bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhancing Recovery from Gut Microbiome Dysbiosis and Alleviating DSS-Induced Colitis in Mice with a Consortium of Rare Short-Chain Fatty Acid-Producing Bacteria
Authors: Ambat Achuthan , Antony Linto , Maji Abhijit , Ghimire Sudeep , Mattiello Samara , Kashyap Purna C. , More Sunil , Sebastian Vanessa , Scaria Joy 
Published: September 2023

AbstractThe human gut microbiota is a complex community comprising hundreds of species, with a few present in high abundance and the vast majority in low abundance. The biological functions and effects of these low-abundant species on their hosts are not yet fully understood. In this study, we assembled a bacterial consortium (SC-4) consisting ofB. paravirosa, C. comes, M. indica, andA. butyriciproducens, which are low-abundant, short-chain fatty acid (SCFA)-producing bacteria isolated from healthy human gut, and tested its effect on host health using germfree and human microbiota-associated colitis mouse models. The selection also favored these four bacteria being reduced in abundance in either Ulcerative Colitis (UC) or Crohn’s disease (CD) metagenome samples. Our findings demonstrate that SC-4 can colonize germ-free (GF) mice, increasing mucin thickness by activating MUC-1 and MUC-2 genes, thereby protecting GF mice from Dextran Sodium Sulfate (DSS)-induced colitis. Moreover, SC-4 aided in the recovery of human microbiota-associated mice from DSS-induced colitis, and intriguingly, its administration enhanced the alpha diversity of the gut microbiome, shifting the community composition closer to control levels. The results showed enhanced phenotypes across all measures when the mice were supplemented with Inulin as a dietary fiber source alongside SC-4 administration. We also showed a functional redundancy existing in the gut microbiome, resulting in the low abundant SCFA producers acting as a form of insurance, which in turn accelerates recovery from the dysbiotic state upon the administration of SC-4. SC-4 colonization also upregulated iNOS gene expression, further supporting its ability to produce an increasing number of goblet cells. Collectively, our results provide evidence that low-abundant SCFA-producing species in the gut may offer a novel therapeutic approach to IBD.
Autophagy adaptors mediate Parkin-dependent mitophagy by forming sheet-like liquid condensates
Authors: Yang Zi , Yoshii Saori R. , Sakai Yuji , Chino Haruka , Knorr Roland L. , Mizushima Noboru 
Published: September 2023

AbstractDuring PINK1 and Parkin-mediated mitophagy, autophagy adaptors are recruited to depolarized mitochondria to promote the selective degradation of mitochondria. Autophagy adaptors such as OPTN and NDP52 bridge mitochondria and autophagosomal membranes by binding to ubiquitinated mitochondrial proteins and autophagosomal ATG8 family proteins. Here, we demonstrate that OPTN and NDP52 form sheet-like phase-separated condensates with liquid-like properties on the surface of ubiquitinated mitochondria. The dynamic and liquid-like feature of OPTN condensates is important for mitophagy activity because reducing the liquidity of OPTN–ubiquitin condensates suppresses the recruitment of ATG9 vesicles and impairs mitophagy. Based on these results, we propose a dynamic liquid-like model of autophagy adaptors, in contrast to a stoichiometric model, to explain their interactions between autophagic membranes (i.e., ATG9 vesicles and isolation membranes) and mitochondrial membranes during Parkin-mediated mitophagy. This model underscores the importance of liquid–liquid phase separation in facilitating membrane– membrane contacts, likely through the generation of capillary forces.
Structural basis for EROS binding to human phagocyte NADPH oxidase NOX2
Authors: Liang Shiyu , Liu Aijun , Liu Yezhou , Wang Fuxing , Zhou Youli , Wang Tao , Liu Zheng , Ren Ruobing , Ye Richard D. 
Published: September 2023

