bluuebunny/crossref_metadata_2025 huggingface dataset:
Severe blistering eruptions induced by immune checkpoint inhibitors: a multicentre international study of 32 cases
Authors: Ingen-Housz-Oro Saskia , Milpied Brigitte , Badrignans Marine , Carrera Cristina , Elshot Yannick S. , Bensaid Benoit , Segura Sonia , Apalla Zoé , Markova Alina , Staumont-Sallé Delphine , Marti-Marti Ignasi , Giavedoni Priscila , Chua Ser-Ling , Darrigade Anne-Sophie , Dezoteux Frédéric , Starace Michela , Torre Ana Clara , Riganti Julia , de Prost Nicolas , Lebrun-Vignes Bénédicte , Bauvin Olivia , Walsh Sarah , Ortonne Nicolas , French Lars E. , Sibaud Vincent
Published: April 2022

Among dermatologic adverse events induced by immune checkpoint inhibitors (ICI), bullous life-threatening reactions are rare. To better define the clinical and histological features, treatment, and prognosis of ICI-related severe blistering cutaneous eruptions. This retrospective case series was conducted between 2014/05/15 and 2021/04/15 by the dermatology departments of four international registries involved in drug reactions. Inclusion criteria were age ≥18 years old, skin eruption with blisters with detachment covering ≥1% body surface area and at least one mucous membrane involved, available pictures, and ICI as suspect drug. Autoimmune bullous disorders were excluded. Each participant medical team gave his own diagnosis conclusion: epidermal necrolysis (EN), severe lichenoid dermatosis (LD), or unclassified dermatosis (UD). After a standardized review of pictures, cases were reclassified by four experts in EN or LD/UD. Skin biopsies were blindly reviewed. Thirty-two patients were included. Median time to onset was 52 days (3–420 days). Cases were originally diagnosed as EN in 21 cases and LD/UD in 11 cases. After review by experts, 10/21 EN were reclassified as LD/UD. The following manifestations were more frequent or severe in EN: fever, purpuric macules, blisters, ocular involvement, and maximal detachment. Most patients were treated with topical with or without systemic corticosteroids. Eight patients (25%) died in the acute phase. The culprit ICI was not resumed in 92% of cases. In three patients, another ICI was given with a good tolerance. Histology did not reveal significant differences between groups. Severe blistering cutaneous drug reactions induced by ICI are often overdiagnosed as EN. Consensus for management is pending.
Associations between e-cigarette use and e-cigarette flavors with cigarette smoking quit attempts and quit success: Evidence from a US large, nationally representative 2018-2019 survey
Authors: Mok Yoonseo , Jeon Jihyoun , Levy David T , Meza Rafael
Published: April 2022

Objectives

While many studies have examined the association between e-cigarette use and smoking cessation, fewer have considered the impact of e-cigarette flavors on cessation outcomes. This study extends previous studies by examining the effects of e-cigarette use and e-cigarette flavors on smoking quit attempts and quit success.

Methods

We used data from the 2018-2019 Tobacco Use Supplement-Current Population Survey (TUS-CPS) survey. Multivariate logistic regression analyses were used to investigate the associations between e-cigarette and flavor use with quit attempts among individuals who smoked 12 months ago and quit success. Two current e-cigarette use definitions were considered; currently use every day or some days vs. 20+ days in the past 30-days.

Results

Compared to those not using e-cigarettes, current everyday or someday e-cigarette use with all non-tobacco flavors had an adjusted odds ratio (AOR) of 2.9 (95% CI: 2.4-3.5) for quit attempts and 1.7 (95% CI: 1.3-2.2) for quit success. 20+ days e-cigarette use with flavors had stronger associations with quit attempts (AOR=4.2, 95% CI: 3.1-5.5) and quit success (AOR=4.0, 95% CI: 2.9-5.4). E-cigarette users with non-tobacco flavors were more likely to succeed in quitting compared to those exclusively using non-flavored or tobacco-flavored e-cigarettes. Menthol/mint flavor users had slightly higher odds of quit attempts and success than users of other non-tobacco flavors.

Conclusions

E-cigarette use is positively associated with both making a smoking quit attempt and quit success. Those using flavored e-cigarettes, particularly menthol/mint, are more likely to quit successfully.

Implications

E-cigarette use is positively associated with both making a quit attempt and quit success, and those using flavored e-cigarettes are more likely to successfully quit smoking, with no statistically significant differences between use of menthol or mint flavored e-cigarettes versus use of other non-tobacco flavored products. This suggests that the potential for e-cigarettes to help people who currently smoke quit could be maintained with the availability of menthol or mint flavored e-cigarettes, even if other non-tobacco flavored products, which are associated with e-cigarette use among youth, were removed from the market.
Diagnostic Accuracy of Simple Postoperative AKI Risk (SPARK) Classification and General Surgery AKI (GS AKI) Index in Predicting Postoperative Acute Kidney Injury among Patients Undergoing Non-Cardiac Surgery at a Tertiary Hospital in the Philippines
Authors: Te Michelle Wendy , Robles Demi Sarah , Boado Carlo Antonio , Naidas Oscar
Published: April 2022

Background

Postoperative AKI is a significant postoperative complication. Clinical risk prediction models are lacking for patients undergoing non-cardiac surgery. SPARK Classification and GS AKI Index are tools that have shown fair discriminative ability to predict post-operative AKI in non-cardiac surgery and have external validation in their original cohorts. There is no study that compares the diagnostic accuracy of both tools.

