bluuebunny/crossref_metadata_2025 huggingface dataset:
Toxicological study on methanol root bark extract ofAcacia sieberiana(Fabaceae) in Wistar rats
Authors: Watafua Miriam , Ejiofor Jane I. , Musa Aminu , Ahmad Mubarak Hussaini
Published: June 2022

Background

The plantAcacia sieberianabelongs to the family Fabaceae. It has been used in ethnomedical practice to manage bleeding, rheumatism, pain, pyrexia, kidney diseases, gastrointestinal problems, parasitic and infectious diseases, hepatitis, cough, epilepsy, mouth ulcer and many more. Phytochemical compounds such as ellagic acid, quercetin, isoferulic acid, gallic acid, kaempferol, luteolin, apigenin, glucoside dihydroacacipetalin, acacipetalin and many others were isolated from Acacia sieberiana. Previous pharmacological investigations have reported that the plant has anticancer, antimicrobial, antidiarrhoeal and antitrypanosomal effects. Despite the therapeutic properties of this plant, no safety information is available in the literature. Hence, this work intends to investigate the sub-acute toxicity effects ofAcacia sieberianaroot bark extract (ASE). The phytochemical and oral median lethal dose (LD50) evaluations on the ASE were done in line with the standard protocols. The sub-acute toxic effects of the ASE (250, 750, and 1,500 mg/kg) were investigated following administration of the ASE daily for 28-consecutive days based on the Organization of Economic Cooperation and Development (OECD) 407 protocols in rats. The weekly body weights were monitored and the rats were euthanized on the 29thday. The blood samples from the animals were obtained for biochemical and haematological determinations. The liver, kidney, lung and heart were removed for histological investigations.

Results

The ASE revealed triterpenes, tannins, saponins, cardiac glycosides, flavonoids, and alkaloids. The oral LD50values was >5,000 mg/kg. The ASE remarkably (p<0.05) declined the body weight of the rats in consideration to the control categories. There was also a remarkable (p<0.05) elevation in ALP, urea and lymphocytes. The cardiac histology revealed no abnormalities. However, the liver produced dose-dependent hepatocellular necrosis and vacuolations. Besides, lymphocyte hyperplasia and glomerular necrosis were observed in the kidneys and alveolar congestion in the lungs.

Conclusions

The ASE is relatively non-toxic on acute administration. In contrast, it could pose slight hepatic and renal toxicity on sub-acute administration.
Cooperation genes are more pleiotropic than private genes in the bacterium Pseudomonas aeruginosa
Authors: Scott Trey J.
Published: June 2022

Pleiotropy may affect the evolution of cooperation by limiting cheater mutants if such mutants also lose other important traits. Because pleiotropy limits cheaters, selection may favor cooperation genes that are more pleiotropic. However, the same should not be true for private genes with functions unrelated to cooperation. Pleiotropy in cooperative genes has mostly been studied with single genes and has not been measured on a wide scale or compared to a suitable set of control genes with private functions. I remedy this gap by comparing genomic measures of pleiotropy in previously identified cooperative and private gene sets in Pseudomonas aeruginosa. I found that cooperative genes in P. aeruginosa tended to be more pleiotropic than private genes according to the number of protein-protein interactions, the number of gene ontology terms, and gene expression specificity. These results show that pleiotropy may be a general way to limit cheating and that cooperation may shape pleiotropy in the genome.
Neurocomputational mechanisms underlying fear-biased adaptation learning in changing environments
Authors: Wang Zhihao , Nan Tian , Goerlich Katharina S. , Li Yiman , Aleman André , Luo Yuejia , Xu Pengfei
Published: June 2022

Humans are able to adapt to the fast-changing world by estimating statistical regularities of the environment. Although fear can profoundly impact adaptive behaviors, the neural mechanisms underlying this phenomenon remain elusive. Here, we conducted a behavioral experiment (n = 21) and a functional magnetic resonance imaging experiment (n = 37) with a novel cue-biased adaptation learning task, during which we simultaneously manipulated emotional valence (fearful/neutral expressions of the cue) and environmental volatility (frequent/infrequent reversals of reward probabilities). Across two experiments, computational modelling consistently revealed a higher learning rate for the environment with frequent versus infrequent reversals following neutral cues. In contrast, this flexible adjustment was absent in the environment with fearful cues, suggesting a suppressive role of fear in adaptation to environmental volatility. This suppressive effect was underpinned by activity of the posterior parietal cortex, ventral striatum, hippocampus and dorsal anterior cingulate cortex (dACC) as well as increased functional connectivity between the dACC and temporal-parietal junction (TPJ) for fear with environmental volatility. Dynamic causal modelling identified that the driving effect was located in the TPJ and was associated with dACC activation, suggesting that the suppression of fear on adaptive behaviors occurs at the early stage of bottom-up processing. These findings provide a neuro-computational account of how fear interferes with adaptation to volatility during dynamic environments.
Ageing leads to nonspecific antimicrobial peptide responses in Drosophila melanogaster
Authors: Shit Biswajit , Prakash Arun , Sarkar Saubhik , Vale Pedro F. , Khan Imroze
Published: June 2022

