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Found 37003 matches. Displaying 101-110
Soto LF, Romani AC, Jimenez-Avalos G, Silva Y, Ordinola-Ramirez CM, Lapa RML, Requena D
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Immunoinformatic analysis of the whole proteome for vaccine design: An application to Clostridium perfringens

FRONTIERS IN IMMUNOLOGY 2022 AUG 30; 13(?):? Article 942907
Clostridium perfringens is a dangerous bacterium and known biological warfare weapon associated with several diseases, whose lethal toxins can produce necrosis in humans. However, there is no safe and fully effective vaccine against C. perfringens for humans yet. To address this problem, we computationally screened its whole proteome, identifying highly immunogenic proteins, domains, and epitopes. First, we identified that the proteins with the highest epitope density are Collagenase A, Exo-alpha-sialidase, alpha n-acetylglucosaminidase and hyaluronoglucosaminidase, representing potential recombinant vaccine candidates. Second, we further explored the toxins, finding that the non-toxic domain of Perfringolysin O is enriched in CTL and HTL epitopes. This domain could be used as a potential sub-unit vaccine to combat gas gangrene. And third, we designed a multi-epitope protein containing 24 HTL-epitopes and 34 CTL-epitopes from extracellular regions of transmembrane proteins. Also, we analyzed the structural properties of this novel protein using molecular dynamics. Altogether, we are presenting a thorough immunoinformatic exploration of the whole proteome of C. perfringens, as well as promising whole-protein, domain-based and multi-epitope vaccine candidates. These can be evaluated in preclinical trials to assess their immunogenicity and protection against C. perfringens infection.
Barreiros LA, Sousa JL, Geier C, Leiss-Piller A, Kanegae MPP, Franca TT, Boisson B, Lima AM, Costa-Carvalho BT, Aranda CS, de Moraes-Pinto MI, Segundo GRS, Ferreira JFS, Tavares FS, Guimaraes FATD, Toledo EC, Ain ACD, Moreira IF, Soldatelli G, Grumach AS, Dorna MD, Weber CW, Di Gesu RSW, Dantas VM, Fernandes FR, Torgerson TR, Ochs HD, Bustamante J, Walter JE, Condino-Neto A
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SCID and Other Inborn Errors of Immunity with Low TRECs - the Brazilian Experience

Severe combined immunodeficiency, SCID, is a pediatric emergency that represents the most critical group of inborn errors of immunity (IEI). Affected infants present with early onset life-threatening infections due to absent or non-functional T cells. Without early diagnosis and curative treatment, most die in early infancy. As most affected infants appear healthy at birth, newborn screening (NBS) is essential to identify and treat patients before the onset of symptoms. Here, we report 47 Brazilian patients investigated between 2009 and 2020 for SCID due to either a positive family history and/or clinical impression and low TRECs. Based on clinical presentation, laboratory finding, and genetic information, 24 patients were diagnosed as typical SCID, 14 as leaky SCID, and 6 as Omenn syndrome; 2 patients had non-SCID IEI, and 1 remained undefined. Disease onset median age was 2 months, but at the time of diagnosis and treatment, median ages were 6.5 and 11.5 months, respectively, revealing considerable delay which affected negatively treatment success. While overall survival was 51.1%, only 66.7% (30/45) lived long enough to undergo hematopoietic stem-cell transplantation, which was successful in 70% of cases. Forty-three of 47 (91.5%) patients underwent genetic testing, with a 65.1% success rate. Even though our patients did not come from the NBS programs, the diagnosis of SCID improved in Brazil during the pilot programs, likely due to improved medical education. However, we estimate that at least 80% of SCID cases are still missed. NBS-SCID started to be universally implemented in the city of Sao Paulo in May 2021, and it is our hope that other cities will follow, leading to early diagnosis and higher survival of SCID patients in Brazil.
Ivens ABF, Kronauer DJC
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Aphid-farming ants

CURRENT BIOLOGY 2022 AUG 8; 32(15):R813-R817
Tur C, Dubessy AL, Otero-Romero S, Amato MP, Derfuss T, Di Pauli F, Iacobaeus E, Mycko M, Abboud H, Achiron A, Bellinvia A, Boyko A, Casanova JL, Clifford D, Dobson R, Farez MF, Filippi M, Fitzgerald KC, Fonderico M, Gouider R, Hacohen Y, Hellwig K, Hemmer B, Kappos L, Ladeira F, Lebrun-Frenay C, Louapre C, Magyari M, Mehling M, Oreja-Guevara C, Pandit L, Papeix C, Piehl F, Portaccio E, Ruiz-Camps I, Selmaj K, Simpson-Yap S, Siva A, Sorensen PS, Sormani MP, Trojano M, Vaknin-Dembinsky A, Vukusic S, Weinshenker B, Wiendl H, Winkelmann A, Rodas MIZ, Tintore M, Stankoff B
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The risk of infections for multiple sclerosis and neuromyelitis optica spectrum disorder disease-modifying treatments: Eighth European Committee for Treatment and Research in Multiple Sclerosis Focused Workshop Review. April 2021

