bluuebunny/crossref_metadata_2025 huggingface dataset:
Nucleome Browser: An integrative and multimodal data navigation platform for 4D Nucleome
Authors: Zhu Xiaopeng , Zhang Yang , Wang Yuchuan , Tian Dechao , Belmont Andrew S. , Swedlow Jason R. , Ma Jian
Published: February 2022

We introduce Nucleome Browser (http://www.nucleome.org), an interactive, multimodal data visualization and exploration platform for 4D Nucleome research. Our tool effectively integrates heterogeneous datasets (e.g., genomics, imaging, 3D genome structure models, and single-cell data) and external data portals by a new adaptive communication mechanism. Nucleome Browser provides a scalable solution for integrating massive amounts of 4D Nucleome data to navigate multiscale nuclear structure and function in a wide range of biological contexts, enabling hypothesis generation and data sharing with the broad community.
Novel feature selection methods for construction of accurate epigenetic clocks
Authors: Li Adam , Kane Alice E , Mueller Amber , English Brad , Arena Anthony , Vera Daniel , Sinclair David A
Published: February 2022

Epigenetic clocks allow the accurate prediction of age based on the methylation status of specific CpG sites in a variety of tissues. These predictive models can be used to distinguish the biological age of an organism from its chronological age, and are a powerful tool to measure the effectiveness of aging interventions. There is a growing need for methods to efficiently construct epigenetic clocks. The most common approach is to create clocks using elastic net regression modelling of all measured CpG sites, without first identifying specific features or CpGs of interest. The addition of feature selection approaches provides the opportunity to reduce the cost and time of clock development by decreasing the number of CpG sites included in clocks. Here, we apply both classic feature selection methods and novel combinatorial methods to the development of epigenetic clocks. We perform feature selection on the human whole blood methylation dataset of ∼470,000 CpG features published by Hannum and colleagues (2015). We develop clocks to predict age, using a variety of feature selection approaches, and all clocks have R2 correlation scores of greater than 0.73. The most predictive clock uses 35 CpG sites for a R2 correlation score of 0.87. The five most frequent sites across all clocks are also modelled to build a clock with a R2 correlation score of 0.83. These two clocks are validated on two external datasets where they maintain excellent predictive accuracy and outperform Hannum et al’s model in accuracy of age prediction despite using significantly less CpGs. We also identify the associated gene regulatory regions of these CpG sites, which may be possible targets for future aging studies. These novel feature selection algorithms will lower the number of sites needed to be sequenced to build clocks and allow conventionally expensive aging epigenetic studies to cost a fraction of what it would normally.
An averaging model for analysis and interpretation of high-order genetic interactions
Authors: Katagiri Fumiaki
Published: February 2022

While combinatorial genetic data collection from biological systems in which quantitative phenotypes are controlled by functional and non-functional alleles of multiple genes (multi-gene systems) is becoming common, a standard analysis method for such data has not been established. A common additive model of the non-functional allele effects contrasted against the functional alleles, based on ANOVA with interaction, has three issues. First, although it is a long tradition in genetics, modeling the effect of the non-functional allele (a null mutant allele) contrasted against that of the functional allele (the wild-type allele) is not suitable for mechanistic understanding of multi-gene systems. Second, an additive model fails in estimation of interactions among more than two genes when the phenotypic response is not linear. Third, interpretation of higher-order interactions defined by an additive model is not intuitive. I propose an averaging model, which is suitable for mechanistic understanding of multi-gene systems: the effect of the functional allele is contrasted against the effect of the non-functional allele for easier mechanistic interpretations; it is stable in estimation of higher-order interactions even when the phenotypic response is not linear; and the higher-order interactions it defines are highly intuitive. Yet, the averaging model is still a general linear model, so model fitting is easy and accurate using common statistical tools.
Multimodal Thrombectomy Device for Treatment of Acute Deep Venous Thrombosis
Authors: Ismail Usama , Rowe Roger A. , Cashin John , Genin Guy M. , Zayed Mohamed
Published: February 2022

Deep vein thrombosis (DVT) is a potentially deadly medical condition that is costly to treat and impacts thousands of Americans every year. DVT is characterized by the formation of blood clots within the deep venous system of the body. If a DVT dislodges it can lead to venous thromboembolism (VTE) and pulmonary embolism (PE), both of which can lead to significant morbidity or death. Current treatment options for DVT are limited in both effectiveness and safety, in part because the treatment of the DVT cannot be confined to a defined sequestered treatment zone. We therefore developed and tested a thrombectomy device that enables the sequesteration of a DVT to a defined treatment zone during fragmentation and evacuation. We observed that, compared to a predicate thrombectomy device, the sequestered approach reduced distal DVT embolization during ex vivo thrombectomy. The sequestered approach also facilitated isovolumetric infusion and suction that enabled clearance of the sequestered treatment zone without significantly impacting vein wall diameter. Results suggest that our novel device using sequestered therapy holds promise for the treatment of high risk large-volume DVTs.
SexFindR: A computational workflow to identify young and old sex chromosomes
Authors: Grayson Phil , Wright Alison , Garroway Colin J. , Docker Margaret F.
Published: February 2022

