bluuebunny/crossref_metadata_2025 huggingface dataset:
Laboratory-confirmed respiratory viral infection triggers for acute myocardial infarction and stroke: systematic review protocol
Authors: Nguyen Tu Q , Vlasenko Diana , Shetty Aishwarya N , Reid Christopher M , Clothier Hazel J , Buttery Jim P
Published: April 2024

Background

Cardiovascular disease contributes substantially to global mortality and morbidity. Respiratory tract infections, particularly influenza, may trigger an increase in the short-term risk of acute myocardial infarction and stroke. Recent studies have also linked this risk to other respiratory viruses, including respiratory syncytial virus (RSV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the pathogen-specific relative contributions, the strength of their associations, and overall public health significance are poorly understood. Assuming causal links, understanding, quantifying, and comparing the effects of different pathogens as triggering factors for acute cardiovascular events is critical to guide future research and prevention. Our aim is to conduct a systematic review to examine the relative effects of laboratory-confirmed respiratory virus infections as triggers for acute myocardial infarction and stroke.

Methods

We will conduct a comprehensive search of Ovid MEDLINE, PubMed, Ovid Embase, Cochrane Library Central Register of Controlled Trials, and Web of Science, from inception to the end of March 2024. We will include the following analytical epidemiological study types: randomised controlled trials, cohort and case-control studies, self-controlled case series, and case-crossover designs. We will not impose restrictions on the date, language, geographical region, or sample size, to minimise the risk of introducing biases. Search results will be screened for eligibility by two independent reviewers, and discrepancies resolved by consensus and/or arbitration by a third reviewer. We will assess the risk of bias among the included studies by adopting the Cochrane Collaboration tools for randomised and non-randomised studies. The overall quality of studies will be assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. We will examine sources of heterogeneity, and if studies are sufficiently homogeneous, a meta-analysis will be conducted to calculate the pooled effect sizes. Reporting will adhere to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

Registration

International Prospective Register of Systematic Reviews (PROSPERO) registration number: CRD42024494997
Folate receptor alpha protein expression in ovarian serous cystadenocarcinoma tumors of The Cancer Genome Atlas: exploration beyond single-agent therapy
Authors: Persenaire Christianne , Bitler Benjamin G. , Corr Bradley R.
Published: April 2024

Epithelial ovarian cancer (EOC) can be highly lethal, with limited therapeutic options for patients with non-homologous recombination deficient (HRD) disease. Folate receptor alpha (FOLR1/FRα)-targeting agents have shown promise both alone and in combination with available therapies, but the relationship of FRα to other treatment-driving biomarkers is unknown. The Cancer Genome Atlas (TCGA) was queried to assess protein and mRNA expression and mutational burden in patients with differential FRα protein-expressing ovarian tumors, and the results referenced against the standard 324 mutations currently tested through FoundationOne Companion Diagnostics to identify targets of interest. Of 585 samples within TCGA, 121 patients with serous ovarian tumors for whom FRα protein expression was quantified were identified. FRα protein expression significantly correlated with FOLR1 mRNA expression (p=7.19×10-14). Progression free survival (PFS) for the FRα-high group (Q1) was 20.7 months, compared to 16.6 months for the FRα-low group (Q4, Logrank, p=0.886). Overall survival (OS) was 54.1 months versus 36.3 months, respectively; however, this result was not significant (Q1 vs. Q4, Logrank, p=0.200). Mutations more commonly encountered in patients with high FRα-expressing tumors included PIK3CA and FGF family proteins. Combinations of FRα-targeting agents with PI3K, mTOR, FGF(R) and VEGF inhibitors warrant investigation to evaluate their therapeutic potential.

Simple Summary

Epithelial ovarian cancer can be highly lethal, with limited therapeutic options for patients without BRCA mutations or non-homologous recombination deficient disease. Folate receptor alpha (FRα)-targeting agents have shown promise in the setting of platinum-sensitive and platinum-resistant ovarian cancer, both alone and in combination with available therapies, but the relationship of FRα to other treatment-driving biomarkers is unknown. This study identifies potential targetable mutations in FRα-expressing tumors, including PIK3CA and FGF/R family proteins, and provides a basis for future investigations of novel combinations of FRα-targeting agents with PIK3CA, mTOR, FGF/R, and VEGF inhibitors.
Sex-Specific Regulation of Stress Susceptibility by the Astrocytic GeneHtra1
Authors: Parise Eric M. , Gyles Trevonn M. , Godino Arthur , Sial Omar K. , Browne Caleb J. , Parise Lyonna F. , Torres-Berrío Angélica , Salery Marine , Durand-de Cuttoli Romain , Rivera Matthew T. , Cardona-Acosta Astrid M. , Holt Leanne , Markovic Tamara , van der Zee Yentl Y. , Lorsch Zachary S. , Cathomas Flurin , Garon Juliet B. , Teague Collin , Issler Orna , Hamilton Peter J. , Bolaños-Guzmán Carlos A. , Russo Scott J. , Nestler Eric J.
Published: April 2024

