bluuebunny/crossref_metadata_2025 huggingface dataset:
Natural is divine: Religious leaders’ nuanced views on birth spacing and contraceptives in Sierra Leone - qualitative insights
Authors: Yillah Regina , Bull Florence , Sawneh Alhaji , Reindorf Beryl , Turay Hamid , Wurie Haja , Hodges Mary
Published: October 2023

This research explored the viewpoints of 116 religious leaders in Sierra Leone including 32 Muslims and 84 Christians from nine different denominations. The study’s primary objectives were to understand their perspectives on family planning, modern contraceptives, sexual reproductive health education, and the religious doctrines influencing these beliefs. The study also aimed to gauge their knowledge of family planning and modern contraceptive methods.

In September 2021, data was collected from religious figures purposefully selected from 11 districts and the Western Area Urban through 16 focus group discussions. The discussions, initially conducted in local languages, were translated and transcribed into English. The data was then subjected to a thematic analysis using NVIVO 12 software.

The analysis revealed diverse opinions, both across different religions and within specific denominations. A common thread was the general support from both Christian and Muslim leaders for natural birth spacing methods, with some reservations about artificial techniques. There were clear distinctions in beliefs among denominations: Catholics largely considered artificial contraceptives to be against the divine will, while Pentecostals and some Muslims found them permissible under certain conditions.

The findings underscore the potential of religious leaders in Sierra Leone to act as influential advocates for family planning, given their support for natural birth spacing. To maximize the impact of advocacy efforts, the study suggests a focus on engaging Pentecostals and Muslim leaders rather than Catholics. Additionally, religious leaders with professional backgrounds in health or education appear more receptive to modern contraceptive methods and could be particularly valuable allies in these endeavours.
Population-specific responses to developmental temperature in the arboviral vectorAedes albopictus: implications for climate change
Authors: Carlassara Martina , Khorramnejad Ayda , Oker Helen , Bahrami Romina , Lozada-Chávez Alejandro Nabor , Mancini Maria Vittoria , Body Mélanie J.A. , Lahondère Chloé , Bonizzoni Mariangela
Published: October 2023

The increase of environmental temperature due to current global warming is not only favoring the expansion of the distribution range of many insect species, but it is also changing their phenology. Insect phenology is tightly linked to developmental timing, which is regulated by environmental temperatures. However, the degree to which effects of developmental temperatures extend across developmental stages and their inter-stage relationships have not been thoroughly quantified in mosquitoes. Here, we used the mosquitoAedes albopictus, which is an aggressive invasive species and an arboviral vector to study how developmental temperature influences fitness across developmental stages, thermal traits, energy reserves, transcriptome, andWolbachiaprevalence in populations from either temperate or tropical regions. We show that hatchability, larval and pupal viability, and developmental speed are strongly influenced by temperature and these effects extend to wing length, body mass, longevity, content of water, protein and lipids in adults, in a population-specific manner. On the contrary, neither adult thermal preference nor heat resistance significantly change with temperature. Development at 18°C revealed to be a limiting factor for the proliferation ofWolbachiain adults and transcriptome analysis showed enrichment for functions linked to stress responses (i.e. cuticle proteins and chitin, cytochrome p450, and heat shock proteins) in mosquitoes reared at both 18°C and 32°C. Our data showed an overall reduced vector fitness performance when mosquitoes were reared at 32°C, and the absence of isomorphy in the relationship between developmental stages and temperature in the temperate population. Altogether these results have important implications for reliable model projections of the invasion potentials ofAe. albopictusand its epidemiological impact.
Revisiting genomes of non-model species with long reads yields new insights into their biology and evolution
Authors: Guiglielmoni Nadège , Villegas Laura I. , Kirangwa Joseph , Schiffer Philipp H.
Published: October 2023

High-quality genomes obtained using long-read data allow not only for a better understanding of heterozygosity levels, repeat content, and more accurate gene annotation, and prediction when compared to those obtained with short-read technologies, but also allow to understand haplotype divergence. Advances in long-read sequencing technologies in the last years have made it possible to produce such high-quality assemblies for non-model organisms. This allows us to revisit genomes, which have been problematic to scaffold to chromosome-scale with previous generations of data, and assembly software. Nematoda, one of the most diverse, and speciose animal phyla within metazoans, remains poorly studied, and many previously assembled genomes are fragmented. Using long reads obtained with Nanopore R10.4.1 and PacBio HiFi, we generated highly contiguous assemblies of a diploid nematode of the Mermithidae family, for which no closely related genomes are available to date, as well as a collapsed assembly and a phased assembly for a triploid nematode from the Panagrolaimidae family. Both genomes had been analysed before, but the fragmented assemblies had scaffold sizes comparable to the length of long reads prior to assembly. Our new assemblies illustrate how long-read technologies allow for a much better representation of species genomes. We are now able to conduct more accurate downstream assays based on more complete gene and transposable element predictions.
Deep indel mutagenesis reveals the impact of amino acid insertions and deletions on protein stability and function
Authors: Topolska Magdalena , Beltran Antoni , Lehner Ben
Published: October 2023

