bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of Endosomal Sodium/Hydrogen Exchangers NHE6 and NHE9 in a Neurobiological Model of Disease
Authors: Hack Anniesha , Kondapalli Kalyan C. , Rao Rajini
Published: June 2021

Ionic and pH gradients must be tightly regulated for many aspects of neuronal signaling and synaptic cleft homeostasis, including neurotransmitter uptake and astrocytic clearance through transporters, receptor recycling, and communication through gap junctions. Recently, several independent studies have correlated a range of neurological disorders, including autism, X‐linked mental retardation, epilepsy, attention deficit hyperactivity disorder and addiction, to mutations in a subgroup of sodium‐hydrogen exchangers, NHE6 and NHE9. These transporters are widely expressed in the brain and localize to early (NHE6) and recycling endosomes (NHE9), where they are thought to mediate the electrically silent counter transport of cations with protons to regulate luminal pH and control cargo trafficking. We have tested the hypothesis that NHE6 and NHE9 share overlapping functions in regulating intravesicular pH to control the delivery and turnover of glial specific glutamate transporters at the synapse. We have shown that isoform‐specific overexpression of NHE9 alters trafficking with increased surface expression of general (transferrin) receptors and synapse specific (glutamate) transporters. These findings provide the first insight into the neurobiological basis of NHE dysfunction. We will further elucidate the molecular mechanisms by measuring the pH of the endosomes, as well as create single and double knock down lines of NHE6 and NHE9 to demonstrate their potential overlapping functions..
Characterisation of TLR4 signalling and function in two brain endothelial cell lines
Authors: Nilsson Olov Karl , Hellqvist Hedvig
Published: June 2021

The blood‐brain barrier (BBB) plays a crucial role in maintaining brain homeostasis. During pathologies such as stroke the function of the BBB is altered into a pro‐inflammatory phenotype and there is increased expression of adhesion molecules, cytokines and chemokines. Toll‐like receptors (TLR), in particular TLR4 and TLR2, are involved in the outcome of experimental stroke manifested by a protective effect in TLR4 and TLR2 knock out animals. In this study we aim to characterize two brain endothelial cell lines, GPNT and bEND5, with regards to TLR4 signalling and function in order for them to be used for in vitro studies of the blood‐brain barrier investigating the role of these receptors in neutrophil migration. The cell lines were exposed to various concentrations of LPS and intracellular signalling molecules were quantified by Western blot and cytokine release by ELISA, respectively. In the rat GPNT cell line a rapid increase (5–15 min) in MAPK p38 phosphorylation was detected. In these cells the release of the chemotactic cytokine CINC‐1 was increased 5‐fold by 1 ng/ml of LPS compared to untreated control. In the bEND5 cells a rapid increase (15 min) in p38 phosphorylation was also detected whereas phosphorylation of JNK could not be observed. These results warrants further investigation of these cell lines for their suitability for in vitro studies of the role of TLR4 signalling in neutrophil transmigration
Brain Inflammatory Mediators induced by high fat diet are significantly blunted with the deletion of MCP‐1
Authors: Gordon Benjamin Thomas , McClellan Jamie , Murphy E. Angela , Carmichael Martin D. , Davis J. Mark
Published: June 2021

Consumption of a high fat diet (HFD) can lead to central nervous system (CNS) inflammation. Monocyte chemoattractant protein (MCP‐1) is fundamental in the release of inflammatory mediators, but its role in HFD induced CNS inflammation has not yet been determined. The purpose of this study was to determine the role of MCP‐1 on brain inflammation following 15 weeks of HFD feedings. C57BL/6 wildtype mice (n=20) and MCP‐1 −/− mice (n=32), 4 weeks of age were randomly assigned to one of four groups: normal diet wildtype (ND‐WT), HFD wildtype (HFD‐WT), normal diet MCP‐1−/− (ND‐MCP‐1−/−) or HFD MCP‐1 −/− (HFD‐MCP‐1−/−). The mice were fed the HFD (41% of total caloric intake from fat) or normal diet (11.5% of total caloric intake from fat) for 15 weeks. Mice were sacrificed at 19 weeks of age and the brainstem was dissected and analyzed for mRNA gene expression of TLR4, F4/80, CD11c and TNF‐α using real time RT‐PCR. Gene expression of TLR4, CD11c and TNF‐α was increased in the brainstem of HFD‐WT relative to ND‐WT (p<0.05), whereas HFD‐MCP‐1−/− was not different from ND‐WT. A similar effect was observed for F4/80, but this did not reach statistical significance. No differences were found among the other groups. These data support a necessary role of MCP‐1 on the brain inflammatory response following HFD feedings. MCP‐1 may be an important therapeutic target in HFD‐induced brain inflammation.
Exercise and neuroprotection in an animal model of multiple sclerosis
Authors: Pryor Bill , White Lesley
Published: June 2021