Objectives

This study aims to compare the diagnostic accuracy of SPARK Classification vs GS-AKI Risk Index in predicting post-operative AKI among patients who will undergo non-cardiac surgery at a tertiary hospital in the Philippines.

Methods

This is a cross-sectional study, including adult patients who underwent non-cardiac surgeries from January 2019 to July 2021. The individual risk of post-operative AKI for both models were determined. Descriptive data was described using t-test and logistic regression. Measures of accuracy were described using sensitivity, specificity, positive and negative predictive value, positive and negative likelihood ratio, and discriminative ability using concordance (c) statistic.

Results

Of the 340 patients in this study, 77 (22.65%) developed post-operative AKI and 24 (7.06%) developed critical AKI. Based on demographic data, older age, pre-existing renal disease, longer duration of surgery, anemia, hypoalbuminemia, and hyponatremia were associated with higher incidence of post-operative AKI. SPARK had a sensitivity ranging from 17-43% and specificity ranging from 58-93% for Class B to C. GS AKI had a sensitivity ranging from 10-26% and specificity ranging from 61-97% for Class I to V. SPARK had a discriminative power (c statistic) ranging from 0.46 to 0.61 while GS AKI had a discriminative power ranging from 0.41 to 0.54.

Conclusion

Based on this study, there is an association between higher risk classification in both SPARK and GS AKI and postoperative AKI. However, both clinical prediction models demonstrate poor discriminative power to predict post-operative AKI.
Toxicity of extracellular alpha-synuclein is independent of intracellular alpha-synuclein
Authors: Dening Yanina , Straßl Theresa , Ruf Viktoria , Dirscherl Petra , Chovsepian Alexandra , Stievenard Alicia , Khairnar Amit , Schmidt Felix , Giesert Florian , Herms Jochen , Levin Johannes , Dieterich Marianne , Falkai Peter , Weisenhorn Daniela Vogt , Wurst Wolfgang , Giese Armin , Pan-Montojo Francisco
Published: April 2022

Parkinson′s disease (PD) pathology progresses throughout the nervous system affecting numerous neuronal structures. It has been postulated that the progression of the pathology is based on a prion-like disease mechanism partly due to the seeding effect of endocytosed alpha-synuclein (ASYN) on the endogenous ASYN. The appearance of the pathology in dopaminergic neurons leads to neuronal cell death and motor symptoms. However, the effect on other neuronal structures is more inconsistent, leading to a higher variability in the prevalence of non-motor symptoms. Thus, the sensitivity to the pathology seems to vary among neuronal subtypes. Here, we analyzed the role of endogenous ASYN in the progression of PD-like pathology and the effect of monomeric and oligomeric ASYN as well as paraquat and rotenone on primary enteric, dopaminergic and cortical neurons from wild-type mice. Our results showed that pathology progression did not occur in the absence of endogenous ASYN and that dopaminergic neurons were more sensitive to ASYN and rotenone when compared to all other neuronal subtypes. Remarkably, the toxic effect of ASYN was independent of the presence of endogenous ASYN and directly related to the disturbance of the mitochondrial membrane potential. Thus, we suggest that the interaction between ASYN and mitochondria plays an important role in the toxicity of trans-synaptically transported ASYN and in the progression of PD pathology. These results question the prion-disease hypothesis and propose that endocytosed ASYN impairs the host′s mitochondrial function thereby also contributing to PD-pathology progression.
Transmission of SARS-CoV-2 in standardised First Few X cases and household transmission investigations: a systematic review and meta-analysis
Authors: Lewis Hannah C , Marcato Adrian J , Meagher Niamh , Valenciano Marta , Villanueva-Cabezas Juan-Pablo , Spirkoska Violeta , Fielding James E , Karahalios Amalia , Subissi Lorenzo , Nardone Anthony , Cheng Brianna , Rajatonirina Soatiana , Okeibunor Joseph , Aly Eman A , Barakat Amal , Jorgensen Pernille , Azim Tasnim , Wijesinghe Pushpa Ranjan , Le Linh-Vi , Rodriguez Angel , Vicari Andrea , Van Kerkhove Maria , McVernon Jodie , Pebody Richard , Price David J , Bergeri Isabel ,   the Unity Studies Collaborator Group
Published: April 2022

We aimed to estimate the household secondary infection attack rate (hSAR) of SARS-CoV-2 in investigations aligned with the WHO Unity Studies Household Transmission Investigations (HHTI) protocol. We conducted a systematic review and meta-analysis according to PRISMA 2020 guidelines.

We searched Medline, Embase, Web of Science, Scopus and medRxiv/bioRxiv for ‘Unity-aligned’ First Few X cases (FFX) and HHTIs published between 1 December 2019 and 26 July 2021. Standardised early results were shared by WHO Unity Studies collaborators (to 1 October 2021). We used a bespoke tool to assess investigation methodological quality. Values for hSAR and 95% confidence intervals (CIs) were extracted or calculated from crude data. Heterogeneity was assessed by visually inspecting overlap of CIs on forest plots and quantified in meta-analyses.