Evolutionary theory predicts a late-life decline in the force of natural selection, possibly leading to late-life deregulations of the immune system. A potential outcome of such immune-deregulation is the inability to produce specific immunity against target pathogens. We tested this possibility by infecting multiple Drosophila melanogaster lines (with bacterial pathogens) across age-groups, where either individual or different combinations of Imd- and Toll-inducible antimicrobial peptides (AMPs) were deleted using CRISPR gene editing. We show a high degree of non-redundancy and pathogen-specificity of AMPs in young flies: in some cases, even a single AMP could confer complete resistance. In contrast, ageing led to a complete loss of such specificity, warranting the action of multiple AMPs across Imd- and Toll-pathways during infections. Moreover, use of diverse AMPs either had no survival benefits, or even accompanied survival costs post-infection. These features were also sexually dimorphic: females expressed a larger repertoire of AMPs than males, but extracted equivalent survival benefits. Finally, age-specific expansion of the AMP-pool was associated with downregulation of negative-regulators of the Imd-pathway and a potential damage to renal function, as features of poorly-regulated immunity, Overall, we could establish ageing as an important driver of nonspecific AMP responses, across sexes and bacterial infections.
First De novo whole genome sequencing and assembly of mutant Dendrobium hybrid cultivar ‘Emma White’
Authors: Sherpa Rubina , Devadas Ramgopal , Suprasanna P , Bolbhat Sadashiv Narayan , Nikam Tukaram Dayaram
Published: June 2022

Dendrobium hybrid cultivar ‘Emma White’ is an ornamental orchid with high commercial demand. We have used gamma-ray induced ‘early flowering mutant’ to generate draft genome sequences with total length (bp) with 678,650,699 and contigs at 447,500 with N50 at 1,423 using the Illumina HiSeqX10 sequencing platform. Here, we report first de novo whole genome sequencing and assembly of an early flowering gamma mutant of Emma White hybrid for developing a genomics resource for further studies. The GC content of genome was 33.48%, and predicted 95,529 genes from contig assembly. The predicted genes from the MaSuRCA (version 4.0.3) assembled contigs, when compared with uniprot database using BLASTX program with e-valuecutoff of 10−3 resulted 60,741 potential genes governing different pathways in terms for molecular functions, biological process and cellular components. We also identified 216,232 SSRs and 138,856 microsatellite markers. Chromosome level genome assembly of Dendrobium huoshanense species was used to RagTag scaffold the available contigs of mutant, where it contained total length of 687,254,899 bp with N50 value 2,096. Largest contiguous length was found with 18,000,059 bp from 30,571 bp. The genome completeness for Emma White RagTag scaffold assembly was assessed to be 93.6% complete using BUSCO v5.2.1 against the Viridiplantae odb10 orthologous dataset. De novo whole genome sequencing of gamma mutant Dendrobium hybrid cultivar Emma White (10Gy) isolate was deposited to National Centre for Biotechnology Information (NCBI) with SRA accession SRR16008784, Genebank assembly accession GCA_021234465.1(https://www.ncbi.nlm.nih.gov/assembly/GCA_021234465.1#/st) and Transcriptional Shot Gun assembly accession GJVE00000000 under BioProject ID PRJNA763052. This study could provide valuable information for investigating the potential mechanisms of mutation, and guidance for developing Dendrobium hybrid cultivars using mutation breeding.
Targeted nanopore resequencing and methylation analysis of LINE-1 retrotransposons
Authors: Sarkar Arpita , Lanciano Sophie , Cristofari Gael
Published: June 2022

Retrotransposition of LINE-1 (L1) elements represent a major source of insertional polymorphisms in mammals and their mutagenic activity is restricted by silencing mechanisms, such as DNA methylation. Despite a very high level of sequence identity between copies, their internal sequence contains small nucleotide polymorphisms (SNPs) that can alter their activity. Such internal SNPs can also appear in different alleles of a given L1 locus. Given their repetitive nature and relatively long size, short-read sequencing approaches have limited access to L1 internal sequence or DNA methylation state. Here we describe a targeted method to specifically sequence more than a hundred L1-containing loci in parallel and measure their DNA methylation levels using nanopore long-read sequencing. Each targeted locus is sequenced at high coverage (∼45X) with unambiguously mapped reads spanning the entire L1 element, as well as its flanking sequences over several kilobases. Our protocol, modified from the nanopore Cas9 targeted sequencing (nCATS) strategy, provides a full and haplotype-resolved L1 sequence and DNA methylation levels. It introduces a streamlined and multiplex approach to synthesize guide RNAs and a quantitative PCR (qPCR)-based quality check during library preparation for cost-effective L1 sequencing. More generally, this method can be applied to any type of transposable elements and organisms.
Disruptive selection via pollinators and seed predators on the height of flowers in a wind-dispersed alpine herb
Authors: Chen Kai-Hsiu , Pannell John R.
Published: June 2022

Premise of the study

Floral stalk height is known to affect pollination and seed dispersal in wind-dispersed grassland species, but it may also affect the attractiveness of flowers and fruits in animal-pollinated and animal-dispersed plants. Stalk height may thus be responsive to selection via interactions with both mutualist pollinators and seed dispersers, but also antagonist florivors and seed predators. In this study, we aimed to determine the effect of pollinators and seed predators on selection on floral stalk height in the insect-pollinated and wind-dispersed alpine andromonoecious herbPulsatilla alpina, whose flowers also vary in their sex allocation and thus in the resources available to both mutualists and antagonists.

