bluuebunny/crossref_metadata_2025 huggingface dataset:
Human Papillomavirus Within Psoriasis Plaques in a Patient With Psoriasis: A Case Report
Authors: Lema-Matehu Karen P. , Lascano-Gallegos Nathalie P. , Palacios-Álvarez Santiago A.
Published: January 2022

Introduction:

Psoriasis may be triggered by several factors, and its pathophysiology is related to inflammatory cellular processes.

We herein describe a patient with psoriasis who developed warts on multiple psoriasis plaques and was successfully treated with systemic subcutaneous methotrexate.

Case presentation:

A 67-year-old man who had been diagnosed with psoriasis 14 years previously developed an outbreak of small erythematous desquamative plaques distributed symmetrically on his arms and trunk. Multiple spiny whitish papules had developed over his previously established psoriasis lesions. The appearance of the papules was consistent with viral warts. The patient was treated with systemic methotrexate injected subcutaneously and oral folic acid, both dosed weekly. This treatment produced good results.

Discussion:

A remarkable feature of this case is that psoriasis was the first diagnosis and that human papillomavirus (HPV) appeared over widespread erythematous squamous plaques. The pathophysiology of psoriasis is related to inflammatory cellular processes. Some authors have reported that HPV proteins may stimulate keratinocyte proliferation. Others have reported that HPV infection mostly stimulates systemic interleukin 17 production; consequently, HPV infection could provide a better environment for interleukin 17 secretion and facilitate new onset of psoriasis. One report indicated that methotrexate was discontinued in a patient who presented with both pathologies, although we had very good results.

Conclusion:

Psoriasis and HPV may be pathophysiologically related. HPV may stimulate keratinocyte proliferation and systemic interleukin 17 production, resulting in a better environment for psoriasis. Systemic methotrexate injected subcutaneously resulted in a good outcome in our patient.
Relationship Between Preoperative Anxiety and Atrial Fibrillation After Coronary Artery Bypass Graft Surgery
Authors: ALKAN KAYHAN Semiha , GÜNER Ebru , HANEDAN Muhammet Onur , TOPAL ÇOLAK Esengül , MATARACI İlker
Published: January 2022

Background

Atrial fibrillation is a form of arrhythmia that frequently occurs after coronary artery bypass graft surgery. Psychological factors may be involved in the development of atrial fibrillation, although the specific effect of anxiety remains unclear.

Purpose

This study was designed to evaluate the relationship between preoperative anxiety levels and atrial fibrillation after coronary artery bypass graft surgery.

Methods

This descriptive design study recruited a sample of 126 patients. The data were collected by the researcher using a patient information form and the State-Trait Anxiety Scale.

Results

Atrial fibrillation developed in 26.5% of the sample. Those who developed atrial fibrillation had a mean trait anxiety scale score of 40.2 ± 7.8, which is statistically significant. According to the results of logistic regression, it was observed that increased trait anxiety score, increased age, presence of comorbid disease, and noncompliance with respiratory physiotherapy increased the risk of developing atrial fibrillation.

Conclusion/Implications for Practice

Preoperative anxiety levels were shown to be a significant factor promoting the development of atrial fibrillation after coronary artery bypass graft surgery. The results support measuring anxiety levels in patients as a standard procedure before performing this surgical procedure.
How Broad Should Gram‐Negative Coverage Be for Febrile Parenteral Nutrition Dependent Short Bowel Syndrome Patients?
Authors: Stultz Jeremy S. , Fly James H. , Bagga Bindiya , Arnold Sandra R. , Algotar Anushree , Lee Kelley R.
Published: January 2022

Broader spectrum Gram‐negative antibiotics are commonly utilized empirically for central line‐associated bloodstream infections (CLABSI) in febrile short bowel syndrome (SBS) patients receiving home parenteral nutrition compared to those used empirically for inpatient‐acquired CLABSI. This analysis reports 57 CLABSI in 22 patients with SBS admitted from the community and 78 inpatient‐acquired CLABSI in 76 patients over a 5‐year period. Proportional Gram‐negative CLABSI was similar between the SBS and inpatient‐acquired cohorts (43.8% vs42.3%, respectively, P = 0.78). 1.8% and 10.3% (P = 0.125) of Gram‐negative CLABSI were non‐susceptible to ceftriaxone and 0% and 3.8% (P = 0.52) were non‐susceptible to ceftazidime in the SBS and inpatient‐acquired cohorts, respectively. In the SBS cohort, home ethanol lock therapy and prior culture results impacted Gramnegative pathogen distribution. Broader empiric Gram‐negative coverage for CLABSI among SBS patients compared to inpatients is unnecessary. Third‐generation cephalosporins represent appropriate empiric Gramnegative agents for febrile SBS patients presenting from the community to our institution.
An insight into multifunctional tool box: Akkermansia muciniphila provides dynamic benefits to the human gut
Authors: Tiwari Kartikeya
Published: January 2022

Akkermansia muciniphila is a mucin degrader that plays a major role in the human gut. Multiple studies have shown that the level of abundance of this organism in the human body is inversely related to diseases, such as diabetes, obesity and inflammatory bowel disease. This organism has abilities to regulate the intestinal permeability, gut barrier and inflammatory responses in various metabolic disorders by activating various transcription factors and enhance the expression of receptors (TLRs, NLRs). Pangenome of A. muciniphila provides comprehensive detail and role of encoding genes in mitigation of metabolic dysbiosis. The present review discusses and summarizes the role of A. muciniphila in diabetes mellitus type 2, obesity, nonalcoholic fatty liver disease and other metabolic disorders.
Prevotella herbatica sp. nov., a plant polysaccharide-decomposing anaerobic bacterium isolated from a methanogenic reactor
Authors: Ueki Atsuko , Tonouchi Akio , Kaku Nobuo , Ueki Katsuji
Published: January 2022

An obligately anaerobic bacterial strain (WR041T) was isolated from a plant residue sample in a methanogenic reactor. Cells of the strain were Gram-stain-negative, non-motile, non-spore-forming rods.

