bluuebunny/crossref_metadata_2025 huggingface dataset:
Evolutionary implications of recombination differences across diverging populations ofAnopheles
Authors: Nelson Joel T. , Cornejo Omar E. ,   Ag1000G Consortium
Published: February 2021

Recombination is one of the main evolutionary mechanisms responsible for changing the genomic architecture of populations; and in essence, it is the main mechanism by which novel combinations of alleles, haplotypes, are formed. A clear picture that has emerged across study systems is that recombination is highly variable, even among closely related species. However, it is only until very recently that we have started to understand how recombination variation between populations of the same species impact genetic diversity and divergence. Here, we used whole-genome sequence data to build fine-scale recombination maps for nine populations within two species ofAnopheles,Anopheles gambiaeandAnopheles coluzzii. The genome-wide recombination averages were on the same order of magnitude for all populations except one. Yet, we identified significant differences in fine-scale recombination rates among all population comparisons. We report that effective population sizes, and presence of a chromosomal inversion has major contribution to recombination rate variation along the genome and across populations. We identified over 400 highly variable recombination hotspots across all populations, where only 9.6% are shared between two or more populations. Additionally, our results are consistent with recombination hotspots contributing to both genetic diversity and absolute divergence (dxy) between populations and species ofAnopheles. However, we also show that recombination has a small impact on population genetic differentiation as estimated with FST. The minimal impact that recombination has on genetic differentiation across populations represents the first empirical evidence against recent theoretical work suggesting that variation in recombination along the genome can mask or impair our ability to detect signatures of selection. Our findings add new understanding to how recombination rates vary within species, and how this major evolutionary mechanism can maintain and contribute to genetic variation and divergence within a prominent malaria vector.
Discovery and Functional Characterization of Pro-growth Enhancers in Human Cancer Cells
Authors: Chen Poshen B. , Fiaux Patrick C. , Li Bin , Zhang Kai , Kubo Naoki , Jiang Shan , Hu Rong , Wu Sihan , Wang Mengchi , Wang Wei , McVicker Graham , Mischel Paul S. , Ren Bing
Published: February 2021

Precision medicine depends critically on developing treatment strategies that can selectively target cancer cells with minimal adverse effects. Identifying unique transcriptional regulators of oncogenic signaling, and targeting cancer-cell-specific enhancers that may be active only in specific tumor cell lineages, could provide the necessary high specificity, but a scarcity of functionally validated enhancers in cancer cells presents a significant hurdle to this strategy. We address this limitation by carrying out large-scale functional screens for pro-growth enhancers using highly multiplexed CRISPR-based perturbation and sequencing in multiple cancer cell lines. We used this strategy to identify 488 pro-growth enhancers in a colorectal cancer cell line and 22 functional enhancers for theMYCandMYBkey oncogenes in an additional nine cancer cell lines. The majority of pro-growth enhancers are accessible and presumably active only in cancer cells but not in normal tissues, and are enriched for elements associated with poor prognosis in colorectal cancer. We further identify master transcriptional regulators and demonstrate that the cancer pro-growth enhancers are modulated by lineage-specific transcription factors acting downstream of growth signaling pathways. Our results uncover context-specific, potentially actionable pro-growth enhancers from cancer cells, yielding insight into altered oncogenic transcription and revealing potential therapeutic targets for cancer treatment.
CRISPR interference identifies vulnerable cellular pathways with bactericidal phenotypes inMycobacterium tuberculosis
Authors: McNeil Matthew B. , Keighley Laura M , Cook Josephine R. , Cheung Chen-Yi , Cook Gregory M.
Published: February 2021

Mycobacterium tuberculosisremains a leading cause of death for which new drugs are needed. The identification of drug targets has been advanced by high-throughput and targeted genetic deletion strategies. Each though has limitations including the inability to distinguish between levels of vulnerability, lethality and scalability as a molecular tool. Using mycobacterial CRISPR interference in combination with phenotypic screening we have overcome these individual issues to investigate essentiality, vulnerability and lethality for 96 target genes from a diverse array of cellular pathways, many of which are potential antibiotic targets. Essential genes involved in cell wall synthesis and central cellular functions were equally vulnerable and often had bactericidal consequences. Conversely, essential genes involved in metabolism, oxidative phosphorylation or amino acid synthesis were less vulnerable to inhibition and frequently bacteriostatic. In conclusion, this study provides novel insights into mycobacterial genetics and biology that will help to prioritise potential drug targets.
Mosquito community composition shapes virus prevalence patterns along anthropogenic disturbance gradients
Authors: Hermanns Kyra , Marklewitz Marco , Zirkel Florian , Kopp Anne , Kramer-Schadt Stephanie , Junglen Sandra
Published: February 2021

Previously unknown pathogens often emerge from primary ecosystems, but there is little knowledge on the mechanism behind. Most studies analyzing the influence of land-use change on pathogen emergence focus on a single host-pathogen system and often observe contrary effects. We studied virus diversity and prevalence patterns in natural and disturbed ecosystems using a multi-host and multi-taxa approach.