MULTIPLE SCLEROSIS JOURNAL 2022 AUG; 28(9):1424-1456 Article 13524585211069068
Over the recent years, the treatment of multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) has evolved very rapidly and a large number of disease-modifying treatments (DMTs) are now available. However, most DMTs are associated with adverse events, the most frequent of which being infections. Consideration of all DMT-associated risks facilitates development of risk mitigation strategies. An international focused workshop with expert-led discussions was sponsored by the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) and was held in April 2021 to review our current knowledge about the risk of infections associated with the use of DMTs for people with MS and NMOSD and corresponding risk mitigation strategies. The workshop addressed DMT-associated infections in specific populations, such as children and pregnant women with MS, or people with MS who have other comorbidities or live in regions with an exceptionally high infection burden. Finally, we reviewed the topic of DMT-associated infectious risks in the context of the current SARS-CoV-2 pandemic. Herein, we summarize available evidence and identify gaps in knowledge which justify further research.
Herre M, Goldman OV, Lu TC, Caballero-Vidal G, Qi YY, Gilbert ZN, Gong ZY, Morita T, Rahiel S, Ghaninia M, Ignell R, Matthews BJ, Li HJ, Vosshall LB, Younger MA
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Non-canonical odor coding in the mosquito

CELL 2022 AUG 18; 185(17):3104-+
Aedes aegypti mosquitoes are a persistent human foe, transmitting arboviruses including dengue when they feed on human blood. Mosquitoes are intensely attracted to body odor and carbon dioxide, which they detect using ionotropic chemosensory receptors encoded by three large multi-gene families. Genetic mutations that disrupt the olfactory system have modest effects on human attraction, suggesting redundancy in odor cod-ing. The canonical view is that olfactory sensory neurons each express a single chemosensory receptor that defines its ligand selectivity. We discovered that Ae. aegypti uses a different organizational principle, with many neurons co-expressing multiple chemosensory receptor genes. In vivo electrophysiology demon-strates that the broad ligand-sensitivity of mosquito olfactory neurons depends on this non-canonical co-expression. The redundancy afforded by an olfactory system in which neurons co-express multiple chemosensory receptors may increase the robustness of the mosquito olfactory system and explain our long-standing inability to disrupt the detection of humans by mosquitoes.
Barad DH, Albertini DF, Gleicher N
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In science truth ultimately wins, and PGT-A is no exception

HUMAN REPRODUCTION 2022 AUG 25; 37(9):2216-2218 Article deac151
Mehta MM, Hanna N, Lowes MA, Alavi A
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The Incidence and Risk of Respiratory Tract Infections in Patients Using Biologics for Hidradenitis Suppurativa: A Systematic Review and Meta-analysis

Background: Patients treated with biological therapy for hidradenitis suppurativa (HS) are at an increased risk of infectious complications. However, it is unclear whether these patients are at an increased risk of acquiring infections. The most common infection reported in patients taking biologic therapies are respiratory tract infections. The purpose of this study is to review the risk and incidence rate of upper respiratory tract infections (URTI), nasopharyngitis, and influenza in patients treated with biologics for HS. Methods: A comprehensive literature search was completed using databases (MEDLINE and EMBASE) and clinical trial registries ( to identify trials that reported the risk and incidence rate of URTIs, nasopharyngitis, and influenza in patients using biological therapy for moderate to severe HS. Each study was assessed for bias using the GRADE system. Findings: There were nine studies included in this review including five placebo-controlled studies of patients with moderate to severe HS treated with biological therapy. We found the risk of URTI, nasopharyngitis, and influenza was not significantly different in patients taking biological therapy when compared to placebo (RR 1.23; 95% CI 0.66-2.30and RR 0.93; 95% CI 0.66-1.31, RR 1.03; 95% CI 0.41-2.56, respectively). Conclusions: This systematic review and meta-analysis did not find significantly different risks of URTI, nasopharyngitis, and influenza in patients taking biological therapy when compared to placebo. However, these data were limited by the sample size and number of studies available. Future high-quality, high-power, and long-term studies are needed to support the data available on this topic.
Kim J, Moreno A, Krueger JG
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The imbalance between Type 17 T-cells and regulatory immune cell subsets in psoriasis vulgaris