Prevotella paludivivens

JCM 13650T was the closest species of the strain based on 16S rRNA gene sequencing (98.9 % similarity). Genome analysis of strain WR041T indicated that the genome size of the strain was 3.52 Mb and the genomic DNA G+C content was 37.5 mol%. Although the 16S rRNA gene sequence similarity of strain WR041T with the closest species was higher than the threshold value of the recommended species delineation (98.7 %), the average nucleotide identity and the digital DNA–DNA hybridization value between them were 91–92 and 45.5 %, respectively, suggesting that strain WR041T represents a novel species in the genus. Strain WR041T essentially required haemin and CO2/Na2CO3 for growth. The strain was saccharolytic and decomposed various polysaccharides (glucomannan, inulin, laminarin, pectin, starch and xylan) and produced acetate and succinate. The optimum growth conditions were 35 °C and pH 6.8. The major cellular fatty acids were branched-chain fatty acids such as anteiso-C15 : 0 and iso-C15 : 0. Menaquinones MK-11 and MK-12 were the major respiratory quinones. Many protein-coding genes which were not found in the genome of

P. paludivivens

as orthologous genes were detected in the genome of strain WR041T. Based on the differences in the phylogenetic, genomic and physiological characteristics between strain WR041T and related species, the name Prevotella herbatica sp. nov. is proposed to accommodate strain WR041T (=NBRC 115134T = DSM 112534T).
Long dsRNA mediated RNA interference (dsRNAi) is antiviral in interferon competent mammalian cells
Authors: Semple SL , Jacob RA , Mossman K , DeWitte-Orr SJ
Published: January 2022

In invertebrate cells, RNA interference (RNAi) acts as a powerful defense against virus infection by cleaving virally produced long dsRNA into siRNA by Dicer and loaded into RISC which can then destroy/disrupt complementary viral mRNA sequences. Comparatively in mammalian cells, the type I interferon (IFN) pathway is the cornerstone of the innate antiviral response. Although the cellular machinery for RNAi functions in mammalian cells, its role in the antiviral response remains controversial. Here we show that IFN competent mammalian cells engage in dsRNA-mediated RNAi. We found that pre-soaking mammalian cells with concentrations of sequence-specific dsRNA too low to induce IFN production could significantly inhibit viral replication, including SARS-CoV-2. This phenomenon was dependent on dsRNA length, was comparable in effect to transfected siRNAs, and could knockdown multiple sequences at once. Additionally, Dicer-knockout cell lines were incapable of this inhibition, confirming use of RNAi. This represents the first evidence that soaking with gene-specific dsRNA can generate viral knockdown in mammalian cells. Furthermore, demonstrating RNAi below the threshold of IFN induction has uses as a novel therapeutic platform.
Retention of Neutralizing response against SARS-CoV-2 Omicron variant in Sputnik V vaccinated individuals
Authors: Lapa D , Grousova DM , Matusali G , Meschi S , Colavita F , Bettini A , Gramigna G , Francalancia M , Garbuglia AR , Girardi E , Puro V , Antinori A , Kovyrshina AV , Dolzhikova IV , Shcheblyakov DV , Tukhvatulin AI , Zubkova OV , Logunov DY , Naroditsky BS , Vaia F , Gintsburg AL
Published: January 2022

The new variant Omicron (B.1.1.529) of SARS-CoV-2, first identified in November 2021, is rapidly spreading all around the world. The Omicron becomes the dominant variant of SARS-CoV-2. There are many ongoing studies evaluating the effectiveness of existing vaccines. Studies on neutralizing activity of vaccinated sera against Omicron variant are currently being carried out in many laboratories.

In this study, we have shown the neutralizing activity of sera against SARS-CoV-2 Omicron (B.1.1.529) variant compared to the reference Wuhan D614G (B.1) variant in individuals vaccinated with 2 doses of Sputnik V or BNT162b2 in different time points up to 6 months after vaccination. We performed analysis on sample pools with comparable NtAb to Wuhan D614G variant. The decrease in neutralizing antibody (NtAb) to the Omicron variant was 8.1 folds for group of Sputnik V-vaccinated and 21.4 folds for group of BNT162b2-vaccinated. Analysis showed that 74.2% of Sputnik V- and 56.9% of BNT162b2-vaccinated sera had detectable NtAb to SARS-CoV-2 Omicron variant.