Methods

We measured the resource status of individuals in terms of their size and the height of the vegetation surrounding plants ofP. alpinaat eleven sites. In one population, we recorded the dynamics of floral stalk height over the course of an entire growing season and its association with floral morphology and floral sex allocation (pistil and stamen number), and we used leaf-removal manipulations to assess the effect of herbivory on floral stalk height. Finally, in four populations we studied phenotypic selection on floral stalk height in four female components of reproductive success before seed dispersal.

Key results

Stalk height was positively associated with female allocation of the respective flower, the resource status of the individual, and the height of the surrounding vegetation, and negatively affected by leaf removal. Our results point to disruptive selection on stalk height in terms of both selection differentials and selection gradients for fertilization, seed predation, and seed maturation rates, and to positive selection on stalk height in terms of a selection differential for mature seed number.

Conclusions

Stalk height inP. alpinais a costly trait that affects female reproductive success via interactions with both mutualists and antagonists. We discuss the interplay between the resource status and selection imposed on female reproductive success and its likely role in the evolution of sex-allocation strategies, especially andromonoecy.
TREE-QMC: Improving quartet graph construction for scalable and accurate species tree estimation from gene trees
Authors: Han Yunheng , Molloy Erin K.
Published: June 2022

Summary methods are one of the dominant approaches for estimating species trees from genome-scale data. However, they can fail to produce accurate species trees when the input gene trees are highly discordant due to gene tree estimation error as well as biological processes, like incomplete lineage sorting. Here, we introduce a new summary method TREE-QMC that offers improved accuracy and scalability under these challenging scenarios. TREE-QMC builds upon the algorithmic framework of QMC (Snir and Rao 2010) and its weighted version wQMC (Avni et al. 2014). Their approach takes weighted quartets (four-leaf trees) as input and builds a species tree in a divide-and-conquer fashion, at each step constructing a graph and seeking its max cut. We improve upon this methodology in two ways. First, we address scalability by providing an algorithm to construct the graph directly from the input gene trees. By skipping the quartet weighting step, TREE-QMC has a time complexity ofO(n3k) with some assumptions on subproblem sizes, wherenis the number of species andkis the number of gene trees. Second, we address accuracy by normalizing the quartet weights to account for “artificial taxa,” which are introduced during the divide phase so that solutions on subproblems can be combined during the conquer phase. Together, these contributions enable TREE-QMC to outperform the leading methods (ASTRAL-III, FASTRAL, wQFM) in an extensive simulation study. We also present the application of these methods to an avian phylogenomics data set.
Insulin signaling and extended longevity in ants
Authors: Yan Hua , Opachaloemphan Comzit , Carmona-Aldana Francisco , Mancini Giacomo , Mlejnek Jakub , Descostes Nicolas , Sieriebriennikov Bogdan , Leibholz Alexandra , Zhou Xiaofan , Ding Long , Traficante Maria , Desplan Claude , Reinberg Danny
Published: June 2022

In most organisms, the cost of reproduction is a shorter lifespan. However, the reproductive caste in eusocial insect species (queen) exhibits an extraordinarily longer lifespan than non-reproductive castes (workers) despite having a similar genome, thus contradicting the aging dogma. In the absence of the queen, Harpegnathos saltator ants can undergo a caste switch from workers to reproductive pseudo-queens (gamergates). Gamergates exhibit a dramatically prolonged lifespan. When placed in the presence of a reproductive, they revert to worker status and their lifespan is then shortened accordingly.

To understand this unique relationship between reproduction and longevity, we analyzed tissue-specific gene expression between castes. Insulin is upregulated in the gamergate brain that leads to oogenesis, but surprisingly correlates with extended longevity. This correlates with increased lipid synthesis and elevated production of vitellogenin in the fat body, which are both transported to the egg. We show that the production of vitellogenin in the fat body is due to the systemic activation of the MAPK branch of the insulin/IGF signaling (IIS)-pathway. In contrast, reduced expression of insulin receptors in the fat body of gamergates and the production in their developing ovary of an anti-insulin (Imp-L2) lead to the downregulation of the AKT/FOXO branch of the IIS-signaling pathway in the fat body, and to the dramatically extended longevity. This reveals a dual-pathway mechanism that reconciles increased longevity in the context of active reproduction in eusocial insects.

One Sentence Summary

Insulin-dependent reproduction in ants correlates with extended longevity through insulin inhibition by anti-insulin Imp-L2.
Machine learning predictions of MHC-II specificities reveal alternative binding mode of class II epitopes
Authors: Racle Julien , Guillaume Philippe , Schmidt Julien , Michaux Justine , Larabi Amédé , Lau Kelvin , Perez Marta A. S. , Croce Giancarlo , Genolet Raphaël , Coukos George , Zoete Vincent , Pojer Florence , Bassani-Sternberg Michal , Harari Alexandre , Gfeller David
Published: June 2022

CD4+ T cells orchestrate the adaptive immune response against pathogens and cancer by recognizing epitopes presented on MHC-II molecules. The high polymorphism of MHC-II genes represents an important hurdle towards accurate prediction and identification of CD4+ T-cell epitopes in different individuals and different species. Here we collected and curated a dataset of 627,013 unique MHC-II ligands identified by mass spectrometry. This enabled us to precisely determine the binding motifs of 88 MHC-II alleles across human, mouse, cattle and chicken. Analysis of these binding specificities combined with X-ray crystallography refined our understanding of the molecular determinants of MHC-II motifs and revealed a widespread reverse binding mode in MHC-II ligands. We then developed a machine learning framework to accurately predict binding specificities and ligands of any MHC-II allele. This tool improves and expands predictions of CD4+ T-cell epitopes, and enabled us to discover and characterize several viral and bacterial epitopes following the aforementioned reverse binding mode.
A deep learning approach reveals unexplored landscape of viral expression in cancer
Authors: Elbasir Abdurrahman , Ye Ying , Schäffer Daniel E. , Hao Xue , Wickramasinghe Jayamanna , Tsingas Konstantinos , Lieberman Paul M. , Long Qi , Morris Quaid , Zhang Rugang , Schäffer Alejandro A. , Auslander Noam
Published: June 2022

