bluuebunny/crossref_metadata_2025 huggingface dataset:
PNLDC1 catalysis and postnatal germline function are required for piRNA trimming, LINE1 silencing, and spermatogenesis in mice
Authors: Wei Chao , Yan Xiaoyuan , Mann Jeffrey M. , Geng Ruirong , Xie Huirong , Demireva Elena Y. , Sun Liangliang , Ding Deqiang , Chen Chen
Published: December 2023

PIWI-interacting RNAs (piRNAs) play critical and conserved roles in transposon silencing and gene regulation in the animal germline. Two distinct piRNA populations are present during mouse spermatogenesis: pre-pachytene piRNAs in fetal/neonatal testes and pachytene piRNAs in adult testes. PNLDC1 is required for both pre-pachytene piRNA and pachytene piRNA 3’ end maturation in multiple species. However, whether PNLDC1 is the bona fide piRNA trimmer and the physiological role of 3’ trimming of two distinct piRNA populations in spermatogenesis remain unclear. Here, by inactivatingPnldc1exonuclease activity in vitro and in mice, we reveal that PNLDC1 trimmer activity is required for both pre-pachytene piRNA and pachytene piRNA 3’ end trimming and male fertility. Furthermore, conditional inactivation ofPnldc1in postnatal germ cells causes LINE1 transposon de-repression and spermatogenic arrest in mice. This indicates that pachytene piRNA trimming, but not pre-pachytene piRNA trimming, is essential for mouse germ cell development and transposon silencing. Our findings highlight the potential of inhibiting germline piRNA trimmer activity as a potential means for male contraception.
Revealing the spatial characteristics of rice heat exposure in Japan through panicle temperature analysis
Authors: Toda Yusuke , Ishigooka Yasushi , Yoshimoto Mayumi , Takimoto Takahiro , Kuwagata Tsuneo , Makowski David , Hasegawa Toshihiro
Published: December 2023

Elevated temperatures during the flowing stage contribute to heat-induced spikelet sterility in rice, posing a major threat to production considering climate change projections. Developing effective strategies for stable rice production through breeding and crop management is critical; however, our understanding of regional, seasonal, and long-term trends in rice heat exposure remains limited. Previous studies on spikelet sterility revealed that panicle temperature, estimated using a micrometeorological model and common meteorological factors, serves as a reliable indicator of rice heat exposure. In this study, we employed this model to identify the differences between panicle and air temperatures (DPAT) and their causes over the past 45 years in Japan. A gridded daily meteorological dataset covering Japan was interpolated at an hourly time step and used as input data of the micrometeorology model for estimating panicle temperatures during flowering. Statistical analysis of the resulting data revealed an increasing trend in the frequency of rice panicle heat exposure over time across many locations in Japan. During heat-receptive periods, panicle temperature generally exceeded air temperature, indicating the inadequacy of relying solely on air temperature to gauge rice heat stress. DPAT values showed substantial inter-regional variations in both mean values (from −0.5℃ to 3.0℃) and seasonality. Through machine learning and statistical methods, the relationship between DPAT and meteorological factors was characterized, delineating the effects of the meteorological factors on regional and seasonal DPAT variations. Focusing on major high-risk regions, we show that mitigation strategies should be adapted to consider regional characteristics and avoid high DPAT conditions during rice heading periods.
Single-cell transcriptional mapping reveals genetic and non-genetic determinants of aberrant differentiation in AML
Authors: Zeng Andy G.X. , Iacobucci Ilaria , Shah Sayyam , Mitchell Amanda , Wong Gordon , Bansal Suraj , Chen David , Gao Qingsong , Kim Hyerin , Kennedy James A. , Arruda Andrea , Minden Mark D. , Haferlach Torsten , Mullighan Charles G. , Dick John E.
Published: December 2023

In acute myeloid leukemia (AML), genetic mutations distort hematopoietic differentiation, resulting in the accumulation of leukemic blasts. Yet, it remains unclear how these mutations intersect with cellular origins and whether they converge upon similar differentiation patterns. Single-cell RNA sequencing (scRNA-seq) has enabled high-resolution mapping of the relationship between leukemia and normal cell states, yet this application is hampered by imprecise reference maps of normal hematopoiesis and small sample sizes among patient cohorts. As a first step we constructed a reference atlas of human bone marrow hematopoiesis from 263,519 single-cell transcriptomes spanning 55 cellular states, that was benchmarked against independent datasets of immunophenotypically pure hematopoietic stem and progenitor cells. Using this reference atlas, we mapped over 1.2 million single-cell transcriptomes spanning 318 AML, mixed phenotype acute leukemia (MPAL), and acute erythroid leukemia (AEL) samples. This large-scale analysis, together with systematic mapping of genotype-to-phenotype associations between driver mutations and differentiation landscapes, revealed convergence of diverse genetic alterations on twelve recurrent patterns of aberrant differentiation in AML. This included unconventional lymphoid and erythroid priming linked toRUNX1andTP53mutations, respectively. We also identified non-genetic determinants of AML differentiation such as two subgroups ofKMT2A-rearranged AML that differ in the identity of their leukemic stem cells (LSCs), likely reflecting distinct cellular origins. Furthermore, distinct LSC-driven hierarchies can co-exist within individual patients, providing insights into AML evolution. Together, precise mapping of normal and malignant cell states provides a framework for advancing the study and disease classification of hematologic malignancies thereby informing therapy development.
Potential survival strategies of novel comammox and nitrite-oxidizingNitrospirapresent in a reactor treating high-ammonia brackish landfill leachate
Authors: Yasuda Shohei , Palomo Alejandro , Smets Barth F. , Terada Akihiko
Published: December 2023