Major depressive disorder (MDD) is linked to impaired structural and synaptic plasticity in limbic brain regions. Astrocytes, which regulate synapses and are influenced by chronic stress, likely contribute to these changes. We analyzed astrocyte gene profiles in the nucleus accumbens (NAc) of humans with MDD and mice exposed to chronic stress.Htra1, which encodes an astrocyte-secreted protease targeting the extracellular matrix (ECM), was significantly downregulated in the NAc of males but upregulated in females in both species. ManipulatingHtra1in mouse NAc astrocytes bidirectionally controlled stress susceptibility in a sex-specific manner. SuchHtra1manipulations also altered neuronal signaling and ECM structural integrity in NAc. These findings highlight astroglia and the brain’s ECM as key mediators of sex-specific stress vulnerability, offering new approaches for MDD therapies.
Frontotemporal dementia patient-derived iPSC neurons show cell pathological hallmarks and evidence for synaptic dysfunction and DNA damage
Authors: Huber Nadine , Hietanen Tomi , Heikkinen Sami , Shakirzyanova Anastasia , Hoffmann Dorit , Rostalski Hannah , Dhingra Ashutosh , Rodriguez-Nieto Salvador , Kärkkäinen Sari , Koskuvi Marja , Korhonen Eila , Hartikainen Päivi , Pylkäs Katri , Krüger Johanna , Malm Tarja , Takalo Mari , Hiltunen Mikko , Koistinaho Jari , Portaankorva Anne M. , Solje Eino , Haapasalo Annakaisa
Published: April 2024

Frontotemporal dementia (FTD) is the second most common cause of dementia in patients under 65 years, characterized by diverse clinical symptoms, neuropathologies, and genetic background. Synaptic dysfunction is suggested to play a major role in FTD pathogenesis. Disturbances in the synaptic function can also be associated with theC9orf72repeat expansion (C9-HRE), the most common genetic mutation causing FTD. C9-HRE leads to distinct pathological hallmarks, such asC9orf72haploinsufficiency and development of toxic RNA foci and dipeptide repeat proteins (DPRs). FTD patient brains, including those carrying the C9-HRE, are also characterized by neuropathologies involving accumulation of TDP-43 and p62/SQSTM1 proteins. This study utilized induced pluripotent stem cell (iPSC)-derived cortical neurons from C9-HRE-carrying or sporadic FTD patients and healthy control individuals. We report that the iPSC neurons derived from C9-HRE carriers developed typical C9-HRE-associated hallmarks, including RNA foci and DPR accumulation. All FTD neurons demonstrated increased TDP-43 nucleus-to-cytosolic shuttling and p62/SQSTM1 accumulation, and changes in nuclear size and morphology. In addition, the FTD neurons displayed reduced number and altered morphologies of dendritic spines and significantly altered synaptic function indicated by a decreased response to stimulation with GABA. These structural and functional synaptic disturbances were accompanied by upregulated gene expression in the FTD neurons related to synaptic function, including synaptic signaling, glutamatergic transmission, and pre- and postsynaptic membrane, as compared to control neurons. Pathways involved in DNA repair were significantly downregulated in FTD neurons. Only one gene,NUPR2,potentially involved in DNA damage response, was differentially expressed between the sporadic and C9-HRE-carrying FTD neurons. Our results show that the iPSC neurons from FTD patients recapitulate pathological changes of the FTD brain and strongly support the hypothesis of synaptic dysfunction as a crucial contributor to disease pathogenesis in FTD.
soibean: High-resolution Taxonomic Identification of Ancient Environmental DNA Using Mitochondrial Pangenome Graphs
Authors: Vogel Nicola Alexandra , Rubin Joshua Daniel , Pedersen Anders Gorm , Sackett Peter Wad , Pedersen Mikkel Winther , Renaud Gabriel
Published: April 2024

Ancient environmental DNA (aeDNA) is becoming a powerful tool to gain insights about past ecosystems. However, several methodological challenges remain, particularly for classifying the DNA to species level and conducting phylogenetic placement. Current methods, primarily tailored for modern datasets, fail to capture several idiosyncrasies of aeDNA, including species mixtures from closely related species and ancestral divergence. We introducesoibean, a novel tool that utilises pangenomic graphs for identifying species from ancient environmental mitochondrial reads. It outperforms existing methods in accurately identifying species from multiple sources within a sample, enhancing phylogenetic analysis for aeDNA.soibeanemploys a damage-aware likelihood model for precise identification at low-coverage with high damage rate, demonstrating effectiveness through simulated data tests and empirical validation. Notably, our method uncovered new empirical results in published datasets, including using porpoise whales as food in a Mesolithic community in Sweden, demonstrating its potential to reveal previously unrecognised findings in aeDNA studies.
Functions of the Bloom Syndrome Helicase N-terminal Intrinsically Disordered Region
Authors: Bereda Colleen C. , Dewey Evan B. , Nasr Mohamed A. , Sekelsky Jeff
Published: April 2024

