bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety and Efficacy of Revisional Surgery as a Treatment for Malnutrition after Bariatric Surgery
Authors: Vahibe Ahmet , Aizpuru Matthew J , Sarr Michael G , Mundi Manpreet S , Vierkant Robert A , McKenzie Travis , Abu Dayyeh Barham K , Ghanem Omar M
Published: September 2022

BACKGROUND:

Malnutrition after bariatric operation is a rare but potentially life-threatening complication. The safety and efficacy of revisional bariatric operation in malnourished patients are not well elucidated.

STUDY DESIGN:

We performed a retrospective chart review of patients who underwent revisional bariatric operation for severe malnutrition at our institution between 2008 and 2020. Associations of demographic and clinical characteristics with dichotomous outcomes of interest were examined using Fisher’s exact tests, Cochran-Armitage tests for trend, and two-sample t-tests when appropriate.

RESULTS:

Fifty-three patients underwent revisional bariatric operation for malnutrition from 2008 and 2020. The median follow-up was 24 months. The anatomy before revision was Roux-en-Y gastric bypass (n = 40, 75%), biliopancreatic diversion with duodenal switch (n = 6, 11%), sleeve gastrectomy (n = 4, 8%), and mini gastric bypass (n = 3, 6%). The percentage of patients requiring supplemental or total nutritional support decreased from 89% preoperatively (47% on enteral feedings and 42% on total parenteral nutrition (TPN) with or without tube feeding) to 13.2% at the last encounter after revision (7.5% still requiring enteral feedings and 5.7% on TPN). There was an association between the number of prior abdominal operations and postoperative pneumonia (p 0.03) and need for blood transfusion (p 0.01). There were no associations between major complications or last encounter nutrition and any preoperative variables other than age at the time of operation. There were 2 mortalities during a median follow-up of 24 months, and both occurred more than 1 year postoperatively.

CONCLUSION:

Revisional operation for severely malnourished bariatric operation patients is effective in the discontinuation of supportive nutrition. Postoperative complications are increased but not prohibitive.
Association of Textbook Outcome and Surgical Case Volume with Long-Term Survival in Patients Undergoing Surgical Resection for Pancreatic Cancer
Authors: Kalagara Roshini , Norain Abdullah , Chang Yu-Hui , Stucky Chee-Chee , Wasif Nabil
Published: September 2022

BACKGROUND:

Current literature has identified textbook outcome (TO) as a quality metric after cancer surgery. We studied whether TO after pancreatic resection has a stronger association with long-term survival than individual hospital case volume.

STUDY DESIGN:

Patients undergoing surgery for pancreatic adenocarcinoma from 2010 to 2015 were identified from the National Cancer Database. Hospitals were stratified by volume (low less than 6, medium 6 to 19, and high 20 cases or more per year), and overall survival data were abstracted. We defined TO as adequate lymph node count, negative margins, length of stay less than the 75th percentile, appropriate systemic therapy, timely systemic therapy, and without a mortality event or readmission within 30 days. The association of TO and case volume was assessed using a multivariable Cox regression model for survival.

RESULTS:

Overall, 7270 patients underwent surgery, with 30.7%, 48.7%, and 20.6% performed at low-, medium-, and high-volume hospitals, respectively. Patients treated at low-volume hospitals were more likely to be Black, be uninsured or on Medicaid, have higher Charlson comorbidity scores, and be less likely to achieve TO (23.4% TO achievement vs 37.5% achievement at high-volume hospitals). However, high hospital volume was no longer associated with overall survival once TO was added to the multivariable model stratified by volume status. Achievement of TO corresponded to a 31% decrease in mortality (hazard ratio 0.69; p < 0.001), independent of hospital volume.

CONCLUSIONS:

Improved long-term survival after pancreatic resection was associated with TO rather than high hospital volume. Quality improvement efforts focused on TO criteria have the potential to improve outcomes irrespective of case volume.
Beyond Recidivism: Hospital-Based Violence Intervention and Early Health and Social Outcomes
Authors: Gorman Elizabeth , Coles Zachary , Baker Nazsa , Tufariello Ann , Edemba Desiree , Ordonez Michael , Walling Patricia , Livingston David H , Bonne Stephanie
Published: September 2022

BACKGROUND:

Hospital-based violence intervention programs (HVIPs) are aimed at decreasing recurrent injury and improving the social determinants of health. We hypothesized that the HVIP intervention should be evaluated by how well it can address the immediate health and social needs of patients after injury. Our study sought to describe the experience of our nascent HVIP.

STUDY DESIGN:

Case management records of patients treated by the HVIP of a level 1 trauma center from July 1, 2017 to October 1, 2020 were reviewed. Inclusion criteria were as follows: age between 18 and 60 with injury mechanisms that resulted from intentional violence. Patient-stated goals and social worker designation of patient services provided were analyzed. A subset of HVIP patients who completed the three planned study visit surveys at discharge and 1 and 3 months were compared with a cohort of violently injured patients to whom HVIP services were not available. Participants in both groups were asked to complete a battery of validated surveys to assess social outcomes and post-traumatic stress disorder (PTSD). Repeated-measures ANOVA was used to compare the two groups.