Nitrification is mediated by numerous different microorganisms, but knowledge of their ecophysiologies is insufficient. Leachate in the late stages of landfill operation provides a brackish environment with a high ammonia concentration, and methanol is added as an electron donor for denitrification. Such a unique environment may contain novel nitrifiers. Here, we present metagenomic analysis of the microbiome from a closed landfill leachate treatment facility to investigate the identity and functions of nitrifiers. Using a genome-centric approach with metagenomic analysis, we retrieved draft genomes for a novel complete ammonia-oxidizing (comammox) bacteriumNitrospiraLAS72; and canonicalNitrospiraLAS18, clustered within a novel sub-lineage VII ofNitrospira;CandidatusNitrosocosmicus LAS21 andNitrosarchaeumLAS73, belonging to the ammonia-oxidizing archaea (AOA). This is the first evidence of comammoxNitrospirain a high-ammonia-containing brackish environment. Canonical ammonia-oxidizing bacteria were not detected. Given the brackish environment and supplementation of methanol used in the facility, we also investigated the methanol metabolism of these nitrifiers and their potential to produce compatible solutes as osmoprotectants. Uniquely amongNitrospira, comammoxNitrospiraLAS72 possesses genes associated with formaldehyde reductase and glycine betaine biosynthesis. Thus,NitrospiraLAS72 may proliferate because of the availability of formaldehyde upstream of carbon metabolism and adapt to fluctuating osmotic pressure by producing a variety of compatible solutes. The discovery of this novel comammoxNitrospira,and canonicalNitrospiraforming a new sub-lineage VII in an ammonia-concentrated brackish environment broadens our knowledge of the diversity and functions of nitrifying microorganisms.
Decoding mutational hotspots in human disease through the gene modules governing thymic regulatory T cells
Authors: Raposo Alexandre A. S. F. , Rosmaninho Pedro , Silva Susana L. , Paço Susana , Brazão Maria E. , Godinho-Santos Ana , Tokunaga Yumie , Nunes-Cabaço Helena , Serra-Caetano Ana , Almeida Afonso R. M. , Sousa Ana E.
Published: December 2023

ABTRACT

Computational strategies to extract meaningful biological information from multiomics data are in great demand for effective clinical use. This is most relevant in immune-mediated disorders, where the combined impact of multiple variants is difficult to determine. Regulatory T cells (Tregs), particularly those lineage-committed in the thymus, are essential for immune homeostasis and self-tolerance, controlling inflammatory and autoimmune processes in many diseases with a multigenic basis. Here, we quantify the Transcription Factor (TF) differential occupancy landscape to uncover the Gene Regulatory Modules governing human thymic Tregs, providing a tool to prioritise variants in complex diseases. Combined RNA-seq and ATAC-seq generated a matrix of differential TF binding to genes differentially expressed in Tregs, in contrast to their counterpart conventional CD4 single-positive thymocytes. The gene loci of both established and novel genetic interactions uncovered by the Gene Regulatory Modules were significantly enriched in rare variants carried by patients with common variable immunodeficiency, here used as a model of polygenic-based disease with severe inflammatory and autoimmune manifestations. The Gene Regulatory Modules controlling the Treg signature can, therefore, be a valuable resource for variant classification, and to uncover new therapeutic targets. Overall, we provide a tool to decipher mutational hotspots in individual genomes.
Species-specific design of artificial promoters by transfer-learning based generative deep-learning model
Authors: Xia Yan , Du Xiaowen , Liu Bin , Guo Shuyuan , Huo Yi-Xin
Published: December 2023

Native prokaryotic promoters share common sequence patterns, but are species dependent. For understudied species with limited data, it is challenging to predict the strength of existing promoters and generate novel promoters. Here, we developed PromoGen, a collection of nucleotide language models to generate species-specific functional promoters, across dozens of species in a data and parameter efficient way. Twenty-seven species-specific models in this collection were finetuned from the pretrained model which was trained on multi-species promoters. When systematically compared with native promoters, theEscherichia coli-andBacillus subtilis-specific artificial PromoGen-generated promoters (PGPs) were demonstrated to hold all distribution patterns of native promoters. A regression model was developed to score generated either by PromoGen or by another competitive neural network, and the overall score of PGPs is higher. Encouraged byin silicoanalysis, we further experimentally characterized twenty-twoB. subtilisPGPs, results showed that four of tested PGPs reached the strong promoter level while all were active. Furthermore, we developed a user-friendly website to generate species-specific promoters for 27 different species by PromoGen. This work presented an efficient deep-learning strategy forde novospecies-specific promoter generation even with limited datasets, providing valuable promoter toolboxes especially for the metabolic engineering of understudied microorganisms.
PDGFRα/β heterodimer activation negatively affects downstream ERK1/2 signaling and cellular proliferation
Authors: Campaña Maria B. , Perkins Madison R. , McCabe Maxwell C. , Neumann Andrew , Larson Eric D. , Fantauzzo Katherine A.
Published: December 2023

