bluuebunny/crossref_metadata_2025 huggingface dataset:
Worlds Apart: Does Perceptual Congruence Between Leaders and Older Employees Regarding Age-Friendly Organizational Climate, Management, and Work Design Matter?
Authors: Finsel Julia S , Venz Laura , Wöhrmann Anne M , Wilckens Max R , Deller Jürgen
Published: April 2023

Research on the effectiveness of age-friendly organizational practices tends to focus on older employees’ perceptions of these. Drawing on perceptual congruence and psychological contract theory, we hypothesize that leaders’ perceptions of these organizational practices are relevant as well. Specifically, we argue that (dis)agreement between leaders’ and older employees’ perceptions (i.e., perceptual (in)congruence) of organizational practices related to age-friendly organizational climate, management, and work design plays a role in older employees’ well-being. Polynomial regression and response surface analysis were applied to a dyadic sample of 484 older employees and their leaders from 100 diverse organizations. Results reveal that leader-employee perceptual congruence on high levels of perceived age-friendly work design was related to higher employee well-being. By contrast, older employees’ well-being was lower when leaders evaluated the three age-friendly organizational practices higher than their older employees. Our findings suggest that further theoretical consideration of the role of leader-employee perceptual (in)congruence for aging workforces is needed, and that scholars and organizations should acknowledge the relevance and interplay of different stakeholders’ perceptions within an organization.
Sensory Loss and its Association with Different Types of Departures from the Labor Force Among Older Adults in the US
Authors: Garcia Morales Emmanuel E , Powel Danielle S , Gray Andrew , Assi Lama , Reed Nicholas S
Published: April 2023

To investigate the association between sensory loss and the timing and type of self-reported departures from the labor force, via retirement or disability, we used data from the Health and Retirement Study, cycles 2004–2018. Based on self-reported sensory loss, we classified individuals into four groups: no sensory loss, hearing loss only, vision loss only, and dual sensory loss (vision and hearing loss). We assumed that older adults could leave the labor force either by retirement or due to disability. Because once one type of exit is observed the other type cannot be observed, we implemented a competing risk approach to estimate the instantaneous rate of departure (sub-distribution hazard rate) for leaving the labor force due to disability, treating retirement as a competing risk, and for departures via retirement, with disability as the competing risk. We found that compared to older adults with no sensory loss, adults with vision loss are at a higher risk for leaving the labor force via disability (when treating retirement as a competing risk). Compared to no sensory loss, hearing loss was associated with a higher risk for retirement in models treating disability as a competing risk. Given the differences between disability and retirement benefits (before and after retirement age), policies intended to keep people with sensory loss from early labor force departures, such as accommodations in the workplace and/or hearing and vision care coverage, might contribute to better retiring conditions and healthy aging among older adults with sensory loss.
Identification and characterization of a hepatic IL-13–producing ILC3-like population potentially involved in liver fibrosis
Authors: Raabe Jan , Kaiser Kim M. , ToVinh Michael , Finnemann Claudia , Lutz Philipp , Hoffmeister Christoph , Bischoff Jenny , Goeser Felix , Kaczmarek Dominik J. , Glowka Tim R. , Manekeller Steffen , Charpentier Arthur , Langhans Bettina , Nischalke Hans Dieter , Toma Marieta , Strassburg Christian P. , Spengler Ulrich , Abdallah Ali T. , Krämer Benjamin , Nattermann Jacob
Published: April 2023

Background and Aims:

Human innate lymphoid cells (ILCs) are critically involved in the modulation of homeostatic and inflammatory processes in various tissues. However, only little is known about the composition of the intrahepatic ILC pool and its potential role in chronic liver disease. Here, we performed a detailed characterization of intrahepatic ILCs in both healthy and fibrotic livers.

Approach and Results:

A total of 50 livers (nonfibrotic = 22, and fibrotic = 29) were analyzed and compared with colon and tonsil tissue (each N = 14) and peripheral blood (N = 32). Human intrahepatic ILCs were characterized ex vivo and on stimulation using flow cytometry and single-cell RNA sequencing. ILC differentiation and plasticity were analyzed by both bulk and clonal expansion experiments. Finally, the effects of ILC-derived cytokines on primary human HSteCs were studied. Unexpectedly, we found that an “unconventional” ILC3-like cell represented the major IL-13-producing liver ILC subset. IL-13+ ILC3-like cells were specifically enriched in the human liver, and increased frequencies of this cell type were found in fibrotic livers. ILC3-derived IL-13 production induced upregulation of proinflammatory genes in HSteCs, indicating a potential role in the regulation of hepatic fibrogenesis. Finally, we identified KLRG1-expressing ILC precursors as the potential progenitor of hepatic IL-13+ ILC3-like cells.

Conclusions:

We identified a formerly undescribed subset of IL-13–producing ILC3-like cells that is enriched in the human liver and may be involved in the modulation of chronic liver disease.
Evaluation of serum vitamin D concentration and blood eosinophil and basophil counts in patients with vitiligo: cross-sectional study from Rafsanjan and Zarand, Iran
Authors: Taghizadeh Ghavamabadi Razieh , Pishgooie Reihaneh , Behfar Shadi , Taghavi Mohammad Mohsen , Babaee Abdolreza , Taghipour Zahra
Published: April 2023

Objective:

Vitiligo is a chronic autoimmune depigmenting skin disorder. In this disease, the destruction of functional melanocytes can lead to reduced or absent pigmentation of the skin. Vitamin D deficiency has been reported in some autoimmune diseases. The association of eosinophils and basophils with autoimmune diseases has also been recently examined.

