bluuebunny/crossref_metadata_2025 huggingface dataset:
μ‐­opioid Receptor: Opioid Painkillers Redefined
Authors: Chou Chris , Bonner Trevor , Drewes Jake , Harroun Haleakala , Jacobi Adrienne , Lippard Maya , Martyr Justin , Santucci Alexander , Schumacher Chase , Swope Danielle , Martyr Richard , Cunningham Christopher
Published: June 2021

According to the CDC, common opioid painkillers kill twice as many people as cocaine and five times as many as heroin. They cause addiction, detrimental side effects, and become less effective over time, motivating chemists to seek less flawed painkillers. This quest is being pursued through the investigation of G‐­protein‐­coupled μ‐­opioid receptors (μ­‐OR). These μ‐­ORs are composed of seven amphipathic alpha helices that span the hydrophobic middle of the cellular membrane; extending into the hydrophilic exterior and interior regions of the cell. The Longmont High School SMART (Students Modeling A Research Topic) Team modeled the μ‐­OR using 3D modeling technology. Opioid ligands are bound deeply in the solvent exposed site of the ­μ­‐OR, perhaps altering its tertiary structure. A significant feature of the μ‐­OR is the crystallization of the protein, which shows formation of a dimer resulting in complementary, interlocking structures between transmembrane segments T5 and T6 that may elicit different reactions to binding opioids. The μ­‐OR may be manipulated by agonists such as morphine, and antagonists like naloxone, due to its large and deep active site, allowing for differential specificity of reversible reactions. Active μ‐­OR receptors couple with Gi, the inhibitory G protein for adenylyl cyclase, and arrestins. Activation of arrestins produce side effects including drug tolerance, respiratory problems, and constipation. Further investigation of this μ‐­OR receptor and its signaling pathways may help biochemists find a potent painkiller with minimal side effects.
Alveolar macrophages express membrane CD200 that inhibits mast cell activation
Authors: Santerre Kim , Lauzon‐Joset Jean‐François , Langlois Anick , Marsolais David , Bissonnette Elyse
Published: June 2021

Alveolar Macrophages are central regulators of pulmonary immune responses, yet their regulatory functions are misunderstood. CD200, a transmembrane protein, and its receptor (CD200R) play a critical role in the resolution of inflammation, but their role in asthma is still unclear. CD200 is expressed on many cell types such as leukocytes, T cells, B cells, epithelial cells, and endothelial cells, while CD200R is expressed exclusively on myeloid cells including alveolar macrophages (AM) and mast cells (MC), which play a key role in asthma. Recent study showed that leukocytes from asthmatic patients express lower level of CD200 during exacerbations, suggesting a dysregulation of CD200 pathway. Thus, we investigated the modulation of CD200 expression on AM following allergen challenge and the inhibition of MC functions by AM CD200.
Expression of CD200 and CD200R were measured on AM from naive and sensitized rats before and after allergen challenge using flow cytometry. AM modulation of antigen‐stimulated MC was investigated in vitro using co‐culture and MC degranulation and cytokine production.
AM from naive and sensitized rats express similar level of CD200. However, allergen exposure increased CD200 expression on AM of naïve rats (that do not develop signs of asthma), but not on AM of sensitized rats (that develop experimental asthma). No difference between groups was observed for CD200R expression. Naive AM inhibited antigen‐stimulated MC degranulation and cytokine production. The addition of neutralizing anti‐CD200R antibody abrogated AM inhibitory effects.
These results suggest that modulation of CD200 expression on AM could have an important role in asthma regulation.
The Role of Hemagglutinin in Influenza Virus Transmission
Authors: Fassler Amy , Babinski Alex , Georgieva Darina , Gui David , Gui Michael , Fernandez Michelle , Prebble Lara , Schultz Eric , Shukla Ayush , Belongia Edward
Published: June 2021

Influenza is a rapidly mutating RNA virus causing mortality and morbidity in humans.The three different strains of influenza are characterized by different surface glycoproteins. Hemagglutinin (HA) is one of the primary binding proteins of Influenza A, the most prevalent strain of the virus. HA is a trimer, with each macromolecule consisting of a head and stalk region. The head region recognizes sialic acid on the host cell surface, initiating viral infection. The sialic acid binding site is highly susceptible to antigenic drift, and is the primary target of current vaccine development. The binding site consists of a loop‐helix‐loop region that allows for the attachment between HA and sialic acid. Because this region is both constantly mutating and strain specific, new vaccines need to be developed annually. Most antigenic drift is located within two antigenic sites. The Marshfield High School SMART (Students Modeling A Research Topic) Team will be modeling the sialic acid binding site on HA to demonstrate how the protein triggers viral infection. The stalk domain functions to mediate fusion of the viral and endosomal membranes. During this process, the domain undergoes extensive structural rearrangement. As such, the stalk domain is a more suitable vaccine target because it is conserved across strains and is not as susceptible to genetic drift. Therefore, emerging research has focused on the stalk region for more promising vaccinations, and maybe an eventual elimination of the need to develop a new vaccine every year. The Marshfield Research Foundation is currently studying influenza vaccine effectiveness and safety including the effects of repeated vaccination on immunity.
Performance on Paper‐Pencil Cognitive Tests: A Comparison between Hindi and English Language
Authors: Dixit Abhinav , Rai Ankit
Published: June 2021

Introduction

Letter Cancellation tasks (LCTs) are a group of paper‐pencil based psychomotor tasks that are commonly used to assess cognitive functions.

Lack of proficiency in the language of the test can lead to erroneous results on LCTs. This is particularly important in a country like India where most of the population is not fluent in English.

