bluuebunny/crossref_metadata_2025 huggingface dataset:
A study of the expression of germline-specific paralogs of the ubiquitously expressed NAC complex revealed their association with centrosomes
Authors: Mikhaleva Elena A. , Akulenko Natalia V. , Olenkina Oxana M. , Abramov Yuri A. , Lavrov Sergey A. , Leinsoo Thoomas A. , Kogan Galina L. , Gvozdev Vladimir A.
Published: December 2022

Protein homeostasis involves the ubiquitously expressed heterodimeric protein NAC (ribosome associated nascent polypeptide complex), consisting of α- and β-subunits. We previously found inDrosophila melanogasterthe presence of germline-specific paralogous genes for NAC subunits (gNACs): unique for the α-subunit and several highly homologous amplified genes for the β-subunit, indistinguishable by the antibodies used, while they were detected as different phosphorylated isoforms in 2D electrophoresis with immunostaining. The distinct increase in gNAC expression in growing spermatocytes compared with their predecessors, gonioblasts, is accompanied by a clear presence of gNAC in the cytoplasm of dividing meiotic cells and spermatids. In oogenesis, gNAC expression is significantly lower than in the testis, but gNAC accumulation is found at the posterior pole of the mature oocyte, known as the germplasm region responsible for the germ cell formation in the offspring. gNAC-associated ribosomes from mature oocytes are enriched in mRNA sets encoding known germplasm and centrosome proteins. gNAC is also detected in a pericentriolar component of centrosomes: in syncytial dividing nuclei in the early embryos, in primordial germ cells and spermatocytes, including meiotic divisions stage. CRISPR/Cas9-mediated deficiency of the gNAC-alpha subunit causes female infertility. We propose the role of the gNAC phosphoregulatory paralog system as a component of the germline proteostasis network, coordinated with the centrosome functions. Here, we also extended our results by identifying cross-links between ubiquitous and germline-specific NAC-β paralogs, finding an additional case of functional cross-talk between heterodimeric ubNAC and gNAC α-subunit paralogs, which may maintain the robustness of proteostasis and fly fecundity.
Trivalent SARS-CoV-2 S1 Subunit Protein Vaccination Induces Broad Humoral Responses in BALB/c Mice
Authors: Khan Muhammad S. , Kim Eun , Huang Shaohua , Kenniston Thomas W. , Gambotto Andrea
Published: December 2022

This paper presents a novel approach for improving the efficacy of COVID-19 vaccines against emergent SARS-CoV-2 variants. We have evaluated the immunogenicity of unadjuvanted wild-type (WU S1-RS09cg) and variant-specific (Delta S1-RS09cg and OM S1-RS09cg) S1 subunit protein vaccines delivered either as a monovalent or a trivalent antigen in BALB/c mice. Our results show that a trivalent approach induced a broader humoral response with more coverage against antigenically distinct variants, especially when compared to monovalent Omicron-specific S1. This trivalent approach was also found to have increased or equivalent ACE2 binding inhibition, and increased S1 IgG endpoint titer at early timepoints, against SARS-CoV-2 spike variants when compared monovalent Wuhan, Delta, or Omicron S1. Our results demonstrate the utility of protein subunit vaccines against COVID-19 and provide insights into the impact of variant-specific COVID-19 vaccine approaches on the immune response in the current SARS-CoV-2 variant landscape. Particularly, our study provides insight into effects of further increasing valency of currently approved SARS-CoV-2 vaccines, a promising approach for improving protection to curtail emerging viral variants.
Fortuitous Somatic Mutations during Antibody Evolution Endow Broad Neutralization against SARS-CoV-2 Omicron Variants
Authors: Wu Jianbo , Chen Zhenguo , Gao Yidan , Wang Zegen , Wang Jiarong , Chiang Bing-Yu , Zhou Yunjiao , Han Yuru , Zhan Wuqiang , Xie Minxiang , Jiang Weiyu , Zhang Xiang , Hao Aihua , Xia Anqi , He Jiaying , Xue Song , Mayer Christian T. , Wu Fan , Wang Bin , Zhang Lunan , Sun Lei , Wang Qiao
Published: December 2022

Striking antibody evasion by emerging circulating SARS-CoV-2 variants drives the identification of broadly neutralizing antibodies (bNAbs). However, how a bNAb acquires increased neutralization breadth during antibody evolution is still elusive. Here, we identified a clonally-related antibody family from a convalescent individual. One of the members, XG005, exhibited potent and broad neutralizing activities against SARS-CoV-2 variants, while the other members showed significant reductions in neutralization breadth and potency, especially against the Omicron sublineages. Structural analysis visualizing the XG005-Omicron spike binding interface revealed how crucial somatic mutations endowed XG005 with greater neutralization potency and breadth. A single administration of XG005 with extended half-life, reduced antibody-dependent enhancement (ADE) effect, and increased antibody product quality, exhibited a high therapeutic efficacy in BA.2- and BA.5-challenged mice. Our results provided a natural example to show the importance of somatic hypermutation during antibody evolution for SARS-CoV-2 neutralization breadth and potency.
Genome-wide association study of multiple neuropathology endophenotypes identifies novel risk loci and provides insights into known Alzheimer’s risk loci
Authors: Shade Lincoln M.P. , Katsumata Yuriko , Claas Steven A. , Ebbert Mark T. W. , Abner Erin L. , Hohman Timothy J. , Mukherjee Shubhabrata , Nho Kwangsik , Saykin Andrew J. , Bennett David A. , Schneider Julie A. ,   The Alzheimer’s Disease Genetics Consortium, Nelson Peter T. , Fardo David W. ,   Alzheimer’s Disease Neuroimaging Initiative
Published: December 2022

