bluuebunny/crossref_metadata_2025 huggingface dataset:
IgA nephropathy with minimal change disease associated with primary Sjögren’s syndrome: A case report
Authors: Choi Jungyoon , Lee Tae Won , Bae Eunjin , Jang Ha Nee , An Hyo Jung , Chang Se-Ho , Park Dong Jun
Published: June 2023

Rationale:

Only 1 case of IgA nephropathy (IgAN) with minimal change disease (MCD) associated with primary Sjögren’s syndrome (SS) has been reported. We additionally describe IgAN with MCD associated with primary SS.

Patient concerns:

A 80-year-old woman visited our hospital complaining of generalized edema that had started 4 weeks prior. She reported a sense of thirst and dry eye for the last 5 years.

Diagnoses:

Her initial laboratory findings were compatible with nephrotic syndrome; both the antinuclear antibody (1:80) and anti-SS-A (Ro) antibody (200 U/mL) tests were positive. A salivary gland scan revealed markedly decreased uptake for both the parotid and submandibular glands. The Schirmer test was positive. The random urine protein/creatinine ratio was 10 mg/mg. Renal biopsy was compatible with IgAN with superimposed MCD.

Interventions:

Furosemide was intravenously administered with intermittent albumin infusion for her edema control. She was started on prednisone 40mg daily for 6 weeks, which was tapered to 5 mg for another 6 months after starting prednisolone.

Outcomes:

Over the next 6 months, her edema improved and the proteinuria decreased significantly.

Lessons:

Physician should suspect IgA with MCD when patient with SS clinically showed nephrotic syndrome, and perform renal biopsy for pathologically diagnosis and appropriate treatment.
Development of giant cell arteritis after vaccination against SARS-CoV2: A case report and literature review
Authors: Wakabayashi Hiroki , Iwayanagi Misa , Sakai Daiki , Sugiura Yoshiya , Hiruta Nobuyuki , Matsuzawa Yasuo , Kaneko Kaichi
Published: June 2023

Rationale:

Giant cell arteritis (GCA) is an autoimmune vasculitis that affects large and medium-sized blood vessels. The mRNA vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) has been associated with the development of immune-mediated diseases. In this article, we present a case of GCA that developed after vaccination against SARS-CoV2.

Patient concerns:

A 77-year-old man developed fever, general fatigue, and headache 1 day after the third dose of vaccination against SARS-CoV2. Nodular swelling and tenderness of the bilateral temporal arteries were observed.

Diagnoses:

Although right temporal artery biopsies were negative, the patient was diagnosed with GCA based on criteria established by the American College of Rheumatology for the classification of GCA.

Interventions:

The patient received methylprednisolone 1000 mg for 3 days. This was followed by prednisolone 1 mg/kg/d, which was decreased by 10 mg every week to 30 mg. From day 16 of hospitalization, the patient received tocilizumab 162 mg/wk every other week.

Outcomes:

There was no occurrence of acute side effects. After 38 days of treatment, the condition improved and the patient was discharged from the hospital; as stated above, the dose of prednisolone was tapered to 30 mg/d.

Lessons:

We experienced a case of GCA that occurred immediately after vaccination against SARS-CoV2 with an mRNA vaccine. Early signs of GCA include fever, fatigue, and headache, and often resemble those noted after vaccination against SARS-CoV2. The potential presence of GCA should be determined in individuals with persistent fever and headache after vaccination against SARS-CoV2.
Use of extracorporeal membrane oxygenation during resection of recurrent laryngeal papillomatosis: A case report
Authors: Wang Wenyang , Zhu Zhirui , He Wenlong , Hu Yaoqin , Zeng Qiao
Published: June 2023

Rationale:

Recurrent laryngeal papillomatosis (RLP) is a common benign tumor in the larynx of children, which is characterized by high recurrence rate and rapid growth, leading to clinical symptoms such as hoarseness and difficulty breathing. Low-temperature plasma radiofrequency ablation (RFA) is the main treatment, but ventilation problems are often encountered during surgery.

Patient concerns:

We report a case of a 2-year-old child with RLP who underwent low-temperature plasma RFA with the assistance of a laryngoscope. However, the surgery had to be temporarily stopped due to ventilation difficulties and difficulty in maintaining blood oxygen saturation during the procedure.

Diagnosis:

The child was diagnosed with RLP.

Interventions:

The child underwent low-temperature plasma RFA supported by laryngoscopy assisted by ECMO.

Outcomes:

Despite ventilation problems during surgery, the use of ECMO support helped maintain good oxygen saturation in the child and provided a clear surgical field, enabling the tumor to be quickly and cleanly removed. Therefore, the use of ECMO provided critical support during the surgery.