Multiple Sclerosis (MS) is an autoimmune disease that affects the central nervous system resulting in accumulated loss of cognitive, sensory, and motor function.

PURPOSE

To evaluate the neuropathological effects of voluntary exercise in mice with experimental autoimmune encephalomyelitis (EAE), an animal model of MS.

METHODS

Two groups of C57BL/6J mice were immunized with myelin oligodendrocyte glycoprotein (MOG) and then randomized to a cage with a running wheel or a locked wheel.

RESULTS

Exercising EAE mice exhibited less severe neurological disease score (0.95 ± 0.97 exercise, 1.51 ± 0.85 sedentary), and later onset of disease when compared to sedentary EAE animals (14.83 ± 0.75 days, exercise, 12.67 ± 0.82 days, sedentary). Immune cell infiltration in the ventral white matter tracts of the lumbar spinal cord was reduced in the EAE exercise group by 47.5% when compared to sedentary EAE animals. Neurofilament immunolabeling in the anterior corticospinal tract displayed a more random distribution of axons and apparent loss of smaller diameter axons with a 44% greater loss of fluorescence immunolabeling in the sedentary EAE animals.

CONCLUSION

Our findings provide evidence that voluntary exercise results in reduced and attenuated disability, reductions in autoimmune cell infiltration, and preservation of axons within the lumbar spinal cord of mice with EAE.
Exposure to air pollution during pregnancy influences placental growth
Authors: de Fátima Soto Sônia , dos Santos Letícia Pereira , Veras Mariana Matera , Heimann Joel Claudio
Published: June 2021

Objective

To evaluate the consequences of exposure to air pollution during the pre‐gestational or gestational period.

Methods

Female Wistar rats were exposed to filtrated (F) or polluted (P) air in a concentrator of atmospheric particles during 3 weeks before or during pregnancy. At 12 weeks of age, the female rats were mated with adult males and were divided in four subgroups exposed to F or P before or during pregnancy (FF, FP, PF, PP). At the 19th day of pregnancy, the animals were euthanized and placentas and fetus were collected. Weekly dams weight (W), placenta (Pl), deciduous (Dc) and fetus (F) mass were measured.

Results

(mean±SEM – p<0.05): W was higher in FF (282,3) and PP (289,2) than in PF (271,1). Pl mass was higher in FP (0.4640±0.009) than FF (0.4348±0.006), PF (0.4222±0.006) and PP (0.4364±0.005). Dc mass was higher in FP (0.1882±0.013) than FF (0.1442±0.006), PF (0.1501±0.007) and PP (0.1403±0.01). No difference was observed in fetus mass among all experimental groups.

Conclusions

Exposure to air pollution during pregnancy causes high placental weight, but does not affect fetal weight gain. Supported by FAPESP and CNPq.
Inhibition of dipeptidyl peptidase IV by sitagliptin increases GLUT4 expression in insulin‐sensitive tissues of SHR
Authors: Valentini Vanessa , Giannocco Gisele , Oliveira Kellen C , Salles Thiago A , Crajoinas Renato O , Girardi Adriana C
Published: June 2021