RESULTS:

Two hundred and ninety-five patients met the inclusion criteria. One hundred and forty-six patients (49%) achieved their stated goals within 6 months of hospital discharge. Sixteen patients who achieved their stated goals disengaged from the program. Engagement in the HVIP resulted in significantly less PTSD at the time of hospital discharge. HVIP patients also experienced higher positive affect at hospital discharge, as described in the Positive and Negative Affect Schedule. HVIP participants were significantly more likely to achieve early positive health outcomes, such as completion of victim of crime compensation and return to school.

CONCLUSIONS:

Our HVIP successfully achieved patient-stated short-term health and social goals in nearly half of all enrollees, indicating that HVIP patients are more likely to improve their social determinants of health than non-HVIP patients. Short-term health and social outcomes were improved in HVIP patients compared with non-HVIP patients, indicating increased engagement with the healthcare system. We suggest that these outcomes should replace recidivism as a metric for the efficacy of HVIP programs.
The Robin and Neumann problems for the nonlinear Schrödinger equation on the half-plane
Authors: Alexandrou Himonas A. , Mantzavinos Dionyssios
Published: September 2022

This work studies the initial-boundary value problem (ibvp) of the two-dimensional nonlinear Schrödinger equation on the half-plane with initial data in Sobolev spaces and Neumann or Robin boundary data in appropriate Bourgain spaces. It establishes well-posedness in the sense of Hadamard by using the explicit solution formula for the forced linear ibvp obtained via Fokas’s unified transform, and a contraction mapping argument.
Joint cmICA: auto-linking of structural and functional connectivity
Authors: Wu Lei , Calhoun Vince
Published: September 2022

The study of human brain connectivity, including structural connectivity (SC) and functional connectivity (FC), provides insights into the neurophysiological mechanism of brain function and its relationship to human behavior and cognition. Both types of connectivity measurements provide crucial yet complementary information. However, integrating these two modalities into a single framework remains a challenge, because of the differences in their quantitative interdependencies as well as their anatomical representations due to distinctive imaging mechanisms. In this study, we introduced a new method, joint cmICA (connectivity matrix ICA), which provides a data-driven parcellation and automated-linking of SC and FC information simultaneously using a joint analysis of functional MRI and diffusion-weighted MRI data. We showed that these two connectivity modalities produce common cortical segregation, though with various degrees of (dis)similarity. Moreover, we show conjoint functional connectivity networks and structural white matter tracts that directly link these cortical parcellations/sources, within one analysis. Overall, data driven joint cmICA provides a new approach for integrating or fusing structural connectivity and functional connectivity systematically and conveniently, and provides an effective tool for connectivity-based multimodal data fusion in brain.
Comparing the efficiency of six clearing methods in developing seeds of Arabidopsis thaliana
Authors: Attuluri Venkata Pardha Saradhi , Sánchez López Juan Francisco , Maier Lukáš , Paruch Kamil , Robert Hélène S.
Published: September 2022

Tissue clearing methods eliminate the need for sectioning, thereby helping better understand the 3D organization of tissues and organs. In the past fifteen years, clearing methods have been developed to preserve endogenous fluorescent protein tags. Some of these methods (ClearSee, TDE, PEA-Clarity, etc.) were adapted to clear various plant species, with the focus on roots, leaves, shoot apical meristems, and floral parts. However, these methods have not been used in developing seeds beyond the early globular stage. Tissue clearing is problematic in post-globular seeds due to various apoplastic barriers and secondary metabolites. In this study, we compared six methods for their efficiency in clearing Arabidopsis thaliana seeds at post-globular embryonic stages. Three methods (TDE, ClearSee, and ClearSee alpha) have been already reported in plants whereas the others (fsDISCO, FAST9, and CHAPS clear) are used in this context for the first time. These methods were assessed for seed morphological changes, clearing capacity, removal of tannins, and spectral properties. We tested each method in seeds from globular to mature stages. The pros and cons of each method are listed herein. ClearSee alpha appears to be the method of choice as it preserves seed morphology and prevents tannin oxidation. However, FAST9 with 60% iohexol as a mounting medium is faster, clears better, and appears suitable for embryonic shape imaging. Our results may guide plant researchers to choose a suitable method for imaging fluorescent protein-labeled embryos in intact Arabidopsis seeds.

Key message

ClearSee alpha and FAST9 were optimized for imaging Arabidopsis seeds up to the torpedo stages. The methods preserve the fluorescence of reporter proteins and seed shape, allowing phenotyping embryos in intact seeds.
Measuring the similarity of SMLM-derived point-clouds
Authors: Baragilly Mohammed , Nieves Daniel J. , Williamson David J. , Peters Ruby , Owen Dylan M.
Published: September 2022

Single-molecule localisation microscopy produces data in the form of point-clouds. Here, we present a tool for assessing the similarity of two such point-clouds, which, unlike measures such as co-localisation, is insensitive to differences that are not preserved between data sets. The presented method can determine whether two point-clouds were generated from the same conditions and can identify from which of two experimental conditions an unseen point-cloud was likely derived.
Neural correlates of object-extracted relative clause processing across English and Chinese
Authors: Dunagan Donald , Stanojević Miloš , Coavoux Maximin , Zhang Shulin , Bhattasali Shohini , Li Jixing , Brennan Jonathan , Hale John
Published: September 2022