Lessons:

This case highlights the importance of airway management during laryngeal papillomatosis surgery. A thorough airway assessment should be performed before anesthesia, and early use of ECMO can reduce harm to the child and ensure the child’s safety.
One-year follow-up evaluation of radiological and respiratory findings and functional capacity in COVID-19 survivors without comorbidities
Authors: Ogun Hamza , Gül Merve , Akkoyunlu Yasemin , Hayat Esat , Gökbulut Nuran , Sümbül Bilge , Karaçöp Handan Başel , Yurtsever İsmail , Yabaci Ayşegül , Kansu Abdullah , Okyaltirik Fatmanur
Published: June 2023

The aim of this study was to assess clinical findings, radiological data, pulmonary functions and physical capacity change over time and to investigate factors associated with radiological abnormalities after coronavirus disease 2019 (COVID-19) in non-comorbid patients. This prospective cohort study was conducted between April 2020 and June 2020. A total of 62 symptomatic in non-comorbid patients with COVID-19 pneumonia were included in the study. At baseline and the 2nd, 5th and 12th months, patients were scheduled for follow-up. Males represented 51.6% of the participants and overall mean age was 51.60 ± 12.45 years. The percentage of patients with radiological abnormalities at 2 months was significantly higher than at 5 months (P < .001). At 12 months, dyspnea frequency (P = .008), 6-minute walk test (6MWT) distance (P = .045), BORG-dyspnea (P < .001) and BORG-fatigue (P < .001) scores was significantly lower, while median SpO2 after 6MWT (P < .001) was significantly higher compared to results at 2 months. The presence of radiological abnormalities at 2 months was associated with the following values measured at 5 months: advanced age (P = .006), lung involvement at baseline (P = .046), low forced expiratory volume in 1 second (P = .018) and low forced vital capacity (P = .006). Even in COVID-19 patients without comorbidities, control computed tomography at 2 months and pulmonary rehabilitation may be beneficial, especially in COVID-19 patients with advanced age and greater baseline lung involvement.
Identifying individuals at risk of esophageal adenocarcinoma: challenges, existing tools and future steps
Authors: Kunzmann Andrew T. , Rubenstein Joel H.
Published: June 2023

Purpose of review

This review aims to discuss some of the clinical and epidemiological challenges of risk prediction models; summarize the evidence supporting existing models; and highlight the translational requirements.

Recent findings

A variety of risk prediction models exist to identify prevalent Barrett's esophagus or predict future esophageal adenocarcinoma. External validation studies have investigated performance of these models in a variety of settings. These models appear to be more predictive than use of symptoms alone, but the added complexity means that implementation challenges may require investigation.

Risk prediction models could be useful for identifying individuals at an increased risk of esophageal adenocarcinoma, which could assist screening decisions. However, risk prediction models must be implemented with care. Implementation science to assist the translation of existing models into practice may be an important next step.
Metrics for Monitoring Preoperative Optimization Programs for Total Joint Arthroplasty
Authors: Dlott Chloe C. , Miguez Sofia , Wilkins Sarah G. , Khunte Akshay , Johnson Charla B. , Kurek Donna , Wiznia Daniel H.
Published: June 2023

Preoperative optimization programs are becoming more common for patients seeking total joint arthroplasty; yet, limited research has been conducted to monitor the long-term effects of these programs on patient outcomes. Our aim was to develop a set of metrics that programs can use to monitor the success of preoperative optimization programs. As part of a larger survey of orthopaedic nurses, we collected data regarding current monitoring techniques for preoperative optimization programs and the feasibility of collecting specific variables. Surgical factors such as length of stay and 30-day readmissions were most often used to monitor the success of preoperative optimization programs. Surgical factors were the most likely to be accessible using the electronic medical record. Surgical factors and patient characteristics are the most feasible components for programs to monitor in order to track the outcomes of patients participating in preoperative optimization programs.
Right Ventricular Strain Analysis By Tissue Tracking Cardiac Magnetic Resonance Imaging In Pediatric Patients With End-Stage Renal Disease
Authors: Tawfik Ahmed M. , Sobh Donia M. , Gadelhak Basma , Zedan Mohamed M. , Sobh Hoda M. , Eid Riham , Hamdy Nashwa , Batouty Nihal M.
Published: June 2023

Purpose:

To investigate right ventricular (RV) volume and mass by cardiac magnetic resonance (CMR) and the added value of tissue tracking strain analysis as markers of RV dysfunction in pediatric patients with end-stage renal disease (ESRD) and preserved RV ejection fraction.

Materials and Methods:

Twenty-five children with ESRD and preserved RVEF (>50%) and 10 healthy control children were enrolled. Tissue tracking CMR was used to assess Global Longitudinal, circumferential (GCS), and radial short and long axes (GRS SAX and GRS LAX) RV strains in the patients group compared with controls. Correlations between strain parameters and other CMR parameters and clinical biomarkers were assessed. Binary logistic regression was used to test the independence of cofounders and detect their significance.

Results:

RV end-diastolic volume and mass (RVMi) were significantly higher in patients (97.2±19.3 mL/m2 and 26.6±7gr/m2) than control (71±7.8 mL/m2 and 11.9±2 gr/m2, P values 0.000). All RV global strain parameters were significantly impaired in patients compared with control (all P values <0.05). RV Global Longitudinal was significantly correlated to LVEF (r=−0.416, P=0.039), LVEDVi (r=0.481, P=0.015), LVMi (r=0.562, P=0.004), and systolic blood pressure index (r=0.586, P=0.002). RV GRS (LAX) was significantly correlated to LV GCS (r=−0.462, P=0.020) and LV GRS (SAX) (r=0.454, P=0.023). GRS (SAX) and GCS demonstrated the highest diagnostic accuracy (area under curve: 0.82 and 0.81) to detect strain impairment. Univariate binary logistic regression with patients versus control as dependent variables identified LVMi, RV end-diastolic volume, RVMi, weight, body surface area, RV GCS, RV GRS (LAX), RV GRS (SAX), LV GCS, and LV GRS (SAX) as significantly correlated to patients with ESRD. When adjusted to other cofounders in the multivariable model, only RVMi remained as an independent significant cofounder (Odds ratio:0.395, P=0.046).