Of 9988 records retrieved, 80 articles (64 from databases; 16 provided by Unity Studies collaborators) were retained in the systematic review and 62 were included in the primary meta-analysis. hSAR point estimates ranged from 2%–90% (95% prediction interval: 3%–71%; I2=99.7%); I2 values remained >99% in subgroup analyses, indicating high, unexplained heterogeneity and leading to a decision not to report pooled hSAR estimates.

FFX and HHTI remain critical epidemiological tools for early and ongoing characterisation of novel infectious pathogens. The large, unexplained variance in hSAR estimates emphasises the need to further support standardisation in planning, conduct and analysis, and for clear and comprehensive reporting of FFX and HHTIs in time and place, to guide evidence-based pandemic preparedness and response efforts for SARS-CoV-2, influenza and future novel respiratory viruses.
Inferring the true number of SARS-CoV-2 infections in Japan
Authors: McKenzie Lauren , Shoukat Affan , Wong Kai On , Itahashi Koju , Yasuda Eiji , Demarsh Alex , Khan Kamran
Published: April 2022

Introduction

In Japan, as of December 31, 2021, more than 1.73 million laboratory-confirmed cases have been reported. However, the actual number of infections is likely to be under-ascertained due to the epidemiological characteristics such as mild and subclinical infections and limited testing availability in the early days of the pandemic. In this study, we infer the true number of infections in Japan between January 16, 2020, and December 31, 2021, using a statistical modelling framework that combines data on reported cases and fatalities.

Methods

We used reported daily COVID-19 deaths stratified into 8 distinct age-groups and age-specific infection fatality ratios (IFR) to impute the true number of infections. Estimates of IFR were informed from published studies as well seroprevalence studies conducted in Japan. To account for the uncertainty in IFR estimates, we sampled values from relevant distributions.

Results

We estimated that as of December 31, 2021, 2.90 million (CrI: 1.77 to 4.27 million) people had been infected in Japan, which is 1.68 times higher than the 1.73 million reported cases. Our meta-analysis confirmed that these findings were consistent with the intermittent seroprevalence studies conducted in Japan.

Conclusions

We have estimated that a substantial number of COVID-19 infections in the country were unreported, particularly in adults. Our approach provides a more realistic assessment of the true underlying burden of COVID-19. The results of this study can be used as fundamental components to strengthen population health control and surveillance measures.
Viability of AMURA biomarkers from single-shell diffusion MRI in Migraine Clinical Studies
Authors: Martín-Martín Carmen , Planchuelo-Gómez Álvaro , Guerrero Ángel L. , García-Azorín David , Tristán-Vega Antonio , de Luis García Rodrigo , Aja-Fernández Santiago
Published: April 2022

Diffusion Tensor Imaging (DTI) is the most employed method to assess white matter properties using quantitative parameters derived from diffusion MRI, but it presents known limitations that restricts the evaluation of complex structures. The objective of this study was the assessment of complementary diffusion measures extracted with a novel approach, Apparent Measures Using Reduced Acquisitions (AMURA), in comparison with DTI in clinical studies. Fifty healthy controls, 51 episodic migraine and 56 chronic migraine patients underwent single-shell diffusion MRI. Three DTI-based and eight AMURA-based parameters were compared between groups with tract-based spatial statistics. On the other hand, following a region-based analysis, the measures were assessed for multiple subsamples with diverse reduced sample sizes and their stability was evaluated with the coefficient of quartile variation. Compared to DTI, statistically significant differences in additional regions and group comparisons were found with AMURA-based measures. Additionally, some AMURA-based measures showed a remarkable discriminative power for quite reduced sample size and, simultaneously, lower stability (higher coefficient of quartile variation) than DTI-based measures. These findings suggest that AMURA presents favorable characteristics to identify differences of specific microstructural properties between clinical groups in regions with complex fiber architecture and lower dependency on the sample size or assessing technique than DTI.
Near-neutral pH increased n-caprylate production in a microbiome with product inhibition of methanogenesis
Authors: Palomo-Briones Rodolfo , Xu Jiajie , Spirito Catherine M. , Usack Joseph G. , Trondsen Lauren H. , Guzman Juan J. L. , Angenent Largus T.
Published: April 2022

The pH is a critical parameter in chain-elongating bioreactors, affecting: (1) the concentration of inhibitory undissociated carboxylic acids, which in turn affects the efficiency of product extraction; (2) the thermodynamics; and (3) the kinetics. Here, we examined the effect of five different pH levels (5.5 to 7.0) on n-caprylate (C8) production using an anaerobic sequencing batch reactor (ASBR) with continuous membrane-based liquid-liquid extraction (pertraction). We found that the product spectrum was directed by pH: mildly acidic pH (5-6) led to n-caproate (C6) production, while near-neutral and neutral pH (6.75-7) favored n-caprylate production. In particular, the pH of 6.75 led to the maximum values of volumetric n-caprylate production rate (75.6 ± 0.6 mmol C L−1 d−1; 0.06 g L−1 d−1) and n-caprylate concentration in the fermentation broth (420 mM C; 7.57 g L−1). Given that methane production remained low at near-neutral and neutral pH, we theorized that the high concentration of undissociated n-caprylic acid (5.71 mM C) inhibited methanogenesis. We then demonstrated such an inhibitory effect at neutral pH in: (1) microcosm experiments; and (2) the continuous bioreactor by adding methanogenic sludge. Furthermore, 16S rRNA gene sequencing analysis revealed that near-neutral and neutral pH led to more diverse microbial communities than at mildly-acidic pH. For the first time, we report predominant n-caprylate production in a microbiome at near-neutral and neutral pH conditions where methanogenesis was controlled by the inhibitory effects of undissociated n-caprylic acid. At the same time, extraction of this species occurred even at near-neutral and neutral pH.
Modulation of Receptor-like Trans-Membrane Kinase 1 nuclear localisation by DA1 peptidases in Arabidopsis
Authors: Gu Benguo , Dong Hui , Smith Caroline , Bevan Michael W.
Published: April 2022

