bluuebunny/crossref_metadata_2025 huggingface dataset:
Establishing a Core Outcome Set for Creatine Transporter Deficiency and Guanidinoacetate Methyltransferase Deficiency
Authors: Nasseri Moghaddam Zahra , Reinhardt Emily K. , Thurm Audrey , Potter Beth K. , Smith Maureen , Graham Celeste , Tiller Beth H. , Baker Steven A. , Bilder Deborah A. , Bogar Regina , Britz Jacobus , Cafferty Rachel , Coller Daniel P. , DeGrauw Ton J. , Hall Vicky , Lipshutz Gerald S. , Longo Nicola , Mercimek-Andrews Saadet , Miller Judith S. , Pasquali Marzia , Salomons Gajja S. , Schulze Andreas , Wheaton Celine P. , Williams Kayla F. , Young Sarah P. , Li Jasmine , Balog Sofia , Selucky Theresa , Stockler-Ipsiroglu Sylvia , Wallis Heidi
Published: September 2024

Creatine transporter (CTD) and guanidinoacetate methyltransferase (GAMT) deficiencies are rare inborn errors of creatine metabolism, resulting in cerebral creatine deficiency. Patients commonly exhibit intellectual and developmental disabilities, often accompanied by behavior problems, delayed speech, seizures, and motor impairments. There is currently no efficacious treatment for CTD, while the current management for GAMT requires lifelong treatment with a protein restricted diet and intake of high amounts of oral supplements. Efforts to develop effective, sustainable treatments for these disorders are limited by the lack of clinical and patient-derived meaningful outcomes. A core outcome set (COS) can facilitate consensus about outcomes for inclusion in studies. Unfortunately, patient and caregiver perspectives have historically been overlooked in the COS development process, thus limiting their input into the outcome selection. We partnered with caregivers and health professionals to establish the first COS for CTD and GAMT. The COS developed includes seven outcomes (“Adaptive Functioning”, “Cognitive Functioning”, “Emotional Dysregulation”, “MRS Brain Creatine”, “Seizure/Convulsions”, “Expressive Communication”, and “Fine Motor Functions”) for both CTD and GAMT, and an additional outcome for GAMT (“Serum/Plasma Guanidinoacetate”) that are important to stakeholders and consequently should be considered for measurement in every clinical trial. Caregivers were valued partners throughout the COS development process, which increased community engagement and facilitated caregiver empowerment. We expect this COS will ensure a patient-centered approach for accelerating drug development for CTD and GAMT, make clinical trial results comparable, minimize bias in clinical trial outcome selection, and promote efficient use of resources.

1-sentence take home message

A core outcome set for creatine transporter (CTD) and guanidinoacetate methyltransferase (GAMT) deficiencies was created through a multiphase process in partnership with caregivers and health professionals.
Effects of Statin Therapy in Patients Treated with Drug-Eluting and Drug- Coated Stents for Femoropopliteal Lesions: STAR-FP Study Outcomes
Authors: Takei Tatsuro , Tokuda Takahiro , Yoshioka Naoki , Ogata Kenji , Tanaka Akiko , Kojima Shunsuke , Yamaguchi Kohei , Yanagiuchi Takashi , Nakama Tatsuya
Published: September 2024

Background

The effects of statins on drug-eluting stents (DESs) and drug-coated stents (DCSs) for femoropopliteal (FP) lesions are not well known. Therefore, this multicenter retrospective evaluated the impact of statins on DES and DCS patency.

Methods

Between January 2018 and December 2021, 449 patients were treated with DES and DCS at eight cardiovascular centers in Japan (LEADers FP registry). These lesions were divided into statin-treated and non-statin-treated arms. After propensity score matching, the effects of statins on DES and DCS were evaluated. The 2-year primary outcome measure was stent patency. The secondary outcomes included secondary patency, clinically driven target lesion revascularization (CD-TLR), limb salvage, major adverse limb events (MALE, CD-TLR+ major amputation), and a composite of overall survival and MALE or all-cause death at 2 years.

Results

After propensity score matching, the baseline and procedural characteristics did not differ significantly between the 135 patient pairs in the statin and non-statin groups. The primary patency at two years was significantly better in the statin group than in the non-statin group (86.9% vs. 75.1%, p=0.041). Regarding the secondary endpoints, the statin group demonstrated significantly superior secondary patency and freedom from MALE or all-cause mortality (95.5% vs. 87.0%, p=0.023 and 73.7% vs. 60.0%, p=0.012, respectively).