The platelet-derived growth factor receptor (PDGFR) family of receptor tyrosine kinases allows cells to communicate with one another by binding to growth factors at the plasma membrane and activating intracellular signaling pathways to elicit responses such as migration, proliferation, survival and differentiation. The PDGFR family consists of two receptors, PDGFRα and PDGFRβ, that dimerize to form PDGFRα homodimers, PDGFRα/β heterodimers and PDGFRβ homodimers. Here, we overcame prior technical limitations in visualizing and purifying PDGFRα/β heterodimers by generating a cell line stably expressing C-terminal fusions of PDGFRα and PDGFRβ with bimolecular fluorescence complementation fragments corresponding to the N-terminal and C-terminal regions of the Venus fluorescent protein, respectively. We found that these receptors heterodimerize relatively quickly in response to PDGF-BB ligand treatment, with a peak of receptor autophosphorylation following 5 minutes of ligand stimulation. Moreover, we demonstrated that PDGFRα/β heterodimers are rapidly internalized into early endosomes, particularly signaling endosomes, where they dwell for extended lengths of time. We showed that PDGFRα/β heterodimer activation does not induce downstream phosphorylation of ERK1/2 and significantly inhibits cell proliferation. Further, we characterized the PDGFR dimer-specific interactome and identified MYO1D as a novel protein that preferentially binds PDGFRα/β heterodimers. We demonstrated that knockdown of MYO1D leads to retention of PDGFRα/β heterodimers at the plasma membrane, resulting in increased phosphorylation of ERK1/2 and increased cell proliferation. Collectively, our findings impart valuable insight into the molecular mechanisms by which specificity is introduced downstream of PDGFR activation to differentially propagate signaling and generate distinct cellular responses.

One-sentence summary

PDGFRα/β heterodimer binding to MYO1D contributes to rapid internalization of the dimerized receptors, thereby negatively affecting downstream ERK1/2 signaling and cellular proliferation.
The genetic consequences of population marginality: a case study in maritime pine
Authors: Theraroz Adélaïde , Guadaño-Peyrot Carlos , Archambeau Juliette , Pinosio Sara , Bagnoli Francesca , Piotti Andrea , Avanzi Camilla , Vendramin Giovanni G. , Alía Ricardo , Grivet Delphine , Westergren Marjana , González-Martínez Santiago C.
Published: December 2023

Aim

Marginal tree populations, either those located at the edges of the species’ range or in suboptimal environments, are often a valuable genetic resource for biological conservation. However, there is a lack of knowledge about the genetic consequences of population’s marginality, estimated across entire species’ ranges. Our study addresses this gap by providing information about several genetic indicators and their variability in marginal and core populations identified using quantitative marginality indices.

Location

Southwestern Europe and North Africa.

Methods

Using 10,185 SNPs across 82 populations of maritime pine (Pinus pinasterAit.), a widespread and economically important conifer characterised by a fragmented range, we modelled the relationship of seven genetic indicators potentially related to population evolutionary resilience, namely genetic diversity (based on all SNPs and two kind of outlier loci), inbreeding, genetic differentiation, recessive genetic load and genomic offset, with population geographical, demo-historical and ecological marginality (as estimated by nine quantitative indices). Models were constructed for both regional (introducing gene pool as random factor) and range-wide spatial scales.

Results

We showed a trend towards decreasing overall genetic diversity (albeit not necessarily for genetic diversity estimates based on outlier loci) and increasing differentiation with geographic marginality, supporting the centre-periphery hypothesis (CPH). Moreover, we found no correlation between population inbreeding and marginality, while geographically marginal populations had a lower recessive genetic load (only models without the gene pool effect) and ecologically marginal populations had a higher genomic offset, suggesting higher maladaptation to future climate.

Main conclusions

Overall, our results indicate that marginal populations could be at higher risk of maladaptation to climate change than core populations, despite reduced levels of genetic load, a risk that is exacerbated by typically small effective population sizes and increasing human impact.
Structural basis for constitutive activation and CXCL1 recognition of human herpesvirus 8-encoded G protein-coupled receptor KSHV-GPCR
Authors: Liu Aijun , Liu Yezhou , Llinàs del Torrent Masachs Clàudia , Zhang Weijia , Pardo Leonardo , Ye Richard D.
Published: December 2023

