC1H1 at multiple periods throughout development affect 30 morphological, locomotor, sensory and learning phenotypes. We found that phenotypic reversibility was possible for each gene studied. However, the temporal requirements of gene function and degree of rescue varied by gene and phenotype. This work highlights the critical need to assess multiple windows of degradation and re-expression and a large number of phenotypes to understand the many roles a gene can have across the lifespan. This work also demonstrates the benefits of using a high-throughput model system to prioritize NDD risk genes for re-expression studies in other organisms.
      PubDate: Fri, 06 May 2022 00:00:00 GMT
       
  • Subcellular localization of mutant P23H rhodopsin in an RFP fusion
           knock-in mouse model of retinitis pigmentosa

    • Authors: Robichaux MA; Nguyen V, Chan F, et al.
      Abstract: ABSTRACTThe P23H mutation in rhodopsin (Rho), the rod visual pigment, is the most common allele associated with autosomal-dominant retinitis pigmentosa (adRP). The fate of misfolded mutant Rho in rod photoreceptors has yet to be elucidated. We generated a new mouse model, in which the P23H-Rho mutant allele is fused to the fluorescent protein Tag-RFP-T (P23HhRhoRFP). In heterozygotes, outer segments formed, and wild-type (WT) rhodopsin was properly localized, but mutant P23H-Rho protein was mislocalized in the inner segments. Heterozygotes exhibited slowly progressing retinal degeneration. Mislocalized P23HhRhoRFP was contained in greatly expanded endoplasmic reticulum (ER) membranes. Quantification of mRNA for markers of ER stress and the unfolded protein response revealed little or no increases. mRNA levels for both the mutant human rhodopsin allele and the WT mouse rhodopsin were reduced, but protein levels revealed selective degradation of the mutant protein. These results suggest that the mutant rods undergo an adaptative process that prolongs survival despite unfolded protein accumulation in the ER. The P23H-Rho-RFP mouse may represent a useful tool for the future study of the pathology and treatment of P23H-Rho and adRP.This article has an associated First Person interview with the first author of the paper.
      PubDate: Fri, 06 May 2022 00:00:00 GMT
       
  • Epigenetic downregulation of Socs2 contributes to mutant N-Ras-mediated
           hematopoietic dysregulation

    • Authors: Jin X; Ng V, Zhao M, et al.
      Abstract: ABSTRACTRAS mutations occur in a broad spectrum of human hematopoietic malignancies. Activating Ras mutations in blood cells leads to hematopoietic malignancies in mice. In murine hematopoietic stem cells (HSCs), mutant N-RasG12D activates Stat5 to dysregulate stem cell function. However, the underlying mechanism remains elusive. In this study, we demonstrate that Stat5 activation induced by a hyperactive Nras mutant, G12D, is dependent on Jak2 activity. Jak2 is activated in Nras mutant HSCs and progenitors (HSPCs), and inhibiting Jak2 with ruxolitinib significantly decreases Stat5 activation and HSPC hyper-proliferation in vivo in NrasG12D mice. Activation of Jak2-Stat5 is associated with downregulation of Socs2, an inhibitory effector of Jak2/Stat5. Restoration of Socs2 blocks NrasG12D HSC reconstitution in bone marrow transplant recipients. SOCS2 downregulation is also observed in human acute myeloid leukemia (AML) cells that carry RAS mutations. RAS mutant AML cells exhibited suppression of the enhancer active marker H3K27ac at the SOCS2 locus. Finally, restoration of SOCS2 in RAS mutant AML cells mitigated leukemic growth. Thus, we discovered a novel signaling feedback loop whereby hyperactive Ras signaling activates Jak2/Stat5 via suppression of Socs2.
      PubDate: Fri, 06 May 2022 00:00:00 GMT
       
  • Accessible analysis of longitudinal data with linear mixed effects models

    • Authors: Murphy JI; Weaver NE, Hendricks AE.
      Abstract: ABSTRACTLongitudinal studies are commonly used to examine possible causal factors associated with human health and disease. However, the statistical models, such as two-way ANOVA, often applied in these studies do not appropriately model the experimental design, resulting in biased and imprecise results. Here, we describe the linear mixed effects (LME) model and how to use it for longitudinal studies. We re-analyze a dataset published by Blanton et al. in 2016 that modeled growth trajectories in mice after microbiome implantation from nourished or malnourished children. We compare the fit and stability of different parameterizations of ANOVA and LME models; most models found that the nourished versus malnourished growth trajectories differed significantly. We show through simulation that the results from the two-way ANOVA and LME models are not always consistent. Incorrectly modeling correlated data can result in increased rates of false positives or false negatives, supporting the need to model correlated data correctly. We provide an interactive Shiny App to enable accessible and appropriate analysis of longitudinal data using LME models.
      PubDate: Fri, 06 May 2022 00:00:00 GMT
       
  • Modeling the catarrhal stage of Bordetella pertussis upper respiratory
           tract infections in mice

    • Authors: Soumana IH; Dewan KK, Linz B, et al.
      Abstract: ABSTRACTPertussis (whooping cough) is a highly transmissible human respiratory disease caused by Bordetella pertussis, a human-restricted pathogen. Animal models generally involve pneumonic infections induced by depositing large numbers of bacteria in the lungs of mice. These models have informed us about the molecular pathogenesis of pertussis and guided development of vaccines that successfully protect against severe disease. However, they bypass the catarrhal stage of the disease, when bacteria first colonize and initially grow in the upper respiratory tract. This is a critical and highly transmissible stage of the infection that current vaccines do not prevent. Here, we demonstrate a model system in which B. pertussis robustly and persistently infects the nasopharynx of TLR4-deficient mice, inducing localized inflammation, neutrophil recruitment and mucus production as well as persistent shedding and occasional transmission to cage mates. This novel experimental system will allow the study of the contributions of bacterial factors to colonization of and shedding from the nasopharynx, as occurs during the catarrhal stage of pertussis, and interventions that might better control the ongoing circulation of pertussis.
      PubDate: Tue, 03 May 2022 00:00:00 GMT
       
 
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