The decrease in NtAb to SARS-CoV-2 Omicron variant compared to Wuhan variant has been shown for many COVID-19 vaccines in use, with some showing no neutralization at all. Today the necessity of third booster vaccination is obvious. And the most effective approach, already shown in several studies, is the use of heterologous booster vaccination pioneered in COVID-19 vaccines by Sputnik V.
Mitochondrial diversity in the ribbed mussel, Geukensia demissa, relative to high marsh plant diversity at the southern edge of the distribution
Authors: Francis Ivy G. , Wares John P.
Published: January 2022

Genomic diversity and relatedness among sample sites are often used to explore landscape-level processes of how and where organisms are limited in movement. In many cases, these patterns of diversity and relatedness can be useful for understanding larger ecological patterns. A prior study has suggested that larval input – inferred from landscape genomic data – of the ribbed mussel Geukensia demissa, a species with important roles in stabilizing salt marsh ecosystems, could be indicative of longer-term recruitment patterns of high marsh plant species. Here we use new observations of mitochondrial diversity in the same region but with more sites sampled to show that this prior study was wrong in suggesting that relationship. The same mitochondrial data are useful for monitoring cryptic patterns of climate response in these mussels relative to a subtropical congener.
Royal knifefish generate powerful suction feeding through large neurocranial elevation and high epaxial muscle power
Authors: Li Ellen Y. , Kaczmarek Elska B. , Olsen Aaron M. , Brainerd Elizabeth L. , Camp Ariel L.
Published: January 2022

Suction feeding in ray-finned fishes involves powerful buccal cavity expansion to accelerate water and food into the mouth. Previous XROMM studies in largemouth bass (Micropterus salmoides), bluegill sunfish (Lepomis macrochirus), and channel catfish (Ictalurus punctatus) have shown that more than 90% of suction power in high performance strikes comes from the axial musculature. Thus, the shape of the axial muscles and skeleton may impact suction feeding mechanics. Royal knifefish (Chitala blanci) have an unusual postcranial morphology, with a ventrally flexed vertebral column and relatively large mass of epaxial muscle. Based on their body shape, we hypothesized that royal knifefish would generate high power strikes by utilizing large neurocranial elevation, vertebral column extension, and epaxial shortening. As predicted, C. blanci generated high suction expansion power compared to the other three species studied to date (up to 160 W), which was achieved by increasing both the rate of volume change and the intraoral subambient pressure. The large epaxial muscle (25% of body mass) shortened at high velocities to produce large neurocranial elevation and vertebral extension (up to 41 deg, combined), as well as high muscle mass-specific power (up to 800 W kg-1). For the highest power strikes, axial muscles generated 95% of the power, and 64% of the axial muscle mass consisted of the epaxial muscles. The epaxial-dominated suction expansion of royal knifefish supports our hypothesis that postcranial morphology may be a strong predictor of suction feeding biomechanics.

SUMMARY STATEMENT

Royal knifefish rely on their distinct postcranial morphology--with a curved vertebral column and large dorsal body muscles--to produce large neurocranial elevation and powerful suction feeding.
Machine learning guided signal enrichment for ultrasensitive plasma tumor burden monitoring
Authors: Widman Adam J. , Shah Minita , Øgaard Nadia , Khamnei Cole C. , Frydendahl Amanda , Deshpande Aditya , Arora Anushri , Zhang Mingxuan , Halmos Daniel , Bass Jake , Langanay Theophile , Rajagopalan Srinivas , Steinsnyder Zoe , Liao Will , Rasmussen Mads Heilskov , Jensen Sarah Østrup , Nors Jesper , Therkildsen Christina , Sotelo Jesus , Brand Ryan , Shah Ronak H. , Cheng Alexandre Pellan , Maher Colleen , Spain Lavinia , Krause Kate , Frederick Dennie T. , Malbari Murtaza S. , Marton Melissa , Manaa Dina , Winterkorn Lara , Callahan Margaret K. , Boland Genevieve , Wolchok Jedd D. , Saxena Ashish , Turajlic Samra , Imielinski Marcin , Berger Michael F. , Altorki Nasser K. , Postow Michael A. , Robine Nicolas , Andersen Claus Lindbjerg , Landau Dan A.
Published: January 2022

In solid tumor oncology, circulating tumor DNA (ctDNA) is poised to transform care through accurate assessment of minimal residual disease (MRD) and therapeutic response monitoring. To overcome the sparsity of ctDNA fragments in low tumor fraction (TF) settings and increase MRD sensitivity, we previously leveraged genome-wide mutational integration through plasma whole genome sequencing (WGS). We now introduce MRD-EDGE, a composite machine learning-guided WGS ctDNA single nucleotide variant (SNV) and copy number variant (CNV) detection platform designed to increase signal enrichment. MRD-EDGE uses deep learning and a ctDNA-specific feature space to increase SNV signal to noise enrichment in WGS by 300X compared to our previous noise suppression platform MRDetect. MRD-EDGE also reduces the degree of aneuploidy needed for ultrasensitive CNV detection through WGS from 1Gb to 200Mb, thereby expanding its applicability to a wider range of solid tumors. We harness the improved performance to track changes in tumor burden in response to neoadjuvant immunotherapy in non-small cell lung cancer and demonstrate ctDNA shedding in precancerous colorectal adenomas. Finally, the radical signal to noise enrichment in MRD-EDGE enablesde novomutation calling in melanoma without matched tumor, yielding clinically informative TF monitoring for patients on immune checkpoint inhibition.
Chronic social stress induces isolated deficits in reward anticipation on a neuroeconomic foraging task
Authors: Durand-de Cuttoli Romain , Martínez-Rivera Freddyson J. , Li Long , Minier-Toribio Angélica , Russo Scott J. , Nestler Eric J. , Sweis Brian M.
Published: January 2022