Methods:

The present study was performed to evaluate the serum vitamin D concentration and blood eosinophil and basophil counts in patients with vitiligo.

Results:

This descriptive cross-sectional study involved 30 patients with vitiligo. The average serum vitamin D concentration was significantly lower in the case group than in the control group (P = 0.01). Furthermore, the mean serum vitamin D concentration was significantly lower in women than in men (P = 0.03). The average eosinophil and basophil counts were not significantly different between the case and control groups.

Discussion:

The results of this study showed that the serum vitamin D concentration is low in patients with vitiligo. However, whether this reduction is a factor in the promotion of vitiligo or occurs after the onset of vitiligo remains unknown. Further studies on the serum vitamin D concentration in patients with vitiligo are needed to clarity this issue and develop effective treatments.
Association Between Rosacea and Frequent Changes in Moisturizing Products: A Multicenter Retrospective Case–control Survey
Authors: Jiang Yu-Meng , Yao Ya-Nan , Li Guo , Zheng Bo-Lan , Xie Hong-Fu , Li Ji , Huang Ying-Xue
Published: April 2023

Objective:

To investigate the detailed relationship between frequent replacement of moisturizing product brands and the development of rosacea, with the overall goal of establishing guidelines for patients with rosacea.

Methods:

A multicenter retrospective case–control survey of 849 patients with rosacea and 980 controls with healthy skin was conducted using a standardized questionnaire. The questionnaire mainly included demographic data, the behavior of frequently changing moisturizing product brands, history of skin allergy or sensitivity symptoms within 2 years before rosacea onset for the patient group and within the most recent 2 years for the control group, current symptoms and signs, and self-reported symptoms. A comparative analysis was performed using the chi-square test and logistic regression analysis.

Results:

The behavior of frequently replacing moisturizing product brands was positively correlated with rosacea (P < 0.001, odds ratio [OR] = 1.522, 95% confidence interval [CI] = 1.148-2.018), and this correlation was more apparent in individuals with non-sensitive skin (P = 0.008, OR = 1.634, 95% CI = 1.135-2.352). With respect to different subtypes of rosacea, frequent replacement of moisturizing product brands was more likely to be associated with papulopustular rosacea (P = 0.003, OR = 1.804, 95% CI = 1.219-2.672) than with erythematotelangiectatic rosacea (P = 0.031, OR = 1.432, 95% CI = 1.033-1.984) compared with people who did not frequently replace their moisturizing product brands; however, these effects were not observed for phymatous rosacea (P > 0.05). We further investigated the clinical features of patients who frequently replaced their moisturizing products. Among invisible symptoms, these patients most often reported a stinging sensation (P = 0.007, OR = 1.497, 95% CI = 1.119-2.003), and among visible symptoms, telangiectasia was most common (P = 0.027, OR = 1.411, 95% CI = 1.041-1.913).

Conclusion:

Frequent replacement of moisturizing product brands was closely associated with the occurrence of rosacea. Our study provides useful information regarding skin care habits to the public and will help to promote the prevention and management of rosacea.
Epidemiology of depression and suicidal ideation in patients with psoriasis: A meta-analysis of prospective cohort studies
Authors: Yu Yi-Hui , Zhang San-Quan , Li Qian , Li Wei , Zhou Xin , Xue Ru-Jun , Liang Jing-Yao , Zhang Xi-Bao
Published: April 2023

Background:

Psoriasis is an immune-mediated inflammatory, chronic, recurrent skin disease associated with a high risk of developing psychiatric disorders, especially depression and suicidal ideation, leading to functional disability and poor quality of life.

Objective:

To comprehensively review and assess the epidemiologic association between psoriasis and the risk ratios (RRs) of depression or suicidal ideation.

Methods:

Five databases (PubMed, Wanfang Database, CNKI, The Cochrane Library, and EMBASE) were searched for prospective cohort studies on the prevalence of depression and/or suicidal ideation in patients with psoriasis updated to 2 February 2023. Two independent reviewers evaluated and extracted the data, which were then pooled into a summary RR with corresponding 95% confidence interval (CI) using random-effects models in Stata/MP14.0.

Results:

Sixteen cohort studies comprising 1,166,840 patients with psoriasis and 3,294,205 controls were eligible for the final analysis. The pooled RR for depression was 1.43 (95% CI = 1.13–1.81) in patients with psoriasis and1.55 (95% CI = 1.40–1.71) in patients with psoriatic arthritis. In the subgroup analysis, Asian patients with psoriasis (RR=1.38, 95% CI =1.17–1.63) had a lower pooled RR for depression than non-Asian patients (RR=1.45, 95% CI = 1.07–1.97), and patients with moderate to severe psoriasis (RR=1.69, 95% CI = 1.15–2.50) showed a higher RR for depression than patients with mild psoriasis (RR=1.60, 95% CI= 1.06–2.42). We also found no increase in the RR for suicidal ideation among people with psoriasis (RR=1.25, 95% CI =0.95–1.65).

