bluuebunny/crossref_metadata_2025 huggingface dataset:
Interleukin-1α and Leukemia Inhibitory Factor Promote Extramedullary Hematopoiesis
Authors: Barisas Derek A.G. , Kim Minseo , Subramanian Madhav , Kabir Ashraf Ul , Krchma Karen , Wu Jun , Zinselmeyer Bernd H. , Stewart Colin L , Choi Kyunghee
Published: July 2022

Extramedullary hematopoiesis (EMH) expands hematopoietic capacity outside of the bone marrow in response to inflammatory conditions, including infections and cancer. Because of its inducible nature, EMH offers a unique opportunity to study the interaction between hematopoietic stem and progenitor cells (HSPCs) and their niche. In cancer patients, the spleen frequently serves as an EMH organ and provides myeloid cells that may worsen pathology. Here, we examined the relationship between HSPCs and their splenic niche in EMH secondary to solid tumor. We identify an inflammatory gene signature characterized by TNFα expression in HSPCs. We show a role for IL-1α in producing this gene signature and TNFα expression in HSPCs in activating splenic niche activity. We also demonstrate that tumor-derived Leukemia Inhibitory Factor (LIF) induces proliferation of splenic niche cells. IL-1α and LIF display cooperative effects in activating EMH and are both upregulated in some human cancers. Together, these data expand avenues for developing niche-directed therapies and further exploring EMH accompanying inflammatory pathologies like cancer.
Using polygenic risk score about complex traits to predict production performance in crossbreeding of yeast
Authors: Dai Yi , Shi Guohui , Chen Mengmeng , Chen Guotao , Wu Qi
Published: July 2022

The cultivation of hybrids with favorable complex traits is one of the important goals for animal, plant, and microbial breeding practices. A method that can well predict the production performance of hybrids will be of great significance to the whole research and practice. In our study, polygenic risk scores (PRS) were introduced to estimate the production performance of Saccharomyces Cerevisiae. The genetic variation of 971 published isolates and their growth ratios under 35 medium conditions were analyzed by genome-wide association analysis, and the precise p-value threshold for each phenotype was calculated. Risk markers for the above 35 phenotypes were obtained. By estimating genotype of F1 hybrids according to that of the parents, the PRS of 613 F1 hybrids was predicted. There was a significant linear correlation between YPD40 and PRS in F1 and their parents (R2=0.2582, R2=0.2414, respectively), which indicates that PRS can be used to estimate the production performance of individuals and their hybrids. Our method can provide a reference for strains selection and F1 prediction in yeasts cross-breeding, reduce the workload and improve the work efficiency.
Faecal carriage of ESBL-producingEscherichia coliin a remote region of Niger
Authors: Jacquier Hervé , Assao Bachir , Chau Françoise , Guindo Ousmane , Condamine Bénédicte , Magnan Mélanie , Bridier-Nahmias Antoine , Sayingoza-Makombe Nathan , Moumouni Aissatou , Page Anne-Laure , Langendorf Céline , Coldiron Matthew E , Denamur Erick , de Lastours Victoire
Published: July 2022

Objective

Whole genome sequencing (WGS) of extended-spectrum β-lactamase-producingEscherichia coli(ESBL-E. coli) in developing countries is lacking. Here we describe the population structure and molecular characteristics of ESBL-E. colifaecal isolates in rural Southern Niger.

Methods

Stools of 383 healthy participants were collected among which 92.4% were ESBL-E. colicarriers; 90 of these ESBL-E. colicontaining stools (109 ESBL-E. coliisolates) were further analysed by WGS, using short- and long-reads.

Results

Most isolates belonged to the commensalism-adapted phylogroup A (83.5%), with high clonal diversity. TheblaCTX-M-15gene was the major ESBL determinant (98.1%), chromosome-integrated in approximately 50% of cases, in multiple integration sites. When plasmid-borne,blaCTX-M-15was found in IncF (57.4%) and IncY plasmids (26.2%). Closely related plasmids were found in different genetic backgrounds. Genomic environment analysis ofblaCTX-M-15in closely related strains argued for mobilisation between plasmids or from plasmid to chromosome.

Conclusions

Massive prevalence of community faecal carriage of CTX-M-15-producingE. coliwas observed in a rural region of Niger due to the spread of highly diverse A phylogroup commensalism-adapted clones, with frequent chromosomal integration ofblaCTX-M-15. Plasmid spread was also observed. These data suggest a risk of sustainable implementation of ESBL in community faecal carriage.
Mechanisms for the prevention of adolescent intimate partner violence: a realist review of interventions in low- and middle-income countries
Authors: Lowe Hattie , Dobbin Jo , Kiss Ligia , Mak Joelle , Mannell Jenevieve , Watson Daniella , Devakumar Delanjathan
Published: July 2022

