bluuebunny/crossref_metadata_2025_split 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 InformationSupported 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 InformationFunding: 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

ObjectiveTo determine baseline wellness characteristics of students participating in a community‐based participatory research intervention to reduce obesity among college students.MethodsAn 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.ResultsTotal 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.ConclusionSurvey 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 InformationThis 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 InformationNSF #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 InformationNIH, 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 InformationThis 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.
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

AbstractDrug 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.