Sex chromosomes have evolved frequently across the tree of life, and have been a source of fascination for decades due to their unique evolutionary trajectories. They are hypothesised to be important drivers in a broad spectrum of biological processes and are the focus of a rich body of evolutionary theory. Whole-genome sequencing provides exciting opportunities to test these theories through contrasts between independently evolved sex chromosomes across the full spectrum of their evolutionary lifecycles. However, identifying sex chromosomes, particularly nascent ones, is challenging, often requiring specific combinations of methodologies. This is a major barrier to progress in the field and can result in discrepancies between studies that apply different approaches. Currently, no single pipeline exists to integrate data across these methods in a statistical framework to identify sex chromosomes at all ages and levels of sequence divergence. To address this, we present SexFindR, a comprehensive workflow to improve robustness and transparency in identifying sex-linked sequences. We validate our approach using publicly available data from five species that span the continuum of sex chromosome divergence, from homomorphic sex chromosomes with only a single SNP that determines sex, to heteromorphic sex chromosomes with extensive degeneration. Next, we apply SexFindR to our large-scale population genomics dataset for sea lamprey, a jawless vertebrate whose sex determination system remains a mystery despite decades of research. We decisively show that sea lamprey do not harbour sex-linked sequences in their somatic genome, leaving open the possibility that sex is determined environmentally or within the germline genome.
Cryptic Genes for Interbacterial Antagonism distinguish Rickettsia species Infecting Blacklegged Tick from other Rickettsia pathogens
Authors: Verhoeve Victoria I. , Fauntleroy Tyesha D. , Risteen Riley G. , Driscoll Timothy P. , Gillespie Joseph J.
Published: February 2022

Background

Genus Rickettsia (Alphaproteobacteria: Rickettsiales) encompasses numerous obligate intracellular species with predominantly ciliate and arthropod hosts. Notable species are pathogens transmitted to mammals by blood-feeding arthropods. Mammalian pathogenicity evolved from basal, non-pathogenic host-associations; however, some non-pathogens are closely related to pathogens. One such species, Rickettsia buchneri, is prevalent in the blacklegged tick, Ixodes scapularis. While I. scapularis transmits several pathogens to humans, it does not transmit Rickettsia pathogens. We hypothesize that R. buchneri established a mutualism with I. scapularis, blocking tick superinfection with Rickettsia pathogens.

Methods

To improve estimates for assessing R. buchneri infection frequency in blacklegged tick populations, we used comparative genomics to identify an R. buchneri gene (REIS_1424) not present in other Rickettsia species present throughout the I. scapularis geographic range. Bioinformatic and phylogenomics approaches were employed to propose a function for the hypothetical protein (263 aa) encoded by REIS_1424.

Results

REIS_1424 has few analogs in other Rickettsiales genomes and greatest similarity to non-Proteobacteria proteins. This cohort of proteins varies greatly in size and domain composition, possessing characteristics of Recombination hotspot (Rhs) and contact dependent growth inhibition (CDI) toxins, with similarity limited to proximal C-termini (∼145 aa). This domain was named CDI-like/Rhs-like CT toxin (CRCT). As such proteins are often found as toxin-antidote (TA) modules, we interrogated REIS_1423 (151 aa) as a putative antidote. Indeed, REIS_1423 is similar to proteins encoded upstream of CRCT domain-containing proteins. Accordingly, we named these proteins CDI-like/Rhs-like C-terminal toxin antidotes (CRCA). R. buchneri expressed both REIS_1423 and REIS_1424 in tick cell culture, and PCR assays showed specificity for R. buchneri over other rickettsiae and utility for positive detection in three tick populations. Finally, phylogenomics analyses uncovered divergent CRCT/CRCA modules in varying states of conservation; however, only R. buchneri and related Tamurae/Ixodes Group rickettsiae carry complete TA modules.

Conclusion

We hypothesize that Rickettsia CRCT/CRCA modules circulate in the Rickettsia mobile gene pool, arming rickettsiae for battle over arthropod colonization. While its functional significance remains to be tested, R. buchneri CRCT/CRCA serves as a marker to positively identify infection and begin deciphering the role this endosymbiont plays in the biology of the blacklegged tick.
Clinical severity of COVID-19 patients admitted to hospitals during the Omicron wave in South Africa
Authors: Jassat Waasila , Abdool Karim Salim S , Mudara Caroline , Welch Richard , Ozougwu Lovelyn , Groome Michelle J. , Govender Nevashan , von Gottberg Anne , Wolter Nicole , Wolmarans Milani , Rousseau Petro ,   DATCOV author group, Blumberg Lucille , Cohen Cheryl
Published: February 2022

Background

Clinical severity of patients hospitalised with SARS-CoV-2 infection during the Omicron (fourth) wave was assessed and compared to trends in the D614G (first), Beta (second), and Delta (third) waves in South Africa.

