bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes in the prevalence of the common risk factors for non-communicable diseases in Uganda between 2014 and 2023: Informed by nationally representative cross-sectional surveys
Authors: Kusolo Ronald , Mutungi Gerald , Mbuliro Mary , Kajjura Richard , Wesonga Ronald , Bahendeka Silver K. , Guwatudde David
Published: September 2024

Background

Non-communicable diseases (NCDs) remain the biggest contributor to global mortality. Although communicable diseases still contribute highest to mortality in the African region, the proportion contributed by NCDs continues to rise. An important way to control NCDs is to focus on reducing the prevalence of the common NCD risk factors. As such, monitoring changes in the prevalence of these risk factors is essential for better NCD prevention planning. Uganda conducted its first nationally representative NCD risk factor survey in 2014, and a second in 2023. We analyzed the prevalence of the common NCD risk factors using data from the two surveys to identify which risk factors changed between 2014 and 2023.

Methods

Both surveys drew countrywide samples stratified by the four regions of the country, and by rural-urban locations. The World Health Organization’s STEPs tool was used to collect data on demographic and behavioral characteristics, and physical and biochemical measurements. We defined and calculated weighted prevalence of the following common NCD risk factors: high blood pressure, high blood glucose, overweight and obesity, current use of alcohol, current tobacco use, inadequate consumption of fruits and vegetables, inadequate physical activity, and sedentariness.

Results

The 2014 survey enrolled a total of 3906 participants, whereas that of 2023 enrolled 3694 participants. The NCD risk factor prevalences that increased significantly were: high blood glucose from 1.3% in 2014, to 2.9% in 2023 (p< 0.001); overweight and obesity from 19.4% in 2014 to 24.1% in 2023 (p< 0.001); current alcohol consumption from 28.5% in 2014, to 31.1% in 2023 (p=0.013); and sedentariness from 26.6% in 2014, to 31.9% in 2023 (p< 0.001). It is only the prevalence of current smoke tobacco use that decreased significantly from 9.6% in 2014, to 8.3% in 2023 (p= 0.046). Nationally, no significant changes were observed in the prevalence of high blood pressure, inadequate consumption of fruits and vegetables, and inadequate physical activity.

Conclusions

Most of the common NCD risk factors increased between 2014 and 2023. There is an agent need for the various stakeholders in Uganda to implement interventions targeting reduction in the prevalence of NCD risk factors to prevent the currently increasing burden of NCDs and associated mortality.
The prevalence of chronic kidney disease in people with severe mental illness: A systematic review protocol
Authors: Carswell C. , Bramham K. , Chilcot J. , Jacobs R. , Osborn D. , Siddiqi N.
Published: September 2024

Background

People with severe mental illness (SMI) are more likely to develop long-term physical health conditions, including type 2 diabetes and cardiovascular disease, compared to people without SMI. This contributes to an inequality in life expectancy known as the ‘mortality gap’. Chronic kidney disease (CKD) is a growing global health concern set to be the 5th leading cause of life-years lost by 2040. However, there is limited research exploring the relationship between CKD and SMI. This systematic review will aim to examine the prevalence and incidence of CKD among people with SMI.

Methods

We will search Medline, Embase, PsycINFO, CINAHL, Scopus and Web of Science for primary epidemiological research reporting the prevalence or incidence of CKD among people with SMI in any setting. Retrieved records will be managed in Covidence and screened by two independent reviewers. Data will be extracted from included studies using a piloted data extraction form, and the quality of studies will be evaluated using the appropriate JBI Critical Appraisal Checklist. The certainty of evidence will be assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach. Data from the included studies will be narratively synthesised. Meta-analyses will be conducted using random effects models to examine the prevalence and incidence of CKD among people with SMI.

Discussion

There is limited research exploring the relationship between CKD and SMI, and this proposed systematic review will be the first to examine the prevalence of CKD among people with SMI. This review will highlight the extent of the problem and provide a foundation for future research to improve health outcomes for people with SMI.
Chemical genetic interactions elucidate pathways controlling tuberculosis antibiotic efficacy during infection
Authors: Oluoch Peter O. , Koh Eun-Ik , Proulx Megan K. , Reames Charlotte J. , Papavinasasundaram Kadamba G. , Murphy Kenan C. , Zimmerman Matthew D. , Dartois Véronique , Sassetti Christopher M.
Published: September 2024

Successful tuberculosis therapy requires treatment with an unwieldy multidrug combination for several months. Thus, there is a growing need to identify novel genetic vulnerabilities that can be leveraged to develop new, more effective antitubercular drugs. Consequently, recent efforts to optimize TB therapy have exploited Mtb chemical genetics to identify pathways influencing antibiotic efficacy, novel mechanisms of antibiotic action, and new targets for TB drug discovery. However, the influence of the complex host environment on these interactions remains largely unknown, leaving the therapeutic potential of the identified targets unclear. In this study, we leveraged a library of conditional mutants targeting 467 essential Mtb genes to characterize the chemical-genetic interactions (CGIs) with TB drugs directly in the mouse infection model. We found that thesein vivoCGIs differ significantly from those identifiedin vitro. Both drug-specific and drug-agnostic effects were identified, and many were preserved during treatment with a multidrug combination, suggesting numerous strategies for enhancing therapy. This work also elucidated the complex effects of pyrazinamide (PZA), a drug that relies on aspects of the infection environment for efficacy. Specifically, our work supports the importance of coenzyme A synthesis inhibition during infection, as well as the antagonistic effect of iron limitation on PZA activity. In addition, we found that inhibition of thiamine and purine synthesis increases PZA efficacy, suggesting novel therapeutically exploitable metabolic dependencies. Our findings present a map of the uniquein vivoCGIs, characterizing the mechanism of PZA activityin vivoand identifying novel targets for TB drug development.

