bluuebunny/crossref_metadata_2025 huggingface dataset:
m6A-ELISA, a simple method for quantifyingN6-methyladenosine from mRNA populations
Authors: Ensinck Imke , Sideri Theodora , Modic Miha , Capitanchik Charlotte , Toolan-Kerr Patrick , van Werven Folkert J.
Published: September 2022

N6-methyladenosine (m6A) is a widely studied and abundant RNA modification. The m6A mark regulates the fate of RNAs in various ways, which in turn, drives changes in cell physiology, development, and disease pathology. Over the last decade, numerous methods have been developed to map and quantify m6A sites genomewide through deep sequencing. Alternatively, m6A levels can be quantified from a population of RNAs using techniques such as liquid chromatography-mass spectrometry or thin layer chromatography. However, many methods for quantifying m6A levels involve extensive protocols and specialized data analysis, and often only a few samples can be handled in a single experiment. Here, we developed a simple method for determining m6A levels in mRNA populations from various sources based on enzyme-linked immunosorbent-based assay (m6A-ELISA). We have optimized various steps of m6A-ELISA such as sample preparation and the background signal resulting from the primary antibody. We validated the method using mRNA populations from budding yeast and mouse embryonic stem cells. The full protocol takes less than a day, requiring only 25 ng of mRNA. The m6A-ELISA protocol is therefore quick, cost-effective, and scalable, making it a valuable tool for determining relative m6A levels in samples from various sources that could be adapted to detect other mRNA modifications.
A Purinergic Mechanism Underlying Metformin Regulation of Hyperglycemia
Authors: Senfeld J. , Peng Q. , Shi Y. , Qian S. , Shen J.
Published: September 2022

Metformin, created in 1922, has been the first-line medication treating type 2 diabetes mellitus for almost 70 years; however, its mechanism of action has been heavily debated, partly because most prior studies used supratherapeutic concentrations exceeding 1mM. Here we report that at a clinically relevant concentration of 10 μM, metformin blocks high glucose-stimulated ATP secretion from hepatocytes mediating its antihyperglycemic action. Following glucose administration, mice demonstrate increased circulating ATP concentrations, which are prevented by metformin. Extracellular ATP through P2Y2 receptors (P2Y2R) compromises insulin-induced AKT activation and increases hepatic glucose production. In addition, metformin-dependent improvement in glucose tolerance is abolished in P2Y2R-null mice. Thus, removing the target of extracellular ATP, P2Y2R, mimics the effects of metformin, revealing a novel purinergic antidiabetic mechanism for metformin.

One-Sentence Summary

Metformin abolishes high glucose-stimulated ATP secretion, preventing purinergic mechanism-mediated hepatic insulin resistance and glucose production.
Activation of SARS-CoV-2 by trypsin-like proteases in the clinical specimens of patients with COVID-19
Authors: Igarashi Emiko , Shimada Takahisa , Yazawa Shunsuke , Saga Yumiko , Itamochi Masae , Inasaki Noriko , Hasegawa Sumiyo , Morinaga Yoshitomo , Oishi Kazunori , Tani Hideki
Published: September 2022

SARS-CoV-2 enters host cells through the angiotensin converting enzyme 2 (ACE2) receptor and/or transmembrane protease, serine 2 (TMPRSS2). Serine proteases, such as TMPRSS2 and trypsin, promote viral entry.

In this study, we investigated whether proteases increased SARS-CoV-2 infectivity using pseudotyped viruses and clinical specimens from patients with COVID-19. First, we investigated how trypsin increased infectivity using the pseudotyped virus. Our findings revealed that trypsin increased infectivity after the virus was adsorbed on the cells, but no increase in infectivity was observed when the virus was treated with trypsin. We examined the effect of trypsin on SARS-CoV-2 infection in clinical specimens and found that the infectivity of the SARS-CoV-2 delta variant increased 36,000-fold after trypsin treatment. By contrast, the infectivity of SARS-CoV-2 omicron variant increased to less than 20-fold in the clinical specimens. Finally, infectivity of clinical specimens containing culture supernatants of Fusobacterium necrophorum was increased from several- to 10-fold. Because SARS-CoV-2 infectivity increases in the oral cavity, which may contain anaerobic bacteria, keeping the oral cavities clean may help prevent SARS-CoV-2 infection.

Importance

In this study, we examined whether trypsin-like proteases increased the infectivity of SARS-CoV-2. We found that trypsin-like proteases increased the infectivity of both the pseudotyped viruses and the live virus in the clinical specimens. The increase in infectivity was significantly higher for the delta than the omicron variant. A large amount of protease in the oral cavity during SARS-CoV-2 infection is expected to increase infectivity. Therefore, keeping the oral cavity clean is important for preventing infection.
The Arabidopsis SHORTROOT network coordinates shoot apical meristem development with auxin dependent lateral organ initiation
Authors: Bahafid Elmehdi , Bradtmöller Imke , Thies Ann Marlene , Nguyen Thi Thuy Oanh Nicole , Gutierrez Crisanto , Desvoyes Bénédicte , Stahl Yvonne , Blilou Ikram , Simon Rüdiger
Published: September 2022

Unlike animals, plants have the capacity to produce new organs post-embryonically throughout their entire life cycle. This is due to stem cells present in the shoot and the root apical meristems (SAM and RAM, respectively). In the SAM, stem cells are located in the central zone (CZ) where they divide slowly. Stem cell daughters are displaced laterally and enter the peripheral zone (PZ). Here, their mitotic activity increases, and lateral organ primordia (LOP) are formed. How the spatial arrangement of these different domains is initiated and controlled during SAM growth and development, and how sites of LOP are determined in the PZ is not yet completely understood.