Kaposi’s sarcoma-associated herpesvirus (KSHV) encodes a viral G protein-coupled receptor, KSHV-GPCR, that contributes to KSHV immune evasion and pathogenesis of Kaposi’s Sarcoma. KSHV-GPCR shares a high similarity with CXC chemokine receptors CXCR2 and can be activated by selected chemokine ligands. KSHV-GPCR is also unique for its constitutive activity by coupling to various G proteins. We investigated the structural basis of ligand-dependent as well as constitutive activity of KSHV-GPCR through cryo-EM structural determination of KSHV-GPCR-Gi signaling complexes with and without bound CXCL1 chemokine ligand. Analysis of the apo-KSHV-GPCR-Gi structure, with an overall resolution of 2.81 Å, unraveled the involvement of extracellular loop 2 in constitutive activation of the receptor. This and other structural motifs serve to stabilize the constitutively-active KSHV-GPCR. The CXCL1-bound KSHV-GPCR-Gi structure was solved to an overall resolution of 3.01 Å, and showed a two-site binding of the chemokine by the receptor. Together with functional validations, this work shed light on the structural basis for constitutive as well as CXCL1-induced activation of KSHV-GPCR. The work also demonstrates evolutionary advantage in immune evasion by KSHV through its virally encoded chemokine receptor, with potential implications in developing therapeutic strategies for KSHV infection.
Chitinase 3-like-1 (CHI3L1) Inhibits Innate Anti-Tumor and Tissue Remodeling Immune Responses by Regulating CD47-SIRPα and CD24-Siglec10-Mediated Phagocytosis
Authors: Ma Bing , Kamle Suchitra , Lee Chang-Min , Lee Joyce H , Yee Daniel C , Zhu Zhou , Silverman Edwin K. , DeMeo Dawn L. , Choi Augustine M.K. , Lee Chun Geun , Elias Jack A.
Published: December 2023

Innate immune responses such as phagocytosis are critically linked to the generation of adaptive immune responses against the neoantigens in cancer and the efferocytosis that is essential for homeostasis in diseases characterized by lung injury, inflammation, and remodeling as in Chronic Obstructive Pulmonary Disease (COPD). Chitinase 3-like-1 (CHI3L1) is induced in many cancers where it inhibits adaptive immune responses by stimulating immune checkpoint molecules (ICPs) and portends a poor prognosis. CHI3L1 is also induced in COPD where it regulates epithelial cell death. Here we demonstrate that pulmonary melanoma metastasis inhibits macrophage phagocytosis by stimulating the CD47-SIRPα and CD24-Siglec10 phagocytosis checkpoint pathways while inhibiting macrophage “eat me” signals from calreticulin and HMGB1. We also demonstrate that these effects on macrophage phagocytosis are mediated by CHI3L1 stimulation of the SHP-1 and SHP-2 phosphatases and the inhibition of the accumulation and phosphorylation of cytoskeleton-regulating non-muscle myosin IIa. This inhibition of innate immune responses like phagocytosis provides a mechanistic explanation for the ability of CHI3L1 to stimulate ICPs and inhibit adaptive immune responses in cancer and diseases like COPD. The ability of CHI3L1 to simultaneously inhibit innate immune responses, stimulate ICPs, inhibit T cell co-stimulation, and regulate a number of other oncogenic and inflammation pathways suggest that CHI3L1-targeted therapeutics are promising interventions in cancer, COPD and other disorders.
Identification of genes supporting cold resistance of mammalian cells: lessons from a hibernator
Authors: Sone Masamitsu , Mitsuhashi Nonoka , Sugiura Yuki , Matsuoka Yuta , Maeda Rae , Yamauchi Akari , Okahashi Ryoto , Yamashita Junpei , Sone Kanako , Enju Sachiyo , Anegawa Daisuke , Yamaguchi Yoshifumi
Published: December 2023

Susceptibility of human cells to cold stress restricts the use of therapeutic hypothermia and long-term preservation of organs at low temperatures. In contrast, cells of mammalian hibernators possess remarkable cold resistance, but little is known about the molecular mechanisms underlying this phenomenon. In this study, we conducted a gain-of-function screening of genes that confer cold resistance to cold-vulnerable human cells using a cDNA library constructed from the Syrian hamster, a mammalian hibernator, and identified Gpx4 as a potent suppressor of cold-induced cell death. Additionally, genetic or pharmacological inhibition of Gpx4 in a hamster cell line under prolonged cold culture led to cell death, which resembles ferroptosis characterized by accumulation of lipid peroxide and ferrous iron dependency. Genetic disruption of other ferroptosis-suppressing pathways, namely biopterin synthesis and mitochondrial or plasma membrane CoQ reduction pathways, accelerated cold-induced cell death under Gpx4 dysfunction. Collectively, ferroptosis-suppressing pathways protect the cells of a mammalian hibernator from cold-induced cell death and the augmentation of these pathways renders cold resistance to cells of non-hibernators, including humans.
Neuroprotective Effects of VEGF-B in a Murine Model of Aggressive Neuronal Loss With Childhood Onset
Authors: Pérez-Revuelta L. , Pérez-Boyero D. , Pérez-Martín E. , Cabedo VL , Téllez de Meneses PG , Weruaga E , Díaz D , Alonso JR
Published: December 2023