Conclusions

The results of this retrospective multicenter study demonstrated the superior primary patency in the statin group compared with the non-statin group at two years. These findings suggest that statins improve patency in patients undergoing DES and DCS.
Proteomic profiling of the large vessel vasculitis spectrum identifies shared signatures of innate immune activation and stromal remodelling
Authors: Maughan Robert T. , MacDonald-Dunlop Erin , Haroon-Rashid Lubna , Sorensen Louise , Chaddock Natalie , Masters Shauna , Porter Andrew , Peverelli Marta , Pericleous Charis , Hutchings Andrew , Robinson James , Youngstein Taryn , Luqmani Raashid A. , Mason Justin C. , Morgan Ann W. , Peters James E.
Published: September 2024

Takayasu arteritis (TAK) and giant cell arteritis (GCA) are the primary forms of large vessel vasculitis (LVV) and can result in serious cardiovascular morbidity. Improved understanding of the molecular basis of these diseases is required to develop novel biomarkers and targeted treatments. Moreover, it is unclear whether shared or distinct pathogenic processes underpin the LVV spectrum. To address this, we performed plasma proteomic profiling, quantifying 184 plasma proteins using Olink immunoassays in two independent cohorts totalling 405 individuals. In Cohort 1, comparison of patients with TAK (N=96) and large vessel-GCA (LV-GCA) (N=35) versus healthy controls (HCs) (N=35) revealed 52 and 72 significant differentially abundant proteins, respectively. Correlation with disease activity status identified novel TAK and LV-GCA disease activity markers. Cohort 2 consisted of patients presenting acutely with possible cranial GCA (C-GCA); C-GCA was subsequently confirmed (n=150) or excluded (n=89). 31 proteins were associated with C-GCA. Analyses stratified by temporal artery biopsy results revealed enrichment of the proteomic signal in biopsy-proven GCA, suggesting the presence of distinct endotypes within C-GCA. Cross-disease comparison revealed that active TAK, LV-GCA and biopsy-proven C-GCA had highly similar plasma proteomic profiles. Twenty-six proteomic associations were shared across all three groups including IL6, monocyte/macrophage related proteins (CCL5, CCL7, CSF1), tissue remodelling proteins (VEGFA, TIMP1, TNC) and proteins not previously linked to LVV (TNFSF14, IL7R). We also observed disease-specific associations including increased CXCL9 in LV-GCA and C-GCA but not in TAK and decreases in the extracellular matrix protein COMP in TAK but not in LV-GCA or C-GCA. Evaluation of publicly available transcriptomic data from LV-GCA aortic tissue revealed that 47 of the 112 proteins significantly altered in ≥1 LVV type had significantly altered mRNA expression in LVV aortic tissue. Similarities in LVV proteomic profiles suggest shared pathobiology involving innate immunity, particularly monocyte/macrophages, lymphocyte homeostasis and tissue remodelling processes. Our results highlight a signature of immune-stromal cross talk in LVV and identify potential novel therapeutic targets in this axis (e.g. TNFSF14). The correspondence of plasma signatures to tissue phenotype highlights the potential for non-invasive monitoring of arterial inflammation and injury.
Knowledge mobilization with and for equity-deserving communities invested in research: A scoping review protocol
Authors: Barhouche Ramy , Tse Samson , Inglis Fiona , Chaves Debbie , Allison Erin , Colaco Tina , Morton Ninomiya Melody E.
Published: September 2024

The practice of putting research into action is known by various names, depending on disciplinary norms. Knowledge mobilization, translation, and transfer (collectively referred to as K*) are three common terminologies used in research literature. Knowledge-to-action opportunities and gaps in academic research often remain obscure to non-academic researchers in communities, policy and decision makers, and practitioners who could benefit from up-to-date information on health and wellbeing. Academic research training, funding, and performance metrics rarely prioritize or address non-academic community needs from research. We propose to conduct a scoping review on reported K* in community-driven research contexts, examining the governance, processes, methods, and benefits of K*, and mapping who, what, where, and when K* terminology is used. This protocol paper outlines our approach to gathering, screening, analyzing, and reporting on available published literature from four databases.
Development and calibration of a mathematical model of HIV outcomes among Rwandan adults: informing equitable achievement of targets in Rwanda
Authors: Kimmel April D. , Pan Zhongzhe , Brazier Ellen , Murenzi Gad , Muhoza Benjamin , Yotebieng Marcel , Anastos Kathryn , Nash Denis
Published: September 2024

Background

We developed and calibrated the Central Africa-International epidemiology Databases to Evaluate AIDS (CA-IeDEA) HIV policy model to inform equitable achievement of global goals, overall and across sub-populations, in Rwanda.

Methods

We created a deterministic dynamic model to project adult HIV epidemic and care continuum outcomes, overall and for 25 subpopulations (age group, sex, HIV acquisition risk, urbanicity). Data came from the Rwanda cohort of CA-IeDEA, 2004–2020; Rwanda Demographic and Health Surveys, 2005, 2010, 2015; Rwanda Population-based HIV Impact Assessment, 2019; and the literature and reports. We calibrated the model to 47 targets by selecting the 50 best-fitting parameter sets among 20,000 simulations. Calibration targets reflected epidemic (HIV prevalence, incidence), global goals (percentage on antiretroviral therapy (ART) among diagnosed, percentage virally suppressed among on ART) and other (number on ART, percentage virally suppressed) indicators, overall and by sex. Best-fitting sets minimized the summed absolute value of the percentage deviation (AVPD) between model projections and calibration targets. Good model performance was mean AVPD<5% across the 50 best-fitting sets and/or projections within the target confidence intervals; acceptable was mean AVPD >5% and<15%.