Measuring reward anticipation distinct from other aspects of reward value, including costs required to obtain a reward or the intrinsic hedonic value of consuming the reward itself, can be difficult to disentangle. Here, we show that mice trained on a self-paced neuroeconomic foraging task convey reward anticipation via differentially invigorated travel times between uniquely flavored feeding sites separate from willingness to wait, consummatory behaviors, or place preferences measured within the same trial. Following exposure to chronic social defeat stress, we found that only stress-susceptible but not stress-resilient mice revealed deficits in this metric after consuming but not after rejecting a reward on the previous trial, indicating that blunted anticipation in these animals is state-dependent, or punctuated by recent reward receipt. After increasing economic pressure and task demands, locomotion was globally invigorated and, in turn, masked stress-related deficits in reward anticipation. These findings suggest that the ability to detect changes in specific aspects of motivational deficits associated with depression and other stress-related disorders depends on an interaction between the state of an individual and environmental circumstances.
Predator-prey interactions in a warming world: the critical role of cold tolerance
Authors: Ge Xuezhen , Griswold Cortland K. , Newman Jonathan A.
Published: January 2022

Thermal tolerance mismatch within predator-prey systems may have pro-found effects on species population abundances and geographical distributions. To examine the generalized responses of a predator-prey system to climate change, we construct a biologically detailed stage-structured population dynamic model of interactions between ladybird beetles and aphids. We explore the model’s dynamics across the entire feasible parameter space of mean temperature and seasonality. Within this space, we explore different scenarios of predator and prey thermal tolerance mismatch to gain insight into how these thermal sensitivities affect the interacting species’ responses to climatic change. Our results indicate a predator’s cold tolerance has a larger effect on prey abundance than its heat tolerance. Mismatches between the predator’s and prey’s thermal tolerances also affect the species’ response to climate change. We identify three common patterns of species abundance across the feasible parameter space that relate to the type of thermal tolerance mismatches. Our study highlights the importance of understanding the complex interplay between climate change and species interactions.
A systematic evaluation of yeast sample preparation protocols for spectral identifications, proteome coverage and post-isolation modifications
Authors: den Ridder Maxime , Knibbe Ewout , van den Brandeler Wiebeke , Daran-Lapujade Pascale , Pabst Martin
Published: January 2022

The importance of obtaining comprehensive and accurate information from cellular proteomics experiments asks for a systematic investigation of sample preparation protocols, particularly when working with unicellular organisms with strong cell walls, such as found in the model organism and cell factory S. cerevisiae. Sample preparation protocols may bias towards specific protein fractions or challenge the analysis of native protein modifications due to reagent-induced artefacts. Here, we performed a systematic comparison of sample preparation protocols using a matrix of different conditions commonly applied in whole cell lysate proteomics. The different protocols were evaluated for their overall fraction of identified spectra, proteome and amino acid sequence coverage, GO-term distribution and number of peptide modifications, by employing a combination of database and unrestricted modification search approaches. The best proteome and amino acid sequence coverage was achieved by using Urea combined with filter-aided or in-solution digestion protocols, where the overall outcomes were strongly influenced by the employed quenching procedure. Most importantly, the use of moderate incubation temperatures and times, circumvented excessive formation of modification artefacts. Extensive reagent-induced peptide modifications, however, were observed when using solvents such as acetone or additives such as formic acid. Moreover, several filter material-related modifications were observed when employing the filter-aided procedures. Ultimately, the best protocols enabled the identification of approximately 65–70% of all acquired fragmentation spectra, where additional de novo sequencing suggests that unidentified spectra were largely of too low spectral quality to provide confident spectrum matches. This study demonstrates the large impact of different sample preparation procedures on the proteomic analysis outcome, where the collected protocols and large sets of associated mass spectrometric raw data provide a resource to evaluate and design new protocols and guide the analysis of (native) peptide modifications in the model eukaryote yeast.
TGFβ receptor inhibition unleashes interferon-β production by tumor-associated macrophages and enhances radiotherapy efficacy
Authors: Hamon Pauline , de Thoré Marine Gerbé , Classe Marion , Signolle Nicolas , Liu Winchygn , Bawa Olivia , Meziani Lydia , Clémenson Céline , Milliat Fabien , Deutsch Eric , Mondini Michele
Published: January 2022

Background

Transforming growth factor-beta (TGFβ) can limit the efficacy of cancer treatments, including radiotherapy (RT), by inducing an immunosuppressive tumor environment. The association of TGFβ with impaired T cell infiltration and antitumor immunity is known, but the mechanisms by which TGFβ participates in immune cell exclusion and limits the efficacy of antitumor therapies warrant further investigations.

Methods

We used the clinically relevant TGFβ receptor 2 (TGFβR2)-neutralizing antibody MT1 and the small molecule TGFβR1 inhibitor LY3200882 and evaluated their efficacy in combination with RT against murine orthotopic models of head and neck and lung cancer.