Conclusions:

Patients with psoriasis are at increased risk of depression. Among patients with psoriasis, those with psoriatic arthritis, those who are non-Asian, and those with moderate to severe psoriasis are at higher risk for depression. However, the available evidence does not support an association between psoriasis and suicidal ideation.
Oral Chinese medicines for treating diabetic macular edema: Protocol for a systematic search of randomized studies and meta-analysis
Authors: Gao Miaoran , Huang Sheng , Zhou Jian , Yang Yiqiu , Luo Xianke , Yang Changlu , Yu Xinning , Tang Mengdan , Yan Xiaoling
Published: April 2023

Introduction

The diabetic macular edema (DME) is a relevant cause of visual impairment in diabetes. The current treatments are limited by high costs, risk of infections and damage to retinal cells. Randomized controlled studies (RCTs) have investigated oral traditional Chinese medicines (TCMs) for the treatment of DME. We aimed at determining the efficacy and safety of oral TCMs by systematically reviewing the full set of studies.

Methods and analysis

Published RCTs will be searched through 12 databases until October 1, 2022. Two investigators will conduct independent literature search, data extraction and assessment of quality. The risk of bias will be judged with the version 2 of the Cochrane risk-of-bias tool. The RevMan software will be utilized to analyze data. Dichotomous data will be assessed by using odds ratios and 95% confidence intervals (CIs). We will evaluate continuous data by using weighted mean differences and 95% CIs. We are going to assess heterogeneity by Cochran’s Q test and the I2statistics. We plan sensitivity analysis and subgroup analysis to identify sources of heterogeneity. Funnel plots, Egger’s tests and Begg’s tests will be also performed.

Protocol registration number

The study protocol is registered on PROSPERO (CRD42022379268).

Strengths and limitations

This is the first systematic study examining the efficacy and safety of orally administered Chinese medicines for DME.

We will search randomized controlled trials in 12 databases.

We will implement subgroup analysis and sensitivity analysis to explore any source of heterogeneity.

The presence of several types of macular oedema might challenge the workload for this study.
Systematic mapping of chemoreceptor specificities forPseudomonas aeruginosa
Authors: Xu Wenhao , Cerna-Vargas Jean Paul , Tajuelo Ana , Montoya Andrea Lozano , Kivoloka Melissa , Krink Nicolas , Monteagudo-Cascales Elizabet , Matilla Miguel A. , Krell Tino , Sourjik Victor
Published: April 2023

The chemotaxis network, one of the most prominent prokaryotic sensory systems, is present in most motile bacteria and archaea. Although the conserved signaling core of the network is well characterized, ligand specificities of a large majority of diverse chemoreceptors encoded in bacterial genomes remain unknown. Here we performed a systematic identification and characterization of new chemoeffectors for the opportunistic pathogenPseudomonas aeruginosa, which has 26 chemoreceptors possessing most of the common types of ligand binding domains. By performing capillary chemotaxis assays for a library of growth-promoting compounds, we first identified a number of novel chemoattractants of varying strength. We subsequently mapped specificities of these ligands by performing Förster resonance energy transfer (FRET) and microfluidic measurements for hybrids containing ligand binding domains ofP. aeruginosachemoreceptors and the signaling domain of theEscherichia coliTar receptor. Direct binding of ligands to chemoreceptors was further confirmedin vitrousing thermal shift assay and microcalorimetry. Altogether, the combination of methods enabled us to assign several new attractants, including methyl 4-aminobutyrate, 5-aminovalerate, L-ornithine, 2-phenylethylamine and tyramine, to previously characterized chemoreceptors and to annotate a novel purine-specific receptor PctP. Our screening strategy could be applied for the systematic characterization of unknown sensory domains in a wide range of bacterial species.

Importance

Chemotaxis of motile bacteria has multiple physiological functions. It enables bacteria to locate optimal ecological niches, mediates collective behaviors, and can play an important role in infection. These multiple functions largely depend on ligand specificities of chemoreceptors, and the number and identities of chemoreceptors show high diversity between organisms. Similar diversity is observed for the spectra of chemoeffectors, which include not only chemicals of high metabolic value but also bacterial, plant and animal signaling molecules. However, the systematic identification of chemoeffectors and their mapping to specific chemoreceptors remains a challenge. Here, we combined severalin vivoandin vitroapproaches to establish a systematic screening strategy for the identification of receptor ligands, and we applied it to identify a number of new physiologically relevant chemoeffectors for the important opportunistic human pathogenP. aeruginosa. This strategy can be equally applicable to map specificities of sensory domains from a wide variety of receptor types and bacteria.
Broad functional profiling of fission yeast proteins using phenomics and machine learning
Authors: Rodríguez-López María , Bordin Nicola , Lees Jon , Scholes Harry , Hassan Shaimaa , Saintain Quentin , Kamrad Stephan , Orengo Christine , Bähler Jürg
Published: April 2023

Many proteins remain poorly characterized even in well-studied organisms, presenting a bottleneck for research. We applied phenomics and machine-learning approaches withSchizosaccharomyces pombefor broad cues on protein functions. We assayed colony-growth phenotypes to measure the fitness of deletion mutants for 3509 non-essential genes in 131 conditions with different nutrients, drugs, and stresses. These analyses exposed phenotypes for 3492 mutants, including 124 mutants of ‘priority unstudied’ proteins conserved in humans, providing varied functional clues. For example, over 900 proteins were newly implicated in the resistance to oxidative stress. Phenotype-correlation networks suggested roles for poorly characterized proteins through ‘guilt by association’ with known proteins. For complementary functional insights, we predicted Gene Ontology (GO) terms using machine learning methods exploiting protein-network and protein-homology data (NET-FF). We obtained 56,594 high-scoring GO predictions, of which 22,060 also featured high information content. Our phenotype-correlation data and NET-FF predictions showed a strong concordance with existing PomBase GO annotations and protein networks, with integrated analyses revealing 1,675 novel GO predictions for 783 genes, including 47 predictions for 23 priority unstudied proteins. Experimental validation identified new proteins involved in cellular ageing, showing that these predictions and phenomics data provide a rich resource to uncover new protein functions.
Antibacterial Activity ofAndrographis paniculataandPiper betleand their Interactive Effects with Amoxicillin Against Selected Respiratory Pathogens
Authors: Mejos Cristian B. , Poblete Joshua G. , Sarino Paula Jean C. , Cruzada Ma. Fatima I.
Published: April 2023