In the RAM, the GRAS family transcription factor SHORTROOT (SHR) acts as a master regulator of signalling pathways that maintain the root stem cell niche and control formation of ground tissue layers. We hypothesized that SHR could perform a similar role in the SAM, and found that SHR, together with its target transcription factors SCARECROW (SCR), SCARECROW-LIKE23 (SCL23) and JACKDAW (JKD), controls shoot meristem size by regulating cell division rates, and promotes formation of lateral organs. SHR, SCR, SCL23 and JKD are expressed in very distinct patterns in the SAM. Where these expression domains overlap, they can physically interact to activate expression of the key cell cycle regulator CYCLIND6;1 (CYCD6;1) and thereby promote the formation of new cell layers.

In the PZ, upregulation of SHR expression at sites of organ initiation depends on the phytohormone auxin, acting through the auxin response factor MONOPTEROS (MP) and auxin response elements in the SHR promoter. In the CZ, the SHR-target SCL23 physically interacts with WUS, a key regulator of stem cell maintenance, and both SCL23 and WUS expression are subject to negative feedback regulation from stem cells through the CLAVATA signalling pathway. Together, our findings illustrate how SHR-dependent transcription factor complexes act in different domains of the shoot meristem to mediate cell division and auxin dependent organ initiation in the PZ, and coordinate this activity with stem cell maintenance in the CZ of the SAM.
School Distress in UK school children: A story dominated by neurodivergence and unmet needs
Authors: Connolly Sophie E. , Constable Hannah , Mullally Sinéad L.
Published: September 2022

Background

The Covid-19 pandemic has brought into sharp focus a school attendance crisis in many countries, although this likely pre-dates the pandemic. Children and young people (CYP) with school attendance problems (SAPs) often display extreme emotional distress when required to attend school. We term this School Distress (SD). Here we sought to elucidate the characteristics of the CYP struggling to attend school in the UK.

Methods

Using a case-control, concurrent embedded mixed-method research design, 947 parents of CYP with experience of SD completed a bespoke online questionnaire (February/March 2022), alongside an aged-matched control group (n=149) and a smaller group of parents who electively home-educate (n=25).

Results

In 94.3% of cases, SAPs were underpinned by significant emotional distress, with often harrowing accounts of this distress provided by parents. Whilst the mean age of the CYP in this sample was 11.6 years (StDev 3.1 years), their SD was evident to parents from a much younger age (7.9 years). Notably, 92.1% of CYP currently experiencing SD were described as neurodivergent (ND) and 83.4% as autistic. The Odds Ratio of autistic CYP experiencing SD was 46.61 (95% CI [24.67, 88.07]). Autistic CYP displayed SD at a significantly earlier age, and it was significantly more enduring. Multi-modal sensory processing difficulties and ADHD (amongst other ND conditions) were also commonly associated with SD; with SD CYP having an average of 3.62 NDs (StDev 2.68). In addition, clinically significant anxiety symptomology (92.5%; ASC-ASD-P) and elevated demand avoidance (EDA-8) were also pervasive. Mental health difficulties in the absence of a ND profile were, however, relatively rare (6.17%). Concerningly, despite the striking levels of emotional distress and disability reported by parents, parents also reported a dearth of meaningful support for their CYP at school.

Conclusion

Whilst not a story of exclusivity relating solely to autism, SD is a story dominated by complex neurodivergence and a seemingly systemic failure to meet the needs of these CYP in UK schools. Given the disproportionate number of disabled CYP impacted, we ask whether the UK is upholding its’ responsibility to ensure the “right to an education” for all CYP (Human Rights Act 1998).
Cardiorespiratory signature of neonatal sepsis: Development and validation of prediction models in 3 NICUs
Authors: Kausch Sherry L. , Brandberg Jackson G. , Qiu Jiaxing J. , Panda Aneesha , Binai Alexandra , Isler Joseph , Sahni Rakesh , Vesoulis Zachary A. , Moorman J. Randall , Fairchild Karen D. , Lake Douglas E. , Sullivan Brynne A.
Published: September 2022

Background

Heart rate characteristics aid early detection of late-onset sepsis (LOS), but respiratory data contain additional signatures of illness due to infection. Predictive models using cardiorespiratory data may improve early sepsis detection. We hypothesized that heart rate (HR) and oxygenation (SpO2) data contain signatures that improve sepsis risk prediction over HR or demographics alone.

Methods

We analyzed cardiorespiratory data from very low birth weight (VLBW, <1500g) infants admitted to three NICUs. We developed and externally validated four machine learning models to predict LOS using features calculated every 10m: mean, standard deviation, skewness, kurtosis of HR and SpO2, and cross-correlation. We compared feature importance, discrimination, calibration, and dynamic prediction across models and cohorts. We built models of demographics and HR or SpO2 features alone for comparison with HR-SpO2 models.

Results

Performance, feature importance, and calibration were similar among modeling methods. All models had favorable external validation performance. The HR-SpO2 model performed better than models using either HR or SpO2 alone. Demographics improved the discrimination of all physiologic data models but dampened dynamic performance.