ABSTRACTEROS (essential for reactive oxygen species) is a recently identified molecular chaperone of NOX2 (gp91phox), the catalytic subunit of phagocyte NADPH oxidase. Deficiency in NOX2 expression or function due to genetic mutations leads to chronic granulomatous disease (CGD) with recurrent bacterial and fungal infections. To delineate how EROS interacts with NOX2, we solved the cryo-EM structure of the EROS-NOX2-p22phoxheterotrimeric complex. EROS binds to NOX2 in plasma membrane through its anti-parallel α-helices H1 and H2, and in cytoplasm through multiple β-strands that form hydrogen bonds with the C terminal fragment of NOX2. EROS binding alters the conformation of the TM2 and TM6 transmembrane helices, increases the distance between the two hemes, and causes dislocation of the binding site for flavin adenine dinucleotide (FAD). EROS colocalizes with NOX2 on cell surface of neutrophil-like HL-60 cells and forms a heterotrimer with mature NOX2-p22phoxin transfected cells. Phorbol myristate acetate, an activator of NOX2, induces dissociation of EROS from NOX2 in a NanoLuc complementation assay with concurrent production of superoxide in reconstituted cells. Taken together, these findings provide a structural basis for EROS-NOX2 interaction and suggest a previously unidentified function of EROS in regulating NOX2 activation.
Suppression of progesterone by influenza A virus mediates adverse maternal and fetal outcomes in mice
Authors: Creisher Patrick S. , Parish Maclaine A. , Lei Jun , Liu Jin , Perry Jamie L. , Campbell Ariana D. , Sherer Morgan L. , Burd Irina , Klein Sabra L. 
Published: September 2023

AbstractInfluenza A virus infection during pregnancy can cause adverse maternal and fetal outcomes, but the mechanism responsible remains elusive. Infection of outbred mice with 2009 H1N1 at embryonic day (E) 10 resulted in significant maternal morbidity, placental tissue damage and inflammation, fetal growth restriction, and developmental delays that lasted through weaning. Restriction of pulmonary virus replication was not inhibited during pregnancy, but infected dams had suppressed circulating and placental progesterone (P4) concentrations that were caused by H1N1-induced upregulation of pulmonary cyclooxygenase (COX)-1, but not COX-2-, dependent synthesis and secretion of prostaglandin (PG) F2α. Treatment with 17-α-hydroxyprogesterone caproate (17-OHPC), a synthetic progestin that is safe to use in pregnancy, ameliorated the adverse maternal and fetal outcomes from H1N1 infection and prevented placental cell death and inflammation. These findings highlight the therapeutic potential of progestin treatments for influenza during pregnancy.ImportancePregnant individuals are at risk of severe outcomes from both seasonal and pandemic influenza A viruses. Influenza infection during pregnancy is associated with adverse fetal outcomes at birth and adverse consequences for offspring into adulthood. We developed an outbred mouse model of 2009 H1N1 influenza virus infection during pregnancy, with semi-allogenic fetuses. When dams are infected with 2009 H1N1, in addition to pulmonary virus replication, tissue damage, and inflammation, the placenta shows evidence of transient damage and inflammation that is mediated by increased activity along the arachidonic acid pathway leading to suppression of circulating progesterone. Placental damage and suppressed progesterone are associated with long-term effects on perinatal growth and developmental delays in offspring. Treatment of H1N1-infected pregnant mice with 17-OHPC, a synthetic progestin treatment safe that is safe to use in pregnancy, prevents placental damage and inflammation and adverse fetal outcomes. This provided a novel therapeutic option for treatment of influenza during pregnancy that should be explored clinically.
Influenza A virus activates the unfolded protein response and induces the accumulation of insoluble protein aggregates that are essential for efficient viral propagation
Authors: Marques Mariana , Ramos Bruno , Albuquerque Hélio , Pereira Marisa , Ribeiro Diana Roberta , Nunes Alexandre , Sarabando Jéssica , Brás Daniela , Ferreira Ana Rita , Vitorino Rui , Amorim Maria João , Silva Artur M. S. , Soares Ana Raquel , Ribeiro Daniela 
Published: September 2023