In recent decades, the scientific community has faced a major challenge in the search for new therapies that can slow down or alleviate the process of neuronal death that accompanies neurodegenerative diseases. This study aimed at identifying an effective therapy using neurotrophic factors to delay the rapid and aggressive cerebellar degeneration experienced by the Purkinje Cell Degeneration (PCD) mouse, a model of childhood-onset neurodegeneration with cerebellar atrophy (CONDCA). Initially, we analyzed the changes in the expression of several neurotrophic factors related to the degenerative process itself, identifying changes in insulin-like growth factor 1 (IGF-1) and Vascular Endothelial Growth Factor B (VEGF-B) in the affected animals. Then, we administered pharmacological treatments using human recombinant IGF-1 (rhIGF-1) or VEGF-B (rhVEGF-B) proteins, considering their temporal variations during the degenerative process. The effects of these treatments on motor, cognitive, and social behavior, as well as on cerebellar destructuration were analyzed. Whereas treatment with rhIGF-1 did not demonstrate any neuroprotective effect, rhVEGF-B administration at moderate dosages stopped the process of neuronal death and restored motor, cognitive, and social functions altered in PCD mice (and CONDCA patients). Additionally, we demonstrate that this neuroprotective effect was achieved through a partial inhibition or delay of apoptosis. These findings provide strong evidence supporting the use of rhVEGF-B as a pharmacological agent to limit severe cerebellar neurodegenerative processes.
Cell-Specific Gene Networks and Drivers in Rheumatoid Arthritis Synovial Tissues
Authors: Pelissier Aurelien , Laragione Teresina , Gulko Percio S. , Martínez María Rodríguez
Published: December 2023

Rheumatoid arthritis (RA) is a common autoimmune and inflammatory disease characterized by inflammation and hyperplasia of the synovial tissues. RA pathogenesis involves multiple cell types, genes, transcription factors (TFs) and networks. Yet, little is known about the TFs, and key drivers and networks regulating cell function and disease at the synovial tissue level, which is the site of disease. In the present study, we used available RNA-seq databases generated from synovial tissues and developed a novel approach to elucidate cell type-specific regulatory networks on synovial tissue genes in RA. We leverage established computational methodologies to infer sample-specific gene regulatory networks and applied statistical methods to compare network properties across phenotypic groups (RA versus osteoarthritis). We developed computational approaches to rank TFs based on their contribution to the observed phenotypic differences between RA and controls across different cell types. We identified 18,16,19,11 key regulators of fibroblast-like synoviocyte (FLS), T cells, B cells, and monocyte signatures and networks, respectively, in RA synovial tissues. Interestingly, FLS and B cells were driven by multiple independent co-regulatory TF clusters that included MITF, HLX, BACH1 (FLS) and KLF13, FOSB, FOSL1 (synovial B cells). However, monocytes were collectively governed by a single cluster of TF drivers, responsible for the main phenotypic differences between RA and controls, which included RFX5, IRF9, CREB5. Among several cell subset and pathway changes, we also detected reduced presence of NKT cell and eosinophils in RA synovial tissues. Overall, our novel approach identified new and previously unsuspected KDG, TF and networks and should help better understanding individual cell regulation and co-regulatory networks in RA pathogenesis, as well as potentially generate new targets for treatment.
Gene Network Analyses Identify Co-regulated Transcription Factors and BACH1 as a Key Driver in Rheumatoid Arthritis Fibroblast-like Synoviocytes
Authors: Pelissier Aurelien , Laragione Teresina , Harris Carolyn , Martínez María Rodríguez , Gulko Percio S.
Published: December 2023

RNA-sequencing and differential gene expression studies have significantly advanced our understanding of pathogenic pathways underlying Rheumatoid Arthritis (RA). Yet, little is known about cell-specific regulatory networks and their contributions to disease. In this study, we focused on fibroblast-like synoviocytes (FLS), a cell type central to disease pathogenesis and joint damage in RA. We used a strategy that computed sample-specific gene regulatory networks (GRNs) to compare network properties between RA and osteoarthritis FLS. We identified 28 transcription factors (TFs) as key regulators central to the signatures of RA FLS. Six of these TFs are new and have not been previously implicated in RA, and included BACH1, HLX, and TGIF1. Several of these TFs were found to be co-regulated, and BACH1 emerged as the most significant TF and regulator. The main BACH1 targets included those implicated in fatty acid metabolism and ferroptosis. The discovery of BACH1 was validated in experiments with RA FLS. Knockdown of BACH1 in RA FLS significantly affected the gene expression signatures, reduced cell adhesion and mobility, interfered with the formation of thick actin fibers, and prevented the polarized formation of lamellipodia, all required for the RA destructive behavior of FLS. This is the first time that BACH1 is shown to have a central role in the regulation of FLS phenotypes, and gene expression signatures, as well as in ferroptosis and fatty acid metabolism. These new discoveries have the potential to become new targets for treatments aimed at selectively targeting the RA FLS.
Community-based peptidomic clustering reveals pathogen-specific proteolytic signatures in wounds
Authors: Hartman Erik , Forsberg Fredrik , Kjellström Sven , Petrlova Jitka , Luo Congyu , Scott Aaron , Puthia Manoj , Malmström Johan , Schmidtchen Artur
Published: December 2023