Background

Alzheimer’s disease is highly heritable and exhibits neuropathological hallmarks of neurofibrillary tau tangles and neuritic amyloid plaques. Previous genome-wide association studies (GWAS) have identified over 70 genomic risk loci of clinically diagnosed Alzheimer’s disease. However, upon autopsy, many Alzheimer’s disease patients have multiple comorbid neuropathologies that may have independent or pleiotropic genomic risk factors. Autopsy data combined with GWAS provides the opportunity to study the genetic risk factors of individual neuropathologies.

Methods

We studied the genome-wide risk factors of eleven Alzheimer’s disease-related neuropathology endophenotypes. We used four sources of neuropathological data: National Alzheimer’s Coordinating Center, Religious Orders Study and Rush Memory and Aging Project, Adult Changes in Thought study, and Alzheimer’s Disease Neuroimaging Initiative. We used generalized linear mixed models to identify risk loci, followed by Bayesian colocalization analyses to identify potential functional mechanisms by which genetic loci influence neuropathology risk.

Results

We identified two novel loci associated with neuropathology: onePIK3R5locus (lead variant rs72807981) with neurofibrillary pathology, and oneCOL4A1locus (lead variant rs2000660) with cerebral atherosclerosis. We also confirmed associations between known Alzheimer’s genes and multiple neuropathology endophenotypes, includingAPOE(neurofibrillary tangles, neuritic plaques, diffuse plaques, cerebral amyloid angiopathy, and TDP-43 pathology);BIN1(neurofibrillary tangles and neuritic plaques); andTMEM106B(TDP-43 pathology and hippocampal sclerosis). After adjusting forAPOEgenotype, we identified a locus nearAPOC2(lead variant rs4803778) associated with cerebral amyloid angiopathy that influences DNA methylation at nearby CpG sites in the cerebral cortex.

Conclusions

rs2000660 is in strong linkage disequilibrium with a synonymous coding variant (rs650724) ofCOL4A1, providing a candidate functional variant. Two CpG sites affected by the cerebral amyloid angiopathy-associatedAPOC2locus were previously associated with dementia in an independent cohort, suggesting that the effect of this locus on disease may be mediated by DNA methylation.BIN1is associated with neurofibrillary tangles and neuritic plaques but not with amyloid pathology.TMEM106Bis associated with hippocampal sclerosis and TDP-43 pathology but not the canonical Alzheimer’s disease pathologies. These findings provide insights into known Alzheimer’s disease risk loci by refining the pathways affected by these risk genes.
Relationship between blood bone metabolic biomarkers and anemia in CKD patients
Authors: Li Fan , Yang Guang , Ye Xiaoxue , Zeng Ming , Huang Hui , Bian Anning , Xing Changying , Tang Shaowen , Zhang Jing , Jiang Yao , Chen Huimin , Yin Caixia , Zhang Lina , Wang Jing , Huang Yaoyu , Zhou Wenbin , Wan Huiting , Zha Xiaoming , Wang Ningning
Published: December 2022

Introduction

Blood bone metabolic biomarkers are non-invasive indexes for evaluating renal osteodystrophy (ROD). Here the relationships between blood bone metabolic biomarkers and anemia in chronic kidney disease (CKD) patients are investigated, the effects of parathyroidectomy (PTX) on above indices are analyzed.

Methods

In this cross-sectional study, 100 healthy controls and 239 CKD patients, including 46 secondary hyperparathyroidism (SHPT) subgroup with PTX, were enrolled. A prospective study with 28 PTX patients was followed up. The degree of anemia was classified as mild, moderate, and severe based on the tertiles of hemoglobin (Hb) levels of the anemic CKD patients, with cutoff values of 83g/L and 102g/L. Bone metabolic biomarkers, including calcium (Ca), phosphorus (P), intact parathyroid hormone (iPTH), fibroblast growth factor 23 (FGF23) and α-klotho were tested.

Results

The mean eGFR in CKD patients was 25.74±35.99 ml/min/1.73 m2and 84.10% patients had anemia. The baseline Hb levels in the mild, moderate, and severe anemia subgroups were 110.86±5.99g/L, 92.71±5.96g/L and 67.38±10.56g/L, respectively. CKD patients had higher adjusted Ca, P, ALP, iPTH and FGF23 levels, and lower α-klotho levels than controls. Baseline adjusted Ca, P, iPTH and α-klotho levels were associated with Hb in CKD patients. Blood adjusted Ca, P, iPTH levels were correlated with anemia severity. After PTX (median interval: 6.88 months), anemia and high blood adjusted Ca, P, iPTH and FGF23 levels were ameliorated, while α-klotho levels increased.

