bluuebunny/crossref_metadata_2025 huggingface dataset:
Is the electrogenic Na/HCO3 cotransporter a CO2 channel?
Authors: Occhipinti Rossana , Lu Jing , Boron Walter F
Published: June 2021

It has now become clear that not all gases cross all biological membranes simply by dissolving into the lipid phase of the membrane, but that in some cases dissolved gases cross membranes via channels formed by integral membrane proteins.

Currently, we know of three families of gas channels—the aquaporins (AQPs), rhesus (Rh) proteins, and urea transporters (UTs)—that can augment CO2 and/or NH3 permeability. In this study, we investigate the possibility that a fourth family exists, exemplified by the electrogenic Na/HCO3 cotransporter (NBCe1, SLC4A4), which may be a CO2 channel.

We investigate the CO2 permeability of NBCe1 by combining electrophysiology experiments with mathematical modeling. In the electrophysiology work, we use microelectrodes to monitor intracellular pH (pHi) of oocytes injected with water (controls) or cRNA encoding human NBCe1‐A, which transports one Na+ and one CO3= (carbonate) ion into the cell. We determine the maximal rate of pHi change, (dpHi/dt)max, as we switch the extracellular solution from CO2/HCO3−‐free to (1) equilibrated (EQ) CO2/HCO3− at pH 7.50, or (2) an out‐of‐equilibrium (OOE) solution at the same pH, but containing only CO2 (“pure CO2”), or (3) an OOE solution containing only HCO3− (“pure HCO3−”).

We find that exposing control oocytes to “pure HCO3−” elicits virtually no change in pHi, whereas exposing them to “pure CO2” or EQ CO2/HCO3− causes pHi to fall rapidly and at nearly the same rate. Exposing NBCe1‐A oocytes to “pure HCO3−” causes pHi to rise moderately fast (CO3= uptake), whereas exposing them to “pure CO2” causes pHi to fall rapidly (CO2 uptake). Intuition suggests that exposing an NBCe1‐A oocyte to EQ CO2/HCO3− will produce a pHi trajectory halfway between those of “pure HCO3−” and “pure CO2”. Surprisingly, we find that exposing NBCe1‐A oocytes to EQ causes pHi to fall about as rapidly as with “pure CO2”. Thus, NBCe1‐A, in the presence of HCO3−, appears to increase CO2 permeability.

To assist us in interpreting our pHi data, we extended our 3D reaction‐diffusion mathematical model of CO2 fluxes across the oocyte membrane to include NBCe1‐mediated transmembrane fluxes of CO3= (informed by two‐electrode voltage clamp data). The model can reproduce the pHi data over the first 15 sec of a physiological experiment, for both “pure HCO3−” and “pure CO2”. However, reproducing the fast pHi decrease of EQ CO2/HCO3− requires that we increase CO2 permeability, thereby supporting the hypothesis that NBCe1 may conduct CO2 while transporting CO3=.

Support or Funding Information

Supported by grants from the Office of Naval Research (N00014‐11‐1‐0889, N00014‐14‐1‐0716) and NIH (U01‐GM111251, K01‐DK107787)
Developmental Regulation of Chloride Currents in the Dorsal Motor Nucleus of the Vagus of the Rat
Authors: McMenamin Caitlin A , Anselmi Laura , Browning Kirsteen N , Travagli R. Alberto
Published: June 2021

Tonically firing parasympathetic neurons of the dorsal motor nucleus of the vagus (DMV) modulate the functions of the proximal gastrointestinal (GI) tract. The pacemaker activity of DMV neurons is modulated by synaptic inputs from adjacent autonomic areas, including the nuclei of the tractus solitarius. Functional maturation of these vagal sensorimotor neurocircuits results from intense synaptogenesis and neuronal reorganization in the first postnatal weeks and their maturation may be assessed by the analysis of their time constant of synaptic current decay.

Prior studies have shown that, in adult rats, perfusion with the GABAA antagonist bicuculline (BIC) increases the firing rate of DMV neurons, and BIC microinjection in the DMV increase gastric motility and pancreatic exocrine secretions, indicating a prominent role of brainstem GABA synapses in the modulation of GI functions. Conversely, glycine synapses do not appear to be present in GI‐related brainstem neurocircuits of adult rats.

The aim of the present study was to examine GABA and glycine‐ mediated chloride currents in the development of synaptic inputs onto DMV neurons. Using whole cell recordings, miniature inhibitory currents were recorded in rats from postnatal day 1 (P1) to postnatal day 30 (P30), and analyzed for decay constant and event frequency. Between P1–15, the baseline frequency was 1.9±0.35 events.s−1 and the current decay constant was 10.3±1.4 ms (N=30). These values were not altered by maturation (P>0.05 for both parameters).

Perfusion of the slice with the GABAA antagonist bicuculline (1 or 10uM) either abolished completely or decreased the frequency and the decay constant of the inhibitory events to a similar extent in neurons from P1–15 rats or >P15 rats (N=37 and N=65 for 1 and 10uM, respectively). Conversely, while perfusion with the glycine antagonist strychnine (1μM) did not decrease event frequency significantly in any of the groups, it increased the current decay constant (from 8.2±0.65 to 11.9±0.75ms and from 7.6±0.57 to 10.5±0.79ms, in P1–15 and >P15,neurons, respectively). Strychnine altered inhibitory currents in a significantly larger percentage of P1–15 (N=67) neurons, and blocked all events in 3 cells from P1–15 rats, but not in >P15 rats (n=58; p<0.05 vs P1–15).

