bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypothalamic representation of the imminence of predator threat detected by the vomeronasal organ in mice
Authors: Nguyen Quynh Anh Thi , Rocha Andrea , Chhor Ricky , Yamashita Yuna , Stadler Christian , Pontrello Crystal , Yang Hongdian , Haga-Yamanaka Sachiko
Published: September 2023

Animals have the innate ability to select optimal defensive behaviors with appropriate intensity in response to predator threats within specific contexts. Such innate behavioral decisions are thought to be computed in the medial hypothalamic nuclei, which contain neural populations that directly control defensive behavioral outputs. The vomeronasal organ (VNO) serves as a primary sensory channel for detecting predator cues by relaying signals to the medial hypothalamic nuclei, particularly the ventromedial hypothalamus (VMH), via the medial amygdala (MeA) and bed nucleus of the stria terminalis (BNST). Here, we demonstrate that cat saliva contains predator cues that signal the imminence of predator threat and modulate the intensity of freezing behavior through the VNO in mice. Cat saliva activates neurons expressing the V2R-A4 subfamily of sensory receptors, suggesting that specific receptor groups are responsible for inducing the freezing behavior. The number of VNO neurons activated in response to saliva correlates with both the freshness of saliva and the intensity of freezing behavior. In contrast, the downstream neurons in the accessory olfactory bulb (AOB) and the defensive behavioral circuit are activated to a similar extent by fresh and old saliva. Strikingly, however, the number of VMH neurons activated by fresh, but not old, saliva positively correlates with the intensity of freezing behavior. Detailed analysis of the spatial distribution of neurons responding to fresh and old saliva, as well as the overlap of those activated within the same individual mice, revealed that fresh and old saliva predominantly activate distinct neuronal populations within the VMH. Collectively, this study suggests that there is an accessory olfactory circuit in mice that is specifically tuned to time-sensitive components of cat saliva, which optimizes their defensive behavior to maximize their chance of survival according to the imminence of threat.
Gut feeling: Extent of virulence and antibiotic resistance genes inHelicobacter pyloriand campylobacteria
Authors: Rao R. Shyama Prasad , Ghate Sudeep D. , Pinto Larina , Suravajhala Prashanth , Patil Prakash , Shetty Praveenkumar , Ahsan Nagib
Published: September 2023

Background

Helicobacter pylori, a member of campylobacteria, is the leading cause of chronic gastritis and gastric cancer. Virulence and antibiotic resistance ofH. pyloriare of great concern to public health. However, the relationship between virulence and antibiotic resistance genes inH. pyloriin relation to other campylobacteria remains unclear.

Materials and Methods

By using the virulence and comprehensive antibiotic resistance databases, we explored all available 354 complete genomes ofH. pyloriand compared it with 90 species of campylobacteria for virulence and antibiotic resistance genes/proteins.

Results

On average,H. pylorihad 129 virulence genes, highest amongHelicobacter spp. and 71 antibiotic resistance genes, one of the lowest among campylobacteria. Just 2.6% of virulence genes were shared by all campylobacterial members, whereas 9.4% were unique toH. pylori.

The cytotoxin-associated genes (cags) seemed to be exclusive toH. pylori. Majority of the isolates from Asia and South America werecag2-negative and many antibiotic resistance genes showed isolate-specific patterns of occurrence. Just 15 (8.8%) antibiotic resistance genes, but 103 (66%) virulence genes including 25 cags were proteomically identified inH. pylori.

Arcobacterial members showed large variation in the number of antibiotic resistance genes and there was a positive relation with the genome size.

Conclusion

Large repository of antibiotic resistance genes in campylobacteria and a unique set of virulence genes might have important implications in shaping the course of virulence and antibiotic resistance inH. pylori.
iMAXFRET (Information Maximized FRET) for multipoint single-molecule structural analysis
Authors: Joshi Bhagyashree S. , de Lannoy Carlos , Howarth Mark , Kim Sung Hyun , Joo Chirlmin
Published: September 2023

Understanding the structure of biomolecules is vital for deciphering their characteristics and roles in biological systems. While current structural analysis techniques like nuclear magnetic resonance and X-ray crystallography excel in many aspects, they fall short in capturing comprehensive single-molecule information. To address this limitation and to better capture the heterogeneity and dynamic range of biomolecular reactions, there is a need for single-molecule structural analysis tools. To achieve this, we introduce iMAX FRET, a one-pot FRET-based single-molecule method integrated with geometrical 3D reconstruction, offering comprehensiveab initiostructural analysis. Through the stochastic exchange of fluorescent weak binders, iMAX FRET allows simultaneous assessment of multiple spatial coordinates on a biomolecule within a few minutes of time to generate distinct FRET fingerprints for 3D structural profiling. We demonstrate a mathematical approach forde novostructural prediction using iMAX data, opening avenues for native biomolecule analysis. Furthermore, this method facilitates the investigation of conformational changes in individual molecules, illuminating single-molecule structural dynamics. Our technique has the potential to emerge as a powerful approach to advance our understanding of biomolecular structures.
The expression of PKM1 and PKM2 in developing, benign, and cancerous prostatic tissues
Authors: Li Lin , Cheng Siyuan , Yeh Yunshin , Shi Yingli , Henderson Nikayla , Price David , Gu Xin , Yu Xiuping
Published: September 2023

Neuroendocrine prostate cancer (NEPCa) is the most aggressive type of prostate cancer. However, energy metabolism, one of the hallmarks of cancer, in NEPCa has not been well studied. Pyruvate kinase M (PKM), which catalyzes the final step of glycolysis, has two main splicing isoforms, PKM1 and PKM2. PKM2 is known to be upregulated in various cancers, including prostate adenocarcinoma (AdPCa). In this study, we used immunohistochemistry, immunofluorescence staining, and bioinformatic analysis to examine the expression of PKM1 and PKM2 in mouse and human prostatic tissues, including developing, benign and cancerous prostate. We found that PKM2 was the predominant isoform expressed throughout prostate development and PCa progression, with slightly reduced expression in some NEPCa samples.