Bloom Syndrome helicase (Blm) is a RecQ family helicase involved in DNA repair, cell-cycle progression, and development. Pathogenic variants in humanBLMcause the autosomal recessive disorder Bloom Syndrome, characterized by predisposition to numerous types of cancer. Prior studies ofDrosophila Blmmutants lacking helicase activity or protein have shown sensitivity to DNA damaging agents, defects in repairing DNA double-strand breaks (DSBs), female sterility, and improper segregation of chromosomes in meiosis. Blm orthologs have a well conserved and highly structured RecQ helicase domain, but more than half of the protein, particularly in the N-terminus, is predicted to be unstructured. Because this region is poorly conserved across multicellular organisms, we compared closely related species to identify regions of conservation, potentially indicating important functions. We deleted two of theseDrosophila-conserved regions inD. melanogasterusing CRISPR/Cas9 gene editing and assessed the effects on different Blm functions. Each deletion had distinct effects on different Blm activities. Deletion of either conserved region 1 (CR1) or conserved region 2 (CR2) compromised DSB repair through synthesis-dependent strand annealing and resulted in increased mitotic crossovers. In contrast, CR2 is critical for embryonic development but CR1 is not as important. CR1 deletion allows for proficient meiotic chromosome segregation but does lead to defects in meiotic crossover designation and patterning. Finally, deletion of CR2 does not lead to significant meiotic defects, indicating that while each region has overlapping functions, there are discreet roles facilitated by each. These results provide novel insights into functions of the N-terminal disordered region of Blm.
Neural dynamics of visual working memory representation during sensory distraction
Authors: Degutis Jonas Karolis , Weber Simon , Soch Joram , Haynes John-Dylan
Published: April 2024

Recent studies have provided evidence for the concurrent encoding of sensory percepts and visual working memory contents (VWM) across visual areas; however, it has remained unclear how these two types of representations are concurrently present. Here, we reanalyzed an open-access fMRI dataset where participants memorized a sensory stimulus while simultaneously being presented with sensory distractors. First, we found that the VWM code in several visual regions did not fully generalize between different time points, suggesting a dynamic code. A more detailed analysis revealed that this was due to shifts in coding spaces across time. Second, we collapsed neural signals across time to assess the degree of interference between VWM contents and sensory distractors, specifically by testing the alignment of their encoding spaces. We find that VWM and feature-matching sensory distractors are encoded in coding spaces that do not fully overlap, but the separation decreases when distractors negatively impact behavioral performance in recalling the target. Together, these results indicate a role of dynamic coding and temporally stable coding spaces in helping multiplex perception and VWM within visual areas.
Chemogenetic stimulation of phrenic motor output and diaphragm activity
Authors: Benevides Ethan S. , Thakre Prajwal P. , Rana Sabhya , Sunshine Michael D. , Jensen Victoria N. , Oweiss Karim , Fuller David D.
Published: April 2024

Impaired respiratory motor output contributes to morbidity and mortality in many neurodegenerative diseases and neurologic injuries. We investigated if expressing designer receptors exclusively activated by designer drugs (DREADDs) in the mid-cervical spinal cord could effectively stimulate phrenic motor output to increase diaphragm activation. Two primary questions were addressed: 1) does effective DREADD-mediated diaphragm activation require focal expression in phrenic motoneurons (vs. non-specific mid-cervical expression), and 2) can this method produce a sustained increase in inspiratory tidal volume? Wild type (C57/bl6) and ChAT-Cre mice received bilateral intraspinal (C4) injections of an adeno-associated virus (AAV) encoding the hM3D(Gq) excitatory DREADD. In wild-type mice, this produced non-specific DREADD expression throughout the mid-cervical ventral horn. In ChAT-Cre mice, a Cre-dependent viral construct was used to drive neuronal DREADD expression in the C4 ventral horn, targeting phrenic motoneurons. Diaphragm EMG was recorded in isoflurane-anesthetized spontaneously breathing mice at 4-9 weeks post-AAV delivery. The DREADD ligand JHU37160 (J60) caused a bilateral, sustained (>1 hour) increase in inspiratory EMG bursting in both groups; the relative increase was greater in ChAT-Cre mice. Additional experiments in ChAT-Cre rats were conducted to determine if spinal DREADD activation could increase inspiratory tidal volume (VT) during spontaneous breathing, assessed using whole-body plethysmography without anesthesia. Three-to-four months after intraspinal (C4) injection of AAV driving Cre-dependent hM3D(Gq) expression, intravenous J60 resulted in a sustained (>30 min) increase in VT. Subsequently, phrenic nerve recordings performed under urethane anesthesia confirmed that J60 evoked a > 200% increase in inspiratory output. We conclude that targeting mid-cervical spinal DREADD expression to the phrenic motoneuron pool enables ligand-induced, sustained increases in phrenic motor output and VT. Further development of this technology may enable application to clinical conditions associated with impaired diaphragm activation and hypoventilation.
Metastasis of colon cancer requires Dickkopf-2 to generate cancer cells with Paneth cell properties
Authors: Shin Jae Hun , Park Jooyoung , Lim Jaechul , Jeong Jaekwang , Dinesh Ravi K. , Maher Stephen E. , Kim Jeonghyun , Park Soyeon , Hong Jun Young , Wysolmerski John , Choi Jungmin , Bothwell Alfred L. M.
Published: April 2024