Results

We demonstrated that TGFβ pathway inhibition strongly increased the efficacy of RT. TGFβR2 antibody upregulated interferon beta (IFNβ) expression in tumor-associated macrophages (TAMs) within the irradiated tumors and favored T cell infiltration at the periphery and within the core of the tumor lesions. We highlighted that both the antitumor efficacy and inhibition of immune exclusion observed with the combination of MT1 and RT were dependent on type I interferon signaling.

Conclusions

These data shed new light on the role of TGFβ in limiting the efficacy of RT, identifying a novel mechanism involving the inhibition of macrophage-derived type I interferon production, and fostering the use of TGFβR inhibition in combination with RT in therapeutic strategies for the management of head and neck and lung cancer.
Alveolar cell fate selection and lifelong maintenance of AT2 cells by FGF signaling
Authors: Brownfield Douglas G. , de Arce Alex Diaz , Ghelfi Elisa , Gillich Astrid , Desai Tushar J. , Krasnow Mark A.
Published: January 2022

The lung’s gas exchange surface comprises thin alveolar type 1 (AT1) cells and cuboidal surfactant-secreting AT2 cells that are corrupted in some of the most common and deadly diseases including adenocarcinoma, emphysema, and SARS/Covid-19. These cells arise from an embryonic progenitor whose development into an AT1 or AT2 cell is thought to be dictated by differential mechanical forces. Here we show the critical determinant is FGF signaling. FGF Receptor 2 (Fgfr2) is expressed in mouse progenitors then restricts to nascent AT2 cells and remains on throughout life. Its ligands are expressed in surrounding mesenchyme and can, in the absence of differential mechanical cues, induce purified, uncommitted E16.5 progenitors to form alveolus-like structures with intermingled AT2 and AT1 cells. FGF signaling directly and cell autonomously specifies AT2 fate; progenitors lacking Fgfr2 in vitro and in vivo exclusively acquire AT1 fate. Fgfr2 loss in AT2 cells perinatally results in reprogramming to AT1 fate, whereas loss or inhibition later in life immediately triggers AT2 apoptosis followed by a compensatory regenerative response. We propose Fgfr2 signaling directly selects AT2 fate during development, induces a cell non-autonomous secondary signal for AT1 fate, and stays on throughout life to continuously maintain healthy AT2 cells.

One Sentence Summary

FGF signaling induces and distinguishes the two cell types of the lung’s gas exchange surface, and the pathway remains on throughout life to maintain one that can be transformed into lung cancer or targeted in the deadly form of SARS/Covid-19.
Acclimation of phenology relieves leaf longevity constraints in deciduous forests
Authors: Marqués Laura , Hufkens Koen , Bigler Christof , Crowther Thomas W. , Zohner Constantin M. , Stocker Benjamin D.
Published: January 2022

Leaf phenology is key for regulating total growing season mass and energy fluxes. Long-term temporal trends towards earlier leaf unfolding are observed across Northern Hemisphere forests. Phenological dates also vary between years, whereby end-of-season (EOS) dates correlate positively with start-of-season (SOS) dates and negatively with growing season total net CO2 assimilation (Anet). These associations have been interpreted as the effect of a constrained leaf longevity or of premature carbon (C) sink saturation - with far-reaching consequences for long-term phenology projections under climate change and rising CO2. Here, we use multi-decadal ground and remote-sensing observations to show that the relationships between Anet and EOS are opposite at the interannual and the decadal time scales. A decadal trend towards later EOS persists in parallel with a trend towards increasing Anet - in spite of the negative Anet-EOS relationship at the interannual scale. This indicates that acclimation of phenology has enabled plants to transcend a constrained leaf longevity or premature C sink saturation over the course of several decades, leading to a more effective use of available light and a sustained extension of the vegetation CO2 uptake season over time.
Structural changes after early life adversity in rodents: a systematic review with meta-analysis
Authors: Joëls Marian , Kraaijenvanger Eline , Sarabdjitsingh R. Angela , Bonapersona Valeria
Published: January 2022

Early life adversity (ELA) is a well-documented risk factor for psychiatric illnesses in humans. This risk may, in part, be conferred by structural changes induced by ELA, lasting into adulthood. We here review the evidence for such lasting structural changes in rodent models for ELA involving altered maternal care during the first two postnatal weeks. In total, we extracted data from 64 studies reporting on 260 comparisons in adult rats or mice which experienced ELA or control treatment. Most of the observations concerned structural changes in the hippocampus of adult male rats earlier exposed to maternal separation. A 3-level meta-analysis revealed that ELA reduced hippocampal volume and the number of dendritic branches as well as dendritic length of principal hippocampal cells. No differences were observed across the hippocampal subfields. In terms of adult neurogenesis in the dentate subgranular zone, both staining for BrdU and the early neuronal marker DCX were significantly reduced, while the general proliferation marker Ki67 remained unchanged. The neuronal growth factor BDNF did not show significant changes, although the unexplained heterogeneity was moderate. Generally, the effect of ELA compared to control on structural markers was not affected by additional stressors experienced in life. Overall, the data available support the notion that ELA, at least in the hippocampus of male rats, lastingly reduces volume, hampers dendritic growth and suppresses adult neurogenesis.
An evolutionary algorithm for inverse RNA folding inspired by Lévy flights
Authors: Merleau Nono S. C. , Smerlak Matteo
Published: January 2022