Adolescent girls are among those at the greatest risk of experiencing intimate partner violence (IPV). Despite adolescence being widely regarded as a window of opportunity to influence attitudes and behaviours related to gender equality, evidence on what works to prevent IPV at this critical stage is limited outside of high-income school-based settings. Even less is understood about the mechanisms of change in these interventions. We conducted a realist review of primary prevention interventions for adolescent IPV in low- and middle-income countries (LMICs) to synthesise evidence on how they work, for whom, and under which circumstances. The review took place in four iterative stages: 1) exploratory scoping, 2) developing initial programme theory, 3) systematic database search, screening and extraction, and 4) purposive searching and refinement of programme theory. We identified eleven adolescent IPV prevention interventions in LMICs, most of which demonstrated a positive impact on IPV experience and/or perpetration (n=10). Most interventions (n=9) implemented school-based or community-based interactive peer-group education to transform attitudes and norms around gender and relationships for behaviour change. The central mechanism of change related to gender transformative content prompting adolescents to critically reflect on their attitudes and relationships, leading to a reconceptualisation of their values and beliefs. This central mechanism was supported by two secondary implementation mechanisms: 1) the design and delivery of interventions: interactive, age-appropriate education delivered in peer-groups provided adolescents a safe space to engage with content and build communication skills, and 2) the target group: social norms interventions targeting the wider community created enabling environments supportive of individual change. This review highlights the immense potential of gender transformative interventions during the critical period of adolescence for IPV prevention. Future interventions should consider the broader drivers of adolescent IPV and ensure intersectionality informed approaches to maximise their potential to capitalise on this window of opportunity.
Medical complaints after 3 vs 2 doses SARS-CoV-2 mRNA vaccination
Authors: Methi Fredrik , Gran Jon Michael , Valberg Morten , Kinge Jonas Minet , Telle Kjetil , Magnusson Karin
Published: July 2022

Aims

To examine whether individuals vaccinated with three doses of mRNA SARS-CoV-2 vaccines have an altered incidence of medical complaints compared to individuals not vaccinated with three doses.

Methods

Using longitudinal exact 1:1 matching on days since 2nd dose, calendar month and a set of covariates, we obtained a matched sample with 138 581 individuals aged 18-70 years that had the 3rd dose at 20-30 weeks after the 2nd dose and an equally large control group that did not. Main outcomes were medical records of common complaints seen in primary care for up to 90 days after the treatment.

Results

Depending on type of complaint, the estimated 90-day cumulative incidence varied between 70 and 5000 per 100 000 individuals. Among individuals aged 18-44 years, the number of medical complaints was lower for individuals with three doses: Fatigue: 662, 95% confidence interval=473-850, shortness of breath: 160 (90-230) and brain fog: 65 (22-108) fewer per 100 000 vaccinated. No decrease in incidence was observed for musculoskeletal pain, cough or heart palpitations. When individuals where censored from the analysis from the date of positive SARS-CoV-2 test, these absolute differences were smaller. Similar analyses gave higher estimates among individuals aged 45-70 years, yet more ambiguous results when censored at positive test.

Conclusion

Individuals vaccinated with dose 3 had reduced incidence of complaints compared to matched controls with only 2 doses. Analyses with vs without censoring at positive test implied that this reduction might be explained by a reduced COVID-19 incidence among the 3-dose-vaccinated.
Influence of family history on penetrance of hereditary cancers in a population setting
Authors: Jackson L , Weedon MN , Harrison JW , Wood AR , Ruth KS , Tyrrell J , Wright CF
Published: July 2022

Background

We sought to investigate how penetrance of familial cancer syndromes varies with family history using a population-based cohort.

Methods

We analysed 454,712 UK Biobank participants with exome sequence and clinical data. We identified participants with a self-reported family history of breast or colorectal cancer and a pathogenic/likely pathogenic variant in the major genes responsible for hereditary breast cancer or Lynch syndrome. We calculated survival to cancer diagnosis (controlled for age, sex, death, recruitment centre, screening and prophylactic surgery).

Results

Women with a pathogenic BRCA1 or BRCA2 variant had an increased risk of breast cancer that was significantly higher in those with a first-degree family history (relative hazard 10.29 and 7.82, respectively) than those without (7.82 and 4.66). Penetrance to age 60 was also higher in those with a family history (44.7% and 24.1%) versus those without (22.8% and 17.9%). A similar pattern was seen in Lynch syndrome: individuals with a pathogenic MLH1, MSH2 or MSH6 variant had an increased risk of bowel cancer that was significantly higher in those with a family history (relative hazard 63.7, 68.4 and 12.1) than those without (20.9, 18.6 and 5.9). Penetrance to age 60 was also higher for carriers of a pathogenic MLH1 or MSH2 variant in those with a family history (27.1% and 25.2%) versus those without (15.2% and 3.2%).

Conclusions

Individuals with pathogenic cancer syndrome variants are at significantly less elevated risk of cancer in the absence of family history (risk ratio 0.57), so invasive follow-up may be unwarranted.
Establishing causal relationships between sleep and adiposity traits using Mendelian randomisation
Authors: Hayes Bryony L , Vabistsevits Marina , Martin Richard M , Lawlor Deborah A , Richmond Rebecca C , Robinson Timothy
Published: July 2022

Objective

To systematically evaluate the direction of any potential causal effect between sleep and adiposity traits.

Methods

Two-sample Mendelian randomization (MR) was used to assess the association of genetically predicted sleep traits on adiposity and vice versa. Using data from UK Biobank and 23andme, the sleep traits explored were morning-preference (chronotype) (N=697,828), insomnia (N=1,331,010), sleep duration (N=446, 118), napping (N=452,633) and daytime-sleepiness (N=452,071). Using data from the GIANT and EGG consortia, the adiposity traits explored were adult BMI, hip circumference (HC), waist circumference (WC), waist-to-hip ratio (WHR) (N=322,154) and child-BMI (N=35,668).