Conclusions

Blood adjusted Ca, P, iPTH and α-klotho levels were correlated with Hb in CKD patients, correcting ROD is supposed to be therapeutic targets for anemia.
The effects of sleep disturbance on dyspnoea and impaired lung function following COVID-19 hospitalisation: a prospective multi-centre cohort study
Authors: Jackson C. , Stewart I. , Plekhanova T. , Cunningham P. , Hazel A. L. , Al-Sheklly B. , Aul R. , Bolton C. E. , Chalder T. , Chalmers J. D. , Chaudhuri N. , Docherty A. B. , Donaldson G. , Edwardson C. L. , Elneima O. , Greening N. J. , Hanley N. A. , Harris V. C. , Harrison E. M. , Ho L-P. , Houchen-Wolloff L. , Howard L. S. , Jolley C. J. , Jones M. G. , Leavy O. C. , Lewis K. E. , Lone N. I. , Marks M. , McAuley H. J. C. , McNarry M. A. , Patel B. , Piper-Hanley K. , Poinasamy K. , Raman B. , Richardson M. , Rivera-Ortega P. , Rowland-Jones S. , Rowlands A. V. , Saunders R. M. , Scott J. T. , Sereno M. , Shah A. , Shikotra A. , Singapuri A. , Stanel S. C. , Thorpe M. , Wootton D. G. , Yates T. , Jenkins R. G. , Singh S. , Man W. D-C. , Brightling C. E. , Wain L. V. , Porter J. C. , Thompson A. A. R. , Horsley A. , Molyneaux P. L. , Evans R. A. , Jones S. E. , Rutter M. K. , Blaikley J. F.
Published: December 2022

Background

Sleep disturbance is common following hospitalisation both for COVID-19 and other causes. The clinical associations are poorly understood, despite it altering pathophysiology in other scenarios. We, therefore, investigated whether sleep disturbance is associated with dyspnoea along with relevant mediation pathways.

Methods

Sleep parameters were assessed in a prospective cohort of patients (n=2,468) hospitalised for COVID-19 in the United Kingdom in 39 centres using both subjective and device-based measures. Results were compared to a matched UK biobank cohort and associations were evaluated using multivariable linear regression.

Findings

64% (456/714) of participants reported poor sleep quality; 56% felt their sleep quality had deteriorated for at least 1-year following hospitalisation. Compared to the matched cohort, both sleep regularity (44.5 vs 59.2, p<0.001) and sleep efficiency (85.4% vs 88.5%, p<0.001) were lower whilst sleep period duration was longer (8.25h vs 7.32h, p<0.001). Overall sleep quality (effect estimate 4.2 (3.0–5.5)), deterioration in sleep quality following hospitalisation (effect estimate 3.2 (2.0–4.5)), and sleep regularity (effect estimate 5.9 (3.7–8.1)) were associated with both dyspnoea and impaired lung function (FEV1and FVC). Depending on the sleep metric, anxiety mediated 13–42% of the effect of sleep disturbance on dyspnoea and muscle weakness mediated 29-43% of this effect.

Interpretation

Sleep disturbance is associated with dyspnoea, anxiety and muscle weakness following COVID-19 hospitalisation. It could have similar effects for other causes of hospitalisation where sleep disturbance is prevalent.

Funding

UK Research and Innovation, National Institute for Health Research, and Engineering and Physical Sciences Research Council.
The genomic and epidemiological virulence patterns ofSalmonella entericaserovars in the United States
Authors: Fenske Gavin J. , Pouzou Jane G. , Pouillot Régis , Taylor Daniel D. , Costard Solenne , Zagmutt Francisco J.
Published: December 2022

The serovars ofSalmonella entericadisplay dramatic differences in pathogenesis and host preferences. We developed a process (patent pending) for groupingSalmonellaisolates and serovars by their public health risk to provide better Salmonellacontrol targets along the food chain. We collated a curated set of 12,337S. entericaisolate genomes from human, beef, and bovine sources in the US. After annotating a virulence gene catalog for each isolate, we used unsupervised random forest methods to estimate the proximity (similarity) between isolates based upon the genomic presentation of putative virulence traits We then grouped isolates (virulence clusters) using hierarchical clustering (Ward’s method), used non-parametric bootstrapping to assess cluster stability, and externally validated the virulence clusters against epidemiological virulence measures from FoodNet, the National Outbreak Reporting System (NORS), and US federal sampling of beef products. We identified five stable virulence clusters ofS. entericaserovars. Cluster 1 (higher virulence) serovars yielded an annual incidence rate of domestically acquired sporadic cases roughly one and a half times higher than the other four clusters combined (Clusters 2-5, lower virulence). Compared to other clusters, cluster 1 also had a higher proportion of infections leading to hospitalization and was implicated in more foodborne and beef-associated outbreaks, despite being isolated at a similar frequency from beef products as other clusters. We also identified subpopulations within 11 serovars. Remarkably, we foundS.Infantis andS.Typhimurium subpopulations that significantly differed in genome length and clinical case presentation. Further, we found that the presence of the pESI plasmid accounted for the genome length differences between theS.Infantis subpopulations. Our results demonstrate thatS. entericastrains with the highest incidence of human infections share a common virulence repertoire. This work could be used in combination with foodborne surveillance information to best target serovars of public health concern.
Label-free digital holotomography reveals ibuprofen-induced morphological changes to red blood cells
Authors: Bergaglio Talia , Bhattacharya Shayon , Thompson Damien , Nirmalraj Peter Niraj
Published: December 2022