About 15% of human cancer cases are attributed to viral infections. To date, virus expression in tumor tissues has been mostly studied by aligning tumor RNA sequencing reads to databases of known viruses. To allow identification of divergent viruses and rapid characterization of the tumor virome, we develop viRNAtrap, an alignment-free pipeline to identify viral reads and assemble viral contigs. We utilize viRNAtrap, which is based on a deep learning model trained to discriminate viral RNAseq reads, to explore viral expression in cancers and apply it to 14 cancer types from The Cancer Genome Atlas (TCGA). Using viRNAtrap, we uncover expression of unexpected and divergent viruses that have not previously been implicated in cancer and disclose human endogenous viruses whose expression is associated with poor overall survival. The viRNAtrap pipeline provides a way forward to study viral infections associated with different clinical conditions.
Infection-competent monkeypox virus contamination identified in domestic settings following an imported case of monkeypox into the UK
Authors: Atkinson Barry , Burton Christopher , Pottage Thomas , Thompson Katy-Anne , Ngabo Didier , Crook Ant , Pitman James , Summers Sian , Lewandowski Kuiama , Furneaux Jenna , Davies Katherine , Brooks Timothy , Bennett Allan M , Richards Kevin S.
Published: June 2022

An imported case of monkeypox was diagnosed in December 2019 in a traveller returning from Nigeria to the UK. Subsequently, environmental sampling was performed at two adjoining single room residences occupied by the patient and their sibling. Monkeypox virus DNA was identified in multiple locations throughout both properties, and monkeypox virus was isolated from several samples three days after the patient was last in these locations. Positive samples were identified following use of both vacuum and surface sampling techniques; these methodologies allowed for environmental analysis of potentially contaminated porous and non-porous surfaces via real-time quantitative PCR analysis in addition to viral isolation to confirm the presence of infection-competent virus.

This report confirms the potential for infection-competent monkeypox virus to be recovered in environmental settings associated with known positive cases and the necessity for rapid environmental assessment to reduce potential exposure to close contacts and the general public. The methods adopted in this investigation may be used for future confirmed cases of monkeypox in order to establish levels of contamination, confirm the presence of infection-competent material, and to identify locations requiring additional cleaning.

Originality-Significance Statement

Several imported cases of human monkeypox infection, an emerging infectious disease with a case fatality rate of up to 10%, have been identified in recent years including importations into the United Kingdom, the United States, Israel, and Singapore. It is likely that this phenomenon relates to decreased immunity against monkeypox infection in endemic regions that was previously provided via the smallpox vaccination programme. It is therefore likely that further imported cases of monkeypox will be reported in future; such occurrences will require significant clinical oversight, including suitable infection control measures. Environmental sampling to identify contaminated sites that may pose a risk can inform infection control guidance. This report documents an environmental sampling response following an imported case detected in late 2019 in the UK. Monkeypox virus DNA was readily identified in numerous locations throughout two domestic residences associated with the infected patient and infectious virus was isolated from several environmental samples confirming that contaminated environmental settings may pose a risk for onward transmission. The methods utilised in this report may advise future environmental responses following cases of this high consequence emerging viral disease in order to prevent secondary cases in close contacts or members of the public.
Digitalization impacts the COVID-19 pandemic and the stringency of government measures
Authors: Heinrichs Helen , Mueller Florian , Rohfleisch Lucia , Schulz Volkmar , Talbot Steven R. , Kiessling Fabian
Published: June 2022

COVID-19 poses a significant burden on populations worldwide. Although the pandemic has accelerated digital transformation, little is known about digitalization’s influence on pandemic developments. Using the Digital Adoption Index (DAI), we examined the effects of digitalization on early COVID-19 cases, deaths, and stringency indices (SI) of government measures. Gradient Tree Boosting pinpointed essential features, such as populations’ smoker fraction, age, poverty, and DAI. Then, regression analyses indicated that higher DAI was associated with significant declines in new cases (β=-362.25/pm;p<0.001) and deaths (β=-5.53/pm;p<0.001) months after the peak. Over the entire range, higher DAI was associated with higher mean SI (β=4.86;p<0.01). Interestingly, however, in countries with high DAI >0.68, the correlation inverted (β=-55.26;p<0.05). Finally, a scoping review identified 70 publications providing valuable arguments for our findings. Thus, digitalization is evident for handling current and future pandemics but can also facilitate stronger government actions restricting individual freedom.
The Effect of Negative Pressure on IOP in the Living Human Eye
Authors: Fazio Massimo A. , Bianco Gianfranco , Karuppanan Udayakumar , Hubbard Meredith , Bruno Luigi , Girkin Christopher A.
Published: June 2022

Purpose

To quantify the effect of negative pressure applied to the anterior surface of the eye on absolute IOP.

Subjects

Participants, and/or Controls. Three eyes from three research-consented brain-dead organ donors.