Metastasis is the leading cause of cancer-related mortality. Paneth cells provide stem cell niche factors in homeostatic conditions, but the underlying mechanisms of cancer stem cell niche development are unclear. Here we report that Dickkopf-2 (DKK2) is essential for the generation of cancer cells with Paneth cell properties during colon cancer metastasis. Splenic injection ofDkk2-knockout (KO) cancer organoids into C57BL/6 mice resulted in a significant reduction of liver metastases. Transcriptome analysis showed reduction of Paneth cell markers such as lysozymes in KO organoids. Single cell RNA sequencing analyses of murine metastasized colon cancer cells and patient samples identified the presence of lysozyme positive cells with Paneth cell properties including enhanced glycolysis. Further analyses of transcriptome and chromatin accessibility suggested Hepatocyte nuclear factor 4-alpha (HNF4A) as a downstream target of DKK2. Chromatin immunoprecipitation followed by sequencing analysis revealed that HNF4A binds to the promoter region ofSox9, a well-known transcription factor for Paneth cell differentiation. In the liver metastatic foci, DKK2 knockout rescued HNF4A protein levels followed by reduction of lysozyme positive cancer cells. Taken together, DKK2-mediated reduction of HNF4A protein promotes the generation of lysozyme positive cancer cells with Paneth cell properties in the metastasized colon cancers.
How does plant chemodiversity evolve? Testing five hypotheses in one population genetic model
Authors: Wittmann Meike J. , Bräutigam Andrea
Published: April 2024

Plant chemodiversity, the diversity of plant specialized metabolites, is an important dimension of biodiversity. However, there are so far few quantitative models to test verbal hypotheses on how chemodiversity evolved. Here we develop such a model to test predictions of five hypotheses: the “fluctuating selection hypothesis”, the “dominance reversal hypothesis”, the interaction diversity hypothesis, the synergy hypothesis, and the screening hypothesis.

We build a population genetic model of a plant population attacked by herbivore species whose occurrence fluctuates over time. We study the model using mathematical analysis and individual-based simulations.

As predicted by the “dominance reversal hypothesis”, chemodiversity can be maintained if alleles conferring a defense metabolite are dominant with respect to the benefits, but recessive with respect to costs. However, even smaller changes in dominance can maintain polymorphism. Moreover, our results underpin and elaborate predictions of the synergy and interaction diversity hypotheses, and, to the extent that our model can address it, the screening hypotheses. By contrast, we found only partial support for the “fluctuating selection hypothesis”.

In summary, we have developed a flexible model and tested various verbal models for the evolution of chemodiversity. Next, more mechanistic models are needed that explicitly consider the organization of metabolic pathways.
Top-down Mass Spectrometric Analysis of a Lipooligosaccharide from the Human CommensalBacteroides fragilis
Authors: Yang Tiandi , Daugherty Jason , Kasper Dennis L.
Published: April 2024

Lipopolysaccharides (LPS) and lipooligosaccharides (LOS) are ubiquitous structures found on the outer membrane of gram-negative bacteria.Bacteroides fragilis, is a gram-negative anaerobe commonly inhabiting the human colon. The LOS of this organism is known to trigger a type I interferon response in dendritic cells. However, detailed structural analysis of this LOS has been largely elusive. Using top-down mass spectrometry, we have unraveled the comprehensive fine structure ofB. fragilisLOS. Our analysis reveals that this LOS has a poly-galactose-rhamnose-KDO-lipid A architecture, which can be modified by hexuronic acid and ethanolamine via phosphodiester linkages. The lipid moiety typically includes three to five acyl chains of varying length on a glucosamine disaccharide. This investigation lays the groundwork for deeper immunological exploration ofB. fragilisLOS and underscores the efficacy of top-down mass spectrometry in characterizing intact LOS/LPS structures and their modifications.
Transcatheter versus Surgical Interventions for Severe Aortic Stenosis: A Contemporary Evaluation against Conservative Management
Authors: Ma Zhiyuan , Shadman Shahrad , Maddahi Yaniv , Krishnamurthy Mahesh , Puleo Peter , Shirani Jamshid
Published: April 2024

Background

Aortic valve replacement (AVR), through transcatheter (TAVR) or surgical (SAVR) means, serves as a pivotal therapeutic approach for severe aortic stenosis (AS). While both modalities show advantages over conservative management, the long-term mortality benefits post-AVR, especially when comparing TAVR with SAVR, remain uncertain.

Objectives

This study aimed to perform an in-depth meta-analysis of randomized controlled trials (RCT) comparing TAVR versus SAVR, as well as their outcomes against conservative management.

Methods

Electronic databases were searched up to December 7, 2023. Individual patient data extracted from Kaplan-Meier plots, underwent pooling and modeling with stratification by surgical risk. The primary endpoint was all-cause mortality at 5 years.

Results

The study included eleven RCTs and twelve non-RCTs, encompassing 4215 patients undergoing TAVR, 4017 undergoing SAVR and comparing 11,285 AVR patients with 23,358 receiving conservative management. TAVR exhibited significantly lower all-cause mortality at 6 months (HR 0.62, 95% CI: 0.52-0.74) compared to SAVR, with no significant difference beyond 6 months (HR 1.08, 95% CI: 0.98-1.19). Additionally, over a 5-year period, there were no significant disparities in cardiovascular mortality (HR 0.98, 95% CI: 0.83-1.16) or stroke (HR 1.02, 95% CI: 0.75-1.38) between TAVR and SAVR, while TAVR exhibited a notable advantage with a markedly reduced risk of cardiovascular mortality in the initial 6 months (HR 0.64, 95% CI: 0.46-0.87) and stroke within the first month post-procedure (HR 0.31, 95% CI: 0.19-0.51). Furthermore, the mean aortic valve area and pressure gradient remained comparable between TAVR and SAVR, exhibiting stability throughout the 5-year follow-up period. AVR markedly reduced all-cause mortality compared to medical therapy (P < 0.001), with 5-year crude mortality rates of 31.6% versus 49.3%, and a difference in restricted mean survival time of 8.9 months. Similar outcomes were observed across high, intermediate, and low surgical risk categories.