Conclusion:

RV global strain, volume, and mass by CMR are markers of RV dysfunction in ESRD pediatric patients with preserved RVEF.
Pharyngeal Arches, Chapter 1: Normal Development and Derivatives
Authors: Toro-Tobon Sara , Manrique Monica , Paredes-Gutierrez Juliana , Mantilla-Rivas Esperanza , Oh Haley , Ahmad Laiba , Oh Albert K. , Rogers Gary F.
Published: June 2023

The pharyngeal arches form the cornerstone of the complex anatomy of the face and neck. These embryologic structures are the foundation of face and neck development, and anomalous growth can result in craniofacial abnormalities. Surgeons who manage head and neck pathology and pathoanatomy will invariably encounter conditions associated with aberrant pharyngeal arch anatomy, and a thorough understanding of the normal and pathological development of these important structures is paramount to accurate diagnosis and treatment.

This manuscript is the first of a three-part educational series that addressed the pharyngeal/branchial arch embryology, development, nomenclature, and normal anatomy (Part I), pathologic anomalies of ear and neck derived from abnormal development of the arches (Part II), and different types of orofacial clefts, including Tessier clefts (Part III).
Comparative genomics uncovered differences between clinical and environmental populations of Vibrio parahaemolyticus in New Zealand
Authors: Vasey Jack , Jones Dan , Deng Cecilia H. , Hedderley Duncan , Martinez-Urtaza Jaime , Powell Andy , Wang Jing , Wright Jackie , Merien Anne-Marie P. , Fletcher Graham C. , Vidovic Sinisa
Published: June 2023

Vibrio parahaemolyticus

has been identified as an emerging human pathogen worldwide with cases undergoing a global expansion over recent decades in phase with climate change. New Zealand had remained free of outbreaks until 2019, but different outbreaks have been reported consecutively since then. To provide new insights into the recent emergence of cases associated with outbreak clones over recent years, a comparative genomic study was carried out using a selection of clinical (mostly outbreak) and environmental isolates of

V. parahaemolyticus

obtained in New Zealand between 1973 and 2021. Among 151 isolates of clinical (n=60) and environmental (n=91) origin, 47 sequence types (STs) were identified, including 31 novel STs. The population of environmental isolates generated 30 novel STs, whereas only 1 novel ST (ST2658) was identified among the population of clinical isolates. The novel clinical ST was a single-locus variant of the pandemic ST36 strain, indicating further evolution of this pandemic strain. The environmental isolates exhibited a significant genetic heterogeneity compared to the clinical isolates. The whole-genome phylogeny separated the population of clinical isolates from their environmental counterparts, clearly indicating their distant genetic relatedness. In addition to differences in ancestral profiles and genetic relatedness, these two groups of isolates exhibited a profound difference in their virulence profiles. While the entire population of clinical isolates harboured the thermostable direct haemolysin (tdh) and/or the thermostable-related haemolysin (trh), only a few isolates of environmental origin possessed the same virulence genes. In contrast to tdh and trh, adhesin-encoding genes, vpadF and MSHA, showed a significantly (P<0.001) greater association with the environmental isolates compared to the clinical isolates. The effectors, VopQ, VPA0450 and VopS, which belong to T3SS1, were ubiquitous, being present in each isolate regardless of its origin. The effectors VopC and VopA, which belong to T3SS2, were rarely detected in any of the examined isolates. Our data indicate that the clinical and environmental isolates of

V. parahaemolyticus

from New Zealand differ in their population structures, ancestral profiles, genetic relatedness and virulence profiles. In addition, we identified numerous unique non-synonymous single-nucleotide polymorphisms (nsSNPs) in adhesins and effectors, exclusively associated with the clinical isolates tested, which may suggest a possible role of these mutations in the overall virulence of the clinical isolates.
Biofilms as protective cocoons against biocides: from bacterial adaptation to One Health issues
Authors: Charron Raphaël , Boulanger Marine , Briandet Romain , Bridier Arnaud
Published: June 2023

Bacteria in the food chain mostly live in communities associated with surfaces known as biofilms, which confer specific survival and adaptive abilities. In such communities, the bacteria mostly exhibit higher tolerance to external stress, and their recurrent exposure along the food chain to biocides used during cleaning and disinfection procedures raises concern about the adaptation routes they develop, both at single-cell and communal levels. In recent years, an increasing number of research subjects have focused on understanding the specific features of biofilms that enable bacterial populations to adapt to biocide exposure within a ‘protective cocoon’. The first part of this review concentrates on the diversity of adaptive strategies, including structural modulation of these biofilms, physiological response or the acquisition of genetic resistance. The second part discusses the possible side effects of biofilm adaptation to biocides on antimicrobial cross-resistance, virulence and colonization features from a One Health perspective.
Foveal RGCs develop altered calcium dynamics weeks after photoreceptor ablation
Authors: Xu Zhengyang , Kunala Karteek , Murphy Peter , Patak Laura , Puthussery Teresa , McGregor Juliette
Published: June 2023

Objective or purpose

Physiological changes in retinal ganglion cells (RGCs) have been reported in rodent models of photoreceptor (PR) loss but this has not been investigated in primates. By expressing both a calcium indicator (GCaMP6s) and an optogenetic actuator (ChrimsonR) in foveal RGCs of the macaque, we reactivated RGCsin vivoand assessed their response in the weeks and years following PR loss.