Are the brain bases of language comprehension the same across all human languages, or do these bases vary in a way that corresponds to differences in linguistic typology? English and Mandarin Chinese attest such a typological difference in the domain of relative clauses. Using fMRI with English and Chinese participants, who listened to the same translation-equivalent story, we analyzed neuroimages time-aligned to object-extracted relative clauses in both languages. In a GLM analysis of these naturalistic data, comprehension was selectively associated with increased hemodynamic activity in left posterior temporal lobe, angular gyrus, inferior frontal gyrus, precuneus, and posterior cingulate cortex in both languages. This result suggests the processing of object-extracted relative clauses is subserved by a common collection of brain regions, regardless of typology. However, there were also regions that were activated uniquely in our Chinese participants albeit not to a significantly greater degree. These were in the temporal lobe. These Chinese-specific results could reflect structural ambiguity-resolution work that must be done in Chinese but not English ORCs.
A possible genomic footprint of polygenic adaptation on population divergence in seed beetles?
Authors: Arnqvist Göran , Sayadi Ahmed
Published: September 2022

Efforts to unravel the genomic basis of incipient speciation are hampered by a mismatch between our toolkit and our understanding of the ecology and genetics of adaptation. While the former is focused on detecting selective sweeps involving few independently acting or linked speciation genes, the latter states that divergence typically occurs in polygenic traits under stabilizing selection. Here, we ask whether a role of stabilizing selection on polygenic traits in population divergence may be unveiled by using a phenotypically informed integrative approach, based on genome-wide variation segregating in divergent populations. We compare three divergent populations of seed beetles (Callosobruchus maculatus) where previous work has demonstrated a prominent role for stabilizing selection on, and population divergence in, key life history traits that reflect rate-dependent metabolic processes. We derive and assess predictions regarding the expected pattern of covariation between genetic variation segregating within populations and genetic differentiation between populations. Population differentiation was considerable (mean FST = 0.23 - 0.26) and was primarily built by genes showing high selective constraints and an imbalance in inferred selection in different populations (positive Tajima’s DNS in one and negative in one) and this set of genes was enriched with genes with a metabolic function. Repeatability of relative population differentiation was low at the level of individual genes but higher at the level of broad functional classes, again spotlighting metabolic genes. Absolute differentiation (dXY) showed a very different general pattern at this scale of divergence, more consistent with an important role for genetic drift. Although our exploration is consistent with stabilizing selection on polygenic metabolic phenotypes as an important engine of genome-wide relative population divergence and incipient speciation in our study system, we note that it is exceedingly difficult to firmly exclude other scenarios.
Intranasal oxytocin enhances social preference for parents over peers in male but not female peri-adolescent California mice (Peromyscus californicus)
Authors: Guoynes Caleigh D. , Marler Catherine A.
Published: September 2022

Peri-adolescence is a critical developmental stage marked by profound changes in the valence of social interactions with parents and peers. We hypothesized that the oxytocin (OXT) and vasopressin (AVP) systems, known for influencing social behavior, would be involved in the maintenance and breaking of bonding behavior expressed by peri-adolescent males and females. In rodents, OXT is associated with mother-pup bonding and may promote social attachment to members of the natal territory. AVP, on the other hand, can act in contrasting ways to OXT and has been associated with aggression and territoriality. Specifically, we predicted that in peri-adolescent male and female juveniles of the biparental and territorial California mouse (Peromyscus californicus), a) OXT would increase the social preferences for the parents over unfamiliar age-matched peers (one male and one female), and b) AVP would break the parent-offspring bond and either increase time in the neutral chamber and/or approach to their unfamiliar and novel peers. We examined anxiety and exploratory behavior using an elevated plus maze and a novel object task as a control. Peri-adolescent mice were administered an acute intranasal (IN) treatment of 0.5 IU/kg IN AVP, 0.5 IU/kg IN OXT, or saline control; five minutes later, the behavioral tests were conducted. As predicted, we found that IN OXT enhanced social preference for parents; however, this was only in male and not female peri-adolescent mice. IN AVP did not influence social preference in either sex. These effects appear specific to social behavior and not anxiety, as neither IN OXT nor AVP influenced behavior during the elevated plus maze or novel object tasks. To our knowledge, this is the first evidence indicating that OXT may play a role in promoting peri-adolescent social preferences for parents and delaying weaning in males.

HIGHLIGHTS

In a 3-chambered choice test, peri-adolescent female and male California mice prefer their parents over peers or an empty chamber

Intranasal oxytocin (IN OXT) enhances male but not female peri-adolescent social preference for their parents

Intranasal arginine vasopressin (IN AVP) did not influence social preference in either sex

Neither IN OXT nor AVP alter peri-adolescent behavior in an elevated plus maze or novel object task

OXT may play a role in delaying weaning in males
Variation in mutation, recombination, and transposition rates inDrosophila melanogasterandDrosophila simulans
Authors: Wang Yiguan , McNeil Paul , Abdulazeez Rashidatu , Pascual Marta , Johnston Susan E. , Keightley Peter D. , Obbard Darren J.
Published: September 2022