PKM1 was mostly expressed in stromal cells but low-level PKM1 was also detected in prostate basal epithelial cells. Its expression was absent in the majority of PCa specimens but present in a subset of NEPCa. Additionally, we evaluated the mRNA levels of ten PKM isoforms that express exon 9 (PKM1-like) or exon 10 (PKM2-like). Some of these isoforms showed notable expression levels in PCa cell lines and human PCa specimens. These findings lay the groundwork for understanding PKMs’ role in PCa carcinogenesis and NEPCa progression. The distinct expression pattern of PKM isoforms in different PCa subtypes may offer insights into potential therapeutic strategies for treating PCa.
A Multimodality Video-Based AI Biomarker For Aortic Stenosis Development And Progression
Authors: Oikonomou Evangelos K. , Holste Gregory , Yuan Neal , Coppi Andreas , McNamara Robert L. , Haynes Norrisa , Vora Amit N. , Velazquez Eric J. , Li Fan , Menon Venu , Kapadia Samir R. , Gill Thomas M , Nadkarni Girish N. , Krumholz Harlan M. , Wang Zhangyang , Ouyang David , Khera Rohan
Published: September 2023

Importance

Aortic stenosis (AS) is a major public health challenge with a growing therapeutic landscape, but current biomarkers do not inform personalized screening and follow-up.

Objective

A video-based artificial intelligence (AI) biomarker (Digital AS Severity index [DASSi]) can detect severe AS using single-view long-axis echocardiography without Doppler. Here, we deploy DASSi to patients with no or mild/moderate AS at baseline to identify AS development and progression.

Design, Setting, and Participants

We defined two cohorts of patients without severe AS undergoing echocardiography in the Yale-New Haven Health System (YNHHS) (2015-2021, 4.1[IQR:2.4-5.4] follow-up years) and Cedars-Sinai Medical Center (CSMC) (2018-2019, 3.4[IQR:2.8-3.9] follow-up years). We further developed a novel computational pipeline for the cross-modality translation of DASSi into cardiac magnetic resonance (CMR) imaging in the UK Biobank (2.5[IQR:1.6-3.9] follow-up years). Analyses were performed between August 2023-February 2024.

Exposure

DASSi (range: 0-1) derived from AI applied to echocardiography and CMR videos.

Main Outcomes and Measures

Annualized change in peak aortic valve velocity (AV-Vmax) and late (>6 months) aortic valve replacement (AVR).

Results

A total of 12,599 participants were included in the echocardiographic study (YNHHS:n=8,798, median age of 71 [IQR (interquartile range):60-80] years, 4250 [48.3%] women, and CSMC:n=3,801, 67 [IQR:54-78] years, 1685 [44.3%] women). Higher baseline DASSi was associated with faster progression in AV-Vmax(per 0.1 DASSi increments: YNHHS: +0.033 m/s/year [95%CI:0.028-0.038], n=5,483, and CSMC: +0.082 m/s/year [0.053-0.111], n=1,292), with levels ≥ vs <0.2 linked to a 4-to-5-fold higher AVR risk (715 events in YNHHS; adj.HR 4.97 [95%CI: 2.71-5.82], 56 events in CSMC: 4.04 [0.92-17.7]), independent of age, sex, ethnicity/race, ejection fraction and AV-Vmax. This was reproduced across 45,474 participants (median age 65 [IQR:59-71] years, 23,559 [51.8%] women) undergoing CMR in the UK Biobank (adj.HR 11.4 [95%CI:2.56-50.60] for DASSi ≥vs<0.2). Saliency maps and phenome-wide association studies supported links with traditional cardiovascular risk factors and diastolic dysfunction.

Conclusions and Relevance

In this cohort study of patients without severe AS undergoing echocardiography or CMR imaging, a new AI-based video biomarker is independently associated with AS development and progression, enabling opportunistic risk stratification across cardiovascular imaging modalities as well as potential application on handheld devices.
Impact of Fludrocortisone on the Outcomes of Subarachnoid Hemorrhage Patients: A Retrospective Analysis
Authors: Mistry Akshitkumar M. , Naidugari Janki , Feldman Michael J. , Magarik Jordan A. , Ding Dale , Abecassis Isaac J. , Semler Matthew W. , Rice Todd W.
Published: September 2023

Background

Whether the use of fludrocortisone affects outcomes of patients with aneurysmal subarachnoid hemorrhage (aSAH) and its usage rate in the United States remain unknown.