Design

We used anin vivocalcium imaging approach to record optogenetically evoked activity in deafferented RGCs in primate fovea. Cellular scale recordings were made longitudinally over a 10 week period following photoreceptor ablation and compared to responses from RGCs that had lost photoreceptor input more than two years prior.

Participants

Three eyes received photoreceptor ablation, OD of a maleMacaca mulatta(M1), OS of a femaleMacaca fascicularis(M2) and OD of a maleMacaca fascicularis(M3). Two animals were used forin vivorecording, one for histological assessment.

Methods

Cones were ablated with an ultrafast laser delivered through an adaptive optics scanning light ophthalmoscope (AOSLO). A 0.5 s pulse of 25Hz 660nm light optogenetically stimulated RGCs, and the resulting GCaMP fluorescence signal was recorded using AOSLO. Measurements were repeated over 10 weeks immediately after PR ablation, at 2.3 years and in control RGCs.

Main Outcome measures

The calcium rise time, decay constant and sensitivity index of optogenetic mediated RGC were derived from GCaMP fluorescence recordings from 221 RGCs (Animal M1) and 218 RGCs (Animal M2)in vivo.

Results

Following photoreceptor ablation, the mean decay constant of the calcium response in RGCs decreased 1.5 fold (1.6±0.5 s to 0.6±0.3 s SD) over the 10 week observation period in subject 1 and 2.1 fold (2.5±0.5 s to 1.2±0.2 s SD) within 8 weeks in subject 2. Calcium rise time and sensitivity index were stable. Optogenetic reactivation remained possible 2.3 years after PR ablation.

Conclusions

Altered calcium dynamics developed in primate foveal RGCs in the weeks after photoreceptor ablation. The mean decay constant of optogenetic mediated calcium responses decreased 1.5 - 2-fold. This is the first report of this phenomenon in primate retina and further work is required to understand the role these changes play in cell survival and activity.
MFGE8 inhibits insulin signaling through PTP1B
Authors: Datta Ritwik , Podolsky Michael J , Yang Christopher D , Alba Diana L. , Singh Sukhmani , Koliwad Suneil , Lizama Carlos O , Atabai Kamran
Published: June 2023

The role of integrins in regulating insulin signaling is incompletely understood. We have previously shown that binding of the integrin ligand milk fat globule epidermal growth factor like 8 (MFGE8) to the αvβ5 integrin promotes termination of insulin receptor signaling in mice. Upon ligation of MFGE8, β5 complexes with the insulin receptor beta (IRβ) in skeletal muscle resulting in dephosphorylation of IRβ and reduction of insulin-stimulated glucose uptake. Here we investigate the mechanism by which the interaction between β5 and IRβ impacts IRβ phosphorylation status. We show that β5 blockade inhibits and MFGE8 promotes PTP1B binding to and dephosphorylation of IRβ resulting in reduced or increased insulin-stimulated myotube glucose uptake respectively. The β5-PTP1B complex is recruited by MFGE8 to IRβ leading to termination of canonical insulin signaling. β5 blockade enhances insulin-stimulated glucose uptake in wild type but notPtp1bKO mice indicating that PTP1B functions downstream of MFGE8 in modulating insulin receptor signaling. Furthermore, in a human cohort, we report serum MFGE8 levels correlate with indices of insulin resistance. These data provide mechanistic insights into the role of MFGE8 and β5 in regulating insulin signaling.
Gene Expression and Physiological traits in Mice
Authors: Ramos Rafael , Nelson Igor
Published: June 2023

Background

Gene expression regulates several complex traits observed. In this study, datasets comprising of transcriptome information and clinical traits regarding fat composition and vitals were analyzed via several statistical methods in order to find relations between genes and clinical outcomes.

Results

Biological big data is diverse and numerous, which makes for a complex case study and difficulties to stablish a metric. Histological data with semi-quantitative scores proved unreliable to correlate with other vitals, such as cholesterol composition, which complicates prediction of clinical outcomes. A composition of vitals, turned out to be a better variable for regression and factors for gene analysis. Several genes were found to be statistically significant after statistical analysis by ANOVA regarding the progressive categories of the preferred clinical variable.

Conclusions

ANOVA is proposed as a method for genetic information retrieval in order to extract biological meaning from RNA seq or microarray data, accounting for multiple classes of target variables. It Provides a reliable statistical method to associate genes or clusters of genes with particular traits.