Significance

The inevitable rise of multi-drug-resistant tuberculosis underscores the urgent need for new TB drugs and novel drug targets while prioritizing synergistic drug combinations. Chemical-genetic interaction (CGI) studies have delineated bacterial pathways influencing antibiotic efficacy and uncovered druggable pathways that synergize with TB drugs. However, most studies are conductedin vitro, limiting our understanding of how the host environment influences drug-mutant interactions. Using an inducible mutant library targeting essential Mtb genes to characterize CGIs during infection, this study reveals that CGIs are both drug-specific and drug-agnostic and differ significantly from those observedin vitro. Synergistic CGIs comprised distinct metabolic pathways mediating antibiotic efficacy, revealing novel drug mechanisms of action, and defining potential drug targets that would synergize with frontline antitubercular drugs.
Peptide inhibitors targeting FOXO4-p53 interactions and inducing senescent cancer cell-specific apoptosis
Authors: Kang Donghoon , Lim Yeji , Ahn Dabin , Lee Jaeseok , Park Chin-Ju
Published: September 2024

Cellular senescence, marked by irreversible cell cycle arrest and the secretion of proinflammatory factors, contributes to aging and cancer recurrence. Chemotherapy can also induce senescence; senescent cells often resist apoptosis and promote tumor recurrence. The interaction between FOXO4 and p53 sustains cell survival. Herein, we used biophysical techniques and conducted cellular experiments to develop a peptide inhibitor targeting this interaction to eliminate senescent cancer cells. We identified key regions in the p53 transactivation domain (TAD) involved in FOXO4 binding and designed an optimized peptide inhibitor (CPP-CAND) with improved cell permeability. CPP-CAND showed high selectivity and potency in inducing apoptosis in senescent cells by disrupting FOXO4-p53 foci and activating caspase pathways. It is effective against senescent cancer cells induced by doxorubicin and cisplatin, highlighting its potential as a senolytic drug. Thus, CPP-CAND is a promising therapeutic candidate with improved selectivity, efficacy, and cost-effectiveness.
Polyol sugar osmolyte - sorbitol corrects chromosome cohesion and translational defects in cohesin mutants
Authors: Marathe Sayali , Chougule Haripriya , Nikam Vandana , Majumdar Amitabha , Bose Tania
Published: September 2024

The cohesin protein complex plays a very important role in chromosome segregation, transcription, DNA replication and chromosome condensation. Mutations in cohesin proteins give rise to a disease collectively referred to as Cohesinopathies. The major cause of Cohesinopathies arise due to defects associated with gene expression, that give rise to developmental disorders. In this study, we have usedSaccharomyces cerevisiaeto mimic the Cohesinopathy disorder Roberts syndrome with mutations (eco1W216G) homologous to that of humans (esco2). Our data suggests that polyol sugars like sorbitol, can repair misfolded proteins and reduce ER and proteostatic stress. We have used sorbitol as a chemical chaperone, to check how it can restore chromosome segregation, gene expression, misregulation, protein misfolding, autophagy and translational defects in the cohesin mutant of the Roberts’ phenotype.In silicoscreening has helped us identify the possible sites on eco1, which could be possibly altering the phenotypic traits.

Article Highlights

In presence of sorbitol

Temperature sensitivity of the Roberts mutants is rescued.

Chromosome cohesion defect is reduced.

Translational defects are minimized.

Autophagy is enhanced

Molecular docking shows its interaction with the acetyltransferase domain of ESCO2.
Nitrous oxide production, mechanisms, and modeling from a denitrifying phosphorus removal bioreactor
Authors: Farmer McKenna , Sabba Fabrizio , Wells George
Published: September 2024

Nitrous oxide (N2O) is a potent greenhouse gas produced as an unintentional, undesired byproduct in many nitrogen removal bioprocesses. Given the considerable challenges in managing N2O emissions from wastewater treatment, N2O could be reframed as a value-added product if intentionally generated and captured. This study assesses N2O production and mechanisms in a Coupled Aerobic-anoxic Nitrous Decomposition Operation with Phosphorus removal (CANDO+P) reactor. Optimal performance was achieved when the reactor was fed with a mixture of propionate and glucose, resulting in N2O was production up to 50% of influent nitrogen. Through 16S rRNA amplicon and shotgun metagenomic sequencing, we found thatCandidatusAccumulibacter were the dominant phosphorus accumulating organism (PAO). Assembly of a high-quality metagenome-assembled genome showed thatCa.Accumulibacter encoded a full complete denitrification pathway from nitrite to nitrogen gas. We also found abundant populations of denitrifying glycogen accumulating organisms (GAO) and ordinary heterotrophic organisms (OHO). We also incorporated truncated denitrification pathways into a process model to predict N2O generation. N2O predictions were the most similar to observed results when the denitrification pathways of PAO, GAO, and OHO model populations reflected denitrification gene abundances from the metagenomic sequencing analysis. Our work demonstrates the feasibility of using non-VFA carbon for intentional N2O generation and provides broader insights into N2O generation and truncated denitrification pathways of denitrifying PAO and GAO.
Multiple extracellular polymeric substances pathways expressed byAccumulibacterand the flanking community during aerobic granule formation and after influent modification
Authors: Cardona Laëtitia , Saini Jaspreet Singh , Rodilla Ramírez Pilar Natalia , Adler Aline , Holliger Christof
Published: September 2024