Recent advances in mass spectrometry-based peptidomics has catalyzed the identification and quantification of thousands endogenous peptides across diverse biological systems. However, the large theoretical peptidomic landscape and high proportion of missing values poses several challenges for downstream analyses and limits the comparability of clinical samples. Here, we present a generalizable computational workflow that clusters peptides with overlapping sequences to reduce the dimensionality of peptidomic data, improve the definition of protease cut-sites, enhance inter-sample comparability, and enable the implementation of reliable and large-scale data analysis methods akin to those employed in other omics fields. We showcase the algorithm by performing large-scale quantitative analysis of wound fluid peptidomes of highly defined porcine wounds and human clinical non-healing wounds. The analysis revealed signature phenotype-specific peptide regions reflecting pathogen-specific proteolytic activity at the earliest stages of colonization, resulting in novel class of potential peptide cluster-based biomarkers.
Higher-order correction of persistent batch effects in correlation networks
Authors: Micheletti Soel , Schlauch Daniel , Quackenbush John , Guebila Marouen Ben
Published: December 2023

Systems biology methods often rely on correlations in gene expression profiles to infer co-expression networks, commonly used as input for gene regulatory network inference or to identify functional modules of co-expressed or co-regulated genes. While systematic biases, including batch effects, are known to induce spurious associations and confound differential gene expression analyses (DE), the impact of batch effects on gene co-expression has not been fully explored. Methods have been developed to adjust expression values, ensuring conditional independence of mean and variance from batch or other covariates for each gene. These adjustments have been shown to improve the fidelity of DE analysis. However, these methods do not address the potential for spurious differential co-expression (DC) between groups. Consequently, uncorrected, artifactual DC can skew the correlation structure, leading network inference methods that use gene co-expression to identify false, nonbiological associations, even when the input data is corrected using standard batch correction.

In this work, we demonstrate the persistence of confounders in covariance after standard batch correction using synthetic and real-world gene expression data examples. Subsequently, we introduce Co-expression Batch Reduction Adjustment (COBRA), a method for computing a batch-corrected gene co-expression matrix based on estimating a conditional covariance matrix. COBRA estimates a reduced set of parameters expressing the co-expression matrix as a function of the sample covariates, allowing control for continuous and categorical covariates. COBRA is computationally efficient, leveraging the inherently modular structure of genomic data to estimate accurate gene regulatory associations and facilitate functional analysis for high-dimensional genomic data.
Economic recovery through the money supply and public spending in Morocco: an empirical investigation
Authors: Benkhaira Jihane , El Hassani Hafid
Published: December 2023

Purpose

The present article aims to estimate an autoregressive vector model covering the period of 1990–2021 to analyze the effect of public spending and monetary supply increases in economic activity in Morocco.

Design/methodology/approach

A literature review on the policy of recovery with fiscal and monetary tools and its theoretical foundations was established. Then, an empirical study on the Moroccan context was executed to study the effectiveness of these instruments in Morocco from 1990 to 2021, using autoregressive vector modeling.

Findings

The results present a state of a positive relationship and statistical significance of public spending, money supply and economic growth. The impulse response function analysis and the forecast error variance decomposition showed that public spending does not have a large impact on gross domestic product, while the money supply has a real power to stimulate the growth of economic activity in Morocco.

Originality/value

This study aims to demonstrate the positive effect of the coordination of public spending and monetary supply increases on gross domestic product in Morocco. Additionally, the analysis using vector autoregressive modeling, impulse response functions, variance decomposition techniques and causality tests, provides crucial insights to guide researchers, practitioners and policymakers in developing more effective and resilient economic strategies. The findings from this study not only illuminate immediate recovery strategies but also contribute to strengthening the resilience of economies against potential future shocks.
Territoriality and social values: textual analysis of the #ConMuchoAcento campaign by Cruzcampo beer
Authors: López-Agulló Pérez-Caballero José Manuel , Ávila Rodríguez-de-Mier Belén , García-Chamizo Fernando
Published: December 2023

Purpose

The aim of this research is to analyze the territorialization strategy developed by the Spanish brewing company Cruzcampo through its campaign #ConMuchoAcento (#With a strong accent) launched in January 2021.

Design/methodology/approach

The work is framed within the case study methodology. Semiotics will be the discipline used to establish the set of cultural units or signs that the company puts into play in its campaign #ConMuchoAcento.

Findings

Cruzcampo beer makes use of place branding by highlighting the Andalusian accent as a way of creating a unique positioning strategy. By doing so, the brewing company faces the issue of being associated with the negative Andalusian stereotype, sometimes regarded as if it were uneducated and low class. The use of dialectic must be seen as a step further in place branding strategy since it brings locality to the commercial message.

Social implications

The social effects of the cultural units brought into play by the #ConMuchoAcento campaign remain to be analyzed, that is, the political dimension of this exercise of signifying agency of Andalusian culture. In other words, it remains to be seen how the accent represents that romantic Andalusian ideal of “authenticity” as that form of subjectivity at the margins of the cultural and rational organization of modern global capitalism.

Originality/value

This study is one of the first to be conducted on the multi-award-winning #ConMuchoAcento campaign. Furthermore, it will analyze the place branding strategy carried out by the brand from a semiotic perspective.
Breaking barriers in accessing and uptaking climate change adaptation information by smallholder tomato farmers in Tanzania
Authors: Siyao Peter Onauphoo , Sanga Evaristo Eliakim
Published: December 2023

Purpose

This study aims to assess barriers in accessing and uptaking climate change adaptation information among smallholder tomato farmers in Tanzania.