Mutation, recombination, and transposition occurring during meiosis provide the variation on which natural selection can act and the rates at which they occur are important parameters in models of evolution. Thede novomutation rate determines levels of genetic diversity, responses to ongoing selection, and levels of genetic load. Recombination breaks up haplotypes and reduces the effects of linkage, helping to spread beneficial alleles and purge deleterious ones. Transposable elements (TE) selfishly replicate themselves through the genome, imposing fitness costs on the host and introducing complex mutations that can affect gene expression and give rise to new genes. However, even for key evolutionary models such asDrosophila melanogasterandD. simulansfew estimates of these parameters are available, and we have little idea of how rates vary between individuals, sexes, populations, or species. Here, we provide direct estimates of mutation, recombination, and transposition rates and their variation in a West African and a European population ofD. melanogasterand a European population ofD. simulans. Across 89 flies, we observe 58 single nucleotide mutations, 286 crossovers, and 89 TE insertions. Compared to the EuropeanD. melanogaster, we find the West African population has a lower mutation rate (1.67vs. 4.86 × 10−9site−1gen−1) and transposition rate (8.99vs. 23.36 × 10−5copy−1gen−1), but a higher recombination rate (3.44vs. 2.06 cM/Mb). The EuropeanD. simulanspopulation has a similar mutation rate to EuropeanD. melanogasterbut a significantly higher recombination rate and a lower but not significantly different transposition rate. Overall, we find paternal-derived mutations are more frequent than maternal ones in both species.

Highlights

De novomutation rates are 1.67 × 10−9site−1gen−1(95% HPD CI: 0.54 – 3.14 × 10−9), 4.86 × 10−9site−1gen−1(2.11 – 8.02 × 10−9), and 4.51 × 10−9site−1gen−1(1.94 – 7.75 × 10−9) for the West AfricanD. melanogaster, the EuropeanD. melanogasterand the EuropeanD. simulanspopulation, respectively.

In females, recombination rates in the absence of large genomic inversions are 3.44 cM/Mb (2.72 – 4.18), 2.06 cM/Mb (1.57 - 2.57), and 3.04 cM/Mb (2.45 - 3.73) for the three populations, respectively. There was no strong evidence of recombination observed in males.

Mutations (SNMs and indels) are male-biased.

The West AfricanD. melanogasterpopulation has a lower TE activity than the other populations andCMC-Transibis the dominant active TE. The EuropeanD. melanogasterpopulation has multiple active TEs:Gypsy, CMC-Transib, Pao, JockeyandhAT-hobo; while in EuropeanD. simulans, they areGypsy, CMC-Transib, Pao, hAT-hobo, CopiaandTcMar-Mariner.
Robust residue-level error detection in cryo-electron microscopy models
Authors: Reggiano Gabriella , Farrell Daniel , DiMaio Frank
Published: September 2022

Building accurate protein models into moderate resolution (3-5Å) cryo-electron microscopy (cryo-EM) maps is challenging and error-prone. While the majority of solved cryo-EM structures are at these resolutions, there are few model validation metrics that can precisely evaluate the local quality of atomic models built into these maps. We have developed MEDIC (Model Error Detection in Cryo-EM), a robust statistical model to identify residue-level errors in protein structures built into cryo-EM maps. Trained on a set of errors from obsoleted protein structures, our model draws off two major sources of information to predict errors: the local agreement of model and map compared to expected, and how “native-like” the neighborhood around a residue looks, as predicted by a deep learning model. MEDIC is validated on a set of 28 structures that were subsequently solved to higher-resolutions, where our model identifies the differences between low- and high-resolution structures with 68% precision and 60% recall. We additionally use this model to rebuild 12 deposited structures, fixing 2 sequence registration errors, 51 areas with improper secondary structure, 51 incorrect loops, and 16 incorrect carbonyls, showing the value of this approach to guide model building.
The Respiratory Syncytial Virus G Protein Enhances the Immune Responses to the RSV F Protein in an Enveloped Virus-like Particle Vaccine Candidate
Authors: Cullen Lori McGinnes , Luo Bin , Wen Zhiyun , Zang Lan , Durr Eberhard , Morrison Trudy G.
Published: September 2022

Respiratory syncytial virus (RSV) is a serious human respiratory pathogen, but no RSV vaccine has been licensed. Many of the vaccine candidates are focused on the viral F protein. However, it is the G protein that binds the likely receptor, CX3CR1, in human alveolar lung cells raising the question of the importance of the G protein in vaccine candidates. Using virus-like particle (VLP) vaccine candidates, we have directly compared VLPs containing only the pre-fusion F protein, only the G protein, or both glycoproteins. We report that VLPs containing both glycoproteins bind to anti-F protein specific monoclonal antibodies differently than VLPs containing only the pre-fusion F protein. Using RSV naïve cotton rats as an animal model, we have found that VLPs assembled only with the pre-F protein stimulated extremely weak neutralizing antibody (NAb) titers as did VLPs assembled with G protein. However, VLPs assembled with both glycoproteins stimulated quite robust neutralizing antibody titers, titers that were significantly higher than the combined titers induced by pre-F only or G only VLPs. VLPs assembled with both glycoproteins induced improved protection of the animals from RSV challenge compared to pre-F VLPs and induced significantly higher levels of antibodies specific for F protein antigenic sites 0, site III, and AM14 binding site compared with VLPs containing only the pre-F protein. These combined results indicate that assembly of pre-F protein with G protein in VLPs further stabilized the pre-fusion conformation or otherwise altered the conformation of the F protein increasing the induction of protective antibodies.