Results

Across indicators, 1,841 of 2,350 (78.3%) model projections were a good or acceptable fit to calibration targets. For HIV epidemic indicators, 256 of 300 (85.3%) projections were a good fit to targets, with the model performing better for women (83.3% a good fit) than for men (71.7% a good fit). For global goals indicators, 96 of 100 (96.0%) projections were a good fit; model performance was similar for women and men. For other indicators, 653 of 950 (68.7%) projections were a good or acceptable fit. Fit was better for women than for men (percentage virally suppressed only) and when restricting targets for number on ART to 2013 and beyond.

Conclusions

The CA-IeDEA HIV policy model fits historical data and can inform policy solutions for equitably achieving global goals to end the HIV epidemic in Rwanda. High-quality, unbiased population-based data, as well as novel approaches that account for calibration target quality, are critical to ongoing use of mathematical models for programmatic planning.
Industry differences in managers’ experiences of work capacity in employees with common mental disorders: a cross-sectional study on the Swedish labour market
Authors: Björk Lisa , Hultquist Jenny , Hensing Gunnel , Bertilsson Monica
Published: September 2024

The aim of this study was to assess industry differences in managers’ experiences and ratings of work capacity in employees with common mental disorders (CMDs). Swedish managers (N=1819) were grouped into three industry classifications. Differences between industries in managers’ experiences were investigated by chi-squared tests. The managers’ ratings of how work capacity was affected by CMDs were analysed using MANCOVA, adjusted for organizational size and managers’ span of control. The proportion of managers who had experienced several employees with CMDs was higher in municipalities and counties, and in pink-collar work, education, health and social care settings compared with other industries. There was no significant effect of industry on managers’ ratings of how work capacity may be affected by CMDs. Contrary to assumptions, there were no differences in how managers perceived capacity to work between industries. Therefore, it is more urgent that managers receive the support they need to handle employees with reduced work capacity due to CMDs rather than to tailor such support to different industries.
Transfer RNA levels are tuned to support differentiation during Drosophila neurogenesis
Authors: Wint Rhondene , Cleary Michael D.
Published: September 2024

Neural differentiation requires a multifaceted program to alter gene expression along the proliferation to differentiation axis. While critical changes occur at the level of transcription, post-transcriptional mechanisms allow fine-tuning of protein output. We investigated the role of tRNAs in regulating gene expression during neural differentiation by quantifying tRNA abundance in neural progenitor-biased and neuron-biasedDrosophilalarval brains. We found that tRNA profiles are largely consistent between progenitor-biased and neuron-biased brains but significant variation occurs for 10 cytoplasmic isodecoders (individual tRNA genes) and this establishes differential tRNA levels for 8 anticodon groups. We used these tRNA data to investigate relationships between tRNA abundance, codon optimality- mediated mRNA decay, and translation efficiency in progenitors and neurons. Our data reveal that tRNA levels strongly correlate with codon optimality-mediated mRNA decay within each cell type but generally do not explain differences in stabilizing versus destabilizing codons between cell types. Regarding translation efficiency, we found that tRNA expression in neural progenitors preferentially supports translation of mRNAs whose products are in high demand in progenitors, such as those associated with protein synthesis. In neurons, tRNA expression shifts to disfavor translation of proliferation-related transcripts and preferentially support translation of transcripts tied to neuron-specific functions like axon pathfinding and synapse formation. Overall, our analyses reveal that changes in tRNA levels along the neural differentiation axis support optimal gene expression in progenitors and neurons.

AUTHOR SUMMARY

Wint et al. quantified tRNA expression inDrosophilalarval brains, using wildtype brains composed primarily of neurons and mutant brains composed primarily of neural progenitors (neuroblasts). These neuron-biased and neuroblast-biased tRNA measurements, combined with mRNA decay data and computational modeling of translation efficiency, revealed that: 1) tRNA abundance is largely constant between neural progenitors and neurons but significant variation exists for 10 nuclear tRNA genes and 8 corresponding anticodon groups, 2) tRNA abundance correlates with codon-mediated mRNA decay in neuroblasts and neurons but does not completely explain the different stabilizing or destabilizing effects of certain codons, and 3) changes in tRNA levels during differentiation shift translation optimization from a program supporting proliferation to a program supporting differentiation. These findings reveal coordination between tRNA expression and codon usage in transcripts that regulate neural development.
TheDrosophilamyogenic inhibitorHimgene is essential for adult muscle function and muscle stem cell maintenance
Authors: Mitchell-Gee Robert , Hoff Robert , Vishal Kumar , Hancock Daniel , McKitrick Sam , Newnes-Querejeta Cristina , Lovato TyAnna L. , Cripps Richard M. , Taylor Michael V.
Published: September 2024