These data suggest that the development of brainstem vagal neurocircuits involves an early phase, during which GABA and glycine neurotransmission appear co‐released by the same neurons. The role of glycine in synaptic transmission appears to start declining at approximately P15. Disruption of this developmental switch from GABA‐glycine to purely GABAergic transmission may occur in response to early life stress, infection or inflammation, which may lead to adverse consequences in vagal efferent control of visceral functions.

Support or Funding Information

Funding: NIH DK 99350 and DK 78364 & NSF IOS‐1148978
Wellness Characteristics of College Freshmen at West Virginia University
Authors: Morris Allison M , Barr Makenzie L , Famodu Oluremi A , Colby Sarah E , Zhou Wenjun , Hagedorn Rebecca L , Clark Rashel L , Riggsbee Kristin , Olfert Melissa Diann
Published: June 2021

Objective

To determine baseline wellness characteristics of students participating in a community‐based participatory research intervention to reduce obesity among college students.

Methods

An online‐based survey was offered during the first four weeks of the Fall 2016 semester. The survey was available to all students, however freshmen received a $5 incentive for taking the survey and their responses were kept for analysis. The survey was distributed through in‐person tabling, flyering and requests to faculty members to share with students. The survey included questions to determine fruit and vegetable consumption, physical activity level, stress score, and sleep hours. BMI was determined through self‐reported height and weight. Each student received their results in a personalized wellness report card that documented their health scores compared with the campus average and general recommendations, as well as health improvement tips.

Results

Total respondents (n=360) were 69% female and ethnic diversity (83% Caucasian, 6% African American, 4% Asian, 3% Hispanic, 4% other) was similar to the total university population. Respondents had an average fruit and vegetable consumption of 3 serving per day (2.71± 2.25 SD), a physical activity level (IPAQ) of 3224 (3.224.40± 2652.6 SD), a stress score of 25 (24.92±7.91 SD) out of 50, averaged 7 hours of sleep (6.95± 1.13 SD) and the campus have an average BMI of 24 (24.22±4.41 SD). Participants were asked if they identified themselves as being from the Appalachian region (n= 114). Those who self‐ identified as Appalachian had a FV consumption of 3 servings per day (2.97± 2.24 SD), a PA level of 3381 (3381± 2755.3 SD), a stress score of 25 (24.54± 8.40 SD), an average of 7 (6.99± 1.41 SD) sleep hours and a BMI of 24 (24.12± 4.41 SD). Scores of self‐ identified Appalachian students' health behaviors were not statically significant different than the general student population.

Conclusion

Survey results provide insight into the health behaviors of college students. As Appalachian populations are often at higher risk of health disparities, having Appalachian students with similar health behaviors to the general population suggest a possible protective factor of high educational attainment.

Support or Funding Information

This abstract is based upon work that is supported by the National Institute of Food and Agriculture, U.S. Department of Agriculture, under award number 2014‐67001‐21851.
Discovery Recovery Methods and Detection of food borne parasites
Authors: Aralu Angel
Published: June 2021

In 2013, more than 640 individuals acquired Cyclospora infection in the US. Illness was associated with consumption of imported salad mixes and cilantro that were commercially processed and rinsed. To date, there is no protocol that would allow testing of large volumes of water to detect small number of parasites in produce wash‐waters. Cryptosporidium parvum and Cyclospora cayetanensis are protozoan parasites causing gastrointestinal illness in humans and animals both immunocompetent and immunocompromised hosts. Cryptosporidium parvum are spherical, 4–5μm in size, it can be acquired when ingesting foods and drinking, or accidentally ingesting, water contaminated with feces containing Cryptosporidium oocysts. The illnesses are characterized by acute diarrhea, stomach cramps, nausea, vomiting, and weight loss. Cyclospora cayetanensis are spherical as well, it is 8–10μm in size, it can also be acquired by person‐to‐person transmission and when in contact with infected animals; it is also spread via the fecal‐oral route (the host must ingest something that had been contaminated with feces that contain infectious oocysts). For oocysts to be termed infectious, the oocyst has to be sporulated (produce or form spores). The related disease Cyclosporiasis is acquired by ingestion of water or foods contaminated with human feces containing Cyclospora oocysts. Water samples were collected from a wash site in the southern area of Georgia every other day. The objective of this study was to compare two methods for oocyst recovery and detection from carrot wash‐water. The carrots were grated and washed with the water sample. The carrot wash‐water was spiked with ten and fifty oocysts of Cryptosporidium and Cyclospora. Two types of produce wash solutions fresh water and chlorinated water used by the fresh produce industry were evaluated ten liters of wash water were flocculated or filtered and then concentrated by centrifuging. Cryptosporidium oocysts from the concentrated water sample was treated with immunomagnetic separation (IMS) and detected by immunofluorescence assay (IFA). Cyclospora oocysts were concentrated by discontinuous sucrose gradients and examined by Nomarski microscopy. All samples were further examined by nested Polymerase Chain Reaction (PCR) specific for each parasite. Though both methods effectively recovered parasites, our trial also suggests that filtration and flocculation does not completely remove Cryptosporidium and Cyclospora oocysts in the wash water. In conclusion, these methods can significantly contribute to environmental testing during outbreak investigations and surveillance studies.