Conclusions

Cardiorespiratory signatures detect LOS in VLBW infants at 3 NICUs. Demographics risk-stratify, but predictive modeling with both HR and SpO2 features provides the best dynamic risk prediction.
Comparative IgG responses to SARS-CoV-2 after natural infection or vaccination
Authors: Olds Kaylan M. , Humphreys Devon P. , Gavin Kathleen M. , Wyllie Anne L. , Bauer Timothy A.
Published: September 2022

Background

Whether vaccination or natural infection provides greater benefit regarding the development of sustained immunity against SARS-CoV-2 remains unknown. Therefore, the aim of this study was to provide a direct comparison of IgG durability in vaccinated and unvaccinated adults.

Methods

This was a prospective, cross-sectional study of antibody durability in 1087 individuals with a median (IQR) age of 42 (35, 52) years who were unvaccinated and previously infected with SARS-CoV-2 (Arm 1, n=351) or vaccinated against the virus (Arm 2, n=737). Participants self-reported vaccination and infection history and provided self-collected serology samples using mailed collection kits.

Results

Anti-S1 IgG seroprevalence was 15.6% higher in vaccinated versus unvaccinated, previously-infected individuals across intervals ranging from 1 to 12 months and antibody survival was sustained near 100% through 12 months in the vaccinated group.

Conclusions

These findings suggest that vaccination as opposed to natural infection alone provides significant advantages in terms of sustained and effective immunity against prior variants of SARS-CoV-2. Future efforts to characterize SARS-CoV-2 immune responses should address hybrid immunity, booster status and formulation, and protection against (sub)variants of Omicron and future lineages, as well as weigh the potential impact of other immune system mechanisms.
Sudden cardiac death in the young: A qualitative study of experiences of family members with cardiogenetic evaluation
Authors: van den Heuvel Lieke , Do Judy , Yeates Laura , Burns Charlotte , Semsarian Chris , Ingles Jodie
Published: September 2022

Introduction

Sudden cardiac death (SCD) is a devastating event for the family and the community, especially when it occurs in a young person (<45 years). Genetic heart diseases, including cardiomyopathies and primary arrhythmia syndromes, are an important cause of SCD in the young. Although cardiogenetic evaluation, i.e., clinical evaluation, genetic testing and psychological support, is increasingly performed after SCD, it is unknown how suddenly bereaved family members experience the process. We aimed to explore the experiences of family members with cardiogenetic evaluation after SCD, and their perception of the process and care received.

Methods

In-depth interviews were conducted with eighteen family members of young people (<45 years old) who died suddenly, including parents, siblings and partners. The interviews were thematically analysed by two researchers independently.

Results

In total, 18 interviews were conducted from 17 families. The following themes were identified: (1) Experiences with postmortem genetic testing including managing expectations and psychological impact, (2) appreciation of care such as access to genetic counselling and relief following cardiac evaluation of relatives, and (3) need for support including unmet psychological support needs and better coordination of care immediately after the death.

Conclusion

Although participants appreciated the opportunity for cardiogenetic evaluation, they also experienced a lack of coordination of cardiogenetic and psychological care. Our findings stress the importance of access to expert multidisciplinary teams, including psychological care, to adequately support these families after a SCD in a young family member.
eIF4E phosphorylation recruits β-catenin to mRNA cap and selectively promotes Wnt pathway translation in dentate gyrus LTP maintenance in vivo
Authors: Patil Sudarshan , Chalkiadaki Kleanthi , Mergiya Tadiwos Feyissa , Simbriger Konstanze , Amorim Inês S. , Akerkar Shreeram , Gkogkas Christos G. , Bramham Clive R.
Published: September 2022

The mRNA cap-binding protein, eukaryotic initiation factor 4E (eIF4E), is crucial for translation and regulated by Ser209 phosphorylation. However, the biochemical and physiological role of eIF4E phosphorylation in translational control of long-term synaptic plasticity is unknown. We demonstrate that phospho-ablated Eif4eS209A knockin mice are profoundly impaired in dentate gyrus LTP maintenance in vivo, while basal perforant path-evoked transmission and LTP induction are intact. mRNA cap-pulldown assays show that phosphorylation is required for synaptic activity-induced removal of translational repressors from eIF4E, allowing initiation complex formation. Using ribosome profiling, we identified selective, phospho-eIF4E-dependent translation of the Wnt signaling pathway in in vivo LTP. Surprisingly, the canonical Wnt effector, β-catenin, was massively recruited to the eIF4E cap complex following LTP induction in wild-type, but not Eif4eS209A, mice. These results demonstrate a critical role for activity-evoked eIF4E phosphorylation in dentate gyrus LTP maintenance, bidirectional remodeling of the mRNA cap-binding complex, and mRNA-specific translational control linked to Wnt pathway.