Methods

Weekly incidence of 30 laboratory-confirmed SARS-CoV-2 cases/100,000 population defined the start and end of each wave. Hospital admission data were collected through an active national COVID-19-specific surveillance programme. Disease severity was compared across waves by post-imputation random effect multivariable logistic regression models. Severe disease was defined as one or more of acute respiratory distress, supplemental oxygen, mechanical ventilation, intensive-care admission or death.

Results

335,219 laboratory-confirmed SARS-CoV-2 admissions were analysed, constituting 10.4% of 3,216,179 cases recorded during the 4 waves. In the Omicron wave, 8.3% of cases were admitted to hospital (52,038/629,617) compared to 12.9% (71,411/553,530) in the D614G, 12.6% (91,843/726,772) in the Beta and 10.0% (131,083/1,306,260) in the Delta waves (p<0.001). During the Omicron wave, 33.6% of admissions experienced severe disease compared to 52.3%, 63.4% and 63.0% in the D614G, Beta and Delta waves (p<0.001). The in-hospital case fatality ratio during the Omicron wave was 10.7%, compared to 21.5%, 28.8% and 26.4% in the D614G, Beta and Delta waves (p<0.001). Compared to the Omicron wave, patients had more severe clinical presentations in the D614G (adjusted odds ratio [aOR] 2.07; 95% confidence interval [CI] 2.01-2.13), Beta (aOR 3.59; CI: 3.49-3.70) and Delta (aOR 3.47: CI: 3.38-3.57) waves.

Conclusion

The trend of increasing cases and admissions across South Africa’s first three waves shifted in Omicron fourth wave, with a higher and quicker peak but fewer admitted patients, who experienced less clinically severe illness and had a lower case-fatality ratio. Omicron marked a change in the SARS-CoV-2 epidemic curve, clinical profile and deaths in South Africa. Extrapolations to other populations should factor in differing vaccination and prior infection levels.
Impact of BNT162b2 mRNA Vaccination on the Development of Short and Long-term Vaccine-Related Adverse Events in Inflammatory Bowel Disease: A Multi-Center Prospective Study
Authors: Shehab Mohammad , Alrashed Fatema , Abdullah Israa , Alfadhli Ahmad , Ali Hamad , Abu-Farha Mohamed , Channanath Arshad , Abubaker Jehad , Al-Mulla Fahd
Published: February 2022

Introduction

SARS-CoV-2 vaccination has been effective in protecting against severe COVID-19 infections and related mortality. It is recommended for all individuals including patients with inflammatory bowel disease (IBD). However, safety data is lacking in this group of patients. Therefore, we aim to evaluate the short- and long-term vaccine related adverse events (AEs) in patients with IBD.

Method

This is a prospective, observational cohort study investigating short- and long-term AEs related to BNT162b2 vaccine in patients with IBD (study group) after first and second dose compared to healthy participants (study group). Patients were recruited at the time of attendance to clinic or infusion rooms. Short term (<3 weeks) localized and systemic AEs were assessed via questionnaire. Follow-up phone-based survey was made to collect data on long term (up to 24 weeks) AEs.

Results

A total of 408 patients answered the questionnaires, 204 patients in each group, the study and control group. No serious adverse events were reported in either the study nor the control group after the first or the second dose. Participants in the control group reported more frequent pain at the injection site than those in the study group after the first dose (58 (57%) vs 38 (37%) respectively, P-value= 0.005). After the second dose, tiredness was reported more frequently in the control group [49 (48%)] compared to the study group [25 (24%), (P-value<0.001)]. At 20-24 weeks post vaccination, 386 out of 408 (94.6%) patients were willing to participate in the follow-up phone based questionnaire (196 (96.1%) in the study group vs 190 (93.1%) in the control group). In both groups, none of the patients reported local, systemic or severe adverse events (0 out of 386) at week 20-244 post second dose.

Conclusion

The BNT162b2 vaccine is safe in patients with IBD. No severe or long-term adverse events were reported in our study. The frequency of local and systemic adverse events after the second dose was generally higher among healthy participants compared to patients with IBD. Further studies including a larger cohort with longer follow-up duration are needed to assess for possible rare adverse events.
Tie-lines reveal interactions driving heteromolecular condensate formation
Authors: Qian Daoyuan , Welsh Timothy J. , Erkamp Nadia A. , Qamar Seema , Nixon-Abell Jonathon , Krainer Georg , George-Hyslop Peter St , Michaels Thomas C. T. , Knowles Tuomas P. J.
Published: February 2022

Phase separation of biomolecules give rise to membraneless organelles that contribute to the spatiotemporal organisation of the cell. In most cases, such biomolecular condensates contain multiple components, but the manner in which interactions between components control the stability of condensates remained challenging to elucidate. Here, we develop an approach to determine tie-line gradients in ternary liquid-liquid phase separation (LLPS) systems, based on measurements of the dilute phase concentration of only one component. We show that the sign of the tie-line gradient is related to the cross-interaction energy between the polymers in the system and discriminates between competitive and cooperative phase separation. Using this approach, we studied the interaction between protein Fused in Sarcoma (FUS) and polyethylene glycol (PEG) polymer chains, and measured positive tie-line gradients. Our results show that PEG drives LLPS through an associative interaction with FUS and is not an inert crowder. We further studied the interaction between PolyA RNA (3.0±0.5kDa) and the protein G3BP1, and using the tie-line gradient as a reporter for the stoichiometry of polymers in the condensate we determined a G3BP1-to-PolyA RNA molar ratio of 1:4 in the dense phase. Our framework for measuring tie-line gradients opens up a route for the characterisation of interaction types and compositions in ternary LLPS systems.
The RNA binding protein Nab2 genetically interacts with multiple RNA exosome cofactors to regulate target RNAs
Authors: Kinney Christy E. , Mills-Lujan Katherine , Fasken Milo B. , Corbett Anita H.
Published: February 2022