The goal of the present study was to investigate whether the dipeptidyl peptidase IV (DPPIV) inhibitor sitagliptin, which has been shown to exert both anti‐hyperglycemic and anti‐hypertensive actions, modulates GLUT4 expression in skeletal and cardiac muscles of SHR. To this end, male SHR at 5 and 20 weeks of age were treated with either sitagliptin (40 mg/kg twice daily) or vehicle for the period of ten days. Age‐matched Wistar Kyoto (WKY) rats were used as normotensive controls. Sitagliptin treatment inhibited the activity of DPPIV in the plasma of both young and adult SHR and also decreased the circulating levels of the enzyme. Sitagliptin only suppressed blood pressure rising in Y‐SHR. Levels of plasma insulin were not significantly different between the strains at young age. In contrast, adult SHR displayed enhanced plasma insulin concentration with fasting normoglycemia. Inhibition of DPPIV by sitagliptin restored plasma insulin levels of A‐SHR. GLUT4 in the plasma membrane (PM) was lower in Y‐SHR than in Y‐WKY in the heart, the slow‐twich oxidative soleus, the fast‐twich glycolytic EDL and the fast‐twich glycolytic‐oxidative gastrocnemius. DPPIV inhibition normalized PM GLUT4 in myocytes from Y‐SHR. Reduction of GLUT4 PM expression in the skeletal and cardiac myocytes was more pronounced in A‐SHR vs. A‐WKY than in Y‐SHR vs. YWKY. Inhibition of DPPIV by sitagliptin increased GLUT4 PM, total protein and GLUT4‐mRNA expression in the heart, soleus, EDL and gastrocnemius of treated‐A‐SHR to levels higher than those found in the A‐WKY. Collectively, our data demonstrate that DPPIV inhibition upregulates GLUT4 in skeletal and cardiac muscles of SHR.
Low RIP140 expression rescues basal FA uptake via differential expression of FATP1 and CD36 in skeletal muscle cells exposed to high palmitate
Authors: Constantinescu Silvana , Turcotte Lorraine P
Published: June 2021

We have shown in L6 skeletal muscle cells that high fatty acid (FA) exposure decreases basal FA uptake and oxidation and that low receptor interacting protein 140 (RIP140) increases FA uptake. To provide mechanistic insights for this adaptation, we measured the expression of proteins and genes involved in the regulation of FA metabolism under high FA availability. L6 myotubes were silenced using RNAi sequences for either RIP140 (RIP) or a negative control (NC) and incubated ± palmitate (HF: 400μM) in the basal state. siRNA treatment reduced (P<0.05) RIP140 mRNA (55%) and protein (75%) levels. HF treatment reduced (P<0.05) mRNA expression of markers of oxidative capacity by 48–64% (COX4, MCAD, CPT1, PGC‐1α) but increased CPT1 protein levels (56%) in NC cells. Low RIP140 in HF‐treated cells restored COX4 mRNA and CPT1 protein levels back to control levels. HF treatment increased (P<0.05) FATP1 mRNA (100%) and total CD36 protein content (95%) but decreased (P<0.05) CD36 mRNA (63%) and FATP1 protein (59%) expression. Low RIP140 in HF‐treated cells restored CD36 mRNA and protein content back to control levels but did not affect the already high FATP1 mRNA levels. Plasma membrane CD36 content was not affected (P>0.05) by either treatment. HF treatment increased (P<0.05) basal pAKTser473 (443%), pAKTthr308 (126%) and pPKC‐ζ (96%) in NC cells. Low RIP140 in HF‐treated cells restored pPKC‐ζ back to control levels and reduced (P<0.05) pAKTthr308. Our data suggest that the rise in basal FA uptake induced by low RIP140 expression in HF‐treated cells is partially mediated by an increase in FATP1 mRNA expression.