Supplementary information

Supplementary data are available in annexes.
Highly pathogenic avian influenza A virus (HPAIV) H5N1 infection in two European grey seals (Halichoerus grypus) with encephalitis
Authors: Mirolo Monica , Pohlmann Anne , Ahrens Ann Kathrin , Kühl Bianca , Rubio-Garcìa Ana , Kramer Katharina , Meinfelder Ulrike , Rosenberger Tanja , Morito Hannah Leah , Beer Martin , Ludlow Martin , Wohlsein Peter , Baumgärtner Wolfgang , Harder Timm , Osterhaus Albert
Published: June 2023

Recent reports documenting sporadic infections in carnivorous mammals worldwide with highly pathogenic avian influenza virus (HPAIV) H5N1 clade 2.3.4.4b have raised concerns about the potential risk of adaptation to sustained transmission in mammals, including humans. We report H5N1 clade 2.3.4.4b infection of two grey seals (Halichoerus grypus) from coastal waters of The Netherlands and Germany in December 2022 and February 2023, respectively. Histological and immunohistochemical investigations showed in both animals a non-suppurative and necrotizing encephalitis with viral antigen restricted to the neuroparenchyma. Whole genome sequencing showed the presence of HPAIV H5N1 clade 2.3.4.4b strains in brain tissue, which were closely related to sympatric avian influenza viruses. Viral RNA was also detected in the lung of the seal from Germany by real-time quantitative PCR. No other organs tested positive. The mammalian adaptation PB2-E627K mutation was identified in approximately 40% of the virus population present in the brain tissue of the German seal. Retrospective screening for nucleoprotein specific antibodies, of sera collected from 251 seals sampled in this region from 2020 to 2023, did not show evidence of influenza A virus specific antibodies. Similarly, screening by reverse transcription PCR of lung and brain tissue of 101 seals that had died along the Dutch coast in the period 2020-2021, did not show evidence of influenza virus infection. Collectively, these results indicate that individual seals are sporadically infected with HPAIV-H5N1 clade 2.3.4.4b, resulting in an encephalitis in the absence of a systemic infection, and with no evidence thus far of onward spread between seals.
Direct and indirect consequences ofPAB1deletion in the regulation of translation initiation, translation termination, and mRNA decay
Authors: Mangkalaphiban Kotchaphorn , Ganesan Robin , Jacobson Allan
Published: June 2023

Cytoplasmic poly(A)-binding protein (PABPC; Pab1 in yeast) is thought to be involved in multiple steps of post-transcriptional control, including translation initiation, translation termination, and mRNA decay. To understand these roles of PABPC in more detail for endogenous mRNAs, and to distinguish its direct effects from indirect effects, we have employed RNA-Seq and Ribo-Seq to analyze changes in the abundance and translation of the yeast transcriptome, as well as mass spectrometry to assess the abundance of the components of the yeast proteome, in cells lacking thePAB1gene. We observed drastic changes in the transcriptome and proteome, as well as defects in translation initiation and termination, inpab1Δcells. Defects in translation initiation and the stabilization of specific classes of mRNAs inpab1Δcells appear to be partly indirect consequences of reduced levels of specific initiation factors, decapping activators, and components of the deadenylation complex in addition to the general loss of Pab1’s direct role in these processes. Cells devoid of Pab1 also manifested a nonsense codon readthrough phenotype indicative of a defect in translation termination, but this defect may be a direct effect of the loss of Pab1 as it could not be attributed to significant reductions in the levels of release factors.

AUTHOR SUMMARY

Many human diseases are caused by having too much or too little of certain cellular proteins. The amount of an individual protein is influenced by the level of its messenger mRNA (mRNA) and the efficiency of translation of the mRNA into a polypeptide chain by the ribosomes. Cytoplasmic poly(A)-binding protein (PABPC) plays numerous roles in the regulation of this multi-staged process, but understanding its specific role has been challenging because it is sometimes unclear whether experimental results are related to PABPC’s direct role in a specific biochemical process or to indirect effects of its other roles, leading to conflicting models of PABPC’s functions between studies. In this study, we characterized defects of each stage of protein synthesis in response to loss of PABPC in yeast cells by measuring whole-cell levels of mRNAs, ribosome-associated mRNAs, and proteins. We demonstrated that defects in most steps of protein synthesis other than the last can be explained by reduced levels of mRNAs that code for proteins important for that step in addition to loss of PABPC’s direct role on that step. Our data and analyses serve as resources for the design of future studies of PABPC’s functions.
“Evolution of the mutation spectrum across a mammalian phylogeny”
Authors: Beichman Annabel C. , Robinson Jacqueline , Lin Meixi , Moreno-Estrada Andrés , Nigenda-Morales Sergio , Harris Kelley
Published: June 2023

Little is known about how the spectrum and etiology of germline mutagenesis might vary among mammalian species. To shed light on this mystery, we quantify variation in mutational sequence context biases using polymorphism data from thirteen species of mice, apes, bears, wolves, and cetaceans. After normalizing the mutation spectrum for reference genome accessibility andk-mer content, we use the Mantel test to deduce that mutation spectrum divergence is highly correlated with genetic divergence between species, whereas life history traits like reproductive age are weaker predictors of mutation spectrum divergence. Potential bioinformatic confounders are only weakly related to a small set of mutation spectrum features. We find that clocklike mutational signatures previously inferred from human cancers cannot explain the phylogenetic signal exhibited by the mammalian mutation spectrum, despite the ability of these clocklike signatures to fit each species’ 3-mer spectrum with high cosine similarity. In contrast, parental aging signatures inferred from human de novo mutation data appear to explain much of the mutation spectrum’s phylogenetic signal when fit to non-context-dependent mutation spectrum data in combination with a novel mutational signature. We posit that future models purporting to explain the etiology of mammalian mutagenesis need to capture the fact that more closely related species have more similar mutation spectra; a model that fits each marginal spectrum with high cosine similarity is not guaranteed to capture this hierarchy of mutation spectrum variation among species.
Cell motility modes are selected by the interplay of mechanosensitive adhesion and membrane tension
Authors: Chen Yuzhu , Saintillan David , Rangamani Padmini
Published: June 2023