Support or Funding Information

NSF #1067896
Piceatannol May Slow Cancer Cachexia‐Induced Weight‐Loss In Vivo
Authors: Kershaw Jonathan , Kim Kee‐Hong
Published: June 2021

Cancer‐associated cachexia (CAC) is the ongoing loss of lean muscle and adipose that results in functional impairment. CAC reduces chemotherapy effectiveness, lowers quality of life, and is considered the direct cause of death in up to 20% of all cancer mortalities. Strategies that preserve body weight can improve survival and quality of life. Recent reports indicate that preserving adipose mass, specifically, is a key strategy to protect body weight and increase survival in CAC. Piceatannol is resveratrol analog with anti‐inflammatory and anti‐adipogenic properties. We recently demonstrated that piceatannol, unlike resveratrol, inhibits lipolysis, the main mechanism of adipose loss in CAC, in cancer‐associated conditions in vitro. In this study, we evaluated piceatannol's effect in tumor‐induced weight loss. Five‐week‐old female BALB/c mice were inoculated with C26 colon carcinoma cells, an established model of CAC wasting. Following tumor establishment, mice received daily piceatannol injection for two weeks. Piceatannol treatment showed a strong trend in protecting against tumor‐induced weight loss and wasting. The effect of piceatannol appeared to be independent of tumor growth, as no difference in tumor size and volume was detected between piceatannol‐treated and vehicle‐treated tumor‐bearing mice. In addition, mice receiving piceatannol treatment exhibited higher serum triglycerides than vehicle‐treated tumor‐bearing mice. Dual‐energy X‐ray absorptiometry revealed a trend for preserved lean muscle in piceatannol‐treated mice with little effect on fat mass. This study lays the foundation for the use of piceatannol, a natural small‐molecule, in the preservation of body weight in CAC.

Support or Funding Information

NIH, 5R03CA184544‐01A1 and U.S. Department of Agriculture National Needs Fellowship
Inhibition of Gliadin Digestion by Green Tea Polyphenols and the Potential Implications for Celiac Disease
Authors: Van Buiten Charlene B. , Lambert Joshua D. , Sae‐tan Sudathip , Elias Ryan J.
Published: June 2021

Green tea has been suggested to have beneficial effects on human health through a variety of biological mechanisms. (−)‐Epigallocatechin‐3‐gallate (EGCG), the major phenolic constituent of green tea, has been reported to mitigate a number of inflammatory and hypersensitivity disorders in laboratory models, and has been shown to moderate pathways related to food allergies in vitro. Previous studies by our group have characterized interactions between EGCG and a2‐gliadin (amino acids 57–89), an immunodominant peptide associated with stimulation of the immune response in celiac disease, and have demonstrated that this polyphenol is able to form complexes with proline‐rich immunostimulatory epitopes on the peptide. Here, we sought to determine the impact of decaffeinated green tea extract (GTE) on the digestion of gliadin protein and production of smaller immunostimulatory peptides in vitro. Complexation of GTE and gliadin was confirmed via an increase in turbidity as a result of co‐precipitation upon titration of GTE into a gliadin solution. Co‐precipitation was observed again during in vitro digestion when gliadin was exposed to digestive proteases pepsin and trypsin. SDS‐PAGE of post‐digestion suspensions and supernatants revealed that GTE not only precipitated gliadin from solution, but also impeded the hydrolytic activity of pepsin and trypsin, resulting in decreased production of low molecular weight gliadin digestion products. An enzyme inhibition assay revealed the GTE dose‐dependently inhibits trypsin (IC50 = 113 mg/ml) in an uncompetitive manner with regard to substrate concentration. Ongoing studies are focused on determining the inhibitory effect of GTE against pepsin, and characterizing the effects of GTE on the immunogenic properties of gliadin using a cell‐culture based model of intestinal permeability and inflammation. We expect that the sequestration of gliadin via GTE complexation will result in decreased permeability and inflammation. Our results to date provide further support for the potential beneficial effects of GTE in the context of celiac disease.

Support or Funding Information

This project was supported by a National Institute of Food and Agriculture Predoctoral Fellowship awarded to C.V. under Grant no. 2016‐67011‐24702, USDA Agriculture and Food Research Initiative.
The Femoral Head-Shaft Angle Is Not a Predictor of Hip Displacement in Children Under 5 Years With Cerebral Palsy: A Population-based Study of Children at GMFCS Levels III-V
Authors: Terjesen Terje , Horn Joachim
Published: June 2021

Background:

The aim of this study was to evaluate whether the femoral head-shaft angle (HSA) is a predictor of hip displacement in children with cerebral palsy (CP).

Methods:

The patients were recruited from a population-based hip surveillance program. Inclusion criteria were age under 5 years, bilateral CP, Gross Motor Function Classification System (GMFCS) levels III-V, and migration percentage (MP) of both hips <40% at the primary radiograph. With these criteria, 101 children (61 boys) were included. GMFCS was level III in 26 patients, level IV in 23, and level V in 52. An anteroposterior radiograph of the pelvis was taken at diagnosis and at the last follow-up. Only the worst hip of each patient (the hip with the largest MP) was used for the analyses.

Results:

The mean age at the primary radiograph was 2.4 years (range, 0.8 to 4.9 y). The mean primary HSA was 171.0 degrees (range, 152 to 190 degrees). The mean follow-up time was 4.3 years (range, 0.9 to 11.8 y). The mean MP at the primary radiograph was 17.5% (range, 0% to 39%) and at the last follow-up 41.9% (range, 0% to 100%). At that point, MP was <40% in 54 hips and ≥40% in 47 hips. There was no significant difference in primary HSA between patients with final MP<40% and those with final MP≥40% (170.8 and 171.3 degrees, respectively; P=0.761). At the last follow-up, the mean HSA was significantly larger in hips with final MP≥40% than in hips with final MP<40% (171.1 vs. 167.4 degrees; P=0.029).