Methods

We conducted a retrospective analysis of 78 consecutive patients with a ruptured aSAH at a single academic center in the United States. The primary outcome was the score on the modified Rankin scale (mRS, range, 0 [no symptoms] to 6 [death]) at 90 days. We adjusted the primary outcome for age, hypertension, aSAH grade, and time from aSAH onset to aneurysm treatment. Secondary outcomes were brain and cardiopulmonary dysfunction events.

Results

Among 78 patients at a single center, the median age was 58 years [IQR, 49 to 64.5]; 64% were female, and 41 (53%) received fludrocortisone. The adjusted common odds ratio, aOR, of a proportional odds regression model of fludrocortisone use with mRS was 0.33 (95% CI, 0.14-0.80; P=0.02), with values <1.0 favoring fludrocortisone. Organ-specific dysfunction events were not statistically different: delayed cerebral ischemia (22% vs. 39%, P=0.16); cardiac dysfunction (0% vs. 11%; P=0.10); and pulmonary edema (15% vs. 8%; P=0.59).

Conclusions

The risk of disability or death at 90 days was lower with the use of fludrocortisone in aSAH patients.
Video feedback for young babies and maternal perinatal mental illness: Adaptation, feasibility and qualitative interviews
Authors: Barnicot Kirsten , Stevens Eloise , Robinson Fiona , Labovitch Sarah , Ballman Rajinder , Miele Maddalena , Lawn Tara , Sundaresh Sushma , Iles Jane
Published: September 2023

Aims/ Background

We aimed to adapt, test and explore experiences of the video feedback intervention for positive parenting (VIPP) for 2 to 6 month old babies and for mothers experiencing moderate to severe perinatal mental health difficulties.

Design/ Methods

The VIPP intervention was adapted to include developmentally appropriate activities and developmental psychoeducation for 2 to 6 month olds, alongside psychoeducation on emotion regulation. Subsequently, the adapted intervention was trialled in 14 mothers experiencing moderate to severe perinatal mental health difficulties (registrationISRCTN64237883). Observational and self-reported pre-post outcome data was collected, and post-intervention qualitative interviews were conducted with participating mothers and clinicians.

Results

Consent (67%), intervention completion (79%) and follow-up rates (93%) were high. Effect sizes on pre-post outcome measures indicated large improvements in parenting confidence and perceptions of the parent-infant relationship, and a medium-size improvement in maternal sensitivity. Qualitative interviews suggested that clinicians and mothers were able to use the video feedback to identify young babies’ subtle behavioural cues and moments of mother-infant connection, enhancing maternal sensitivity. Mothers’ initial anxieties about being filmed were overcome by the experience of receiving positive and strengths-focussed feedback, boosting their confidence in themselves as parents. The interviews also generated recommendations for minor modifications to optimise intervention feasibility and acceptability, such as streamlining the information provided on maternal emotion regulation, and allowing increased use of clinical judgement to tailor intervention delivery.

Conclusion

VIPP can potentially be beneficial for enhancing maternal sensitivity with very young babies in mothers experiencing perinatal mental health difficulties.
Non-invasive vagus nerve stimulation conditions increased invigoration and wanting in depression
Authors: Ferstl Magdalena , Kühnel Anne , Klaus Johannes , Lin Wy Ming , Kroemer Nils B.
Published: September 2023

Background

Major depressive disorder (MDD) is often marked by impaired motivation and reward processing, known as anhedonia. Many patients do not respond to first-line treatments, and improvements in motivation can be slow, creating an urgent need for rapid interventions. Recently, we demonstrated that transcutaneous auricular vagus nerve stimulation (taVNS) acutely boosts effort invigoration in healthy participants, but its effects on depression remain unclear.

Objective

To assess the impact of taVNS on effort invigoration and maintenance in a sample that includes patients with MDD, evaluating the generalizability of our findings.

Methods

We used a single-blind, randomized crossover design in 30 patients with MDD and 29 matched (age, sex, and BMI) healthy control participants (HCP).

Results

Consistent with prior findings, taVNS increased effort invigoration for rewards in both groups during Session 1 (p=.040), particularly for less wanted rewards in HCP (pboot<.001). However, invigoration remained elevated in all participants, and no acute changes were observed in Session 2 (Δinvigoration=3.52,p=.093). Crucially, throughout Session 1, we found taVNS-induced increases in effort invigoration (pboot=.008) and wanting (pboot=.010) in patients with MDD, with gains in wanting maintained across sessions (Δwanting=0.06,p=.97).

Conclusions

Our study replicates the invigorating effects of taVNS in Session 1 and reveals its generalizability to depression. Furthermore, we expand upon previous research by showing taVNS-induced conditioning effects on invigoration and wanting within Session 1 in patients that were largely sustained. While enduring motivational improvements present challenges for crossover designs, they are highly desirable in interventions and warrant further follow-up research.

Graphical abstract
COVID-related Excess Missed HIV Diagnoses in the United States in 2021: Follow-up to 2020
Authors: Viguerie Alex , Song Ruiguang , Johnson Anna Satcher , Lyles Cynthia M. , Hernandez Angela , Farnham Paul G.
Published: September 2023

Objective

COVID-19 and related disruptions led to a significant drop in HIV diagnoses in the US in 2020. Recent analyses found 18% fewer diagnoses than expected among persons with HIV (PWH) acquiring infection in 2019 or earlier, suggesting that the drop in diagnoses cannot be attributed solely to decreased transmission. This analysis evaluates the progress made towards closing the 2020 diagnosis deficit in 2021.