Importance

RSV causes significant disease in infants, young children, and the elderly. Thus, development of an effective vaccine for these populations is a priority. Most ongoing efforts in RSV vaccine development have focused on the viral fusion (F) protein, however, the importance of inclusion of G in vaccine candidates is unclear. Here, using VLPs assembled with only the F protein or only the G protein or both glycoproteins, we show that VLPs assembled with both glycoproteins are a far superior vaccine, in a cotton rat model, than VLPs containing only F protein or only G protein. The results show that the presence of G protein in the VLPs influences the conformation of the F protein and the immune responses to F protein resulting in significantly higher neutralizing antibody titers and better protection from RSV challenge. These results suggest that inclusion of G protein in a vaccine candidate may improve its effectiveness.
Trans-synaptic dwelling of SARS-CoV-2 particles perturbs neural synapse organization and function
Authors: Partiot Emma , Hirschler Aurélie , Colomb Sophie , Lutz Willy , Claeys Tine , Delalande François , Deffieu Maika S. , Roels Judith R.E. , Bons Joanna , Callon Domitille , Andreoletti Laurent , Labrousse Marc , Jacobs Frank M.J. , Rigau Valérie , Charlot Benoit , Martens Lennart , Carapito Christine , Ganesh Gowrishankar , Gaudin Raphael
Published: September 2022

SARS-CoV-2 infection is associated with short- and long-term neurological and psychiatric complications, referred to as neuroCOVID. These symptoms are relatively heterogenous and fluctuating, hampering the discovery of molecular mechanisms underlying viro-induced brain perturbations. Here, we show that the human cerebral cortex poorly supports SARS-CoV-2 dissemination using post-mortem COVID-19 patient samples, ex vivo organotypic cultures of human brain explants and stem cell-derived cortical organoids. Despite restricted infection, the sole exposure of neural cells to SARS-CoV-2 particles is sufficient to induce significant perturbations on neural synapse organization associated to electrical activity dysfunction. Single-organoid proteomics revealed that exposure to SARS-CoV-2 is associated to trans-synaptic proteins upregulation and unveiled that incoming virions dwell at LPHN3/FLRT3-containing synapses. Our study provides new mechanistic insights on the origin of SARS-CoV-2-induced neurological disorders.

One-Sentence Summary

SARS-CoV-2 modulates neural plasticity and electrical activity as viral particles lodge at the trans-synaptic interface.
Reaction pathways for the enzymatic degradation of poly(ethylene terephthalate): What characterizes an efficient PET-hydrolase?
Authors: Schubert Sune , Schaller Kay , Bååth Jenny Arnling , Hunt Cameron , Borch Kim , Jensen Kenneth , Brask Jesper , Westh Peter
Published: September 2022

Bioprocessing of polyester waste has emerged as a promising tool in the quest for a cyclic plastic economy. One key step is the enzymatic breakdown of the polymer, and this entails a complicated pathway with substrates, intermediates, and products of variable size and solubility. We have elucidated this pathway for poly(ethylene terephthalate) (PET) and four enzymes. Specifically, we combined different kinetic measurements and a novel stochastic model, and found that the ability to hydrolyze internal bonds in the polymer (endo-lytic activity) was a key parameter for overall enzyme performance. Endo-lytic activity promoted the release of soluble PET fragments with two or three aromatic rings, which, in turn, were broken down with remarkable efficiency (kcat/KM-values of about 105M-1s-1) in the aqueous bulk. This meant that about 70% of the final, monoaromatic products was formed via soluble di-or tri-aromatic intermediates.
Role of UCP2 in the energy metabolism of the cancer cell line A549
Authors: Segalés Jessica , Sánchez-Martín Carlos , Pujol Aleida , Martín-Ruiz Marta , Rial Eduardo
Published: September 2022

The uncoupling protein UCP2 is a mitochondrial carrier whose transport activity remains controversial. The physiological contexts in which UCP2 is expressed have led to the assumption that, like UCP1, it uncouples oxidative phosphorylation and as a result it lowers the generation of reactive oxygen species. Other reports have involved UCP2 in the Warburg effect and results showing that UCP2 catalyzes the export of matrix C4 metabolites to facilitate glutamine utilization, suggests that the carrier could be involved in the metabolic adaptations required for cell proliferation. We have examined the role of UCP2 in the energy metabolism of the lung adenocarcinoma cell line A549 and show that UCP2 silencing decreased the basal rate of respiration although this inhibition was not compensated by an increase in glycolysis. Silencing did not lead to changes in proton leakage, as determined from the rate of respiration in the absence of ATP synthesis, or changes in the rate of formation of reactive oxygen species. The decrease in energy metabolism did not alter the cellular energy charge. The decreased cell proliferation observed in UCP2-silenced cells would explain the decreased cellular ATP demand. We conclude that UCP2 does not operate as an uncoupling protein while our results are consistent with its activity as a C4-metabolite carrier involved in the metabolic adaptations of proliferating cells.