Conclusions:

There was a markedly increased valgus position of the proximal femur in nonambulatory children with CP. However, the primary HSA in children below 5 years of age was not a predictor of later hip displacement, defined as MP≥40%.

Clinical Relevance:

Measurement of HSA is not necessary in routine hip surveillance in children below 5 years.

Level of Evidence:

Level I—investigating a diagnostic test.
Sexually Predatory Behavior in an Adolescent Female
Authors: DEESING MICHOLE A. , BUTTLAIRE ANNA , NIKJOO ARYA , JOSHI PARAMJIT
Published: June 2021

This report describes a rare case of an adolescent female with a history of unspecified depressive disorder, disinhibited social engagement disorder, and significant history of sexual trauma at an early age, who initially presented with suicidal ideation. During the initial evaluation, the patient was found to have engaged in sexually predatory behavior toward younger boys, including solicitation and inappropriate sexual behavior. This report discusses relevant literature on the prevalence, risk factors, and treatment for this behavior among female adolescent sexual predators, as sex offenders are primarily thought to be men. General recommendations for health care professionals caring for female sexual offenders are addressed as well as the importance of early treatment and appropriate training for professionals. The patient has been deidentified.
Adherence to daily HIV pre-exposure prophylaxis in a large-scale implementation study in New South Wales, Australia
Authors: Jin Fengyi , Amin Janaki , Guy Rebecca , Vaccher Stefanie , Selvey Christine , Zablotska Iryna , Holden Jo , Price Karen , Yeung Barbara , Ogilvie Erin , Quichua Gesalit Cabrera , Clackett Shawn , McNulty Anna , Smith David , Templeton David J. , Bavinton Benjamin , Grulich Andrew E.
Published: June 2021

Objectives:

To examine patterns of long-term pre-exposure prophylaxis (PrEP) adherence and its association with HIV seroconversion in NSW, Australia.

Design:

Population-based HIV PrEP implementation study.

Methods:

Expanded PrEP Implementation in Communities in New South Wales was an open-label study of daily oral PrEP which recruited participants from March 2016 to April 2018. Adherence was measured using dispensing records. PrEP discontinuation was defined as an at least 120-day period without PrEP coverage. Long-term adherence patterns were identified using group-based trajectory modelling.

Results:

Participants dispensed at least once (n = 9586) were almost all male (98.5%), identified as gay (91.3%), with a median age of 34 years (range: 18–86). Of the 6460 (67.4%) participants who had at least 9 months of follow-up since first dispensing, 1942 (30.1%) discontinued. Among these, 292 (15.0%) restarted later. Four distinct groups were identified [‘Steep decline’ in adherence (15.8%), ‘Steady decline’ (11.6%), ‘Good adherence’ (37.4%), and ‘Excellent adherence’ (35.2%)]. Older (P < 0.001) and gay-identified (P < 0.001) participants were more likely to have higher adherence, so were those living in postcodes with a higher proportion of gay-identified male residents (P < 0.001). Conversely, those who at baseline reported recent crystal methamphetamine use and had a recent diagnosis of sexually transmitted infection (STI) had lower adherence (P < 0.001). Overall HIV incidence was 0.94 per 1000 person-years (95% confidence interval: 0.49–1.81; n = 9) and was highest in the ‘steep decline’ group (5.45 per 1000 person-years; P = 0.001).

Conclusion

: About 15% of participants stopped PrEP during study follow-up and were at increased risk of HIV infection. They were more likely to be younger and report a recent STI or methamphetamine use prior to PrEP initiation.
Drug Repurposing of potential drug targets for treatment of COVID-19
Authors: Gupta Rajaneesh K. , Nwachuku Enyinna L. , Zusman Benjamin E. , Jha Ruchira M. , Puccio Ava M.
Published: June 2021

Drug repurposing has the potential to bring existing de-risked drugs for effective intervention in an ongoing pandemic—COVID-19 that has infected over 131 million, with 2.8 million people succumbing to the illness globally (as of April 04, 2021). We have used a novel `gene signature’-based drug repositioning strategy by applying widely accepted gene ranking algorithms to prioritize the FDA approved or under trial drugs. We mined publically available RNA sequencing (RNA-Seq) data using CLC Genomics Workbench 20 (QIAGEN) and identified 283 differentially expressed genes (FDR<0.05, log2FC>1) after a meta-analysis of three independent studies which were based on severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) infection in primary human airway epithelial cells. Ingenuity Pathway Analysis (IPA) revealed that SARS-CoV-2 activated key canonical pathways and gene networks that intricately regulate general anti-viral as well as specific inflammatory pathways. Drug database, extracted from the Metacore and IPA, identified 15 drug targets (with information on COVID-19 pathogenesis) with 46 existing drugs as potential-novel candidates for repurposing for COVID-19 treatment. We found 35 novel drugs that inhibit targets (ALPL, CXCL8, and IL6) already in clinical trials for COVID-19. Also, we found 6 existing drugs against 4 potential anti-COVID-19 targets (CCL20, CSF3, CXCL1, CXCL10) that might have novel anti-COVID-19 indications. Finally, these drug targets were computationally prioritized based on gene ranking algorithms, which revealed CXCL10 as the common and strongest candidate with 2 existing drugs. Furthermore, the list of 283 SARS-CoV-2-associated proteins could be valuable not only as anti-COVID-19 targets but also useful for COVID-19 biomarker development.
Health-related quality of life of female sex workers living with HIV in South Africa: a cross-sectional study
Authors: Wang Linwei , Dowdy David W. , Comins Carly A. , Young Katherine , Mcingana Mfezi , Mulumba Ntambue , Mhlophe Hlengiwe , Chen Claire , Hausler Harry , Schwartz Sheree R. , Baral Stefan , Mishra Sharmistha
Published: June 2021

Introduction

Health-related quality of life (HRQoL) is an important HIV outcome beyond viral suppression. However, there are limited data characterizing HRQoL of key populations including female sex workers (FSW) living with HIV.