Since most of the cognitive tests are in English, it greatly limits the population that can be used for cognitive testing. It is therefore essential to develop tests in vernacular languages like Hindi and compare the results obtained with tests in English.

The present study evaluated the effect of Hindi and English language on performance of one, two and three letter cancellation task.

Methodology

50 healthy male volunteers between the age group of 18‐ 40 years were recruited for the study after taking their written, informed consent. The study was approved by the Institute Ethics Committee and funded by Indian Council of Medical Research.

Subjects were asked to cancel out letters in One, Two and Three LCTs in Hindi and English language. Each LCT consisted of 960 letters with 25% as target letters.

The total time taken to complete each test and number of errors were analyzed statistically using SPSS by unpaired t test.

Results

The results revealed a significantly longer time to complete Hindi LCTs than English LCTs. The error rates were significantly more in Hindi one LCT as compared to English One LCT. The error rates in two and three LCT in Hindi were more than in English but the difference was not significant.

Conclusion

Hindi is perhaps a more complex language as compared to English, thereby requiring more attention and visuo‐spatial processing. Indian subpopulation therefore needs a separate battery of cognitive tests in vernacular languages.
Arginase‐1 Expression in Human Peripheral Blood is Associated With an Impaired Ability to Support Lymphocyte Proliferation Following Ischemic Brain Injury
Authors: O'Connell Grant , Petrone Ashley , Barr Taura
Published: June 2021

Ischemic brain injury produces an immediate inflammatory response followed by systemic immune suppression. This immunosuppressed state, characterized by lymphopenia and impaired macrophage function, facilitates further tissue damage and is associated with impaired recovery. The primary factors modulating post‐ischemic immune suppression have yet to be realized. Arginase‐1 (ARG1) is an immunomodulatory ureohydrolase with immunosuppressive properties. Data produced by our laboratory have shown that ARG1 is strongly induced in peripheral blood following ischemic stroke in humans. Thus, we tested the hypothesis that ARG1 plays a critical role in propagating the immunosuppressed state following ischemic neurological insult. To address this hypothesis, total RNA and serum was extracted from peripheral blood samples obtained from 9 male human subjects within 24 hours of transient ischemic attack or ischemic stroke. qRT‐PCR was performed to quantify peripheral blood ARG1 expression levels, and a CSFE‐based proliferation assay was used to evaluate the capacity of post‐ischemic serum to support proliferation of the Jurkat human T‐cell line in‐vitro. Peripheral blood ARG1 expression was negatively associated with Jurkat proliferation, however this correlation failed to reach statistical significance at a confidence interval of 0.95 (Spearman correlation: r=‐0.64, p=0.06). Based on the relative strength of association observed in this small clinical sample, we believe that the role of ARG1 as a post‐ischemic immune modulator warrants further investigation, as ARG1 may represent a critical factor driving immune suppression following ischemic brain injury.
Evaluation of radiation of Aral sea residential area
Authors: Ismailovа A. , Kamiev M. , Jakenova A.
Published: June 2021

Radiospectrometer aspects of radiation safety habitats are an integral part of the solution to environmental problems as pollution objects ecosystems of natural and technological hazards radiation play a negative role in the health status of the population living in the zone of ecological distress.

Purpose of Study

Assessment of the radioecological situation in the territory of the settlements included in the area of Aral Sea.

Results

Made gamma‐spectrometric shooting areas the study areas of the Aral sea has allowed to establish that the performance of the equivalent dose of gamma radiation ranged from 0.01 to 0.18 μsv/h. In the soil samples of the investigated areas, found the content of natural radionuclides as thorium ‐ 232 (from 45 to 50.3%), radium ‐ 226 (3.7 to 4.1%) and potassium ‐ 40 (from 10.7 to 11.3%).

The values of the flux density of radon from the ground surface in the target territories of settlements ranged for, Aralsk ‐ from 31,22 to 56.8 MBq/m2*s; village Aiteke bi ‐ from 41.2 per cent to 50,31 MBq/m2*s; and the village of Zhosaly from 22,15 to 44,10 MBq/m2*s; and the village of Zhalagash from 30,2 to 41,10 MBq/m2*s and the village Shieli from 43,16 to 52,19 MBq/m2*s.
Radiation situation of territory uranium mining deposit of Kazakhstan
Authors: Bakhtin M.M. , Kashkinbaev E.T. , Altaeva N.Z.
Published: June 2021

Since 2010 Republic of Kazakhstan became the largest supplier of uranium in the world, having headed the list of leading producers of natural uranium.Reserves and resources of uranium in Kazakhstan make now about 1,7 million tons, or about 12% of the total amount of world reserves and uranium resources (according to IAEA).

Out of sanitary protection zone of uranium mining deposits Mynkuduk, Uvanas and Moyunkum, Tortkuduk were carried out automobile and pedestrian gamma survey, measurement of density of streams alpha, beta particles, radio spectrometric and radiochemical analysis of tests of water and the soil.Out of sanitary protection zone of depositsMynkuduk and Uvanas of radioactive anomalies aren't found.

At distance of 5 km from area No. 1 Moyunkum near a well is revealed an anomal area with an area of 93 sq.m where the power of an equivalent dose of gamma radiations varies from 0,41 to 1,43 μSv/hour.

In the samples of the water which have been selected from an anomal area total alpha activity to 29 times, radium‐226 to 10 times, radium‐228 to 32 times exceeds standard value.