Methods

We apply modified versions of previously developed methods analyzing 2021 diagnosis data from the National HIV Surveillance System to determine whether the 2021 diagnosis levels of PWH infected pre-2020 are above or below the projected pre-COVID trends. We apply these analyses on stratifications based on assigned sex at birth, transmission group, geographic region, and race/ethnicity.

Results

In 2021, HIV diagnoses returned to pre-COVID levels among all PWH acquiring infection 2011-19. Among Hispanic/Latino PWH and males, diagnoses returned to pre-COVID levels. White PWH, men who have sex with men, and PWH living in the south and northeast showed higher-than-expected levels of diagnosis in 2021. For the remaining populations, there were fewer HIV diagnoses in 2021 than expected.

Conclusions

While overall diagnoses returned to pre-COVID levels, the large diagnosis gap observed in 2020 remained unclosed at the end of 2021. Lower than expected diagnosis levels among certain populations indicates that COVID-19 related disruptions to HIV diagnosis trends were present in 2021. Although some groups showed higher-than-projected levels of diagnoses, such increases were smaller than the corresponding 2020 decreases. Expanded testing programs designed to close these gaps are essential.
Effectiveness of the adjuvanted Sanofi/GSK (VidPrevtyn Beta) and Pfizer-BioNTech (Comirnaty Original/Omicron BA.4-5) bivalent vaccines against hospitalisation amongst adults aged 75 years and older in England, estimated using a test-negative case control study design
Authors: Kirsebom Freja Cordelia Møller , Andrews Nick , Stowe Julia , Dabrera Gavin , Ramsay Mary , Bernal Jamie Lopez
Published: September 2023

Background

In England, the Joint Committee for Vaccination and Immunisation recommended a spring 2023 booster programme for all adults aged 75 years and older and the immunosuppressed. The vaccines advised were the Sanofi/GSK AS03-adjuvanted monovalent beta variant (VidPrevtyn Beta) booster vaccine and the Pfizer-BioNTech mRNA (Comirnaty Original/Omicron BA.4-5) bivalent vaccine. This is the first time an adjuvanted COVID-19 vaccine has been administered as part of a UK COVID-19 vaccination programme. In clinical trials, the antibody levels generated by the Sanofi/GSK vaccine were comparable to levels generated by COVID-19 mRNA vaccines but to date there are no real-world data on the effectiveness or duration of protection of this vaccine.

Methods

We used a test-negative case-control study design to estimate the incremental vaccine effectiveness of the Sanofi/GSK and Pfizer bivalent BA.4-5 boosters against hospitalisation amongst those aged 75 years and older in England. The study period for tests contributing to all analyses was from 3rd April 2022 to 27th August 2023. Vaccine effectiveness was estimated relative to those who had received at least two doses prior to their spring booster, with their last dose being an autumn 2022 booster given at least 3 months prior.

Findings

Overall, there were 14,174 eligible tests from hospitalised individuals aged 75 years and older, with 3,005 being cases and 11,169 being controls. Effectiveness against hospitalisation was highest in the period 9 to 13 days post vaccination for both manufacturers at about 50%; 43.6% (95% C.I.; 20.1 to 60.2%) and 56.4% (95% C.I; 25.8 to 74.4%) for Sanofi/GSK and Pfizer BA.4-5, respectively. There was some evidence of waning with a reduction to about 30% for both manufacturers 5-9 weeks post vaccination.

Interpretation

Together, these results provide reassuring evidence that both the adjuvanted Sanofi/GSK and Pfizer BA.4-5 booster vaccines provided a good boost to protection against hospitalisation amongst adults aged 75 years and older. The finding that the adjuvanted vaccine targeting the now distant Beta strain had similar effectiveness to the mRNA vaccine targeting more closely matched Omicron sub-lineages BA.4-5 during a period of Omicron circulation may reflect improved protection due to the adjuvant in the Sanofi/GSK product.

Funding

No external funding.
A Type VI Secretion System inBurkholderiaSpeciescenocepaciaandorbicolaTriggers Distinct Macrophage Death Pathways Independent of the Pyrin Inflammasome
Authors: Loeven Nicole A. , Reuven Arianna D. , McGee Abigail P. , Dabi Clarrisa , Mwaura Bethany W. , Bliska James B.
Published: September 2023