AbstractInfluenza A virus (IAV) is one of the main causes of annual respiratory epidemics in humans. IAV employs multiple strategies to evade host immunity and hijack cellular mechanisms to support proper virion formation and propagation. Some of these strategies encompass the manipulation of pathways involved in protein homeostasis, leading to changes in the host proteome and protein distribution within the cell. In this study, we performed a detailed analysis of the interplay between IAV and the host cells’ proteostasis mechanisms throughout the entire infectious cycle. We reveal that IAV infection induces the activation of the inositol requiring enzyme 1 (IRE1) branch of the unfolded protein response (UPR), at an infection stage that coincides with high rates of viral protein translation. This activation is particularly important for infection, as attenuation of virus production was observed upon IRE1 inhibition. Concomitantly to UPR activation, we observed the accumulation of virus-induced insoluble protein aggregates, which contain both viral and host proteins and are associated with a dysregulation of the host cell RNA metabolism. We demonstrate that this accumulation is important for IAV propagation, as its prevention using a quinoline-steroid hybrid compound significantly reduces the number of produced infectious virus particles. Our data suggests that the formation of these insoluble protein aggregates favors the final steps of the infection cycle, more specifically the virion assembly. Our findings reveal additional mechanisms by which IAV disrupts the host cell proteostasis to favor infection and uncover new cellular targets that can be explored for the development of host-directed antiviral strategies.
Row1, a member of a new family of conserved fungal proteins involved in infection, is required for appressoria functionality in Ustilago maydis
Authors: Pejenaute-Ochoa María Dolores , Tomás-Gallardo Laura , Ibeas José I. , Barrales Ramón R. 
Published: September 2023

SummaryThe appressorium of phytopathogenic fungi is a specific structure with a crucial role in plant cuticle penetration. Pathogens with melanized appressoria break the cuticle through cell wall melanization and intracellular turgor pressure. However, in fungi with non-melanized appressorium, the mechanisms governing cuticle penetration are poorly understood. Here we characterize Row1, a previously uncharacterized appressoria-specific protein ofUstilago maydisthat localizes to membrane and secretory vesicles. Deletion ofrow1decrease appressoria formation and plant penetration, thereby reducing virulence. Specifically, the Δrow1mutant has a thicker cell wall that is more resistant to glucanase degradation. We also observed that the Δrow1mutant has secretion defects. Our data suggest that Row1 could modify the glucans that form the fungal cell wall and may be involved in unconventional protein secretion, thereby promoting both appressoria maturation and penetration. We show that Row1 is functionally conserved at least among Ustilaginaceae and belongs to the Row family, which consists of five other proteins that are highly conserved among Basidiomycota fungi and are involved inU. maydisvirulence. We observed similarities in localization between Row1 and Row2, which is also involved in cell wall remodelling and secretion, suggesting similar molecular functions for members of this protein family.
SIRT1 and SIRT3 impact host mitochondrial function and host-SalmonellapH balance during infection
Authors: Hajra Dipasree , Yadav Vikas , Singh Amit , Chakravortty Dipshikha 
Published: September 2023

ABSTRACTMitochondria are an important organelle regulating energy homeostasis. Mitochondrial health and dynamics are crucial determinants of the outcome of several bacterial infections. SIRT3, a major mitochondrial sirtuin, along with SIRT1 regulates key mitochondrial functions. This led to considerable interest in understanding the role of SIRT1 and SIRT3 in governing mitochondrial functions duringSalmonellainfection. Here, we show that loss of SIRT1 and SIRT3 function either by shRNA-mediated knockdown or inhibitor treatment led to increased mitochondrial dysfunction with alteration in mitochondrial bioenergetics alongside increased mitochondrial superoxide generation in theSalmonella-infected macrophages. Consistent with dysfunctional mitochondria, mitophagy was induced along with altered mitochondrial fusion-fission dynamics inS.Typhimurium-infected macrophages. Additionally, the mitochondrial bioenergetic alteration promotes acidification of the infected macrophage cytosolic pH. This host cytosolic pH imbalance skewed the intra-phagosomal and intra- bacterial pH in the absence of SIRT1 and SIRT3, resulting in decreased SPI-2 gene expression. Our results suggest a novel role of SIRT1 and SIRT3 in maintaining the intracellularSalmonellaniche by modulating the mitochondrial bioenergetics and dynamics in the infected macrophages.Graphical Abstract
SCCmectransformation requires living donor cells in mixed biofilms
Authors: Maree Mais , Ushijima Yuri , Higashide Masato , Morikawa Kazuya 
Published: September 2023