USC Women in Science and Engineering, USC Integrative and Evolutionary Biology and USC Zumberge Research Innovation Fund
The effects of passive heating and subsequent exercise in the heat on lipid metabolism
Authors: OˈHearn Katharine Jean , Pinet Bernard M , Mauger Jean-Francois , Haman Francois
Published: June 2021

The goal of this study was to examine the effects of heat exposure on lipid metabolism during passive heating and subsequent exercise in the heat by focusing on changes in whole‐body lipid utilization and plasma lipids. Male participants (n=8) were passively heated for 120 min at 42°C, then exercised on a treadmill in the heat at 50% VO2peak for 30 min (HEAT), and on a separate occasion followed the same procedure at 23°C (CON). Results showed that whole‐body lipid utilization rates were not different between HEAT and CON during passive heating and during exercise. At rest, non‐esterified fatty acid (NEFA) concentrations were significantly higher following passive heating (618 ± 59 μmol/l) compared to CON (391 ± 51 μmol/l). The same trend was observed following exercise (2036 ± 183 μmol/l and 1350 ± 147 μmol/l for HEAT and CON respectively). Triglyceride, phospholipid and cholesterol levels were not different between HEAT and CON following passive heating or exercise. We conclude that heat exposure results in higher circulating NEFAs both at rest and during exercise without significant changes in whole‐body lipid utilization.

CIHR graduate student scholarship and NSERC to F. Haman
Lipophilic And Hydrophilic Statins Differentially Modulate Endoplasmic Reticulum Stress Response In Cardiac Myocytes
Authors: Godoy Joseph C. , Asfaw Elizabeth K. , Alvarez Erika A. , Dalton Nancy D. , Niesman Ingrid , Patel Hemal H. , Zemljic-Harpf Alice E.
Published: June 2021

Statins inhibit HMG‐CoA reductase, target mevalonic acid synthesis, and limit cholesterol biosynthesis. HMG‐CoA reductase is expressed in the membrane of the endoplasmic reticulum (ER). Statins are prescribed to prevent cardiovascular events.

In cultured neonatal mouse cardiac myocytes the lipophilic statin atorvastatin and the hydrophilic statin pravastatin both up‐regulated PDI, indicating unfolded protein response (UPR) meant to relieve ER stress. Only atorvastatin increased ER stress, growth arrest, and induced apoptosis via induction of CHOP, Puma, active Caspase‐3 and PARP. Dose‐dependent release of LDH was only observed in atorvastatin treated cells (1–10 μM). Hearts of mice treated with atorvastatin (5mg/kg/day for 7 months) showed protein aggresomes and autophagosomes when compared to vehicle treated controls. While atorvastatin changed mitochondrial ultrastructure, no differences in cardiac function, exercise ability or creatine kinase levels were found.

We show differential activation of ER stress by atorvastatin and pravastatin in cardiac myocytes. Our results provide a novel mechanism through which specific statins therapeutically modulate the balance of UPR/ER stress responses thereby possibly influencing cardiac remodeling.
Age‐dependent differences in whole‐genome gene expression response to contraction‐induced muscle injury
Authors: Ensey James , Li Shengqiao , Kashon Michael L , Hollander Melinda S , Cutlip Robert G , Baker Brent A
Published: June 2021

Differential age‐dependent contraction‐induced muscle injury has been reported to result in soft‐tissue trauma at the physiological level, but no consensus exists at the molecular level to a genomic signature accounting for these disparities. Thus, the purpose herein was to identify if a differential age‐dependent genomic signature exists in skeletal muscle following contraction‐induced muscle injury. The left dorsiflexor muscles of young (3 mo) and old (30 mo) male Fischer 344 x BN rats were injured using 150 stretch‐shortening contractions at a velocity of 500°/s in vivo. Seventy‐two hours following exposure the left tibialis anterior muscle was harvested and RNA was isolated. cRNA samples were prepared and loaded onto Sentrix Rat‐Ref12 Beadchips for gene array analyses. Among the ~1000 differentially responsive genes expressed in both injured groups, there was an intense upregulation of genes related to the inflammatory response (i.e. IL‐18, CCL7), cell death (ANXA2, BCL10) and muscle regeneration (i.e. TGFb1, PCNA, Myog) in young rats following injury, yet these same genes were minimally responsive in old rats. These data suggest that, at the molecular level, old rats may be desensitized to launch an appropriate response to an injury stimulus compared with young rats, and the disparity in these specific molecular signals could impact recovery kinetics following contraction‐induced injury with aging.
SIRT1‐independent epigenetic effects of resveratrol mediated through the estrogen receptor
Authors: Wakeling Luisa Anne , Alatawi Fatema , Ions Laura Jane , Hesketh John , Ford Dianne
Published: June 2021