Methods

We used baseline data (June 22, 2018-March 23, 2020) of FSW who were diagnosed with HIV and enrolled into a randomized trial in Durban, South Africa. HRQoL information was collected by a generic preference-accompanied tool with five domains (EQ-5D), and summarized into a single score (range 0-1) which represents health utility. We employed multivariable beta regression models to identify determinants of HRQoL and to estimate subgroup-specific HRQoL score. Using external estimates of life expectancy and population size, we estimated the number of quality adjusted life years reduced among FSW living with HIV in South Africa associated with violence and drug use.

Results

Of 1363 individuals (mean age: 32.4 years; mean HRQoL score: 0.857) in our analysis, 62.6% used drugs, 61.3% experienced physical or sexual violence, and 64.6% self-reported taking antiretroviral treatment (ART). The following were associated with a reduction in the average marginal HRQoL score: older age (per decade: 0.018 [95% confidence interval (CI): 0.008, 0.027]), drug use (0.022 [0.007, 0.036]), experience of violence (0.024 [0.010, 0.038]), and moderate (vs. no) level of internalized stigma (0.023 [0.004, 0.041]). Current ART use was associated with a 0.015-point (−0.001, 0.031) increase in the HRQoL score. The estimated mean (95%CI) HRQoL scores ranged from 0.838 (0.816, 0.860) for FSW who used drugs, experienced violence, and were not on ART; to 0.899 (0.883, 0.916) for FSW who did not use drugs nor experience violence and were on ART. Our results can be translated into a reduction in 37,184 and 39,722 quality adjusted life years related to drug use and experience of violence, respectively in South Africa.

Conclusions

These results demonstrate the association of ART with higher HRQoL among FSW and the need to further address structural risks including drug use, violence, and stigma. Population-specific estimates of HRQoL score can be further used to calculate quality-adjusted life years in economic evaluations of individual and structural interventions addressing the needs of FSW living with HIV.

Clinical Trial Registration

NCT03500172 (April 17, 2018)
Prevalence of dysphagia in patients with multiple sclerosis; a systematic review and meta-analysis
Authors: Mirmosayyeb Omid , Ebrahimi Narges , Shekarian Arman , Bagherieh Sara , Afshari-Safavi Alireza , Shaygannejad Vahid , Barzegar Mahdi
Published: June 2021

Objectives

Dysphagia is a major comorbidity observed in patients with multiple sclerosis, yet different prevalence rates are reported for it. Therefore, we have designed this systematic review to estimate the pooled prevalence of dysphagia in patients with MS.

Method

We searched PubMed, Scopus, EMBASE, Web of Science, and gray literature including references from the identified studies, reviews studies, and conference abstracts which were published up to February 2021. Articles that were relevant to our topic and could provide information regarding the prevalence of dysphagia among MS patients were included; however, articles with self-report screening strategies were excluded.

Results

The literature search found 1993 articles. After eliminating duplicates, 1272 articles remained. Sixteen abstract conference papers were included for final analysis. A total of 10846 MS cases and 4913 MS patients with dysphagia included in the analysis. The pooled prevalence of dysphagia in the included studies was 45.3% (95% CI: [40.7%-50%])

Conclusion

The results of this systematic review shows that the prevalence of dysphagia in MS patients is 45% which is greatly higher compared to the general population.
Mapping Potential Antigenic Drift Sites (PADS) on SARS-CoV-2 Spike in Continuous Epitope-Paratope Space
Authors: Miller Nathaniel L. , Clark Thomas , Raman Rahul , Sasisekharan Ram
Published: June 2021

SARS-CoV-2 mutations with antigenic effects pose a risk to immunity developed through vaccination and natural infection. While vaccine updates for current variants of concern (VOCs) are underway, it is likewise important to prepare for further antigenic mutations as the virus navigates the heterogeneous global landscape of host immunity. Toward this end, a wealth of data and tools exist that can augment existing genetic surveillance of VOC evolution. In this study, we integrate published datasets describing genetic, structural, and functional constraints on mutation along with computational analyses of antibody-spike co-crystal structures to identify a set of potential antigenic drift sites (PADS) within the receptor binding domain (RBD) and N-terminal domain (NTD) of SARS-CoV-2 spike protein. Further, we project the PADS set into a continuous epitope-paratope space to facilitate interpretation of the degree to which newly observed mutations might be antigenically synergistic with existing VOC mutations, and this representation suggests that functionally convergent and synergistic antigenic mutations are accruing across VOC NTDs. The PADS set and synergy visualization serve as a reference as new mutations are detected on VOCs, enable proactive investigation of potentially synergistic mutations, and offer guidance to antibody and vaccine design efforts.

Graphical Abstract
Conservation and diversity in transcriptional responses among host plants forming distinct arbuscular mycorrhizal morphotypes
Authors: Tominaga Takaya , Miura Chihiro , Sumigawa Yuuka , Hirose Yukine , Yamaguchi Katsushi , Shigenobu Shuji , Mine Akira , Kaminaka Hironori
Published: June 2021

The morphotype of arbuscular mycorrhizal (AM) roots is distinct mostly depending on AM host species:Arum,Paris, and Intermediate types. We previously reported that gibberellin (GA) promotes the establishment ofParis-type AM symbiosis inEustoma grandiflorumdespite its negative effects onArum-type AM symbiosis in model plants. However, the molecular mechanisms underlying the differential effects of GA on different morphotypes, including Intermediate-type AM symbiosis, remain elusive.