AbstractMethicillin-resistantStaphylococcus aureus(MRSA) is an important human pathogen that has emerged through the horizontal acquisition of the staphylococcus cassette chromosomemec(SCCmec). Previously, we showed that SCCmecfrom heat-killed donors can be transferred via natural transformation in biofilms at frequencies of 10-8-10-7. Here, we show an improved transformation assay of SCCmecwith frequencies up to 10-2using co-cultured biofilms with living donor cells. The Ccr-attB system played an important role in SCCmectransfer, and the deletion ofccrABrecombinase genes reduced the frequency ∼30-fold. SCCmeccould be transferred from either MRSA or methicillin-resistant coagulase-negative staphylococci to some of methicillin-sensitiveS. aureusrecipients. In addition, the transformation of other plasmid or chromosomal genes is enhanced by using living donor cells. This study emphasizes the role of natural transformation as an evolutionary ability ofS. aureusand in MRSA emergence.ImportanceMethicillin-resistantStaphylococcus aureus(MRSA) stands out as the leading contributor to fatalities attributed to antibiotic-resistant infections. To comprehend its emergence and dissemination, it is crucial to understand the mechanisms behind it. MRSA has arisen through the horizontal acquisition of the methicillin resistance genemecA, which is harboured within the staphylococcal cassette chromosome (SCCmec). Our study sheds light on a noteworthy discovery: when methicillin-sensitiveS. aureusrecipient cells are grown alongside viable methicillin-resistant donor cells in co-cultured biofilms, a highly efficient transfer of SCCmecoccurs, both within the same species and between different species. This remarkable transfer process is facilitated by natural transformation, underscoring its pivotal role in the evolution of staphylococci and the emergence of MRSA.
NRF2 pathway activation reverts high-glucose-induced transcriptional memory in endothelial cells
Authors: Wilson-Verdugo Martí , Bustos-García Brandon , Adame-Guerrero Olga , Hersch-González Jaqueline , Cano-Dominguez Nallely , Soto-Nava Maribel , Acosta Carlos A. , Tusie-Luna Teresa , Avila-Rios Santiago , Noriega Lilia G. , Valdes Victor J. 
Published: September 2023

ABSTRACTVarious diabetes complications, including nephropathy, retinopathy, and cardiovascular disease, arise from vascular dysfunction. In this context, it has been observed that past hyperglycaemic events can induce long-lasting transcriptional changes, a phenomenon termed “metabolic memory”. Yet, the underlying mechanisms driving these persistent effects are not fully characterized. In this study, we evaluated the genome-wide gene expression and chromatin accessibility alterations caused by transient high glucose exposure in human endothelial cells (ECs). We found that cells exposed to a transient high glucose episode had decreased glycolytic and oxygen consumption rates. Transcriptional profiling indicated that high glucose exposure induced substantial changes in the expression of genes belonging to pathways known to be impaired in diabetes, such as TGF-beta, TNF, FoxO, p53, and NRF2 pathways, many of which were retained after normalization of glucose concentrations. Furthermore, analysis of chromatin accessibility showed that transient hyperglycaemia can induce persistent modifications in the accessibility landscape, with the majority of differentially accessible regions located in non-promoter regions. Some of these regions were identified as putative enhancers with neighbouring genes persistently altered after transient high glucose exposure. Finally, we showed that activation of the NRF2 pathway through either NRF2 overexpression or supplementation with the plant-derived compound sulforaphane, was able to substantially revert the glucose-induced transcriptional memory in ECs. Our findings demonstrate that transient high glucose can induce persistent changes in both the transcriptomic and chromatin accessibility profiles of ECs, and that pharmacological NRF2 pathway activation is able to prevent and revert the high-glucose-induced transcriptional memory.Abstract Figure
ALS-associated FUS mutation reshapes the RNA and protein composition of Stress Granules
Authors: Mariani Davide , Setti Adriano , Castagnetti Francesco , Vitiello Erika , Mecarelli Lorenzo Stufera , Timoteo Gaia di , Giuliani Andrea , Perego Eleonora , Zappone Sabrina , Liessi Nara , Armirotti Andrea , Vicidomini Giuseppe , Bozzoni Irene 
Published: September 2023