We detected 331 viral sequences pertaining to 49 viruses of ten RNA-virus families. Highest host and virus diversity was observed in pristine and intermediately disturbed habitats. The majority of the viruses was detected with low prevalence. However, nine viruses were found frequently of which five viruses increased in prevalence from pristine to disturbed habitats, in congruence with the dilution effect hypothesis. Interestingly, the observed increased prevalence of these five viruses in disturbed habitats was not caused by higher host infection rates but by increased host abundance, an effect tentatively named abundance effect.

Impact statement

Our data show that ecosystem disturbance can lead to a turnover in host community composition and that more individuals of a single species is a key driver of virus emergence.
LSD’s effects are differentially modulated in arrestin knockout mice
Authors: Rodriguiz Ramona M. , Nadkarni Vineet , Means Christopher R. , Chiu Yi-Ting , Roth Bryan L. , Wetsel William C.
Published: February 2021

Recent evidence suggests that psychedelic drugs can exert beneficial effects on anxiety, depression, and ethanol and nicotine abuse in humans. However, the hallucinogenic side-effects of psychedelics often preclude their clinical use. Lysergic acid diethylamide (LSD) is a prototypical hallucinogen and its psychedelic actions are exerted through the 5-HT2Aserotonin receptor (5-HT2AR). 5-HT2AR activation stimulates Gq- and β-arrestin-(βArr) mediated signaling. To separate effects of these signaling modes, we have used βArr1 and βArr2 mice. We find that LSD stimulates motor activities to similar extents in WT and βArr1-KO mice, with non-significant effects in βArr2-KOs. LSD robustly stimulates many surrogates of psychedelic drug actions including head twitches, grooming, retrograde walking, and nose poking in WT and βArr1-KO animals. In contrast, LSD only slightly stimulates head twitches in βArr2-KO mice, without effects on retrograde walking or nose poking. The 5-HT2AR antagonist MDL100907 (MDL) blocks these LSD effects. LSD also disrupts prepulse inhibition (PPI) in WT and βArr1-KOs; PPI is unaffected in βArr2-KOs. MDL restores PPI in WT mice, but this antagonist is without effect and haloperidol is required in βArr1-KOs. LSD produces a biphasic body-temperature response in WT mice, a monophasic response in βArr1-KOs, and is without effect in βArr2 mutants. Both MDL and the 5-HT1AR antagonist, WAY 100635 (WAY), block the effects of LSD on body temperatures in WT mice, whereas WAY is effective in βArr1-KOs. Collectively, these results reveal that LSD produces diverse behavioral effects through βArr1 and βArr2, and that LSD’s psychedelic drug-like actions appear to require βArr2.
Human brain mitochondrial-nuclear cross-talk is cell-type specific and is perturbed by neurodegeneration
Authors: Fairbrother-Browne Aine , Ali Aminah T. , Reynolds Regina H. , Garcia-Ruiz Sonia , Zhang David , Chen Zhongbo , Ryten Mina , Hodgkinson Alan
Published: February 2021

Mitochondrial dysfunction contributes to the pathogenesis of many neurodegenerative diseases as mitochondria are essential to neuronal function. The mitochondrial genome encodes a small number of core respiratory chain proteins, whereas the vast majority of mitochondrial proteins are encoded by the nuclear genome. Here we focus on establishing a profile of nuclear-mitochondrial transcriptional relationships in healthy human central nervous system tissue data, before examining perturbations of these processes in Alzheimer’s disease using transcriptomic data originating from affected human brain tissue. Through cross-central nervous system analysis of mitochondrial-nuclear gene pair relationships, we find that the cell type composition underlies regional variation, and variation is driven at the subcellular level by heterogeneity of nuclear-mitochondrial coordination in post-synaptic regions. We show that nuclear genes causally implicated in sporadic Parkinson’s disease and Alzheimer’s disease show much stronger relationships with the mitochondrial genome than expected by chance, and that nuclear-mitochondrial relationships are significantly perturbed in Alzheimer’s disease cases, particularly amongst genes involved in synaptic and lysosomal pathways. Finally, we present MitoNuclearCOEXPlorer, a web tool designed to allow users to interrogate and visualise key mitochondrial-nuclear relationships in multi-dimensional brain data. We conclude that mitochondrial-nuclear relationships differ significantly across regions of the healthy brain, which appears to be driven by the functional specialisation of different cell types. We also find that mitochondrial-nuclear co-expression in critical pathways is disrupted in Alzheimer’s disease, potentially implicating the regulation of energy balance and removal of dysfunctional mitochondria in the etiology or progression of the disease and making the case for the relevance of bi-genomic co-ordination in the pathogenesis of neurodegenerative diseases.
Uncovering Differences in Hydration Free Energies and Structures for Model Compound Mimics of Charged Sidechains of Amino Acids
Authors: Fossat Martin J. , Zeng Xiangze , Pappu Rohit V.
Published: February 2021