Conclusions

While TAVR demonstrated early mortality reduction compared to SAVR, no distinctions emerged in the overall 5-year follow-up, regardless of surgical risk. AVR notably improved survival over conservative therapy. This study advocates for the preference of TAVR or SAVR in severe AS patients when feasible.
Physical activity, low-grade inflammation, and psychological responses to the COVID-19 pandemic among older adults in England
Authors: Danka Martin N. , Steptoe Andrew , Iob Eleonora
Published: April 2024

Mental health responses to the COVID-19 pandemic have been widely studied, but less is known about the potentially protective role of physical activity (PA) and the impact of low-grade inflammation. Using a sample of older adults from England, this study tested (1) if pre-pandemic PA and its changes during the pandemic were associated with mental health responses; (2) if older adults with low-grade inflammation experienced greater increases in depression and anxiety, compared to pre-pandemic levels; (3) if PA attenuated the association between inflammation and depression/anxiety. The study used data from the English Longitudinal Study of Ageing, a cohort study following a national sample aged 50+. Information on mental health and PA were collected before the pandemic (2016/17 and 2018/19) and during November and December 2020. Inflammation was ascertained using pre-pandemic C-reactive protein (CRP). Analyses were adjusted for sociodemographic and health-related factors and pre-pandemic mental health. Increasing PA from before to during the pandemic was linked to reduced odds of depression (OR= 0.955, 95%CI[0.937, 0.974]) and anxiety (OR= 0.954, 95%CI[0.927;0.982]). Higher pre-pandemic PA was associated with reduced odds of depression (OR= 0.964, 95%CI[0.948, 0.981]) and anxiety (OR= 0.976, 95%CI[0.953, 1.000]), whereas elevated CRP was associated with 1.343 times higher odds of depression (95%CI[1.100, 1.641]). PA did not attenuate the inflammation-depression association. The findings suggest that PA may contribute to psychological resilience among older adults, independently of inflammation. Further research is needed to explore the psychobiological pathways underlying this protective mechanism.
Evaluation of a Bayesian hierarchical pharmacokinetic-pharmacodynamic model for predicting parasitological outcomes in Phase 2 studies of new antimalarial drugs
Authors: Tully Meg K , Dini Saber , Flegg Jennifer A , McCarthy James S , Price David J , Simpson Julie A
Published: April 2024

The rise of multidrug resistant malaria requires accelerated development of novel antimalarial drugs. Pharmacokinetic-pharmacodynamic (PK-PD) models relate blood antimalarial drug concentrations with the parasite-time profile to inform dosing regiments. We performed a simulation study to assess the utility of a Bayesian hierarchical mechanistic PK-PD model for predicting parasite-time profiles for a Phase 2 study of a new antimalarial drug, cipargamin.

We simulated cipargamin concentration- and malaria parasite-profiles based on a Phase 2 study of 8 volunteers who received cipargamin 7 days after inoculation with malaria parasites. The cipargamin profiles were generated from a 2-compartment PK model and parasite profiles from a previously published biologically informed PD model. One-thousand PK-PD datasets of 8 patients were simulated, following the sampling intervals of the Phase 2 study. The mechanistic PK-PD model was incorporated in a Bayesian hierarchical framework and the parameters estimated.

Population PK model parameters describing absorption, distribution and clearance were estimated with minimal bias (mean relative bias ranged from 1.7 to 8.4%). The PD model was fitted to the parasitaemia profiles in each simulated dataset using the estimated PK parameters. Posterior predictive checks demonstrate that our PK-PD model successfully captures both the pre- and post-treatment simulated PD profiles. The bias of the estimated population average PD parameters was low-moderate in magnitude.

This simulation study demonstrates the viability of our PK-PD model to predict parasitological outcomes in Phase 2 volunteer infection studies. This work will inform the dose-effect relationship of cipargamin, guiding decisions on dosing regimens to evaluate in Phase 3 trials.
Newly synthesized mRNA selectively escapes translational repression following acute stress
Authors: Zedan Mostafa , Schürch Alexandra P. , Heinrich Stephanie , Gómez García Pablo Aurelio , Khawaja Sarah , Weis Karsten
Published: April 2024

When cells encounter environmental stress, they rapidly mount an adaptive response by switching from pro-growth to stress-responsive gene expression programs. It is poorly understood how cells selectively silence pre-existing, pro-growth transcripts, yet efficiently translate transcriptionally-induced stress mRNA, and whether these transcriptional and post-transcriptional responses are coordinated. Here, we show that following acute glucose withdrawal in S. cerevisiae, pre-existing mRNAs are not first degraded to halt protein synthesis, nor are they sequestered away in P-bodies. Rather, their translation is rapidly repressed through a sequence-independent mechanism that differentiates between mRNAs produced before and after stress followed by their decay. Transcriptional induction of endogenous transcripts and reporter mRNAs during stress is sufficient to escape translational repression, while induction prior to stress leads to repression. Our results reveal a timing-controlled coordination of the transcriptional and translational responses in the nucleus and cytoplasm ensuring a rapid and widescale reprogramming of gene expression following environmental stress.
The asymptomatic proportion of SARS-CoV-2 Omicron-variant infections in households: A systematic review
Authors: Shi Nancy DJ , Marcato Adrian J , Spirkoska Violeta , Meagher Niamh , Villanueva-Cabezas Juan-Pablo , Price David J
Published: April 2024