The activities of proteins can depend on their cleavage, which influences their cellular location, stability and functions. The cleavage of intracellular domains of Receptor -Like Kinases (RLK) has an important functional role in the transduction of signals from the cell surface to the nucleus in many organisms. However, the peptidases that catalyse protein cleavage during signal transduction remain poorly understood despite their crucial roles in diverse signalling processes. Here we report in the flowering plant Arabidopsis thaliana that members of the DA1 family of ubiquitin-regulated Zn metallopeptidases cleave the cytoplasmic kinase domain of TransMembrane Kinase 1 (TMK1), releasing it for nuclear localisation where it represses auxin-responsive cell growth during apical hook formation by phosphorylation and stabilisation of the transcriptional repressors IAA32 and IAA34. Mutations in DA1 family members exhibited reduced apical hook formation, and DA1 family mediated cleavage of TMK1 was promoted by auxin treatment. Expression of the DA1 family - generated intracellular kinase domain of TMK1 by an auxin-responsive promoter fully restored apical hook formation in a tmk1 mutant, establishing the function of DA1 family peptidase activities in TMK1-mediated differential cell growth and apical hook formation. DA1 family peptidase activity therefore modulates TMK1 kinase activity between a membrane location where it stimulates acid cell growth and initiates an auxin-dependent kinase cascade controlling cell proliferation in lateral roots and a nuclear localisation where it represses auxin mediated gene expression and growth.
Simultaneous adjustments of major mitochondrial pathways through redox regulation of dihydrolipoamide dehydrogenase (mtLPD1)
Authors: Timm Stefan , Klaas Nicole , Niemann Janice , Jahnke Kathrin , Alseekh Saleh , Zhang Youjun , Souza Paulo V.L. , Hou Liang-Yu , Geigenberger Peter , Daloso Danilo M. , Fernie Alisdair R. , Hagemann Martin
Published: April 2022

Thioredoxins (TRX) are pivotal for the redox regulation of enzyme activities to adjust metabolic fluxes towards environmental changes. Previous reports demonstrated TRXo1andh2impact on mitochondrial metabolism including photorespiration and the tricarboxylic acid (TCA) cycle. Here, we aimed to unravel potential specificities between regulation modes of both TRXs, especially under conditions with short-term changes in photorespiration. Therefore, short-term metabolite responses of singleTRXmutants were analyzed after exposure to altered CO2/O2ratios during darkness and illumination. This approach was complemented by comprehensive characterization of multiple Arabidopsis mutants lacking either one or bothTRXin the wild-type Arabidopsis or the glycine decarboxylase (GDC) T-protein knock down line (gldt1). The results provided evidence for additive effects of combined TRXo1andh2deficiency to suppress growth, photosynthesis and mitochondrial metabolism. Quantification of pyrimidine nucleotides in conjunction with metabolite and13C-labelling approaches revealed a rather uniform impact on mitochondrial dihydrolipoamide dehydrogenase (mtLPD1) dependent pathways. Biochemical analysis of recombinant mtLPD1 demonstrated its inhibition by NADH, pointing at an additional measure to fine-tune it’sin vivoactivity. Collectively, we propose that TRXo1andh2contribute to the communication of altered subcellular redox-states through direct and indirect regulation of mtLPD1. This regulation module might represent a common intercept for simultaneous adjustments in the operation of photorespiration, the TCA-cycle and the degradation of branched chain amino acids.

One-sentence summary

Redox regulation of mitochondrial dihydrolipoamide dehydrogenase (mtLPD1) simultaneously modulates photorespiration, the tricarboxylic acid (TCA)-cycle and branched chain amino acid (BCAA) degradation in response to rapid environmental changes.
Melanization is an important antifungal defense mechanism in Galleria mellonella hosts
Authors: Smith Daniel F. Q. , Dragotakes Quigly , Kulkarni Madhura , Hardwick J. Marie , Casadevall Arturo
Published: April 2022