The initiation of directional cell motion requires symmetry breaking that can happen both with or without external stimuli. During cell crawling, forces generated by the cytoskeleton and their transmission through mechanosensitive adhesions to the extracellular substrate play a crucial role. In a recently proposed 1D model (Sens, PNAS 2020), a mechanical feedback loop between force-sensitive adhesions and cell tension was shown to be sufficient to explain spontaneous symmetry breaking and multiple motility patterns through stick-slip dynamics, without the need to account for signaling networks or active polar gels. We extended this model to 2D to study the interplay between cell shape and mechanics during crawling. Through a local force balance along a deformable boundary, we show that the membrane tension coupled with shape change can regulate the spatiotemporal evolution of the stochastic binding of mechanosensitive adhesions. Linear stability analysis identified the unstable parameter regimes where spontaneous symmetry breaking can take place. Using simulations to solve the fully coupled nonlinear system of equations, we show that starting from a randomly perturbed circular shape, this instability can lead to keratocyte-like shapes. Simulations predict that different adhesion kinetics and membrane tension can result in different cell motility modes including gliding, zigzag, rotating, and sometimes chaotic movements. Thus, using a minimal model of cell motility, we identify that the interplay between adhesions and tension can select emergent motility modes.
Metagenomic domain substitution for the high-throughput modification of non-ribosomal peptide analogues
Authors: Messenger Sarah R. , McGuinniety Edward M. R. , Stevenson Luke J. , Owen Jeremy G. , Challis Gregory L. , Ackerley David F. , Calcott Mark J.
Published: June 2023

Non-ribosomal peptides are a diverse and medically important group of natural products. They are biosynthesised by modular non-ribosomal peptide synthetase (NRPS) assembly-lines in which domains from each module act in concert to incorporate a specific amino acid into a peptide. This modular biosynthesis has driven efforts to generate new peptide analogues by substituting amino acid specifying domains. Rational NRPS engineering has increasingly focused on using evolutionarily favoured recombination sites for domain substitution. Here, we present an alternative approach inspired by evolution, which involves large-scale diversification and screening. By adopting a metagenomic approach of amplifying amino acid specifying domains from metagenomic DNA derived from soil, we were able to substitute over 1,000 unique domains into a pyoverdine NRPS. To identify functional domain substitutions, we employed fluorescence and mass spectrometry screening techniques, followed by sequencing. This comprehensive screening process successfully identified more than 100 functional domain substitutions, resulting in the production of 16 distinct pyoverdines as major products. The significance of this metagenomic approach lies in its ability to shift the focus of engineering non-ribosomal peptide biosynthesis. Instead of relying on a high success rate of individual domain substitution, we have developed effective methods that enable the exploration of a broader range of substitutions. This opens new possibilities for the discovery and production of novel non-ribosomal peptides with diverse biological activities.

Abstract Figure
Atg15 is a vacuolar phospholipase that disintegrates organelle membranes
Authors: Watanabe Yasunori , Iwasaki Yurina , Sasaki Kyoka , Suzuki Kuninori
Published: June 2023

Atg15 (autophagy-related 15) is a vacuolar phospholipase essential for the degradation of cytoplasm-to-vacuole targeting (Cvt) bodies and autophagic bodies, hereinafter referred to as intravacuolar autophagic compartments (IACs), but it remains unknown if Atg15 directly disrupts IAC membranes. Here we show that the recombinantChaetomium thermophilumAtg15 lipase domain (CtAtg15(73–475)) possesses phospholipase activity that in acidic environments digests phospholipid to generate lysophospholipid and free fatty acid. The activity of CtAtg15(73–475) was markedly elevated by limited digestion with proteinase K. Proteinase K–treated CtAtg15(73–475) was detected as three fragments, with cleavage between S159 and V160, and between F209 and N210. We inserted the human rhinovirus 3C protease recognition sequence into the two sites and found that cleavage between S159 and V160 was important to activate CtAtg15(73–475). We confirmed that CtAtg15 compensated for the absence ofATG15inSaccharomyces cerevisiaecells, indicating that CtAtg15 could disintegrateS. cerevisiaeIACin vivo. Further, both mitochondria and IAC were disintegrated by CtAtg15 inS. cerevisiae. This study suggests that Atg15 can degrade any organelle membrane, indicating that Atg15 plays a role in disrupting organelle membranes delivered to vacuoles by autophagy.
Functional characterisation of rare variants in genes encoding the MAPK/ERK signalling pathway identified in long-lived Leiden Longevity Study participants
Authors: Hinterding Helena , Baghdadi Maarouf , Gehrmann Thies , Putter Pasquale , Neuerburg Mara , Lakenberg Nico , van den Akker Erik B. , Slagboom P. Eline , Deelen Joris , Partridge Linda
Published: June 2023