This study was undertaken to determine the antibacterial activity and interactive effects of the methanol, ethanol and aqueous extract ofAndrographis paniculataandPiper betleleaves with amoxicillin against selected clinical isolates of respiratory pathogens:Escherichia coliUSTCMS 1030,Pseudomonas aeruginosa USTCMS10013, andStaphylococcus aureusUSTCMS 1097. Antibacterial activity of the plant extracts using disk diffusion showed that the methanol extract ofP. betleexhibited inhibitory activity against all the test organisms, whereas the methanol and ethanol extracts ofA. paniculataexhibited antibacterial activity toS. aureusUSTCMS 1097 only. The antimicrobial properties of each plant extract were further evaluated using broth microdilution. Results showed that the ethanol extract ofP. betlehad the most potent antibacterial activity against all test bacteria with minimum inhibitory concentrations of 6.5 mg/mL, 3.25 mg/mL, and 0.2 mg/mL forE. coliUSTCMS 1030,P. aeruginosaUSTCMS 10013 andS. aureusUSTCMS 1097, respectively. However, resazurin showed an inhibitory activity againstS. aureusUSTCMS 1097 in usual concentrations used in the assay, which is a novel finding since it is typically used as an indicator. Based on disk diffusion, the methanol and aqueous extracts ofP. betleshowed promising synergistic effect with the antibiotic amoxicillin. This was confirmed by checkerboard assay wherein the aqueous extract ofP. betleshowed an additive effect to amoxicillin againstE. coliUSTCMS 1030 (FICI = 0.66), while the methanol extract ofP. betleexhibited true synergism with amoxicillin againstP. aeruginosaUSTCMS 10013 (FICI = 0.33). This synergism between the ethanol extract ofP. betleand amoxicillin was significant since the activity of amoxicillin increased by 128-fold. This combination has potential in treating diseases associated with amoxicillin- resistantP. aeruginosa.
The central nervous system is a potential reservoir and possible origin of drug resistance in HBV
Authors: Xu Lijun , Zhou Minghan , Peng Xiuming , Xu Yufan , Huang Fan , Wang Linyun , Peng Xiaorong , Yang Zongxing , Tao Ran , Lang Guanjing , Cao Qing , Li Minwei , Huang Ying , Zhu Biao , Xu Yan
Published: April 2023

The significance of HBV in cerebrospinal fluid (CSF) is unclear. In the present study,synchronous serum and CSF samples were collected from 13 patients. HBV-DNA, full-length genome, quasispecies, phylogenetic tree, compartmentalization and mutation of reverse transcriptase (RT) region analyses were performed based on PCR and sequencing methods. We found HBV-DNA was detected in the CSF of 3 antiviral-naïve patients and one patient after successful antiviral therapy. Complete full-length HBV genomes were isolated from the CSF of 5 patients, including 2 patients with undetectable serum HBV-DNA. Ten patients exhibited distinct CSF-serum quasispecies, 8 harbored independent CSF-serum genetic compartmentalization and phylogenetic trees, and 5 patients presented lamivudine/entecavir-associated resistance mutations in only the CSF. The frequencies of rtL180M and rtM204I/V mutations in both serum and CSF were higher in HIV/HBV-coinfected patients than in HBV-monoinfected patients (serum: rtL180M: 3.9% vs. 0, P = 0.004; rtM204I/V: 21.3% vs. 0, P < 0.001; CSF: rtL180M: 7.6% vs. 0, P = 0.026; rtM204I/V 7.6% vs. 1.6%, P = 0.097). Our data suggested CSF is a potential HBV reservoir, and HBV in CSF harbors distinct evolution and mutation models from that in serum. HIV infection increases the possibility of HBV rtL180M and rtM204I/V mutations in both serum and CSF.
Identification of host-interacting domains of surface layer protein B fromLevilactobacillus brevisand the evidence as glycoprotein
Authors: Tan Zheng Lin , Yamamoto Naoyuki
Published: April 2023

Surface layer proteins (Slps) can be found on the surface of some lactobacilli which involves in host-interaction and show immunomodulatory activity. Despite the capability of Slps to interact with C-type lectins on antigen presenting cells, present of sugar has not been confirmed except forLentilactobacillus kefiri. In this study, we investigated the presence of sugar moiety in the structure of SlpB fromLevilactobacillus brevis, and its involvement in interaction with DC-SIGN of dendritic cells. 4 fragments of sugar containing fragments were identified in SlpB, and the involvement of sugar in DC-SIGN interaction was confirmed by competitive assay against hexoses. The sequences of these fragments were identified based on the mass obtained from mass spectrometry, and the result has confirmed that these fragments were from carbohydrate binding motifs of SlpB. Analysing the binding affinities of these fragments with surface resonance plasmon analysis suggested that 2 fragments possess higher binding affinity compared to the remaining fragments, and the sum of binding affinities of these fragments was approximate the affinity of intact SlpB.
Phytohormone profiling in an evolutionary framework
Authors: Schmidt Vojtěch , Skokan Roman , Kurtović Katarina , Vosolsobě Stanislav , Filepová Roberta , Haluška Samuel , Dobrev Petre , Motyka Václav , Petrášek Jan
Published: April 2023