A key component of insect immunity is melanin encapsulation of microbes. Melanization is also a part of an immune process known as nodulation, which occurs when insect hemocytes surround microbes and produce melanin. Insect nodules are analogous to mammalian immune granulomas. Melanin is believed to kill microbes through the production of toxic intermediates and oxidative damage. However, it is unclear to what extent immune melanin is directly fungicidal during infections of insect hosts. We reported previously that C. neoformans cells are encapsulated with host-derived melanin within hemocyte nodules. Here we report an association between melanin-based immune responses by Galleria mellonella wax moth larvae and fungal cell death of C. neoformans during infection. To monitor melanization in situ, we applied a tissue-clearing technique to G. mellonella larvae, revealing that nodulation occurs throughout the organism. Further, we developed a protocol for time-lapse microscopy of extracted hemolymph following exposure to fungal cells, which allowed us to visualize and quantify the kinetics of the melanin-based immune response. Using this technique, we found evidence that cryptococcal melanins and laccase enhance immune melanization in hemolymph. We used these techniques to also study the fungal pathogen Candida albicans infections of G. mellonella. We find that the yeast form of C. albicans was the primary targets of host melanization, while filamentous structures were melanin-evasive. Approximately 23% of melanin-encapsulated C. albicans yeast survive and break through the encapsulation. Overall, our results provide direct evidence that the melanization reaction functions as a direct antifungal mechanism in insect hosts.
A brain-inspired object-based attention network for multi-object recognition and visual reasoning
Authors: Adeli Hossein , Ahn Seoyoung , Zelinsky Gregory J.
Published: April 2022

The visual system uses sequences of selective glimpses to objects to support goal-directed behavior, but how is this attention control learned? Here we present an encoder-decoder model inspired by the interacting bottom-up and top-down visual pathways making up the recognitionattention system in the brain. At every iteration, a new glimpse is taken from the image and is processed through the “what” encoder, a hierarchy of feedforward, recurrent, and capsule layers, to obtain an object-centric (object-file) representation. This representation feeds to the “where” decoder, where the evolving recurrent representation provides top-down attentional modulation to plan subsequent glimpses and impact routing in the encoder. We demonstrate how the attention mechanism significantly improves the accuracy of classifying highly overlapping digits. In a visual reasoning task requiring comparison of two objects, our model achieves near-perfect accuracy and significantly outperforms larger models in generalizing to unseen stimuli. Our work demonstrates the benefits of object-based attention mechanisms taking sequential glimpses of objects.
Transcriptional reprogramming from innate immune functions to a pro-thrombotic signature upon SARS-CoV-2 sensing by monocytes in COVID-19
Authors: Maher Allison K. , Burnham Katie L. , Jones Emma , Baillon Laury , Selck Claudia , Giang Nicolas , Argüello Rafael , Short Charlotte-Eve , Quinlan Rachael , Barclay Wendy S. , Cooper Nichola , Taylor Graham P. , Davenport Emma E. , Dominguez-Villar Margarita
Published: April 2022

Alterations in the myeloid immune compartment have been observed in COVID-19, but the specific mechanisms underlying these impairments are not completely understood. Here we examined the functionality of classical CD14+monocytes as a main myeloid cell component in well-defined cohorts of patients with mild and moderate COVID-19 during the acute phase of infection and compared them to that of healthy individuals. We found thatex vivoisolated CD14+monocytes from mild and moderate COVID-19 patients display specific patterns of costimulatory and inhibitory receptors that clearly distinguish them from healthy monocytes, as well as altered expression of histone marks and a dysfunctional metabolic profile. Decreased NFκB activation in COVID-19 monocytesex vivois accompanied by an intact type I IFN antiviral response. Subsequent pathogen sensingex vivoled to a state of functional unresponsiveness characterized by a defect in pro-inflammatory cytokine expression, NFκB-driven cytokine responses and defective type I IFN response in moderate COVID-19 monocytes. Transcriptionally, COVID-19 monocytes switched their gene expression signature from canonical innate immune functions to a pro-thrombotic phenotype characterized by increased expression of pathways involved in hemostasis and immunothrombosis. In response to SARS-CoV-2 or other viral or bacterial components, monocytes displayed defects in the epigenetic remodelling and metabolic reprogramming that usually occurs upon pathogen sensing in innate immune cells. These results provide a potential mechanism by which innate immune dysfunction in COVID-19 may contribute to disease pathology.
Dominance vs. epistasis: the biophysical origins and plasticity of genetic interactions within and between alleles
Authors: Xie Xuan , Lehner Ben , Li Xianghua
Published: April 2022

A central challenge in genetics, evolutionary biology and biotechnology is to understand and predict how mutations combine to alter phenotypes, including molecular activities, fitness and disease. In diploid organisms, two mutations in the same gene can either combine on the same chromosome or on different chromosomes, with interactions between the mutations quantified as epistasis and dominance, respectively. However, a direct comparison of the extent, sign and stability of interactions within and between alleles is lacking. Here we show that, even in the simplest biophysical systems, interactions between mutations are frequent, context-dependent and different when variants are combined within and between alleles. Whereas protein folding alone generates epistasis, the addition of a single molecular interaction is sufficient to cause dominance. Epistasis and dominance interactions change quantitatively, qualitatively and differently as a system becomes more complicated or the conditions change. Altering the concentration of a ligand can, for example, switch an allele from dominant to recessive. Our results show that epistasis and dominance should be widely expected in even the simplest biological systems but also reinforce the view that they are plastic system properties and so a formidable challenge to predict. Accurate prediction of epistasis and dominance will require either detailed mechanistic understanding and experimental parameterization or brute-force measurement and learning.
SARS-CoV-2 spike S375F mutation characterizes the Omicron BA.1 variant
Authors: Kimura Izumi , Yamasoba Daichi , Nasser Hesham , Zahradnik Jiri , Kosugi Yusuke , Wu Jiaqi , Nagata Kayoko , Uriu Keiya , Tanaka Yuri L , Ito Jumpei , Shimizu Ryo , Tan Toong Seng , Butlertanaka Erika P , Asakura Hiroyuki , Sadamasu Kenji , Yoshimura Kazuhisa , Ueno Takamasa , Takaori-Kondo Akifumi , Schreiber Gideon ,   The Genotype to Phenotype Japan (G2P-Japan) Consortium, Toyoda Mako , Shirakawa Kotaro , Irie Takashi , Saito Akatsuki , Nakagawa So , Ikeda Terumasa , Sato Kei
Published: April 2022