Understanding the dose-dependent effect of over-the-counter drugs on red blood cells (RBCs) is crucial for hematology and digital pathology. Yet, it is challenging to continuously record the real-time, drug-induced nanoscopic shape changes of RBCs in a label-free manner. Here, we demonstrate digital holotomography (DHTM) enabled real-time, label-free concentration-dependent and time-dependent monitoring of ibuprofen on RBCs from a healthy donor. The RBCs are segmented based on 3D and 4D refractive index tomograms and their morphological and chemical parameters are retrieved with their shapes classified using machine learning. We directly observed the formation and motion of spicules on the RBC membranes when aqueous solutions of ibuprofen were drop cast on wet blood, creating rough-membraned echinocyte forms. At low concentrations of 0.25-0.50 mM, the ibuprofen-induced morphological change was transient but at high concentrations (1.5-3 mM) the spiculated RBC remained over a period of up to 1.5 hours. Molecular simulations confirmed that aggregates of ibuprofen molecules at high concentrations significantly disrupted the RBC membrane structural integrity and lipid order, but produced negligible effect at low ibuprofen concentrations. Control experiments on the effect of urea, hydrogen peroxide and aqueous solutions on RBCs showed zero spicule formation. Our work elucidates the dose-dependent chemical effects on RBCs using label-free microscopes that can be deployed for the rapid detection of overdosage of over-the-counter and prescribed drugs.

Significance

The interaction between drugs and blood cells is an important field of study in order to understand the risk for drug-induced haematological adverse effects. Using digital holo-tomographic microscopy (DHTM), we can resolve the real-time effect of medications on the morphological and chemical properties of red blood cells with high spatial and temporal resolution and in a label-free manner. We show that our approach can be used as a haematology platform for the diagnosis of blood disorders and for monitoring the dose-dependent effect of prescribed and over-the-counter medications in a cost-effective manner, with significant implications for its applicability in resource-limited settings and in the field of personalized medicine.
Schooling of Light Reflecting Fish
Authors: Pertzelan Assaf , Ariel Gil , Kiflawi Moshe
Published: December 2022

One of the hallmarks of the collective movement of large schools of pelagic fish are waves of shimmering flashes that propagate across the school, usually following an attack by a predator. Such flashes arise when sunlight is reflected off the specular (mirror-like) skin that characterizes many pelagic fishes, where it is otherwise thought to offer a means for camouflage in open waters. While it has been suggested that these ‘shimmering waves’ are a visual manifestation of the synchronized escape response of the fish, the phenomenon has been regarded only as an artifact of esthetic curiosity. In this study we apply agent-based simulations and deep learning techniques to show that, in fact, shimmering waves contain information on the behavioral dynamics of the school. Our analyses are based on a model that combines basic rules of collective motion and the propagation of light beams in the ocean, as they hit and reflect off the moving fish. We use the resulting reflection patterns to infer the essential dynamics and inter-individual interactions which are necessary to generate shimmering waves. Using an artificial neural network, trained to classify the direction of attack and the shape of the school based only on the flashes, we also provide a proof-of-concept, showing that flash patterns are indeed indicative of the state and dynamics of the school and the individuals composing it. Moreover, we show that light flashes observed by the school members themselves extends the range at which information can be communicated across the school. To the extent that the fish pay heed to this information, for example by entering an apprehensive state of reduced response-time, our analysis suggests that it may speed up the propagation of information across the school.
Bacterial colonizers ofNematostella vectensisare initially selected by the host before interactions between bacteria determine further succession
Authors: Domin H , Zimmermann J , Taubenheim J , Fuentes Reyes G , Saueressig L , Prasse D , Höppner M , Schmitz RA , Hentschel U , Kaleta C , Fraune S
Published: December 2022

The microbiota of multicellular organisms undergoes considerable changes during development but the general mechanisms that control community assembly and succession are poorly understood. Here, we use bacterial recolonization experiments inNematostella vectensisas a model to understand general mechanisms determining bacterial establishment and succession. We compared the dynamic establishment of the microbiome on the germfree host and on inert silica. Following the dynamic reconstruction of microbial communities on both substrates, we show that the initial colonization events are strongly influenced by the host but not by the tube, while the subsequent bacteria-bacteria interactions are the main cause of bacterial succession. Interestingly, the recolonization pattern on adult hosts resembles the ontogenetic colonization succession. This process occurs independently of the bacterial composition of the inoculum and can be followed at the level of individual bacteria, suggesting that priority effects are neglectable for early colonization events inNematostella. To identify potential metabolic traits associated with initial colonization success and potential metabolic interactions among bacteria associated with bacterial succession, we reconstructed the metabolic networks of bacterial colonizers based on their genomes. These analyses revealed that bacterial metabolic capabilities reflect the recolonization pattern, and the degradation of chitin might be a selection factor during early colonization of the animal. Concurrently, transcriptomic analyses revealed thatNematostellapossesses two chitin synthase genes, one of which is upregulated during early recolonization. Our results show that early colonization events are strongly controlled by the host while subsequent colonization depends on metabolic bacteria-bacteria interactions largely independent of host development.
Mechanistic dissection of alga recognition and uptake in coral-algal endosymbiosis
Authors: Hu Minjie , Bai Yun , Zheng Xiaobin , Zheng Yixian
Published: December 2022