TheBurkholderia cepaciacomplex contains opportunistic pathogens that cause chronic infections and inflammation in lungs of people with cystic fibrosis. Two closely related species within this complex areBurkholderia cenocepaciaand the recently classifiedBurkholderia orbicola. B. cenocepaciaandB. orbicolaencode a type VI secretion system and the effector TecA, which is detected by the pyrin/caspase-1 inflammasome, and triggers macrophage inflammatory death. In our earlier study the pyrin inflammasome was dispensable for lung inflammation in mice infected withB. orbicolaAU1054, indicating this species activates an alternative pathway of macrophage inflammatory death. Notably,B. cenocepaciaJ2315 and K56-2 can damage macrophage phagosomes and K56-2 triggers activation of the caspase-11 inflammasome, which detects cytosolic LPS. Here we investigated inflammatory cell death in pyrin-deficient (Mefv−/−) mouse macrophages infected withB. cenocepaciaJ2315 or K56-2 orB. orbicolaAU1054 or PC184. Macrophage inflammatory death was measured by cleavage of gasdermin D protein, release of cytokines IL-1α and IL-1β and plasma membrane rupture. Findings suggest that J2315 and K56-2 are detected by the caspase-11 inflammasome inMefv−/−macrophages, resulting in IL-1β release. In contrast, inflammasome activation is not detected inMefv−/−macrophages infected with AU1054 or PC184. Instead, AU1054 triggers an alternative macrophage inflammatory death pathway that requires TecA and results in plasma membrane rupture and IL-1α release. Amino acid variation between TecA isoforms inB. cenocepaciaandB. orbicolamay explain how the latter species triggers a non-inflammasome macrophage death pathway.
Human disturbance increases spatiotemporal associations among mountain forest terrestrial mammal species
Authors: Li Xueyou , Bleisch William V. , Hu Wenqiang , Li Quan , Wang Hongjiao , Chen Zhongzheng , Bai Ru , Jiang Xuelong
Published: September 2023

Spatial and temporal associations between sympatric species underpin biotic interactions, structure ecological assemblages, and sustain ecosystem functioning and stability. However, the resilience of interspecific spatiotemporal associations to human activity remains poorly understood, particularly in mountain forests where anthropogenic impacts are often pervasive. Here we applied context-dependent Joint Species Distribution Models to a systematic camera-trap survey dataset from a global biodiversity hotspot in eastern Himalaya to understand how prominent human activities in mountain forests influence species associations within terrestrial mammal communities. We obtained 10,388 independent detections of 17 focal species (12 carnivores and five ungulates) from 322 stations over 43,163 camera days of effort. We identified a higher incidence of positive associations in habitats with higher levels of human modification (87 %) and human presence (83 %) compared to those located in habitats with lower human modification (64 %) and human presence (65 %) levels. We also detected a significant reduction of pairwise encounter time at increasing levels of human disturbance, corresponding to more frequent encounters between pairs of species. Our findings indicate that human activities can push mammals together into more frequent encounters and associations, which likely influences the coexistence and persistence of wildlife, with potential far-ranging ecological consequences.
Microinterfaces in bicontinuous hydrogels guide rapid 3D cell migration
Authors: Xu Karen L. , Caprio Nikolas Di , Fallahi Hooman , Dehghany Mohammad , Davidson Matthew D. , Cheung Brian C. H. , Laforest Lorielle , Wu Mingming , Shenoy Vivek , Han Lin , Mauck Robert L. , Burdick Jason A.
Published: September 2023

Cell migration is critical for tissue development and regeneration but requires extracellular environments that are conducive to motion. Cells may actively generate migratory routes in vivo by degrading or remodeling their environments or may instead utilize existing ECM microstructures or microtracks as innate pathways for migration. While hydrogels in general are valuable tools for probing the extracellular regulators of 3D migration, few have recapitulated these natural migration paths. Here, we developed a biopolymer-based (i.e., gelatin and hyaluronic acid) bicontinuous hydrogel system formed through controlled solution immiscibility whose continuous subdomains and high micro-interfacial surface area enabled rapid 3D migration, particularly when compared to homogeneous hydrogels. Migratory behavior was mesenchymal in nature and regulated by biochemical and biophysical signals from the hydrogel, which was shown across various cell types and physiologically relevant contexts (e.g., cell spheroids, ex vivo tissues, in vivo tissues). Our findings introduce a new design that leverages important local interfaces to guide rapid cell migration.
Central pore-opening structure and gating of the mechanosensitive PIEZO1 channel
Authors: Liu Sijia , Yang Xuzhong , Chen Xudong , Zhang Xiaochun , Jiang Jinghui , Wang Li , Yuan Jingyi , Liu Wenhao , Zhou Heng , Wu Kun , Tian Boxue , Li Xueming , Xiao Bailong
Published: September 2023

PIEZO1 is a mechanically activated cation channel that undergoes force-induced activation and inactivation to control diverse physiological processes1–4. However, the distinct functional states and gating transitions remain structurally undefined. In response to changes in membrane forces, PIEZO1 transitions from a curved to a flattened shape, which might lead to opening and subsequent inactivation of the ion-conducting pore5,6. Here we employed a PIEZO1 mutant to capture various conformational states including an intermediate state with an opened central pore, allowing us to reveal the gating dynamics of this multiple-gate system. Upon transition from the curved to the partially flattened intermediate state, the trimeric cap undergoes a downward and rotational motion to open the lateral cap-gate, while the loop that connects the cap to the pore-lining inner helix acts as a spring-linker, switching from an extended to a compressed state. Along with the partial flattening of the peripheral blades, these conformational changes collectively dilate the cap-gate, spring-gate and the hydrophobic transmembrane-gate, leading to ion permeation through the transmembrane pore. Upon inactivation, while the blades remain flattened, the cap and spring-linker return to an up and extended state. Molecular dynamics simulations verify the ion-permeating pathway and the distinct ion-conducting states of the assigned close, intermediate, open, and inactivated structures. Mutagenesis and electrophysiological characterizations reveal that domains and residues involved in conformational dynamics of the cap and spring-linker are critical for mechanical activation of PIEZO1. Together, these studies have structurally defined the distinct functional states and the curvature-based activation and inactivation mechanisms of PIEZO1.
Lysine-36 ofDrosophilahistone H3.3 supports adult longevity
Authors: Brown John C. , McMichael Benjamin D. , Vandadi Vasudha , Mukherjee Aadit , Salzler Harmony R. , Matera A. Gregory
Published: September 2023