Free energies of hydration are of fundamental interest for modeling and understanding conformational and phase equilibria of macromolecular solutes in aqueous phases. Of particular relevance to systems such as intrinsically disordered proteins are the free energies of hydration and hydration structures of model compounds that mimic charged sidechains of Arg, Lys, Asp, and Glu. Here, we deploy a Thermodynamic Cycle based Proton Dissociation (TCPD) approach in conjunction with data from direct measurements to obtain estimates for the free energies of hydration for model compounds that mimic the sidechains of Arg+, Lys+, Asp-, and Glu-. Irrespective of the choice made for the hydration free energy of the proton, the TCPD approach reveals clear trends regarding the free energies of hydration for Arg+, Lys+, Asp-, and Glu-. These trends include asymmetries between the hydration free energies of acidic (Asp-and Glu-) and basic (Arg+and Lys+) residues. Further, the TCPD analysis, which relies on a combination of experimental data, shows that the free energy of hydration of Arg+is less favorable than that of Lys+. We sought a physical explanation for the TCPD derived trends free energies of hydration. To this end, we performed temperature dependent calculations of free energies of hydration and analyzed hydration structures from simulations that use the polarizable AMOEBA (Atomic Multipole Optimized Energetics for Biomolecular Applications) forcefield and water model. At 298 K, the AMOEBA model generates estimates of free energies of hydration that are consistent with TCPD values with a free energy of hydration for the proton of ≈ -259 kcal / mol. Analysis of temperature dependent simulations leads to a structural explanation for the observed differences in free energies of hydration of ionizable residues and reveals that the heat capacity of hydration is positive for Arg+and Lys+and negative for Asp-and Glu-.
Cryo-EM Structure of Bacterioferritin Nanocages Provides Insight into the Bio-mineralization of Ferritins
Authors: Jobichen Chacko , Chong Tan Ying , Rattinam Rajesh , Basak Sandip , Srinivasan Mahalashmi , Pandey Kannu Priya , Ngoc Tran Bich , Shi Jian , Angayarkanni Jayaraman , Sivaraman J
Published: February 2021

Iron is an essential element involved in various metabolic processes. The ferritin family of proteins forms nanocage assembly and are involved in iron oxidation, storage and mineralization. Although several structures of human ferritin and bacterioferritin subunits have been resolved, there is still no complete structure that shows both the trapped Fe-biomineral cluster along with the nanocage. Furthermore, whereas the mechanism of iron trafficking has been explained using various approaches, an atomic-level description of the pathway and the biomineralization that occurs inside the cavity are lacking. Here, we report three cryo-EM structures of different states of theStreptomyces coelicolorbacterioferritin nanocage (i.e., apo, holo) at 3.4 Å to 4.6 Å resolution and the subunit crystal structure at 2.6 Å resolution. The holo forms show different stages of Fe-biomineral accumulation inside the nanocage and suggest the possibility of a different Fe biomineral accumulation process. The cryo-EM map shows connections between the Fe-biomineral cluster and residues such as Thr157 and Lys42 from the protein shell, which are involved in iron transport. Mutation and truncation of the bacterioferritin residues involved in these connections can significantly reduce iron binding as compared with wild type bacterioferritin. Moreover,S. coelicolorbacterioferritin binds to various DNA fragments, similar to Dps (DNA-binding protein from starved cells) proteins. Collectively, our results represent a prototype for the ferritin nanocage, revealing insight into its biomineralization and the potential channel for ferritin-associated iron trafficking.
BGvar - a comprehensive resource for blood group immunogenetics
Authors: Rophina Mercy , Pandhare Kavita , Jadhao Sudhir , Nagaraj Shivashankar H. , Scaria Vinod
Published: February 2021

Background

Blood groups form the basis of effective and safe blood transfusion. There are about 41 well recognized human blood group systems presently known. Blood groups are molecularly determined by the presence of specific antigens on the red blood cells and are genetically determined and inherited following Mendelian principles. The lack of a comprehensive, relevant, manually compiled and genome-ready dataset of red cell antigens limited the widespread application of genomic technologies to characterise and interpret the blood group complement of an individual from genomic datasets.

Materials and Methods

A range of public datasets were used to systematically annotate the variation compendium for its functionality and allele frequencies across global populations. Details on phenotype or relevant clinical importance were collated from reported literature evidence.

Results

We have compiled the Blood Group Associated Genomic Variant Resource (BGvar), a manually curated online resource comprising all known human blood group related allelic variants including a total of 1672 ISBT approved alleles and 1552 alleles predicted and curated from literature reports. This repository includes 1606 Single Nucleotide Variations (SNVs), 270 Insertions, Deletions (InDels) and Duplications and about 1310 combination mutations corresponding to 41 human blood group systems and 2 transcription factors. This compendium also encompasses gene fusion and rearrangement events occurring in human blood group genes.