Many corals form a mutually beneficial relationship with the dinoflagellate algae calledSymbiodiniaceae. Cells in the coral gastrodermis recognize, phagocytose, and house the algae in an organelle called symbiosome, which supports algae photosynthesis and nutrient exchange with corals1–3. Rising ocean temperature disrupts this endosymbiotic relationship, leading to alga loss, coral bleaching and death, and the degradation of marine ecosystems4–6. Mitigation of coral death requires a mechanistic understanding of coral-algal endosymbiosis. We have developed genomic resources to enable the use of a soft coralXenia speciesas a model to study coral-algal endosymbiosis7. Here we report an effective RNA interference (RNAi) method and its application in the functional studies of genes involved in early steps of endosymbiosis. We show that an endosymbiotic cell marker called LePin (for itsLectin and kazalProteaseinhibitor domains) is a secreted lectin that binds to algae to initiate the formation of alga-containing endosymbiotic cells. The evolutionary conservation of LePin among marine endosymbiotic anthozoans suggests a general role in coral-algal recognition. Coupling bioinformatics analyses with RNAi and single cell (sc)-RNA-seq, we uncover three gene expression programs (GEP) influenced by LePin during the early and middle stages of endosymbiotic lineage development. Further studies of genes in these GEPs lead to the identification of two scavenger receptors that support the formation of alga-containing endosymbiotic cells, most likely by initiating phagocytosis and modulating coral immune response. We also identify two actin regulators for endosymbiosis, which shed light on the phagocytic machinery and a possible mechanism for symbiosome formation. Our findings should usher in an era of mechanistic studies of coral-algal endosymbiosis.
Combined administration of novobiocin and apomorphine mitigates cholera toxin mediated cellular toxicity
Authors: Bhalerao Sonali Eknath , Sen Himanshu , Raychaudhuri Saumya
Published: December 2022

Cholera is a dreadful disease. The scourge of this deadly disease is still evident in the developing world. Though several therapeutic strategies are in practice to combat and contain the disease, there is still a need for new drugs to control the disease safely and effectively. Keeping in view the concern, we screened a small molecule library against a yeast model of cholera toxin A subunit. Our effort resulted in the discovery of a small molecule, apomorphine effective in reducing the lethality of toxic subunit in yeast model. In addition, novobiocin, an inhibitor of ADP ribosylation process, a key biochemical event through which cholera toxin exerts its action on host, was also found to rescue yeast cells from cholera toxin A subunit mediated toxicity. Finally, both molecules prevented cholera toxin mediated cellular toxicity on HT29 intestinal epithelial cells. We also observed that combined administration of both drug molecules worked better than single drug in countering toxin driven lethality.
Interplay of physical and cognitive performance using hierarchical continuous-time dynamic modelling and a dual-task training regime in Alzheimer’s patients
Authors: Schwarck S. , Voelkle M. C. , Becke A. , Busse N. , Glanz W. , Düzel E. , Ziegler G.
Published: December 2022

Background

Training studies typically investigate the cumulative rather than the analytically challenging immediate effect of exercise on cognitive outcomes.

Methods

We investigated the dynamic interplay between single-session exercise intensity and time-locked cognition in older adults with suspected Alzheimer’s dementia (N = 17) undergoing a 24-week dual-task regime. We specified a state of the art hierarchical Bayesian continuous- time dynamic model with fully connected state variables to analyze the bidirectional effects between physical and cognitive performance over time.

Results

Higher physical performance was dynamically linked to improved memory recognition (-1.335,SD= 0.201, 95 BCI [-1.725, -0.954]). The effect was short-term, lasting up to five days (-0.368, SD = 0.05, 95 BCI [-0.479, -0.266]). Clinical scores supported the validity of the model and observed temporal dynamics.

Conclusion

Higher physical performance predicted improved memory recognition in a day- by-day manner, providing a proof-of-concept for the feasibility of linking exercise training and cognition in patients with Alzheimer’s dementia.

Highlights

Hierarchical Bayesian continuous-time dynamic modelling approach

72 repeated physical exercise (PP) and cognitive (COG) performance measurements

PP is dynamically linked to session-to-session variability of COG

Higher PP improved COG in subsequent sessions in subjects with Alzheimer’s dementia

Short-term effect: lasting up to four days after training session

Research in Context

Systematic review:Training-induced effects on cognitive outcomes in Alzheimer’s dementia and/or associated dynamic Bayesian modelling approaches were reviewed. Although studies showed exercise-induced cognitive improvements or maintenance, most of these studies fail to capture the dynamic nature of the change and interplay of physical (PP) and cognitive (COG) performance.

Interpretation:Using a sophisticated hierarchical Bayesian continuous-time dynamic modelling approach, a fully connected state variable model was specified. PP is dynamically linked to COG, i.e. higher PP predicted improved COG in subsequent sessions. This effect was rather short term, lasting for up to five days.