Results

We found evidence that insomnia symptoms increased mean WC, BMI and WHR (difference in means WC=0.39 SD (95% CI=0.13, 0.64), BMI=0.47 SD (0.22, 0.73) and WHR=0.34 SD (0.16, 0.52)). Napping increased mean WHR (0.23 SD (0.08, 0.39). Higher HC, WC, and adult-BMI increased odds of daytime-sleepiness (HC=0.02 SD (0.01, 0.04), WC=0.04 SD (0.01, 0.06) and BMI 0.02 SD (0.00, 0.04), respectively). We also found that higher mean child-BMI resulted in lower odds of napping (−0.01 SD (0.02, 0.00).

Conclusions

The effects of insomnia on adiposity, and adiposity on daytime-sleepiness, suggest that poor sleep and weight gain may contribute to a feedback loop that could be detrimental to overall health.
Brain imaging and neuropsychological assessment of individuals recovered from a mild to moderate SARS-CoV-2 infection
Authors: Petersen Marvin , Nägele Felix Leonard , Mayer Carola , Schell Maximilian , Petersen Elina , Kühn Simone , Gallinat Jürgen , Fiehler Jens , Pasternak Ofer , Matschke Jakob , Glatzel Markus , Twerenbold Raphael , Gerloff Christian , Thomalla Götz , Cheng Bastian
Published: July 2022

As SARS-CoV-2 infections have been shown to affect the central nervous system, the investigation of associated alterations of brain structure and neuropsychological sequelae is crucial to help address future health care needs. Therefore, we performed a comprehensive neuroimaging and neuropsychological assessment of 223 non-vaccinated individuals recovered from a mild to moderate SARS-CoV-2 infection (100 female/123 male, age [years], mean ± SD, 55.54 ± 7.07; median 9.7 months after infection) in comparison with 223 matched controls (93 female/130 male, 55.74 ± 6.60) within the framework of the Hamburg City Health Study. Primary study outcomes were advanced diffusion magnetic resonance imaging (MRI) measures of white matter microstructure, cortical thickness, white matter hyperintensity load and neuropsychological test scores. Among all 11 MRI markers tested, significant differences were found in global measures of mean diffusivity and extracellular free-water which were elevated in the white matter of post-SARS-CoV-2 individuals comparing to matched controls (free-water: 0.148 ± 0.018 vs. 0.142 ± 0.017,P<.001; mean diffusivity [10−3mm2/s]: 0.747 ± 0.021 vs. 0.740 ± 0.020,P<.001). Group classification accuracy based on diffusion imaging markers was up to 80%. Neuropsychological test scores did not significantly differ between groups. Collectively, our findings suggest that subtle changes in white matter extracellular water content last beyond the acute infection with SARS-CoV-2. However, in our sample, a mild to moderate SARS-CoV-2 infection was not associated with neuropsychological deficits, significant changes in cortical structure or vascular lesions several months after recovery. External validation of our findings and longitudinal follow-up investigations are needed.

Significance statement

In this case-control study, we demonstrate that non-vaccinated individuals recovered from a mild to moderate SARS-CoV-2 infection show significant alterations of the cerebral white matter identified by diffusion weighted imaging, such as global increases in extracellular free-water and mean diffusivity. Despite the observed brain white matter alterations in this sample, a mild to moderate SARS-CoV-2 infection was not associated with worse cognitive functions within the first year after recovery. Collectively, our findings indicate the presence of a prolonged neuroinflammatory response to the initial viral infection. Further longitudinal research is necessary to elucidate the link between brain alterations and clinical features of post-SARS-CoV-2 individuals.
Extensive gut virome variation and its associations with host and environmental factors in a population-level cohort
Authors: Nishijima Suguru , Nagata Naoyoshi , Kiguchi Yuya , Kojima Yasushi , Miyoshi-Akiyama Tohru , Kimura Moto , Ohsugi Mitsuru , Ueki Kohjiro , Oka Shinichi , Mizokami Masashi , Itoi Takao , Kawai Takashi , Uemura Naomi , Hattori Masahira
Published: July 2022

Indigenous bacteriophage communities (virome) in the human gut have a huge impact on the gut bacterial communities (bacteriome), but virome variation at a population scale is not fully investigated yet. Here, we analyse the gut virome in a population-level cohort of 4,198 deeply phenotyped individuals. We discovered thousands of high-quality phage genomes including previously uncharacterized ones with different bacterial hosts than known major phage clades. The distribution of host bacteria was a strong determinant for the distribution of phages, and virome diversity was highly correlated with anti-viral defence mechanisms of the bacteriome, such as CRISPR-Cas and restriction-modification systems. We identified 97 various intrinsic/extrinsic factors that significantly affect the virome, including age, sex, lifestyle, and diet, most of which showed consistent associations with both phages and their predicted bacterial hosts. Among the metadata categories, disease and medication had the strongest effects on the virome structure. Overall, these results present a basis to understand the symbiotic communities of bacteria and their viruses in the human gut, which will facilitate the medical and industrial applications of indigenous viruses.
Integrative solution structure of a PTBP1-viral IRES complex reveals strong compaction and ordering with residual conformational flexibility
Authors: Dorn Georg , Gmeiner Christoph , de Vries Tebbe , Dedic Emil , Novakovic Mihajlo , Damberger Fred F. , Maris Christophe , Finol Esteban , Sarnowski Chris P. , Kohlbrecher Joachim , Welsh Timothy J. , Bolisetty Sreenath , Mezzenga Raffaele , Aebersold Ruedi , Leitner Alexander , Yulikov Maxim , Jeschke Gunnar , Allain Frédéric H.-T.
Published: July 2022