Highlights

UCP2 silencing decreases respiration without a compensatory increase in aerobic glycolysis

ATP levels remain unchanged despite the reduction in energy metabolism

UCP2 silencing decreases cell proliferation that could explain the decrease in energy demand

UCP2 silencing does not change the proton leakage rate

Data support the proposed involvement of UCP2 in the Warburg effect
Continuous millisecond conformational cycle of a DEAH box helicase reveals control of domain motions by atomic-scale transitions
Authors: Becker Robert A. , Hub Jochen S.
Published: September 2022

Helicases are motor enzymes found in every living organism and viruses, where they maintain the stability of the genome and control against false recombination. The DEAH-box helicase Prp43 plays a crucial role in pre-mRNA splicing in unicellular organisms by translocating single-stranded RNA. The molecular mechanisms and conformational transitions of helicases are not understood at the atomic level. We present a complete conformational cycle of RNA translocation by Prp43 in atomic detail based on molecular dynamics simulations. To enable the sampling of such complex transition on the millisecond timescale, we combined two enhanced sampling techniques, namely simulated tempering and adaptive sampling guided by crystallographic data. During RNA translocation, the center-of-mass motions of the RecA-like domains followed the established inchworm model, whereas the domains crawled along the RNA in a caterpillar-like movement, suggesting an inchworm/caterpillar model. However, this crawling required a complex sequence of atomic-scale transitions involving the release of an arginine finger from the ATP pocket, stepping of the hook-loop and hook-turn motifs along the RNA backbone, and several others. These findings high-light that large-scale domain dynamics may be controlled by complex sequences of atomic-scale transitions.
Extensions of mean-field approximations for environmentally-transmitted pathogen networks
Authors: Davies Kale , Lenhart Suzanne , Day Judy , Lloyd Alun L. , Lanzas Cristina
Published: September 2022

Many pathogens spread via environmental transmission, without requiring host- to-host direct contact. While models for environmental transmission exist, many are simply constructed intuitively with structures analogous to standard models for direct transmission. As model insights are generally sensitive to the underlying model assumptions, it is important that we are able understand the details and consequences of these assumptions. We construct a simple network model for an environmentally-transmitted pathogen and rigorously derive systems of ordinary differential equations (ODEs) based on different assumptions. We explore two key assumptions, namely homogeneity and independence, and demonstrate that relaxing these assumptions can lead to more accurate ODE approximations. We compare these ODE models to a stochastic implementation of the network model over a variety of parameters and network structures, demonstrating that with fewer restrictive assumptions we are able to achieve higher accuracy in our approximations and highlighting more precisely the errors produced by each assumption. We show that less restrictive assumptions lead to more complicated systems of ODEs and the potential for unstable solutions. Due to the rigour of our derivation, we are able to identify the reason behind these errors and propose potential resolutions.
Biosynthesis of iridoid sex pheromones in aphids
Authors: Köllner Tobias G. , David Anja , Luck Katrin , Beran Franziska , Kunert Grit , Zhou Jing-Jiang , Caputi Lorenzo , O’Connor Sarah E.
Published: September 2022

Iridoid monoterpenes, widely distributed in plants and insects, have many ecological functions. While the biosynthesis of iridoids has been extensively studied in plants, little is known about how insects synthesize these natural products. Here, we elucidated the biosynthesis of the iridoids cis-trans-nepetalactol and cis-trans-nepetalactone in the pea aphid Acyrthosiphon pisum [Harris], where they act as sex pheromones. The exclusive production of iridoids in hind legs of sexual female aphids allowed us to identify iridoid genes by searching for genes specifically expressed in this tissue. Biochemical characterization of candidate enzymes revealed that the iridoid pathway in aphids proceeds through the same sequence of intermediates as described for plants. The six identified aphid enzymes are unrelated to their counterparts in plants, conclusively demonstrating an independent evolution of the entire iridoid pathway in plants and insects. In contrast to the plant pathway, at least three of the aphid iridoid enzymes are likely membrane-bound. We demonstrated that a lipid environment facilitates the cyclization of a reactive enol intermediate to the iridoid cyclopentanoid-pyran scaffold in vitro, suggesting that membranes are an essential component of the aphid iridoid pathway. Altogether, our discovery of this complex insect metabolic pathway establishes the genetic and biochemical basis for the formation of iridoid sex pheromones in aphids and this discovery also serves as a foundation for understanding the convergent evolution of complex metabolic pathways between kingdoms.