Vertebrate muscle fibres have a population of Muscle Stem Cells (MuSCs), or “satellite cells”, vital to muscle growth, homeostasis and repair. InDrosophila, adult MuSCs with similar characteristics have only recently been described. This has opened up theDrosophilasystem for analysing how MuSCs operate in muscle maintenance, repair and ageing. Here we show that theHimgene is expressed in the adult muscle progenitors (AMPs), or myoblasts, that make the adultDrosophilathoracic flight and jump muscles. Notably, we also show that Him is expressed in the flight muscle MuSCs identifyingHimas only the second genetic marker of these insect MuSCs. We then exploredHimfunction.Himmutants have disrupted organisation of the thoracic jump muscle, resulting in reduced jumping ability.Himmutants also have a reduced pool of the myoblasts that will develop into the flight muscles. In the flight muscles themselves,Himmutants have an age-dependent decrease in the number of MuSCs, indicating thatHimis required for maintenance of the adult muscle stem cell population. Moreover, this decrease in MuSCs coincides with a functional effect: there is an age-dependent decline in flight ability. Overall,Himis a novel marker of theDrosophilaadult MuSC, and is required during ageing both to maintain MuSC number and flight ability.
ABBA, a novel tool for whole-brain mapping, reveals brain-wide differences in immediate early genes induction following learning
Authors: Chiaruttini Nicolas , Castoldi Carlo , Requie Linda Maria , Camarena-Delgado Carmen , dal Bianco Beatrice , Gräff Johannes , Seitz Arne , Silva Bianca A.
Published: September 2024

Unbiased characterization of whole-brain cytoarchitecture represents an invaluable tool for understanding brain function. For this, precise mapping of histological markers from 2D sections onto 3D brain atlases is pivotal. Here, we present two novel software tools facilitating this process: Aligning Big Brains and Atlases (ABBA), designed to streamline the precise and efficient registration of 2D sections to 3D reference atlases, and BraiAn, an integrated suite for multi-marker automated segmentation, whole-brain statistical analysis, and data visualisation. Combining these tools, we performed a comprehensive comparative study of the whole-brain expression of three of the most widely used immediate early genes (IEGs). Thanks to their neural activity-dependent expression, IEGs have been used for decades as a proxy of neural activity to generate unbiased mapping of activity following behaviour, but their respective induction in response to neuronal activation across the entire brain remains unclear. To address this question, we systematically compared the brain-wide expression cFos, Arc and NPAS4, three abundantly used IEGs, across three different behavioural conditions related to memory. Our results highlight major differences in both their distribution and induction patterns, indicating that they do not represent equivalent markers across brain areas or activity states, but can provide instead complementary information.
Distinct Non-occluding Functions of Septate Junction Components in Signaling Pathway Regulation and Cell Polarity During Epithelial Development
Authors: Holtwick V. , Schubert A. , Rust K.
Published: September 2024

Occluding junctions are essential for tissue integrity and barrier function in epithelial tissues. Here we identify several non-occluding functions of septate junction components, the invertebrate occluding junctions, in follicle epithelium development. We show that the morphogenesis of the follicular stalk is an actin-driven process that requires intact apical-basal cell polarity, which is controlled by septate junction components. Septate junction components further regulate signaling pathways in a cell-type specific manner. In undifferentiated stem cells and immediate daughters, septate junction components promote effective Wnt signaling to control proliferation, while they limit Jak-STAT signaling activity induced by polar cells. Together, our data emphasize the multiple roles of septate junction components independent of their classical role in forming the paracellular barrier.
PIEZO-dependent mechano-sensing of the niche is essential for intestinal stem cell fate decision and maintenance
Authors: Baghdadi Meryem B. , Houtekamer Ronja M. , Perrin Louisiane , Rao-Bhatia Abilasha , Whelen Myles , Decker Linda , Bergert Martin , Pérez-Gonzàlez Carlos , Bouras Réda , Gropplero Giacomo , Loe Adrian KH , Afkhami-Poostchi Amin , Chen Xin , Huang Xi , Descroix Stephanie , Wrana Jeffrey L. , Diz-Muñoz Alba , Gloerich Martijn , Ayyaz Arshad , Vignjevic Danijela Matic , Kim Tae-Hee
Published: September 2024

Stem cells continuously perceive and respond to various environmental signals to maintain homeostasis. In addition to biochemical factors, the stem cell niche is subjected to mechanical and physical cues. However, it remains unclear how stem cells can sense mechanical signals from their nichein vivo. Since intestinal stem cells constantly and directly face the external environment, we investigated the roles of mechano-sensing PIEZO ion channels in the gut stem cell niche. By employing mouse genetics and performing single-cell RNAseq analysis, we revealed the absolute requirement for PIEZO channels in intestinal stem cell (ISC) state dynamics and maintenance.In vivomeasurement of basement membrane region stiffness demonstrated that ISCs reside in a more rigid microenvironment at the bottom of the crypt. Using 3D and 2D organoid systems combined with bioengineered substrates and a cell stretching device, we found that PIEZO channels are activated by high extracellular matrix stiffness and tissue tension to modulate ISC behavior. This study delineates the mechanistic cascade of PIEZO channel activation in ISCs from the upstream extracellular stimuli through the downstream signaling activation that coordinates stem cell fate decision and maintenance.
Like sisters but not twins – vasopressin and oxytocin excite BNST neurons via cell type-specific expression of oxytocin receptor to reduce anxious arousal
Authors: Francesconi Walter , Olivera-Pasilio Valentina , Berton Fulvia , Olson Susan L. , Chudoba Rachel , Monroy Lorena M. , Krabichler Quirin , Grinevich Valery , Dabrowska Joanna
Published: September 2024