Recent studies have revealed the unique virological characteristics of Omicron, the newest SARS-CoV-2 variant of concern, such as pronounced resistance to vaccine-induced neutralizing antibodies, less efficient cleavage of the spike protein, and poor fusogenicity. However, it remains unclear which mutation(s) in the spike protein determine the virological characteristics of Omicron. Here, we show that the representative characteristics of the Omicron spike are determined by its receptor-binding domain. Interestingly, the molecular phylogenetic analysis revealed that the acquisition of the spike S375F mutation was closely associated with the explosive spread of Omicron in the human population. We further elucidate that the F375 residue forms an interprotomer pi-pi interaction with the H505 residue in another protomer in the spike trimer, which confers the attenuated spike cleavage efficiency and fusogenicity of Omicron. Our data shed light on the evolutionary events underlying Omicron emergence at the molecular level.

Highlights

Omicron spike receptor binding domain determines virological characteristics

Spike S375F mutation results in the poor spike cleavage and fusogenicity in Omicron

Acquisition of the spike S375F mutation triggered the explosive spread of Omicron

F375-H505-mediated π-π interaction in the spike determines the phenotype of Omicron
Gain-of-function genetic screens in human cells identify SLC transporters overcoming environmental nutrient restrictions
Authors: Rebsamen Manuele , Girardi Enrico , Sedlyarov Vitaly , Scorzoni Stefania , Papakostas Konstantinos , Vollert Manuela , Konecka Justyna , Guertl Bettina , Klavins Kristaps , Wiedmer Tabea , Superti-Furga Giulio
Published: April 2022

Solute carrier (SLC) transporters control fluxes of nutrients and metabolites across membranes and thereby represent a critical interface between the microenvironment and cellular and subcellular metabolism. Because of substantial functional overlap, the interplay and relative contributions of members of this family in response to environmental stresses remain poorly elucidated. In order to infer functional relationships between SLCs and metabolites, we developed a strategy to identify human SLCs able to sustain cell viability and proliferation under growth-limiting concentrations of essential nutrients. One-by-one depletion of 13 amino acids required for cell proliferation enabled gain-of-function genetic screens using a SLC-focused CRISPR/Cas9-based transcriptional activation approach to uncover transporters relieving cells from the growth-limiting metabolic bottleneck. We identified the cationic amino acid transporter SLC7A3 as a gene that, when upregulated, overcame low availability of arginine and lysine by increasing their uptake. SLC7A5 (LAT1), on the other hand, was able to sustain cellular fitness upon deprivation of several neutral amino acids. A genome-wide screen identified SLC7A3 as the single main gene product able to rescue cell survival in the limiting arginine conditions tested, demonstrating the potentially decisive role of transporters in overcoming nutrient limitations. Moreover, we identified metabolic compensation mediated by the glutamate/aspartate transporters SLC1A2 and SLC1A3 under glutamine-limiting conditions. Overall, this gain-of-function approach using human cells led to the definition of functional transporter-nutrient relationships and revealed that upregulation of transport activity may be sufficient to overcome environmental metabolic restrictions.
Saving the Devils is in the details: Tasmanian Devil facial tumor disease can be eliminated with interventions
Authors: Drawert Brian , Matthew Sean , Powell Megan , Rumsey Bryan
Published: April 2022

Abstract

Tasmanian Devils facial tumor disease is severely impacting the population of this wild animal. We developed a computational model of the population of Tasmanian Devils, and the change induced by DFTD. We use this model to test possible intervention strategies Tasmanian conservationists could do. We investigate bait drop vaccination programs, diseased animal removals programs, and evolution of natural immunity. We conclude that a combination of intervention strategies gives the most favorable outcome.

An additional goal of this paper is for reproducibility of our results. Our StochSS software platform features the ability to share and reproduce the computational notebooks that created all of the results in the paper. We endeavor that all readers should be able to reproduce our results with minimum effort.
Evolutionary adaptation of the folding pathway for secretability
Authors: Smets Dries , Tsirigotaki Alexandra , Smit Jochem H. , Krishnamurthy Srinath , Portaliou Athina G. , Vorobieva Anastassia , Vranken Wim , Karamanou Spyridoula , Economou Anastassios
Published: April 2022