A Lévy flight is a random walk with step sizes that follow a heavy-tailed probability distribution. This type of random walk, with many small steps and a few large ones, has inspired many applications in genetic programming and evolutionary algorithms in recent years, but is yet to be applied to RNA design. Here we study the inverse folding problem for RNA, viz. the discovery of sequences that fold into given target secondary structures. We implement a Lévy mutation scheme in an updated version ofaRNAque, an evolutionary inverse folding algorithm, and apply it to the design of RNAs with and without pseudoknots. We find that the Lévy mutation scheme increases the diversity of designed RNA sequences and reduces the average number of evaluations of the evolutionary algorithm. The results show improved performance on bothPseudobase++and theEterna100datasets, outperforming existing inverse folding tools. We propose that a Lévy flight offers a better standard mutation scheme for optimizing RNA design.
Serological screening suggests single SARS-CoV-2 spillover events to cattle
Authors: Wernike Kerstin , Böttcher Jens , Amelung Silke , Albrecht Kerstin , Gärtner Tanja , Donat Karsten , Beer Martin
Published: January 2022

Widespread human SARS-CoV-2 infections pose a constant risk for virus transmission to animals. Here, we serologically investigated 1000 cattle samples collected in late 2021 in Germany. Eleven sera tested antibody-positive, indicating that cattle may be occasionally infected by contact to SARS-CoV-2-positive keepers, but there is no indication of further spreading.
Improvements in estimating bioaccumulation metrics in the light of toxicokinetic models and Bayesian inference
Authors: Ratier Aude , Lopes Christelle , Charles Sandrine
Published: January 2022

The surveillance of chemical substances in the scope of Environmental Risk Assessment (ERA) is classically performed through bio-assays from which data are collected and then analysed and/or modelled. Some analysis are based on the fitting of toxicokinetic (TK) models to assess the bioaccumulation capacity of chemical substances via the estimation of bioaccumulation metrics as required by regulatory documents. Given that bio-assays are particularly expensive and time consuming, it is of crucial importance to deeply benefit from all information contained in the data. By revisiting the calculation of bioaccumulation metrics under a Bayesian framework, this paper suggests changes in the way of characterising the bioaccumulation capacity of chemical substances. For this purpose, a meta-analysis of a data-rich TK database was performed, considering uncertainties around bioaccumulation metrics. Our results were statistically robust enough to suggest an additional criterion to the single median estimate of bioaccumulation metrics to assign a chemical substance to a given bioaccumulation capacity. Our proposal is to use the 75th percentile of the uncertainty interval of the bioaccumulation metrics, which revealed an appropriate complement for the classification of chemical substances (e.g., PBT (persistent, bioaccumulative and toxic) and vPvB (very persistent and very bioaccumulative) under the EU chemicals legislation). The 75% quantile proved its efficiency, similarly classifying 90% of the chemical substances as the conventional method.
Re-routing metabolism by the mitochondrial pyruvate carrier inhibitor MSDC-0160 attenuates neurodegeneration in a rat model of Parkinson’s disease
Authors: Mallet David , Goutaudier Raphael , Barbier Emmanuel L. , Carnicella Sebastien , Colca Jerry R. , Fauvelle Florence , Boulet Sabrina
Published: January 2022

Background

A growing body of evidence supports the idea that mitochondrial dysfunction might represent a key feature of Parkinson’s disease (PD). Central regulators of energy production, mitochondria are also involved in several other essential functions such as cell death pathways and neuroinflammation which make them a potential therapeutic target for PD management. Interestingly, recent studies related to PD have reported a neuroprotective effect of targeting mitochondrial pyruvate carrier (MPC) by the insulin sensitizer MSDC-0160. As the sole point of entry of pyruvate into the mitochondrial matrix, MPC plays a crucial role in energetic metabolism which is impacted in PD. This study therefore aimed at providing insights into the mechanisms underlying the neuroprotective effect of MSDC-0160.

Methods

We investigated behavioral, cellular and metabolic impact of chronic MSDC-0160 treatment in unilateral 6-OHDA PD rats. We evaluated mitochondrial related processes through the expression of pivotal mitochondrial enzymes in dorsal striatal biopsies and the level of metabolites in serum samples using nuclear magnetic resonance spectroscopy (NMR)-based metabolomics.

Results

MSDC-0160 treatment in unilateral 6-OHDA rats improved motor behavior, decreased dopaminergic denervation and reduced mTOR activity and neuroinflammation. Concomitantly, MSDC-0160 administration strongly modified energy metabolism as revealed by increased ketogenesis, beta oxidation and glutamate oxidation to satisfy energy needs and maintain energy homeostasis.

Conclusion

MSDC-0160 exerts its neuroprotective effect through reorganization of multiple pathways connected to energy metabolism.
Symbolic Kinetic Models in Python (SKiMpy): Intuitive modeling of large-scale biological kinetic models
Authors: Weilandt Daniel R. , Salvy Pierre , Masid Maria , Fengos Georgios , Denhardt-Erikson Robin , Hosseini Zhaleh , Hatzimanikatis Vassily
Published: January 2022

Motivation

Large-scale kinetic models are an invaluable tool to understand the dynamic and adaptive responses of biological systems. The development and application of these models have been limited by the availability of computational tools to build and analyze large-scale models efficiently. The toolbox presented here provides the means to implement, parametrize and analyze large-scale kinetic models intuitively and efficiently.