Aerobic granular sludge is a biological wastewater treatment process in which a microbial community forms a granular biofilm. The role ofCandidatusAccumulibacter in the production of a biofilm matrix composed of extracellular polymeric substances was studied in a sequencing batch reactor enriched with polyphosphate-accumulating organisms. The metabolisms of the microbial populations were investigated using de novo metatranscriptomics analysis. Finally, the effect of decreasing the influent phosphate concentration was investigated.

A few weeks after the reactor start-up, the microbial community was dominated byAccumulibacter. Up to nine species were active in parallel. However, the most active species differed according to sampling time. Reducing the phosphate concentration led to a dominance of the glycogen-accumulating organismPropionivibrio, with someAccumulibacterspecies still abundant.De novometatranscriptomic analysis indicated a high diversity of potential extracellular substances produced mainly byAzonexus, Accumulibacter, CandidatusContendobacter, andPropionivibrio. Moreover, the results suggest thatAzonexus, ContendobacterandPropionivibriorecycle the neuraminic acid produced byAccumulibacter. Changes in the microbial community did not cause the granules to disintegrate, indicating that aPropionivibrio-dominated community can maintain stable granules.
MLX phosphorylation stabilizes the ChREBP-MLX heterotetramer on tandem E-boxes to control carbohydrate and lipid metabolism
Authors: Cadena del Castillo Carla E , Deniz Onur , van Geest Femke , Rosseels Lore , Stockmans Ingrid , Robciuc Marius , Carpentier Sebastien , Wölnerhanssen Bettina K. , Meyer-Gerspach Anne Christin , Peterli Ralph , Hietakangas Ville , Shimobayashi Mitsugu
Published: September 2024

The heterodimeric ChREBP-MLX transcription factor complex is a key mediator that couples intracellular sugar levels to carbohydrate and lipid metabolism. To promote the expression of target genes, two ChREBP-MLX heterodimers form a heterotetramer to bind a tandem element with two adjacent E-boxes, called Carbohydrate Responsive Element (ChoRE). How the ChREBP-MLX hetero-tetramerization is achieved and regulated, remains poorly understood. Here we show that MLX phosphorylation on an evolutionarily conserved motif is necessary for the heterotetramer formation on the ChoRE and the transcriptional activity of the ChREBP-MLX complex. We identified CK2 and GSK3 as MLX kinases that coordinately phosphorylate MLX. High intracellular glucose-6-phosphate accumulation inhibits MLX phosphorylation and heterotetramer formation on the ChoRE, impairing ChREBP-MLX activity. Physiologically, MLX phosphorylation is necessary inDrosophilato maintain sugar tolerance and lipid homeostasis. Our findings suggest that MLX phosphorylation is a key mechanism for the ChREBP-MLX heterotetramer formation to regulate carbohydrate and lipid metabolism.
TgGloL is an atypical glyoxalase/VOC domain-containing apicoplast protein that is important for the growth ofToxoplasma
Authors: Sanchez Syrian G. , Pouzet Esther , Guimbaud Loïc , Graindorge Arnault , Berry Laurence , Besteiro Sébastien
Published: September 2024

Glycolysis is a conserved metabolic pathway that converts glucose into pyruvate in the cytosol, producing ATP and NADH. InToxoplasma gondiiand several other apicomplexan parasites, some glycolytic enzymes have isoforms located in their plastid (called the apicoplast). In this organelle, glycolytic intermediates like glyceraldehyde 3-phosphate (GAP) and dihydroxyacetone phosphate (DHAP) are imported from the cytosol and further metabolized, providing ATP, reducing power, and precursors for anabolic pathways such as isoprenoid synthesis. However, GAP and DHAP can spontaneously convert into methylglyoxal, a toxic by-product detoxified by the glyoxalase system, typically involving Glyoxalase-1 (Glo-1) and Glyoxalase-2 (Glo-2). In T. gondii, we identified an atypical protein, TgGloL, containing a Glo-1-like motif but with limited homology to typical Glo enzymes. TgGloL localizes to the apicoplast, and its conditional knockdown impairs parasite growth, indicating its importance. While a specific and direct role for TgGloL in methylglyoxal detoxification within the apicoplast remains unclear, it is crucial for maintaining organelle homeostasis and for overall parasite fitness.
From tissue to subcellular level : imaging human precision-cut lung slices (PCLS) to gain insight into pandemic bacterial or viral infections
Authors: Eymieux Sébastien , Bull-Maurer Anne , Pichon Julien , Sizaret Damien , Maquart Marianne , Carreras Florence , Saint-Vanne Maïa , Doz-Deblauwe Emilie , Bounab Badreddine , Lipan Béatrice , Handala Lynda , Chesnel Florentine , Burlaud-Gaillard Julien , Mammano Fabrizio , Brand Denys , Legras Antoine , Winter Nathalie , Remot Aude
Published: September 2024