Key highlights

Synaptic activity-induced eIF4E phosphorylation controls DG-LTP maintenance in vivo

eIF4E phosphorylation triggers release of translational repressors from cap complex

eIF4E phosphorylation recruits β-catenin to cap complex

eIF4E phosphorylation selectively enhances translation of Wnt pathway
Integrated single-cell chromatin and transcriptomic analyses of human scalp reveal etiological insights into genetic risk for hair and skin disease
Authors: Ober-Reynolds Benjamin , Wang Chen , Ko Justin M , Rios Eon J , Aasi Sumaira Z , Davis Mark M , Oro Anthony E , Greenleaf William J
Published: September 2022

Genome-wide association studies (GWAS) of hair and skin disease have identified many genetic variants associated with disease phenotypes, but identifying causal variants and interpreting their function requires deciphering gene-regulatory networks in disease-relevant cell types. To this end, we generated matched scRNA- and scATAC-seq profiles of human scalp biopsies, identifying diverse cell types of the hair follicle niche. By interrogating the integrated datasets across multiple levels of cellular resolution, we infer 50-100% more enhancer-gene links than prior approaches, and show that the aggregate accessibility at linked enhancers for highly-regulated genes predicts expression. We use these gene-regulatory maps to prioritize cell types, genes, and causal variants implicated in the pathobiology of androgenetic alopecia (AGA), eczema, and other complex traits. AGA GWAS signals are strongly and specifically enriched in dermal papilla cell open chromatin regions, supporting the role of these cells as key drivers of AGA pathogenesis. Finally, we trained machine-learning models to nominate SNPs that affect gene expression through disruption of specific transcription factor binding motifs, identifying candidate functional SNPs linked to expression of WNT10A in AGA and IL18RAP in eczema. Together, this work reveals principles of gene regulation and identifies gene regulatory consequences of natural genetic variation in complex skin and hair diseases.
Bacteriophages targeting protective commensals impair resistance againstSalmonellaTyphimurium infection in gnotobiotic mice
Authors: von Strempel Alexandra , Weiss Anna S. , Wittmann Johannes , Salvado Silva Marta , Ring Diana , Wortmann Esther , Clavel Thomas , Debarbieux Laurent , Kleigrewe Karin , Stecher Bärbel
Published: September 2022

Gut microbial communities protect the host against a variety of major human gastrointestinal pathogens. Bacteriophages (phages) are ubiquitous in nature and frequently ingested via food and drinking water. Moreover, they are an attractive tool for microbiome engineering due to the lack of known serious adverse effects on the host. However, the functional role of phages within the gastrointestinal microbiome remain poorly understood. Here, we investigated the effects of microbiota-directed phages on infection with the human enteric pathogenSalmonella entericaserovar Typhimurium (S. Tm), using a gnotobiotic mouse model (OMM12) for colonization resistance (CR). We show that phage cocktails targetingEscherichia coliandEnterococcus faecalisacted in a strain-specific manner. They transiently reduced the population density of their respective target before establishing coexistence for up to 9 days. Infection susceptibility toS. Tm was markedly increased at an early time point after phage challenge. Surprisingly, OMM12mice were more susceptible 7 days after a single phage inoculation, when the targeted bacterial populations were back to pre-phage administration density. The presence of phages that dynamically modulates the density of protective members of the gut microbiota provides opportunities for invasion of bacterial pathogens.
svep1 and tie1 genetically interact and affect aspects of facial lymphatic development in a Vegfc-independent manner
Authors: Hußmann Melina , Weischer Sarah , Carlantoni Claudia , Stainier Didier Y. R. , Zobel Thomas , Schulte-Merker Stefan
Published: September 2022

Multiple factors are required to form functional lymphatic vessels. Here, we uncover an essential role for the secreted protein Svep1 and the transmembrane receptor Tie1 during the development of subpopulations of the zebrafish facial lymphatic network. This specific aspect of the facial network forms independently of Vegfc signalling, which otherwise is the most prominent signalling axis in all other lymphatic beds. Additionally, we find that multiple specific and newly uncovered phenotypic hallmarks of svep1 mutants are also present in tie1, but not in tie2 or vegfc mutants. These phenotypes are observed in the lymphatic vasculature of both head and trunk, as well as in the development of the dorsal longitudinal anastomotic vessel (DLAV) under reduced flow conditions. Furthermore, we show genetic interaction between svep1 and tie1 during the migration of parachordal lymphangioblasts (PLs). Therefore, our study demonstrates an important function for Tie1 signalling during lymphangiogenesis as well as blood vessel development in zebrafish and provides the first in vivo evidence for zebrafish Svep1 and Tie1 interaction. Since compound heterozygous mutations for SVEP1 and TIE2 have recently been reported in human glaucoma patients, our data have clinical relevance in demonstrating a role for Svep1 in Tie signalling in an in vivo setting.
A host defense peptide mimetic, brilacidin, potentiates caspofungin antifungal activity against human pathogenic fungi
Authors: Fernanda dos Reis Thaila , Alves de Castro Patrícia , Bastos Rafael Wesley , Pinzan Camila Figueiredo , Souza Pedro F. N. , Ackloo Suzanne , Hossain Mohammad Anwar , Drewry David Harold , Alkhazraji Sondus , Ibrahim Ashraf S. , Jo Hyunil , deGrado William F. , Goldman Gustavo H.
Published: September 2022