Multiple phytohormones act as conserved developmental regulators in land plants. Although the closely related streptophyte green algae typically lack full complements of molecular pathways underlying these responses, scattered reports of endogenous phytohormone production in these organisms exist. In this study, we performed a detailed LC/MS-based analysis of several phytohormones, their precursors and metabolites in all lineages of streptophyte algae. We also included chlorophyte algae and early-diverging land plants as outgroups. Free auxin, tRNA-derived cytokinins and certain phenolics including salicylic acid were found ubiquitously. However, land plants differed from green algae by the consistent detection of abscisic acid and the presence of auxin and cytokinin conjugates andtrans-zeatin, supporting the hypotheses that these three phytohormones likely came to regulate development in the ancestral land plant. By contrast, we observed a patchy distribution of jasmonates among streptophytes. We additionaly analyzed the corresponding culture and empty media to account for phytohormone excretion and environmental contamination. Extracellular auxins and cytokinins were frequently detected, while agar constituted a major external source of phenolic compounds. We provide a highly comprehensive evolution-directed screen of phytohormone compound occurrence and thoroughly discuss our data in the context of current plant hormonomics and phylogenomics.

GRAPHICAL ABSTRACT
The ketone body β-hydroxybutyrate ameliorates neurodevelopmental deficits in the GABAergic system ofdaf-18/PTEN Caenorhabditis elegansmutants
Authors: Giunti Sebastián , Blanco María Gabriela , De Rosa María José , Rayes Diego
Published: April 2023

A finely tuned balance between excitation and inhibition (E/I) is essential for proper brain function. Disruptions in the GABAergic system, which alter this equilibrium, are a common feature in various types of neurological disorders, including Autism Spectrum Disorders (ASDs).

Mutations in PTEN, the main negative regulator of the PI3K/Akt pathway, are strongly associated with ASD. However, it is unclear whether PTEN deficiencies can differentially affect inhibitory and excitatory signaling. Using theC. elegansneuromuscular system, where both excitatory (cholinergic) and inhibitory (GABAergic) inputs regulate muscle activity, we found thatdaf-18/PTENmutations specifically impact GABAergic (but not cholinergic) neurodevelopment and function. This selective impact results in a deficiency in inhibitory signaling. The specific defects observed in the GABAergic system indaf-18/PTENmutants are due to reduced activity of DAF-16/FOXO during development. Ketogenic diets (KGDs) have proven effective for disorders associated with E/I imbalances. However, the mechanisms underlying their action remain largely elusive. We found that a diet enriched with the ketone body β-hydroxybutyrate during early development induces DAF-16/FOXO activity, therefore improving GABAergic neurodevelopment and function indaf-18/PTENmutants. Our study provides valuable insights into the link between PTEN mutations and neurodevelopmental defects and delves into the mechanisms underlying the potential therapeutic effects of KGDs.

Highlights

*daf-18/PTENdeficiency inC. elegansresults in a specific impairment of inhibitory GABAergic signaling, while the excitatory cholinergic signaling remains unaffected.

*The dysfunction of GABAergic neurons in these mutants arises from the inactivity of the transcription factor DAF-16/FOXO during their development, resulting in conspicuous morphological and functional alterations.

*A diet enriched with the ketone body β-hydroxybutyrate, which induces DAF-16/FOXO activity, mitigates the functional and morphological defects in the development of GABAergic neurons

*β-hydroxybutyrate supplementation during the early stages of development is both necessary and sufficient to achieve these rescuing effects on GABAergic signaling indaf-18/PTENmutants.

Graphical Abstract
Topographic barriers drive the pronounced genetic subdivision of a range-limited fossorial rodent
Authors: Reuber Victoria M. , Westbury Michael V. , Rey-Iglesia Alba , Asefa Addisu , Farwig Nina , Miehe Georg , Opgenoorth Lars , Sumbera Radim , Wraase Luise , Wube Tilaye , Lorenzen Eline D. , Schabo Dana G.
Published: April 2023

Due to their limited dispersal ability, fossorial species with predominantly belowground activity usually show increased levels of population subdivision across relatively small spatial scales. This may be exacerbated in harsh mountain ecosystems, where landscape geomorphology limits species’ dispersal ability and leads to small effective population sizes, making species susceptible to environmental change. The giant root-rat (Tachyoryctes macrocephalus) is a highly fossorial rodent confined to the afro-alpine ecosystem of the Bale Mountains in Ethiopia. Using mitochondrial and low-coverage nuclear genomes, we investigated 77 giant root-rat individuals sampled from nine localities across its whole ∼1,000 km2range. Our data revealed a distinct division into a northern and southern subpopulation, with no signs of gene flow, and higher nuclear genetic diversity in the south. Landscape genetic analyses of the mitochondrial genomes indicated that population subdivision was driven by steep slopes and elevation differences of up to 500 m across escarpments separating the north and south, potentially reinforced by glaciation of the south during the Late Pleistocene (∼42,000 to 16,000 years ago). Despite the pronounced subdivision observed at the range-wide scale, weak geographic structuring of sampling localities within subpopulations indicated gene flow across distances of at least 16 km, suggesting aboveground dispersal and high mobility for relatively long distances. Our study highlights how topographic barriers can lead to the genetic subdivision of fossorial species, despite their potential to maintain gene flow at the local scale. These factors can reduce genetic variability, which should be considered when developing conservation strategies.
Benchmarking imputation methods for discrete biological data
Authors: Gendre Matthieu , Hauffe Torsten , Pimiento Catalina , Silvestro Daniele
Published: April 2023