RNA binding proteins play important roles in the processing and precise regulation of RNAs. Highlighting the biological importance of RNA binding proteins is the increasing number of human diseases that result from mutations in genes that encode these proteins. We recently discovered that mutations in theZC3H14gene, which encodes an evolutionarily conserved polyadenosine RNA-binding protein, cause intellectual disability. Studies of the budding yeast orthologue of ZC3H14, Nuclear Poly(A) Binding protein 2 (Nab2), have provided insight into the functions of this protein. TheNAB2gene is essential inS. cerevisiae, and conditionalnab2mutants cause defects in a number of steps in RNA processing. To explore the critical functions of the Nab2/ZC3H14 protein family, we performed a high-copy suppressor screen onnab2mutant cells. This screen identified genes encoding two core subunits of the RNA exosome, as well as Nrd1 and Ski7, nuclear and cytoplasmic cofactors of the RNA exosome, respectively. Nrd1 is an RNA binding protein that is part of the Nrd1-Nab3-Sen1 (NNS) complex, which plays an important role in transcription termination of non-coding RNAs. Ski7 is a GTP-binding protein that mediates interaction between the RNA exosome and the Ski complex, which targets RNA transcripts to the exosome for processing and degradation in the cytoplasm. To explore the functional interactions between the RNA exosome and Nab2, we employed RNA-seq analysis to identify the transcripts most impacted by overexpression of these exosome cofactors innab2mutant cells. This analysis revealed that many transcripts show small changes in steady-state levels, consistent with a global role of Nab2 in modulating transcript stability. This study uncovers functional interactions between the RNA exosome and Nab2 in both the nucleus and the cytoplasm.
Sinking the way: a dual role for CCR7 in collective leukocyte migration
Authors: Alanko Jonna , Ucar Mehmet Can , Canigova Nikola , Stopp Julian , Schwarz Jan , Merrin Jack , Hannezo Edouard , Sixt Michael
Published: February 2022

Immune responses crucially rely on the rapid and coordinated locomotion of leukocytes. While it is well established that single-cell migration is often guided by gradients of chemokines and other chemoattractants, it remains poorly understood how such gradients are generated, maintained and modulated. Combining experiment and theory on leukocyte chemotaxis guided by the G protein-coupled receptor (GPCR) CCR7, we demonstrate that in addition to its role as the sensory receptor that steers migration, CCR7 also acts as a generator and modulator of chemotactic gradients. Upon exposure to the CCR7 ligand CCL19, dendritic cells (DCs) effectively internalize the receptor and ligand as part of the canonical GPCR-desensitization response. We show that CCR7 internalization also acts as an effective sink for the chemoattractant, thereby dynamically shaping the spatio-temporal distribution of the chemokine. This mechanism drives complex collective migration patterns, enabling DCs to create or sharpen chemotactic gradients. We further show that these self-generated gradients can sustain the long-range guidance of DCs, adapt collective migration patterns to the size and geometry of the environment, as well as provide a guidance cue for other co-migrating cells. Such dual role of CCR7 as a GPCR that both senses and consumes its ligand can thus provide a novel mode of cellular self-organization.
Inactivation of B. cereus Spores in Whole Milk and Almond Milk by Novel Serpentine Path Coiled Tube UV-C System
Authors: Pendyala Brahmaiah , Patras Ankit , Gopisetty Vybhav Vipul Sudhir , Vashisht Pranav , Ravi Ramasamy
Published: February 2022

A novel continuous thin-film (1.59 mm) serpentine path coiled tube (SPCT) UV system operating at 254 nm wavelength was designed and compared with flow field distribution of whole milk with helical path coiled tube (HPCT) UV system using computational fluid dynamics. The results revealed efficient velocity magnitude distribution at serpentine bend geometric locations of the SPCT UV system. Further in this study, we evaluated B. cereus Spores inactivation in whole milk (WM) and almond milk (AM) using the developed SPCT UV system. Experimental data showed that > 4 log reduction of spores was achieved after six and ten passes of WM and AM at a flow rate of 70 and 162 mL/min, respectively. The biodosimetry method was used to verify the delivered reduction equivalent fluence (REF) and reported as 33 ± 0.73 and 36.5 ± 1.9 mJ/cm2. We noticed no significant effect on lipid oxidation and volatiles profile (p > 0.05) up to delivered REF of 60 mJ/cm2. This study demonstrated that high levels of inactivation of B. cereus spores could be feasible with minimal impact on product quality by UV-C processing of dairy and non-dairy opaque scattering fluids.
Blockage of Lamin-A/C loss diminishes the pro-inflammatory macrophage response
Authors: Mehl Johanna L. , Earle Ashley , Lammerding Jan , Mhlanga Musa , Vogel Viola , Jain Nikhil
Published: February 2022