In case of water use for an irrigation melon field and kitchen gardens, a cattle pasture on pollution areas, individual doses of internal radiation when using by the population in production food from these areas could reach values 20‐40 mSv / year an annual effective dose shouldn't exceed 1 mSv/year.
Expression of Inflammatory Markers in Visceral Fat of Obesity‐prone Rats is Increased by High Fat Diet Consumption
Authors: Souza‐Smith Flavia , Braymer H. Doug , Allerton Timothy , Tzeng Tony , Harrison‐Bernard Lisa , Primeaux Stefany
Published: June 2021

Excess visceral adiposity, rather than total adiposity, is associated with obesity‐related increases in the risk for developing cardiovascular disease (CVD). As a consequence of expanding visceral adiposity, inflammation is prevalent and may link obesity and CVD. The current study tested the hypothesis that high fat diet (HFD) consumption leads to an increase in the expression of inflammatory markers in visceral fat, not subcutaneous fat, in obesity‐prone, Osborne‐Mendel (OM), rats. OM rats were fed either a HFD (60% fat; n=6) or low fat diet (LFD, 10% fat; n=6) for 7 weeks. As expected, body weight and % adiposity were increased by HFD intake. A multiplex rat cytokine/chemokine panel was used to assess the expression of inflammatory markers in epididymal fat, mesenteric fat and subcutaneous fat. Expression of IL‐1α, IL‐1ᵦ, IL‐6, IL‐10, TNF‐α, GM‐CSF, MIP‐1α (CCL3) and MIP‐2 (CXCL2) was increased by HFD intake in the epididymal fat of OM rats (p<.05). In mesenteric fat, the expression of IL‐1α, IL‐6 and IL‐10 was increased by the consumption of HFD (p<.05). GM‐CSF and MIP‐2 (CXCL2) were undetectable in the mesenteric fat of LFD fed OM rats. Subcutaneous fat expression of MIP‐2 (CXCL2) was decreased in the HFD fed group, compared to the LFD fed group (p<.05). An increase in cytokine/chemokine expression in the visceral adipose depots, but not in the subcutaneous fat, of obesity‐prone OM rats following HFD intake supports the role of visceral fat in the deleterious effects of obesity. These data suggest that HFD‐induced inflammation in obesity‐prone rats will enhance the risk for cardiovascular disease. Support: NIH 1P30GM106392‐01A1.
Folliculogenesis and Oocyte Quality in Awassi Sheep
Authors: Al Fahel Christabelle , Nassif Charbel , Bou Karroum Rima , Ibrahim Joe , Sahakian Joseph , Houchaymi Khaled , Hajj Elham , Aad Pauline
Published: June 2021

Female reproductive performance of Awassi ewe, the predominant breed of fat‐tail sheep of Lebanon are not well studied; we aimed to evaluate oocyte morphology and quality. 36 Awassi ovaries (Exp 1) from local slaughterhouses were collected from May to October and Follicles (>3 mm) aspirated for oocyte morphology evaluation. Furthermore, 10 Awassi ewes at the Lebanese Agricultural Research Institute (Exp 2) were monitored via ultrasonography from May to July to determine dominant and subordinate follicles; ovaries and ooyctes collected, and evaluated following slaughter. AMH, ZAR‐1 and BMP15 gene expression amplified using qRTPCR with SYBR and normalized to 18S rRNA. Results showed (exp 1) that 68% of collected oocytes were medium vs. 9% large oocytes, and 60% of Awassi oocytes satisfied more than 3 criteria of good quality, more frequently in October, but detected as early as May. Folliculogenesis in Awassi ewes (exp 2) showed an estrous cycle of 17±3 days with 2 waves and a dominant follicle of 4±0.9 mm. Of the dominant follicles, only 24.4% contained morphologically good vs. 17.8% bad oocytes. In the search for an oocyte quality marker, AMH mRNA was high in small and dominant follicles, but not subordinate; BMP‐15 was down‐regulated in small oocytes while ZAR‐1 did not differ among different quality oocytes. Therefore, these genes can be used to distinguish between different quality oocytes.
This research was supported by a grant from the LCNRS and NDU
Protective Effects of Endurance or Resistance Training Exercise on Chemotherapy‐Induced Skeletal Muscle Weakness and Fatigue
Authors: Hydock David , Bredahl Eric , Quinn Colin , Hayward Reid
Published: June 2021

This study analyzed the effects of prior endurance exercise or resistance training exercise on skeletal muscle dysfunction induced by the chemotherapy drug doxorubicin (DOX). Furthermore, this study examined the time course of the protective effects of endurance/resistance training on DOX‐induced muscle dysfunction and the effects of endurance/resistance training and DOX on different muscle types. Male rats were trained on a motorized treadmill (endurance training), housed in cages with elevated food/water (resistance training), or remained in standard cages (sedentary) for 10 weeks. Animals then received DOX or saline injections, and maximal twitch force and fatigue were analyzed ex vivo in the soleus (type I muscle) and extensor digitorum longus (EDL, type II muscle) 1 day, 3 days, or 5 days following injection. Overall, DOX treatment resulted in decreased maximal twitch force and increased fatigue, but exercise protected against much of this dysfunction at days 1, 3, and 5. Specifically, the greatest degree of protection in the soleus was found with endurance training and the greatest degree of protection in the EDL was found with resistance training suggesting that exercise mode and muscle type are important factors to consider in managing DOX‐induced myotoxicity.
Influence of Habitual Carbohydrate Intake on Exercise‐Induced Inflammation in Ultra‐Endurance Athletes
Authors: Bartley Jenna , Munoz Colleen , Kunces Laura , Saenz Catherine , Creighton Brent , Freidenreich Daniel , Lee Elaine , Maresh Carl , Volek Jeff
Published: June 2021

Low carbohydrate diets (LCD) decrease systemic inflammatory markers in humans with chronic inflammation, such as obesity and metabolic syndrome; however it is unknown whether LCD can mitigate systemic inflammation in acute situations, such as exercise bouts.