Conclusion

To the best of our knowledge, BGvar is a comprehensive and a user friendly resource with most relevant collation of blood group alleles in humans. BGvar is accessible online at URL:http://clingen.igib.res.in/bgvar/
Expanded Asgard archaea shed new light on the origin of eukaryotes and support a 2-domain tree of life
Authors: Xie Ruize , Wang Yinzhao , Huang Danyue , Hou Jialin , Li Liuyang , Hu Haining , Zhao Xiaoxiao , Wang Fengping
Published: February 2021

The hypothesis that eukaryotes originated from within the domain Archaea has been strongly supported by recent phylogenomic analyses placing Heimdallarchaeota from the Asgard superphylum as the closest known archaeal sister-group to eukaryotes. At present, only seven phyla are described in the Asgard superphylum, which limits our understanding of the relationship between eukaryotes and archaea, as well as the evolution and ecological functions of Asgard archaea. Here, we describe five novel phylum-level Asgard archaeal lineages, tentatively named Tyr-, Sigyn-, Freyr-, Hoder- and Balderarchaeota. Comprehensive phylogenomic analyses supported a new Asgard lineage Tyrarchaeota was identified as a deeper branching lineage cluster with the eukaryotic nuclear host lineage than Heimdallarchaeota that were previously considered as the closest archaeal relatives of eukaryotes. Metabolic reconstruction of Tyrarchaeota suggests a mixotrophic lifestyle of this archaea, capable of peptides and amino acids utilization while having the potential using the Wood-Ljungdahl pathway for carbon fixation and acetogenesis. This study largely expands the Asgard superphylum, provides additional evidences to support the 2-domain life tree thus sheds new light on the evolution and geochemical functions of the Asgard archaea.
Cellular management of Zinc in group BStreptococcussupports bacterial resistance against metal intoxication and promotes disseminated infection
Authors: Sullivan Matthew J. , Goh Kelvin G. K. , Ulett Glen C.
Published: February 2021

Zinc (Zn) is an essential trace element for normal bacterial physiology but divergently, can intoxicate bacteria at high concentrations. Here, we define the molecular systems for Zn detoxification inStreptococcus agalactiae, also known as group B Streptococcus, and examine the effects of resistance to Zn stress on virulence. We compared the growth of wild-type bacteria and mutants deleted for the Zn exporter,czcD, and the response regulator,sczA, using Zn-stress conditionsin vitro.Macrophage antibiotic protection assays and a mouse model of disseminated infection were used to assess virulence. Global bacterial transcriptional responses to Zn stress were defined by RNA-sequencing and qRTPCR.czcDandsczAenabledS. agalactiaeto survive Zn stress, with the putative CzcD efflux system activated by SczA. Additional genes activated in response to Zn stress encompassed divalent cation transporters that contribute to regulation of Mn and Fe homeostasis.In vivo, theczcD-sczAZn-management axis supported virulence in the blood, heart, liver and bladder. Additionally, several genes not previously linked to Zn stress in any bacterium, including most notably,arcAfor arginine deamination also mediated resistance to Zn stress; representing a novel molecular mechanism of bacterial resistance to metal intoxication. Taken together, these findings show thatS. agalactiaeresponds to Zn stress bysczAregulation ofczcD, with additional novel mechanisms of resistance supported byarcA, encoding arginine deaminase. Cellular management of Zn stress inS. agalactiaesupports virulence by facilitating bacterial survival in the host during systemic infection.

Importance Statement

Streptococcus agalactiae, also known as group B streptococcus, is an opportunistic pathogen that causes various diseases in humans and animals. This bacterium has genetic systems that enable Zinc (Zn) detoxification in environments of metal stress, but these systems remain largely undefined. Using a combination of genomic, genetic and cellular assays we show that this pathogen controls Zn export through CzcD to manage Zn stress, and utilizes a system of arginine deamination never previously linked to metal stress responses in bacteria to survive metal intoxication. We show that these systems are crucial for survival ofS. agalactiae in vitroduring Zn stress and also enhance virulence during systemic infection in mice. These discoveries establish new molecular mechanisms of resistance to metal intoxication in bacteria; we suggest these mechanisms are likely to operate in other bacteria as a way to sustain microbial survival in conditions of metal stress, including in host environments.
Serological Profile Of Specific Antibodies Against Dominant Antigens Of SARS-CoV-2 In Chilean COVID-19 Patients.
Authors: Cereceda K. , González-Stegmaier R. , Briones JL. , Selman C. , Aguirre A. , Valenzuela-Nieto G. , Caglevic C. , Gazitua R. , Rojas-Fernandez A. , Villarroel-Espíndola F.
Published: February 2021

Coronavirus disease 2019 (COVID-19) is caused by SARS-CoV-2 and has been a pandemic since March 2020. Currently, the virus has infected more than 50 million people worldwide and more than half a million in Chile. For many coronaviruses, Spike (S) and Nucleocapsid (N) proteins are described as major antigenic molecules, inducing seroconversion and production of neutralizing antibodies. In this work, we evaluated the presence in serum of IgM, IgA and IgG antibodies against N and S proteins of SARS-CoV-2 using western blot, and developed an ELISA test for the qualitative characterization of COVID-19 patients. Patients with an active infection or who have recovered from COVID-19 showed specific immunoblotting patterns for the recombinants S protein and its domains S1 and S2, as well as for the N protein of SARS-CoV-2. Anti-N antibodies were more frequently detected than anti-S or anti-S1-RBD antibodies. People who were never exposed to SARS-CoV-2 did not show reactivity. Finally, indirect ELISA assays using N and S1-RBD proteins, alone or in combination, were established with variable sensitivity and specificity depending on the antigen bound to the solid phase. Overall, Spike showed higher specificity than the nucleocapsid, and comparable sensitivity for both antigens. Both approaches confirmed the seroconversion after infection and allowed us to implement the analysis of antibodies in blood for research purposes in a local facility.
Insights intoMus musculuspopulation structure across Eurasia revealed by whole-genome analysis
Authors: Fujiwara Kazumichi , Kawai Yosuke , Moriwaki Kazuo , Takada Toyoyuki , Shiroishi Toshihiko , Saitou Naruya , Suzuki Hitoshi , Osada Naoki
Published: February 2021