Mutations and defects in nuclear lamins can cause major pathologies in affected tissues. Recent studies have also established potential links between lamins, inflammation, and inflammatory diseases but the underlying molecular mechanisms are unknown. We now report that pro-inflammatory activation of macrophages reduces levels of Lamin-A/C to augment pro-inflammatory gene expression and cytokine secretion. We show that activation of bone-marrow derived macrophages (BMDMs) degrades Lamin-A/C, as preceded by its phosphorylation, which is mediated by Caspase-6 and CDK1, respectively. Inhibiting Lamin-A/C phosphorylation and degradation severely inhibits pro-inflammatory gene expression and cytokine secretion. Using LPS-activated Lamin-A/C Knock Out BMDMs, we confirmed that the activation of the IFN-β-STAT pathway is amplified due to Lamin-A/C reduction, which ultimately augments the pro-inflammatory response. As Lamin-A/C is a previously unappreciated regulator of the pro-inflammatory macrophage response, our findings could provide novel opportunities to treat inflammatory diseases. In first proof-of-concept studies we show that macrophage pro-inflammation, as induced by Lipopolysaccharide or pathogenic E. coli, could be reduced by inhibiting Lamin-A/C phosphorylation and degradation. The inhibition of macrophage pro-inflammation could also be achieved by inhibiting members of the Lamin-A/C regulated IFN-β-STAT pathway, i.e., phospho-STAT1 and phospho-STAT3. This newly found mechanism to suppress the pro-inflammatory response of macrophages will provoke a re-thinking of how inflammation can be addressed therapeutically.
Estrogen suppresses DMRT1 expression during ovarian development in the chicken
Authors: Zhao Debiao , Liu Long , Nandi Sunil , Ioannidis Jason , Yang Xiurong , Gong Daoqing , McGrew Mike J. , Clinton Michael
Published: February 2022

Primary sex determination is the choice between two different developmental fates, a testis or an ovary. This selection is thought to require the action of a master regulator gene that triggers expression of a gene cascade in the bipotential gonad precursor in one sex. The selection of a particular developmental pathway is also thought to suppress the alternative developmental pathway.

In birds, where the male is the homogametic sex (ZZ) and females the heterogametic sex (ZW), the Z-linked transcription factor DMRT1 is considered the master regulator and has been shown to be essential for testis development, and to also inhibit the ovarian pathway. Here, we characterise in detail, DMRT1 transcription and protein levels during gonadal development in the chick. Our analysis suggests that DMRT1 protein levels are equivalent in male and female gonads during the bipotential phase of development, and that DMRT1 protein levels are reduced in the developing ovary during the differentiation phase. The reduction in DMRT1 protein levels in the somatic cells of the female medulla, coincides with the induction of aromatase expression and the initiation of estrogen synthesis. Analysis of sex-reversed gonads and mixed-sex chimeric gonads, suggests that the reduction in DMRT1 protein is due to inhibition of DMRT1 expression by estrogen.

Our data suggests that estrogen signalling is involved in primary sex determination by regulation of DMRT1 protein expression.
Structural Basis of HIV-1 Maturation Inhibitor Binding and Activity
Authors: Sarkar Sucharita , Zadrozny Kaneil K. , Zadorozhnyi Roman , Russell Ryan W. , Quinn Caitlin M. , Kleinpeter Alex , Ablan Sherimay , Xu Chaoyi , Perilla Juan R. , Freed Eric O. , Ganser-Pornillos Barbie K. , Pornillos Owen , Gronenborn Angela M. , Polenova Tatyana
Published: February 2022

HIV-1 maturation inhibitors (MIs) interfere with the final step in the viral lifecycle by disrupting the ordered proteolytic processing of the viral Gag polyprotein into its individual domains. Bevirimat (BVM) and its analogs interfere with the final catalytic cleavage of spacer peptide 1 (SP1) from the capsid protein (CA) C-terminal domain (CACTD), by binding to and stabilizing the CACTD-SP1 region. MIs are under development as alternative drugs to augment current antiretroviral therapies. Although promising, their mechanism of action and associated virus resistance pathways remain poorly understood at the molecular, biochemical, and structural levels. Here, we report atomic-resolution magic angle spinning (MAS) NMR structures of microcrystalline assemblies of CACTD-SP1 complexed with BVM and/or the assembly cofactor inositol hexakisphosphate (IP6). BVM and IP6 can bind simultaneously to SP1, with BVM positioned in the center of its 6-helix bundle in a unique conformation. Importantly, the NMR-observed structural effects of BVM on IP6 binding suggest that the inhibitor stabilizes the 6-helix bundle in multiple ways. In addition, BVM-resistant SP1-A1V and SP1-V7A variants exhibit distinct conformational and binding characteristics. Taken together, our results reveal a novel allosteric mechanism by which BVM disrupts maturation and provide a structural explanation for BVM resistance as well as important guidance for the design of new MIs.
Social dominance and reproduction result in increased integration of oxidative state in males of an African cichlid fish
Authors: Fialkowski Robert J. , Border Shana E. , Bolitho Isobel , Dijkstra Peter D.
Published: February 2022