RNA-binding proteins (RBPs) are crucial regulators of gene expression and often comprise well-defined domains interspersed by flexible, intrinsically disordered regions. The structure determination of ribonucleoprotein complexes involving such RBPs is not common practice and requires integrative structural modeling approaches due to the fact that they often do not form a single stable globular state. Here, we integrate data from magnetic resonance, mass spectrometry, and small angle scattering to determine the solution structure of the polypyrimidine-tract binding protein 1 (PTBP1 also called hnRNP I) bound to an RNA which is part of the internal ribosome entry site (IRES) of the encephalomyocarditis virus (EMCV). PTBP1 binding to this IRES element enhances translation of the viral RNA. The determined structural ensemble reveals that both RNA and protein experience a strong compaction upon complex formation, get ordered but still maintain a substantial conformational flexibility. The C-terminal RNA recognition motif (RRM4) of PTBP1 rigidifies the complex by binding a single-strand RNA linker and, in turn, is essential for IRES-mediated translation. PTBP1 acts as an RNA chaperone for the IRES, by ordering the RNA into a few discrete conformations that expose the RNA stems to the outer surface of the RNP complex for subsequent interactions with the translation machinery. The conformational diversity within this structural ensemble is likely common among RNP complexes and important for their functionality. The presented approach opens the possibility to characterize heterogeneous RNP structures at atomic level.
Glioma-derived CCL2 and CCL7 mediate migration of immune suppressive CCR2+ myeloid cells into the tumor microenvironment in a redundant manner
Authors: Takacs Gregory P. , Kreiger Christian J. , Luo Defang , Tian Guimei , Garcia Julia S. , Deleyrolle Loic P. , Mitchell Duane A. , Harrison Jeffrey K.
Published: July 2022

Glioblastoma (GBM) is the most common and malignant primary brain tumor, resulting in poor survival despite aggressive therapies. GBM is characterized in part by a highly heterogeneous and immunosuppressive tumor microenvironment (TME) made up predominantly of infiltrating peripheral immune cells. One significant immune cell type that contributes to glioma immune evasion is a population of immunosuppressive, hematopoietic cells, termed myeloid-derived suppressor cells (MDSCs). Previous studies suggest that a potent subset of myeloid cells, expressing monocytic (M)-MDSC markers, distinguished by dual expression of chemokine receptors CCR2 and CX3CR1, utilize CCR2 to infiltrate into the TME. This study evaluated the T cell suppressive function and migratory properties of CCR2+/CX3CR1+ MDSCs. Bone marrow-derived CCR2+/CX3CR1+ cells adopt an immune suppressive cell phenotype when cultured with glioma-derived factors. Recombinant and glioma-derived CCL2 and CCL7 induce the migration of CCR2+/CX3CR1+ MDSCs with similar efficacy. KR158B-CCL2 and -CCL7 knockdown murine gliomas contain equivalent percentages of CCR2+/CX3CR1+ MDSCs compared to KR158B gliomas. Combined neutralization of CCL2 and CCL7 completely blocks CCR2-expressing cell migration to KR158B cell conditioned media. High levels of CCL2 and CCL7 are also associated with negative prognostic outcomes in GBM patients. These data provide a more comprehensive understanding of the function of CCR2+/CX3CR1+ MDSCs and the role of CCL2 and CCL7 in the recruitment of these immune suppressive cells and further support the significance of targeting this chemokine axis in GBM.
Multisensory learning binds modality-specific neurons into a cross-modal memory engram
Authors: Okray Zeynep , Jacob Pedro F. , Stern Ciara , Desmond Kieran , Otto Nils , Vargas-Gutierrez Paola , Waddell Scott
Published: July 2022

Associating multiple sensory cues with objects and experience is a fundamental brain process that improves object recognition and memory performance. However, neural mechanisms that bind sensory features during learning and augment memory expression are unknown. Here we demonstrate multisensory appetitive and aversive memory in Drosophila. Combining colors and odors improved memory performance, even when each sensory modality was tested alone. Temporal control of neuronal function revealed visually-selective mushroom body Kenyon Cells (KCs) to be required for both enhancement of visual and olfactory memory after multisensory training. Voltage imaging in head-fixed flies showed that multisensory learning binds activity between streams of modality-specific KCs, so that unimodal sensory input generates a multimodal neuronal response. Binding occurs between regions of the olfactory and visual KC axons, which receive valence-relevant dopaminergic reinforcement, and is propagated downstream. Dopamine locally releases GABA-ergic inhibition to permit specific microcircuits within KC-spanning serotonergic neurons to function as an excitatory bridge between the previously ‘modality-selective’ KC streams. Cross-modal binding thereby expands the olfactory memory engram by recruiting visual path KCs to become odor responsive. This broadening of the engram improves memory performance after multisensory learning and permits a single sensory feature to retrieve the memory of the multimodal experience.
IL11 stimulates IL33 expression and proinflammatory fibroblast activation
Authors: Widjaja Anissa A. , Chothani Sonia , Viswanathan Sivakumar , Wei Ting Joyce Goh , Lim Wei-Wen , Cook Stuart A.
Published: July 2022