FRONTIERS IN IMMUNOLOGY 2022 AUG 30; 13(?):? Article 1005115
Psoriasis vulgaris is a common inflammatory disease affecting 7.5 million adults just in the US. Previously, psoriasis immunopathogenesis has been viewed as the imbalance between CD4(+) T-helper 17 (Th17) cells and regulatory T-cells (Tregs). However, current paradigms are rapidly evolving as new technologies to study immune cell subsets in the skin have been advanced. For example, recently minted single-cell RNA sequencing technology has provided the opportunity to compare highly differing transcriptomes of Type 17 T-cell (T17 cell) subsets depending on IL-17A vs. IL-17F expression. The expression of regulatory cytokines in T17 cell subsets provided evidence of T-cell plasticity between T17 cells and regulatory T-cells (Tregs) in humans. In addition to Tregs, other types of regulatory cells in the skin have been elucidated, including type 1 regulatory T-cells (Tr1 cells) and regulatory dendritic cells. More recently, investigators are attempting to apply single-cell technologies to clinical trials of biologics to test if monoclonal blockade of pathogenic T-cells will induce expansion of regulatory immune cell subsets involved in skin homeostasis.
Caballero M, Ge T, Rebelo AR, Seo S, Kim S, Brooks K, Zuccaro M, Kanagaraj R, Vershkov D, Kim D, Smogorzewska A, Smolka M, Benvenisty N, West SC, Egli D, Mace EM, Koren A
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Comprehensive analysis of DNA replication timing across 184 cell lines suggests a role for MCM10 in replication timing regulation

HUMAN MOLECULAR GENETICS 2022 AUG 25; 31(17):2899-2917
Cellular proliferation depends on the accurate and timely replication of the genome. Several genetic diseases are caused by mutations in key DNA replication genes; however, it remains unclear whether these genes influence the normal program of DNA replication timing. Similarly, the factors that regulate DNA replication dynamics are poorly understood. To systematically identify trans-acting modulators of replication timing, we profiled replication in 184 cell lines from three cell types, encompassing 60 different gene knockouts or genetic diseases. Through a rigorous approach that considers the background variability of replication timing, we concluded that most samples displayed normal replication timing. However, mutations in two genes showed consistently abnormal replication timing. The first gene was RIF1, a known modulator of replication timing. The second was MCM10, a highly conserved member of the pre-replication complex. Cells from a single patient carrying MCM10 mutations demonstrated replication timing variability comprising 46% of the genome and at different locations than RIF1 knockouts. Replication timing alterations in the mutated MCM10 cells were predominantly comprised of replication delays and initiation site gains and losses. Taken together, this study demonstrates the remarkable robustness of the human replication timing program and reveals MCM10 as a novel candidate modulator of DNA replication timing.
Yadav N, Noble C, Niemeyer JE, Terceros A, Victor J, Liston C, Rajasethupathy P
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Prefrontal feature representations drive memory recall

NATURE 2022 AUG 4; 608(7921):153-+
Memory formation involves binding of contextual features into a unitary representation(1-4), whereas memory recall can occur using partial combinations of these contextual features. The neural basis underlying the relationship between a contextual memory and its constituent features is not well understood; in particular, where features are represented in the brain and how they drive recall. Here, to gain insight into this question, we developed a behavioural task in which mice use features to recall an associated contextual memory. We performed longitudinal imaging in hippocampus as mice performed this task and identified robust representations of global context but not of individual features. To identify putative brain regions that provide feature inputs to hippocampus, we inhibited cortical afferents while imaging hippocampus during behaviour. We found that whereas inhibition of entorhinal cortex led to broad silencing of hippocampus, inhibition of prefrontal anterior cingulate led to a highly specific silencing of context neurons and deficits in feature-based recall. We next developed a preparation for simultaneous imaging of anterior cingulate and hippocampus during behaviour, which revealed robust population-level representation of features in anterior cingulate, that lag hippocampus context representations during training but dynamically reorganize to lead and target recruitment of context ensembles in hippocampus during recall. Together, we provide the first mechanistic insights into where contextual features are represented in the brain, how they emerge, and how they access long-range episodic representations to drive memory recall.