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Found 36142 matches. Displaying 21-30
Gilligan CJ, Cohen SP, Fischetti VA, Hirsch JA, Czaplewski LG
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Chronic low back pain, bacterial infection and treatment with antibiotics

SPINE JOURNAL 2021 JUN; 21(6):903-914
The contribution of bacterial infection to chronic low back pain and its treatment with antibiotics have generated considerable controversy in literature. If efficacious, antibiotics have the potential to transform the treatment of chronic low back pain in a significant subset of patients. Some microbiology studies of disc tissue from patients with CLBP have shown that bacteria are present, most likely due to infection, while others conclude they are absent or if found, it is due to surgical contamination. Clinical studies testing the efficacy of oral antibiotics to treat CLBP have either shown that the treatment is efficacious leading to significantly reduced pain and disability or that their effect is modest and not clinically significant. Critical review of the literature on CLBP, bacterial infection and treatment with antibiotics identified five well-designed and executed microbiology studies characterizing bacteria in disc samples that demonstrate that bacteria do infect herniated disc tissue, but that the bacterial burden is low and may be below the limits of detection in some studies. Two randomized, controlled clinical trials evaluating oral antibiotics in patients with CLBP indicate that for certain subsets of patients, the reduction in pain and disability achieved with antibiotic therapy may be significant. In patients for whom other therapies have failed, and who might otherwise progress to disc replacement or fusion surgery, antibiotic therapy may well be an attractive option to reduce the individual suffering associated with this debilitating condition. Additional clinical research is recommended to refine the selection of patients with CLBP caused or complicated by bacterial infection and most likely to respond to antibiotics, to optimize antibiotic therapy to maximize patient benefit, to minimize and manage side effects, and to address legitimate concerns about antibiotic stewardship. (C) 2021 The Author(s). Published by Elsevier Inc.
Durkin SM, Chakraborty M, Abrieux A, Lewald KM, Gadau A, Svetec N, Peng JH, Kopyto M, Langer CB, Chiu JC, Emerson JJ, Zhao L
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Behavioral and Genomic Sensory Adaptations Underlying the Pest Activity of Drosophila suzukii

Studying how novel phenotypes originate and evolve is fundamental to the field of evolutionary biology as it allows us to understand how organismal diversity is generated and maintained. However, determining the basis of novel phenotypes is challenging as it involves orchestrated changes at multiple biological levels. Here, we aim to overcome this challenge by using a comparative species framework combining behavioral, gene expression, and genomic analyses to understand the evolutionary novel egg-laying substrate-choice behavior of the invasive pest species Drosophila suzukii. First, we used egg-laying behavioral assays to understand the evolution of ripe fruit oviposition preference in D. suzukii compared with closely related species D. subpulchrella and D. biarmipes as well as D. melanogaster. We show that D. subpulchrella and D. biarmipes lay eggs on both ripe and rotten fruits, suggesting that the transition to ripe fruit preference was gradual. Second, using two-choice oviposition assays, we studied how D. suzukii, D. subpulchrella, D. biarmipes, and D. melanogaster differentially process key sensory cues distinguishing ripe from rotten fruit during egg-laying. We found that D. suzukii's preference for ripe fruit is in part mediated through a species-specific preference for stiff substrates. Last, we sequenced and annotated a high-quality genome for D. subpulchrella. Using comparative genomic approaches, we identified candidate genes involved in D. suzukii's ability to seek out and target ripe fruits. Our results provide detail to the stepwise evolution of pest activity in D. suzukii, indicating important cues used by this species when finding a host, and the molecular mechanisms potentially underlying their adaptation to a new ecological niche.
Yang CT, Zhou Y, Marcus S, Formenti G, Bergeron LA, Song ZZ, Bi XP, Bergman J, Rousselle MMC, Zhou CR, Zhou L, Deng Y, Fang MQ, Xie D, Zhu YZ, Tan SJ, Mountcastle J, Haase B, Balacco J, Wood J, Chow W, Rhie A, Pippel M, Fabiszak MM, Koren S, Fedrigo O, Freiwald WA, Howe K, Yang HM, Phillippy AM, Schierup MH, Jarvis ED, Zhang GJ
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Evolutionary and biomedical insights from a marmoset diploid genome assembly