Amino acid insertions and deletions (indels) are an abundant class of genetic variants. However, compared to substitutions, the effects of indels on protein stability are not well understood and are poorly predicted. To better understand indels here we analyze new and existing large-scale deep indel mutagenesis (DIM) of structurally diverse proteins. The effects of indels on protein stability vary extensively among and within proteins and are not well predicted by existing computational methods. To address this shortcoming we present INDELi, a series of models that combine experimental or predicted substitution effects and secondary structure information to provide good prediction of the effects of indels on both protein stability and pathogenicity. Moreover, quantifying the effects of indels on protein-protein interactions suggests that insertions can be an important class of gain-of-function variants. Our results provide an overview of the impact of indels on proteins and a method to predict their effects genome-wide.
A primordial TFEB-TGFβ signaling axis systemically regulates diapause and stem cell longevity
Authors: Nonninger Tim J. , Mak Jennifer , Gerisch Birgit , Ramponi Valentina , Kawamura Kazuto , Schilling Klara , Latza Christian , Kölschbach Jonathan , Ripa Roberto , Serrano Manuel , Antebi Adam
Published: October 2023

Fasting/refeeding enhances animal health and lifespan across taxa.C. eleganscan endure months of fasting in adult reproductive diapause (ARD) and upon refeeding, regenerate and reproduce.hlh-30/TFEBis an ARD master regulator whose mutants live mere days in ARD and don’t recover with refeeding. Here we find that downregulation of TGFβ signaling bypasseshlh-30collapse, and restores recovery, germline stem cell proliferation and reproductive competence. Upon fasting, HLH-30/TFEB(+) downregulates TGFβ in sensory neurons, to inhibit Notch and promote reproductive quiescence in the germline. Upon refeeding, these pathways are upregulated to activate stem cells and promote reproduction.hlh-30loss induces a senescent-like DNA damage, immune and growth metabolic signature reversed by inhibiting TGFβ signaling. TFEB’s role is conserved in mammalian diapause models, including mouse embryonic and human cancer diapause. Thus, TFEB-TGFβ axis relays systemic signals matching nutrient supply with growth signaling, to regulate stem cell longevity, senescence and regeneration across species.
Decoding muscle-resident Schwann cell dynamics during neuromuscular junction remodeling
Authors: Guzman Steve D , Abu-Mahfouz Ahmad , Davis Carol S , Ruiz Lloyd P , Macpherson Peter C , Brooks Susan V
Published: October 2023

Understanding neuromuscular junction (NMJ) repair mechanisms is essential for addressing degenerative neuromuscular conditions. Here, we focus on the role of muscle-resident Schwann cells in NMJ reinnervation. In youngSod1-/-mice, a model of progressive NMJ degeneration, we identified a clear NMJ ‘regenerative window’ that allowed us to define regulators of reinnervation and crossingSod1-/-mice withS100GFP-tg mice permitted visualization and analysis of Schwann cells. High-resolution imaging and single-cell RNA sequencing provide a detailed analysis of Schwann cell number, morphology, and transcriptome revealing multiple subtypes, including a previously unrecognized terminal Schwann cell (tSC) population expressing a synapse promoting signature. We also discovered a novel SPP1-driven cellular interaction between myelin Schwann cells and tSCs and show that it promotes tSC proliferation and reinnervation following nerve injury in wild type mice. Our findings offer important insights into molecular regulators critical in NMJ reinnervation that are mediated through tSCs to maintain NMJ function.
Temperature Influences Commensal-Pathogen Dynamics in a Nasal Epithelial Cell Co-culture Model
Authors: Huffines Joshua T. , Boone RaNashia L. , Kiedrowski Megan R.
Published: October 2023

Chronic rhinosinusitis (CRS) is an inflammatory disease of the paranasal sinuses, and microbial dysbiosis associated with CRS is thought to be a key driver of host inflammation that contributes to disease progression.Staphylococcus aureusis a common upper respiratory tract (URT) pathobiont that is associated with higher carriage rates in CRS populations, whereS. aureussecreted toxins can be identified in CRS tissue samples. Although many genera of bacteria colonize the URT, relatively few account for the majority of sequencing reads. These includeS. aureus, as well as several species belonging to the genusCorynebacterium, includingCorynebacterium propinquumandCorynebacterium pseudodiphtheriticum, which are observed at high relative abundance in the URT of healthy individuals. Studies have examined the bacterial interactions between the major microbionts of the URT andS. aureus, but few have done so in the context of a healthy versus diseased URT environment. Here, we examine the role of temperature in commensal, pathogen, and epithelial dynamics using an air-liquid interface cell culture model mimicking the nasal epithelial environment. The healthy URT temperature changes from the nares to the nasopharynx and is altered during disease. Temperatures representative of the healthy URT increase persistence and aggregate formation of commensalC. propinquum and C. pseudodiphtheriticum, reduceS. aureusgrowth, and lower epithelial cytotoxicity compared to higher temperatures correlating with the diseased CRS sinus. Dual-species colonization revealed species-specific interactions between commensalCorynebacteriumspecies andS. aureusdependent on temperature. Our findings suggest that URT mucosal temperature plays a significant role in mediating polymicrobial and host-bacterial interactions that may exacerbate microbial dysbiosis found in chronic URT disease.