We describe a method for the generation and deep imaging of human precision-cut lung slices (PCLS). PCLS bridge the gap betweenin vivoandin vitrostudies, providing a robust system for visualizing events from tissue to subcellular levels in the three-dimensional lung environment, with the preservation of all resident cell types and cell-cell interactions. They also constitute a validated model for studying host cell-pathogen interactions. Here, we detail the generation of human PCLS, followed by their infection and imaging by laser scanning confocal microscopy and transmission electron microscopy (TEM). We establish the conditions forex vivoinfection and replication of two pathogens of relevance to human respiratory health: a virus (SARS-CoV-2) and a bacterium (Mycobacterium tuberculosis,Mtb). PCLS can be obtained in a single day, infected the next day, and were successfully cultivated for up to a week in this study. Imaging was performed on fixed samples. The preparation of PCLS took one day for confocal imaging and five days for TEM imaging. All procedures are readily adaptable to explore other pathogens and other species and are easy to implement by users with experience in tissue culture. Some specialist equipment (an Alabama tissue slicer) is required for PCLS generation.
Fibroblast-specific protein-protein interactions for myocardial fibrosis from MetaCore network
Authors: Frahm Klaus M. , Kotelnikova Ekaterina , Kunduzova Oksana , Shepelyansky Dima L.
Published: September 2024

Myocardial fibrosis is a major pathologic disorder associated with a multitude of cardiovascular diseases (CVD). The pathogenesis is complex and encompasses multiple molecular pathways. Integration of fibrosis-associated genes into the global MetaCore network of protein-protein interactions (PPI) offers opportunities to identify PPI with functional and therapeutic significance. Here, we report the generation of a fibrosis-focused PPI network and identification of fibroblast-specific PPI driving reparative and reactive myocardial fibrosis. In TGFb-mediated fibroblast activation, PPI hubs predict new regulatory mechanisms for fibrosis-associated genes. We introduce an efficient Erdös barrage approach to suppress activation of a number of fibrosis-associated nodes in order to reverse fibrotic cascades. Our results suggest that PPI prediction model can offer network insights into fibrosis mechanisms and can complement future experimental efforts to counteract cardiac fibrosis.
Repurposing tRNA isodecoders for non-canonical functions via tRNA cleavage
Authors: Bhatter Nupur , Advani Vivek M. , Takenaka Yoshika , Lyons Shawn M. , Akiyama Yasutoshi , Anderson Paul J. , Ivanov Pavel
Published: September 2024

Transfer RNAs (tRNAs) are the key adaptor molecules aiding protein synthesis. Hundreds of tRNA genes are found in the human genome but the biological significance of this genetic excess is still enigmatic. The tRNA repertoires are variable between tissues and cells as well as during development. Such variations can only be partially explained by the correlation to the physiological needs in protein production, e.g. by changes in the expression of tRNA isoacceptor sets (tRNAs charged with the same amino acid but bearing different anticodons). However, changes in the expression levels of individual isodecoders (tRNAs with the same anticodon) are less understood. Besides canonical functions in mRNA translation, tRNAs are implicated in non-canonical functions unrelated to protein synthesis. tRNAs are rich source of small non-protein coding RNAs called tRNA-derived RNAs (tDRs), which include tRNA-derived stress-induced RNAs (tiRNAs) formed in response to stress. Here, we show that tiRNAs derived from isodecoders different in a single nucleotide can also differ in their activities. Specifically, we show that isodecoder sets for tRNAHis-GTG, tRNAGly-GCCand tRNACys-GCAare cleaved by ribonucleases to yield 5’-tiRNAs showing differential activity towards mRNA reporter translation. Our data propose a model where cleavage repurposes specific tRNA isodecoders for non-canonical functions.

Significance Statement

The human genome encodes hundreds of transfer RNA (tRNA) genes to decode 61 codons. The basis for such genetic redundancy is unclear but the increase in the number of tRNA genes goes in concert with the complexity of an organism. While changes in the expression of isoacceptor tRNA pools can reflect adaptation to demanding protein synthesis needs and/or codon usage, the variations in the expression of the individual tRNA isodecoders are documented but poorly understood. Such expression variations are hypothesized to contribute to non-canonical tRNA functions, yet physiological relevance remains ambiguous. We report here that specific tRNA isodecoders can be functionally repurposed through cleavage that produces tRNA-derived RNAs (tDRs). The repurposing employs nucleotide variations in isodecoders leading to the production of distinct sets of tDRs with variable bioactivities.
Two functional forms of the Meckel-Gruber syndrome protein TMEM67 generated by proteolytic cleavage by ADAMTS9 mediate Wnt signaling and ciliogenesis
Authors: Ahmed Manu , Fischer Sydney , Robert Karyn L. , Lange Karen I. , Stuck Michael W. , Best Sunayna , Johnson Colin A. , Pazour Gregory J. , Blacque Oliver E. , Nandadasa Sumeda
Published: September 2024