We aimed to determine if epigenetic effects could be a component of the mechanism through which the dietary polyphenol resveratrol brings about its reported beneficial effects on healthspan and if such effects are though activation of SIRT1, the histone deacetylase purported to play a role in lifespan extension resulting from dietary restriction (DR). Resveratrol reduced histone expression in human intestinal Caco‐2 cells through an effect on histone gene expression (opposing an aging‐related observed increase in mouse intestine) and increased DNA methylation. The ER antagonist fulvestrant abrogated the effect on histone expression. SIRT1 overexpression alone had no effect on histone expression or DNA methylation but overexpression abrogated both effects of resveratrol. Genes with altered expression resulting from resveratrol treatment or SIRT1 knockdown did not overlap but both sets of genes showed an overlap greater than expected by chance with genes affected by DR. The findings indicate that resveratrol has epigenetic effects that are mediated through the ER and are independent of SIRT1 and that such actions may contribute to effects of resveratrol to increase healthspan.
Hepatocyte nuclear factor 4α (HNF4α) in coordination with retinoic acid receptors (RARs) increases all‐trans‐retinoic acid (RA)‐dependent CYP26A1 gene expression in hepatocytes
Authors: Zolfaghari Reza , Zhang Yao , Ross A. Catharine
Published: June 2021

CYP26A1, a cytochrome P450, catalyzes exclusively the oxidative inactivation of all‐trans‐RA, the major hormonal metabolite of vitamin A. RA is a pan‐agonist of RARs, promoting RAR binding to DNA response elements of numerous genes. CYP26A1 is very highly induced by RA in the liver, generally to a greater extent than in other tissues, suggesting that a liver‐specific factor may be required for its physiological transcriptional response. In this study, we cotransfected HNF4α, with or without RARs, and demonstrated RA‐dependent activation of a human CYP26A1 promoter‐luciferase construct in HepG2 cells. Analysis of a 2.5‐kbp putative CYP26A1 promoter sequence identified 5 putative HNF4α DNA response elements: H1 located in a proximal region overlapping with an RAR element‐1 (RARE1); H2 and H3 in the distal region, close to RARE2 and RARE3; and H4 and H5 in intermediary regions. Chromatin immunoprecipitation analysis showed significantly increased binding of HNF4α and RARs in the proximal and distal CYP26A1 promoter regions in RA‐treated cells, as compared to the control. Mutational analysis of the individual HNF4α DNA‐response elements identified H1 as the major site for HNF4α binding because H1 mutation inhibited the promoter activity by ~90%, followed by H2 and H3 mutation each with ~50% inhibition. Therefore, our results indicate that HNF4α, as a liver‐enriched nuclear transcription factor, may coordinate with RARs to strongly induce CYP26A1 gene by RA, which may explain the high level of response to RA observed in the liver. (NIH CA‐90214)
Physiological Pathways tool allows intuitive linking of genotype and phenotype data to biological processes in a graphical format
Authors: Munzenmaier Diane H. , Liu Weisong , Jacob Howard J.
Published: June 2021

The Rat Genome Database (RGD) has recently developed a new feature called Physiological Pathways that graphically depicts various physiological systems, allowing intuitive and informative linking of physiological processes to related phenotype and genotype information. These pathways are designed to complement and integrate with the existing molecular pathway features in RGD, allowing coverage of processes that occur within and between cells, tissues, and organs. The user can begin with a pathway of interest and drill down to find information on involved genes, as well applicable strain reports, phenotype data, etc. Alternatively, one can begin at the level of a gene of interest and zoom out to determine physiological and pathological context for the associated gene product.