Methods

Air-tight goggles connected to a negative pressure (NP) pump (Mercury Multi-pressure Dial (MPD); Equinox Ophthalmic, Inc., CA) were tested on three research consented brain-dead organ donors. The MPD was set to generate a vacuum of −20mmHg. A baseline IOP of 10, 20, and 30mmHg was sequentially set by adjusting the height of a balanced salt solution bottle connected to the cornea through a 20G needle. IOP was manually annotated at time = 0s, right before turning on the vacuum pump; after a few seconds with the vacuum pump ON; at 60s; at 120s, right before turning the pump OFF; at 240s with the pump OFF (recovery). Three repetitions per each test at varying baseline IOP were taken for a total of nine series of measures per eye.

MainOutcomeMeasures

IOP change with exposure to NP.

Results

Eye1 and 3 showed an immediate reduction in IOP at all baselines immediately following activation of the MPD NP pump; Eye2 showed an opposite response to NP. Eye1 and 3 showed a reduction in IOP at all baselines with NP pump ON for 60s and 120s, while Eye 2 showed a consistent increase in IOP. After 120s from turning NP OFF (time=240s), IOP partially recovered to its baseline in all eyes.

Conclusions

This study is the first to evaluate changes in manometrically-measured intracameral IOP due to NP applied to the ocular surface in living conditions. The inconsistent response of IOP following exposure to negative pressure warrants further investigations on the mechanism underlaying IOP lowering by NP.
Pre-existing immunity modulates responses to mRNA boosters
Authors: Dangi Tanushree , Sanchez Sarah , Lew Min Han , Visvabharathy Lavanya , Richner Justin , Koralnik Igor J. , Penaloza-MacMaster Pablo
Published: June 2022

mRNA vaccines have shown high efficacy in preventing severe COVID-19, but breakthrough infections, emerging variants and waning antibody levels have warranted the use of boosters. Although mRNA boosters have been widely implemented, the extent to which pre-existing immunity influences the efficacy of boosters remains unclear. In a cohort of individuals primed with the mRNA-1273 or BNT162b2 vaccines, we observed that lower antibody levels before boost were associated with higher fold-increase in antibody levels after boost, suggesting that pre-existing antibody modulates the boosting capacity of mRNA vaccines. Mechanistic studies in mice show that pre-existing antibodies significantly limit antigen expression and priming of B cell responses after mRNA vaccination. Furthermore, we demonstrate that the relative superiority of an updated Omicron vaccine over the original vaccine is critically dependent on the serostatus of the host. These data demonstrate that pre-existing immunity dictates responses to mRNA vaccination, elucidating specific circumstances when updated SARS-CoV-2 vaccines confer superior protection to original vaccines.
L-norepinephrine Induces Community Shift, Oxidative Stress Response, Metabolic Reprogramming, and Virulence Potential in Wastewater Microbiomes
Authors: Bains Amrita , Dahal Sanjeev , Manna Bharat , Lyte Mark , Yang Laurence , Singhal Naresh
Published: June 2022

Neuroendocrine compounds discharged into wastewater systems represent an emerging challenge at the intersection of human physiology and environmental microbiology. L-norepinephrine (L-NE) L-NE, which has been recognized to potentiate growth of human and animal bacterial pathogens, is discharged in sewage through urine and feces. While extensive pure culture studies have established L-NE’s capacity to modulate bacterial virulence through iron acquisition and quorum sensing pathways, its impact on complex microbial communities, where intricate metabolic networks and interspecies interactions dominate, remains largely unexplored. This knowledge gap is particularly critical as urbanization drives increasing neuroendocrine compound loads in wastewater influents in metropolitan areas. Through parallel treatments of L-NE (1×10□□ to 1×10□□ M), dextrose, and H□O□ in municipal and agricultural wastewater communities, we uncovered sophisticated metabolic and regulatory mechanisms that challenge the conventional understanding of microbial substrate utilization. Despite containing 10-fold less carbon, L-NE treatments achieved superior growth (10□ CFU mL□¹) while maintainingPseudomonadaceae-dominated communities. Targeted metaproteomics revealed coordinated upregulation of oxidative stress genes (oxyR,soxRS) and antioxidant enzymes, while proteome-constrained metabolic modeling demonstrated distinct pathway modulation in central carbon and nitrogen metabolism. Notably, when compared to dextrose-supplemented controls representing typical carbon substrate utilization, L-NE treatments showed similar taxonomic profiles without preferential enrichment of known pathogenic families. However, L-NE significantly enhanced autoinducer gene (luxS,qseC) expression, suggesting increased virulence potential through community-level metabolic reprogramming. These findings reveal L-NE as a potent modulator of microbial community dynamics in engineered ecosystems, with important implications for treatment process stability and downstream environmental impacts.TOC Figure
Crystal structure of the membrane (M) protein from a SARS-COV-2-related coronavirus
Authors: Wang Xiaodong , Yang Yuwei , Sun Ziyi , Zhou Xiaoming
Published: June 2022