Future direction:Our results support exercise-induced effects on cognition. The cognitive system was still able to fluctuate and change favourably even in a sample with Alzheimer’s dementia. Further studies using dynamic modelling are necessary to replicate findings and examine other contributors to cognitive volatility in dementia.
Type 1 interferon auto-antibodies are elevated in patients with decompensated liver cirrhosis
Authors: Greville Gordon , Cremen Sinead , O’Neill Shauna , Azarian Sarah , Brady Gareth , McCormack William , Touzelet Olivier , Courtney David , Power Ultan , Dowling Paul , Gallagher Tom K , Bamford Connor GG , Robinson Mark W
Published: December 2022

Understanding the biological basis of clinical risk factors for severe COVID-19 is required to ensure at-risk patient populations receive appropriate clinical care. Patients with decompensated liver cirrhosis, in particular those classified as Childs-Pugh class B and C, are at increased risk of severe COVID-19 upon infection with SARS-CoV-2. The biological mechanisms underlying this are unknown. We hypothesised this may be due to changes in expression levels of intrinsic antiviral proteins within the serum as well as alterations in the innate immune response to SARS-CoV-2 infection. We identified significant alterations in the serum proteome of patients with more severe liver disease and an increased frequency of auto-antibodies capable of neutralising type I interferons. No difference in SARS-CoV-2 pseudoparticle infection or live SARS-CoV-2 virus infection was observed with serum from decompensated cirrhotic patients. Principal component analysis of the serum proteome identified two main clinical parameters associated with serum proteome changes – aetiology and MELD-Na score. Among patients with MELD-Na scores >20 we detected significant inhibition of IFN-α2b and IFN-α8 signalling but not IFN-β1a, mediated by auto-antibodies. Our results suggest pre-existing neutralising auto-antibodies targeting type I IFN may increase the likelihood of severe COVID-19 in chronic liver disease patients upon SARS-CoV-2 infection and may also be of relevance to other viral infections in this patient population.
Association between Fuchs Endothelial Corneal Dystrophy, Diabetes Mellitus and Multimorbidity
Authors: Nealon Cari L. , Halladay Christopher W. , Gorman Bryan R. , Simpson Piana , Roncone David P. , Canania Rachael L. , Anthony Scott A. , Sawicki Rogers Lea R. , Leber Jenna N. , Dougherty Jacquelyn M. , Bailey Jessica N. Cooke , Crawford Dana C. , Sullivan Jack M. , Galor Anat , Wu Wen-Chih , Greenberg Paul B. ,   the Million Veteran Program, Lass Jonathan H. , Iyengar Sudha K. , Peachey Neal S.
Published: December 2022

Purpose

To assess risk for demographic variables and other health conditions that are associated with Fuchs endothelial corneal dystrophy (FECD).

Methods

We developed a FECD case-control algorithm based on structured EHR data and accuracy confirmed by individual review of charts at three VA Medical Centers. This algorithm was applied to the Department of Veterans Affairs Million Veteran Program cohort from whom sex, genetic ancestry, comorbidities, diagnostic phecodes and laboratory values were extracted. Single and multiple variable logistic regression models were used to determine the association of these risk factors with FECD diagnosis.

Results

Being a FECD case was associated with female sex, European genetic ancestry, and a greater number of comorbidities. Of 1417 diagnostic phecodes evaluated, 213 had a significant association with FECD, falling in both ocular and non-ocular conditions, including diabetes mellitus (DM). Five of 69 laboratory values were associated with FECD, with the direction of change for four being consistent with DM. Insulin dependency and type 1 DM raised risk to a greater degree than type 2 DM, like other microvascular diabetic complications.

Conclusions

Female gender, European ancestry and multimorbidity increased FECD risk. Endocrine/metabolic clinic encounter codes as well as altered patterns of laboratory values support DM increasing FECD risk. Our results evoke a threshold model in which the FECD phenotype is intensified by DM and potentially other health conditions that alter corneal physiology. DM may modify FECD onset and encourage progression among susceptible individuals, suggesting that optimizing glucose control may be an effective preventative for FECD.
COVID-19db linkage maps of cell surface proteins and transcription factors in immune cells
Authors: Ramjattun Koushul , Ma Xiaojun , Gao Shou-Jiang , Singh Harinder , Osmanbeyoglu Hatice Ulku
Published: December 2022

The highly contagious SARS-CoV-2 and its associated disease (COVID-19) are a threat to global public health and economies. To develop effective treatments for COVID-19, we must understand the host cell types, cell states and regulators associated with infection and pathogenesis such as dysregulated transcription factors (TFs) and surface proteins, including signaling receptors. To link cell surface proteins with TFs, we recently developed SPaRTAN (Single-cell Proteomic and RNA-based Transcription factor Activity Network) by integrating parallel single-cell proteomic and transcriptomic data based on Cellular Indexing of Transcriptomes and Epitopes by sequencing (CITE-seq), which contains gene cis-regulatory information. We apply SPaRTAN to CITE-seq datasets from patients with varying degrees of COVID-19 severity and healthy controls to identify the associations between surface proteins and TFs in host immune cells. Here, we present COVID-19db of Immune Cell States (https://covid19db.streamlit.app/), a web server containing cell surface protein expression, SPaRTAN-inferred TF activities, and their associations with major host immune cell types. The data include four high-quality COVID-19 CITE-seq datasets with a toolset for user-friendly data analysis and visualization. We provide interactive surface protein and TF visualizations across major immune cell types for each dataset, allowing comparison between various patient severity groups for the discovery of potential therapeutic targets and diagnostic biomarkers.
Three assays for in-solution enrichment of ancient human DNA at more than a million SNPs
Authors: Rohland Nadin , Mallick Swapan , Mah Matthew , Maier Robert , Patterson Nick , Reich David
Published: December 2022