For more than 100 years, house mice (Mus musculus) have been used as a key animal model in biomedical research. House mice are genetically diverse, yet their genetic background at the global level has not been fully understood. Previous studies suggested that they originated in South Asia and diverged into three major subspecies almost simultaneously, approximately 350,000–500,000 years ago; however, they have spread across the world with the migration of modern humans in prehistoric and historic times (∼10,000 years ago to present), and undergone secondary contact, which have complicated the genetic landscape of wild house mice. In this study, we sequenced the whole genomes of 98 wild house mice collected from Eurasia, particularly East Asia, Southeast Asia, and South Asia. We found that although wild house mice consist of three major genetic groups corresponding to the three major subspecies, individuals representing admixture between subspecies are much more ubiquitous than previously recognized. Furthermore, several samples showed an incongruent pattern of genealogies between mitochondrial and autosomal genomes. Using samples likely retaining the original genetic components of subspecies with least admixture, we estimated the pattern and timing of divergence among the subspecies. The results are important for understanding the genetic diversity of wild mice on a global level and the information will be particularly useful in future biomedical and evolutionary studies using laboratory mice established from these wild mice.
Bayesian modeling and simulation to inform rare disease drug development early decision-making: application to Duchenne muscular dystrophy
Authors: Lennie Janelle L. , Mondick John T. , Gastonguay Marc R.
Published: February 2021

Rare disease clinical trials are constrained to small sample sizes and may lack placebo-control, leading to challenges in drug development. This paper proposes a Bayesian model-based framework for early go/no-go decision making in rare disease drug development, using Duchenne muscular dystrophy (DMD) as an example. Early go/no-go decisions were based on projections of long-term functional outcomes from a Bayesian model-based analysis of short-term trial data informed by prior knowledge based on 6MWT natural history literature data in DMD patients. Frequentist hypothesis tests were also applied as a reference analysis method. A number of combinations of hypothetical trial designs, drug effects and cohort comparison methods were assessed.The proposed Bayesian model-based framework was superior to the frequentist method for making go/no-go decisions across all trial designs and cohort comparison methods in DMD. The average decision accuracy rates across all trial designs for the Bayesian and frequentist analysis methods were 45.8 and 8.98%, respectively. A decision accuracy rate of at least 50% was achieved for 42 and 7% of the trial designs under the Bayesian and frequentist analysis methods, respectively. The frequentist method was limited to the short-term trial data only, while the Bayesian methods were informed with both the short-term data and prior information. The specific results of the DMD case study were limited due to incomplete specification of individual-specific covariates in the natural history literature data and should be reevaluated using a full natural history dataset. These limitations aside, the framework presented provides a proof of concept for the utility of Bayesian model-based methods for decision making in rare disease trials.
Cancer cells adapt FAM134B-BiP complex mediated ER-phagy to survive hypoxic stress
Authors: Chipurupalli Sandhya , Ganesan Raja , Martini Giulia , Mele Luigi , Kannan Elango , Namasivayam Vigneshwaran , Desiderio Vincenzo , Robinson Nirmal
Published: February 2021

In a tumor microenvironment cancer cells experience hypoxia resulting in the accumulation of misfolded/unfolded proteins in the endoplasmic reticulum (ER) which elicit unfolded protein response (UPR) as an adaptive mechanism. UPR activates autophagy enabling the degradation of misfolded/unfolded proteins. More recently, ER-specific autophagy has been implicated in the removal of damaged ER and restoration of ER-homeostasis. Our investigations reveal that during hypoxia induced ER-stress, the ER-phagy receptor FAM134B targets damaged portions of ER into autophagosomes to restore ER-homeostasis in cancer cells. Loss of FAM134B in breast cancer cells results in increased ER-stress and reduced cell proliferation. Mechanistically, upon sensing hypoxia activated proteotoxic stress, the ER chaperone BiP forms a complex with FAM134B and promotes ER-phagy. Our studies have further led to the identification of a pharmacological agent vitexin that disrupts FAM134B-BiP complex thereby inhibits ER-phagy and suppresses breast cancer progression in vivo.
The Integrity of the Speciation Core Complex is necessary for centromeric binding and reproductive isolation inDrosophila
Authors: Lukacs Andrea , Thomae Andreas W , Krueger Peter , Schauer Tamas , Venkatasubramani Anuroop V , Kochanova Natalia Y , Aftab Wasim , Choudhury Rupam , Forne Ignasi , Imhof Axel
Published: February 2021