The membrane (M) protein is the most abundant structural protein of coronaviruses including SARS-COV-2 and plays a central role in virus assembly through its interaction with various partner proteins. However, mechanistic details about how M protein interacts with others remain elusive due to lack of high-resolution structures. Here, we present the first crystal structure of a coronavirus M protein from Pipistrellus bat coronavirus HKU5 (batCOV5-M), which is closely related to SARS-COV-2 M protein. Furthermore, an interaction analysis indicates that the carboxy-terminus of the batCOV5 nucleocapsid (N) protein mediates its interaction with batCOV5-M. Combined with a computational docking analysis an M-N interaction model is proposed, providing insight into the mechanism of M protein-mediated protein interactions.
Functional unknomics: closing the knowledge gap to accelerate biomedical research
Authors: Rocha Joao , Jayaram Satish Arcot , Stevens Tim J. , Muschalik Nadine , Shah Rajen D. , Emran Sahar , Robles Cristina , Freeman Matthew , Munro Sean
Published: June 2022

The human genome encodes ∼20,000 proteins, many still uncharacterised. Scientific and social factors have resulted in a focus on well-studied proteins, leading to a concern that poorly understood genes are unjustifiably neglected. To address this, we have developed an “Unknome database” that ranks proteins based on how little is known about them. We applied RNAi inDrosophilato 260 unknown genes that are conserved between flies and humans. About a quarter are required for viability, and functional screening of the rest revealed hits for fertility, development, locomotion, protein quality control and resilience to stress. CRISPR/Cas9 gene disruption validated a component of Notch signalling and two genes contributing to male fertility. Our work demonstrates the importance of poorly understood genes, provides a resource for future research acceleration, and highlights a need for our awareness of ignorance to be protected from erosion by automated database annotation.
Functional succession of actively growing soil microorganisms during rewetting is shaped by precipitation history
Authors: Sieradzki Ella T. , Greenlon Alex , Nicolas Alexa M. , Firestone Mary K. , Pett-Ridge Jennifer , Blazewicz Steven J. , Banfield Jillian F.
Published: June 2022

Rewetting of seasonally dry soils induces a burst of microbial activity and carbon mineralization that changes nutrient availability and leads to succession. Yet the microbial functions that underpin this succession are not well described. Further, it’s unclear how previous precipitation frames microbial capacities after rewetting and how long these effects persist. We used isotopically-labeled water to rewet seasonally dry annual grassland soil that experienced either mean annual or reduced precipitation during the previous two years, and sampled at five subsequent time points. We used quantitative stable isotope probing (qSIP)-informed genome- resolved metagenomics to identify growing microorganisms, predict their capabilities, and analyze how these traits differed over time and between precipitation treatments. Organisms that grew after wetup were more abundant than non-growing organisms prior to the wet-up, suggesting that traits that initiate succession are pre-defined at the end of the prior plant growing season or via survival over the summer. Fast-growing organisms had fewer carbohydrate active enzyme (CAZy) genes per genome than slower-growing organisms, suggesting that although fast-growers were capable of degrading complex C, they may not specialize in this process. Differential abundance of CAZy genes in growing organisms throughout the succession implies that substrate availability varied with time. In contrast, the abundance of peptidases in growing organisms differed between precipitation treatments, but not over time following wet-up. Before wet-up, the soil organisms’ gene inventories were different between the two precipitation treatments. Surprisingly, this legacy effect waned after just one week. Thus, pre-wetup differences in microbial functional capacity converged shortly after rewetting.
The conserved, secreted protease inhibitor MLT-11 is necessary for C. elegans molting and embryogenesis
Authors: Ragle James Matthew , Levenson Max T. , Clancy John C. , Vo An A. , Pham Vivian , Ward Jordan D.
Published: June 2022

Apical extracellular matrices (aECMs) are associated with all epithelia and form a protective layer against biotic and abiotic threats in the environment. C. elegans molting offers a powerful entry point to understanding developmentally programmed aECM remodeling. Several protease inhibitors are implicated in molting, but their functions remain poorly understood. Here we characterize mlt-11, an unusual protease inhibitor with 10 conserved Kunitz domains. MLT-11 oscillates and is localized in the cuticle and in lysosomes in larvae and in the embryonic sheath starting at the 3-fold embryo stage. mlt-11 (RNAi) produced a developmental delay, motility defects, failed apolysis, and a defective cuticle barrier. mlt-11 null and C-terminal Kunitz domain deletion mutants are embryonic lethal while N-terminal deletions cause a rolling phenotype indicative of cuticle structure abnormalities. mlt-11 activity is primarily necessary in seam and hypodermal cells and accordingly mlt-11 (RNAi) causes defects in localization of the collagens ROL-6 and BLI-1 over the cuticle. mlt-11 (RNAi) molting phenotypes can be suppressed by genetically inhibiting endocytosis. Our model is that MLT-11 is acting in the aECM to coordinate remodeling and timely ecdysis.
Co-operative halogen bonds and nonconventional sp-C—H...O hydrogen bonds in 1:1 cocrystals formed between diethynylpyridines and N-halosuccinimides
Authors: Bosch Eric , Bowling Nathan P.
Published: June 2022