IMPORTANCE

Chronic rhinosinusitis is a complex inflammatory disease with a significant healthcare burden. Although presence ofS. aureusand microbial dysbiosis are considered mediators of inflammation in CRS, no studies have examined the influence of temperature onS. aureusinteractions with the nasal epithelium and the dominant genus of the healthy URT,Corynebacterium. Interactions betweenCorynebacterium speciesandS. aureushave been documented in several studies, but none to date have examined how environmental changes in the URT may alter their interactions with the epithelium or each other. This study utilizes a polarized epithelial cell culture model at air-liquid interface to study the colonization and spatial dynamics ofS. aureusand clinical isolates ofCorynebacteriumfrom people with CRS to characterize the role temperature has in single-and dual-species dynamics on the nasal epithelium.
Comparative Proteomic Study of Retinal Ganglion Cells Undergoing Various Types of Cellular Stressors
Authors: Starr Christopher R. , Mobley James A. , Gorbatyuk Marina S.
Published: October 2023

Retinal ganglion cell (RGC) damage serves as a key indicator of various retinal degenerative diseases, including diabetic retinopathy (DR), glaucoma, retinal arterial and retinal vein occlusions, as well as inflammatory and traumatic optic neuropathies. Despite the growing body of data on the RGC proteomics associated with these conditions, there has been no dedicated study conducted to compare the molecular signaling pathways involved in the mechanism of neuronal cell death. Therefore, we launched the study using two different insults leading to RGC death: glutamate excitotoxicity and optic nerve crush (ONC). C57BL/6 mice were used for the study and underwent NMDA- and ONC-induced damage. Twenty-four hours after ONC and 1 hour after NMDA injection, we collected RGCs using CD90.2 coupled magnetic beads, prepared protein extracts, and employed LC-MS for the global proteomic analysis of RGCs. Statistically significant changes in proteins were analyzed to identify changes to cellular signaling resulting from the treatment. We identified unique and common alterations in protein profiles in RGCs undergoing different types of cellular stresses. Our study not only identified both unique and shared proteomic changes but also laid the groundwork for the future development of a therapeutic platform for testing gene candidates for DR and glaucoma.
Single-cell RNA sequencing unveils the hidden powers of zebrafish kidney for generating both hematopoiesis and adaptive antiviral immunity
Authors: Hu Chongbin , Zhang Nan , Hong Yun , Tie Ruxiu , Fan Dongdong , Lin Aifu , Chen Ye , Xiang Lixin , Shao Jianzhong
Published: October 2023

The vertebrate kidneys play two evolutionary conserved roles in waste excretion and osmoregulation. Besides, the kidney of fish is considered as a functional ortholog of mammalian bone marrow that serves as a hematopoietic hub for generating blood cell lineages and immunological responses. However, knowledge about the properties of kidney hematopoietic cells, and the functionality of kidney in fish immune systems remain to be elucidated. To this end, our present study generated a comprehensive atlas with 59 hematopoietic stem/progenitor cell (HSPC) and immune-cell types from zebrafish kidney via single-cell transcriptome profiling analysis. These populations included almost all known cells associated with innate and adaptive immunity, and displayed differential responses to viral infection, indicating their diverse functional roles in antiviral immunity. Remarkably, HSPCs were found to have extensive reactivities to viral infection, and the trained immunity can be effectively induced in certain HSPCs. In addition, the antigen-stimulated adaptive immunity can be fully generated in kidney, suggesting kidney acting as a secondary lymphoid organ. These results indicated that fish kidney is a dual-functional entity with functionalities of both primary and secondary lymphoid organs. Our findings illustrated the unique features of fish immune system, and highlighted the multifaced biology of kidney in ancient vertebrates.
Biomechanical stress analysis of Type-A aortic dissection at pre-dissection, post-dissection, and post-repair states
Authors: Sun Christina , Qin Tongran , Kalyanasundaram Asanish , Elefteriades John , Sun Wei , Liang Liang
Published: October 2023

Acute type A aortic dissection remains a deadly and elusive condition, with risk factors such as hypertension, bicuspid aortic valves, and genetic predispositions. As existing guidelines for surgical intervention based solely on aneurysm diameter face scrutiny, there is a growing need to consider other predictors and parameters, including wall stress, in assessing dissection risk. Through our research, we aim to elucidate the biomechanical underpinnings of aortic dissection and provide valuable insights into its prediction and prevention.

We applied finite element analysis (FEA) to assess stress distribution on a rare dataset comprising computed tomography (CT) images obtained from eight patients at three stages of aortic dissection: pre-dissection (preD), post-dissection (postD), and post-repair (postR). Our findings reveal significant increases in both mean and peak aortic wall stresses during the transition from the preD state to the postD state, reflecting the mechanical impact of dissection. Surgical repair effectively restores aortic wall diameter to pre-dissection levels, documenting its effectiveness in mitigating further complications. Furthermore, we identified stress concentration regions within the aortic wall that closely correlated with observed dissection borders, offering insights into high-risk areas.