Aging is a multifactorial process that disturbs homeostasis, increases disease susceptibility, and ultimately results in death. Although the definitive set of molecular mechanisms responsible for aging remain to be discovered, epigenetic change over time is proving to be a promising piece of the puzzle. Several posttranslational histone modifications (PTMs) have been linked to the maintenance of longevity. Here, we focus on lysine-36 of the replication-independent histone protein, H3.3 (H3.3K36). To interrogate the role of this residue inDrosophiladevelopmental gene regulation, we generated a lysine to arginine mutant that blocks the activity of its cognate modifying enzymes. We found that anH3.3BK36Rmutation causes a significant reduction in adult lifespan, accompanied by dysregulation of the genomic and transcriptomic architecture. Transgenic co-expression of wild-typeH3.3Bcompletely rescues the longevity defect. Because H3.3 is known to accumulate in non-dividing tissues, we carried out transcriptome profiling of young vs aged adult fly heads. The data show that loss of H3.3K36 results in age-dependent misexpression of NF-κB and other innate immune target genes, as well as defects in silencing of heterochromatin. We propose H3.3K36 maintains the postmitotic epigenomic landscape, supporting longevity by regulating both pericentric and telomeric retrotransposons and by suppressing aberrant immune signaling.
SETD2 maintains nuclear lamina stability to safeguard the genome
Authors: Khan Abid , Metts James M. , Collins Lucas C. , Mills C. Allie , Li Kelin , Brademeyer Amanda L. , Bowman Brittany M. , Major M. Ben , Aubé Jeffrey , Herring Laura E. , Davis Ian J. , Strahl Brian D.
Published: September 2023

Histone methyltransferases play essential roles in the organization and function of chromatin. They are also frequently mutated in human diseases including cancer1. One such often mutated methyltransferase, SETD2, associates co-transcriptionally with RNA polymerase II and catalyzes histone H3 lysine 36 trimethylation (H3K36me3) – a modification that contributes to gene transcription, splicing, and DNA repair2. While studies on SETD2 have largely focused on the consequences of its catalytic activity, the non-catalytic functions of SETD2 are largely unknown. Here we report a catalysis-independent function of SETD2 in maintaining nuclear lamina stability and genome integrity. We found that SETD2, via its intrinsically disordered N-terminus, associates with nuclear lamina proteins including lamin A/C, lamin B1, and emerin. Depletion of SETD2, or deletion of its N-terminus, resulted in widespread nuclear morphology abnormalities and genome stability defects that were reminiscent of a defective nuclear lamina. Mechanistically, the N-terminus of SETD2 facilitates the association of the mitotic kinase CDK1 with lamins, thereby promoting lamin phosphorylation and depolymerization required for nuclear envelope disassembly during mitosis. Taken together, our findings reveal an unanticipated link between the N-terminus of SETD2 and nuclear lamina organization that may underlie how SETD2 acts as a tumor suppressor.
Identifying individual factors associated with pleasure of eating healthy foods and plant/animal protein food consumption: findings from an exploratory study
Authors: Lambert-De Francesch Jessica , Labrecque JoAnne , Lessard Stéphanie
Published: September 2023

Purpose

This study identifies new factors influencing the adoption of two recently promoted messages in Canada's updated food guide (FG): enhancing pleasure of eating healthy foods (PEHFs) and shifting food choices towards plant protein foods. Currently, limited and contradictory evidence is available regarding associations between environmental values, nutrition literacy, PEHFs, and plant/animal protein food consumption.

Design/methodology/approach

An online survey measuring environmental values; nutrition literacy, distinctively based on previous (2007) and most recent (2019) FG messages; PEHFs; and annual changes in the consumption of protein foods was sent to Quebec residents (N = 128).

Findings

Greater nutrition literacy of both 2007 and 2019 FGs and greater environmental values were associated with greater PEHFs (ß = 0.248, p < 0.01; ß = 0.209, p < 0.05; ß = 0.423, p < 0.001, respectively). Greater PEHFs was associated with greater consumption of plant protein foods (ß = 0.405, p < 0.001). Greater nutrition literacy of the 2007 FG was associated with greater consumption of animal protein foods (ß = 0.409, p < 0.001), whereas greater nutrition literacy of the 2019 FG was linked to lower consumption of animal protein foods (ß = −0.225, p < 0.05).

Practical implications

Enhancing PEHFs may require increasing general FG nutrition literacy and strengthening environmental values. To encourage plant protein food consumption and decrease animal protein food consumption, the authors recommend promoting PEHFs and increasing nutrition literacy based on newest FG recommendations.

Originality/value

This new evidence may help develop strategies promoting PEHFs and plant protein food consumption, thus increasing uptake of new FG recommendations.
A novel strategy segmentation methodology integrating Kraljic portfolio matrix and supplier relationship model: a case study from machinery industry
Authors: Yalcin Ahmet Selcuk , Kilic Huseyin Selcuk , Cevikcan Emre
Published: September 2023

Purpose

The purpose of this article is to develop a new model called strategy segmentation methodology (SSM) by combining the Kraljic portfolio matrix (KPM) and the supplier relationship model (SRM) so that the buyer company can effectively conduct its relations with its suppliers.