Oxidative stress is a potential cost of social dominance and reproduction, which could mediate life history trade-offs between current and future reproductive fitness. However, the evidence for an oxidative cost of social dominance and reproduction is mixed, in part because organisms have efficient protective mechanisms that can counteract oxidative insults. Further, previous studies have shown that different aspects of oxidative balance, including oxidative damage and antioxidant function, varies dramatically between tissue types, yet few studies have investigated oxidative cost in terms of interconnectedness and coordination within the system. Here, we tested whether dominant and subordinate males of the cichlid Astatotilapa burtoni differ in integration of different components of oxidative stress. We assessed 7 markers of oxidative stress, which included both oxidative damage and antioxidant function in various tissue types (total of 14 measurements). Across all oxidative stress measurements, we found more co-regulated clusters in dominant males, suggesting that components of oxidative state are more functionally integrated in dominant males than they are in subordinate males. We discuss how a high degree of functional integration reflects increased robustness or efficiency of the system (e.g. increased effectiveness of antioxidant machinery in reducing oxidative damage), but we also highlight potential costs (e.g. activation of cytoprotective mechanisms may have unwanted pleiotropic effects). Overall, our results suggest that quantifying the extent of functional integration across different components of oxidative stress could reveal insights into the oxidative cost of important life history events.
6-Phosphogluconate dehydrogenase and its crystal structures
Authors: Hanau Stefania , Helliwell John R.
Published: February 2022

6-Phosphogluconate dehydrogenase (6PGDH; EC 1.1.1.44) catalyses the oxidative decarboxylation of 6-phosphogluconate to ribulose 5-phosphate in the context of the oxidative part of the pentose phosphate pathway. Depending on the species, it can be a homodimer or a homotetramer. Oligomerization plays a functional role not only because the active site is at the interface between subunits but also due to the interlocking tail-modulating activity, similar to that of isocitrate dehydrogenase and malic enzyme, which catalyse a similar type of reaction. Since the pioneering crystal structure of sheep liver 6PGDH, which allowed motifs common to the β-hydroxyacid dehydrogenase superfamily to be recognized, several other 6PGDH crystal structures have been solved, including those of ternary complexes. These showed that more than one conformation exists, as had been suggested for many years from enzyme studies in solution. It is inferred that an asymmetrical conformation with a rearrangement of one of the two subunits underlies the homotropic cooperativity. There has been particular interest in the presence or absence of sulfate during crystallization. This might be related to the fact that this ion, which is a competitive inhibitor that binds in the active site, can induce the same 6PGDH configuration as in the complexes with physiological ligands. Mutagenesis, inhibitors, kinetic and binding studies, post-translational modifications and research on the enzyme in cancer cells have been complementary to the crystallographic studies. Computational modelling and new structural studies will probably help to refine the understanding of the functioning of this enzyme, which represents a promising therapeutic target in immunity, cancer and infective diseases. 6PGDH also has applied-science potential as a biosensor or a biobattery. To this end, the enzyme has been efficiently immobilized on specific polymers and nanoparticles. This review spans the 6PGDH literature and all of the 6PGDH crystal structure data files held by the Protein Data Bank.
How can NGO accountability practices be improved with technologies such as blockchain and triple-entry accounting?
Authors: Kuruppu Sanjaya Chinthana , Dissanayake Dinithi , de Villiers Charl
Published: February 2022

Purpose

The purpose of this paper is to explore how blockchain and triple-entry accounting technologies may improve non-governmental organisation (NGO) accountability by amplifying the social and economic outcomes of aid. It also provides a critique of these technologies from an accountability perspective.

Design/methodology/approach

An in-depth case study of a large NGO, relying on semi-structured interviews, document analysis and non-participant observation, provides an understanding of current issues in existing NGO accountability and reporting systems. A novel case-conceptual critical analysis is then used to explore how blockchain and triple-entry accounting systems may potentially address some of the challenges identified with NGO accountability.

Findings

An empirical case study outlines the current processes which discharge accountability to a range of stakeholders, emphasising how “upward” accountability is privileged over other forms. This provides a foundation to illustrate how new technology can improve upward accountability to donors by enabling more efficient, accurate and auditable record-keeping and reporting, creating space for an NGO to focus on horizontal accountability to partner organisations and downward accountability to beneficiaries. Greater accountability exposes NGOs to diverse views from partner organisations and beneficiaries, potentially enhancing opportunities for learning and growth, i.e. greater impact. However, blockchain and triple-entry accounting can also create “over-accounting” and further entrench the power of upward stakeholders, such as donors, if not implemented carefully.

Research limitations/implications

A novel case-conceptual critical analysis furnishes new insights into how existing NGO accountability systems can be improved with technology. Despite the growing excitement about the possibilities of blockchain and triple-entry accounting systems, this paper offers a critical reflection on the limitations of these technologies and suggests avenues for future research.