This study demonstrates the importance of considering biomechanical factors when assessing aortic dissection risk. Despite some limitations, such as uniform wall thickness assumptions and the absence of dynamic blood flow considerations, our patient-specific FEA approach provides valuable mechanistic insights into aortic dissection. These findings hold promise for improving predictive models and informing clinical decisions to enhance patient care.
Non-pharmacological interventions aimed at promoting the mental health of children and adolescents during the COVID-19 pandemic
Authors: Quiroga Carolina Villanova , Caobelli Anna Clara Sarmento Leite , Rodrigues Gabriela Veiga Alano , Viola Thiago Wendt
Published: October 2023

Background

Interventions to promote mental health in pediatrics need to be effective, especially in crisis contexts. This systematic review proposes compile and analyze the findings of non-pharmacological interventions conducted in samples of children and adolescents during the COVID-19 pandemic, focusing on mental health.

Method

The research was carried out in PsycINFO, PubMed and Web of Science databases for empirical studies, including interventions in which measures of outcome variables were collected at least twice (pre and post). The studies’ samples were children and adolescents up to 19 years old, and interventions were developed throughout the COVID-19 pandemic. After eligibility analyses, 16 studies were included in this review.

Results

Studies used different theoretical approaches, focusing on promotion, prevention and treatment in mental health in specifics contexts. Some were delivered online, in-person, or in hybrid formats. Particularly, depression, the most frequently assessed outcome, demonstrated more favorable results within the interventions. However, due to considerable risk of bias, the analysis of results of many included studies should be performed with caution.

Conclusions

Most of the interventions necessitate further validation. However, the emergence of interventions during crises, such as the COVID-19 pandemic, provides an opportunity to expand evidence-based mental health practices, paving the way for their application in other crisis situations. Given that mental health prevention and promotion practices can be integrated into the roles of all healthcare providers, possessing insight into the most suitable evidence-based interventions can elevate the quality of care delivered.
A conserved N-terminal motif of CUL3 mediates assembly and licenses E3 ligase activation of CRL3KLHL22
Authors: Wang Weize , Liang Ling , Dai Zonglin , Zuo Peng , Yu Shang , Lv Yishuo , Ding Dian , Chen Hongyi , Jin Yan , Mao Youdong , Yin Yuxin
Published: October 2023

The CUL3-RING E3 ubiquitin ligases (CRL3s) play an essential role in response to extracellular nutrition and stress stimuli. The ubiquitin ligase function of CRL3s is activated through E3-E3 dimerization. However, how and why such a dimeric assembly is required for its ligase activity remains elusive. Here, we report the cryo-EM structure of the dimeric CRL3KLHL22complex and reveal a conserved N-terminal motif in CUL3 that mediates the dimerization assembly and licenses the activation of CRL3KLHL22. Deletion of the CUL3 N-terminal motif leads to non-stochiometric assembly and impairs E3 activity of both CRL3KLHL22and several other CRL3s. In addition, we found that the dynamics of dimeric E3-E3 superassembly generates a variable ubiquitination zone, potentially facilitating substrate recognition and ubiquitination. These findings demonstrate a CUL3 N-terminal motif-dependent E3-E3 superassembly mechanism and provide insights into the assembly and activation of CRL3s.
Exploiting Intrinsic Noise for Heterogeneous Cell Control Under Time Delays and Model Uncertainties
Authors: May M P , Munsky B
Published: October 2023

The majority of previous research in synthetic biology has focused on enabling robust control performance despite the presence of noise, while the understanding for how controllers may exploit that noise remains incomplete. Motivated by Maxwell’s Demon, we previously proposed a cellular control regime in which the exploitation of stochastic noise can break symmetry between and allow for specific control of multiple cells using a single input signal (i.e., single-input-multiple-output or SIMO control). The current work extends that analysis to include uncertain stochastic systems where system dynamics are are affected by time delays, intrinsic noises, and model uncertainty. We find that noise-exploiting controllers can remain highly effective despite coarse approximations to the model’s scale or incorrect estimations or extrinsic noise in key model parameters, and these controllers can even retain performance under substantial observer or actuator time delays. We also demonstrate how SIMO controllers could drive multi-cell systems to follow different trajectories with different phases and frequencies. Together, these findings suggest that noise-exploiting control should be possible even in the practical case where models are always approximate, where parameters are always uncertain, and where observations are corrupted by errors.
PKHD1L1, A Gene Involved in the Stereocilia Coat, Causes Autosomal Recessive Nonsyndromic Hearing Loss
Authors: Redfield Shelby E. , De-la-Torre Pedro , Zamani Mina , Wang Hanjun , Khan Hina , Morris Tyler , Shariati Gholamreza , Karimi Majid , Kenna Margaret A. , Seo Go Hun , Xu Hongen , Lu Wei , Naz Sadaf , Galehdari Hamid , Indzhykulian Artur A. , Shearer A. Eliot , Vona Barbara
Published: October 2023

Identification of genes associated with nonsyndromic hearing loss is a crucial endeavor given the substantial number of individuals who remain without a diagnosis after even the most advanced genetic testing.PKHD1L1was established as necessary for the formation of the cochlear hair-cell stereociliary coat and causes hearing loss in mice and zebrafish when mutated. We sought to determine if biallelic variants inPKHD1L1also cause hearing loss in humans.