Purpose

To examine exercise‐induced alterations in inflammatory markers in elite ultra‐endurance athletes on a LCD or high carbohydrate diet (HCD).

Methods

Elite ultra‐endurance trained men (n=20, age 33.5±6.4yr VO2max 64.5±4.9mL/kg/min) habitually consuming a LCD (11% CHO, 71% FAT, 19% PRO) or HCD (58% CHO, 28% FAT, 15% PRO) completed a 3 hr treadmill run (65% VO2max). We measured circulating immune cells and select cytokines prior to, during, and post exercise (PE).

Results

Endurance exercise resulted in leukocytosis with elevated neutrophils, monocytes, and lymphocytes immediately PE with greater lymphocytes in LCD (LCD 2873.5±869.8; HCD 1904.7±825.9; cells/uL; p<0.01). Neutrophils and monocytes remained elevated at 2 hr PE, while lymphocytes declined to below baseline levels. Circulating IL‐6 and IL‐8 increased 1 hr into exercise and remained elevated 2 hrs PE. IL‐10 increased 2 hrs into exercise and remained elevated 30 minutes PE. TNFa, IL‐1β, and IL‐12p70 did not change. Cytokines were not significantly different between groups.

Conclusion

Endurance exercise resulted in an acute inflammatory response. LCD did not significantly modulate the selected inflammatory markers. Ongoing research in our lab is examining additional markers of systemic inflammation, as well as potential muscle‐localized effects.
Optimal Vitamin D Status is Associated with Healthier Immune Indices in Untrained, but not Trained Females
Authors: Forney Laura , Johannsen Neil , Barkemeyer Amanda , Dietrich Marilyn , Henagan Tara , Stewart Laura
Published: June 2021

The anti‐inflammatory effects of chronic exercise are well established; less is known about immune changes associated with vitamin D. This study explored the relationship between inflammatory indices in exercise trained (TR) and untrained (UN) individuals with 25‐hydroxyvitamin D (25OHD) concentrations either above (HD) or below (LD) optimal concentrations. Subjects (n=63, 19‐35 years) were evaluated for body composition and maximal aerobic capacity (VO2peak). 25OHD levels, lipopolysaccharide (LPS)‐stimulated interleukin‐6 (IL‐6) production, and inflammatory monocytes and toll like receptor 4 (TLR4) expression were determined in whole blood. TR (n=30) had higher 25OHD levels (p=0.015) and VO2peak (p<0.0001), lower body weight (p=0.039) and percent body fat (p=0.011), and lower LPS‐stimulated IL‐6 production (p=0.0163) compared to UN (n=33). UN with HD had lower numbers of total monocytes, CD14+CD16‐ cells, and lower TLR4 expression on CD14+CD16+ cells compared to UN with LD. Exercise was related to increased 25OHD, improved body composition, and decreased inflammation. Additionally, vitamin D may mediate inflammation in those who do not exercise.
Prior Exercise Training Protects Against Short‐Term High Fat Feeding Induced Weight Gain and Glucose Intolerance
Authors: Snook Laelie , Frendo‐Cumbo Scott , MacPherson Rebecca , Castellani Laura , Peppler Willem , Anderson Zachary , Holloway Graham , Wright David
Published: June 2021

It has recently been shown that high fat diet induced metabolic changes such as impaired glucose tolerance and adipose tissue inflammation occur in as few as three days. We sought to determine whether these changes could be mitigated with prior exercise training. Male C57BL/6J mice (8 weeks old) were fed control diet (10% kcal from lard) and either treadmill trained or kept sedentary for four weeks. Twenty‐four hours after the final bout of exercise, mice were provided with high fat diet (60% kcal from lard), ad libitum, for four days, with no further exercise. Prior training resulted in 68% less weight gain on the high fat diet and 20% (epididymal) and 33% (subcutaneous) smaller fat pad mass. This occurred despite similar food intake. Compared to control fed mice, high fat feeding resulted in increased total AUC following an intraperitoneal glucose tolerance test, which was significantly blunted with prior training. The improvement in high fat feeding induced impaired glucose tolerance following training was mirrored by greater insulin‐induced increases in Akt phosphorylation in skeletal muscle and liver, but not adipose tissue. The blunted impairment in glucose homeostasis was not explained by differences in indices of adipose tissue inflammation and was lost after 6 days of high fat feeding. Further, when compared to sedentary high fat fed mice that were calorie restricted (‐30%) to match the weight gain of the trained high fat fed mice, the same attenuated impairments in glucose tolerance were observed. Taken together, our data suggest that prior exercise protects against high fat diet induced weight gain and glucose intolerance.
Opioid Receptor: Its structure and how it works
Authors: Crowthers Kevin , Melo Hiliana , Chen Yixin , LaGanke Nicole , Rooney Colleen , Clouse Cameron , Cunningham Chris
Published: June 2021