Interleukin 11 (IL11) is upregulated in inflammatory conditions where it is believed to have anti-inflammatory activity. However, recent studies suggest instead that IL11 may promote inflammation, via the stroma. Here, we assessed whether IL11 is pro- or anti-inflammatory in fibroblasts. Primary cultures of human kidney, lung or skin fibroblasts were stimulated with IL11 that resulted in transient STAT3 phosphorylation and bi-modal ERK activation. RNA sequencing over a time course of IL11 stimulation revealed a robust short-lived transcriptional response, which was enriched for gene set hallmarks of inflammation and characterized by upregulation ofSERPINB2, TNFRSF18, IL33, CCL20, IL1RL1, CXCL3/5/8, ICAM1andIL11itself.IL33was the most upregulated signaling factor (38-fold, P=9.8×10−5) andIL1RL1, its cognate receptor, was similarly increased (18-fold, P=1.1×10−34). In proteomic studies, IL11 triggered a proinflammatory secretome with notable upregulation of IL8, IL6, MCP1, CCL20 and CXCL1/5/6, which are important chemotaxins for neutrophils, monocytes and lymphocytes. IL11 induced IL33 expression across fibroblast types and inhibition of STAT3, but not MEK/ERK, prevented this. These data establish IL11 as pro-inflammatory with specific importance for priming the IL33 alarmin response in inflammatory fibroblasts.
Armadillo repeat-containing kinesin represents the versatile plus-end-directed transporter in Physcomitrella
Authors: Yoshida Mari W. , Hakozaki Maya , Goshima Gohta
Published: July 2022

Kinesin-1, also known as conventional kinesin, is widely utilised for microtubule plus-end-directed (“anterograde”) transport of various cargos in animal cells. However, a motor functionally equivalent to the conventional kinesin has not been identified in plants, which lack the kinesin-1 genes. Here, we show that plant-specific armadillo repeat-containing kinesin (ARK) is the long sought-after versatile anterograde transporter in plants. InARKmutants of the mossPhyscomitrium patens, the anterograde motility of nuclei, chloroplasts, mitochondria, and secretory vesicles was suppressed. Ectopic expression of non-motile or tail-deleted ARK did not restore organelle distribution. Another prominent macroscopic phenotype ofARKmutants was the suppression of cell tip growth. We showed that this defect was attributed to the mislocalisation of actin regulators, including RopGEFs; expression and forced apical localisation of RopGEF3 suppressed the growth phenotype of theARKmutant. The mutant phenotypes were partially rescued by ARK homologues inArabidopsis thaliana, suggesting the conservation of ARK functions in plants.
Deciphering of BTH-induced response of tomato (Solanum lycopersicum L.) and its effect on plant virus infection through the multi-omics approach
Authors: Patryk Frąckowiak , Barbara Wrzesińska , Przemysław Wieczorek , Paloma Sanchez-Bel , Laura Kunz , Antje Dittmann , Aleksandra Obrępalska-Stęplowska
Published: July 2022

One of the preventive methods used to limit the losses caused by viruses is the application of synthetic immunity inducers, such as benzo(1,2,3)-thiadiazole-7-carbothioic acid S-methyl ester (BTH). This study aimed to explain how the BTH treatment affects the defence and developmental processes in tomato plants (Solanum lycopersicum L.) as well as plant response to virus infection.

The comparative multi-omics analyses of tomato plants treated with BTH were performed, including transcriptomics (RNA-seq), proteomics (Liquid Chromatography-Mass Spectrometry), and metabolomics (targeted hormonal analysis). To confirm the priming effect of BTH on tomato resistance, the plants were infected with tomato mosaic virus (ToMV) seven days post-BTH treatment.

The combined functional analysis indicated the high impact of BTH on the plant’s developmental processes and activation of the immune response early after the treatment. In the presented experimental model, the increased level of WRKY TRANSCRIPTION FACTORS, ARGONAUTE 2A, thiamine and glutathione metabolism, cell wall reorganization, and detoxification processes, as well as accumulation of three phytohormones: abscisic acid, jasmonic-isoleucine (JA-Ile), and indole-3-carboxylic acid (I3CA), were observed upon BTH application.

The immune response activated by BTH was related to increased expression of genes associated with the cellular detoxification process, systemic acquired resistance, and induced systemic resistance as well as post-transcriptional gene silencing. Increased levels of I3CA and JA-Ile might explain the BTH’s effectiveness in the induction of the plant defence against a broad spectrum of pathogens. For the first time, the BTH impact on the thiamine metabolism was revealed in tomatoes.
Transcriptional drifts associated with environmental changes in endothelial cells
Authors: Afshar Yalda , Ma Feiyang , Quach Austin , Jeong Anhyo , Sunshine Hannah Louise , Freitas Vanessa , Jami-Alahmadi Yasaman , Li Xinmin , Pellegrini Matteo , Wohlschlegel James , Romanoski Casey E. , Iruela-Arispe M. Luisa
Published: July 2022