Results

We present a Python package (SKiMpy) bridging this gap by implementing an efficient kinetic modeling toolbox for the semiautomatic generation and analysis of large-scale kinetic models for various biological domains such as signaling, gene expression, and metabolism. Furthermore, we demonstrate how this toolbox is used to parameterize kinetic models around a steady-state reference efficiently. Finally, we show how SKiMpy can imple-ment multispecies bioreactor simulations to assess biotechnological processes.

Availability

The software is available as a Python 3 package on GitHub:https://github.com/EPFL-LCSB/SKiMpy, along with adequate documentation.

Contact

vassily.hatzimanikatis@epfl.ch
CView: A network based tool for enhanced alignment visualization
Authors: Linheiro Raquel , Lobo Diana , Sabatino Stephen , Archer John
Published: January 2022

To date basic visualization of sequence alignments have largely focused on displaying per-site columns of nucleotide, or amino acid, residues along with associated frequency summarizations. The persistence of this tendency to the more recent tools designed for the viewing of mapped read data indicates that such a perspective not only provides a reliable visualization of per-site alterations, but also offers implicit reassurance to the end user in relation to data accessibility. However, the initial insight gained is limited, something that is especially true when viewing alignments consisting of many sequences representing differing factors, such as geographical location, date and subtype. A basic alignment viewer can have potential to increase initial insight through visual enhancement, whilst not delving into the realms of complex sequence analysis. Here we present CView, a visualizer that expands on the per-site representation of residues through the incorporation of a dynamic network that is based on the summarization of diversity present across different regions of the alignment. Within the network nodes are based on the clustering of sequence fragments spanning windows that are placed consecutively along the alignment. Edges are placed between nodes of neighbouring windows where they share sequence id’s. Thus, if a single node is selected on the network, then the relationship that all sequences passing through that node have to other regions of diversity within the alignment can be instantly observed through the tracing of paths. In addition to augmenting visual insight, CView provides many export features including variant summarization, per-site residue and kmer frequency matrixes, consensus sequence generation, alignment dissection as well as general sequence clustering, each of which are useful across a range of research areas. The software has been designed to be user friendly, intuitive and interactive. It, along with source code, a quick start guide and test data, are available through the SourceForge project page: https://sourceforge.net/projects/cview/.
Sensory system-specific associations between brain structure and balance
Authors: Hupfeld KE , McGregor HR , Hass CJ , Pasternak O , Seidler RD
Published: January 2022

Nearly 75% of older adults in the United States report balance problems. Balance difficulties are more pronounced during sensory feedback perturbation (e.g., standing with the eyes closed or on foam). Although it is known that aging results in widespread brain atrophy, less is known about how brain structure relates to balance performance under varied sensory conditions in older age. We measured postural sway of 36 young (18-34 years) and 22 older (66-84 years) adults during four conditions: eyes open, eyes closed, eyes open on foam, and eyes closed on foam. We calculated three summary measures indicating visual, proprioceptive, and vestibular contributions to balance. We also collectedT1-weighted and diffusion-weighted anatomical MRI scans. We aimed to: 1) test for age group differences in brain structure-balance relationships across a range of structural brain measures (i.e., volumetric, surface, and white matter microstructure); and 2) assess how brain structure measures relate to balance, regardless of age. Across both age groups, thinner cortex in multisensory integration regions was associated with greater reliance on visual inputs for balance. Greater gyrification within sensorimotor and parietal cortices was associated with greater reliance on proprioceptive inputs for balance. Poorer vestibular function was correlated with thinner vestibular cortex, greater gyrification within sensorimotor, parietal, and frontal cortices, and lower free water-corrected axial diffusivity in the superior-posterior corona radiata and across the corpus callosum. These results contribute to our scientific understanding of how individual differences in brain structure relate to balance. This has implications for developing brain stimulation interventions to improve balance.

Significance Statement

Older age is associated with greater postural sway, particularly when sensory information is perturbed (e.g., by closing one’s eyes). Our work contributes to the field by identifying how individual differences in regional brain structure relate to balance under varying sensory conditions in young and older adults. Across both age groups, lower cortical thickness in sensory integration and vestibular regions, greater gyrification within sensorimotor, parietal, and temporal regions, and lower free water-corrected axial diffusivity in the corpus callosum and corona radiata were related to individual differences in balance scores. We identified brain structures that are associated with specific sensory balance scores; therefore, these results have implications for which brain regions to target in future interventions for different populations.
Combined patterns of activity of major neuronal classes underpin a global change in brain state during spontaneous and forced walk inDrosophila
Authors: Aimon Sophie , Cheng Karen Y. , Gjorgjieva Julijana , Grunwald Kadow Ilona C.
Published: January 2022