Human longevity, which is coupled to a compression of age-related disease, has been shown to be heritable. However, the number of identified common genetic variants linked to this trait remains small. This may indicate that longevity is, at least to some extent, determined by rare genetic variants that are potentially family-specific. We therefore investigated whole-genome sequencing data of long-lived families from the Leiden Longevity Study for family-specific variants. We identified variants residing in genes involved in the mitogen-activated protein kinase (MAPK) cascade, a lifespan-associated and evolutionarily conserved pathway emerging from studies in model organisms. We subsequently generated mouse embryonic stem cells (mESCs) harbouring these variants and conductedin vitrofunctional characterisation. Two variants, located inNF1(Phe1112Leu) andRAF1(Asp633Tyr), reduce MAPK/extracellular signal-regulated kinase (ERK) signalling pathway activity in mESCs. At the proteomic and transcriptomic level, we observed prominent changes that were shared (e.g. up-regulation of the ribosome) and opposing between the variants (e.g. down-regulation of mTORC1 signalling in the RAF1Asp633Tyrvariant cell line versus up-regulation in the NF1Phe1112Leuvariant cell lines). These metabolic changes were accompanied by an opposing effect of the variants on proliferation. Moreover, the RAF1Asp633Tyrvariant improved resistance to replication stress, while this was not the case for the NF1Phe1112Leuvariant. In conclusion, we identified two rare genetic variants in long-lived families that influence MAPK/ERK signalling in a manner that has previously been linked to increased lifespan in model organisms. Interestingly, we also observe some opposing and diverging effects between the variants, which indicates that they may either have some pleiotropic effects that are not relevant to longevity or that they target slightly different mechanisms to elicit their effects in mESCs. Our findings suggest that mESCs offer a good starting point forin vitrocharacterisation of rare genetic variants linked to human longevity and can be used to assess which of these variants to take forward toin vivostudies in model organisms.
Prenatal SARS-CoV-2 infection alters postpartum human milk-derived extracellular vesicles
Authors: Chutipongtanate Somchai , Cetinkaya Hatice , Zhang Xiang , Kuhnell Damaris , Benefield Desirée , Haffey Wendy , Wyder Michael , Patel Richa , Conrey Shannon C. , Burrell Allison R. , Langevin Scott , Nommsen-Rivers Laurie , Newburg David S. , Greis Kenneth D. , Staat Mary A. , Morrow Ardythe L.
Published: June 2023

Human milk-derived extracellular vesicles (HMEVs) are crucial functional components in breast milk, contributing to infant health and development. Maternal conditions could affect HMEV cargos; however, the impact of SARS-CoV-2 infection on HMEVs remains unknown. This study evaluated the influence of SARS-CoV-2 infection during pregnancy on postpartum HMEV molecules. Milk samples (9 prenatal SARS-CoV-2 vs. 9 controls) were retrieved from the IMPRINT birth cohort. After defatting and casein micelle disaggregation, 1 mL milk was subjected to a sequential process of centrifugation, ultrafiltration, and qEV-size exclusion chromatography. Particle and protein characterizations were performed following the MISEV2018 guidelines. EV lysates were analyzed through proteomics and miRNA sequencing, while the intact EVs were biotinylated for surfaceomic analysis. Multi-Omics was employed to predict HMEV functions associated with prenatal SARS-CoV-2 infection. Demographic data between the prenatal SARS-CoV-2 and control groups were similar. The median duration from maternal SARS-CoV-2 test positivity to milk collection was 3 months (range: 1-6 months). Transmission electron microscopy showed the cup-shaped nanoparticles. Nanoparticle tracking analysis demonstrated particle diameters of <200 nm and yields of >1e11 particles from 1 mL milk. Western immunoblots detected ALIX, CD9 and HSP70, supporting the presence of HMEVs in the isolates. Thousands of HMEV cargos and hundreds of surface proteins were identified and compared. Multi-Omics predicted that mothers with prenatal SARS-CoV-2 infection produced HMEVs with enhanced functionalities involving metabolic reprogramming and mucosal tissue development, while mitigating inflammation and lower EV transmigration potential. Our findings suggest that SARS-CoV-2 infection during pregnancy boosts mucosal site-specific functions of HMEVs, potentially protecting infants against viral infections. Further prospective studies should be pursued to reevaluate the short- and long-term benefits of breastfeeding in the post-COVID era.
Subjective status perception of entrepreneurs and firm-level international behavior: evidence from Chinese private firms
Authors: Sheng Wei , Niu Zhiyong , Zhou Xiaoyan
Published: June 2023

Purpose

The purpose of this paper is to explore the determinants of entrepreneurs’ subjective social status perception (SSP) on firm international behaviors based on the upper echelons theory and social class theory.

Design/methodology/approach

To test the hypotheses, the authors studied a large sample of 10,823 small- and medium-sized private Chinese enterprises from 2006 to 2014.

Findings

The results showed that entrepreneurs with higher status perception prefer international activity and firms have higher export intensity and intention. In addition, the social capital of entrepreneurs and institutional environment amplifies the positive relationship between SSP and international behavior.

Originality/value

This paper contributes to research on the upper echelon of management and extends our understanding of how managerial social characteristics influence international strategic decision-making. Besides, it also contributes to the emerging stream of social status research in international expansion studies and expand researchers’ limited understanding of the effects of social status in business settings.
Corruption, democracy and the location decisions of emerging multinationals: evidence from China’s cross-border mergers and acquisitions
Authors: Wang Jiang , Shen Xiaohua
Published: June 2023

Purpose

This study investigated the moderating role of democracy in the relationship between corruption and foreign direct investment. The purpose of this study is to understand whether corruption has different effects on the location decisions of multinational enterprises (MNEs) depending on the regime type.