ABSTRACTStress Granules (SG) formation is a cellular protection mechanism, constituting a storage for untranslated mRNAs and RNA-binding proteins (RBPs); however, these condensates can turn into pathological aggregates, related to the onset of neurodegenerative diseases like Amyotrophic Lateral Sclerosis (ALS). This transition towards cytotoxic inclusions is triggered by ALS-causative mutations in the RBP FUS, which lead to its cytoplasmic mis-localization and accumulation in SG. Here, we describe the SG transcriptome in a neural context and describe several features for RNA recruitment in SG. We demonstrate that SG dynamics and RNA content are strongly modified by the incorporation of mutant FUS, switching to a more unstructured, AU-rich SG transcriptome. Moreover, we show that mutant FUS, together with its protein interactors and their target RNAs, are responsible for the reshaping of the mutant SG transcriptome with alterations that can be linked to neurodegeneration. Therefore, our data give a comprehensive view of the molecular differences between physiological and pathological SG in ALS conditions, showing how FUS mutations impact the RNA and protein population of these condensates.
Puran poli [1] to Purna Bramha: an exemplary entrepreneurial journey
Authors: Maheshwari Kalpana 
Published: September 2023

Learning outcomes
This case study aims to understand the role of women entrepreneurship that reconcile the interests of not only business but also the economy as a whole; to map the most common avenues and levers as well as challenges and impediments in entrepreneurship; and to study how women have proved themselves and created value (for company as well as consumer) and driven leadership in business.

Case overview/synopsis
This case study predominantly is an entrepreneurial journey of the protagonist who left her cushy job to follow her dreams and started her own venture in hospitality industry. The case is designed on the basis of rounds of interviews conducted with the owner, hence it is based on primary data. Jayanti Kathale, a technology expert, working with a reputed organization, started Purna Bramha in 2013. The unique selling proposition of her food business was the home-like taste of the Marathi cuisine that she was serving. There were challenges like funding, logistics and pricing just like any other start-up. But Jayanti was determined to excel and her perseverance helped her get through all the challenges. Besides being a successful entrepreneur herself, she played a role in empowering other women also, by offering them franchisees of her restaurant. The food service industry is fast-paced, competitive and constantly evolving. This is taken well into consideration and proper training is organized for the staff. The protagonist's main quandary at this time is her pricing strategy.

Complexity academic level
The case is designed to be taught to the undergraduate and postgraduate management students and any other equivalent course. It can be taught in 2-h class and is expected to require some outside preparation by students. The students should be acquainted with the basic concepts of entrepreneurship and organizational culture in India. The instructor should focus on two aspects in the case. The broader aspect is Entrepreneurship in India and the narrower and more focused ones like Women Leadership.

Subject code
CCS 3: Entrepreneurship

Supplementary materials
Teaching notes are available for educators only.
Dual solutions for general three-dimensional MHD boundary layer stagnation-point flow of hybrid nanofluid and heat transfer
Authors: Zainal Nurul Amira , Khashi'ie Najiyah Safwa , Waini Iskandar , Mohd Kasim Abdul Rahman , Nazar Roslinda , Pop Ioan 
Published: September 2023

PurposeThe evaluation of high thermal efficiency has actively highlighted the unique behaviour of hybrid nanofluid. Thus, the purpose of this paper is to emphasize the hybrid nanofluid’s stagnation point in three-dimensional flow with magnetic field.Design/methodology/approachThe defined ordinary differential equations systems are addressed using the bvp4c solver.FindingsThe results indicate that using dual solutions is possible as long as the physical parameters remain within their specified ranges. Hybrid nanofluid flow has been recognised for its superior heat transfer capabilities in comparison to both viscous flow and nanofluid flow. Furthermore, it has been demonstrated in the current study that augmenting the volume concentration of nanoparticles leads to a corresponding enhancement in the rate of heat transfer. When the velocity gradients ratio is augmented, there is a corresponding reduction in the thermal performance. The separation value grows as the magnetic parameter rises, which signifies the expansion of the boundary layer.Originality/valueThe originality of the paper highlights the general mathematical hybrid model of the three-dimensional problem with the magnetohydrodynamics (MHD) effect in the stagnation point flow. The comprehensive examination of the suggested model has not yet been thoroughly addressed in prior research.