Comparative transcriptomics revealed that several symbiosis-related genes were transcriptionally promoted upon AM fungal colonization inLotus japonicus(Arum-type),Daucus carota(Intermediate-type), andE. grandiflorum(Paris-type). Interestingly, upon GA treatment, the fungal colonization levels and expression of symbiosis-related genes were suppressed inL. japonicusandD. carotabut were promoted inE. grandiflorum.

Exogenous GA transcriptionally inhibited the biosynthetic process of a host-derived signal molecule involved in AM symbiosis, strigolactone, inL. japonicusandE. grandiflorum. Additionally, disaccharides mainly metabolized in AM roots would be different betweenL. japonicusandD. carota/E. grandiflorum.

This study uncovered the conserved transcriptional responses during mycorrhization and diverse responses to GA in AM roots with distinct morphotypes among phylogenetically distant host plants.
NanoDam identifies novel temporal transcription factors conserved between the Drosophila central brain and visual system
Authors: Tang Jocelyn L.Y. , Hakes Anna E. , Krautz Robert , Suzuki Takumi , Contreras Esteban G. , Fox Paul M. , Brand Andrea H.
Published: June 2021

Temporal patterning of neural progenitors is an evolutionarily conserved strategy for generating neuronal diversity. Type II neural stem cells in the Drosophila central brain produce transit-amplifying intermediate neural progenitors (INPs) that exhibit temporal patterning. However, the known temporal factors cannot account for the neuronal diversity in the adult brain. To search for new temporal factors, we developed NanoDam, which enables rapid genome-wide profiling of endogenously-tagged proteins in vivo with a single genetic cross. Mapping the targets of known temporal transcription factors with NanoDam identified Homeobrain and Scarecrow (ARX and NKX2.1 orthologues) as novel temporal factors. We show that Homeobrain and Scarecrow define middle-aged and late INP temporal windows and play a role in cellular longevity. Strikingly, Homeobrain and Scarecrow have conserved functions as temporal factors in the developing visual system. NanoDam enables rapid cell type-specific genome-wide profiling with temporal resolution and can be easily adapted for use in higher organisms.
Core and indicative bacterial and fungal taxa define characteristic soil communities of arable land, grassland, and forest
Authors: Florian Gschwend , Martin Hartmann , Johanna Mayerhofer , Anna Hug , Jürg Enkerli , Andreas Gubler , Meuli Reto G. , Beat Frey , Franco Widmer
Published: June 2021

Soil microbial diversity has major influences on ecosystem functions and services. However, due to its complexity and uneven distribution of abundant and rare taxa, quantification of soil microbial diversity remains challenging and thereby impeding its integration into long-term monitoring programs. Using metabarcoding, we analyzed soil bacterial and fungal communities over five years at thirty long-term soil monitoring sites from the three land-use types, arable land, permanent grassland, and forest. Unlike soil microbial biomass and alpha-diversity, microbial community compositions and structures were site- and land-use-specific with CAP reclassification success rates of 100%. The temporally stable site core communities included 38.5% of bacterial and 33.1% of fungal OTUs covering 95.9% and 93.2% of relative abundances. We characterized bacterial and fungal core communities and their land-use associations at the family-level. In general, fungal families revealed stronger land-use type associations as compared to bacteria. This is likely due to a stronger vegetation effect on fungal core taxa, while bacterial core taxa were stronger related to soil properties. The assessment of core communities can be used to form cultivation-independent reference lists of microbial taxa, which may facilitate the development of microbial indicators for soil quality and the use of soil microbiota for long-term soil biomonitoring.
Bidirectional cooperation between Ubtf1 and SL1 determines RNA Polymerase I promoter recognition in cell and is negatively affected in the UBTF-E210K neuroregression syndrome
Authors: Tremblay Michel G. , Sibai Dany S. , Valère Melissa , Mars Jean-Clément , Lessard Frédéric , Hori Roderick T. , Khan Mohammad M. , Stefanovsky Victor Y. , Ledoux Mark S. , Moss Tom
Published: June 2021

Transcription of the ∼200 mouse and human ribosomal RNA genes (rDNA) by RNA Polymerase I (RPI/PolR1) accounts for 80% of total cellular RNA, around 35% of all nuclear RNA synthesis, and determines the cytoplasmic ribosome complement. It is therefore a major factor controlling cell growth and its misfunction has been implicated in hypertrophic and developmental disorders. Activation of each rDNA repeat requires nucleosome replacement by the architectural multi-HMGbox factor UBTF to create a 15kbp nucleosome free region (NFR). Formation of this NFR is also essential for recruitment of the TBP-TAFI factor SL1 and for preinitiation complex (PIC) formation at the gene and enhancer-associated promoters of the rDNA. However, these promoters show little sequence commonality and neither UBTF nor SL1 display significant DNA sequence binding specificity, making what drives PIC formation a mystery. Here we show that cooperation between SL1 and the longer UBTF1 splice variant generates the specificity required for rDNA promoter recognition in cell. We find that conditional deletion of the Taf1b subunit of SL1 causes a striking depletion UBTF at both rDNA promoters but not elsewhere across the rDNA. We also find that while both UBTF1 and −2 variants bind throughout the rDNA NFR, only UBTF1 is present with SL1 at the promoters. The data strongly suggest an induced-fit model of RPI promoter recognition in which UBTF1 plays an architectural role. Interestingly, a recurrent UBTF-E210K mutation and the cause of a pediatric neurodegeneration syndrome provides indirect support for this model. E210K knock-in cells show enhanced levels of the UBTF1 splice variant and a concomitant increase in active rDNA copies. In contrast, they also display reduced rDNA transcription and promoter recruitment of SL1. We suggest the underlying cause of the UBTF-E210K syndrome is therefore a reduction in cooperative UBTF1-SL1 promoter recruitment that may be partially compensated by enhanced rDNA activation.
Loss of SET1/COMPASS methyltransferase activity reduces lifespan and fertility in Caenorhabditis elegans
Authors: Caron Matthieu , Gely Loïc , Garvis Steven , Adrait Annie , Couté Yohann , Palladino Francesca , Fabrizio Paola
Published: June 2021