Design/methodology/approach

This study was conducted in Iringa and Morogoro regions, Tanzania. It adopted cross-sectional research design. Multistage, purposive and random sampling techniques with a sample size of 183 smallholder tomato farmers were used. Questionnaires containing closed- and open-ended questions, interview guide and focus group discussions were used to collect data. To ensure validity and reliability of data collection instruments, pretesting of the questionnaires was conducted by administering them to a small group of smallholder tomato growers. Statistical Product and Service Solutions software was used to analyse quantitative data while NVivo was used for analysing qualitative data.

Findings

Lack of clear understanding of climate change information (132, 72.1%), scarcity of libraries and information centres (125, 68.3%), inadequate income (125, 68.3%), lack of trust of sources of information (114, 62.3%), lack of sufficient knowledge about climate change (111, 60%), illiteracy (110, 60.1%), poor distribution of electricity in rural areas (109, 59.6%) and use of jargons (93, 50.8%) in explaining climate change adaptation issues are hindrances for smallholder tomato farmers to access and uptake climate change adaptation information.

Research limitations/implications

This study was conducted in only two districts in Tanzania; thus, the findings cannot be generalized.

Practical implications

The government and relevant agencies are recommended to use appropriate strategies for breaking the barriers that impede easy access and uptake of climate change adaptation information by smallholder tomato farmers as one of the interventions to combat the impacts posed by climate change.

Social implications

This study has contributed to the ongoing discourses on climate change issues. Such discourses have influenced attention and understanding of the role of access and uptake of climate change adaptation information by smallholder farmers for planning and implementation of adaptation strategies through awareness creation.

Originality/value

This study is in line with goal number 13.3 of Sustainable Development Goals, which vows on taking necessary actions in combating climate change and its impacts. Thus, smallholder tomato farmers’ awareness about climate change through access and uptake of climate change adaptation information is one of the interventions to combat climate change and its impacts.
Debt overhang and carbon emissions
Authors: Safiullah Md , Houqe Muhammad Nurul , Ali Muhammad Jahangir , Azam Md Saiful
Published: December 2023

Purpose

This study investigates the association between debt overhang and carbon emissions (both direct and indirect emissions) using a sample of US publicly listed firms.

Design/methodology/approach

The study applies generalized least squares (GLS) regression analyses to a sample of 2,043 US firm-year observations over a period of 14 years from 2007 to 2020. The methods include contemporaneous effect, lagged effect, alternative measures of carbon emissions and debt overhang, intensive versus non-intensive analysis, channel analysis, firm fixed effects, change analysis, controlling for credit rating analysis, propensity score matching approach, instrumental variable analysis with industry and year fixed effect.

Findings

This study's findings reveal that the debt overhang problem increases carbon emissions. This finding holds when the authors use alternative measures of carbon emissions and debt overhang. The authors find that carbon abatement investment is a channel that is negatively impacted by debt overhang, which in turn increases carbon emissions. This study's results are robust for several endogeneity tests, including firm fixed effects, change analysis, propensity score matching approach and two-stage least squares (2SLS) instrumental variable analysis.

Practical implications

The outcome of this research has policy implications for several stakeholders, including investors, firms, market participants and regulators. This study's findings offer insights for investors and firms, helping them allocate resources effectively and make financing decisions aimed at reducing carbon emissions. Regulators and policymakers can also use the findings to formulate policies that promote alternative sustainable finance practices.

Originality/value

The outcome of this research is likely to help firms develop their understanding of the debt overhang problem and undertake strategies that yield a significant amount of funding to invest in reducing carbon emissions.
Achieving sustainability through multifaceted green functions in manufacturing
Authors: Rashid Aamir , Rasheed Rizwana , Ngah Abdul Hafaz
Published: December 2023

Purpose

Green practices are essential for sustainability. However, it is challenging due to the socioeconomic and environmental concerns. Similarly, after the induced SDG-12 and SDG-13 by United Nations, the pressure groups forced manufacturers to consider sustainability. Therefore, this research aims to examine the sustainability through multifaceted green functions in manufacturing is examined.

Design/methodology/approach

Data were collected from 293 supply chain professionals of manufacturers from a developing economy. Hypotheses were tested through a quantitative method using partial least squares-structural equation modeling with the help of SmartPLS version 4 to validate the measurement model.

Findings

The findings revealed that all six direct hypotheses were supported. However, out of four hypotheses of mediation, one was not supported. Besides, a sequential mediation of green supply chain environmental cooperation and green human resource management was supported. The findings illustrated that green supply chain practices positively influence all used variables.

Research limitations/implications

This research provides practical insight to practitioners to implement green practices in their supply chain networks for social, economic and environmental sustainability and compliance with SDG-12 and SDG-13. The sustainability was validated in a higher-order construct (HOC) (formative), including sequential mediation in the model with the support of resource dependency theory. Therefore, this study adds substantial literature to the existing body of knowledge.

Originality/value

This research provides an interdisciplinary framework by adding knowledge to the Resource Dependency Theory to address Sustainable Development Goals-12 (SDGs) and SDG-13. Likewise, this research provides an extension towards the body of knowledge on the issue, which can be used in future research and critical examinations for cleaner and sustainable production. So far, in Pakistan, no research has looked at the function of these integrated variables in the manufacturing industry with a diligent focus on sustainability as it was validated in a higher-order construct (formative) with one sequential mediation, which makes this research unique.
Muslim travellers: a bibliometric analysis
Authors: Abdul Shukor Syadiyah , Kattiyapornpong Uraiporn
Published: December 2023

Purpose

This study aims to provide an insight into research related to Muslim travellers in the past 42 years.