Postzygotic isolation by genomic conflict is a major cause for the formation of species. Despite its importance, the molecular mechanisms that result in the lethality of interspecies hybrids are still largely unclear. The genusDrosophila, which contains over 1600 different species, is one of the best characterized model systems to study these questions. We showed in the past that the expression levels of the two hybrid incompatibility factorsHmrandLhrdiverged in the two closely relatedDrosophilaspecies,D. melanogasterandD. simulans, resulting in an increased level of both proteins in interspecies hybrids. This overexpression leads to mitotic defects, a misregulation in the expression of transposable elements and a decreased fertility. In this work, we describe a distinct six subunit Speciation Core Complex (SCC) containing HMR and LHR and analyse the effect ofHmrmutations on complex function and integrity. Our experiments suggest that HMR acts as a bridging factor between centromeric chromatin and pericentromeric heterochromatin, which is required for both its physiological function and its ability to cause hybrid male lethality.
Insights into the mechanisms of LOV domain color tuning from a set of high-resolution X-ray structures
Authors: Remeeva Alina , Nazarenko Vera V. , Kovalev Kirill , Goncharov Ivan , Yudenko Anna , Astashkin Roman , Gordeliy Valentin , Gushchin Ivan
Published: February 2021

Light-oxygen-voltage (LOV) domains are widespread photosensory modules that can be used in fluorescence microscopy, optogenetics and controlled production of reactive oxygen species. All of the currently known LOV domains have absorption maxima in the range of ∼440 to ∼450 nm, and it is not clear whether they can be shifted significantly using mutations. Here, we have generated a panel of LOV domain variants by mutating the key chromophore-proximal glutamine amino acid of a thermostable flavin based fluorescent protein CagFbFP (Gln148) to asparagine, aspartate, glutamate, histidine, lysine and arginine. Absorption spectra of all of the mutants are blue-shifted, with the maximal shift of 8 nm observed for the Q148H variant. While CagFbFP and its Q148N/D/E variants are not sensitive to pH, Q148H/K/R reveal a moderate red shift induced by acidic pH. To gain further insight, we determined high resolution crystal structures of all of the mutants studied at the resolutions from 1.07 Å for Q148D to 1.63 Å for Q148R. Whereas in some of the variants, the amino acid 148 remains in the vicinity of the flavin, in Q148K, Q148R and partially Q148D, the C-terminus of the protein unlatches and the side chain of the residue 148 is reoriented away from the chromophore. Our results explain the absence of color shifts from replacing Gln148 with charged amino acids and pave the way for rational design of color-shifted flavin based fluorescent proteins.
An empirical study of the impact of female labor participation on their subjective well-being in mainland China: evidence from CGSS data
Authors: Lu Jiehua , Nie Jiawei
Published: February 2021

Purpose

Labor participation has always been a hot topic in academic circle and a vital label in the process of China's economic and social development. Therefore, the purpose this paper is to use CGSS 2015 data, starting from labor participation, and make a comparably comprehensive analysis of the influencing factors of subjective well-being of females.

Design/methodology/approach

By conducting probit regressions, the paper reveals the impact of labor participation and socio-demographic conditions on the subjective well-being of females in Mainland China.

Findings

First, the authors’ findings turn out that urban women do have a higher level of women's subjective well-being when compared to rural women. Second, educational attainment has a significantly positive effect on subjective well-being only in urban areas, while having teen children is only statistically significant for rural residents. Third, the overall impact of employment conditions on women's subjective well-being is reduced due to the transition of gender conceptions. In all, the evaluation of subjective well-being of females is reshaped by the overwhelming transition of society in Mainland China.

Research limitations/implications

There remain some limitations of this study. First, because CGSS 2015 data are the only data analyzed here, it is hard and inaccurate to compare the differences between this result and previous outcomes conducted by other scholars using CGSS 2005, 2010 and 2013 data. Second, the categories of employment conditions are not detailed, and thus it adds burden to further analysis. For future studies, a wider range of data should be taken into account and provide data support to have a convincing comparison at different times. The social background of diverse employment conditions could be discussed in-depth as well.

Originality/value

Based on the early literature, this paper is intended to use Chinese data to study the major factors affecting Chinese female labor participation in Mainland China and also discuss the implications in practice.
The effect of audit engagement partner professional experience on audit quality and audit fees: early evidence from Form AP disclosure
Authors: Liu Chenyong , Xu Chunhao
Published: February 2021

Purpose

The purpose of this study is to examine the effect of audit engagement partner's professional experience on audit quality. The authors also investigate the relationship between the audit partner's experience and audit fees in both Big 4 and non-Big 4 accounting firms.

Design/methodology/approach

Since the Public Company Accounting Oversight Board (PCAOB) officially enacted Rule 3211 in 2017, US accounting firms are required to disclose detailed information of engagement partners in Form AP (PCAOB, 2015b). The authors obtained a sample of 2,283 audit partners from Form AP and hand collected their individual professional experience data through Certified Public Accountant (CPA) database, corporate disclosure and social media sites (e.g. Linkedin). Econometric models with fixed effects are used in this study to test our hypotheses. Two-stage least square (2SLS) model is used in the robustness test.