Significance Statement

Plants, animals and microbes produce a plethora of natural products that are important for defense and communication. Most of these compounds show a phylogenetically restricted occurrence, but in rare instances, the same natural product is biosynthesized by organisms in two different kingdoms. The monoterpene-derived iridoids, for example, have been found in more than 50 plant families, but are also observed in several insect orders. The aphid iridoid pathway discovered in this study, one of the longest and most chemically complex insect-derived natural product biosynthetic pathways reported to date, is compared with iridoid biosynthetic pathways in plants and highlights the mechanisms underlying the convergent evolution of metabolic enzymes in insects and plants.
Kinase-independent activity of DYRK1A promotes viral entry of highly pathogenic human coronaviruses
Authors: Strine Madison S. , Cai Wesley L. , Wei Jin , Alfajaro Mia Madel , Filler Renata B. , Biering Scott B. , Sarnik Sylvia , Patil Ajinkya , Cervantes Kasey S. , Collings Clayton K. , DeWeirdt Peter C. , Hanna Ruth E. , Schofield Kevin , Hulme Christopher , Konermann Silvana , Doench John G. , Hsu Patrick D. , Kadoch Cigall , Yan Qin , Wilen Craig B.
Published: September 2022

Identifying host genes essential for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has the potential to reveal novel drug targets and further our understanding of coronavirus disease 2019 (COVID-19). We previously performed a genome-wide CRISPR/Cas9 screen to identify pro-viral host factors for highly pathogenic human coronaviruses. Very few host factors were required by diverse coronaviruses across multiple cell types, but DYRK1A was one such exception. Although its role in coronavirus infection was completely unknown, DYRK1A encodes Dual Specificity Tyrosine Phosphorylation Regulated Kinase 1A and regulates cell proliferation, and neuronal development, among other cellular processes. Interestingly, individuals with Down syndrome overexpress DYRK1A 1.5-fold and exhibit 5-10x higher hospitalization and mortality rates from COVID-19 infection. Here, we demonstrate that DYRK1A regulates ACE2 and DPP4 transcription independent of its catalytic kinase function to support SARS-CoV, SARS-CoV-2, and MERS-CoV entry. We show that DYRK1A promotes DNA accessibility at the ACE2 promoter and a putative distal enhancer, facilitating transcription and gene expression. Finally, we validate that the pro-viral activity of DYRK1A is conserved across species using cells of monkey and human origin and an in vivo mouse model. In summary, we report that DYRK1A is a novel regulator of ACE2 and DPP4 expression that may dictate susceptibility to multiple highly pathogenic human coronaviruses. Whether DYRK1A overexpression contributes to heightened COVID-19 severity in individuals with Down syndrome through ACE2 regulation warrants further future investigation.
Organization of Upstream ESCRT Machinery at the HIV-1 Budding Site
Authors: Hudait Arpa , Hurley James H. , Voth Gregory A.
Published: September 2022

In the late stages of the HIV-1 life cycle, membrane localization and self-assembly of the Gag polyproteins induce membrane deformation and budding. However, release of the immature virion requires direct interaction between Gag lattice and upstream ESCRT machinery at the budding site, followed by assembly of the downstream ESCRT-III factors, culminating in membrane scission. In this work, using “bottom-up” coarse-grained (CG) molecular dynamics (MD) simulations we investigated the interactions between Gag and different upstream ESCRT components to delineate the molecular organization of proteins at the membrane neck of the HIV-1 budding site. We developed CG models of upstream ESCRT proteins and HIV-1 structural protein Gag based on experimental structural data and extensive all-atom MD simulations. We find that ESCRT-I proteins bound to the immature Gag lattice can recruit multiple copies of ESCRT-II coating the membrane neck. ESCRT-I can effectively oligomerize to higher-order complexes both in absence of ESCRT-II and when multiple copies of ESCRT-II are localized at the bud neck. The ESCRT-I/II supercomplexes observed in our simulations exhibit predominantly extended conformations. Importantly, the ESCRT-I/II supercomplex modulates the membrane mechanical properties at the budding site by decreasing the overall Gaussian curvature of membrane neck. Our findings serve to elucidate a network of interactions between the upstream ESCRT machinery, immature Gag lattice, and membrane bud neck that regulate the protein assemblies and enable bud neck constriction.
Surveying mutation density patterns around specific genomic features
Authors: Yu Hui , Ness Scott , Li Chung-I , Bai Yongsheng , Mao Peng , Guo Yan
Published: September 2022

Mutation density patterns reveal unique biological properties of specific genomic regions and shed light on the mechanisms of carcinogenesis. Although previous studies reported insightful mutation density patterns associated with certain genomic regions such as transcription start sites and DNA replication origins, a tool that can systematically investigate mutational spatial patterns is still lacking. Thus, we developed MutDens, a bioinformatic tool for comprehensive analysis of mutation density patterns around genomic features, namely, genomic positions, in humans and model species. By scanning the bidirectional vicinity regions of given positions, MutDens systematically characterizes the mutation density for single-base substitution mutational classes after adjusting for total mutation burden and local nucleotide proportion. Analysis results using MutDens not only verified the previously reported transcriptional strand bias around transcription start sites and replicative strand bias around DNA replication origins, but also identified novel mutation density patterns around other genomics features, such as enhancers and retrotransposon insertion polymorphism sites. To our knowledge, MutDens is the first tool that systematically calculates, examines, and compares mutation density patterns, thus providing a valuable avenue for investigating the mutational landscapes associated with important genomic features.
Small-angle neutron scattering study of mesoscale magnetic disordering and skyrmion phase suppression in the frustrated chiral magnet Co6.75Zn6.75Mn6.5
Authors: White Jonathan S. , Karube Kosuke , Ukleev Victor , Derlet P. M. , Cubitt R. , Dewhurst C. D. , Wildes A. R. , Yu X. Z. , Rønnow H. M. , Tokura Yoshinori , Taguchi Yasujiro
Published: September 2022