Trait datasets are at the basis of a large share of ecology and evolutionary research, being used to infer ancestral morphologies, to quantify species extinction risks, or to evaluate the functional diversity of biological communities. These datasets, however, are often plagued by missing data, for instance due to incomplete sampling limited data and resource availabilities. Several imputation methods exist to predict missing values and have been successfully evaluated and used to fill the gaps in datasets of quantitative traits. Here we explore the performance of different imputation methods on discrete biological traits i.e. qualitative or categorical traits such as diet or habitat. We develop a bioinformatics pipeline to impute trait data combining phylogenetic, machine learning, and deep learning methods while integrating a simulation framework to evaluate their performance on synthetic datasets. Using this pipeline we run a wide range of simulations under different missing rates, mechanisms, and biases and different evolutionary models. Our results indicate that a new ensemble approach, where we combined the imputation results of a selection of imputation methods provides the most robust and accurate prediction of missing discrete traits. We apply our pipeline to an incomplete trait dataset of 1015 elasmobranch species (including sharks and rays) and found a high imputation accuracy of the predictions based on an expert-based assessment of the missing traits. Our bioinformatic pipeline, implemented in an open-source R package, facilitates the application and comparison of multiple imputation methods to make robust predictions of missing trait values in biological datasets.
bettercallsal: better calling ofSalmonellaserotypes from enrichment cultures using shotgun metagenomic profiling and its application in an outbreak setting
Authors: Konganti Kranti , Reed Elizabeth , Mammel Mark , Kayikcioglu Tunc , Binet Rachel , Jarvis Karen , Ferreira Christina M. , Bell Rebecca L. , Zheng Jie , Windsor Amanda M. , Ottesen Andrea , Grim Christopher , Ramachandran Padmini
Published: April 2023

Precise and rapid identification ofSalmonellaserotypes from suspect food matrices is critical for successful source attribution of illness outbreaks (Scallan et al., 2011). Currently, close to 3% of U.S. foodborneSalmonellaoutbreaks have been attributed to multiple Salmonellaserotypes (2.85%, 2000 - 2020) (CDC, 2022). Recent foodborne outbreaks that have been attributed to multipleSalmonellaserotypes force us to question whether these are rare events or if previous methods simply did not have the throughput to provide an accurate picture of the complex ecology that is connected to outbreak etiologies. (Hassan et al., 2019; FDA, 2021; Whitney et al., 2021).

Anin-silicobenchmark dataset, comprising 29 uniqueSalmonella, 46 non-Salmonellabacterial and 10 viral genomes, was generated with varying read depths. For outbreak samples, analysis was performed on previously sequenced pre-enrichments and selective enrichments of papayas and peaches (fruits and leaves) that led to the identification of multiple serovars. Data analyses was performed using a custom-builtk-mertool, SeqSero2, Kallisto and bettercallsal.

Thein-silicodataset analyzed with bettercallsal had accuracy, recall and specificity of 95%, 96% and 98 % respectively. In the papaya outbreak samples, bettercallsal identified multiple serovar presence in concordance with Bioplex assay results and the genome hits assigned to the samples areSalmonellaisolates from the papaya outbreak as evident by NCBI SNP cluster information. In peach outbreak samples, bettercallsal identified both the serovars (Alachua and Gaminara) in concordance withk-mer analysis and the Luminex xMap assay. bettercallsal outperformedk-mer, Kallisto and Seqsero2 in identifying multiple serovars from enrichment cultures using shotgun metagenomics sequencing.

MostSalmonellasubtyping work has relied upon WGS methods which focuses on the high-resolution analysis of single genomes, or multiple single genomes picked from colonies on agar. Here we introduce laboratory and bioinformatics innovations for a metagenomic outbreak response workflow that accurately identifies multipleSalmonellaserovars at the same time in a much higher throughput approach. bettercallsal is one of the first analysis tools that can potentially identify multipleSalmonellaspp. serotypes from a metagenomic or quasi-metagenomic datasets with accuracy and can provide early insights into the etiology of the sample.
Single-cell transcriptome analysis reveals the cellular atlas of human intracranial aneurysm and highlights inflammation features associated with aneurysm rupture
Authors: Ji Hang , Li Yue , Sun Haogeng , Chen Ruiqi , Zhou Ran , Xiao Anqi , Yang Yongbo , Wang Rong , You Chao , Liu Yi
Published: April 2023

Intracranial aneurysm (IA) is pouch-like pathological dilations of cerebral arteries, which often affects middle-aged people and culminates in life-threatening hemorrhagic stroke. A deeper knowledge of the cellular and gene expression perturbations in human IA tissue deepens our understanding of disease mechanisms and facilitates developing pharmacological targets for unruptured IA. In this study, 21,332 qualified cells were obtained from cell-sparse ruptured and unruptured human IA tissues and a detailed cellular profile was determined, including conventional endothelial cells, smooth muscle cells (SMC), fibroblasts and the newly identified pericytes. Notably, striking proportion of immune cells were identified in IA tissue, with the number of monocyte/macrophages and neutrophils being remarkably higher in ruptured IA. By leveraging external datasets and machine learning algorithms, a subset of macrophages characterized by high expression of CCL3 and CXCL3, and transcriptional activation of NF-κB and HIVEP2 was identified as the cell most associated with IA rupture. Further, the interactome of CCL3/CXCL3 macrophages disclosed their role in regulating vascular cell survival and orchestrating inflammation. In summary, this study illustrated the profile and interactions of vascular and immune cells in human IA tissue and the opportunities for targeting local chronic inflammation.
Interferon ε restricts Zika virus infection in the female reproductive tract
Authors: Xu Chuan , Wang Annie , Ebraham Laith , Sullivan Liam , Tasker Carley , Pizutelli Vanessa , Couret Jennifer , Hernandez Cyril , Deb Pratik Q. , Fritzky Luke , Subbian Selvakumar , Gao Nan , Lo Yungtai , Salvatore Mirella , Rivera Amariliz , Lemenze Alexander , Fitzgerald-Bocarsly Patricia , Tyagi Sanjay , Lu Wuyuan , Beaulieu Aimee , Chang Theresa L.
Published: April 2023