Post-translational modification of histones, particularly lysine methylation, are thought to play a crucial role in the aging process. Histone 3 lysine 4 (H3K4) methylation, a modification associated with active chromatin, is mediated by a family of SET1 methyltransferases acting within conserved multiprotein complexes known as COMPASS. Previous work in model organisms with partial or complete deletion of COMPASS subunits has yielded conflicting results about the requirement for H3K4 methylation during aging. Here, we reassessed the role of SET1/COMPASS-dependent H3K4 methylation in Caenorhabditis elegans lifespan regulation and fertility by generating set-2(syb2085) mutant animals that express a catalytically inactive form of SET-2, the C. elegans homolog of SET1. We show that animals bearing catalytically inactive SET-2 retain the ability to form COMPASS complexes but have a marked global loss of H3K4 dimethylation and trimethylation. Consistent with previous work, reduced H3K4 methylation was accompanied by loss of fertility; however, in striking contrast to earlier studies, set-2(syb2085) mutants displayed a significantly shortened, not extended, lifespan and had normal intestinal fat stores. Furthermore, other commonly used set-2 mutants were also short-lived, as was a cfp-1 mutant that lacks a non-catalytic SET1/COMPASS component and displays reduced H3K4 methylation. These results challenge previously held views and establish that wild-type H3K4 methylation levels are necessary to achieve a normal lifespan in C. elegans.
The payoffs and tradeoffs of hygienic behavior: A large-scale field study on a local population of honey bees
Authors: Seltzer Rya , Kahanov Paz , Kamer Yosef , Hetzroni Amots , Bieńkowska Małgorzata , Hefetz Abraham , Soroker Victoria
Published: June 2021

Honey bees (Apis mellifera) are exposed to a variety of risk factors, but the ectoparasitic mite Varroa destructor and its associated viruses are considered to be the most significant problem worldwide. It has been widely recognized that honey bee stocks resistant to the mites are an essential part of any sustainable long-term management of Varroa. The aim of this study was to evaluate the efficacy of hygienic behavior in a local population of honey bees in order to reduce Varroa infestation. A bi-directional selection for high and low rates of hygienic behavior was carried out in Israel using either queen artificially inseminated or naturally mated. Colonies were screened for performance: population size, honey production, control of Varroa infestation, and the level of hygienic behavior. Furthermore, we examined the costs and benefits of selection using measurements of colony performance. Either way, selected lines should be tested for trade-offs and benefits to ensure their productivity. The selection process revealed that the trait is heritable. Maternal phenotype has a significant effect on Varroa load, as colonies founded by hygienic daughter queens showed a significantly lower parasite load. No major trade-offs were found between the rate of hygienic behavior, honey yield, and population size. Measuring the direct benefits of hygienic behavior through colony performance suggests that breeding for this trait makes bees more resistant to Varroa destructor. These results are promising for our successful local bee breeding programs in a Mediterranean climate.
Structural Variation and Polysaccharide Profiling of Intervessel Pit Membranes
Authors: Sun Qiang
Published: June 2021

Functional roles of intervessel pit membrane (PM) depend on its structure and polysaccharide composition, which are mostly unknown or lack of accurate information. This study uses grapevine as a model plant and an immunogold-scanning electron microscopy technique to simultaneously analyze structures and polysaccharide compositions of intervessel PMs in relation to their functions. Intervessel PMs with different structural integrity were found in functional xylem with about 90 % of them being intact with a smooth or relatively smooth surface and the rest 10 % with progressively degraded structures. The results also elucidated details of the removal process of wall materials from surface toward its depth during the natural intervessel PM degradation. Four groups of pectic and hemicellulosic polysaccharides were present in intervessel PMs but displayed differential spatial distributions and quantities: weakly methyl-esterified homogalacturonans abundant in the surficial layers, heavily methyl-esterified homogalacturonans and xylans mostly in deep layers, and fucosylated xyloglucans relatively uniform in presence at different depths of an intervessel PM. This information is crucial to reveal the polysaccharide profiling of primary cell wall and to understand intervessel PM’s roles in the safety and regulation of water transport as well as the plant susceptibility to vascular diseases.
Myofibroblast differentiation is governed by adhesion mechanics, and inhibition of Talin2 reverses lung and kidney fibrosis
Authors: White Michael JV , Ozkan Melis , Gomez Medellin Jorge Emiliano , Solanki Ani , Hubbell Jeffrey A
Published: June 2021

Fibrosis is involved in 45% of deaths in the United States, and no treatment exists to reverse progression of the disease. In order to find novel targets for fibrosis therapeutics, we developed a model for the differentiation of monocytes to myofibroblasts that allowed us to screen for proteins involved in myofibroblast differentiation. Inhibition of a novel protein target generated by our model, talin2, reduces myofibroblast morphology, α-smooth muscle actin content, collagen I content, and lowers the pro-fibrotic secretome of myofibroblasts. We find that knockdown of talin2 de-differentiates myofibroblasts, talin2 knockdown reverses bleomycin-induced lung fibrosis in mice, and Tln2 -/-mice are resistant to unilateral ureteral obstruction-induced kidney fibrosis and are resistant to bleomycin-induced lung fibrosis. Talin2 inhibition is a potential treatment for reversing lung and kidney fibroses.