Interoceptive signals dynamically interact with the environment to shape appropriate defensive behaviors. Hypothalamic hormones arginine-vasopressin (AVP) and oxytocin (OT) regulate physiological states, including water and electrolyte balance, circadian rhythmicity, and defensive behaviors. Both AVP and OT neurons project to dorsolateral bed nucleus of stria terminalis (BNSTDL), which expresses oxytocin receptors (OTR) and vasopressin receptors and mediates fear responses. However, understanding the integrated role of neurohypophysial hormones is complicated by the cross-reactivity of AVP and OT and their mutual receptor promiscuity. Here, we provide evidence that the effects of neurohypophysial hormones on BNST excitability are driven by input specificity and cell type-specific receptor selectivity. We show that OTR-expressing BNSTDLneurons, excited by hypothalamic OT and AVP inputs via OTR, play a major role in regulating BNSTDLexcitability, overcoming threat avoidance, and reducing threat-elicited anxious arousal. Therefore, OTR-BNSTDLneurons are perfectly suited to drive the dynamic interactions balancing external threat risk and physiological needs.

Graphical abstract

Highlights

Exogenous and light-evoked vasopressin (AVP) peptide excites neurons of the bed nucleus of the stria terminalis (BNST) via oxytocin receptor (OTR) in male rats

AVP excites OTR- and Corticotropin-releasing factor (CRF)-expressing neurons, most of which are classified as Type III neurons of the BNST

OTR-expressing BNST neurons increase exploration of open spaces and reduce anxious arousal in fear-potentiated startle in male rats

The dorsolateral BNST receives vasopressinergic inputs from suprachiasmatic, supraoptic, and paraventricular nuclei of the hypothalamus

Internal signal-sensitive hypothalamic inputs directly impact BNST excitability via OTR to balance interoceptive signals and defensive behaviors
Geometrically-derived action potential markers for model development: a principled approach?
Authors: Clerx Michael , Mirams Gary R
Published: September 2024

We explore whether action potential biomarkers can be rederived as functions of a linearisation of the action potential.
A universal limit for mammalian lifespan revealed by epigenetic entropy
Authors: Alba-Linares Juan José , Tejedor Juan Ramón , Fernández Agustín F. , Pérez Raúl F. , Fraga Mario F.
Published: September 2024

Age-associated DNA methylation patterns have shown strong associations with species lifespan. However, it remains unclear whether epigenetic noise levels can account for the observed differences between mammalian species. In this study, we examined the rate of loss of epigenetic information with age by measuring entropy at mammalian conserved CpG sites across a diverse range of species. Longer-lived mammals tend to gain fewer noisy CpGs with age, irrespective of whether these originate from hyper- or hypomethylation processes. Importantly, we found that the rate of epigenetic entropy gain declines in a linear fashion with species maximum lifespan, pointing to the existence of a universal limit for mammalian lifespan in the vicinity of 220 years.
GDF11 secreting cell transplant efficiently ameliorates age-related pulmonary fibrosis
Authors: Guo Li , Duchesneau Pascal , Sawula Evan , Jong Eric D. , Li Chengjin , Waddell Thomas K , Nagy Andras
Published: September 2024

Here, we present a combination of cell and gene therapy that harnesses the regenerative properties of GDF11 in age-related pulmonary fibrosis. Our genome-edited FailSafeTM-GDF11 mouse ESC line provides controlled proliferation and efficient derivation to lung progenitors while inducibly expressing GDF11. When these cells were transplanted into bleomycin-injured aged mice, they acted as a source of reparative cells, restoring the damaged alveolar epithelium. Furthermore, the transplanted cells acted as an “in situ factory”, enabling the production of GDF11 in response to the inducer drug. This approach attenuated age-associated senescence and led to the successful resolution of fibrosis. Our study presents a promising method for treating pulmonary fibrosis. Additionally, this approach offers a versatile tool that can be expanded to incorporate other regenerative and anti-aging factors. This helps overcome limitations such as high production costs and a short half-life of therapeutic factors. One of the strengths of our system is its ability to allow precise regulation of factor-expression when needed to address specific aging phenotypes.
Exploring the Exclusive Isolation ofPseudomonas syringaeinPeltigeraLichens via metabolite analysis and growth assays
Authors: Ramírez Natalia , Vinchira-Villarraga Diana , Rabiey Mojgan , Sigurbjörnsdóttir Margrét Auður , Heidmarsson Starri , Vilhelmsson Oddur , Jackson Robert W.
Published: September 2024