Movement-correlated brain activity has been found across species and brain regions. Here, we used fast whole-brain lightfield imaging in adultDrosophilato investigate the relationship between walk and neuronal activity. We observed brainwide activity that tightly correlated with spontaneous bouts of walk. While imaging specific sets of excitatory, inhibitory, and neuromodulatory neurons highlighted their joint contribution, spatial heterogeneity in forward walk- and turning-induced activity allowed parsing unique responses from subregions and sometimes individual neurons. For example, previously uncharacterized serotonergic neurons were inhibited during walk. While activity onset in some areas preceded walk onset exclusively in spontaneously walking animals, spontaneous and forced walk elicited highly similar activity in most brain regions. These data suggest a major contribution of walk and walk-related sensory or proprioceptive information to brain state. We conclude that walk-related signals induce global but heterogeneous patterns of activity, allowing for local and brain-wide integration of behavioral state into other processes in the brain.
Membrane Stretch Gates NMDA Receptors
Authors: Belin Sophie , Maki Bruce A. , Catlin James , Rein Benjamin A. , Popescu Gabriela K.
Published: January 2022

N-Methyl-D-aspartic (NMDA) receptors are excitatory glutamate-gated ion channels. Their activation is essential for the normal development, maintenance, and plasticity of excitatory synapses in the central nervous system. They function as glutamate-gated Ca2+-permeable channels, require glycine as co-agonist, and can be modulated by myriad of diffusible ligands and cellular cues, including mechanical stimuli. Previously, we found that in cultured astrocytes, shear stress initiates NMDA receptor-mediated Ca2+ entry in the absence of added agonists, suggesting that in addition to being mechanosensitive, NMDA receptors may be mechanically activated. Here, we used controlled expression of recombinant receptors and non-invasive on-cell single-channel current recordings to show that gentle membrane stretch can substitute for the neurotransmitter glutamate in gating NMDA receptor currents. Notably, stretch-activated currents preserved the hallmark features of the glutamate-gated currents, including glycine-requirement, large unitary conductance, high Ca2+ permeability, and voltage-dependent Mg2+ blockade. Further, we found that the stretch-gated current required the receptor’s intracellular domain, which may suggest a force-from-filament sensing mechanism. These results are consistent with the hypothesis that mechanical forces can gate NMDA receptor currents even in the absence of synaptic glutamate release, which has important implications for understanding mechanotransduction and the effect of mechanical forces on cells of the central nervous system.

Highlights

Membrane stretch gates NMDA receptor currents in the absence of the neurotransmitter glutamate.

Stretch-gated currents maintain the characteristic features of glutamate-gated currents, including glycine requirement, Ca2+ permeability, and voltage-dependent Mg2+ block.

Gating of NMDA receptor by membrane stretch requires the receptor’s intracellular domain.

Mild stretch of neuronal membranes gate native NMDA receptor currents.

Membrane stretch gates NMDA receptor currents in the absence of neurotransmitter. Stretch-gated currents have the biophysical hallmarks of the glutamate-gated currents including requirement for glycine, large Na+ conductance, high Ca2+ permeability, and voltage-dependent Mg2+ block.
ScrepYard: an online resource for disulfide-stabilised tandem repeat peptides
Authors: Liu Junyu , Maxwell Michael , Cuddihy Thom , Crawford Theo , Bassetti Madeline , Hyde Cameron , Undheim Eivind A. B. , Mobli Mehdi
Published: January 2022

Receptor avidity through multivalency is a highly sought-after property of ligands. While readily available in nature in the form of bivalent antibodies, this property remains challenging to engineer in synthetic molecules. The discovery of several bivalent venom peptides containing two homologous and independently folded domains (in a tandem repeat arrangement) has provided a unique opportunity to better understand the underpinning design of multivalency in multimeric biomolecules, as well as how naturally occurring multivalent ligands can be identified. In previous work we classified these molecules as a larger class termed secreted cysteine-rich repeat-proteins (SCREPs). Here, we present an online resource; ScrepYard, designed to assist researchers in identification of SCREP sequences of interest and to aid in characterizing this emerging class of biomolecules. Analysis of sequences within the ScrepYard reveals that two-domain tandem repeats constitute the most abundant SCREP domain architecture, while the interdomain “linker” regions connecting the ordered domains are found to be abundant in amino acids with short or polar sidechains and contain an unusually high abundance of proline residues. Finally, we demonstrate the utility of ScrepYard as a virtual screening tool for discovery of putatively multivalent peptides, by using it as a resource to identify a previously uncharacterised serine protease inhibitor and confirm its predicated activity using an enzyme assay.
Assessing the response to genomic selection by simulation
Authors: Buntaran Harimurti , Bernal-Vasquez Angela Maria , Gordillo Andres , Wimmer Valentin , Sahr Morten , Piepho Hans-Peter
Published: January 2022

The goal of any plant breeding program is to maximize genetic gain for traits of interest. In classical quantitative genetics, the genetic gain can be obtained from what is known as “Breeder’s equation”. In the past, only phenotypic data was used to compute the genetic gain. The advent of genomic prediction has opened the door to the utilization of dense markers for estimating genomic breeding values or GBV. The salient feature of genomic prediction is the possibility to carry out genomic selection with the assistance of the kinship matrix, hence, improving the prediction accuracy and accelerating the breeding cycle. However, estimates of GBV as such do not provide the full information on the number of entries to be selected as in the classical response to selection. In this paper, we use simulation, based on a fitted mixed model for genomic prediction in a multi-environmental framework, to answer two typical questions of a plant breeder: (1) How many entries need to be selected to have a defined probability of selecting the truly best entry from the population; (2) What is the probability of obtaining the truly best entries when some top-ranked entries are selected.