Background

Understanding the clinical spectrum of SARS-CoV-2 infection, including the asymptomatic fraction, is important as asymptomatic individuals are still able to infect other individuals and contribute to ongoing transmission. The WHO Unity Household transmission investigation (HHTI) protocol provides a platform for the prospective and systematic collection of high-quality clinical, epidemiological, serological, and virological data from SARS-CoV-2 confirmed cases and their household contacts. These data can be used to understand key severity and transmissibility parameters — including the asymptomatic proportion — in relation to local epidemic context and help inform public health response.

Methods

We aimed to estimate the asymptomatic proportion of SARS-CoV-2 Omicron-variant infections in Unity-aligned HHTIs. We conducted a systematic review and meta-analysis in alignment with the PRISMA 2020 guidelines and registered our systematic review on PROSPERO (CRD42022378648). We searched EMBASE, Web of Science, MEDLINE, and bioRxiv and medRxiv from 1 November 2021 to 22 August 2023.

Results

We identified 8,368 records, of which 98 underwent full text review. We identified only three studies for data extraction, with substantial variation in study design and corresponding estimates of the asymptomatic proportion. As a result, we did not generate a pooled estimate orI2metric.

Conclusions

The limited number of quality studies that we identified highlights the need for improved preparedness and response capabilities to facilitate robust HHTI implementation, analysis and reporting, to better inform national, regional and global risk assessments and policy making.

Key messages

Estimates for the asymptomatic proportion of SARS-CoV-2 Omicron-variant infections are highly heterogeneous

We assessed the proportion of SARS-CoV-2 Omicron-variant infections among household contacts, who were followed prospectively and systematically, per the WHO Unity household transmission investigation protocol.

Given the small number of studies with sufficient data and the observed heterogeneity in the asymptomatic proportion point estimates, we did not provide a pooled estimate of the asymptomatic proportion.

Fit-for-purpose study designs, and improved reporting, are necessary for robust estimation of epidemiological characteristics from household studies and their interpretation.

Ongoing assessment of the asymptomatic proportion of SARS-CoV-2 infection is critical to inform ongoing public health response options such as testing strategies to detect infections and isolation guidance for close contacts.
Extreme genome scrambling in marine planktonicOikopleura dioicacryptic species
Authors: Plessy Charles , Mansfield Michael J. , Bliznina Aleksandra , Masunaga Aki , West Charlotte , Tan Yongkai , Liu Andrew W. , Grašič Jan , del Río Pisula María Sara , Sánchez-Serna Gaspar , Fabrega-Torrus Marc , Ferrández-Roldán Alfonso , Roncalli Vittoria , Navratilova Pavla , Thompson Eric M. , Onuma Takeshi , Nishida Hiroki , Cañestro Cristian , Luscombe Nicholas M.
Published: April 2024

Genome structural variations within species are rare. How selective constraints preserve gene order and chromosome structure is a central question in evolutionary biology that remains unsolved. Our sequencing of several genomes of the appendicularian tunicateOikopleura dioicaaround the globe reveals extreme genome scrambling caused by thousands of chromosomal rearrangements, although showing no obvious morphological differences between these animals. The breakpoint accumulation rate is an order of magnitude higher than in ascidian tunicates, nematodes,Drosophila,or mammals. Chromosome arms and sex-specific regions appear to be the primary unit of macrosynteny conservation. At the microsyntenic level, scrambling did not preserve operon structures, suggesting an absence of selective pressure to maintain them. The uncoupling of the genome scrambling with morphological conservation inO. dioicasuggests the presence of previously unnoticed cryptic species and provides a new biological system that challenges our previous vision of speciation in which similar animals always share similar genome structures.
Kinematical higher-twist corrections in
γ*→M1M2γ
: Charged meson production
Authors: Pire Bernard , Song Qin-Tao
Published: April 2024

Generalized distribution amplitudes (GDAs) of mesons can be probed by the reactions e−e+→M1M2γ, which are accessible at electron-positron colliders such as BESIII and Belle II. After discussing the neutral meson production case in our previous paper, we discuss here the complementary case of the charged meson (M+M−) production, where one can extract the complete information on GDAs from the interference of the amplitudes of the two competing processes where the photon is emitted either in the initial or in the final state. Considering the importance of the charged meson production, we present a complete expression for the interference term of the cross section, which is experimentally accessible thanks to its charge conjugation specific property. We adopt two types of models for leading-twist ππ GDAs to estimate the size of the interference term in the process e−e+→π+π−γ numerically, namely, a model extracted from previous experimental results on γ*γ→π0π0 at Belle and the asymptotic form predicted by QCD evolution equations. We include in the calculation the kinematical power suppressed (sometimes called kinematical higher-twist) corrections up to 1/Q2 for the helicity amplitudes. Both models of GDAs indicate that the kinematical corrections are not negligible for the interference term of the cross section measured at BESIII, thus it is necessary to include them if we try to extract the GDAs precisely. On the other side, the kinematical corrections are very tiny for the measurements at Belle II, and the leading twist-two formula of the interference term will be good enough to describe the charge conjugation odd part of the differential cross section.