The specific association of the potentially plant-pathogenicPseudomonas syringaewithPeltigeralichens raises questions about the factors driving this host specificity. To explore this, the metabolic profile of seven lichen species belonging to three genera (Cladonia, Peltigera, andStereocaulon) was analysed using LC-MSMS. Additionally, we assessed the growth ofP. syringaestrains in media supplemented with extracts from each lichen species. This revealed thatPeltigeraexhibits lower metabolite richness compared to other genera, but shows a higher chemical investment in specific compounds. Growth kinetics showed comparableP. syringaegrowth across lichen-supplemented media, except forC. arbusculaandCladoniasp., where the former exhibited lower growth rates. Inhibition assays with lichen extracts showed no inhibition ofP. syringae. The lichen metabolome is predominantly composed of lipids and organic acids. Furthermore, specific compounds, such as aminoglycosides, may facilitateP. syringaepresence inPeltigeraby inhibitingBacillus subtilisand other antagonists. Additionally, compounds absent inPeltigera, like anthracene, might serve as a carbon source inhibitors likeB. velezensis.
Mitochondrial morphodynamics are modulated by physiological range of temperature and influence host cell outcomes during influenza infection
Authors: McLoughlin Grant J. , Pekosz Andrew
Published: September 2024

Influenza viruses replicate in both the cooler, upper portions of the airway and the warmer, lower portions of the respiratory tract. This study investigates how physiological ranges of temperature, specifically 33°C and 37°C, impact host cell biology and how temperature-dependent differences in host cells influence outcomes during influenza A virus infection. This study prioritizes describing mitochondrial networks due to their importance in maintaining cellular homeostasis and mediating immune responses to viral infection. The temperature at which cells are incubated significantly influences mitochondrial network morphology and mitochondrial function. Moreover, temperature-dependent changes to mitochondrial networks prior to infection result in temperature-specific changes to host cell outcomes during infection. These findings indicate that mitochondrial structure alone can modulate host cell outcomes during viral infection and that both the form and function of mitochondria directly impact influenza A virus production. While not all mitochondrial processes were shown to be affected by temperature or infection, these results highlight the importance of using physiologically relevant temperatures in respiratory pathogen research and elucidate how mitochondrial dynamics contribute to host cell outcomes during influenza A virus infection.

Importance

Respiratory viruses infect the upper and lower respiratory tract but rarely is the impact of physiological ranges of temperature (33°C to 37°C) considered. Mitochondria are central mediators of numerous physiological pathways, and their functions are often modified by virus infection. Physiological ranges of temperature can alter mitochondrial form and function, which is further impacted by virus infection. The study sheds light on how temperature can impact mitochondrial form and function in concert with virus infection.
Iron content of commercial mucin contributes to compositional stability of a cystic fibrosis airway synthetic microbiota community
Authors: Giedraitis Emily , Neve Rachel L. , Phelan Vanessa V.
Published: September 2024

In vitroculture models of mucosal environments are used to elucidate the mechanistic roles of the microbiota in human health. These models often include commercial mucins to reflect thein-siturole of mucins as an attachment site and nutrient source for the microbiota. Two types of mucins are commercially available: porcine gastric mucin (PGM) and bovine submaxillary mucin (BSM). These commercial mucins have been shown to contain iron, an essential element required by the microbiota as a co-factor for a variety of metabolic functions. In these mucin preparations, the concentration of available iron can exceed physiological concentrations present in the native environment. This unexpected source of iron influences experimental outcomes, including shaping the interactions between co-existing microbes in synthetic microbial communities used to elucidate the multispecies interactions within native microbiota. In this work, we leveraged the well-characterized iron-dependent production of secondary metabolites by the opportunistic pathogenPseudomonas aeruginosato aid in the development of a simple, low-cost, reproducible workflow to remove iron from commercial mucins. Using the mucosal environment of the cystic fibrosis (CF) airway as a model system, we show thatP. aeruginosais canonically responsive to iron concentration in the chemically defined synthetic CF medium complemented with semi-purified PGM, and community composition of a clinically relevant, synthetic CF airway microbial community is modulated, in part, by iron concentration in PGM.

IMPORTANCE

Mucins are critical components ofin vitrosystems used to model mucosal microbiota. However, crude commercial mucin preparations contain high concentrations of iron, which impacts interactions between members of the microbiota and influences interpretation of experimental results. Therefore, we developed and applied a simple, reproducible method to semi-purify commercial porcine gastric mucin as an affordable, low-iron mucin source. The development of this simplified workflow for semi-purification of commercial mucin enables researchers to remove confounding iron from a critical nutrient source when modeling clinically relevant microbial communitiesin vitro.
Design and testing of a PCR assay to quantify coliform bacteria in drinking water
Authors: Thom Claire , Moore Graeme , Weir Paul , Smith Cindy J
Published: September 2024

Here we present an enhancedlacZqPCR assay targeting β-galactosidase, encoded by lacZ, to assess coliforms in drinking water. Coliform bacteria are a diverse group of over 80 species, commonly found in enteric environments, and act as indicators of water supply contamination. Due to the significant variation among coliforms, and the size of the group designing a single target was challenging, as previous studies have demonstrated. To address this, a coliformlacZsequence database was created, and the phylogeny of the group was reviewed. The degree of phylogenetic differences both between and among different coliform genera is indeed large, raising questions about their current definition. Using the database, current and new primer sets were tested for specificity and coverage bothin silicoandin vitro. The de novo primer set, LZ1, was found to be the most effective for qPCR. When compared directly with traditional culture-based methods and flow cytometry total cell counts, the LZ1lacZqPCR assay quantifiedE. coliin drinking water down to a concentration of 1.82 x 103cfu/100mL, equivalent to 360 cfu per qPCR reaction.