Environmental cues, such as physical forces and heterotypic cell interactions play a critical role in cell function, yet their collective contributions to transcriptional changes are unclear. Focusing on human endothelial cells, we performed broad individual sample analysis to identify transcriptional drifts associated with environmental changes that were independent of genetic background. Global gene expression profiling by RNA-seq and protein expression by LC-MS directed proteomics distinguished endothelial cells in vivo from genetically matched culture (in vitro) samples. Over 43% of the transcriptome was significantly changed by the in vitro environment. Subjecting cultured cells to long-term shear stress significantly rescued the expression of approximately 17% of genes. Inclusion of heterotypic interations by co-culture of endothelial cells with smooth muscle cells normalized approximately 9% of the original in vivo signature. We identify novel flow depedent genes, as well as, genes that necessitate heterotypic cell interactions to mimic the in vivo transcriptome. Our findings highlight specific genes and pathways that rely on contextual information and physical forces.
Gut microbiota and holobiont metabolome composition of the Medaka fish (Oryzias latipes) are affected by a short exposure to the cyanobacterium Microcystis aeruginosa
Authors: Foucault Pierre , Gallet Alison , Duval Charlotte , Marie Benjamin , Duperron Sébastien
Published: July 2022

Blooms of toxic cyanobacteria are a common stress encountered by aquatic fauna. Evidence indicates that long-lasting blooms affect fauna-associated microbiota. Because of their multiple roles, host-associated microbes are nowadays considered relevant to ecotoxicology, yet the respective timing of microbiota versus functional changes in holobionts response needs to be clarified. The response of gut microbiota and holobiont’s metabolome to exposure to a dense culture of Microcystis aeruginosa was investigated as a microcosm-simulated bloom in the model fish species Oryzias latipes (medaka). Both gut microbiota and gut metabolome displayed significant composition changes after only 2 days of exposure. A dominant symbiont, member of the Firmicutes, plummeted whereas various genera of Proteobacteria and Actinobacteriota increased in relative abundance. Changes in microbiota composition occurred earlier and faster compared to metabolome composition, suggesting that the microbiota drives the holobiont’s response. Liver and muscle metabolome were much less affected than guts, supporting that gut and associated microbiota are in the front row upon exposure. This study highlights that even short cyanobacterial blooms, that are increasingly frequent, trigger changes in microbiota composition and holobiont metabolome. It emphasizes the relevance of multi-omics approaches to explore organism’s response to an ecotoxicological stress.

Graphical abstract

Highlights

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A 2-day exposure to a simulated M. aeruginosa bloom is enough to sharply decrease the Firmicute/Proteobacteria ratio in the gut of Oryzias latipes fish.

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The exposure induced changes in metabolome composition after 2 days in the gut and 4 days in the liver.

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The gut bacterial microbiota response occurred faster than metabolome’s; we hypothesize that changes in gut microbiota may drive the gut metabolome compositional changes.
CENP-A and CENP-B collaborate to create an open centromeric chromatin state
Authors: Nagpal Harsh , Fierz Beat
Published: July 2022

Centromeres, the sites within chromosomes responsible for accurate genome repartitioning, are epigenetically defined via replacement of canonical histone H3 by the histone variant CENP-A forming specific nucleosomes with increased DNA flexibility. In human cells, CENP-A nucleosomes and thus centromeres localize to genomic regions containing extended tandem repeats of alpha-satellite DNA. There, the constitutive centromere associated network (CCAN) and the kinetochore assemble, connecting the centromere to spindle microtubules during cell division. CENP-A provides a major recruitment point for many CCAN member proteins. One factor, CENP-B, binds to a specific DNA sequence contained in about half of alpha-satellite repeats. CENP-B is a dimer and is involved in maintaining centromere stability and, together with CENP-A, shapes the basic layer of the centromeric chromatin state. While recent studies have revealed the structure of large parts of the CCAN complexes, the nanoscale organization of centromeric chromatin is not well understood.

Here, we use single-molecule fluorescence resonance energy transfer (FRET) and colocalization imaging as well as dynamic experiments in cells to show that CENP-A incorporation establishes a far more dynamic and open chromatin state compared to canonical H3. We investigate whether CENP-A marks a landing spot for CENP-B, and find that on the single nucleosome level, CENP-B does not prefer H3 over CENP-A nucleosomes. However, in a chromatin fiber context, CENP-B binding is suppressed by higher-order chromatin structure. The increased dynamics of CENP-A chromatin create an opening, allowing CENP-B access and binding. In turn, bound CENP-B further opens the chromatin fiber structure, potentially via bending the bound DNA. Finally, transient knockdown of CENP-A expression in cells increases CENP-B mobility in cells. Together, our studies show that the two centromere-specific proteins collaborate to reshape chromatin structure, enabling the binding of centromeric factors and establishing a centromeric chromatin state.
Increased mitochondrial Ca2+ contributes to health decline with age and Duchene muscular dystrophy in C. elegans
Authors: Higashitani Atsushi , Teranishi Mika , Nakagawa Yui , Itoh Yukou , Sudevan Surabhi , Szewczyk Nathaniel J , Kubota Yukihiko , Abe Takaaki , Kobayashi Takeshi
Published: July 2022