Physiological Pathways are continually growing and being updated with new pathways in a variety of organ systems. Pathways are currently being added in a manner that attempts to cover a wide range of processes including those in the areas of cardiovascular (vasoconstriction), renal (vasopressin‐mediated water reabsorption), and neuroendocrine (insulin release regulation and action). This new feature promises to be an effective and user‐friendly tool with which to access and retrieve physiological and genomic data for researchers who use the rat as a model to study biological processes and their modulation.
University student evaluation of e‐mail communication for academic purposes
Authors: El-Sabban Farouk
Published: June 2021

University students use multi‐faceted means of nowadays technology, among which is the extensive use of e‐mail. Many benefits of e‐mail use in academia were reported, with improved student‐teacher communication being of most value. The work herein is based on 5 years of experience in utilizing e‐mail and in a variety of courses, in biological sciences and others, at the College for Women of Kuwait University. The course instructor establishes an e‐mail account for each course and students are provided with its password. The main purpose of the e‐mail account is for the instructor to disseminate all relevant information, announcements and send document files. Students are informed of this arrangement and are clearly advised to use the student's personal e‐mail to communicate with the instructor, to avoid cluttering by many student messages. However, students are permitted only to forward any of the inbox messages to their respective e‐mail accounts. A simple 15‐statement questionnaire was designed and administered to students (with 80% response rate) to seek their feedback and opinion. Students favored the use of e‐mail ‐as they felt that it: is convenient (96), saves time (93%), is available any time (90%), is faster to reach the course instructor (83%), is a preferred communication means (82%), made them satisfied with instructor's responses (79%), and made them fully‐informed and provided. While most students would recommend the use of e‐mail in future courses (72%), they prefer to communicate with the course instructor on a face‐to‐face basis (53%, with 21% undecided). As a good number of students expressed different favorable and complimentary comments, a small number wished that communication with them would be by blackboard – an observation that is worthy consideration and implementation. Overall results indicate that the e‐mail system is a valuable means in keeping satisfactory communication between students and their course instructors – for the overall benefit of education.
First steps taken for introducing science advocacy into the curriculum at the University of South Florida: teaching tomorrow's researchers how to translate science for the public and policymakers
Authors: Dean Jay B. , Liller Karen D.
Published: June 2021

Health‐related researchers must be more proactive in promoting science literacy in community groups, to business leaders and politicians. These groups are the conduits for change that influence and implement public policy in the face of competing federal/state budget priorities. If researchers cannot frame their work with messages that are understandable to the public, then policy decisions may be uninformed and we will all live with the consequences. USF has taken first steps towards integrating science advocacy into the curriculum by partnering with Research!America and Pfizer to host a science advocacy workshop and a science and media forum (Let Me Be Clear: Science Journalism in the Age of the Genome and Twitter). Research!America is the nation's largest nonprofit public education and advocacy alliance working to make research to improve health a higher national priority. The science advocacy workshop introduced participants to strategies and tactics for effectively communicating with state/federal policy makers. The science and media forum was staffed with journalists from the local/national media who held discussions about the media, health research, science, and public understanding, followed by Q&A sessions. Knowledge and techniques learned through this event will be used to develop didactic and experiential experiences focused in science advocacy for students (USF, Pfizer & Research!America).
Safety Pharmacology Master of Science (MS) program: design and implementation
Authors: Matlib M. Abdul , Millard Ronald W. , Maggio John E. , Ball W. James , Rapoport Robert M.
Published: June 2021

Safety Pharmacology is a rapidly growing component of drug development distinct from classical toxicology and pharmacology. The importance of training in Safety Pharmacology is underscored by current FDA regulations and the International Committee on Harmonization guidelines on preclinical drug safety studies. A specific advanced degree curriculum is required to prepare future Safety Pharmacologists. However, to our knowledge, none of the current Pharmacology MS programs incorporate a special emphasis in Safety Pharmacology. We describe the design and implementation of a new MS in Pharmacology with Safety Pharmacology emphasis for graduates in the life sciences. A Certificate in Safety Pharmacology program is also designed for training or retraining of employees in drug discovery/development enterprises and for individuals with non‐pharmacology degrees intending to enter the field of Preclinical Safety Pharmacology. The comprehensive curriculum includes a series of didactic courses on drug discovery and preclinical development as well as principles and experimental methods in Safety Pharmacology. The special emphasis Safety Pharmacology MS program begins in August 2012.
A Curriculum for Teaching Scientific Presentation Skills to Graduate Students
Authors: Paul Dennis
Published: June 2021