Design/methodology/approach

The importance weights of the criteria defining the dimensions of each model are calculated with the single-valued neutrosophic analytical hierarchy process (SVN-AHP) method. Subsequently, the derived importance weights are employed in the single-valued neutrosophic technique for order preference by similarity to ideal solution (SVN-TOPSIS) method to obtain the scores of the suppliers and their supplied items. In order to illustrate the feasibility of the proposed methodology, a case study in the machinery industry is performed with the related comparative analysis.

Findings

The implementation of SSM enables to formulate various strategies to manage suppliers taking into account the items they procure, their capabilities and performance and the supplier–buyer relationship strength. Based on the proposed strategies, it is concluded that the firm in the case study should terminate its relationship with six of its suppliers.

Originality/value

Although KPM has become the basis of purchasing strategies for various businesses, it neglects the characteristics of suppliers and the buyer–supplier relationship. In this study, KPM is integrated with the SRM approach presented by Olsen and Ellram (1997) to overcome these disadvantages of KPM. The novel integration of the two approaches enables the realization of a robust and reliable supplier classification model.
Local/volumetric entropy production analysis of natural convective flow using lattice Boltzmann method for heat exchanger application
Authors: Hasani Malekshah Emad , Kolsi Lioua
Published: September 2023

Purpose

The purpose of this study is the hydrothermal analysis of the natural convection phenomenon within the heat exchanger containing nanofluids using the lattice Boltzmann method (LBM).

Design/methodology/approach

The thermal conductivity as well as dynamic viscosity of the CuO–water nanofluid is estimated using the Koo-Kleinstreuer-Li model. The LBM has been used with unique modifications to make it flexible with the curved boundaries. The local as well as total entropy generation assessment, local Nusselt variation, as well as heatline visualization are used.

Findings

The solid volume percentage of the CuO–water nanofluid, a range of Rayleigh numbers (Ra) and thermal settings of internal operational fins and bodies are all factors that have been thoroughly researched to determine their effects on entropy production, heat transfer efficiency and nanofluid flow.

Originality/value

The originality of this work is using a novel numerical method (i.e. curved boundary LBM) as well as the local/volumetric second law analysis for the application of heat exchanger hydrothermal analysis.
Equity capital financing of Swedish SMEs, innovation, and decentralized management
Authors: Ström Viktor , Sanandaji Nima , Esmaeilzadeh Saeid , Esmaeilzadeh Mouna
Published: September 2023

Purpose

The purpose of this paper is to investigate the potential link between Sweden’s high reliance on equity capital financing among small and medium-sized enterprises (SMEs) and its recognition as the most innovative economy in Europe according to the European Innovation Scoreboard (EIS). This paper examines the idea that the high levels of trust within Swedish society can explain why private equity financing is more prevalent among Swedish SMEs.

Design/methodology/approach

To test these ideas, the authors use data from the Survey on Access to Finance for Enterprises to measure the private equity reliance of firms. The authors also use the EIS to measure the innovation capacity of nations and various aspects of SMEs’ innovation activities. Finally, societal levels of trust are measured through the World Value Survey.

Findings

First, the authors find that European countries with a higher proportion of SMEs relying on equity financing tend to be ranked as more innovative by the EIS. Second, the authors find that the correlation between a nation’s share of SMEs relying on equity financing and their level of innovation activities is marginally stronger for product innovations than for business process innovations. Third, the authors find that countries with higher levels of trust tend to have higher equity capital reliance among SMEs.

Originality/value

This study builds upon previous research on equity capital and SMEs’ innovation activity while introducing new insights into the relationship between societal trust and equity financing.
Dimensions and outcomes of electronic service quality in the GCC countries
Authors: Thanasi-Boçe Marsela , Kulakli Atik
Published: September 2023

Purpose

The rapid growth of e-commerce and the increasing importance of online services have prompted the need for managers to understand what consumers value most in online transactions and how to measure electronic service quality (E-SQ). This study aims to conduct a comprehensive review of relevant research publications in the Gulf Cooperation Council countries and propose an agenda for future research to enhance this knowledge.

Design/methodology/approach

The study uses a blended approach between the PRISMA-ScR methodology and Tranfield et al.’s (2003) approach to ensure a rigorous and thorough review of the literature.

Findings

By identifying the antecedents and outcomes of E-SQ, this study develops a classification framework that highlights the main gaps in the current literature and provides guidance for future research in the region.

Practical implications

The findings presented in this paper contribute to the knowledge base for management professionals seeking to enhance E-SQ in practice.

Originality/value

To the best of the authors’ knowledge, this is the first paper to summarize the state of E-SQ in the Gulf region.
Developing capabilities underlying to Industry 4.0 design principles within the manufacturing context
Authors: Ghobakhloo Morteza , Vilkas Mantas , Stefanini Alessandro , Grybauskas Andrius , Marcinkevicius Gediminas , Petraite Monika , Sarvari Peiman Alipour
Published: September 2023

Purpose

Using a dynamic capabilities approach, the present study aims to identify and assess the effects of organizational determinants on capabilities underlying Industry 4.0 design principles, such as integration, virtualization, real-time, automation and servitization.