Exome sequencing was performed on DNA of four families segregating autosomal recessive nonsyndromic sensorineural hearing loss. Compound heterozygous p.[(Gly129Ser)];p.[(Gly1314Val)] and p.[(Gly605Arg)];p[(Leu2818TyrfsTer5)], homozygous missense p.(His2479Gln) and nonsense p.(Arg3381Ter) variants were identified inPKHD1L1that were predicted to be damaging usingin silicopathogenicity prediction methods.In vitrofunctional analysis of two missense variants was performed using purified recombinant PKHD1L1 protein fragments. We then evaluated protein thermodynamic stability with and without the missense variants found in one of the families and performed a minigene splicing assay for another variant.In silicomolecular modelling using AlphaFold2 and protein sequence alignment analysis were carried out to further explore potential variant effects on structure.In vitrofunctional assessment indicated that both engineered PKHD1L1 p.(Gly129Ser) and p.(Gly1314Val) mutant constructs significantly reduced the folding and structural stabilities of the expressed protein fragments, providing further evidence to support pathogenicity of these variants. Minigene assay of the c.1813G>A p.(Gly605Arg) variant, located at the boundary of exon 17, revealed exon skipping leading to an in-frame deletion of 48 amino acids.In silicomolecular modelling exposed key structural features that might suggest PKHD1L1 protein destabilization.

Multiple lines of evidence collectively associatePKHD1L1with nonsyndromic mild-moderate to severe sensorineural hearing loss.PKHD1L1testing in individuals with mild-moderate hearing loss may identify further affected families.
Clinical interpretation ofKCNH2variants using a robust PS3/BS3 functional patch clamp assay
Authors: Thomson Kate L. , Jiang Connie , Richardson Ebony , Westphal Dominik S. , Burkard Tobias , Wolf Cordula M. , Vatta Matteo , Harrison Steven M. , Ingles Jodie , Bezzina Connie R. , Kroncke Brett M. , Vandenberg Jamie I. , Ng Chai-Ann
Published: October 2023

Long QT syndrome (LQTS), caused by the dysfunction of cardiac ion channels, increases the risk of sudden death in otherwise healthy young people. For many variants in LQTS genes there is insufficient evidence to make a definitive genetic diagnosis. We have established a robust functional patch clamp assay to facilitate classification of missense variants inKCNH2, one of the key LQTS genes. A curated set of 30 benign and 30 pathogenic missense variants were used to establish the range of normal and abnormal function. The extent to which variants reduced protein function was quantified using Z-scores; the number of standard deviations from the mean of the normalised current density of the set of benign variant controls. A Z-score of –2 defined the threshold for abnormal loss-of-function, which corresponds to 55% wild-type function. More extreme Z-scores were observed for variants with a greater loss-of-function effect. We propose that the Z-score for each variant can be used to inform the application and weighting of abnormal and normal functional evidence criteria (PS3 and BS3) within the American College of Medical Genetics and Genomics (ACMG) variant classification framework. The validity of this approach was demonstrated using a series of 18KCNH2missense variants detected in a childhood onset LQTS cohort, where the level of function assessed using our assay correlated to the Schwartz score (a scoring system used to quantify the probability of a clinical diagnosis of LQTS1) and the length of the QTc interval.
Brain network hypersensitivity underlies pain crises in sickle cell disease
Authors: Joo Pangyu , Kim Minkyung , Kish Brianna , Nair Vidhya Vijayakrishnan , Tong Yunjie , Harte Steven E , Harris Richard E , Lee UnCheol , Wang Ying
Published: October 2023

Sickle cell disease (SCD) is a genetic disorder causing blood vessel blockages and painful Vaso-occlusive crises (VOCs). VOCs, characterized by severe pain due to blocked blood flow, are recurrent and unpredictable, posing challenges for preventive strategies. In this study we propose explosive synchronization (ES), a phenomenon characterized by abrupt brain network phase transitions, as a novel approach to address this challenge. We hypothesized that the accumulated disruptions in the brain network induced by SCD might lead to strengthened ES and hypersensitivity. We explored ES’s relationship with patient reported outcome measures (PROMs) and VOCs by analyzing EEG data from 25 SCD patients and 18 matched controls. SCD patients exhibited significantly lower alpha wave frequency than controls. SCD patients under painful pressure stimulation showed correlation between frequency disassortativity (FDA), an ES condition, and three important PROMs. Furthermore, patients who had a higher frequency of VOCs in the preceding 12 months presented with stronger FDA. The timing of VOC occurrence relative to EEG recordings was significantly associated to FDA. We also conducted computational modeling on SCD brain network to study FDA’s role in network sensitivity. Stronger FDA correlated with higher responsivity and complexity in our model. Simulation under noisy environment showed that higher FDA could be linked to increased occurrence frequency of crisis. This study establishes connections between SCD pain and the universal network mechanism, ES, offering a strong theoretical foundation. This understanding will aid predicting VOCs and refining pain management for SCD patients.
Effects of COVID-19 mRNA vaccination on HIV viremia and reservoir size
Authors: Duncan Maggie C. , Omondi F. Harrison , Kinloch Natalie N. , Lapointe Hope R. , Speckmaier Sarah , Moran-Garcia Nadia , Lawson Tanya , DeMarco Mari L. , Simons Janet , Holmes Daniel T. , Lowe Christopher F. , Bacani Nic , Sereda Paul , Barrios Rolando , Harris Marianne , Romney Marc G. , Montaner Julio S.G. , Brumme Chanson J. , Brockman Mark A. , Brumme Zabrina L.
Published: October 2023