One Sentence Summary

Silencing the stress sensor Talin2 reverses myofibroblast differentiation and existing fibrosis.
Hippocampal ripples signal contextually-mediated episodic recall
Authors: Sakon John J. , Kahana Michael J.
Published: June 2021

High-frequency oscillatory events, termed ripples, represent synchrony of neural activity in the brain. Recent evidence suggests medial temporal lobe (MTL) ripples support memory retrieval. However, it is unclear if ripples signal the reinstatement of episodic memories. Analyzing electrophysiological MTL recordings from 219 neurosurgical participants performing episodic recall tasks, we find that the rate of hippocampal ripples rises just prior to the free recall of recently-formed memories. This pre-recall ripple effect (PRE) is stronger in the CA1 and dentate gyrus (DG) subfields of hippocampus than neighboring MTL regions entorhinal and parahippocampal cortex. The PRE is also stronger prior to the retrieval of temporally and semantically clustered as compared with unclustered recalls, indicating the involvement of ripples in contextual reinstatement, which is a hallmark of episodic memory.

One sentence summary

High frequency human hippocampal ripples occur prior to those memories most likely retrieved via episodic mechanisms.
Bacterial gasdermins reveal an ancient mechanism of cell death
Authors: Johnson Alex G. , Wein Tanita , Mayer Megan L. , Duncan-Lowey Brianna , Yirmiya Erez , Oppenheimer-Shaanan Yaara , Amitai Gil , Sorek Rotem , Kranzusch Philip J.
Published: June 2021

Gasdermin proteins form large membrane pores in human cells that release immune cytokines and induce lytic cell death. Gasdermin pore formation is triggered by caspase-mediated cleavage during inflammasome signaling and is critical for defense against pathogens and cancer. Here we discover gasdermin homologs encoded in bacteria that execute prokaryotic cell death. Structures of bacterial gasdermins reveal a conserved pore-forming domain that is stabilized in the inactive state with a buried lipid modification. We demonstrate that bacterial gasdermins are activated by dedicated caspase-like proteases that catalyze site-specific cleavage and removal of an inhibitory C-terminal peptide. Release of autoinhibition induces the assembly of >200 Å pores that form a mesh-like structure and disrupt membrane integrity. These results demonstrate that caspase-mediated activation of gasdermins is an ancient form of regulated cell death shared between bacteria and animals.
Assessing student success in a Peer Assisted Learning program using propensity score matching
Authors: Shanbrom Corey , Norris Michelle , Esgana Caitlin , Krauel Matthew , Pigno Vincent , Lundmark Jennifer
Published: June 2021

The Peer Assisted Learning program at Sacramento State University (PAL) was established in 2012 with one section supporting introductory chemistry. It now serves 17 gatekeeper courses in Biology, Chemistry, Mathematics, Physics, and Statistics, enrolling approximately 1,400 students annually. Adapting the Peer-Led Team Learning model, PAL Facilitators do not teach, tutor, or even confirm answers; they do ask scaffolding questions, provide encouragement, and ensure that all group members participate in problem-solving. Here we assess the efficacy of the program in terms of student success in the parent course. As PAL is an opt-in program, we employ propensity score matching techniques to account for confounding factors. Our analysis of 11 classes shows that PAL provides an average course GPA bump ranging from .23 to .71 grade points (mean .42). Compared to the non-PAL baseline course GPA, this amounts to an increase of 9% to 51% (mean 23%). We consider data from over 25,000 students, and our propensity score analysis uses over 10,000 students (4,519 PAL, 5,814 non-PAL) for whom appropriate matches could be found.
eIF2B-capturing viral protein NSs suppresses the integrated stress response
Authors: Kashiwagi Kazuhiro , Shichino Yuichi , Osaki Tatsuya , Sakamoto Ayako , Nishimoto Madoka , Takahashi Mari , Mito Mari , Weber Friedemann , Ikeuchi Yoshiho , Iwasaki Shintaro , Ito Takuhiro
Published: June 2021

Various stressors such as viral infection lead to the suppression of cap-dependent translation and the activation of the integrated stress response (ISR), since the stress-induced phosphorylated eukaryotic translation initiation factor 2 [eIF2(αP)] tightly binds to eIF2B to prevent it from exchanging guanine nucleotides on unphosphorylated eIF2. Sandfly fever Sicilian virus (SFSV) evades this cap-dependent translation suppression through the interaction between its nonstructural protein NSs and host eIF2B. Our cryo-electron microscopy (cryo-EM) analysis revealed that SFSV NSs binds to the α-subunit of eIF2B in a competitive manner with eIF2(αP). Together with SFSV NSs, eIF2B exhibits normal nucleotide exchange activity even in the presence of eIF2(αP). A genome-wide ribosome profiling analysis clarified that SFSV NSs in human cultured cells attenuates the ISR. Furthermore, SFSV NSs exhibited neuroprotective effects against the ISR-inducing stress. Since the ISR inhibition is beneficial in various neurological disease models, SFSV NSs is promising as a therapeutic ISR inhibitor.