The rapid evaporation of 1:1 solutions of diethynylpyridines and N-halosuccinimides, that react together to form haloalkynes, led to the isolation of unreacted 1:1 cocrystals of the two components. The 1:1 cocrystal formed between 2,6-diethynylpyridine and N-iodosuccinimide (C4H4INO2·C9H5N) contains an N-iodosuccinimide–pyridine I...N halogen bond and two terminal alkyne–succinimide carbonyl C—H...O hydrogen bonds. The three-dimensional extended structure features interwoven double-stranded supramolecular polymers that are interconnected through halogen bonds. The cocrystal formed between 3,5-diethynylpyridine and N-iodosuccinimide (C4H4INO2·C9H5N) also features an I...N halogen bond and two C—H...O hydrogen bonds. However, the components form essentially planar double-stranded one-dimensional zigzag supramolecular polymers. The cocrystal formed between 3,5-diethynylpyridine and N-bromosuccinimide (C4H4BrNO2·C9H5N) is isomorphous to the cocrystal formed between 3,5-diethynylpyridine and N-iodosuccinimide, with a Br...N halogen bond instead of an I...N halogen bond.
Malaysia's low-cost housing solid waste management in the era of COVID-19: the role of fourth industrial revolution technologies
Authors: Ebekozien Andrew , Samsurijan Mohamad Shaharudin , Aigbavboa Clinton , Malek Nor Malina
Published: June 2022

Purpose

Studies have shown that managing household solid waste from low-cost housing in urban and sub-urban communities is challenging, especially in developing countries and COVID-19 era. Previous research proved that the fourth industrial revolution (4IR) technologies could be engaged to improve urban public services such as household solid waste. Thus, the study investigated 4IR role in improving low-cost housing solid waste management (LCHSWM) in the COVID-19 era across Malaysia's cities.

Design/methodology/approach

The researchers selected four Malaysian cities (Pulau Pinang, Kuala Lumpur, Kuching and Putrajaya) to achieve the study's objectives via a qualitative research design. The study engaged forty experts through semi-structured virtual interviews. A thematic approach was used to analyse the collected data.

Findings

Findings identified initial high implementation and maintenance costs, unwillingness to accept change, inadequate knowledge and skilled personnel to manage the operation, amongst others, as the perceived challenges facing 4IR technologies in managing low-cost housing solid waste across Malaysian cities in the COVID-19 era. Also, the study proffered measures to improve 4IR technologies usage.

Research limitations/implications

This paper is limited to the perceived contributory challenges and proffered measures to improve 4IR technologies usage in managing LCHSW across Malaysian cities in the COVID-19 era.

Practical implications

Proffered measures will stir policymakers and the political class (city councils) to start thinking of an all-inclusive approach to addressing the issue of LCHSW in the 21st century. As part of the practical implications, the possible outcome might enhance collaboration between the public and private sectors to better service delivery to mitigate environmental degradation.

Originality/value

As revealed in the review, there is a paucity of literature regarding digital technology's roles in mitigating LCHSW across Malaysian cities in the COVID-19 era.
Normal mesenchymal stem cells can improve the abnormal function of T cells in psoriasis via upregulating transforming growth factor‐β receptor
Authors: Jiao Juanjuan , Zhao Xincheng , Wang Ying , Liang Nannan , Li Juan , Yang Xiaohong , Xing Jianxiao , Zhou Ling , Li Junqin , Hou Ruixia , Li Xinhua , Zhang Kaiming
Published: June 2022

Psoriasis, a chronic inflammatory skin disease, is a refractory disorder. Previous studies have shown that the imbalance of the T‐helper (Th)17/regulatory T cells (Treg) results in the immune imbalance of T cells in psoriatic patients, and that mesenchymal stem cells display an immunosuppressive role by promoting the differentiation of T cells into Treg, leading to a reduction in the proportion of Th17/Treg. Utility of mesenchymal stem cells is becoming a new approach for the treatment of immune disorders. Following co‐culture of dermal mesenchymal stromal cells (DMSC) and CD3+ T cells with or without transforming growth factor (TGF)‐β receptor inhibitor, the biological function and relative signal pathway of CD3+ T cells were assessed by flow cytometry, transwell, real‐time polymerase chain reaction and western blotting, respectively. Normal DMSC were more potent than psoriatic DMSC in inhibition of CD3+ T‐cell proliferation, and stimulation of CD3+ T‐cell apoptosis than psoriasis DMSC. Moreover, normal DMSC decreased the ratio of Th17/Treg, while enhancing the immunosuppressive effect of Tregs on effector T cells. However, TGF‐β receptor (TGF‐βR) inhibitor attenuated the effect of normal DMSC on CD3+ T cells and Th17/Treg ratio. Additionally, the normal DMSC were more potent than the psoriatic DMSC in increasing TGF‐β receptors and activation of TGF‐β/SMAD pathway in psoriatic CD3+ T cells. In conclusion, normal DMSC can partially improve the biological function and immunosuppressive ability of psoriatic CD3+ T cells, possibly via upregulating the TGF‐β receptors.
Diagnostic reference value of antibody levels measured using enzyme immunoassay for subacute sclerosing panencephalitis
Authors: Kume Yohei , Hashimoto Koichi , Iida Keiji , Maeda Hajime , Miyazaki Kyohei , Ono Takashi , Chishiki Mina , Suzuki Yuichi , Go Hayato , Suyama Kazuhide , Hosoya Mitsuaki
Published: June 2022