A. fumigatus is the main etiological agent of a group of heterogeneous diseases called aspergillosis of which the most lethal form is the invasive pulmonary aspergillosis (IPA). Fungicidal azoles and amphotericin B are the first line defense against A. fumigatus, but fungistatic echinocandins, such as caspofungin (CAS), can be used as salvage therapy for IPA. Here, we screened repurposing libraries and identified several compounds that potentiate CAS activity against A. fumigatus, including the host defense peptide mimetic, brilacidin (BRI). BRI converts CAS into a fungicidal drug and potentiates voriconazole (VOR) against A. fumigatus. BRI increases the ability of both CAS and VOR to control A. fumigatus biofilm growth. BRI depolarizes the A. fumigatus cell membrane leading to disruption of membrane potential. By using a combination of protein kinase inhibitors and screening of a catalytic subunit null mutant library, we identified the mitogen activated protein kinase (MAPK) MpkA and the phosphatase calcineurin as mediators of the synergistic action of BRI. These results suggest the most likely BRI mechanism of action for CAS potentiation is the inhibition of A. fumigatus cell wall integrity (CWI) pathway. BRI potentiates CAS activity against C. albicans, C. auris, and C. neoformans. Interestingly, BRI overcomes the CAS-acquired resistance in both A. fumigatus and C. albicans and the CAS-intrinsic resistance in C. neoformans. BRI also has an additive effect on the activity of posaconazole (POSA) against several Mucorales fungi. Cell toxicity assays and fungal burden studies in an immunosuppressed murine model of IPA showed that BRI combined with CAS is not toxic to the cells and significantly clears A. fumigatus lung infection, respectively. Our results indicate that combinations of BRI and antifungal drugs in clinical use are likely to improve the treatment outcome of IPA and other fungal infections.
The generation of the first chromosome-level de-novo genome assembly and the development and validation of a 50K SNP array for North American Atlantic salmon
Authors: Gao Guangtu , Waldbieser Geoffrey C. , Youngblood Ramey C. , Zhao Dongyan , Pietrak Michael R. , Allen Melissa S. , Stannard Jason A. , Buchanan John T. , Long Roseanna L. , Milligan Melissa , Burr Gary , Mejía-Guerra Katherine , Sheehan Moira J. , Scheffler Brian E. , Rexroad Caird E. , Peterson Brian C. , Palti Yniv
Published: September 2022

Given the genetic and genomic differences between Atlantic salmon of European origin and North American (N.A.) origin, it is crucial to develop unique genomic resources for each lineage. Here we describe the resources that we recently developed for genomic and genetic research in N.A. Atlantic salmon. Firstly, a new single nucleotide polymorphism (SNP) database for N.A. Atlantic salmon consisting of 3.1 million putative SNPs was generated using data from whole genome resequencing of 80 N.A. Atlantic salmon individuals; Secondly, a high density 50K SNP array enriched for the genic regions of the genome and containing three sex determination and 61 continent of origin markers was developed and validated; Thirdly, a genetic map composed of 27 linkage groups with 36K SNP markers, was generated from 2,512 individuals in 141 full-sib families; Finally, a chromosome level de-novo assembly of a male N.A. Atlantic salmon genome was generated using PacBio long-reads. Information from Hi-C proximity ligation sequences and Bionano optical mapping was used to concatenate the contigs into scaffolds. The assembly contains 1,755 scaffolds and only 1,253 gaps, with a total length of 2.83 Gb and N50 of 17.2 Mb. A BUSCO analysis detected 96.2% of conserved Actinopterygii genes in the assembly and the genetic linkage information was used to guide the formation of 27 chromosome sequences. In contrast, the karyotype of the European Atlantic salmon lineage is composed of 29 chromosomes. Comparative analysis with the reference genome assembly of the European Atlantic salmon confirmed that the karyotype differences between the two linages are caused by a fission in chromosome Ssa01 and three chromosome fusions including the p arm of chromosome Ssa01 with Ssa23, Ssa08 with Ssa29 and Ssa26 with Ssa28. The genomic resources we have generated for Atlantic salmon provide a crucial boost for genetic research and for management of farmed and wild populations in this highly valued species.
Synthetic carbon fixation via the autocatalytic serine threonine cycle
Authors: Wenk Sebastian , Rainaldi Vittorio , He Hai , Schann Karin , Bouzon Madeleine , Döring Volker , Lindner Steffen N. , Bar-Even Arren
Published: September 2022

Atmospheric CO2 poses a major threat to life on Earth by causing global warming and climate change. On the other hand, it is the only carbon source that is scalable enough to establish a circular carbon economy. Accordingly, technologies to capture and convert CO2 to reduced one-carbon (C1) molecules (e.g. formate) using renewable energy are improving fast. Driven by the idea of creating sustainable bioproduction platforms, natural and synthetic C1-utilization pathways are engineered into industrially relevant microbes. The realization of synthetic C1-assimilation cycles in living organisms is a promising but challenging endeavour. Here, we engineer the autocatalytic serine threonine cycle, a synthetic C1-assimilation route in Escherichia coli. Our stepwise engineering approach in tailored selection strains combined with adaptive laboratory evolution experiments enabled the organism to grow on formate. The synthetic strain uses formate as the sole carbon and energy source and is capable of growing at ambient CO2 concentrations, demonstrating the feasibility of establishing synthetic C1-assimilation cycles over laboratory timescales.
Meta-analysis refinement of plasma extracellular vesicle composition identifies proplatelet basic protein as a signaling messenger in type 1 diabetes
Authors: Vallejo Milene C. , Sarkar Soumyadeep , Elliott Emily C. , Henry Hayden R. , Huang Fei , Payne Samuel H. , Ramanadham Sasanka , Sims Emily K. , Metz Thomas O. , Mirmira Raghavendra G. , Nakayasu Ernesto S.
Published: September 2022