Objective

The immunogenic nature of COVID-19 mRNA vaccines led to some initial concern that these could stimulate the HIV reservoir. We analyzed changes in plasma HIV loads (pVL) and reservoir size following COVID-19 mRNA vaccination in 62 people with HIV (PWH) receiving antiretroviral therapy (ART), and analyzed province-wide trends in pVL before and after the mass vaccination campaign.

Design

Longitudinal observational cohort and province-wide analysis.

Methods

62 participants were sampled pre-vaccination, and one month after their first and second COVID-19 immunizations. Vaccine-induced anti-SARS-CoV-2-Spike antibodies in serum were measured using the Roche Elecsys Anti-S assay. HIV reservoirs were quantified using the Intact Proviral DNA Assay; pVL were measured using the cobas 6800 (LLOQ:20 copies/mL). The province-wide analysis included all 290,401 pVL performed in British Columbia, Canada between 2012-2022.

Results

Pre-vaccination, the median intact reservoir size was 77 (IQR:20-204) HIV copies/million CD4+ T-cells, compared to 74 (IQR:27-212) and 65 (IQR:22-174) post-first and -second dose, respectively (all comparisons p>0.07). Pre-vaccination, 82% of participants had pVL<20 copies/mL (max:110 copies/mL), compared to 79% post-first dose (max:183 copies/mL) and 85% post-second dose (max:79 copies/mL) (p>0.4). The magnitude of the vaccine-elicited anti-SARS-CoV-2-Spike antibody response did not correlate with changes in reservoir size nor detectable pVL frequency (p>0.6). We found no evidence linking the COVID-19 mass vaccination campaign to population-level increases in detectable pVL frequency among all PWH in the province, nor among those who maintained pVL suppression on ART.

Conclusion

We found no evidence that COVID-19 mRNA vaccines induced changes in HIV reservoir size nor plasma viremia.
Evolution of genotypic and phenotypic diversity in multispecies biofilms
Authors: Amador Cristina I. , Moscovitz Sofia Zoe , Maccario Lorrie , Herschend Jakob , Kramer Isabel-Sophie , Jeckel Hannah , Cooper Vaughn S. , Drescher Knut , Neu Thomas R. , Burmølle Mette , Røder Henriette L.
Published: October 2023

The fitness and adaptability of bacteria in microbial communities can be influenced by the interactions among the community partners, as well as specific spatial organisation. Here, we investigated the evolutionary dynamics ofBacillus thuringiensisin response to the presence or absence of spatial structure and bacterial interspecies interactions. During evolution experiments, a distinct phenotypic variant ofB. thuringiensisfrequently occurred, irrespective of the conditions tested: planktonic vs. biofilm or monospecies vs. mixed species. Remarkably, selection significantly favored this variant ofB. thuringiensisover its ancestor in biofilm settings and when coexisting withPseudomonas defluviiandPseudomonas brenneri, co-isolated from a wastewater facility. Interestingly, the evolved phenotype displayed lower biomass in mixed species biofilms, shorter generation time, and lacked sporulation compared to the ancestor. The strains displaying this phenotypic variation contained mutations in the regulatorspo0Athat initiates sporulation but also de-represses expression of matrix determinants in other Bacilli. Consistently, matrix proteomics revealed a reduced abundance of TasA in the phenotypic variant, a major biofilm matrix component inBacillusspecies, while higher abundance was found in co-culture withP. brenneri. Our results indicate that interspecies interactions within biofilms not only promoteB. thuringiensisdiversification but also select for altered traits such as reduced biofilm matrix production. Moreover,P. brenneriwas favoured in co-culture biofilm vs. planktonic settings, suggesting that spatial structure andB. thuringiensisdiversification facilitate species co-existence. These findings could impact applications whereBacillusandPseudomonasare utilized in consortia, such as plant growth promoters or biopesticides.
Nitrosative stress under microaerobic conditions triggers inositol metabolism inPseudomonas extremaustralis
Authors: Venero Esmeralda C. Solar , Giambartolomei Lucia , Sosa Ezequiel , Fernández do Porto Darío , López Nancy I. , Tribelli Paula M.
Published: October 2023