High measles‐specific antibody titers in the cerebrospinal fluid (CSF) have important diagnostic significance for subacute sclerosing panencephalitis (SSPE), a progressive neurological disorder caused by measles virus variants. However, the diagnostic reference value of antibody levels and the usefulness of the CSF/serum ratio measured using enzyme immunoassays (EIAs) for SSPE diagnosis remain unclear. To facilitate SSPE diagnosis using EIAs, measles immunoglobulin G (IgG) titers in the CSF and serum of patients with and without SSPE were measured and their CSF/serum antibody ratios evaluated. Serum and CSF antibody levels were compared among three patients with SSPE (59 paired samples), 37 non‐SSPE patients, and 2618 patients of unknown backgrounds. Of the 59 paired samples from three patients with SSPE, 56 paired samples (94.9%) showed CSF measles IgG levels ≥0.5 IU/mL and a CSF/serum ratio ≥0.05, whereas non‐SSPE cases showed CSF measles IgG levels <0.1 IU/mL and a CSF/serum ratio <0.03. Of the 2618 CSF samples with unknown backgrounds, 951 showed measurable IgG levels with EIA, with a CSF/serum ratio peak of 0.005–0.02, with a 90th percentile of 0.05. Assuming the SSPE criteria as CSF measles IgG ≥0.5 IU/mL and a CSF/serum ratio ≥0.05, only 20 samples (0.8%) with unknown backgrounds were categorized as having SSPE. Conversely, assuming the non‐SSPE criteria as CSF measles IgG <0.1 IU/mL and a CSF/serum ratio <0.03, 2403 samples (92%) with unknown backgrounds were categorized as not having SSPE. In conclusion, high CSF/serum ratios (≥0.05) and high measles CSF IgG levels (≥0.5 IU/mL) may be useful for diagnosing SSPE.
Indirect facilitation between prey promotes asymmetric apparent competition
Authors: Lorusso Nicholas S. , Faillace Cara A.
Published: June 2022

Apparent competition is one mechanism that can contribute to the complex dynamics observed in natural systems, yet it remains understudied in empirical systems. Understanding the dynamics that shape the outcome of processes like apparent competition is vital for appreciating how they influence natural systems.

We empirically evaluated the role of indirect trophic interactions in driving apparent competition in a model laboratory system. Our experimental system was designed to let us evaluate combined direct and indirect interactions among species.

Here we describe the results of a factorial experiment using two noncompeting prey (Colpidium kleini, a heterotroph, and Chlamydomonas reinhardtii, an autotroph) consumed by a generalist predator Euplotes eurystomus to explore the dynamics of apparent competition. To gain intuition into the potential mechanism driving the asymmetry in the observed results, we further explored the system using structural equation modelling.

Our results show an important role of positive interactions and indirect effects contributing to apparent competition in this system with a marked asymmetrical outcome favouring one prey, Chlamydomonas. The selected structural equation supports a role of indirect facilitation; although Chlamydomonas (a photoautotroph) and Colpidium (a bacterivore) use different resources and therefor do not directly compete, Colpidium reduces bacteria that may compete with Chlamydomonas. In addition, formation of colonies by Chlamydomonas in response to predation by Euplotes provides an antipredator defence not available to Colpidium.

Asymmetric apparent competition may be more common in natural systems than the symmetric interaction originally proposed in classic theory, suggesting that exploration of the mechanisms driving the asymmetry of the interaction can be a fruitful area of further research to better our understanding of interspecific interactions and community dynamics.
Risk of incident type 2 diabetes in patients with psoriatic arthritis: A systematic review and meta‐analysis of cohort studies
Authors: Yuan Ziqi , Guo Yan
Published: June 2022

Objectives

To determine the risk of type 2 diabetes among patients with psoriatic arthritis (PsA).

Methods

Electronic database searches of PubMed, EMBASE and Cochrane Library were performed from inception to June 2020 and updated in May 2022. Cohort studies were included if they reported hazard ratios (HR) or relative risks with 95% confidence interval (CI) of incident diabetes in patients with PsA compared with non‐rheumatic populations. Pooled HR and 95% CI were calculated using a DerSimonian and Laird method random‐effects model.

Results

A total of 5 studies comprising 37 811 PsA patients with 174 825 patient‐years and 476 838 non‐rheumatic controls with 2 945 358 patient‐years were identified and included in our data analysis. During the follow‐up, 2335 and 23 035 incident diabetes were observed in PsA and non‐rheumatic control groups, corresponding to a crude incidence rate of 13.4 and 7.8 per 1000 patient‐years, respectively. The pooled age‐ and gender‐adjusted, and fully adjusted HR of incident diabetes in patients with PsA compared with non‐rheumatic populations were 1.54 (95% CI: 1.43‐1.67, I2 = 50.8%) and 1.38 (95% CI: 1.31‐1.47, I2 = 0.0%), respectively.

Conclusions

Our study indicates a 38% increase in the risk of type 2 diabetes among patients with PsA, with an incidence rate of 13.4 per 1000 patients‐years. These findings suggest the awareness of managing diabetes with careful screening of PsA patients in daily practice.
Examining the Effects of the Tax Cuts and Jobs Act on Executive Compensation*
Authors: De Simone Lisa , McClure Charles , Stomberg Bridget
Published: June 2022

As part of the Tax Cuts and Jobs Act (TCJA), the US Congress repealed a long‐standing exception that allowed companies to deduct executives' qualified performance‐based compensation in excess of $1 million. The purpose of this study is to examine whether Congress achieved its stated objective of reversing a shift in executive compensation away from cash compensation and toward performance pay, which Congress believed led executives to focus on short‐term results rather than the long‐term success of the company. Across a battery of tests, including a difference‐in‐differences design that exploits the staggered time‐series implementation of the deduction limit, we find evidence compatible with the new deduction limit having no effect on executives' salary, performance pay or total compensation, inconsistent with Congressional intent. Our results suggest that taxes are not a first‐order effect of executive pay and that tax regulation could be relatively ineffective at curbing executive compensation.