TMEM67mutations are the major cause of Meckel-Gruber syndrome. TMEM67 is involved in both ciliary transition zone assembly, and non-canonical Wnt signaling mediated by its extracellular domain. How TMEM67 performs these two separate functions is not known. We identify a novel cleavage motif in the extracellular domain of TMEM67 cleaved by the extracellular matrix metalloproteinase ADAMTS9. This cleavage regulates the abundance of two functional forms: A C-terminal portion which localizes to the ciliary transition zone regulating ciliogenesis, and a non- cleaved form which regulates Wnt signaling. By characterizing threeTMEM67ciliopathy patient variants within the cleavage motif utilizing mammalian cell culture andC. elegans,we show the cleavage motif is essential for cilia structure and function, highlighting its clinical significance. We generated a novel non-cleavable TMEM67 mouse model which develop severe ciliopathies phenocopyingTmem67-/-mice, but in contrast, undergo normal Wnt signaling, substantiating the existence of two functional forms of TMEM67.
Genome-Wide Mapping of RNA-Protein Associations via Sequencing
Authors: Qi Zhijie , Xue Shuanghong , Chen Junchen , Zhao Wenxin , Johnson Kara , Wen Xingzhao , Richard John Lalith Charles , Zhong Sheng
Published: September 2024

RNA-protein interactions are crucial for regulating gene expression and cellular functions, with their dysregulation potentially impacting disease progression. Systematically mapping these interactions is resource-intensive due to the vast number of potential RNA and protein interactions. Here, we introduce PRIM-seq (Protein-RNA InteractionMapping by sequencing), a method for the concurrentde novoidentification of RNA-binding proteins (RBPs) and the elucidation of their associated RNAs. PRIM-seq works by converting each RNA-protein pair into a unique chimeric DNA sequence, which is then decoded through DNA sequencing. Applied to two human cell types, PRIM-seq generated a comprehensive human RNA-protein association network (HuRPA), consisting of more than 350,000 RNA-proteins pairs involving approximately 7,000 RNAs and 11,000 proteins. The data revealed an enrichment of previously reported RBPs and RNA-protein interactions within HuRPA. We also identified LINC00339 as a protein-associating non-coding RNA and PHGDH as an RNA-associating protein. Notably, PHGDH interacts with BECN1 and ATF4 mRNAs, suppressing their protein expression and consequently inhibiting autophagy, apoptosis, and neurite outgrowth while promoting cell proliferation. PRIM-seq offers a powerful tool for discovering RBPs and RNA-protein associations, contributing to more comprehensive functional genome annotations.
LEA_4 motifs function alone and in conjunction with synergistic cosolutes to protect a labile enzyme during desiccation
Authors: Nicholson Vincent , Nguyen Kenny H , Gollub Edith , McCoy Mary , Yu Feng , Holehouse Alex S , Sukenik Shahar , Boothby Thomas C
Published: September 2024

Organisms from all kingdoms of life depend on Late Embryogenesis Abundant (LEA) proteins to survive desiccation. LEA proteins are divided into broad families distinguished by the presence of family-specific motif sequences. The LEA_4 family, characterized by eleven-residue motifs, plays a crucial role in the desiccation tolerance of numerous species. However, the role of these motifs in the function of LEA_4 proteins is unclear, with some studies finding that they recapitulate the function of full-length LEA_4 proteins in vivo, and other studies finding the opposite result. In this study, we characterize the ability of LEA_4 motifs to protect a desiccation-sensitive enzyme, citrate synthase, from loss of function during desiccation. We show here that LEA_4 motifs not only prevent the loss of function of citrate synthase during desiccation, but also that they can do so more robustly via synergistically interactions with cosolutes. Our analysis further suggests that cosolutes induce synergy with LEA_4 motifs in a manner that correlates with transfer free energy (TFE). This research advances our understanding of LEA_4 proteins by demonstrating that during desiccation their motifs can protect specific clients to varying degrees and that their protective capacity is modulated by their chemical environment. Our findings extend beyond the realm of desiccation tolerance, offering insights into the interplay between IDPs and cosolutes. By investigating the function of LEA_4 motifs, we highlight broader strategies for understanding protein stability and function.
RCC1 depletion drives protein transport defects and rupture in micronuclei
Authors: Zych Molly G , Contreras Maya , Vashisth Manasvita , Mammel Anna E , Ha Gavin , Hatch Emily M
Published: September 2024