Extracellular vesicles (EVs) play important roles in cell-to-cell communication and are potential biomarkers as they carry markers of their derived tissues and disease signatures. However, obtaining pure EV preparations from biofluids is challenging due to contaminants with similar physicochemical properties. Here, we performed a meta-analysis of plasma EV proteomics data deposited in public repositories to refine the protein composition of EVs and investigate potential roles in type 1 diabetes development. With the concept that each purification method yields different proportions of distinct contaminants, we grouped proteins into clusters based on their abundance profiles. This allowed us to separate clusters with classical EV markers, such as CD9, CD40, C63 and CD81, from clusters of well-known contaminants, such as serum albumin, apolipoproteins and components of the complement and coagulation pathways. Two clusters containing a total of 1720 proteins combined were enriched with EV markers and depleted in common contaminants; therefore, they were considered to containbona fideEV components. As possible origins of plasma EVs, these clusters had markers of tissues such as spleen, liver, brain, lungs, pancreas, and blood/immune cells. These clusters were also enriched in cell surface markers CD antigens, and proteins from cell-to-cell communication and signaling pathways, such as chemokine signaling and antigen presentation. We also show that the EV component and type 1 diabetes biomarker, platelet basic protein (PPBP/CXCL7) regulates apoptosis in both beta and macrophage cell lines. Overall, our meta-analysis refined the composition of plasma EVs, reinforcing a primary function as messengers for cell-to-cell communication and signaling. Furthermore, this analysis identifies optimal avenues to target EVs for development of disease biomarkers.
Identification and management of thyroid dysfunction using at-home sample collection and telehealth services
Authors: Gavin Kathleen M. , Kreitzberg Daniel , Gaudreau Yvette , Cruz Marisa , Bauer Timothy A.
Published: September 2022

Introduction

Programs aimed at modernizing thyroid care by pairing at-home sample collection methods with telehealth options may serve an important and emerging role in thyroid care. The primary objective of this analysis was to evaluate telehealth utilization, demographics, and clinical characteristics of a cohort of consumer initiated at-home lab thyroid test users who were also offered the option of follow-up telehealth consultations.

Methods

This was a retrospective analysis of real-world data from a de-identified consumer database of home-collected, mail-in Thyroid Tests utilized from March to May 2021 (n=8,152). The mean age was 38.6 (range 18-85) years and 86.6% of individuals identified as female.

Results

Seven percent of test takers fell into a thyroid dysfunction category (0.9% overthypothyroidism, 2.9% subclinical hypothyroidism, 0.1% overt-hypothyroidism, and 3.3% subclinical-hyperthyroidism). Twelve percent of the overall sample opted into a telehealth consultation, with 91.8% receiving a non-treatment telehealth consultation and 8.2% receiving a treatment telemedicine consultation. Sixteen percent of individuals with overt or subclinical thyroid dysfunction engaged in telehealth consultations. Of those opting into a treatment consultation, 59.3% reported a history of thyroid issues, 55.6% indicated wanting to discuss their current thyroid medication, and 48% received a prescription medication.

Discussion

The combination of at-home sample collection and telehealth is an innovative model for screening for thyroid disorders, monitoring thyroid function, and increasing access to care that can be implemented at a large scale and across a wide range of age groups.
The use of social media for a better world: roles of social experience, empathy and personal impulsiveness in charitable crowdfunding
Authors: Li Boying , Hou Fangfang , Guan Zhengzhi , Chong Alain Yee Loong
Published: September 2022

Purpose

Charitable crowdfunding features are embedded in social media platforms to encourage pro-social behaviors. Although such new practice allows practitioners to leverage the power of a highly connected crowd, accomplishing the fundraising goal is still a challenge. This study seeks to understand what drives the donation intention in charitable crowdfunding features on social media platforms by examining the roles of social experience, empathy and personal impulsiveness.

Design/methodology/approach

A survey questionnaire was distributed to social media users in China to collect data. A total of 206 valid responses were analyzed using structural equation modeling to test the proposed hypotheses.

Findings

The results showed that empathy mediates interaction with the fundraiser and perceived proximity with the donatee on a user's donation intention. We also found that social influence on social media platforms positively influences empathy and donation intention. In addition, personal impulsiveness was found to moderate the relationship between empathy and donation intention.

Originality/value

This study contributes to existing literature and practices. It identifies three dimensions of social experience and examines their effects on donation intention, providing insights into the charitable crowdfunding features on social media. Moreover, this study extends the understanding to empathy by delineating its mediating role in the relationship between social experience and donation intention and examining how personal impulsiveness moderates the effect of empathy on donation intention. Furthermore, this study provides valuable insights for practitioners to craft strategies to stimulate pro-social behaviors and increase donations.
Realizing dynamic capabilities and organizational knowledge in effective innovations: the capabilities typological map
Authors: Cordeiro Marcelo , Puig Francisco , Ruiz-Fernández Lorena
Published: September 2022

Purpose

This paper aims to shed light on the mechanisms that connect dynamic capabilities and organizational knowledge in the innovative process to offer a new theoretical and practical solution considering the microfoundations of knowledge management strategies.