The First and Second Opium Wars were two conflicts caused by the the reaction of China over the illegal exportation of the drug opium by the British government. Opium, also known as poppy tears, is a narcotic drug extracted from the plant Papaver somniferum. This drug causes a sensation of euphoria and pain relief by binding to opioid receptors that exist on cell membranes of neurons and the digestive tract. Opioid receptors (OR) are G‐­protein‐coupled receptors (GPCRs) with three main variables, μ‐­OR, δ‐OR and κ­‐OR. The μ­‐OR is the most important opioid receptor for the management of pain. To better understand this receptor's structure and how it can impact function, the Worcester Academy SMART Team has modeled the μ­‐OR using 3D printing technology. Using the irreversible antagonist β‐­FNA, the μ‐OR has a complex shape, consisting of seven transmembrane α‐­helices connected by three extracellular loops and three intracellular loops; transmembrane helices 5 and 6 are involved in receptor dimerization. The binding pocket is relatively open which causes a greater exposure to the extracellular surface, providing evidence as to why potent opioids like buprenorphine and etorphine have a rapid dissociation. β‐­FNA interacts with 14 residues, of which nine have more interaction with the ligand and are conserved in the δ­‐OR and the κ‐­OR. The μ‐­OR contains 11 identical amino acid residues with the the other two ORs. The only differences are the positions E229, K303 and W318, which are Asp, Trp and Leu. Further understanding of opioid receptors and their structure can lead to a way of treating pain without side effects.
The Influence of Excess Postexercise Leucine Ingestion on Markers of Autophagy in Skeletal Muscle of Older Men
Authors: D'Lugos Andrew , Reidy Paul , Gundermann David , Borack Michael , Volpi Elena , Rasmussen Blake , Dickinson Jared
Published: June 2021

The goal of this study was to observe the role of excess post exercise leucine ingestion on the autophagy system in skeletal muscle following resistance exercise (RE) in old adults over a 24h time course. Older men performed a bout of RE and at 1h postexercise ingested 10g of essential amino acids (EAA) containing a leucine content similar to high quality protein (CTRL, 1.8g leucine, n=7) or excess leucine (LEU, 3.5g leucine, n=8). Western blot (protein) and RT‐qPCR (mRNA expression) were used to examine markers of autophagy in skeletal muscle (vastus lateralis) biopsies obtained at rest and at 2, 5, and 24h postexercise. Relative to basal values, mRNA expression of Beclin1 was increased (1.3 fold) in both groups at 5h and 24h post exercise (P<0.05). BNIP3 expression was increased (~1.3 fold) only in LEU at 5h (P<0.05). GABARAP mRNA expression was unchanged in both groups and at all time points (P>0.05). LC3BI protein increased at 5h post exercise for both groups (P<0.05), whereas LC3BII was unchanged (P>0.05). The ratio of LC3BII/LC3BI was reduced in both groups at all time points postexercise (P<0.05), which is associated with a decrease in autophagic flux. These data indicate that autophagy may be reduced in skeletal muscle following the combination of RE and EAA ingestion and that markers associated with autophagy in the skeletal muscle of older men do not appear to be influenced by excess postexercise leucine ingestion.

NIAMS R01AR049877, NIA P30AG024832, NIH T32HD07539, NCATS UL1TR000071
Cellular and Physiological Implications of Dietary Supplementation with Beta‐Hydroxy‐Beta‐Methylbutyrate and Beta‐Alanine in Late Middle‐Aged Mice
Authors: Vallejo Julian , Spence Madoka , Cheng An‐Lin , Brotto Leticia , Edens Neile , Garvey Sean , Brotto Marco
Published: June 2021

Several studies suggest that the decline of muscle function with age can be mitigated by dietary supplementation with beta‐hydroxy‐beta‐methylbutyrate (HMB) or beta‐alanine (BA). The purposes of this study were to investigate the effects of: 1) HMB treatment on murine C2C12 myoblast and myotube cultures; and 2) dietary HMB, BA, and a combination thereof, on muscle contractility in late middle‐aged mice. In C2C12 myotubes, free acid HMB enhanced sarcoplasmic reticulum (SR) calcium release beyond vehicle control in the presence of three separate SR agonists (P<0.05, ANOVA). HMB also improved C2C12 myoblast viability (P<0.05) and proliferation (P=0.017). Furthermore, an ex vivo muscle contractility study was performed on 48 C57BL/6nTac male mice (19 months old at end of study). For 8 weeks, mice were fed control AIN‐93M diet containing calcium HMB monohydrate, BA, or the combination thereof. In EDL muscle, the combination of HMB and BA showed significant increases in relative force (88.6 ± 2.2 mN vs. 79.8 ± 2.4 mN, P=0.025) and specific force (12.2 ± 0.4 N/cm2 vs. 10.8 ± 0.4 N/cm2, P=0.021) at submaximal frequency of stimulation. At maximum frequency of stimulation, BA showed a significant force increase over the control diet (202.0 ± 3.4 mN vs. 188.2 ± 4.6 mN, P=0.023). Effects in soleus muscle did not achieve statistical significance. Our findings suggest calcium signaling as a key pathway contributing to beneficial effects of HMB and BA on skeletal muscle.
Phenotype of Extraocular Muscles from Anophthalmic Rats
Authors: Dunn Michelle , Westerkamp Christopher
Published: June 2021

Extraocular muscles (EOM) are a unique population of muscle cells due to their myosin fiber type, myonuclei and innervation pattern. This group of six muscles control eye movement with high precision and coordination to focus light onto the area of high acuity vision in the eye, the fovea. The EOM, in addition to the common myosin heavy chains I, 2A, 2X, and 2B, also express myosin heavy chains 3, 8, 13, 7b, and 15. The purpose of this project was to compare the EOM fiber type and size of anophthalmic rats to that of normal rats. Muscle fiber size is maintained by an interaction of mechanical and chemical signals. Without those signals, atrophy will occur and fiber type will shift towards a more fatigable phenotype. We used a population of unilaterally anophthalmic Long Evans Sprague Dawley crossed adult rats (male and female, 11‐14 months). The orbital contents with attached EOM of both the anophthalmic and normal eye socket were removed and snap frozen in liquid nitrogen cooled isopentane. These tissues were then sectioned and stained using immunohistochemistry to compare the EOM fiber type and size between normal and anophthalmic eyes. We hypothesized that the anophthalmic EOM would possess a disuse phenotype consistent with atrophied muscle fibers, fewer myonuclei compared to matched normal eyes, and a shift towards fatigue‐prone type II fiber type.
ß2‐Adrenergic Agonist Suppresses Foxo Transcriptional Activity by Regulating Foxo1 Phosphorylation but not Acetylation in Skeletal Muscle
Authors: Goncalves Dawit , Manfredi Leandro , Graça Flávia , Silveira Wilian , Lustrino Danilo , Kettelhut Isis , Navegantes Luiz Carlos
Published: June 2021