Secretory preproteins of the Sec pathway bear signal peptides and are targeted post-translationally to cross the plasma membrane or ER through translocases. After translocation and signal peptide cleavage, mature domains fold to native states in the bacterial periplasm or after further trafficking. During cytoplasmic transit, mature domains must remain non-folded for translocase recognition and translocation. Here, we sought the structural basis for the delayed folding mechanism of mature domains and how this is regulated by signal peptides. To address this, we compared how evolution diversified a periplasmic peptidyl-prolyl isomerase PpiA mature domain from its structural twin cytoplasmic PpiB. Using global and local hydrogen deuterium exchange mass spectrometry we showed that PpiA is a slower folder. We defined at near-residue resolution hierarchical folding initiated by similar foldons in the twins, that displayed different order and rates. Folding is delayed in PpiA by less hydrophobic/bulky native contacts, frustrated residues and a critical β -turn in the early folding region and by signal peptide-driven disorder, which disrupts foldon hierarchy. When selected PpiA residues and its signal peptide were grafted onto PpiB they converted it into a slow folder with enhancedin vivosecretion. These data reveal the structural basis of non-folding in a secretory protein, that allows its trafficking.
Genomic insights into present local adaptation and future climate change vulnerability of a keystone forest tree species in East Asian
Authors: Sang Yupeng , Long Zhiqin , Dan Xuming , Feng Jiajun , Shi Tingting , Jia Changfu , Zhang Xinxin , Lai Qiang , Yang Guanglei , Zhang Hongying , Xu Xiaoting , Liu Huanhuan , Jiang Yuanzhong , Ingvarsson Pär K. , Liu Jianquan , Mao Kangshan , Wang Jing
Published: April 2022

Rapid global climate change is posing a huge threat to biodiversity. Assessments of the adaptive capacity for most taxa is usually performed on the species as a whole, but fails to incorporate intraspecific adaptive variation that may play a fundamental role in buffering future shifting climates. Here we generate a chromosome-scale genome assembly forPopulus koreana, a pioneer and keystone tree species in East Asia temperate forests. We also obtain whole-genome sequences of 230 individuals collected from 24 natural populations. An integration of population genomics and environmental variables was performed to reveal the genomic basis of local adaptation to diverse climate variable. We identify a set of climate-associated single nucleotide polymorphisms (SNPs), insertions-deletions (Indels) and structural variations (SVs), in particular numerous adaptive non-coding variants distributed across the genome ofP. koreana. We incorporate these variants into an environmental modelling scheme to predict spatiotemporal responses ofP. koreanato future climate change. Our results highlight the insights that the integration of genomic and climate data can shed on the future evolutionary adaptive capacities of a species to changing environmental conditions.
Emergence and clonal expansion of Vibrio aestuarianus lineages pathogenic for oysters in Europe
Authors: Mesnil Aurélie , Jacquot Maude , Garcia Céline , Tourbiez Delphine , Canier Lydie , Bidois Audrey , Dégremont Lionel , Cheslett Deborah , Geary Michelle , Vetri Alessia , Roque Ana , Furones Dolors , Garden Alison , Orozova Petya , Arzul Isabelle , Sicard Mathieu , Charrière Guillaume , Destoumieux-Garzón Delphine , Travers Marie-Agnès
Published: April 2022

Crassostrea gigas oysters represent a significant global food source, with 4.7 million tons harvested per year. In 2001, the bacterium V. aesturianus francensis emerged as a pathogen that causes adult oyster mortality in France and Ireland. Its impact on oyster aquaculture has increased in Europe since its reemergence in 2012. To better understand the evolutionary mechanisms leading to the emergence and persistence over time of this pathogen, we conducted a survey of mollusk diseases through national reference laboratories (NRLs) across Europe. We analyzed 54 new genomes of V. aestuarianus (Va) isolated from multiple environmental compartments since 2001, in areas with and without bivalve mortalities. We used a combination of comparative genomics and population genetics approaches to show that Va francensis lineages have undergone clonal expansion in Europe, likely after a recent selective bottleneck. Low mutation and recombination rates may have selected particular virulent genotypes. Furthermore, we identified a specific cus-cop-containing island conferring copper resistance to Va francensis whose acquisition may have favored the emergence of pathogenic lineages adapted to oysters.
Financial strength of banking sector in Bangladesh: a CAMEL framework analysis
Authors: Afroj Farhana
Published: April 2022

Purpose

This paper investigates the financial strength of banks in Bangladesh and factors affecting the financial strength over the years 2010–2015 on 35 banks.

Design/methodology/approach

Additive value function with CAMEL rating (capital stength, asset quality, managerial efficiency, earning ability, liquidity) has been employed to calculate banks’ financial strength index (FSI). In the second stage, panel regression has been exercised to find out the determinants of banks’ financial strength.

Findings

Empirical finding exhibits that the Islamic banks of Bangladesh are financially stronger and outperform conventional and Islamic window banks with higher liquidity. In the ownership category, private banks have more financial strength with higher capital strength, asset quality, managerial efficiency and earning ability than public banks. Bank size, loan recovery, salary and banking sector development positively affect whereas the loan-asset negatively affect the bank’s financial strength in Bangladesh.

Research limitations/implications

This study has its limitations despite its importance. CAMELS is a more improved form than using CAMEL. But because of the data deficiency on “S” which represents sensitivity, it would not be possible to use CAMELS framework. Further researchers could incorporate this.

Practical implications

Government and banks should allow Islamic banks to enter the market on easy terms because of their outstanding performance in the existing market. In addition, banks should provide loans with consideration so that they cannot create credit risk. In addition, they should calculate composite financial strength annually to understand which components they need to work on.