Practical implications

Examples of how blockchain and triple-entry accounting systems can be integrated into NGO systems are presented. This research also raises the importance of creating a strong nexus between humans and technology, which ensures that “socialising” forms of accountability that empower vulnerable stakeholders, are embedded into international aid.

Originality/value

This research provides insight into present challenges with NGO accountability, using empirical evidence, furnishing potential solutions using novel blockchain and triple-entry accounting systems. Greater accountability to partner organisations and beneficiaries is important, as it potentially enables NGOs to learn how to be more impactful. Therefore, this paper introduces rich, contextually embedded perspectives on how NGO managers can exploit such technologies to enhance accountability and impact.
Benchmarking the banking sector of Bangladesh: a comprehensive analysis of performance and efficiency
Authors: Yesmine Tamanna , Hossain Md. Emran , Khan Md. Akhtaruzzaman , Mitra Sandip , Saha Sourav Mohan , Amin Md. Ruhul
Published: February 2022

Purpose

The economic development of Bangladesh is heavily reliant on the banking industry, yet it faces numerous hurdles, including liquidity issues, capital shortages, non-performing loans, inefficiencies and so on. Therefore, this study investigated the performance and efficiency of scheduled banks (state-owned, private commercial, foreign commercial and specialized banks) operating in Bangladesh.

Design/methodology/approach

The research was conducted using secondary data from annual reports of banks. The CAMELS rating system and Data Envelopment Analysis (DEA) methods were employed to measure the performance and efficiency of banks, respectively.

Findings

In the overall bank rankings, results revealed that foreign commercial Standard Chartered Bank and state-owned Sonali Bank Limited came in first and last position, respectively. Among the four categories of banks, foreign commercial banks were the best performer, while state-owned banks were the worst. Only two banks, i.e. Citibank NA and HSBC Bank, were scale efficient while the remaining banks were inefficient. In terms of performance and efficiency, state-owned and specialized banks were deemed wanting.

Practical implications

This study proposes recommendations to the policymakers that could lead to more effective tactics for improving the banking industry's performance and efficiency.

Originality/value

As far as the authors are concerned, this study presents empirical evidence on the performance and efficiency of different types of banks and explores comparisons among them, which has never been done to this extent in the country before.
Bajaj Auto (a) – catering to the African market
Authors: Gupta Nitin
Published: February 2022

Learning outcomes

After working through the case and assignment questions, students will be able to: understand how product markets in a given global region are to be analysed and assessed; assess various dimensions of consumer behaviour that would impact the strategies of a firm under consideration; identify how a firm can create its brand image and value proposition in a given international market; and evaluate and categorize various threat dimensions that a firm would experience in an international market.

Case overview/Synopsis

Bajaj Auto (BA) was India’s largest two-wheeler exporter, with ongoing exports to more than 75 countries worldwide. Besides being in other regions of the world, BA’s foray into the African market had been very successful, and it was growing from strength to strength in this market. BA’s motorcycles, three-wheeler rickshaws and small commercial vehicles had been successfully plying the roads of many countries in Africa such as Egypt, Nigeria and Kenya.

Rakesh Sharma (Sharma), the Executive Director of BA, knew very well that Africa was a high-risk-high-gain market for BA. Intense competition from Indian and international two-wheeler and three-wheeler manufacturers, global supply chain and logistics issues, various economic and legal challenges, and the threat of losing African consumer patronage were the challenging issues that Sharma was facing in this market. Would Sharma be able to effectively assess the market environment and consumer behaviour prevalent in the African countries? Would he be able to recognize BA’s brand and value-propositions and identify the international marketing challenges threatening BA’s smooth ride in this market?

Complexity academic level

The case can be taught in advanced undergraduate, MBA or executive-level programs.

Supplementary materials

Teaching notes are available for educators only.

Subject code

CSS 5: International Business.
The impact of ecotourism on local rural households' livelihood around Wolong Nature Reserve
Authors: Shi Huiyun , Zhang Lu , Song Boyao , He Chao
Published: February 2022

Purpose

The development of tourism around Wolong Nature Reserve changes the local communities' ways of life. This study discusses how ecotourism affects the households' use of their capitals, the livelihood strategies as well as illustrates the impact on the habitats in the reserve through Department for International Development’s (DFID) Sustainable Livelihood Framework (SLF) with data collected during fieldwork.

Design/methodology/approach

The study focuses on (1) Calculating Livelihood Capital Index. (2) The effects of livelihood capitals on livelihood strategy were calculated by multinomial logistic regression.

Findings

The study has yielded the following results: (1) In general, tourism promotes people's livelihood capitals. The growth in different types of households under tourism settings is ranked as full-time tourism operators > part-time tourism operators > traditional living households. (2) Tourism development mainly shifts livelihood strategies in two ways. Firstly, travel operating replaces some traditional practices that make livings; secondly, increased needs for potherbs and herbs from tourists let households enter into the hills to pick the plants more actively, which intensifies the destruction of giant panda's habitats. (3) Nine types of livelihood capitals indicators, namely farmland quality, distance between house and roads, number of laborers, average housing area, average income per person, whether family members being village cadres, and ever having received skills training shape livelihood strategies in different levels.