Findings

The authors find that the relationship between audit engagement partner's professional experience and audit quality is concave. It indicates that audit quality is increasing during the early stage of engagement partners' career and then decreases as the partners approaching the late-career phase. Further, the authors find that partner's professional experience is positively associated with audit fees in non-Big 4 accounting firms but not significantly associated with audit fees in Big 4 accounting firms.

Practical implications

The finding of how auditor experience impacts audit quality can be useful for accounting firms to better plan their staffing in auditing engagements. This study’s results are also helpful for small accounting firms to optimize their pricing strategy.

Originality/value

This study provides new empirical evidence about the relation between auditor professional experience and audit quality. Furthermore, the authors extend the literature of audit fee determinants by testing the joint effects of audit firm-level factors and auditor individual-level professional experience on audit fees.
Employer tenure in gays, lesbians and their straight counterparts
Authors: Fric Karel
Published: February 2021

Purpose

This article aims to shed more light on seemingly contradicting labour market outcomes of lesbians: they were found to have similar unemployment rates as straight women but their unemployment spells are significantly shorter. No such contradiction is observed for gays who seem to have on average a higher unemployment rate and longer unemployment spells compared to straight men.

Design/methodology/approach

The main hypothesis is that lesbian and gay employees spend ceteris paribus shorter time working for a given employer (employer tenure) than comparable straight people. This hypothesis is tested on EU Labour Force Survey data using multi-level regression model.

Findings

Consistently with the predictions, lesbians and gays were found to have significantly shorter employer tenure than their straight counterparts. These differences remained significant after controlling for individual, workplace and occupational characteristics. The results suggest that shorter employer tenure of lesbians and (possibly) gays is driven by labour demand factors.

Originality/value

To author's knowledge this is the first large-scale quantitative study that compares the employer tenure between lesbians, gays and comparable heterosexuals. The study provides additional insight into mechanisms that lead to (lack of) differentials in unemployment probability between these groups.
Stop the pain: Black and minority ethnic scholars on diversity policy obfuscation in universities
Authors: Ahmet Akile
Published: February 2021

Purpose

The author extends the work on diversity policy in UK higher education by centring the voices of Black and minority ethnic scholars and de-centring white comfort with the aim of a call to stop the pain that sanitised university diversity policies cause Black and minority ethnic scholars.

Design/methodology/approach

Using in-depth qualitative and auto-ethographic research methods, this paper engages with both respondents' narratives as well as the author's experience of carrying out the research within the walls of predominately white universities.

Findings

In order for universities to move beyond hollow and sanitised diversity, they must centre the voices of Black and minority ethnic scholars. Respondents spoke of their experiences of pain, and feelings of “taking up” space in predominately white universities. The author also discusses respondents' feelings towards diversity and inclusion policies such as the Race Equality Charter Mark.

Originality/value

The research is built on previous work on diversity by decentring white comfort.
Contrast and conditional polarity rule (CCPR) for detection of positivity and negativity in opinionated sentence with indirect polarity
Authors: Gan Keng Hoon , Krol Noeurn
Published: February 2021

Purpose

Customer reviews are one important source that contains valuable information for quality evaluation of products or services. Review sentences contain sentiment words that show whether a user’s opinion is positive or negative. When review sentence has mix opinions, having sentiment words of both polarities, it is difficult to conclude whether it is positive or negative opinion. The purpose of this study is to improve the detection of polarity in such situation.

Design methodology approach

In this research, methods such as part-of-speech tagging, polarity analysis and rules selection are used to identify the polarity. A set of rules called contrast and conditional polarity rules (CCPR) has been created to improve the polarity detection in cases when there is mixture of sentiment words used in contrast and conditional type of review sentences. The experiment is conducted with data sets from three domains, i.e. restaurant, electronic and Tripadvisor.

Findings

The experimental result confirms that CCPR rules have higher baseline of the polarity aggression. In restaurant domain, CCPR rules (62.07%) have increased 13.79% compared with the Pol_Agg_MPQA baseline (48.28%) and 13.79% compared with Pol_Agg_Senti baseline (48.28%). In electronic domain, CCPR rule (79.17%) is higher by 12.50% compared with the Pol_Agg_MPQA baseline (66.67%) and 16.67% compared with Pol_Agg_Senti baseline (62.50%). Another one, CCPR rule (70.83%) is higher by 8.33% compared with the Pol_Agg_MPQA baseline (62.50%) and 12.50% compared with Pol_Agg_Senti baseline (58.33%). In conclusion, result of experiment shows promising outcome with improvement in detecting the positivity and negativity of indirect sentence, especially for the case of sentence with indirect polarity.

Originality value

To address the problem of mix opinions in terms of polarities, this paper presents a rule-based approach to improve the result of identifying positivity and negativity in sentence with indirect polarities.
When simplicity becomes complexity: negotiations between a Mennonite enterprising community and the Government of Belize
Authors: Roessingh Carel , Verver Michiel
Published: February 2021

Purpose

A central theme in the literature on entrepreneurship in remote communities – be they religious, indigenous, rural or migrant communities – is the balance between continuity and change or tradition and modernity and the role of entrepreneurship in maintaining or uprooting this balance. The purpose of this paper is to examine this dynamic in the context of Springfield, a small settlement of Old Order Mennonites in Belize, Central America.