Interferon ε (IFNε) is a unique type I IFN that has been implicated in host defense against sexually transmitted infections (STIs). Zika virus (ZIKV), an emerging pathogen, can infect the female reproductive tract (FRT) and cause devastating diseases, particularly in pregnant women. How IFNε contributes to protection against ZIKV infectionin vivois unknown. Here, we show that IFNε plays a critical role in host protection against vaginal ZIKV infection in mice. We found that IFNε was expressed not only by epithelial cells in the FRT, but also by certain immune and other cells at baseline or after exposure to viruses or specific TLR agonists. IFNε-deficient mice exhibited abnormalities in the epithelial border and underlying tissue in the cervicovaginal tract, and these defects were associated with increased susceptibility to vaginal, but not subcutaneous ZIKV infection. IFNε-deficiency resulted in an increase in magnitude, duration, and depth of ZIKV infection in the FRT. Critically, intravaginal administration of recombinant IFNε protectedIfnε-/-mice and highly susceptibleIfnar1-/-mice against vaginal ZIKV infection, indicating that IFNε was sufficient to provide protection even in the absence of signals from other type I IFNs and in an IFNAR1-independent manner. Our findings reveal a potentially critical role for IFNε in mediating protection against transmission of ZIKV in the context of sexual contact.

Significance

Interferon ε (IFNε), a unique Type I IFN that is highly expressed in the epithelium of the female reproductive tract (FRT), is thought to protect the host against sexually transmitted infections (STIs) but the mechanism of action is not defined. Zika virus (ZIKV), a causative agent for preterm birth and other severe diseases in pregnant women, can be spread through vaginal transmission. Here, we show that mice lacking theIfnεgene have abnormal epithelial development and tissue architecture in the cervicovaginal tract. The role of IFNε in protecting host against ZIKV is FRT-specific and is independent of IFNAR1 signaling. Our findings suggest potential preventive strategies based on harnessing mucosal immunity against STIs.
A clinical study to evaluate the safe and effective use of Stethoglove, a single use stethoscope cover to reduce pathogen transmission during auscultation
Authors: Nazari-Shafti Timo Z. , Meyborg Heike , Iske Jasper , Schloss Maximilian , Seeber Fabian , Friedrich Aljona , Exarchos Vasileios , Richter Anja , Falk Volkmar , Emmert Maximilian Y
Published: April 2023

Objectives

Stethoscopes carry a significant risk for pathogen transmission. Here, the safe use and performance of Stethoglove®, a non-sterile, single-use cover for stethoscopes, that is impermeable for pathogens, was investigated by different healthcare professionals (HCPs) in the postoperative care setting of an intensive care unit (ICU).

Methods

Fifty-four patients underwent routine auscultations with the use of Stethoglove®. The participating HCPs (n=34) rated each auscultation with Stethoglove®on a 5-point Likert scale. The mean ratings of acoustic quality and Stethoglove®handling were defined as primary and secondary performance endpoint.

Results

534 auscultations with Stethoglove®were performed (average 15.7/user) on the lungs (36.1%), the abdomen (33.2%), the heart (28.8%) or other body-sites (1.9%). No adverse device-effects occurred. The acoustic quality was rated at 4.2±0.7 (mean) with a total of 86.1% of all auscultations being rated at least as 4/5, and with no rating as below 2. The Stethoglove®handling was rated at 3.7±0.8 (mean) with a total of 96.4% of all auscultations being rated at least 3/5.

Conclusions

Using a real-world setting, this study demonstrates that Stethoglove®can be safely and effectively used as cover for stethoscopes during auscultation. Stethoglove®may therefore represent a useful and easy-to-implement tool for preventing stethoscope-mediated infections.
Synthetically mannosylated antigens induce antigen-specific humoral tolerance and reduce anti-drug antibody responses to immunogenic biologics
Authors: Wallace Rachel P. , Refvik Kirsten C. , Antane Jennifer T. , Brünggel Kym , Tremain Andrew C. , Raczy Michal R. , Alpar Aaron T. , Nguyen Mindy , Solanki Ani , Slezak Anna J. , Watkins Elyse A. , Lauterbach Abigail L. , Cao Shijie , Wilson D. Scott , Hubbell Jeffrey A.
Published: April 2023