Published by the American Physical Society
2024
Terrestrial density of strongly-coupled relics
Authors: Berlin Asher , Liu Hangwan , Pospelov Maxim , Ramani Harikrishnan
Published: April 2024

The simplest cosmologies motivate the consideration of dark matter subcomponents that interact significantly with normal matter. Moreover, such strongly coupled relics may have evaded detection to date if upon encountering the Earth they rapidly thermalize down to terrestrial temperatures, T⊕∼300  K∼25  meV, well below the thresholds of most existing dark matter detectors. This shedding of kinetic energy implies a drastic enhancement to the local density, motivating the consideration of alternative detection techniques sensitive to a large density of slowly moving dark matter particles. In this work, we provide a rigorous semianalytic derivation of the terrestrial overdensities of strongly coupled relics, with a particular focus on millicharged particles (MCPs). We go beyond previous studies by incorporating improved estimates of the MCP-atomic scattering cross section, new contributions to the terrestrial density of sub-GeV relics that are independent of the Earth’s gravitational field, and local modifications that can arise due to the cryogenic environments of precision sensors. We also generalize our analysis in order to estimate the terrestrial density of thermalized MCPs that are produced from the collisions of high-energy cosmic rays and become bound by the Earth’s electric field.

Published by the American Physical Society
2024
U
folds from geodesics in moduli space
Authors: Astesiano D. , Ruggeri D. , Trigiante M.
Published: April 2024

We exploit the presence of moduli fields in the AdS3×S3×CY2, where CY2=T4 or K3, solution to type IIB superstring theory, to construct a U-fold solution with geometry AdS2×S1×S3×CY2. This is achieved by giving a nontrivial dependence of the moduli fields in SO(4,n)/SO(4)×SO(n) (n=4 for CY2=T4 and n=20 for CY2=K3), on the coordinate η of a compact direction S1 along the boundary of AdS3, so that these scalars, as functions of η, describe a geodesic on the corresponding moduli space. The backreaction of these evolving scalars on spacetime amounts to a splitting of AdS3 into AdS2×S1 with a nontrivial monodromy along S1 defined by the geodesic. Choosing the monodromy matrix in SO(4,n;Z), this supergravity solution is conjectured to be a consistent superstring background. We generalize this construction starting from an ungauged theory in D=2d, d odd, describing scalar fields nonminimally coupled to (d−1) forms and featuring solutions with topology AdSd×Sd, and moduli scalar fields. We show, in this general setting, that giving the moduli fields a geodesic dependence on the η coordinate of an S1 at the boundary of AdSd is sufficient to split this space into AdSd−1×S1, with a monodromy along S1 defined by the starting and ending points of the geodesic. This mechanism seems to be at work in the known J-fold solutions in D=10 type IIB theory and hints toward the existence of similar solutions in the type IIB theory compactified on CY2. We argue that the holographic dual theory on these backgrounds is a 1+0 CFT on an interface in the 1+1 theory at the boundary of the original AdS3.

Published by the American Physical Society
2024
Supersymmetric Wormholes in String Theory
Authors: Astesiano Davide , Gautason Friðrik Freyr
Published: April 2024

We construct a large family of Euclidean supersymmetric wormhole solutions of type IIB supergravity which are asymptotically AdS5×S5. The solutions are constructed using consistent truncation to maximally gauged supergravity in five dimensions which is further truncated to a four scalar model. Within this model we perform a full analytic classification of supersymmetric domain wall solutions with flat Euclidean domain wall slices. On each side of the wormhole, the solution asymptotes to AdS5 dual to N=4 supersymmetric Yang-Mills deformed by a supersymmetric mass term.

Published by the American Physical Society
2024
Quantum Simulation of Bound State Scattering
Authors: Turco Matteo , Quinta Gonçalo , Seixas João , Omar Yasser
Published: April 2024

The last few years have seen rapid development of applications of quantum computation to quantum field theory. The first algorithms for quantum simulation of scattering have been proposed in the context of scalar and fermionic theories, requiring thousands of logical qubits. These algorithms are not suitable to simulate scattering of incoming bound states, as the initial-state preparation relies typically on adiabatically transforming wavepackets of the free theory into wavepackets of the interacting theory. In this paper we present a strategy to excite wavepackets of the interacting theory directly from the vacuum of the interacting theory, allowing the preparation of states of composite particles. This is the first step towards digital quantum simulation of scattering of bound states. The approach is based on the Haag-Ruelle scattering theory, which provides a way to construct creation and annihilation operators of a theory in a full, nonperturbative framework. We provide a quantum algorithm requiring a number of ancillary qubits that is logarithmic in the size of the wavepackets, and with a success probability vanishing at most like a polynomial in the lattice parameters and the energy of the wavepacket. The gate complexity for a single iteration of the circuit is equivalent to that of a time evolution for a fixed time. Furthermore, we propose a complete protocol for scattering simulation using this algorithm. We study its efficiency and find improvements with respect to previous algorithms in the literature.

Published by the American Physical Society
2024
Experimental evaluation of bamboo natural fiber composite reinforced with SiO2 nanoparticles for aircraft applications
Authors: Gunasekar P. , A. Anderson , T.R. Praveenkumar
Published: April 2024

Purpose

Composite materials have revolutionized the aerospace industry by offering superior structural qualities over traditional elements. This study aims to focus on the development and testing of bamboo natural fiber-based composites enhanced with SiO2 nanoparticles.