Co–Zn–Mn chiral cubic magnets display versatile magnetic skyrmion phases, including equilibrium phases stable far above and far below room temperature, and the facile creation of robust far-from-equilibrium skyrmion states. In this system, compositional disorder and magnetic frustration are key ingredients that have profound effects on the chiral magnetism. Reported here are studies of the magnetism in Co6.75Zn6.75Mn6.5 by magnetometry, small-angle neutron scattering (SANS), magnetic diffuse neutron scattering and Lorentz transmission electron microscopy (LTEM). While features in magnetometry and LTEM often give standard indications for skyrmion formation, they are not readily observed from the measurements on this system. Instead, skyrmion lattice correlations are only revealed by SANS, and they are found to form an orientationally disordered structure in a minority fraction of the sample. The majority fraction of the sample always displays orientationally disordered helical spin correlations, which undergo further disordering along the radial direction on cooling below the critical temperature (T
c ≃ 102 K). The near-complete suppression of the skyrmion phase, and the process of disordering on cooling, are attributed to competing magnetic interactions that dominate over the ferromagnetic interaction expected to favour chiral magnetism in this system. These competing interactions start to develop above T
c and become further enhanced towards low temperatures. The present observations of co-existing and disordered magnetic correlations over multiple length scales are not unique to Co6.75Zn6.75Mn6.5 but are seemingly common to the family of Co–Zn–Mn compounds with finite Mn, and their accurate description presents a challenge for theoretical modelling. In addition, this study highlights a need for neutron instrumentation capable of the comprehensive measurement of magnetic correlations over expanded ranges of momentum transfer in such multiple-length-scale magnets.
The learning model of crisis management: the COVID-19 case in the hospitality industry
Authors: Li Bin , Zhang Tingting , Chen Yuting , Hua Nan
Published: September 2022

Purpose

This study aims to explore the underlying mechanisms that support the resilience of the Chinese hospitality industry during and after the COVID-19 epidemic.

Design/methodology/approach

Content analysis was applied to 133 manually collected text articles about COVID-19 responses and strategies.

Findings

A two-step learning model (emergency reaction, precautions and prevention stages) was identified in the study. In the emergency reaction step, the primary strategies were related to customers, employees, suppliers and facility/food. In the precautions and prevention step, the strategies were related to customers, employees, suppliers and society/public relations. Multiple stakeholders are discussed in the two circles over a continual process in the learning, reacting and adapting stages.

Originality/value

A gap in the literature is filled by this study, providing a learning model and synthesizing various strategies applied in the hotel sector for multiple stakeholders.
A networked understanding of new mathematics teachers' learning, when participating in a lesson-study induction programme
Authors: Skott Charlotte Krog
Published: September 2022

Purpose

The purpose of the article is to identify, describe and explain what and how new mathematics teachers learn when participating in a lesson-study induction programme, by networking theories.

Design/methodology/approach

To explore this phenomenon, the author combines the two theoretical frameworks, Patterns of Participation and the Knowledge Quartet. In a case study with one teacher, the latter framework is used as a zoom into the parts identified as important by the first framework.

Findings

The combination of the two frameworks proved productive as it provides: (1) a more complete insight into what the teacher learned, (2) complementary views on what and how the teacher learned and (3) different insights into the complex situations new teachers find themselves in. These findings contribute to the theorisation of lesson study and to research on new mathematics teachers.

Research limitations/implications

As the study includes only one teacher, its results regarding new teachers' learning are not generalisable to the same extent as are the results regarding the benefits of combining the two frameworks.

Practical implications

In Denmark and other western countries, it is crucial to provide new mathematics teachers with support that focuses specifically on mathematics education. The article proposes a design of such an induction programme based on lesson study.

Originality/value

Outside East Asia, lesson study is rarely used to support the professional development of new mathematics teachers during their first teaching years. The article contributes an exploration of this phenomenon in Denmark.
The interplay between spirituality, compassion and citizenship behaviours in the lives of educators: a study
Authors: Mahipalan Manju
Published: September 2022

Purpose

This study aims to investigate the impact of workplace spirituality on citizenship behaviours of high school teachers. In addition, the moderating role of workplace compassion is examined.

Design/methodology/approach

This study is quantitative in nature. Data were collected from 232 secondary school teachers using a structured questionnaire. Partial least squares-based structural equation modelling was used to analyse the data.

Findings

Results revealed evidence for the positive relationship between spirituality and citizenship behaviours. Compassion was found to be a potential moderator in enhancing the spirituality–citizenship behaviour connection. This study attempts to understand one of the ways in which spirituality affects workplace behaviour by specifying the role of a moderator. The complex nature of the phenomenon is delineated further by identifying the plausible relationship with other variables.

Practical implications

Organisations can leverage the spiritual resources available to their people to compound their proactive behaviours, thus creating a win–win situation for both the parties involved. This is particularly useful for educational institutions where such behaviours are not merely desirable but could significantly elevate the working environment.

Originality/value

This study evaluates the connections between spirituality, compassion and citizenship behaviour, which remain largely unexplored in a non-profit sector. The construct of workplace compassion is not sufficiently mapped, especially in a context where it is thought to be embedded in the work environment.