Design/methodology/approach

PLS-SEM enables a two-stage hierarchical latent variable reflective-formative model which was used for assessing the effect of organizational determinants on Industry 4.0 design principles. Five hundred six manufacturing companies constitute the effective sample, representing a population of manufacturing companies in an industrialized country.

Findings

The findings reveal that Industry 4.0 design principles extensively depend on digitalization resource availability. At the same time, companies that possess digitalization and change management capabilities tend to devote more resources to digitalization. Finally, the paper reveals that networking and partnership capability is the critical enabler for change management and digitalization capabilities.

Practical implications

The paper provides empirical evidence that the successful development of Industry 4.0 design principles and their underlying integration, virtualization, real-time, automation and servitization capabilities are resource dependent, requiring significant upfront investment and continuous resource allocation. Further, the study implies that companies with networking and partnership, change management and digitalization capabilities tend to allocate more resources for Industry 4.0 transformation.

Originality/value

Exclusively focusing on empirical research that reported applied insights into determinants of Industry 4.0 design principles, the study offers unique implications for promoting Industry 4.0 digital transformation among manufacturing companies.
Information literacy and the material objects of the Kente-weaving landscape
Authors: Agyemang Franklin Gyamfi , Wessels Nicoline , du Preez Madely
Published: September 2023

Purpose

This paper aims to examine the ways becoming information literate relates to the material objects in the Kente-weaving landscape.

Design/methodology/approach

An ethnographic research design was adopted wherein data was collected using participant observation and a semi-structured interview with 24 participants through their roles as either master weaver, junior weaver or novice weaver. Thematic analysis through a practice-based approach to information literacy frames the analysis of this study.

Findings

Information literacy relates to the material objects in terms of developing the know-how knowledge regarding the Kente-weaving tools used as well as what constitutes the quality of Kente fabrics.

Practical implications

Information literacy goes beyond having theoretical knowledge of the material objects of an information landscape. It is practical, not merely knowing the names of the material objects and what they are literary used for.

Originality/value

To the best of the authors’ knowledge, this is the first study that contributes to the understanding of how information literacy relates to material objects in the craft workplace.
The optimal decision of e-retailer based on return-freight insurance – considering the loss aversion of customers
Authors: Zhan Wentao , Pan Wenting , Zhao Yi , Zhang Shengyu , Wang Yimeng , Jiang Minghui
Published: September 2023

Purpose

The return behavior of customers has a great impact on the e-retail industry and has resulted in the emergence of return-freight insurance (RI). Additionally, customer loss aversion arising from returns affects e-retailers' decisions and manufacturers' profits. Therefore, the main purpose of the authors' study is to determine how e-retailers and manufacturers choose their RI strategy and pricing according to customers' loss aversion.

Design/methodology/approach

The authors propose three scenarios: no RI, customer purchase RI and free e-retail RI (FRI). Meanwhile, the authors also model a Stackelberg game between e-retailers and manufacturers for analysis. Then, according to customer return behavior and loss aversion, the authors study the optimal pricing decision and RI premium allocation scheme for e-retailers and manufacturers under different scenarios.

Findings

It was found that the loss sensitivity reduces customers' willingness to buy RI, which is not conducive to the development of e-retailers and manufacturers. Additionally, with higher loss sensitivity, e-retailers and manufacturers offer FRI to gain higher profits, which supports the implementation of the FRI strategy.

Originality/value

The authors introduce customers' loss aversion into RI to analyze the optimal pricing decisions and profits of e-retailers and manufacturers, enriching the application of loss aversion theory. In addition, this study analyzes the two-way cost-sharing mechanism between manufacturers and e-retailers to provide FRI, which provides a theoretical basis for RI premium sharing.
Worcester Red Sox: Let's grow our brand
Authors: OHara Elizabeth , Leonard Bridget
Published: September 2023

Research methodology

This case was developed through interviews with Brooke Cooper, Dr. Charles Steinberg and others at the WooSox, as well as a thorough analysis of the Worcester Red Sox’s social media and company websites.

Purpose

The purpose of this marketing case study is to This case focuses on understanding the process involved in conceptualizing and developing a marketing plan and strategy, and the ability to define and articulate the importance of BRAND in a marketing context.

Case overview/synopsis

The Pawtucket Red Sox relocated to Worcester, Massachusetts in Spring of 2019. The citizens of Worcester embraced their new team – the WooSox – as did many of the surrounding towns in Worcester County. The marketing arm of the WooSox worked tirelessly to develop a plan that included immersion in the cultures of the cities and towns within Worcester County; becoming a presence in their schools, businesses and community-based organizations; learning the priorities of the individual communities and supporting those needs; building a consistent, interactive and strong presence on social media; highlighting various interactions with their fan base; providing an outstanding experience at Polar Park; creating a loyal fan base ultimately driving ticket and merchandise sales and cultivating new fans to experience Polar Park; and understanding that word of mouth is the best form of marketing. The WooSox leadership team understood the need to expand its reach into new markets. In this case, the marketing team has been charged with exploring the Western Massachusetts region as a potential growth opportunity. The WooSox have a strong brand in the greater Worcester County area – but can they travel 60–90 min west and establish the same presence?

Complexity academic level

This case was written for undergraduate-level Marketing Principles or Sport Marketing courses.