Design/methodology/approach

This study draws on ethnographic research conducted in the Mennonite settlement of Springfield, Belize, between 2002 and 2019, as well as written correspondence with key stakeholders from Springfield.

Findings

This paper identifies three issues of contention between the Springfield Mennonites and the Belizean state: the agricultural census issue, the buying land issue and the cow tagging issue. Each of these revolves around state demands for assimilation into (digitalized) administrative systems and Mennonite resistance to these demands based on their religious-moral code. This study describes the negotiations around these issues.

Originality/value

The focus in most literature on entrepreneurship in remote communities is on how internal community dynamics shape the balance between continuity and change and, in extension, the space for entrepreneurship. The originality of the paper lies in shifting the focus to the relationship between the community and external stakeholders, especially the state.
Gender and rural economic relations: ethnography of the Nrobo of South Eastern Nigeria
Authors: Ugwu Ugochukwu Titus
Published: February 2021

Purpose

The purpose of this study is to examine gender and rural economic relations of the Nrobo of Southeastern Nigeria. Specifically, the study was designed to examine the subsistence strategies, gendered role patterns and gender gaps in economic relations of the Nrobo.

Design/methodology/approach

This study used ethnographic methods of participant observation – adopting chitchatting and semi-structured interviews. Also, focus group discussion (FGD) was used to cross-check the validity of data from the other instrument.

Findings

This study found among other things, that although there is still verbal expression of gendered roles division, it does not mirror what actually obtains in society, except bio-social roles. Ideological superiority of men reflects the patrilineal kinship arrangement of society. Theoretically, some of the hypotheses of gender inequality theory were disputed for lack of adequate explanation of gender and economic relations in an egalitarian-reflected society such as Nrobo.

Originality/value

This study, to the best of my knowledge, is the first attempt to ethnographically examine gender and economic relations among this group. As such it adds to the corpus of ethnographies on the Igbo of Southeastern Nigeria.
The influence of user generated content on hotel sales: an Indian perspective
Authors: Sharma Himanshu , Aggarwal Anu G.
Published: February 2021

Purpose

Nowadays, various hotels and third party websites allow guests to express their stay experience in the form of textual content and ratings termed as user-generated content (UGC). This study aims to explore the influence of UGC along with the financial aspect on the sales of the hotel. This will help them in making efficient business decisions and revenue generation by realizing the requirements of the guests. The proposed model provides an insight into the theoretical and practical significance of the concerned explanatory variables to the hoteliers.

Design/methodology/approach

This paper considers the number of rooms, six aspect ratings (room, cleanliness, location, service, value and sleep quality), review length and readability as the independent variables. Revenue per available room is taken as the dependent variable. Log-linear regression analysis is performed on a data set of 78 hotels situated in Delhi National Capital Region to validate the relationships. Moreover, the differential impact of hotel type on these exploratory variables is studied.

Findings

Research findings show that along with the financial aspect, the UGC components also play a key role in generating sales for the hotels. It was further observed that the two hotel categories, i.e. luxury and budget have different natures and also the characteristics of luxury hotels overshadow those of budget.

Originality/value

This study uses the textual content of the reviews along with the numerical ratings. This is a unique combination for studying sales of hotels according to the knowledge of authors, where earlier studies focused only on the financial aspects.
Unravelling the process of self-regulated learning of medical specialists in the clinical environment
Authors: Cuyvers Katrien , Donche Vincent , Van den Bossche Piet
Published: February 2021

Purpose

This study aims to unravel the dynamic nature of the process of self-regulated learning (SRL) of medical specialists as it actually unfolds over time in the authentic clinical environment.

Design/methodology/approach

A longitudinal multiple case-study design was used, combining multiple data-collection techniques. Long-term observations offered evidence on overt SRL strategies. Physicians’ observed behaviours were used as cues for in loco stimulated recall interviews, asking about covert SRL strategies and their thoughts regarding a situation at hand. Field notes and audiotaped stimulated recall interviews were transcribed verbatim and integrated in a longitudinal database to map SRL as it actually unfolds moment-by-moment. The transcripts were analysed from an inter- and intra-individual perspective using Nvivo 12.

Findings

Results show a variety of strategies that initiate, advance and evaluate the process of SRL. Different SRL strategies not included in contemporary frameworks on SRL are found and classified as a new category which the authors labelled “learning readiness”. Exemplary for an SRL strategy in this category is awareness of learning needs. Results show that SRL in the clinical environment is found as an interrelated, dynamic process unfolding in time with feedback loops between different SRL strategies. Performance is found to play a leading role in driving SRL.

Originality/value

This study contributes empirically to the conceptual understanding of SRL in the clinical environment. The use of a situated, longitudinal methodology, which goes beyond the common path of retrospective self-report questionnaires, adds to the disentanglement of the process of SRL as it actually unfolds in the work environment.