Sarcopenia is a geriatric syndrome characterized by an age-related decline in skeletal muscle mass and strength. Here, we show that suppression of mitochondrial calcium uniporter (MCU)-mediated Ca2+ influx into mitochondria in the body wall muscles of the nematode Caenorhabditis elegans improved the sarcopenic phenotypes, blunting movement and mitochondrial structural and functional decline with age. We found that normally aged muscle cells exhibited elevated resting mitochondrial Ca2+ levels and increased mitophagy to eliminate damaged mitochondria. Similar to aging muscle, we found that suppressing MCU function in muscular dystrophy improved movement via reducing elevated resting mitochondrial Ca2+ levels. Taken together, our results reveal that elevated resting mitochondrial Ca2+ levels contribute to muscle decline with age and in muscular dystrophy. Further, modulation of MCU activity may act as a potent pharmacological target in various conditions involving muscle loss.
Eliminating elevated p53 signaling fails to rescue skeletal muscle defects or extend survival in Lamin A/C-deficient mice
Authors: Kirby Tyler J. , Zahr Hind C. , Hannah Fong Ern Hwei , Lammerding Jan
Published: July 2022

Lamins A and C, encoded by theLMNAgene, are nuclear intermediate filaments that provide structural support to the nucleus and contribute to chromatin organization and transcriptional regulation.LMNAmutations cause muscular dystrophies, dilated cardiomyopathy, and other diseases. The mechanisms by which manyLMNAmutations result in muscle-specific diseases have remained elusive, presenting a major hurdle in the development of effective treatments. Previous studies using striated muscle laminopathy mouse models found that cytoskeletal forces acting on mechanically fragileLmna-mutant nuclei led to transient nuclear envelope rupture, extensive DNA damage, and activation of DNA damage response (DDR) pathways in skeletal muscle cellsin vitroandin vivo. Furthermore, hearts ofLmnamutant mice have elevated activation of the tumor suppressor protein p53, a central regulator of DDR signaling. We hypothesized that elevated p53 activation could present a pathogenic mechanism in striated muscle laminopathies, and that eliminating p53 activation could improve muscle function and survival in laminopathy mouse models. Supporting a pathogenic function of p53 activation in muscle, stabilization of p53 was sufficient to reduce contractility and viability in wild-type muscle cellsin vitro. Using three laminopathy models, we found that increased p53 activity inLmna-mutant muscle cells primarily resulted from mechanically induced damage to the myonuclei, and not from altered transcriptional regulation due to loss of lamin A/C expression. However, global deletion of p53 in a severe muscle laminopathy model did not reduce the disease phenotype or increase survival, indicating that additional drivers of disease must contribute to the disease pathogenesis.
Mitoguardin-2 is a lipid transporter and its lipid transfer ability is required for function
Authors: Hong Zhouping , Adlakha Jyoti , Guinn Emily , Giska Fabian , Gupta Kallol , Melia Thomas J. , Reinisch Karin M.
Published: July 2022

Lipid transport proteins at membrane contact sites, where organelles are closely apposed, are critical in redistributing lipids from the endoplasmic reticulum (ER), where they are made, to other cellular membranes. Such protein mediated transfer is especially important for maintaining organelles disconnected from secretory pathways, like mitochondria. Here we identify mitoguardin-2, a mitochondrial protein at contacts with the ER and/or lipid droplets (LDs), as a lipid transporter. An X-ray structure shows that the C-terminal domain of mitoguardin-2 has a hydrophobic cavity that binds lipids. Mass spectrometry analysis reveals that both glycerophospholipids and free-fatty acids co-purify with mitoguardin-2 from cells, and that each mitoguardin-2 can accommodate up to two lipids. Mitoguardin-2 transfers glycerophospholipids between membranes in vitro, and this transport ability is required for roles both in mitochondrial and LD biology. While it is not established that protein-mediated transfer at contacts plays a role in LD metabolism, our findings raise the possibility that mitoguardin-2 functions in transporting fatty acids and glycerophospholipids at mitochondria-LD contacts.
A rigidity phase transition of Stomatin condensates governs a switch from transport to mechanotransduction
Authors: Sanfeliu-Cerdán Neus , Mateos Borja , Garcia-Cabau Carla , Català-Castro Frederic , Ribera Maria , Ruider Iris , Porta-de-la-Riva Montserrat , Wieser Stefan , Salvatella Xavier , Krieg Michael
Published: July 2022

A large body of work suggests that biomolecular condensates ensuing from liquid-liquid phase separation mature into various material states. How this aging process is controlled and if the naive and mature phases can have differential functions is currently unknown. Using Caenorhabditis elegans as a model, we show that MEC-2 Stomatin undergoes a rigidity phase transition during maturation from fluid to viscoelastic, glass-like condensates that facilitate either transport or mechanotransduction. This switch is promoted by the SH3 domain of UNC-89/Titin/Obscurin through a direct interaction with MEC-2 and suggests a physiological role for a percolation transition in force transmission during body wall touch. Together, our data demonstrate a novel function for rigidity maturation during mechanotransduction and a previously unidentified role for Titin homologs in neurons.
Financial exposure to environmental liabilities in Lake Huron drainage area farmlands: a GIS and hedonic pricing approach
Authors: Chung Kenneth Hsien Yung , Adriaens Peter
Published: July 2022

Purpose

This paper aims to quantify the impact of environmental contamination on farmland valuation. It applies data fusion and hedonic pricing approaches to quantify the contribution of nitrogen and phosphorus loading on farmland sales transactions. It further suggests approaches to improve internalization of environmental cost in valuation approaches using shadow pricing. The work informs the field of environmental, social and governance (ESG) investing by fusing environmental data with financial transactions.

Design/methodology/approach

This paper is an empirical study implementing hedonic pricing of farmland in the Lake Huron major drainage area. Data sources and fusion were derived from AcreValue, the United States Department of Agriculture's Gridded Soil Survey Geographic database (gSSURGO) and the United States Geological Survey's Spatially Referenced Regression on Watershed Attributes database (SPARROW).