Bacteria are exposed to reactive oxygen and nitrogen species that provoke oxidative and nitrosative stress which can lead to macromolecule damage. Coping with stress conditions involves the adjustment of cellular responses, which helps address metabolic challenges. In this study, we performed a global transcriptomic analysis of the response ofPseudomonas extremaustralisto nitrosative stress, induced by S-nitrosoglutathione (GSNO), a nitric oxide donor, under microaerobic conditions. The analysis revealed the upregulation of genes associated with inositol catabolism; a compound widely distributed in nature whose metabolism in bacteria has aroused interest. The RNA-seq data also showed heightened expression of genes involved in essential cellular processes like transcription, translation, amino acid transport and biosynthesis, as well as in stress resistance including iron-dependent superoxide dismutase, alkyl hydroperoxide reductase, thioredoxin, and glutathione S-transferase in response to GSNO. Furthermore, GSNO exposure differentially affected the expression of genes encoding nitrosylation target proteins, encompassing metalloproteins and proteins with free cysteine and /or tyrosine residues. Notably, genes associated with iron metabolism, such as pyoverdine synthesis and iron transporter genes, showed activation in the presence of GSNO, likely as response to enhanced protein turnover. Physiological assays demonstrated thatP. extremaustraliscan utilize inositol proficiently under both aerobic and microaerobic conditions, achieving growth comparable to glucose-supplemented cultures. Moreover, supplementing the culture medium with inositol enhances the stress tolerance ofP. extremaustralisagainst combined oxidative-nitrosative stress. Concordant with the heightened expression of pyoverdine genes under nitrosative stress, elevated pyoverdine production was observed whenmyo-inositol was added to the culture medium. These findings highlight the influence of nitrosative stress on proteins susceptible to nitrosylation and iron metabolism. Furthermore, the activation ofmyo-inositol catabolism emerges as a protective mechanism against nitrosative stress, shedding light on this pathway in bacterial systems, and holding significance in the adaptation to unfavorable conditions.
Types and outcomes of health promotion interventions led by public health students: a scoping review
Authors: Gonzalez-Aquines Alejandro , Bingham Daniel D , Kiilu Elizabeth M
Published: October 2023

Background

Public health students can contribute to improving population health outcomes; however, this remains an under-researched area. This review aims to assess the extent of the literature related to health promotion interventions led by public health students. This includes what these interventions are and how they are being conducted, as well as their impact on targeted populations.

Methods

A scoping review was conducted according to JBI guidelines. A search strategy was developed using the population, context, concept framework. MEDLINE, CINAHL, Embase and Google Scholar were consulted. The selection process involved the screening of titles and abstracts against the inclusion criteria, followed by a full-text screening and data extraction by two reviewers. Disagreements were solved by consensus.

Results

191 studies were identified, but only five of these were included. The target populations included the general public, university students, and minority groups. Students were trained or supervised by experienced staff. The interventions were delivered using diverse means, including innovative approaches through social media. The student-led interventions increased access to preventive services (screening, vaccinations) and improved health knowledge within the target groups.

Conclusion

Public health students make impactful contributions by increasing both the access to and the use of preventive services, as well as by promoting health knowledge. Our study contributes to the professionalisation of public health, highlighting for the first time the role of public health students in improving health outcomes. Furthermore, our study sheds light on the students’ impact on the reduction of health inequalities, particularly amongst minority groups.
Vinculin-Arp2/3 Interaction Inhibits Branched Actin Assembly to Control Cell Migration and Cell Cycle Progression
Authors: James John , Fokin Artem I. , Guschin Dmitry Y. , Wang Hong , Polesskaya Anna , Rubtsova Svetlana N. , Clainche Christophe Le , Silberzan Pascal , Gautreau Alexis M. , Romero Stéphane
Published: October 2023

Vinculin is a mechanotransducer that reinforces links between cell adhesions and linear arrays of actin filaments upon myosin-mediated contractility. Both adhesions to the substratum and neighboring cells, however, are initiated within membrane protrusions that originate from Arp2/3-nucleated branched actin networks. Vinculin has been reported to interact with the Arp2/3 complex, but the role of this interaction remains poorly understood. Here we compared the phenotypes of vinculin knock-out (KO) cells with those of knock-in (KI) cells, where the point mutation P878A that impairs the Arp2/3 interaction is introduced in the two vinculin alleles of MCF10A mammary epithelial cells. The interaction of vinculin with Arp2/3 inhibits actin polymerization at membrane protrusions and decreases migration persistence of single cells. In cell monolayers, vinculin recruits Arp2/3 and the vinculin-Arp2/3 interaction participates in cell-cell junction plasticity. Through this interaction, vinculin controls the decision to enter a new cell cycle as a function of cell density.
Colorings of patterns fixed by an arbitrary finite-index subgroup of the symmetry group
Authors: Junio Allan O.
Published: October 2023

In this research project, a framework is established that characterizes the colorings of a pattern fixed by an arbitrarily chosen finite-index subgroup of the pattern's symmetry group. This framework is applied to the sphalerite structure to enumerate all colorings fixed by two different subgroups of the symmetry group. These colorings are used to perform ordered substitution on the atoms in the sphalerite structure and demonstrate some of the well known derived structures (e.g. chalcopyrite, stannite). Some results involving equivalences of colorings fixed by the chosen subgroup are also developed.
Three-way interaction and multiple mediation models: Environmental strategy and sustainability marketing commitment applications
Authors: Yu Tai-Yi , Horng Jeou-Shyan , Liu Chih-Hsing , Chou Sheng-Fang , Lee Ming-Tsung , Huang Yung-Chuan , Lapuz Maria Carmen B.
Published: October 2023

Purpose

This study attempts to fill the research gap by extending sustainability literature and providing empirical evidence that considers sustainability marketing commitment (SMC) as a fundamental attribute of effective marketing strategy that consequently improves tourism service quality, as represented by service attractiveness.