Design/methodology/approach

This research has emerged from an in-depth case study of an effective innovation (from just ethanol and sugar-production to an effective biomass plant). The study represents an “inductive inquiry,” useful to understand specific “organizational mechanisms” of innovation, where the main data came from in-depth interviews with 18 key actors. It proved to help search the development of a specific biomass plant, designed and implemented between 2000 and 2007 in a Brazilian ethanol and sugar-production large company, referred to here as “Energyplant.”

Findings

This solution provides a new perspective based on the idea that dynamic capabilities are context-dependent and presents an original typological map that shows and materializes dynamic capabilities as teams of human-based resources. Managerial implications can be drawn from the capabilities typological map highlighting that, although identical dynamic capabilities are not required to change different firms, idiosyncratic dynamic capabilities perform universal knowledge functions that can be mapped, contributing to the planning of a specific innovation.

Originality/value

While the dynamic capabilities research has been seen as one of the most vibrant topics in strategic management, scholars have recently stressed that dynamic capabilities continue to be underrated because the knowledge mechanisms that lead to effective innovations have not been adequately explored. The visual mapping is then applied to solve the reviewed theoretical problems, being also suggested to firms interested in change and adapting their capabilities to the requirements of the business environment.
Being authentic by sharing team vision: mediating role of strengths use within a team
Authors: Matsuo Makoto
Published: September 2022

Purpose

Authenticity, or the extent to which individuals act in accordance with their values, beliefs and characteristics, is recognized as a key component of a fulfilled life. However, little is known about its antecedents in an organizational context. Drawing on goal-setting theory and the broaden-and-build theory, the current study examined the role of team leaders' perceived shared vision in promoting their work authenticity, mediated through strengths use support (SUS) for members as well as leaders' strengths use.

Design/methodology/approach

A two-wave questionnaire survey was conducted to test the hypotheses using a sample of 325 middle managers of a manufacturing firm.

Findings

The results of structural equation modeling show that perceived shared vision promoted work authenticity, mediated through SUS and strengths use.

Originality/value

This study is the first to identify that shared goals can trigger authenticity at work by directing the leader to use their strengths, alongside their team members.
Accounting, hybrids and hybridity – attending to the value dimension in institutional logics
Authors: Ahrens Thomas , Ferry Laurence
Published: September 2022

Purpose

This study is concerned with the institutional value dimension in recent accounting research into hybrids and hybridity. Such research has been cognitively oriented and neglected the affective and emotional qualities of the values in which institutions are grounded. This study assumes that organisational members use accounting for instrumental reasons conditioned by objective facts. This study aims to offer new impetus to this literature by taking seriously the nature of institutional value.

Design/methodology/approach

Essay combined with discussion of published work.

Findings

Cognitive misinterpretations of institutional value underplay the force of institutions. One acts upon these not as a matter of cognitive choice but because of beliefs in deeply held values. In the extreme, the value possesses the actor not vice versa. However, because institutional values are ideal and abstract, they can never be fully and incontrovertibly achieved in practice. Certain practices, such as accounting, can come to stand in for the pursuit of the institutional value. In particular contexts, practicing accounting can come to be regarded as pursing institutional values, which makes it an institutional object.

Originality/value

The explication of accounting as an institutional object can show the potential significance of accounting for institutional values, including hybrid values.
Cognitive diversity, creativity and team effectiveness: the mediations of inclusion and knowledge sharing
Authors: Mathuki Evelyn , Zhang Jian
Published: September 2022

Purpose

This study aims to determine how cognitive diversity at the workplace influences team creativity. In this regard, the authors examined knowledge sharing and team-focused inclusion through which team members’ cognitive diversity was expected to elevate their positive work outcomes.

Design/methodology/approach

A quantitative method is used to accumulate the data. The authors surveyed workers and their respective managers at a single China-based food company. The supervisors rated the outcome variables (creativity and team effectiveness) regarding their employees, whereas employees were asked to rate the cognitive diversity, inclusion and knowledge sharing within the workgroup. The final valid sample size (n = 391) consisted of 137 workgroups with an adequate response rate (62.3%).

Findings

Cognitive diversity is related to team effectiveness but not creativity. The research found that cognitive diversity can increase creativity only through enhanced inclusion and knowledge sharing. Inclusion, likewise, explained the impact of cognitive diversity on effectiveness.

Originality/value

The originality of the current research lies in its contemporary exploration of inclusion and cognitive diversity and their pathways to team creativity and effectiveness. The social capital theory was applied to explain the proposed relationships.
Components of emotion regulation flexibility and psychosis: The association between psychosis‐proneness and context sensitivity
Authors: Bortolon Catherine , Chen Shuquan , Bonanno George A.
Published: September 2022

Objectives

Emotion regulation flexibility has been conceptualized as a multi‐componential construct involving context sensitivity, repertoire and feedback responsiveness. Psychosis research has yet to incorporate these new developments in the study of emotion regulation. Thus, we sought to advance even further the knowledge on emotion regulation in psychosis by adopting the emotion regulation flexibility approach as proposed by Bonanno and Burton (Perspectives on Psychological Science, 2013, 8, 591).

Method

In total, 401 participants completed 4 scales assessing the multi‐components of emotion regulation flexibility and psychosis‐proneness.

Results

Our results indicated that Context Sensitivity (i.e., Cue Absence) and Feedback Responsiveness (i.e., Evaluation) were associated with psychosis‐proneness. Cue absence was specifically associated with the positive dimension, while both Cue Absence and Enhancement ability were associated with the negative dimension.