Originality/value

Three discussions are drawn from the study: (1) Enhancing the exploit for tourism resources to form a diversified competition. (2) Introducing herb growing to fulfill tourists' needs and improve people's livelihood in the meantime. (3) Optimizing the tourism surveillance and management system and improving the rules and regulations.
Management commitment to the ecological environment, green work engagement and their effects on hotel employees’ green work outcomes
Authors: Karatepe Tuna , Ozturen Ali , Karatepe Osman M. , Uner M. Mithat , Kim Taegoo Terry
Published: February 2022

Purpose

Using social exchange, signaling, job demands-resources and reformulation of attitude theories, the purpose of this paper is to propose and test a research model in which green work engagement (GWEN) mediates the impact of management commitment to the ecological environment (MCEE) on green creativity, task-related pro-environmental behavior (PEB) and proactive PEB.

Design/methodology/approach

Data for the paper were obtained from hotel customer-contact employees in Turkey and South Korea. The hypothesized associations were assessed via structural equation modeling.

Findings

The findings in Studies 1 and 2 supported the viability of the model. Specifically, GWEN partially mediated the effect of MCEE on task-related and proactive PEB, while it fully mediated the influence of MCEE on green creativity.

Practical implications

Management should invest and/or go on investing in environmental sustainability to send strong signals to employees that the organization really cares about the environment and is highly committed to the preservation and protection of the environment. With green training, empowerment and rewards, management can boost employees’ GWEN, which motivates them to engage in environmentally responsible behaviors.

Originality/value

The paper advances current knowledge by testing the relationship of MCEE, as appraised by employees, to their GWEN and green work outcomes. More importantly, the paper has explored the impact of GWEN in the intermediate relationship between MCEE and critical green work outcomes, such as green creativity, task-related PEB and proactive PEB. Further, the paper adds to the extant research by assessing the antecedents and outcomes of GWEN.
Effect of debt structure concentration on the investment–cash flow sensitivity of Brazilian companies
Authors: Eça João Paulo Augusto , Tarantin Júnior Wilson , do Valle Maurício Ribeiro
Published: February 2022

Purpose

This paper aims to analyze whether a relationship exists between the debt structure concentration and investment–cash flow sensitivity of Brazilian companies.

Design/methodology/approach

The study is based on a sample of 500 Brazilian firms (337 unlisted and 163 listed) in the 10-year period from 2010 to 2019 analyzed according to the investment–cash flow sensitivity model.

Findings

The results show evidence that companies with more concentrated debt structures tend to have lower investment sensitivity to internal cash flow. In other words, firms with a greater concentration of debts tend to have less investment–cash flow sensitivity. In general, the results are robust to (1) variation of the debt concentration proxy and the independent variable; (2) the control of fixed effects in different dimensions and (3) use of estimator for endogeneity treatment, i.e. two-stage least squares (2SLS) and generalized method of moments (GMM).

Originality/value

Various studies have investigated whether specific financing sources reduce financial constraints, but few have addressed the relationship between debt concentration and these constraints. Besides this, to the best of the authors’ knowledge, no previous study has investigated the mentioned relationship in a sample of unlisted firms. This analysis is relevant since the effects of financial constraints tend to be stronger on companies that have restricted access to the capital market.
Attachment insecurity in unaccompanied refugees: a longitudinal study
Authors: Sleijpen Marieke , Keles Serap , Mooren Trudy , Oppedal Brit
Published: February 2022

Purpose

This study aims to focus on the avoidance and anxiety attachment patterns among unaccompanied refugee minors (URMs) after resettlement in Norway. The authors explored the extent of stability and change in these attachment patterns and the role of demographic and interpersonal predictors of change in levels of attachment insecurity.

Design/methodology/approach

Three waves of data were analyzed with latent growth curve modeling. The sample consisted of 918 refugees who had arrived in Norway as unaccompanied minor asylum seekers and were granted residence. Of the initial sample, 82% were male and the mean age was 18.6 years (SD = 2.61).

Findings

Results revealed substantial stability in attachment patterns: anxiety patterns did not change over time, while avoidance patterns increased, but only marginally.

Research limitations/implications

A large sample of URMs revealed rather stabile attachment patterns over time, underlining the need for social support that fosters their adjustment processes best. More research is needed to clarify the mechanism underlying the stability and change in attachment patterns and to understand better how these young people can be supported emotionally during their resettlement process in the absence of parental care.

Social implications

Host societies could perhaps invest more in promoting successful and sustainable adult relationships for unaccompanied refugees approaching the age of 18 years. This may help them to cope better with acculturation stressors and negative past experiences and may thereby improve their future mental health and social relationships.

Originality/value

Targeting competencies to develop and maintain close relationships may be particularly important for URM’s, because this may alleviate risks for mental health related to past and current stressors as well as loneliness. To the best of the authors’ knowledge, the present study is the first to investigate stability and change in attachment insecurity among unaccompanied refugees.