This study was undertaken to identify: 1) whether ß2‐adrenergic agonist (BA) suppresses Foxo transcriptional activity and the expression of atrophy‐related genes (atrogenes) in skeletal muscles and 2) which post‐translational modification [i.e., phosphorylation (p) and acetylation (ac)] is related to the inhibition of Foxo1. For that, we examined Formoterol (FOR), a newer generation of BA, effects on the levels of p‐Foxo1, ac‐Foxo1, p‐Akt and p‐CREB, a canonical target of BA signaling, by immunoblotting, the activity of Foxo by reporter luciferase assay and the mRNA levels of atrogenes (Atrogin‐1, MuRF1 and Gabarapl1) by qPCR in muscles from 2‐d fasted rodents. Fasting reduced p‐Akt (~80%) and p‐Foxo1 (30%) and increased Foxo activity (~15‐fold) and atrogenes expression (~7‐fold). Thirty min after an injection, FOR in vivo (300 μg.kg‐1) caused an elevation in p‐Akt (~10‐fold), p‐Foxo1 (2‐fold) and p‐CREB (2‐fold). At 4h, FOR reduced Foxo activity (~40%) and atrogenes mRNAs (~40%). In isolated muscles from fasted rats, FOR in vitro (10‐4M) also increased p‐Foxo1, p‐Akt and p‐CREB. Ac‐Foxo1 levels did not alter in any condition. These data suggest FOR counteracts the up‐regulation of atrogenes induced by food deprivation in muscle by activating Akt and inhibiting Foxo. In addition, these effects seem to be related to the induction of Foxo1 phosphorylation, but not acetylation. Supported by FAPESP (12/18861‐0 and 12/24524‐6).
Genetic identity of warm and cool thermosensory relay neurons in the mouse parabrachial nucleus
Authors: Geerling Joel , Kim Minjee , Agostinelli Lindsay , Scammell Thomas
Published: June 2021

The parabrachial nucleus relays skin temperature from the spinal cord to the hypothalamus. Relay neurons for warm and cool thermosensation were localized in rats to the lateral parabrachial nucleus (LPB), but we need more information about their genetic identity for chemogenetic and optogenetic experiments. To determine the developmental‐genetic and neurotransmitter phenotype of these neurons, we analyzed transcription factor expression in Cre‐reporter mice after exposure to warm (36 C) or cool (4 C) ambient temperature. In both conditions, Fos‐activated neurons were found in a continuum of LPB subnuclei known to receive input from the spinal cord. Most Fos+ neurons also expressed FoxP2, a marker for glutamatergic LPB neurons derived from the rhombic lip. These FoxP2+ neurons were GFP+ in reporter mice for vglut2, but not vgat. Dynorphin neurons, visualized using pdyn‐cre reporter mice, formed a caudally skewed subset of these FoxP2+ neurons. After warm exposure, many dynorphin neurons became Fos+ in the dorsal lateral (PBdL) and central lateral subnuclei (PBcL). After cool exposure, non‐dynorphin Fos+ neurons were prominent rostrally, arcing around the external lateral PB. Most cool‐induced Fos was clustered densely here, in a far‐rostral subpopulation of FoxP2+ neurons we designated as the rostral external lateral subnucleus (PBreL). These findings shed new light on the genetic organization of LPB and suggest that pdyn‐cre mice may allow experimental access to warm thermosensory relay neurons in the caudal LPB in order to investigate their role in thermoregulation, sleep, and other homeostatic functions.
Determining Significant Within‐Subject Changes of BOLD MRI Cerebrovascular Reactivity to CO2
Authors: Sobczyk Olivia , Crawley Adrian , Poublanc Julien , Mandell Daniel , Mikulis David , Duffin James , Fisher Joseph
Published: June 2021

Cerebrovascular reactivity (CVR) is the ratio of the cerebral blood flow (CBF) response to an increase in a vasoactive stimulus. Current measurement of CVR uses the BOLD MRI signal as an indicator of CBF in response to standardized changes in CO2. Despite uniform test conditions, there are still test‐to‐test differences in CVR due to variations in physiology and technology over time. Thus performing longitudinal studies requires the quantification of abnormal differences in CVR over time. We therefore generated a database of normal CVR test‐retest variability as a normal reference to statistically score differences in CVR. Two standardized CVR tests were conducted in fifteen healthy males (36.7 ± 16.1 y) within a three week period. All scans were co‐registered into standard space and a normal difference CVR map was calculated from the two time points for all voxels for each of the 15 subjects consisting of the mean and standard deviation of the differences to generate an interval test difference (ID) atlas. We illustrate our concept by generating ID z‐maps for patients with steno‐occlusive disease who had CVR tests done before and after surgical intervention. Differences in CVR values for the patients were compared to the ID atlas and scored as z‐values, the fractional standard deviation from the corresponding voxel of the atlas. The ID z‐maps confirmed improvement brought about by surgical intervention, and gave an indication of the extent and distribution of changes in CVR. The application of ID z‐maps will enable study of the natural history of cerebrovascular disease and response to treatment.
PhUn Week: A One Day Program for K‐8 Students
Authors: Fox Apollonia , Reyes Levy , Serrador Jorge
Published: June 2021