Originality/value

This study extends the extant result on the composite FSI. It is hard to examine the financial strength of banks using only ratio value, which misleads most of the time. The study offers evidence on how the FSI provides more rigorous results and what are the factors contribute most to the financial strength of banks.
A qualitative study on how Danish landscape architectural firms understand and work with accessibility
Authors: Gramkow Marie Christoffersen , Merit Marcus Tang , Stigsdotter Ulrika Karlsson
Published: April 2022

Purpose

During the past decade, Danish policies and legislation have increasingly focused on accessibility, which, by virtue of adopting the UN Sustainable Development Goals, has spurred new demands for the expertise of Danish landscape architects. Surveys indicate as much as 27% of the Danish population have a physical disability. Therefore, landscape architectural firms play an important role in designing accessible, public and green spaces, which could reduce the number of people who experience disability in their everyday life arising from inaccessible designs. Despite this, peer-reviewed research has not attempted to qualitatively understand how landscape architects approach accessibility in their daily practice.

Design/methodology/approach

Based on a grounded theory analysis of 15 semi-structured qualitative interviews with randomly selected landscape architectural firms, this study aims to describe how landscape architectural firms approach and perceive accessibility.

Findings

The results of the study show a complex understanding of accessibility among practising landscape architects, with firms focusing on the role of Danish building regulations, the programming of accessibility and professional aesthetic dilemmas. Moreover, accessibility is perceived with some frustration as an element that takes valuable space from green areas due to clients' lack of willingness to provide resources for integrated solutions, landscape architects' own limited expertise and knowledge of integrated accessibility solutions and insufficient regulatory leeway.

Originality/value

As accessibility is a major element of the tasks within contemporary landscape architecture, graduates need additional training in accessibility, which, in turn, necessitates additional research into accessible design solutions.
Leader, context and CSR: evidence from Taiwan
Authors: Ling Ya-Hui
Published: April 2022

Purpose

This study examines the influence of context on Taiwanese senior managers' corporate social responsibility (CSR) decisions. The study seeks to identify the current profiles of managerial CSR perspectives and organizational CSR investments in Taiwan. In particular, whether a non-Friedman perspective is more prevalent than a Friedman perspective and whether community-related CSR is more prevalent than other CSR practices in Taiwan remain unclear. The study also seeks to identify the relationship between managers' CSR perspective profiles and organizational CSR investment profiles in Taiwan.

Design/methodology/approach

The sample was selected from the Taiwanese top companies list. Altogether, 150 valid responses from senior managers of 150 companies were returned.

Findings

The reported evidence shows that senior managers' Friedman/non-Friedman CSR perspective has a great influence in directing a firm's CSR decision in Taiwan. Managers holding the Friedman perspective are slightly more than those holding the non-Friedman CSR perspective, but both perspectives are popular. There is a tendency for firms to make either more or less investments in all CSR dimensions. A Friedman perspective tends to be associated with low CSR investments, and a non-Friedman perspective tends to be associated with high CSR investments.

Originality/value

A major contribution of this study is to offer a different perspective from the Western view regarding CSR implementation in a Chinese-dominant culture society. The study extends the upper echelon theory that managerial CSR perspectives can be a driver of a firm's CSR decision-making. The study also offers further evidence for the institutional theory that CSR is contextually dependent.
Jute for Life: reconciling the social and business goals through sustainable entrepreneurship
Authors: Tiwari Mitali , Nakra Amit
Published: April 2022

Learning outcomes

The case has practical value exhibiting forces creating sustainable livelihood at grassroots level and at the same time depicting how business and social goals can be reconciled through innovative mechanisms.

Case overview/synopsis

The case covers the journey of a social enterprise lead by a woman entrepreneur, run by women workers and providing livelihood to several rural women entrepreneurs through providing skill development training in making hand-made jute bags.

Complexity academic level

MBA and BBA

Supplementary materials

Teaching notes are available for educators only.

Subject code

CSS 3: Entrepreneurship
How to benefit from digital platform capabilities? Examining the role of knowledge bases and organisational routines updating
Authors: Liu Longjun , Fan Qing , Liu Ruhong , Zhang Guiqing , Wan Wenhai , Long Jing
Published: April 2022

Purpose

This study aims to explore whether digital platform capabilities (integration and reconstruction) affect technological innovation through knowledge bases in the dimensions of breadth and depth and the moderating role of organisational routines updating.

Design/methodology/approach

Hierarchical regression, mediation effect test macro and bootstrap were conducted to empirically analyse two waves of longitudinal survey data from 179 Chinese technology firms.

Findings

Results confirmed that knowledge bases (breadth and depth) mediated the effect of digital platform capabilities (integration and reconstruction) on technological innovation and that updating of organisational routines moderated the relationship between knowledge bases and technological innovation.

Practical implications

These findings offer guidance to firms that aim to achieve technological innovation and advantages, highlighting the importance of digital platform capabilities, knowledge bases and organisational routines updating.

Originality/value

Advancing from existing digital strategies and firm innovation literature, the authors provide a new perspective (knowledge bases) to respond to the information technology (IT) paradox and understand the role of digital platform capabilities in improving technological innovation.