Micronuclei (MN) are a commonly used marker of chromosome instability that form when missegregated chromatin recruits its own nuclear envelope (NE) after mitosis. MN frequently rupture, which results in genome instability, upregulation of metastatic genes, and increased immune signaling. MN rupture is linked to NE defects, but the cause of these defects is poorly understood. Previous work from our lab found that chromosome identity correlates with rupture timing for small MN,i.e.MN containing a short chromosome, with more euchromatic chromosomes forming more stable MN with fewer nuclear lamina gaps. Here we demonstrate that histone methylation promotes rupture and nuclear lamina defects in small MN. This correlates with increased MN size, and we go on to find that all MN have a constitutive nuclear export defect that drives MN growth and nuclear lamina gap expansion, making the MN susceptible to rupture. We demonstrate that these export defects arise from decreased RCC1 levels in MN and that additional loss of RCC1 caused by low histone methylation in small euchromatic MN results in additional import defects that suppress nuclear lamina gaps and MN rupture. Through analysis of mutational signatures associated with early and late rupturing chromosomes in the Pan-Cancer Analysis of Whole Genomes (PCAWG) dataset, we identify an enrichment of APOBEC and DNA polymerase E hypermutation signatures in chromothripsis events on early and mid rupturing chromosomes, respectively, suggesting that MN rupture timing could determine the landscape of structural variation in chromothripsis. Our study defines a new model of MN rupture where increased MN growth, caused by defects in protein export, drives gaps in nuclear lamina organization that make the MN susceptible to membrane rupture with long-lasting effects on genome architecture.
Observation of the protein-inorganic interface of ferritin by cryo-electron microscopy
Authors: Sen Sagnik , Thaker Amar , Williams Dewight , Chiu Po-Lin , Nannenga Brent L.
Published: September 2024

Visualizing the structure of the protein-inorganic interface is critically important for our more complete understanding of biomineralization. Unfortunately, there are limited approaches for the direct and detailed study of biomolecules that interact with inorganic materials. Here we use single particle cryo-EM to study the protein-nanoparticle interactions of human light chain ferritin and visualize the high-resolution details of the protein-inorganic interface. In this work, we determined the 2.85 Å structure of human light chain ferritin bound to its native iron oxide nanoparticle substrate. The resulting cryo-EM maps confirmed and enhanced previously proposed interactions of the protein with the material along the B-helix, and revealed new interaction at the C-terminus of light chain ferritin. This work sheds new light on the mechanisms of ferritin biomineralization and further demonstrates the application of cryo-EM for the study of protein-inorganic systems.
Psoriasis-like inflammation induces mitochondrial function and structure changes in human keratinocytes and fibroblasts
Authors: Kulkovienė Gabrielė , Uldukytė Martyna , Haluts Sofiya , Kairytė Milda , Šoliūnas Jonas , Šalčiūtė Viktorija , Morkūnienė Ramunė , Jekabsone Aistė
Published: September 2024

Mitochondrial structural and functional changes accompany psoriasis; however, the mitochondrial response to psoriatic inflammation in keratinocytes and fibroblasts has not been studied. Here, we investigate the effect of psoriasis-like inflammation (PLI) induced by cytokine cocktail (IL-17, IL-22, TNF-α) on mitochondrial network morphology and function in living cultured keratinocytes (HaCaT) and fibroblasts (BJ-5ta). In both skin cell types, PLI triggered expression of psoriasis-related SKALP/Elafin and high amounts of cytokines (IL-1, IL-6), interferons (IFN-α, IFN-β, IFN-γ), and chemokines (CCL5, CXCL8), accompanied by mitochondrial ROS production, network fragmentation, swelling, and cristae disassembly. STED nanoscopy revealed that the mitochondrial cristae are disappearing in response to PLI, with the process starting faster and being more pronounced in keratinocytes than in fibroblasts. Moreover, in keratinocytes, PLI leads to mitochondrial respiration suppression and elimination of the organelles. These findings of cell-specific mitochondrial responses may guide future investigations into new pharmacological targets for managing psoriasis.

Abstract Figure
Dynamics of recombination, X inactivation and centromere proteins during stick insect spermatogenesis
Authors: Dumas Zoé , Toubiana William , Delattre Marie , Schwander Tanja
Published: September 2024

In eukaryotes, the cellular processes contributing to gamete formation form the building blocks of genetic inheritance across generations. While traditionally viewed as conserved across model organisms, emerging studies reveal significant variation among eukaryotes in meiotic and post-meiotic processes. Extending our knowledge to non-model organisms is therefore critical to improve our understanding of the evolutionary origin, significance and subsequent modifications associated with gamete formation. We describe the mechanisms underlying recombination, chromosome segregation and meiotic sex chromosome inactivation in the stick insect groupTimema. Our results reveal that in males, 1) recombination initiates before synapsis, 2) the mechanisms of X inactivation are variable among species and the X remains silenced despite two waves of transcriptional activation in autosomes during spermatogenesis, 3) chromosome segregation is preceded by the recruitment of centromere proteins that either bind locally or longitudinally along the chromosomes. Together, our observations help understand the evolutionary significance of key cellular processes related to spermatogenesis and shed light on the diversity of their underlying mechanisms among species, includingTimemastick insects.
Sampling Root-Associated Microbiome Communities of Maize (Zea mays)
Authors: Favela Alonso , Raglin Sierra , Wallace Jason G.
Published: September 2024

The soil microbiome of maize shapes its fitness, sustainability, and productivity. Accurately sampling maize's belowground microbial communities is important for identifying and characterizing these functions. Here, we describe a protocol to sample the maize rhizosphere (including the rhizoplane and endorhizosphere) and root zone (still influential but further from the root) in a form suitable for downstream analyses like culturing and DNA extractions. Although this protocol is written withZea maysas the focus, these methods can generally be applied to any plant with similar fibrous root systems.
Sampling the Maize (Zea mays) Leaf Microbiome
Authors: Wallace Jason G.
Published: September 2024