As part of Physiology Understanding Week activities, we developed a one day program of both demonstration and interactive science sessions that were tailored to school children ranging in age from 5‐14 that was presented at a local private catholic primary school. The goal of this program was to encourage creativity and scientific curiosity in primary school children. Sessions ranged from 40‐55 min, depending on age. The program was created to draw on the expertise of three presenters on to engage students with interactive demonstrations. Of the topics covered, we used suggestions from the American Physiological Society as well as added areas of acoustic demonstrations, visual perception and visual/auditory integration, proprioceptive field demonstrations, and finally cardiac and cerebrovascular physiology demonstrations. Examples of these included demonstrations of the occlusion effect (acoustic), the McGurk effect (audio‐visual integration), the waterfall effect (visual illusion), transcranial Doppler (cerebrovascular physiology), and beat‐by‐beat blood pressure demonstrations during resting and activity (exercise physiology). Feedback from these demonstrations was generally positive. Both students and teachers verbalized appreciation of the added material. The goal of this poster is to provide a complete one day program that physiologists can use to encourage interest in physiology among primary school children.
Predictors of angina resolution after percutaneous coronary intervention in stable coronary artery disease
Authors: Verreault-Julien Louis , Bhatt Deepak L. , Jung Richard G. , Di Santo Pietro , Simard Trevor , Avram Robert , Hibbert Benjamin
Published: June 2021

Background

Elective percutaneous coronary intervention (PCI) is performed to relieve symptoms of angina. Identifying patients who will benefit symptomatically after PCI would be clinically advantageous but robust predictors of symptom resolution are ill-defined.

Methods

Prospective indexing of baseline angina status, clinical, and procedural characteristics were collected over a 5-year period in a regional revascularization registry. At 1-year follow-up, angina resolution was assessed. We performed a stepwise selection algorithm to identify predictors of persistent angina at 1 year.

Results

A total of 777 patients were included in the analysis and the median follow-up was 387 days. Mean age of the cohort was 66.6 years, 23.8% were female and 23.3% had baseline Canadian Cardiovascular Society class 3 or 4 angina. Overall, 13.1% had persistent angina. The only predictor of persistent angina was the presence of a residual chronic total occlusion after PCI with odds ratio of 3.06 (95% confidence interval, 1.81–5.17). Residual stenoses 50–69%, 70–89%, and 90–99% were not associated with residual angina after PCI.

Conclusion

Most patients achieved symptom resolution with PCI and optimal medical therapy. A residual chronic total occlusion after PCI was associated with persistent angina. Other degrees of stenoses were not associated with persistent angina.
Growing use of home enteral nutrition: a great tool in nutrition practice toolbox
Authors: Mohamed Elfadil Osman , Ewy Matthew , Patel Jalpan , Patel Ishani , Mundi Manpreet S.
Published: June 2021

Purpose of review

Home enteral nutrition (HEN) is a well-established practical nutrition therapy tool that is typically managed by an interdisciplinary team. Prevalence of HEN is increasing across the globe given significant evidence for utility, feasibility, efficacy, safety, and reliability of HEN in helping patients meeting their nutrition needs. The current review highlights the growing use of HEN in the context of what is novel in the field including trends in HEN practice with regards to tubes and connectors, feeding formula and real food blends, and common complications. The review also highlights that the use of HEN is expected to expand further over coming years emphasizing the need for national consensus recommendations and guidelines for HEN management.

Recent findings

The growing use of HEN has always been parallel to adoption of holistic definitions and concept of malnutrition in clinical nutrition practice and more understanding of the need for malnutrition risk stratification, meeting unmet needs in practice and addressing challenges that lead to suboptimal enteral nutrition.

Research and advancements in technology as well as in tube feeding formula industry have led to the development of more solutions and have helped identify and implement best HEN practices.
Fracture toughness of one- and two-dimensional nanoreinforced cement via scratch testing
Authors: Akono Ange-Therese
Published: June 2021

Cement is the most widely consumed material globally, with the cement industry accounting for 8% of human-caused greenhouse gas emissions. Aiming for cement composites with a reduced carbon footprint, this study investigates the potential of nanomaterials to improve mechanical characteristics. An important question is to increase the fraction of carbon-based nanomaterials within cement matrices while controlling the microstructure and enhancing the mechanical performance. Specifically, this study investigates the fracture response of Portland cement reinforced with one- and two-dimensional carbon-based nanomaterials, such as carbon nanofibres, multiwalled carbon nanotubes, helical carbon nanotubes and graphene oxide nanoplatelets. Novel processing routes are shown to incorporate 0.1–0.5 wt% of nanomaterials into cement using a quadratic distribution of ultrasonic energy. Scratch testing is used to probe the fracture response by pushing a sphero-conical probe against the surface of the material under a linearly increasing vertical force. Fracture toughness is then computed using a nonlinear fracture mechanics model. Nanomaterials are shown to bridge nanoscale air voids, leading to pore refinement, and a decrease in the porosity and the water absorption. An improvement in fracture toughness is observed in cement nanocomposites, with a positive correlation between the fracture toughness and the mass fraction of nanofiller for graphene-reinforced cement. Moreover, for graphene-reinforced cement, the fracture toughness values are in the range of 0.701 to 0.717 MPa

m

. Thus, this study illustrates the potential of nanomaterials to toughen cement while improving the microstructure and water resistance properties.