Immunogenic biologics trigger an anti-drug antibody (ADA) response in patients, which reduces efficacy and increases adverse reactions. Our laboratory has previously shown that targeting protein antigen to the liver microenvironment can reduce antigen-specific T cell responses; herein, we present a strategy to increase delivery of otherwise immunogenic biologics to the liver via conjugation to a synthetic mannose polymer (p(Man)). This delivery leads to reduced antigen-specific T follicular helper cell and B cell responses resulting in diminished ADA production, which is maintained throughout subsequent administrations of the native biologic. We found that p(Man)-antigen treatment impairs the ADA response against recombinant uricase, a highly immunogenic biologic, without a dependence on hapten immunodominance or control by Tregs. We identify increased TCR signaling and increased apoptosis and exhaustion in T cells as effects of p(Man)-antigen treatment via transcriptomic analyses. This modular platform may enhance tolerance to biologics, enabling long-term solutions for an ever-increasing healthcare problem.
Coding of time with non-linear mixed selectivity in Prefrontal Cortex ensembles
Authors: Mikkelsen Catherine A. , Charczynski Stephen J. , Brincat Scott K. , Warden Melissa R. , Miller Earl K. , Howard Marc W.
Published: April 2023

Previous work has identified stimulus specific time cells as a potential mechanism for working memory maintenance. It has been proposed that populations of stimulus specific sequences of cells could support memory for many items in a list over long periods of time. This would require information about one stimulus to persist after the presentation of subsequent stimuli. However, it is not known if sequences triggered by one stimulus persist past the presentation of additional stimuli. It is possible that each new stimulus terminates preceding sequences, making memory for multiple stimuli impossible. To investigate this question, we utilized a data set originally published by (Warden & Miller, 2010), studying the firing of monkey prefrontal neurons during short lists of stimuli. We were able to decode “what happened when” throughout the list, using linear discriminant analysis. Additionally, we were able to decode the first stimulus after the presentation of the second stimulus. Furthermore, we found that stimulus modulated sequences of cells, with discrete temporal fields, continue after the second item was presented. Much of the information about the previous item was carried by neurons that responded to conjunctions of stimuli and the timing of late-firing cells was synchronized to the firing of the second stimulus rather than the first. These properties falsify a simple linear model of sequential time cells. These results suggest that non-linear mixed selectivity extends to continuous variables such as time, but that in this experiment at least, only the timing of the most recent stimulus was explicitly maintained in ongoing firing.
Silymarin Inhibits In Vitro SARS-CoV-2 Infection In Vero E6 Cells
Authors: Nnadi Nnaemeka Emmanuel , Luka Pam Dachung , Omale Simeon , Shehu Nathan Yakubu , Aguiyi John Chinyere
Published: April 2023

The study evaluated the invitro ability of Silymarin to inhibit SARS-COV-2 infection on Vero Cells. We set out to evaluate the hypothesis that Silymarin has both preventive and curative against SARS-COV-2. To study this, we first evaluated the safety profile of Silymarin using the Drosophila melanogaster(Harwich strain) model. Silymarin tablet film coated 140mg(Silybon-140) was used for the study. We evaluated the fly for acute toxicity, Locomotor performance, estimation of total thiol level, determination of Acetylcholinesterases (AchE) activity, Catalase activity, Glutathion-S-transferase(GST) activity and fecundity assay. To evaluate the invitro activity of Silymarin against SARS-COV-2, SARS-COV-2 isolates from oropharyngeal swabs and confirmed using qRT-PCR were cultured in Vero E6 monolayer cells. Different concentrations of silymarin concentration were used to determine pre- or post-exposure activity.

The result showed that daily exposure to silymarin dose between 50% to 2000% adult dose showed no adverse effect after 28 days. Treatment of Vero cells with silymarin at the concentration 250-500ug/ml all revealed a pre-treatment effect to SARS-COV-2 in vitro and no inhibition effect was observed when the virus was first added before the addition of Silymarin. Silymarin had no adverse effect on D. melanogaster and can be used a preventive drug against SARS-COV-2
Intracellular Cytomatrix, Immobilized Biocatalysis, Matrix Micromechanics and The Warburg Effect: Entanglement of Two Age-Old Mysteries of the Normal and Malignant Cell
Authors: Shaiken Tattym E. , Siam Mohamad , Sederstrom Joel M. , Narayanan Padmini
Published: April 2023

For decades cancer studies have focused on molecular genetics while the role of the cytoplasm has remained obscure. Separation of the viscous fluid cytosol and elastic-solid cytomatrix has offered an opportunity to solve an age-old mystery in biochemistry; how millions of complex chemical reactions can occur simultaneously within the cell cytoplasm. The cytomatrix contains structural proteins, ribosomes, and metabolome enzymes responsible for unique biosynthetic pathways that involve immobilized biocatalysis. Immobilizing these catalytic complexes overcomes the spatial limitations for biochemical processes and allows integration of the intracellular and extracellular matrices and receptors with nuclear processes. Together, the cytosol and cytomatrix produce an interconnected synergistic network that maintains the operational flexibility of healthy cells as well as the survival of malignant cells. The cytomatrix is also responsible for cellular micromechanics and cytoplasmic motion. The combination of mechanical and biocatalytic processes triggered by extracellular signals and gene mutations in malignant cells requires additional energy. Cancer cells, consequently, utilize aerobic glycolysis, the Warburg effect, to meet the energy demands of the matrix mechanics that arise in response to imbalanced signaling and excessive biocatalytic activity. Clinical cancer is a rare event despite a high frequency of mutations, as clinical cancer is limited by the requirement for alterations that result in a high energy production state. Without these transformations, potential cancers can only survive in the quiescent state or will be eliminated. Survival of cancer cells indicates that the cancer cells were able to synchronize energy output for matrix mechanics supplying sufficient energy for tumor growth. Thus, the Warburg effect connects genetic aberrations and intracellular matrix mechanics with the ability to provide the energy supply required for the unprecedented complexity of tumor growth.