The microbiota of maize leaves can be beneficial or detrimental to the host. Foliar diseases are the most obvious detrimental impact of the leaf microbiome, though more subtle effects of the normal (nondisease) community are an active area of research. This protocol describes two specific methodologies to sample the maize leaf microbiome: one sampling the surface (epiphyte) microbiome and one sampling the interior (endophyte) microbiome. Each method begins with collected leaf tissue and finishes with a cell suspension suitable for either isolating live microbes or extracting DNA for sequencing.
Manipulating the Maize (Zea mays) Microbiome
Authors: Raglin Sierra S. , Favela Alonso , Laspisa Daniel , Wallace Jason G.
Published: September 2024

Maize (Zea mays) is a multifaceted cereal grass used globally for nutrition, animal feed, food processing, and biofuels, and a model system in genetics research. Studying the maize microbiome sometimes requires its manipulation to identify the contributions of specific taxa and ecological traits (i.e., diversity, richness, network structure) to maize growth and physiology. Due to regulatory constraints on applying engineered microorganisms in field settings, greenhouse-based experimentation is often the first step for understanding the contribution of root-associated microbiota—whether natural or engineered—to plant phenotypes. In this protocol, we describe methods to inoculate maize with a specific microbiome as a tool for understanding the microbiota's influence on its host plant. The protocol involves removal of the native seed microbiome followed by inoculation of new microorganisms; separate protocols are provided for inoculations from pure culture, from soil slurry, or by mixing in live soil. These protocols cover the most common methods for manipulating the maize microbiome in soil-grown plants in the greenhouse. The methods outlined will ultimately result in rhizosphere microbial assemblages with varying degrees of microbial diversity, ranging from low diversity (individual strain and synthetic community [SynCom] inoculation) to high diversity (percent live inoculation), with the slurry inoculation method representing an “intermediate diversity” treatment.
B→Xc(u)ℓν¯ℓγ
and determination of nonperturbative parameters
Authors: Mahajan Namit , Mishra Dayanand
Published: September 2024

This paper explores the calculation of nonperturbative parameters present in the matrix element of semileptonic inclusive B decays. These are important for the inclusive determination of the Cabbibo-Kobayashi-Maskawa parameters in the Standard Model. We focus on calculating the rate for radiative inclusive decay, B→Xcℓν¯ℓγ, where γ is hard. Both the radiative and nonradiative (B→Xcℓν¯ℓ) modes are found to require the same nonperturbative parameters. We propose forming ratios from B→Xcℓν¯ℓγ and B→Xcℓν¯ℓ widths in different lepton energy ranges. Our results provide an efficient way to unambiguously calculate the nonperturbative parameters, especially when combined with total width calculations of B→Xcℓν¯ℓ. This is shown explicitly by working to O(1/mb) and determining λ1 and λ2.

Published by the American Physical Society
2024
Near-horizon properties of trajectories with finite force relevant for Bañados-Silk-West effect
Authors: Ovcharenko H. V. , Zaslavskii O. B.
Published: September 2024

According to the Bañados-Silk-West (BSW) effect, two particles moving toward a black hole can collide near the horizon with an unbounded energy in the center-of-mass frame. This requires one of the particles to have fine-tuned parameters in such a way that the time component of generalized momentum is zero X=0. Thus the existence of such trajectories is a necessary condition for the BSW effect. However, it is insufficient since the forward-in-time condition requires X>0 outside the horizon. We examine this condition for different types of particles and horizons and find configurations for which the BSW effect is possible. In doing so, we take into account a finite force of unspecified nature exerted on particles. It includes relationships between numbers characterizing the rate with which four-velocity, acceleration, and metric functions change near the horizon. For some aforementioned relations, parameters of a system control the sign of X; in other cases they are required for X to be a real quantity. In the simplest case of free particles the BSW effect for the Kerr or Kerr-Newman black hole is impossible if a fine-tuned particle has a negative energy, so in this sense a combination of the Penrose process and the BSW effect is forbidden.

Published by the American Physical Society
2024
Commercialisation of artificial intelligence: a research on entrepreneurial companies with challenges and opportunities
Authors: Güner Gültekin Duygu , Pinarbasi Fatih , Yazici Merve , Adiguzel Zafer
Published: September 2024

Purpose

The research paper’s purpose is to contribute to the literature by analysing the essential resources and processes required for successful commercialisation, the contemporary challenges and opportunities of artificial intelligence initiatives in Türkiye, and the diverse models and methods employed by these initiatives.

Design/methodology/approach

Within the scope of the research, interviews were conducted with 10 entrepreneurs who established artificial intelligence-oriented enterprises in technoparks in Istanbul and Antalya. All 10 interviews were analysed using the MAXQDA20 software tool. Structured qualitative content analysis was used for the data analysis procedure.

Findings

Based on the research, external factors have a significant impact on the future growth opportunities of the market. Expanding the client base, gaining international recognition, and securing financing are crucial for success. However, the findings reveal challenges in the relatively young local ecosystem. One major criticism is the lack of support in marketing and sales activities for refined products. To address this, providing financial incentives and knowledge transfer to those in need is vital.