This article is part of a discussion meeting issue ‘A cracking approach to inventing new tough materials: fracture stranger than friction’.
Contact probing of prestressed adhesive membranes of living cells
Authors: Borodich Feodor M. , Galanov Boris A. , Keer Leon M. , Suarez-Alvarez Maria M.
Published: June 2021

Atomic force microscopy (AFM) studies of living biological cells is one of main experimental tools that enable quantitative measurements of deformation of the cells and extraction of information about their structural and mechanical properties. However, proper modelling of AFM probing and related adhesive contact problems are of crucial importance for interpretation of experimental data. The Johnson–Kendall–Roberts (JKR) theory of adhesive contact has often been used as a basis for modelling of various phenomena including cell-cell interactions. However, strictly speaking the original JKR theory is valid only for contact of isotropic linearly elastic spheres, while the cell membranes are often prestressed. For the first time, effects caused by molecular adhesion for living cells are analytically studied taking into account the mechanical properties of cell membranes whose stiffness depends on the level of the tensile prestress. Another important question is how one can extract the work of adhesion between the probe and the cell. An extended version of the Borodich-Galanov method for non-direct extraction of elastic and adhesive properties of contacted materials is proposed to apply to experiments of cell probing. Evidently, the proposed models of adhesive contact for cells with prestressed membranes do not cover all types of biological cells because the structure and properties of the cells may vary considerably. However, the obtained results can be applied to many types of smooth cells and can be used to describe initial stages of contact and various other processes when effects of adhesion are of crucial importance.

This article is part of a discussion meeting issue ‘A cracking approach to inventing new tough materials: fracture stranger than friction’.
Pattern formation in drying blood drops
Authors: Hertaeg Michael. J. , Tabor Rico F. , Routh Alexander F. , Garnier Gil
Published: June 2021

Patterns in dried droplets are commonly observed as rings left after spills of dirty water or coffee have evaporated. Patterns are also seen in dried blood droplets and the patterns have been shown to differ from patients afflicted with different medical conditions. This has been proposed as the basis for a new generation of low-cost blood diagnostics. Before these diagnostics can be widely used, the underlying mechanisms leading to pattern formation in these systems must be understood. We analyse the height profile and appearance of dispersions prepared with red blood cells (RBCs) from healthy donors. The red cell concentrations and diluent were varied and compared with simple polystyrene particle systems to identify the dominant mechanistic variables. Typically, a high concentration of non-volatile components suppresses ring formation. However, RBC suspensions display a greater volume of edge deposition when the red cell concentration is higher. This discrepancy is caused by the consolidation front halting during drying for most blood suspensions. This prevents the standard horizontal drying mechanism and leads to two clearly defined regions in final crack patterns and height profile.

This article is part of a discussion meeting issue ‘A cracking approach to inventing new tough materials: fracture stranger than friction’.
COMPARATIVE IMMUNOGENICITY OF BNT162b2 mRNA VACCINE WITH NATURAL COVID-19 INFECTION
Authors: Psichogiou Mina , Karabinis Andreas , Poulakou Garyphallia , Antoniadou Anastasia , Kotanidou Anastasia , Degiannis Dimitrios , Pavlopoulou Ioanna D. , Chaidaroglou Antigoni , Roussos Sotirios , Mastrogianni Elpida , Eliadi Irene , Basoulis Dimitrios , Petsios Konstantinos , Leontis Konstantinos , Kakkalou Eleni , Protopapas Konstantinos , Jahaj Edison , Pratikaki Maria , Syrigos Konstantinos N. , Lagiou Pagona , Gogas Helen , Tsiodras Sotirios , Magiorkinis Gkikas , Paraskevis Dimitrios , Sypsa Vana , Hatzakis Angelos
Published: June 2021

The mRNA vaccine BNT162b2 has proven highly effective and currently many millions are being vaccinated. There are limited and conflicting data from immunogenicity studies on the effects of age, gender, vaccination side effects (VSE), risk factors for severe COVID-19 (RFS-COV), obesity (BMI) and previous SARS-CoV-2 (Pr-CoV) Moreover, immunogenicity data from COVID-19 patients comparing various disease categories of natural infection i.e. asymptomatic vs mild vs moderate vs severe infection are sparse, and include limited number of individuals.

This study included 871 vaccinated health care workers (HCW) and 181 patients with natural infection. Immunogenicity was assessed by a quantative assay measuring anti-SARS-CoV-2 against the RBD domain of the spike protein (anti-RBD) and anti-SARS-CoV-2 against nucleocapsid protein (anti-N). Samples were collected 1-2 weeks after completion of the 2nd dose in the vaccinated HCWs and 15-59 days post symptoms onset in patients with natural infection.

The concentration of anti-RBD in vaccinated individuals after multivariable analysis was significantly associated with age, gender, VSE and Pr-CoV. Specifically, anti-RBD median levels (95% CI) were lower by 2,466 (651-5,583), 6,228 (3,254-9,203) and 7,651 (4,479-10,823) AU/ml in 35-44, 45-54, 55-70 yrs respectively, compared with 18-34 yrs group. In females, median levels of anti-RBD were higher by 2,823 (859-4,787) compared with males, in individuals with VSE were higher by 5,024 (3,122-6,926) compared with no VSE, and in HCWs with Pr-CoV were higher by 9,971 (5,158-14,783) AU/ml compared with HCWs without Pr-CoV.

Among individuals with natural infection, the median anti-RBD levels were 14.8 times higher in patients with critical COVID-19 infection compared with non-hospitalized individuals. The ratio of anti-RBD in vaccinated individuals versus those with natural infection varied from 1.0 up to 19.4 according to the clinical subgroup of natural infection.

This study proves the high immunogenicity of BNT162b2 vaccine although its sustainability remains to be seen. The use of comparative data from natural infection serological panels, expressing the clinical heterogeneity of natural infection may facilitate early decisions for vaccine evaluation in clinical trials.