The strategy of in-solution enrichment for hundreds of thousands of single-nucleotide polymorphisms (SNPs) has been used to analyze >70% of individuals with genome-scale ancient DNA published to date. This approach makes it economical to study ancient samples with low proportions of human DNA and increases the rate of conversion of sampled remains into interpretable data. So far, nearly all such data have been generated using a set of bait sequences targeting about 1.24 million SNPs (the “1240k reagent”), but synthesis of the reagent has been cost-effective for only a few laboratories. In 2021, two companies, Daicel Arbor Biosciences and Twist Bioscience, made available assays that target the same core set of SNPs along with supplementary content. We test all three assays on a common set of 27 ancient DNA libraries and show that all three are effective at enriching many hundreds of thousands of SNPs. For all assays, one round of enrichment produces data that are as useful as two. In our testing, the “Twist Ancient DNA” assay produces the highest coverages, greatest uniformity on targeted positions, and almost no bias toward enriching one allele more than another relative to shotgun sequencing. We also identify hundreds of thousands of targeted SNPs for which there is minimal allelic bias when comparing 1240k data to either shotgun or Twist data. This facilitates coanalysis of the large data sets that have been generated using 1240k and Twist capture, as well as shotgun sequencing approaches.
Pursuing alignment of clients' and contractors' perceptions of client satisfaction in Saudi Arabian projects
Authors: Alshihre Fawaz , Chinyio Ezekiel , Nzekwe-Excel Chinny , Daniel Emmanuel I.
Published: December 2022

Purpose

The study explored the disparity between construction clients and contractors on what constitutes “client satisfaction”. Such disparity is important because it can lead to different conclusions and thus disagreement on the assessment of project success.

Design/methodology/approach

The philosophical stance was interpretivism, thus the qualitative methodology was adopted. Employing purposive sampling, 30 interviews with clients and another 30 interviews with contractors were conducted in Saudi Arabia. The data obtained were evaluated by thematic analysis.

Findings

The results indicate differences in the consensus ad idem (meeting of the minds) between clients and contractors in terms of both their perceptions and prioritisation of the attributes that underpin client satisfaction. For example, some contractors thought that using advanced technologies was very important for client satisfaction, whereas some clients preferred the contractors to be honest with them.

Research limitations/implications

The data collection was limited to Saudi Arabia and only the views of clients and contractors were studied, thereby limiting the generalisability of the findings.

Practical implications

The identification of the differing priorities of clients and contractors on client satisfaction provides an informed basis to make more concerted efforts to satisfy clients and minimise disputes on projects in Saudi Arabia.

Originality/value

The study contrasted the views of clients and contractors simultaneously on the subject matter of client satisfaction in relation to project success, and analysed this through the lens of consensus ad idem. The key influences on clients' satisfaction in Saudi Arabia are also presented.
Uncovering the antecedents and motivational determinants of job crafting
Authors: Masood Huda , Podolsky Mark , Budworth Marie-Helene , Karajovic Stefan
Published: December 2022

Purpose

The purpose of this mixed-methods study is to examine the motivational determinants and contextual antecedents of individual job crafting behaviors.

Design/methodology/approach

The current research uses the mixed-methods design to elucidate the relationship between career outcome expectations and different forms of job crafting through external regulation. In Study 1, surveys were collected and analyzed from 151 employees across occupations and ranks using purposeful sampling approach. In Study 2, interview data were thematically analyzed to add complementarity and completeness to the findings.

Findings

In Study 1 (n = 151), a direct relationship between career outcome expectations and different forms of job crafting was established. Mediation analysis indicated an indirect relationship between career outcome expectations and approach crafting through external-social regulation. The authors found support for the accentuating role of turnover intentions on career outcome expectations and external social and material regulations. In Study 2 (n = 25), a thematic analysis of semi-structured interviews confirmed that when employees experience unfulfilled career expectations, employees attempt to realign the work situations. Such expectations may be tied to various forms of work-related external regulations and may lead to job crafting behaviors. The individuals depicted these behaviors while experiencing turnover intentions.

Originality/value

The current study brings together literature from job design, motivation and careers to consider the role of career expectations and external regulation in predicting job crafting behaviors. Taken together, the findings unearth the cognitive and contextual antecedents of job crafting.
Intersectoral approaches: the key to mitigating psychosocial and health consequences of disasters and systemic risks
Authors: Gousse-Lessard Anne-Sophie , Gachon Philippe , Lessard Lily , Vermeulen Valérie , Boivin Maxime , Maltais Danielle , Landaverde Elsa , Généreux Mélissa , Motulsky Bernard , Le Beller Julien
Published: December 2022

Purpose

The current pandemic and ongoing climate risks highlight the limited capacity of various systems, including health and social ones, to respond to population-scale and long-term threats. Practices to reduce the impacts on the health and well-being of populations must evolve from a reactive mode to preventive, proactive and concerted actions beginning at individual and community levels. Experiences and lessons learned from the pandemic will help to better prevent and reduce the psychosocial impacts of floods, or other hydroclimatic risks, in a climate change context.