Design/methodology/approach

The investigation involved fabricating specimens with varying nanoparticle compositions (0, 10 and 20%) and conducting tensile, flexural, impact and fracture toughness tests. Results indicated significant improvements in mechanical properties with the addition of nanoparticles, particularly at a 10% composition level.

Findings

This study underscores the potential of natural fiber composites, highlighting their environmental friendliness, cost-effectiveness and improved structural properties when reinforced with nanoparticles. The findings suggest an optimal ratio for nanoparticle integration, emphasizing the critical role of precise mixing proportions in achieving superior composite performance.

Originality/value

The tensile strength, flexural strength, impact resistance and fracture toughness exhibited notable enhancements compared with the 0 and 20% nanoparticle compositions. The 10% composition showed the most promising outcomes, showcasing increased strength across all parameters.
Computer vision-based real-time monitoring for swivel construction of bridges: from laboratory study to a pilot application
Authors: Zhang Shilong , Liu Changyong , Feng Kailun , Xia Chunlai , Wang Yuyin , Wang Qinghe
Published: April 2024

Purpose

The swivel construction method is a specially designed process used to build bridges that cross rivers, valleys, railroads and other obstacles. To carry out this construction method safely, real-time monitoring of the bridge rotation process is required to ensure a smooth swivel operation without collisions. However, the traditional means of monitoring using Electronic Total Station tools cannot realize real-time monitoring, and monitoring using motion sensors or GPS is cumbersome to use.

Design/methodology/approach

This study proposes a monitoring method based on a series of computer vision (CV) technologies, which can monitor the rotation angle, velocity and inclination angle of the swivel construction in real-time. First, three proposed CV algorithms was developed in a laboratory environment. The experimental tests were carried out on a bridge scale model to select the outperformed algorithms for rotation, velocity and inclination monitor, respectively, as the final monitoring method in proposed method. Then, the selected method was implemented to monitor an actual bridge during its swivel construction to verify the applicability.

Findings

In the laboratory study, the monitoring data measured with the selected monitoring algorithms was compared with those measured by an Electronic Total Station and the errors in terms of rotation angle, velocity and inclination angle, were 0.040%, 0.040%, and −0.454%, respectively, thus validating the accuracy of the proposed method. In the pilot actual application, the method was shown to be feasible in a real construction application.

Originality/value

In a well-controlled laboratory the optimal algorithms for bridge swivel construction are identified and in an actual project the proposed method is verified. The proposed CV method is complementary to the use of Electronic Total Station tools, motion sensors, and GPS for safety monitoring of swivel construction of bridges. It also contributes to being a possible approach without data-driven model training. Its principal advantages are that it both provides real-time monitoring and is easy to deploy in real construction applications.
Fostering social sustainability: unveiling HR’s power in enhancing employee resilience via social exchange and broaden-and-build theories
Authors: Malik Garima , Singh Pratibha
Published: April 2024

Purpose

This study focusses on the intersection of social sustainability and human resource management (HRM) as a strategy for crisis management. It aims to provide detailed insight by exploring the associations between socially sustainable HRM (SSHRM), employee well-being, trust in social capital and employee resilience.

Design/methodology/approach

This study used a cross-sectional research design to test relationships amongst variables. Data was gathered from employees in India’s private-sector information technology (IT) industry, making the framework relevant to this specific context. The study employed the partial least squares structural equation modelling (PLS-SEM) to analyse complex relationships between the variables.

Findings

The results indicate that organisations can boost employee resilience through SSHRM implementation, promote personal well-being (PWB) and family well-being (FWB) and foster trust in social capital. Additionally, the study highlights the moderating impact of employee empowerment, improving the translation of positive employee behaviour in organisational settings.

Practical implications

Our research emphasises the importance of sustainability efforts and strategies focused on social capital to build long-lasting employee connections. This highlights the necessity of incorporating social sustainability objectives into the organisation’s strategic blueprint, ensuring integration into decision-making procedures.

Originality/value

This study uniquely explores the underlying mechanisms through which SSHRM influences employee resilience. An in-depth empirical analysis evinces the causal mechanism between SSHRM, employee well-being, social capital trust and employee resilience.
Before the “fall”: Alan Fox's “intellectual crisis” and early pluralist history and sociology
Authors: Ackers Peter
Published: April 2024

Purpose

This paper presents an historical reconstruction of the radicalisation of Alan Fox, the industrial sociologist and a detailed analysis of his early historical and sociological writing in the classical pluralist phase.

Design/methodology/approach

An intellectual history, including detailed discussion of key Fox texts, supported by interviews with Fox and other Biographical sources.

Findings

Fox’s radicalisation was incomplete, as he carried over from his industrial relations (IR) pluralist mentors, Allan Flanders and Hugh Clegg, a suspicion of political Marxism, a sense of historical contingency and an awareness of the fragmented nature of industrial conflict.

Originality/value

Recent academic attention has centred on Fox’s later radical pluralism with its “structural” approach to the employment relationship. This paper revisits his early, neglected classical pluralist writing. It also illuminates his transition from institutional IR to a broader sociology of work, influenced by AH Halsey, John Goldthorpe and others and the complex nature of his radicalisation.