Design/methodology/approach

This study explored how institutional context influenced the impacts of corruption on the location decisions of MNEs, specifically using a sample of Chinese cross-border mergers and acquisitions between 2000 and 2020.

Findings

This study assessed the role of democracy in the relationship between corruption and the location decisions of Chinese MNEs. In general, this study found that Chinese MNEs were hindered by host country corruption, but that these detrimental effects were weaker in the presence of more effective democratic institutions.

Originality/value

This study contributes to the literature on institutional factors in international business through its simultaneous investigation of the effects of both democracy and corruption on the location decisions of MNEs. Moreover, there is a prevailing view that Chinese MNEs are willing to enter countries with high corruption, but the results of this study indicate that they are risk-averse in ways similar to their Western counterparts.
Application of a novel hybrid accumulation grey model to forecast total energy consumption of Southwest Provinces in China
Authors: Zhao Xuemei , Ma Xin , Cai Yubin , Yuan Hong , Deng Yanqiao
Published: June 2023

Purpose

Considering the small sample size and non-linear characteristics of historical energy consumption data from certain provinces in Southwest China, the authors propose a hybrid accumulation operator and a hybrid accumulation grey univariate model as a more accurate and reliable methodology for forecasting energy consumption. This method can provide valuable decision-making support for policy makers involved in energy management and planning.

Design/methodology/approach

The hybrid accumulation operator is proposed by linearly combining the fractional-order accumulation operator and the new information priority accumulation. The new operator is then used to build a new grey system model, named the hybrid accumulation grey model (HAGM). An optimization algorithm based on the JAYA optimizer is then designed to solve the non-linear parameters θ, r, and γ of the proposed model. Four different types of curves are used to verify the prediction performance of the model for data series with completely different trends. Finally, the prediction performance of the model is applied to forecast the total energy consumption of Southwest Provinces in China using the real world data sets from 2010 to 2020.

Findings

The proposed HAGM is a general formulation of existing grey system models, including the fractional-order accumulation and new information priority accumulation. Results from the validation cases and real-world cases on forecasting the total energy consumption of Southwest Provinces in China illustrate that the proposed model outperforms the other seven models based on different modelling methods.

Research limitations/implications

The HAGM is used to forecast the total energy consumption of the Southwest Provinces of China from 2010 to 2020. The results indicate that the HAGM with HA has higher prediction accuracy and broader applicability than the seven comparative models, demonstrating its potential for use in the energy field.

Practical implications

The HAGM(1,1) is used to predict energy consumption of Southwest Provinces in China with the raw data from 2010 to 2020. The HAGM(1,1) with HA has higher prediction accuracy and wider applicability compared with some existing models, implying its high potential to be used in energy field.

Originality/value

Theoretically, this paper presents, for the first time, a hybrid accumulation grey univariate model based on a new hybrid accumulation operator. In terms of application, this work provides a new method for accurate forecasting of the total energy consumption for southwest provinces in China.
What’s love got to do with it? How does workplace romance provoke workplace ostracism and interpersonal conflict
Authors: Feng Ye , Rana Asif Mehmood , Bashir Hasnain , Sarmad Muhammad , Rasheed Anmol , Ayub Arslan
Published: June 2023

Purpose

Extant research on workplace ostracism has investigated a victimization perspective to understand ostracism at the cost of examining the perpetrator-centric view of ostracism. This study aims to draw on the self-categorization theory and the social exchange theory to investigate the harmful effects of workplace romance in cultivating workplace ostracism from the perspective of perpetrator to combat concerns for victim blaming. This study further proposes that workplace ostracism triggered by workplace romance provokes interpersonal conflict. Besides, this study investigates the moderating role of prosocial behavior in the underlying linkages.

Design/methodology/approach

This study uses a multisource, time-lagged research design to collect data from employees working in the service sector organizations in Pakistan. This study analyzes 367 responses using SmartPLS (v 4.0).

Findings

The findings of this study reveal that workplace romance elicits workplace ostracism, which, in turn, fosters interpersonal conflict among coworkers. In addition, this study finds that ingroup prosocial behavior strengthens the associations between workplace romance and workplace ostracism, and workplace romance and interpersonal conflict, mediated by workplace ostracism such that the associations are more potent at higher levels of ingroup prosocial behavior and vice versa.

Originality/value

To the best of the authors’ knowledge, this is the first study that examines workplace romance as the perpetrator-centric antecedent of workplace ostracism, and ingroup prosocial behavior in exaggerating the outgroup ostracism and interpersonal conflict.
Organizational innovation and business model innovation: bridges from a systematic literature review
Authors: Perilla Maluche Ricardo Benjamín , Orozco Castro Luis Antonio
Published: June 2023

Purpose

The purpose of this paper is to create a model that connects drivers between organizational innovation and business model innovation (BMI) to guide empirical research and the design of innovation management strategies.

Design/methodology/approach

The model was designed based on the results of a systematic literature review over the past 25 years that provides common predictor variables to build bridges between these two types of innovations.

Findings

It is a conceptual relationship between organizational innovation and BMI based on processes, new structures and customer relationship management. Moreover, there are five bridges from common predictors: strategy, top management, exploratory learning, technological innovation and environmental complexity.

Originality/value

The relationships between organizational innovation and BMI have been neglected in the literature. The model fills this gap by proposing hypotheses for empirical research and critical variables and relationships to steer organizational and business model innovation.