Design/methodology/approach

In the current study, data was collected from 313 tourism and hospitality firms. To test the model, this study applied structural equation modeling (SEM) to investigate the relationships among environmental strategy, SMC, supplier trust and service attractiveness in a mediation-moderation setting.

Findings

The results indicate that the multiple mediation effects of environmental strategy may indirectly influence tourist attractiveness through SMC and tourism services. The two-way moderating effects reveal that supplier trust and socialization strengthen the service attractiveness development process, while three-way interaction discovered that socialization and supplier trust positively moderate the relationships between tourism services and service attractiveness.

Originality/value

Sustainable strategy is a future trend for tourism business management; however, unknown to most is the role of marketing and environmental strategy in tourism business due to lack of integration with concepts in marketing strategy, with the multidimensionality of tourism services, and with the function of trust and socialization, critically undermining analyses of service attractiveness. This paper combines corporate sustainability and sustainability marketing methods to explore how an environmental strategy can improve tourism services and enhance a destination's attractiveness based on a mediation-moderation mechanism.
Fostering comparative advantage: the roles of data-driven competitive sustainability, green product innovation and green process innovation through moderated-mediation model
Authors: AL-Shboul Moh'd Anwer
Published: October 2023

Purpose

This study attempts to examine the relationship between reliable big and cloud data analytics capabilities (RB&CDACs) and comparative advantages (CA) of manufacturing firms (MFs) in the Middle East region as developing countries using green product innovation (GPI) and green process innovations (GPrI) mediating factors, further assess the role of data-driven competitive sustainability factor as a moderated factor.

Design/methodology/approach

436 useable online surveys were analyzed using the quantitative approach for the data-gathering process, applying structural equation modeling in the Smart-PLS program as an analysis tool. The sample unit for analysis included all middle- and senior-level managers and employees within MFs. The authors performed convergent validity and discriminant validity tests, bootstrapping also was applied. The authors included GPI and GPrI as mediating factors while using data-driven competitive sustainability as a moderated factor.

Findings

The findings of this study indicated that there is a positive significant effect in the relationship between reliable big and cloud data analytics capabilities and comparative advantages, which is supported by the formulated hypothesis. Furthermore, the findings confirmed that there was a positive and significant effect through the mediating factors (i.e. GPI and GPrI) on comparative advantage, additionally, it confirmed and supported that the moderating factor represented by data-driven competitive advantage suitability has significant effect as well.

Research limitations/implications

This study has some limitations represented by using only one type of methodological approach (i.e. quantitative), further, it was conducted on only Asian countries in the Middle East region.

Originality/value

This piece of work improved the proposed conceptual research model and included several factors such as reliable big and cloud data analytics capabilities, comparative advantage, data-driven competitive sustainability, GPI and GPrI. This research offered new and valuable information and findings for managers, practitioners and decision-makers in the MFs in the Middle East region as a road map and gaudiness for the importance to apply these factors in their firms for enhancing the comparative advantages in their firms. Further, this research fills the gap in SCM literature and makes a bridge of knowledge and contribution to the existence of previous studies.
How does top management team regulatory focus influence management innovation and performance in megaprojects: the moderating role of project uncertainties
Authors: Ma Li , Lu Yongqiang
Published: October 2023

Purpose

Existing research on innovation has mainly focused on how to promote technological innovation in megaprojects and management innovation (MI) in megaprojects is still an unknown research field. The purposes of this study are to examine the effect of MI on megaproject performance and how the top management team (TMT) regulatory focus affects the use of MI in projects. At the same time, the moderating effects of project uncertainties are also tested.

Design/methodology/approach

On the basis of an explorative/exploitative ambidextrous analysis framework, this study divides MI into two dimensions: explorative and exploitative MI, and integrates the theoretical perspectives of the TMT regulatory focus and project uncertainties into a research model. Taking 314 responses from megaprojects’ TMTs in China as research data, this study empirically tests the above model.

Findings

Results show that exploratory MI has a U-shaped relationship with megaproject performance; whereas exploitative MI has an inverted U-shaped relationship with megaproject performance. The TMT promotion focus has a positive effect on exploratory and exploitative MI; and the TMT prevention focus has a negative effect on exploratory MI but has a positive effect on exploitative MI. Project uncertainties have a positive moderating effect on the positive relationship between TMT promotion focus and exploratory MI, whereas it has a negative moderating effect on the negative relationship between the TMT prevention focus and exploratory MI.

Originality/value

By empirically measuring the relationship between two types of MIs and megaproject performance, this study clarifies the differential mechanism of the effect of different MIs on megaproject performance. This study also examines the MI of megaprojects from the perspective of the TMT regulatory focus and expounds how changes in uncertainties affect the relationship between the TMT regulatory focus and MI.