Findings

The results suggest that environmental contamination has statistically significant positive determination power on farmland prices such that prices increase with contamination. Conventional metrics such as percentage of cultivated land in the parcel, root zone depth, whether the parcel is designated by the Natural Resource Conservation Service as prime farmland, and the size of the farmland parcel contribution to farmland value as well. The results indicate that environmental impacts are not accurately accounted for in farmland transactions.

Research limitations/implications

This paper points to inaccurate valuation of environmental contamination in farmland value. While geocoding allowed for positioning of farmland sales transactions relative to modeled areas of contaminant loading in the Lake Huron drainage area, the interpretation indicates that value is driven by cultivation. Hence, generalization to other areas needs a cautious approach. Empirical testing across locations and drainage areas with diverse farmland features will serve to verify the modeled data used in this study.

Practical implications

The lack of integration of externalities in land valuation has implications on lending and disclosure practices, as financial service providers increasingly seek to account for ESG risk on their loan books and broader investment portfolios. The impact of farmland accounting practices for contamination such as shadow pricing may impact land valuation based on future cash flows, and may serve to inform sustainability-linked lending practices to farm operations.

Originality/value

This is the first paper to fuse data from AcreValue, gSSURGO and SPARROW to discover the explanatory power of nutrient contamination in farmland value in the Lake Huron major drainage area.
Factors affecting the probability of formalizing informal sector activities in Sub Saharan Africa: evidence from World Bank enterprise surveys
Authors: Moyo Busani
Published: July 2022

Purpose

This study aims to investigate the factors that affect the likelihood of formalizing informal sector activities in 13 Sub-Saharan African countries, using World Bank enterprise survey data collected between the periods 2009 and 2018. Notwithstanding the great contribution of the informal economy in Africa, developing countries may stand to gain more if they make inroads in formalizing the informal sector.

Design/methodology/approach

Since the dependent variable is binary taking the value of one if the firm is willing to formalize and zero otherwise, the study will employ a discrete choice probit model.

Findings

Results inter alia show that firms that are more likely to formalize are young, owned by individuals with high levels of education and, have registered before. Governments should therefore target firms that are young and provide them with information about the benefits of registration, and if these firms are owned by experienced and educated individuals, the likelihood for them to register would be high.

Research limitations/implications

The study uses cross sectional data and therefore cannot capture time variant factors affecting the probability to register and also cannot correct effectively for endogeneity.

Practical implications

Governments should therefore target firms that are young and provide them with as much information as possible about the benefits of registration, and if these firms are owned by experienced and educated individuals, the likelihood to convince them to register would be high. They should also reduce the cost of registration so as to improve net benefits in line with the rational exit view.

Social implications

Formalizing informal activities will help improve the performance of these firms, reduce vulnerable employment as well as crime, poverty and inequality. Providing decent operating and working conditions to informal players will reduce social and political unrest.

Originality/value

The African continent is home to many informal firms accounting for roughly 55% of economic activity with 90% of workers eking out a living in a sector that does not respect worker rights, provide decent working conditions and where changes in growth have done little to reduce its size. Regulatory reforms have also been implemented resulting in the number of start-up registration procedures falling from 11 in 2003 to seven in 2019. The uniqueness of Sub Saharan Africa in terms of entrepreneurial culture, political, institutional and economic conditions as well as lack of consensus in the extant empirical literature make this study pertinent.
Coevolution of post-merger integration and dual knowledge networks reconstruction: evidence from Chinese overseas acquisitions
Authors: Chen Feiqiong , Wang Wenjing , Zhu Jieru
Published: July 2022

Purpose

Post-merger integration (PMI) is driven by coevolving processes. By integrating the literature on acquisitions with that of knowledge networks, this paper highlights different reconstruction mechanisms for dual knowledge networks during PMI – namely, internal knowledge network coupling and external knowledge network embeddedness. This paper aims to examine their coevolutionary relationships with PMI.

Design/methodology/approach

A coevolutionary framework is tested using a latent growth model and cross-lagged models. The analysis is based on longitudinal data collected from 116 Chinese technology-sourcing overseas merger and acquisition firms.

Findings

This paper unearths a novel idea that variations in post-merger reconstruction of dual knowledge networks can explain why some acquirers increase the degree of integration faster than the others. The results show that the internal knowledge network coupling leads to more knowledge similarity and, in turn, causes a higher degree of integration. The external knowledge network embeddedness also causes higher relative network status of the acquirer, which consequently leads to a higher degree of integration. Furthermore, results from cross-lagged models confirm that an increase in the degree of integration positively influences subsequent changes in the internal knowledge network coupling and external knowledge network embeddedness, thus forming a coevolutionary relationship over time.

Originality/value

This paper responds to recent calls for more insights into the dynamics of PMI. By highlighting different reconstruction mechanisms for internal and external knowledge networks during PMI, this paper explains why it is important to understand PMI dynamics from a dual knowledge network perspective. This paper is the first to adopt a coevolutionary perspective and provide a more comprehensive dynamic framework between PMI and reconstruction of dual knowledge networks. Besides, this paper contributes to the research on emerging market multinational corporations’ cross-border merger and acquisition integration from a dynamic perspective, revealing the time effects of traditionally favored light-touch integration.