NATURE 2021 JUN 10; 594(7862):227-233
The accurate and complete assembly of both haplotype sequences of a diploid organism is essential to understanding the role of variation in genome functions, phenotypes and diseases(1). Here, using a trio-binning approach, we present a high-quality, diploid reference genome, with both haplotypes assembled independently at the chromosome level, for the common marmoset (Callithrix jacchus), an primate model system that is widely used in biomedical research(2,3). The full spectrum of heterozygosity between the two haplotypes involves 1.36% of the genome-much higher than the 0.13% indicated by the standard estimation based on single-nucleotide heterozygosity alone. The de novo mutation rate is 0.43 x 10(-8) per site per generation, and the paternal inherited genome acquired twice as many mutations as the maternal. Our diploid assembly enabled us to discover a recent expansion of the sex-differentiation region and unique evolutionary changes in the marmoset Y chromosome. In addition, we identified many genes with signatures of positive selection that might have contributed to the evolution of Callithrix biological features. Brain-related genes were highly conserved between marmosets and humans, although several genes experienced lineage-specific copy number variations or diversifying selection, with implications for the use of marmosets as a model system.
Liu YY, Birsoy K
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Asparagine, a Key Metabolite in Cellular Response to Mitochondrial Dysfunction

TRENDS IN CANCER 2021 JUN; 7(6):479-481
The mitochondrial electron transport chain (ETC) has been an attractive target for cancer therapy due to its essentiality for tumor growth. Krall et al. found that under ETC dysfunction, a decrease in asparagine limits cancer cell proliferation and activates the integrated stress response, creating a therapeutically exploitable metabolic vulnerability.
Mahdaviani SA, Marjani M, Jamee M, Khavandegar A, Ghaffaripour H, Eslamian G, Ghaini M, Eskandarzadeh S, Casanova JL, Bustamante J, Mansouri D, Velayati AA
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Disseminated Mycobacterium simiae Infection in a Patient with Complete IL-12p40 Deficiency

Mendelian susceptibility to mycobacterial disease (MSMD) is a rare group of genetic disorders characterized by infections with weakly virulent environmental mycobacteria (EM) or Mycobacterium bovis bacillus Calmette-Guerin (BCG). Herein, we described the case of a 4.5-year-old boy with protein-losing enteropathy, lymphoproliferation, and candidiasis, who was found to have disseminated Mycobacterium simiae infection. A homozygous mutation in the IL12B gene, c.527_528delCT (p.S176Cfs*12) was identified, responsible for the complete IL-12p40 deficiency. He was resistant to anti-mycobacterial treatment and finally died due to sepsis-related complications.
Laszlo M
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SARS-CoV-2 infection and COVID-19 in Gaucher disease: indications for vaccination

ORVOSI HETILAP 2021 JUN; 162(24):938-942
At the start of the pandemic caused by the novel coronavirus (SARS-CoV-2), the Gaucher disease community anticipated that infection with this emerging viral pathogen would be associated with high morbidity and mortality in individuals with this chronic metabolic disorder. Surprisingly, however, preliminary studies suggest that Gaucher disease does not confer a higher risk of severe, life-threatening effects of SARS-CoV-2 infection, and no severe cases have been reported in large cohorts of patients from the United States, Europe and Israel. It is thought that the accumulation of glucocerebroside in the cells of Gaucher patients may promote immune tolerance rather than inflammation on exposure to SARS-CoV-2. We review here the current concepts of Gaucher disease and SARS-CoV-2 infection, focusing particularly on general prevention and vaccination. We also discuss the susceptibility to COVID-19 of patients with inborn errors of type 1 interferon (IFN alpha and IFN omega) immunity.
Choe H, Jarvis ED
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The role of sex chromosomes and sex hormones in vocal learning systems

HORMONES AND BEHAVIOR 2021 JUN; 132(?):? Article 104978
Vocal learning is the ability to imitate and modify sounds through auditory experience, a rare trait found in only a few lineages of mammals and birds. It is a critical component of human spoken language, allowing us to verbally transmit speech repertoires and knowledge across generations. In many vocal learning species, the vocal learning trait is sexually dimorphic, where it is either limited to males or present in both sexes to different degrees. In humans, recent findings have revealed subtle sexual dimorphism in vocal learning/spoken language brain regions and some associated disorders. For songbirds, where the neural mechanisms of vocal learning have been well studied, vocal learning appears to have been present in both sexes at the origin of the lineage and was then independently lost in females of some subsequent lineages. This loss is associated with an interplay between sex chromosomes and sex steroid hormones. Even in species with little dimorphism, like humans, sex chromosomes and hormones still have some influence on learned vocalizations. Here we present a brief synthesis of these studies, in the context of sex determination broadly, and identify areas of needed investigation to further understand how sex chromosomes and sex steroid hormones help establish sexually dimorphic neural structures for vocal learning.
Weinberg DN, Rosenbaum P, Chen X, Barrows D, Horth C, Marunde MR, Popova IK, Gillespie ZB, Keogh MC, Lu C, Majewski J, Allis CD
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Two competing mechanisms of DNMT3A recruitment regulate the dynamics of de novo DNA methylation at PRC1-targeted CpG islands