Importance

Coliform bacteria and E. coli are key indicators of faecal contamination in drinking water. Compliance with U.K., U.S.A., or European regulations requires that drinking water be free of these organisms. However, the culture-based methods used to quantify these bacteria have remained unchanged for over 100 years, relying on the culturability of the organisms, sampling only a small volume at a single time point, and lacking direct correlation to pathogenic microbes. There is a pressing need for a rapid, high-throughput analysis capable of detecting coliforms more representatively, without relying solely on culturability. By analysing larger volumes or more replicates, this qPCR assay could potentially be used to assess the risk of drinking water contamination over longer periods of time, offering a more comprehensive evaluation compared to traditional, culture-dependent methods.
Nodal Modulator (NOMO) is a force-bearing transmembrane protein required for muscle differentiation
Authors: Naughton Brigitte S , Devarkar Swapnil C , Mallik Sunanda , Oxendine Stacey , Junnarkar Sanjana , Ren Yuan , Todorow Vanessa , Berro Julien , Kirstein Janine , Xiong Yong , Schlieker Christian
Published: September 2024

The endoplasmic reticulum (ER) relies on specialized membrane-shaping proteins to maintain a continuous network of sheets and tubules that host distinct biological processes. How this intricate structure of the ER membrane system is maintained under conditions of mechanical strain is incompletely understood. NOMO is an ER-resident transmembrane protein that contributes to ER morphology and is highly expressed in striated muscle. In this study, we identify a critical interface between distal Ig domains that enables NOMO to maintain ER morphology and buffer mechanical forces. By incorporating two independent tension sensors in the luminal domain of NOMO, we demonstrate that NOMO assemblies experience forces in the single piconewton (pN) range, with a significant contribution from the identified interface. These newly defined features are important, if not indispensable, for myogenesis, as interface mutations affecting mechanosensing fail to restore the essential role of NOMO during myogenesis in a C2C12 differentiation model. Moreover, NOMO depletion impairs nematode motility, underscoring a broader functional importance in muscle physiology.
Mouse nephron formation is impaired by moderate-dose arsenical exposure
Authors: Alonso Carlos Agustin Isidro , Haverfield Jenna , Regalado Gabriela , Sellami Sihem , Gagnon Natascha , Rajaram Ajay , Fiset Pierre Olivier , Ryan Aimee K , Mann Koren K , Gupta Indra R
Published: September 2024

Background

Arsenic is a naturally occurring toxicant and industrial byproduct with significant health risks. Globally, millions of people are exposed to arsenic concentrations that exceed the World Health Organization’s recommended limit of 10 μg/L. Chronic arsenic exposure is linked to an increased risk of chronic kidney disease (CKD); however, the effects of arsenic exposure on kidney development remain unclear. Eukaryotes methylate inorganic arsenic (iAsIII) using the enzyme arsenic 3 methyltransferase (As3mt), that converts it to methylated intermediates, mono and dimethyl arsonous acid (MMAIII and DMAIII), and mono and dimethyl arsonic acid (MMAV and DMAV). We hypothesized that arsenicals exposure during mouse kidney development impairs nephron formation.

Methods

Cultured mouse embryonic kidney explants were treated with inorganic arsenite (iAsIII), MMAIII, MMAV, and DMAV. Female mice harboring a humanized version ofAS3MTand wild-type mice with murineAs3mtwere exposed to iAsIII throughout gestation and weaning and their offspring were analyzed for kidney defects.

Results

Inorganic arsenic, iAsIII (200 μg/L), inhibited ureteric bud branching morphogenesis and growth of mouse kidneys at embryonic day 11.5 (E11.5) and E12.5, but not at E13.5. MMAIII, but not MMAV or DMAV, impaired ureteric bud branching and kidney explant growth. Additionally, iAsIII exposure increased apoptosis in the metanephric mesenchyme of E11.5 explants and decreasedGdnftranscription, which may explain the impairment in ureteric bud branching. Humanized mouse pups exposed to 200μg/LiAsIIIin utero, showed a 20% reduction in kidney weight normalized to body weight and a 28% reduction in nephron number, compared to kidneys of wild-type mice.

Conclusion

Exposure to arsenicals during embryonic development impairs ureteric bud branching morphogenesis and decreases nephron endowment, which may predispose to CKD in adulthood.
Enhancing fairness, transparency and accountability during tendering under Ghana’s procurement system: a systematic review
Authors: Asare Samuel Owusu , Fobiri Godfred , Bondinuba Francis Kwesi
Published: September 2024

Purpose

Ghana’s legal framework for procurement has undergone substantial reform to increase its efficacy. However, disregard for legal obligations set forth has resulted in issues of fraud, corruption and poor oversight. This study seeks to synthesize literature on the recognition of legal obligations arising from tendering procedures and measures to promote fairness, transparency and accountability under Ghana’s procurement framework.

Design/methodology/approach

Legal frameworks and publications from diverse countries have been synthesized using a systematic literature review across three databases (Scopus, JSTOR and HeinOnline) to illuminate key concepts, issues and best practices relevant to the study. Data obtained from included publications was synthesized using Sandelowski and Barroso’s two-step approach by using a qualitative meta-summary and thematic synthesis.