Conclusions

Overall, our results suggest that emotional context insensitivity is the most relevant component of regulatory flexibility in the case of psychosis‐proneness. Thus, the disruption in this first step of flexible emotion regulation might be already present in those prone to psychosis. Difficulties in decoding appropriately the contextual cues might further disrupt the other steps of emotion regulation contributing to the psychotic (−like) experiences. This study needs replication in clinical and non‐clinical samples.
Adaptive, maladaptive, neutral, or absent plasticity: Hidden caveats of reaction norms
Authors: Eriksson Martin , Kinnby Alexandra , De Wit Pierre , Rafajlović Marina
Published: September 2022

Adaptive phenotypic plasticity may improve the response of individuals when faced with new environmental conditions. Typically, empirical evidence for plasticity is based on phenotypic reaction norms obtained in reciprocal transplant experiments. In such experiments, individuals from their native environment are transplanted into a different environment, and a number of trait values, potentially implicated in individuals' response to the new environment, are measured. However, the interpretations of reaction norms may differ depending on the nature of the assessed traits, which may not be known beforehand. For example, for traits that contribute to local adaptation, adaptive plasticity implies nonzero slopes of reaction norms. By contrast, for traits that are correlated to fitness, high tolerance to different environments (possibly due to adaptive plasticity in traits that contribute to adaptation) may, instead, result in flat reaction norms. Here we investigate reaction norms for adaptive versus fitness‐correlated traits and how they may affect the conclusions regarding the contribution of plasticity. To this end, we first simulate range expansion along an environmental gradient where plasticity evolves to different values locally and then perform reciprocal transplant experiments in silico. We show that reaction norms alone cannot inform us whether the assessed trait exhibits locally adaptive, maladaptive, neutral, or no plasticity, without any additional knowledge of the traits assessed and species' biology. We use the insights from the model to analyse and interpret empirical data from reciprocal transplant experiments involving the marine isopod Idotea balthica sampled from two geographical locations with different salinities, concluding that the low‐salinity population likely has reduced adaptive plasticity relative to the high‐salinity population. Overall, we conclude that, when interpreting results from reciprocal transplant experiments, it is necessary to consider whether traits assessed are locally adaptive with respect to the environmental variable accounted for in the experiments or correlated to fitness.
Should We Give All We Have to Live On? A Theological Proposal for the Ethics of Generosity
Authors: Blosser Andrew
Published: September 2022

Recent ethical literature has called attention to subtle yet profound difficulties in determining what types of generosity are moral, and what situations call for generosity. This article contributes to this discussion by advancing a perspective drawn from Christian theology, according to which philanthropic endeavours must follow a downwards trajectory, modelled on God’s self‐donation. Once this model is understood, potentially problematic rhetorical frameworks of generosity—such as that of Anselm of Canterbury—can be identified. This article further argues that the downwards trajectory of generosity has important implications for institutions that use philanthropic rhetoric in their fundraising, as well as for philosophers seeking to establish conditions for ethical generosity.
Brilliance and Blindspots: New Light on C.S. Lewis’s The Four Loves
Authors: Lepojärvi Jason
Published: September 2022

This paper is a critical re‐evaluation of C.S. Lewis’s classic study of Christian love, The Four Loves (1960) that celebrated its 60th anniversary in 2020. After discussing important and neglected differences between the celebrated book and the largely forgotten radio talks which predate it, the paper asks and answers three important questions: Are there really four loves? What is the definition of love itself? What exactly is Charity? Lewis’s answers to these questions are more eclectic than is generally assumed. The paper offers an appreciative rereading of The Four Loves that seeks to correct or at least challenge a number of longstanding misunderstandings about Lewis’s taxonomy of love.
Etiologies of outpatient medically attended acute respiratory infections among young Ecuadorian children prior to the start of the 2020 SARS‐CoV‐2 pandemic
Authors: Suryadevara Manika , Fajardo Freddy Pizarro , Aponte Cinthya Cueva , Carrillo Aponte Jorge Luis , Prado Esteban Ortiz , Hidalgo Ivan , Bonville Cynthia A. , Torres Irene , Domachowske Joseph B.
Published: September 2022

Background

Implementation of respiratory virus prevention measures requires detailed understanding of regional epidemiology; however, data from many tropical countries are sparse. We describe etiologies of ambulatory pediatric acute respiratory tract infections (ARTI) in Ecuador immediately preceding the onset of the SARS‐CoV‐2 pandemic.

Methods

Children < 5 years presenting to a designated study site with an ARTI were eligible. Informed consent was obtained. Demographic and clinical data were recorded. A nasopharyngeal swab was collected, processed, and analyzed using multiplex polymerase chain reaction (PCR) for common respiratory pathogens. Rhinovirus/enterovirus positive samples were further characterized by genomic sequencing.

Results

A total of 820 subjects were enrolled in the study between July 2018 and March 2020. A total of 655 (80%) samples identified at least one pathogen. Rhinoviruses (44%) were most common, followed by enteroviruses (17%), parainfluenza viruses (17%), respiratory syncytial virus (RSV) (15%), and influenza viruses (13%). Enterovirus D68 was the most common enterovirus detected and was among the leading causes of bronchiolitis. Seasonal RSV and influenza virus activity were different along the coast compared with the highlands.

Conclusions

Ongoing regional surveillance studies are necessary to optimize available and emerging pathogen‐specific preventative measures.