NATURE GENETICS 2021 JUN; 53(6):794-800
Precise deposition of CpG methylation is critical for mammalian development and tissue homeostasis and is often dysregulated in human diseases. The localization of de novo DNA methyltransferase DNMT3A is facilitated by its PWWP domain recognizing histone H3 lysine 36 (H3K36) methylation(1,2) and is normally depleted at CpG islands (CGIs)(3). However, methylation of CGIs regulated by Polycomb repressive complexes (PRCs) has also been observed(4-8). Here, we report that DNMT3A PWWP domain mutations identified in paragangliomas(9) and microcephalic dwarfism(10) promote aberrant localization of DNMT3A to CGIs in a PRC1-dependent manner. DNMT3A PWWP mutants accumulate at regions containing PRC1-mediated formation of monoubiquitylated histone H2A lysine 119 (H2AK119ub), irrespective of the amounts of PRC2-catalyzed formation of trimethylated histone H3 lysine 27 (H3K27me3). DNMT3A interacts with H2AK119ub-modified nucleosomes through a putative amino-terminal ubiquitin-dependent recruitment region, providing an alternative form of DNMT3A genomic targeting that is augmented by the loss of PWWP reader function. Ablation of PRC1 abrogates localization of DNMT3A PWWP mutants to CGIs and prevents aberrant DNA hypermethylation. Our study implies that a balance between DNMT3A recruitment by distinct reader domains guides de novo CpG methylation and may underlie the abnormal DNA methylation landscapes observed in select human cancer subtypes and developmental disorders.
Weaver MD, Sletten TL, Foster RG, Gozal D, Klerman EB, Rajaratnam SMW, Roenneberg T, Takahashi JS, Turek FW, Vitiello MV, Young MW, Czeisler CA
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Adverse impact of polyphasic sleep patterns in humans: Report of the National Sleep Foundation sleep timing and variability consensus panel

SLEEP HEALTH 2021 JUN; 7(3):293-302
Polyphasic sleep is the practice of distributing multiple short sleep episodes across the 24-hour day rather than having one major and possibly a minor (& ldquo;nap & rdquo;) sleep episode each day. While the prevalence of poly phasic sleep is unknown, anecdotal reports suggest attempts to follow this practice are common, particularly among young adults. Polyphasic-sleep advocates claim to thrive on as little as 2 hours of total sleep per day. However, significant concerns have been raised that polyphasic sleep schedules can result in health and safety consequences. We reviewed the literature to identify the impact of polyphasic sleep schedules (excluding nap or siesta schedules) on health, safety, and performance outcomes. Of 40,672 potentially relevant publications, with 2,023 selected for full-text review, 22 relevant papers were retained. We found no evidence supporting benefits from following polyphasic sleep schedules. Based on the current evidence, the consensus opinion is that polyphasic sleep schedules, and the sleep deficiency inherent in those schedules, are associated with a variety of adverse physical health, mental health, and performance outcomes. Striving to adopt a schedule that significantly reduces the amount of sleep per 24 hours and/or fragments sleep into multiple episodes throughout the 24-hour day is not recommended. (c) 2021 The Authors. Published by Elsevier Inc. on behalf of National Sleep Foundation. This is an open access article under the CC BY-NC-ND license (
Bournazos S, Vo HTM, Duong V, Auerswald H, Ly S, Sakuntabhai A, Dussart P, Cantaert T, Ravetch JV
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Antibody fucosylation predicts disease severity in secondary dengue infection

SCIENCE 2021 JUN 4; 372(6546):1102-1105
Although antiviral antibodies generally confer protective functions, antibodies against dengue virus (DENV) are associated with enhanced disease susceptibility. Antibodies can mediate DENV infection of leukocytes via Fcg receptors, likely contributing to dengue disease pathogenesis. To determine if this mechanism accounts for variable disease severity, we examined Fab and Fc structures of anti-DENV antibodies from patients before and after infection and with variable disease outcomes. Neither antibody titers nor neutralizing activity correlated with disease severity in DENV-infected populations. Rather, DENV infection induced a specific increase in immunoglobulin G1 (IgG1) afucosylation, and the levels of afucosylated IgG1 were predictive of dengue disease severity. Thus, the IgG1 fucosylation status represents a robust prognostic tool for dengue disease, highlighting the key role of the Fc glycan structure in dengue pathogenesis.