Design/methodology/approach

Using 342 articles collected from the Scopus database from 1981 to 2023, this study adopted the Bibliometrix in RStudio package and Biblioshiny Web application to analyse the research on Muslim travellers in two main categories: overview and intellectual structures.

Findings

The first publication related to Muslim travellers occurred in 1981 and number of publications remained few in the first three decades. Starting 2015, publications on Muslim travellers experienced a growing development of discussions and publications. Four prominent research clusters were identified: “halal tourism”, “hajj”, “Islamic tourism” and “tourist post-purchase”. Themes within the research on Muslim travellers have evolved from the “pilgrimage” to “Islamic tourism” theme. Then, the “Islamic tourism” theme has been expanded to a variety of topics that were primarily relevant to Muslim tourist behaviour. Themes related to “climate change” and “Syria” have been identified as the niche themes that need further study.

Research limitations/implications

Scopus database is regularly updated as the number of papers and journals may increase or decrease from time to time. This may impact on the fluctuation of the theme analysis from the article search at that time.

Originality/value

This study reviews publications related to Muslim travellers over the past four decades. Accordingly, it can aid interested researchers and stakeholders in gaining a more thorough understanding of Muslim traveller research.
Raising interest rates was the wrong medicine
Authors: Nersisyan Yeva , Wray L. Randall
Published: December 2023

Purpose

In this paper, the authors examine the causes of 2021–2023 inflation and evaluate whether raising interest rates is the right solution.

Design/methodology/approach

The authors evaluate both the macroeconomic (too much demand) and microeconomic (monopoly pricing and supply chains) explanations for the causes of inflation.

Findings

The authors argue that the spike in inflation is due to disrupted supply chains and corporations taking advantage of the situation to raise their prices. The aggregate demand stimulus from fiscal policy had all but played out by the time inflation arose, making it an unlikely cause of said inflation.

Originality/value

The authors' paper demonstrates that raising interest rates is the wrong solution to tackling the problem of inflation, especially since it's coming from the supply side.
CEO anger: a catalyst for error recognition and learning
Authors: Olson Bradley J. , Parayitam Satyanarayana , Cristofaro Matteo , Bao Yongjian , Yuan Wenlong
Published: December 2023

Purpose

This paper elucidates the role of anger in error management (EM) and organizational learning behaviors. The study explores how anger can catalyze learning, emphasizing its strategic implications.

Design/methodology/approach

A double-layered moderated-mediated model was developed and tested using data from 744 Chinese CEOs. The psychometric properties of the survey instrument were rigorously examined through structural equation modeling, and hypotheses were tested using Hayes's PROCESS macros.

Findings

The findings reveal that anger is a precursor for recognizing the value of significant errors, leading to a positive association with learning behavior among top management team members. Additionally, the study uncovers a triple interaction effect of anger, EM culture and supply chain disruptions on the value of learning from errors. Extensive experience and positive grieving strengthen the relationship between recognizing value from errors and learning behavior.

Originality/value

This study uniquely integrates affect-cognitive theory and organizational learning theory, examining anger in EM and learning. The authors provide empirical evidence that anger can drive error value recognition and learning. The authors incorporate a more fine-grained approach to leadership when including executive anger as a trigger to learning behavior. Factors like experience and positive grieving are explored, deepening the understanding of emotions in learning. The authors consider both negative and positive emotions to contribute to the complexity of organizational learning.
Cost of organizational citizenship behaviors: serial mediation model of citizenship fatigue
Authors: Ali Nisar Qasim , Haider Shahbaz , Waqas Ali , Khan Waris Ali , Selem Kareem M.
Published: December 2023

Purpose

Recently, a shift regarding the negative consequences of organizational citizenship behaviors (OCBs) has put them forward as employees’ negative aspects carrying dangerous consequences for organizations. Considering this issue’s seriousness, the purpose of this paper is to examine the process through which compulsory citizenship behavior fosters citizenship fatigue.

Design/methodology/approach

A total of 370 nurses working in Pakistani public-sector hospitals were this study’s final data set sample using SmartPLS4.

Findings

Partial least squares structural equation modeling (PLS-SEM) results revealed that when employees are compelled to engage in extra-role actions, they frequently experience work-life conflict, which results in citizenship fatigue. The higher the employee’s age and the lower the education level, the lower his/her citizenship fatigue. On the other hand, findings revealed that workaholic personality aspects tend to reduce the strength of the relationship between work-life conflict and citizenship fatigue.

Originality/value

To the best of the authors’ knowledge, this paper is the first attempt to examine the recently emerged concept of citizenship fatigue among health-care professionals through conservation of resources theory. Besides, this research will highlight how the demand for voluntary actions in routine or forced citizenship behavior can become the reason for work–family conflict and ultimately create citizenship fatigue. Additionally, this paper presents the novel concept of workaholic personality and how it can play a positive role in the linkage between work–family conflict and citizenship fatigue.