Research limitations/implications

Since the research was conducted only with entrepreneurs who established and successfully commercialised artificial intelligence-oriented enterprises, it is recommended that future studies be performed with a widespread sample group, considering this limited situation. Furthermore, to overcome survivorship bias, it is recommended that posterior studies include failed commercialisation attempts in AI ventures.

Practical implications

It can be argued that there is no deliberate approach or model for commercialization. Entrepreneurs often draw from their own prior experiences or observe industry trends. Given the limited financial resources available in the domestic market and the challenge of attracting foreign investors to Turkish brands, entrepreneurs tend to rely on internal approaches for commercialisation.

Originality/value

This research delves into the commercialisation prospects and obstacles encountered by AI start-ups in Türkiye. It comprises qualitative insights into business models, commercialisation approaches, opportunities, and challenges. The data were obtained from interviews with entrepreneurs operating in the industry.
The thermal-mechanical deformations of CO2 mixture gases dry gas seal based on two-way thermal-fluid-solid coupling model
Authors: Chen Wei , Xu Hengjie , Mao Wenyuan , Liu Meihong , Sun Xuejian , Deng Qiangguo
Published: September 2024

Purpose

This study aims to investigate the influence mechanism of thermal-mechanical deformations on the CO2 mixture gases dry gas seal (DGS) flow field and compare the deformation characteristics and sealing performance between two-way and one-way thermal-fluid-solid coupling models.

Design/methodology/approach

The authors established a two-way thermal-fluid-solid coupling model by using gas film thickness as the transfer parameter between the fluid and solid domain, and the model was solved using the finite difference method and finite element method. The thermal-mechanical deformations of the sealing rings, the influence of face deformation on the flow field and sealing performance were obtained.

Findings

Thermal-mechanical deformations cause a convergent gap between the two sealing end faces, resulting in an increase in the gas film thickness, but a decrease in the gas film temperature and sealing ring temperature. The axial relative deformations of rotating and stationary ring end faces caused by mechanical and thermal loads in the two-way coupling model are less than those in the one-way coupling (OWC) model, and the gas film thickness and leakage rate are larger than those in the OWC model, whereas the gas film stiffness is the opposite.

Originality/value

This paper provides a theoretical support and reference for the operational stability and structural optimization design of CO2 mixture gases DGS under high-pressure and high-speed operation conditions.
Network power and firm innovation: the moderating roles of power distance and procedural justice
Authors: Yang Naiding , Zhu Xianglin , Zhang Mingzhen , Wang Yu
Published: September 2024

Purpose

This study aims to investigate the influence of network power on exploratory and exploitative innovation and examines the moderating effects of power distance and procedural justice on these untested relationships.

Design/methodology/approach

This study uses survey data collected from firms in China and explores the influential mechanisms of network power, power distance and procedural justice in firm innovation.

Findings

This study empirically shows that network power has an inverted U-shaped effect on exploratory and exploitative innovation. Power distance weakens the effect of network power on exploratory and exploitative innovation, and procedural justice enhances the effect of network power on exploratory and exploitative innovation.

Research limitations/implications

This study extends resource dependence theory and contributes to the literature on innovation management. Future studies should use different collection channels or research methods to provide more evidence for model promotion. In addition, the dynamic power game among network members and the roles of other mediators or moderators warrant further consideration.

Practical implications

Managers should exercise power strategies properly and ensure that their innovation income exceeds expenditures. Managers need to pay serious attention to power distance and procedural justice in the network and formulate suitable cooperation strategies based on actual conditions.

Originality/value

This study applies the resource dependence theory to investigate the influence of network power on exploratory and exploitative innovation. In addition, the moderating roles of power distance and procedural justice in the above relationships, which have rarely been discussed in previous studies, were tested.
Contemporaneous and lagged R2 decomposed connectedness technique to explore interlinkages between green logistics, environmental issues and green and dirty energy consumption in Vietnam
Authors: Ha Le Thanh
Published: September 2024

Purpose

This study aims to empirically connect green logistics performance, renewable energy, non-renewable energy, CO2 emissions and gross domestic product in Vietnam from 2000 to 2022.

Design/methodology/approach

Within this study, the author uses innovative tools, specifically a R2 decomposed linkage method, to scrutinize the connections between green logistics, environmental issues and the use of green and dirty energy.

Findings

The results highlight the two-way relationship between green logistics and energy security in Vietnam. Green logistics plays various roles in diverse periods, from a net shock transmitter to a net shock receiver in the designed system. Using a dynamic and contemporaneous dynamic linkage method, this study emphasizes the change in the role and the dominance of green logistics and renewable energy consumption. Notably, the unexpected shocks also lead to changes in these variables’ roles.

Originality/value

This paper presents two significant contributions to the existing body of literature. Firstly, as previously emphasized, this research marks a pioneering effort to examine the connection between green logistics, environmental issues and the use of green and dirty energy when it comes to developing nations such as Vietnam. Secondly, this research introduces a novel approach to investigating the interconnectedness of volatility across diverse markets, offering a more suitable method for such analyses. Within this study, the author uses innovative tools, specifically an R2 decomposed linkage method, to scrutinize the connections between green logistics, environmental issues and the use of green and dirty energy. In this analysis, the author examined data from 2000 through 2022. A thorough analysis is presented using the data, exploring the connections between the volatilities resulting from various problems in Vietnam.