Design/methodology/approach

The present paper first describes the complexity and the challenges associated with climate change and systemic risks. It also presents some systemic frameworks of mental health determinants, and provides an overview of the different types of psychosocial impacts of disasters. Through various Quebec case studies and using lessons learned from past and recent flood-related events, recommendations are made on how to better integrate individual and community factors in disaster response.

Findings

Results highlight the fact that people who have been affected by the events are significantly more likely to have mental health problems than those not exposed to flooding. They further demonstrate the adverse and long-term effects of floods on psychological health, notably stemming from indirect stressors at the community and institutional levels. Different strategies are proposed from individual-centered to systemic approaches, in putting forward the advantages from intersectoral and multirisk researches and interventions.

Originality/value

The establishment of an intersectoral flood network, namely the InterSectoral Flood Network of Québec (RIISQ), is presented as an interesting avenue to foster interdisciplinary collaboration and a systemic view of flood risks. Intersectoral work is proving to be a major issue in the management of systemic risks, and should concern communities, health and mental health professionals, and the various levels of governance. As climate change is called upon to lead to more and more systemic risks, close collaboration between all the areas concerned with the management of the factors of vulnerability and exposure of populations will be necessary to respond effectively to damages and impacts (direct and indirect) linked to new meteorological and compound hazards. This means as well to better integrate the communication managers into the risk management team.
Penetrating or expanding: the dilemma at Raushangul atelier studio, Kazakhstan
Authors: Mirzaliyeva Sanam Sunnatullayevna , Chakraborty Kamalika , Biswas Samir , Berikkyzy Dina , Tleubek Dina
Published: December 2022

Learning outcomes

After the case discussion in class, the audience is expected to:▪ Apply the use of management tools in identifying core competencies in the sustenance and growth of a venture.▪ Evaluate the sustainability of the core competencies using relevant tools and frameworks.▪ Assess using relevant criteria whether firms should diversify or not?

Case overview/synopsis

The case highlights the experience and obstacles encountered by a Kazakh entrepreneur, Moldakhmetova, who is exploring her long-term business continuity choices. Moldakhmetova ran her own tailoring business, which focused mostly on designing and creating national costumes worn at weddings and concerts. However, she was confronted with a number of obstacles pertaining to the long-term viability of her enterprise, especially with the commencement of the Covid pandemic. The volume of national costume sales was affected by the declaration of the lockdown and restrictions on concerts and celebrations. As the lockdown lifted and orders started to pour in, Moldakhmetova pondered the long-term viability of her business venture. In addition, the availability of inexpensive ready-made Moldakhemetova costumes in Almaty (one of the major cities) made her question whether or not they were her competitors. Thus, Atlas contemplated many choices as potential answers to the question of the enterprise's long-term viability. She was currently faced with the dilemma of selecting the most feasible solution from the possibilities she had identified.

Complexity academic level

BBA and MBA programs.

Supplementary materials

Teaching notes are available for educators only. Students are recommended to watch the video about the Kazakh folk style of clothing at: https://www.youtube.com/watch?v=ddVzrUeSn64 (25 minutes). Students can watch the following video about specific embroidery styles applied in Kazakh national clothing at: https://www.youtube.com/watch?v=wB0XJE09N9w (first 10 minutes of video). The case could be used in online teaching via the Padlet platform.

Subject Code

CSS: 11: Strategy.
Beardo’s strategic partnership with Marico
Authors: Saxena Meetali , Mahajan Harleen
Published: December 2022

Learning outcomes

• The students will be able to compare various perspectives and concepts of strategic alliance as a tool of corporate expansion.

• The students will be able to identify the trade-offs between financial and non-financial gains and losses for corporate expansion.

• The students will be able to identify strategic partnership as a better alternative in comparison to acquisition and vice versa according to the different situations being faced by the companies.

• The students will be able to identify different approaches for brand building.

Case overview/synopsis

Shah and Valani, owners of Zed Lifestyle Pvt Ltd which owned Beardo, had to decide whether they should accept the offer of a strategic partnership with Marico Industries, a fast-moving consumer goods company (FMCG) in the global beauty and wellness space. Marico nurtured leading brands across categories of hair care, skin care, edible oils, healthy foods, hygiene, male grooming and fabric care. The decision was not easy as Marico was a leader in the FMCG segment in India and had a strong brand presence in both online and offline distribution channels. Beardo, on the other hand, had its presence marked mostly on the online channel with a hundred offline salon outlets. Partnering with Marico would ensure access to the massive distribution channel owned by Marico but, on the other hand, would lead to possible loss of independence and an early exit from their business. They were not prepared to let go of their ownership as there was no clarity on what would happen if the projected growth figures were not met. There were many other questions too that crossed their minds which had to be answered before they decided on a yes or a no.

The case highlighted the decision dilemma faced by the brand owners, the market scenario, competitive landscape and the situational facts so as to help the students critically analyse the decision situation and develop decision-making competencies by evaluating the possible course of actions and their possible outcomes.

Complexity academic level

Corporate-level strategies.

Supplementary materials

Teaching notes are available for educators only.

Subject code

CSS 11: Strategy.