Findings

The study reveals that issues of conflict of interest, corruption, lack of capacity, inadequate oversight and insufficient legal follow-through hinder the effectiveness of procurement regulations. The findings highlight the need for targeted improvements in resource allocation for consistent application of transparency measures, regular publication of notices and robust enforcement of accountability mechanisms. The report proposes the creation of a common data environment for networking and information dissemination, implementing feedback systems and trust rating schemes.

Practical implications

The study contributes to the body of knowledge on procurement regulation by providing a thorough analysis of Ghana’s procurement framework. The findings will help policymakers close the observed implementation gaps by guiding the revision of current legislation and the introduction of new regulations. Research findings can be used to guide the creation of focused training courses.

Originality/value

This study, one of the first of its kind in Ghana, examines the current procurement framework, including legal obligations and implementation challenges. It contributes to the body of knowledge on the subject by providing a current and fact-based analysis as well as relevant recommendations for strengthening the framework.
Employment discrimination against transgender women in England
Authors: Drydakis Nick
Published: September 2024

Purpose

The study aimed to assess whether transgender women, who were students at a university in London, England, faced hiring discrimination when seeking employment.

Design/methodology/approach

Three comparable university classmates—a cisgender woman, a cisgender man and a transgender woman—studying Engineering applied to the same job openings. Similarly, another set of three university classmates—a cisgender woman, a cisgender man and a transgender woman—studying Social Work applied to the same job openings. The degree of discrimination was quantified by calculating the difference in the number of interview invitations received by each group.

Findings

When three comparable university classmates apply for the same job openings, the rate of interview invitations differs based on gender identity. For cisgender women, the invitation rate is 31.3%, while for cisgender men, it stands at 35.1%. However, for transgender women, the rate drops significantly to 10.4%. Additionally, transgender women face further challenges in male-dominated sectors (STEM), where their chance of being invited for a job interview is even lower compared to those in female-dominated sectors, with a reduction of 8.7 percentage points. The study also reveals that firms with written equality policies on gender identity diversity show a 25.7 percentage point increase in invitation rates for transgender women compared to firms without such policies. Furthermore, the research highlights that negative beliefs among job recruiters regarding various aspects of transgender women, including their gender identity status, disclosure, job performance, vocational relationships and turnover, contribute to their exclusion from job interviews. Moreover, for transgender women who do receive interview invitations, these tend to be for lower-paid jobs compared to those received by cisgender women (by 20%) and cisgender men (by 21.3%). This wage sorting into lower-paid vacancies suggests a penalty in terms of lower returns on education, which could drive wage and income differences.

Practical implications

Transgender women received a higher number of job interview invitations when firms had written equality policies on gender identity diversity. This outcome can help policymakers identify actions to reduce the exclusion of transgender people from the labour market.

Originality/value

The study gathers information from job recruiters to quantify the roots of hiring discrimination against transgender women. It also enables an examination of whether workplaces' written equality policies on gender identity diversity are related to transgender women’s invitations to job interviews.
Examining the carbon reduction effect of renewable resource utilization: based on national “urban mining” demonstration base
Authors: Xiao Junfu , Chen Siying , Tan Zhixiong , Chen Yanyu , Wang Jiayi , Jingwei Han
Published: September 2024

Purpose

Given the inevitable transition to renewable resource utilization and the urgent need to reduce carbon emissions, this study conducted quasi natural experiments to assess the impact of renewable resource utilization on carbon emissions based on the national “urban mining” demonstration bases (NUMDB).

Design/methodology/approach

This study uses panel data from 275 prefecture-level cities in China from 2006 to 2019. The paper selects NUMDB as the proxy variable and conducts a quasi-natural experiment using a multi-period differences-in-differences model. We examine the impact of NUMDB on reducing carbon emissions, and then deeply explore its mechanism and spatial spillover effect.

Findings

This study found that: (1) the construction of NUMDB can significantly decrease the carbon emission in the host cities; (2) NUMDB’s construction has more significantly reduced the carbon emission in regions with higher levels of circular economy development, green technology innovation, regional environmental pollution, digital economy development and financial development; (3) by means of green technology innovation, optimized energy structure, and high-quality talent aggregation, NUMDB reduces urban carbon emissions; (4) NUMDB construction positively affects the carbon reduction efficiency of neighboring regions.

Research limitations/implications

We propose corresponding policy suggestions to further promote the carbon emission reduction effect of NUMDB and develop the renewable resources industry in China based on the research findings.

Practical implications

The contributions of this paper are as follows. Our study contributes to expanding the research scope on the environmental impact of the renewable resource industry, as there are few quantitative studies in this area.

Social implications

We further consider the spatial heterogeneity of policies and analyze the carbon reduction effect of the NUMDB from the city level, which is beneficial to exploring more targeted and operable carbon reduction paths.

Originality/value

This study on identifying the causal relationship between renewable resource utilization and carbon emission reduction helps to explore the sustainable development path of renewable resource more comprehensively. Meanwhile, this paper provides a reference for other countries to improve the utilization of renewable resource and effectively reduce carbon emissions.