Communication of ideas is critical to the careers of all scientists. Scientists with superior presentation and teaching skills are more likely to secure employment and be recognized by their peers. Typically, training of these skills is left to the individual's mentor, which can vary greatly. Instead, we have designed a course to teach scientific presentation skills. The curriculum comprises introductory didactic instruction and laboratory/Socratic sessions for each skill. Abstract writing, poster design, slide design, 10 min. conference presentations, seminars, lecturing and question writing skills are practiced in a low‐stress setting. For all oral presentations, we employ peer and instructor critique followed by revision and re‐presentation. Development of an appropriate personal style is stressed. We have developed exercises to address critical thinking, and nervousness/panic situations. Over 15 years that the course has been offered, 76% of students have received formal recognition for a presentation, at local or national meetings, including two ASPET student awards.
Establishing core competencies in respiratory physiology when educating both physicians and physicians‐in‐training
Authors: Lechner Andrew J. , Matuschak George M , Brink David S
Published: June 2021

Ensuring that physicians possess sufficient knowledge of physiology to manage patients is a challenge when educating both medical students and established practitioners. For the former, we must lay a coherent physiological base on which students build a mechanistic understanding of how form subserves organ and organismal function, so they apply evidence‐based therapies to future patients’ myriad constellations of symptoms. For the latter, continuing education must reinforce core physiological principles for physicians whose disparate training or current practices may lack scientific rigor to optimize patient care. We describe models for teaching respiratory physiology to each audience, as this discipline permeates subspecialties in pulmonary, intensive/critical care, sleep, and anesthesiology. Our curriculum for medical students reflects the 14‐year evolution of a “Respiratory Module” taken by this institution's 2nd‐year medical students. Comprising 40 lectures plus labs and discussions over 5 weeks, we use physiological principles both to introduce the module and to underscore subsequent advanced topics. Our curriculum for residents, fellows, and community physicians employs a 6–8 lecture series over 2–4 days, “How to Injure the Lungs”, that challenges its audience to identify the underlying pathophysiology of both common and obscure pulmonary diseases encountered daily in their practices.
Higher Order Concept Activities (HOCA) enhances non science student performance in Biology course
Authors: Yamazaki Katrina Go , Combs Matthew , Pozos Robert
Published: June 2021

This study explored the effectiveness of HOCA to improve student learning and retention by comparing improvement and retention of biological concepts in an introductory non science majors biology course taught to three different classes at San Diego State University: 50 students class (HOCAc) that was given HOCA throughout the term, online/lecture (250 students) (HB) or solely online (250 students) (OL). Previous to registration, students answered questions in BioChemistry, Cell Metabolism, DNA and Physiology. Student demographics were similar between the classes and the HB and OL groups did not receive HOCA during the term. Analysis of the grades at midterm demonstrated that 49% of the students of the HOCAc received an 80% or above whereas 33.5% of the students in the HB (*p<0.05) and OL (*p<0.05) groups performed at that level. The DOCAc demonstrated a significantly greater improvement in precourse questions than the HB and OL groups. Although the overall median grade in all three classes was approximately the same, the data suggests that HOCA approach may contribute to the number who excel in the course. (Supported by NIH IRACDA #GM06852)
Protein Portfolios: Active learning exercises integrated into a one‐semester biochemistry course that examine protein structure and function
Authors: Dutnall Robert N , Mills Stephen A , Plesniak Leigh A
Published: June 2021

Protein Portfolios is a collection of active learning exercises that are integrated into a one‐semester biochemistry lecture course. This course covers macromolecular structure, enzyme kinetics and mechanisms, and metabolism (focusing on glycolysis, the citric acid cycle and oxidative phosphorylation). In an effort to show students how to explore and interpret current knowledge of protein structure and function, we introduced the Protein Portfolios exercises. Students work in small groups and are assigned the primary sequence of a specific enzyme as the basis for five exercises. The exercises integrate with lecture and introduce current bioinformatics and molecular graphics programs as well as online databases to identify, compare and analyze protein sequences, view three‐dimensional structures and find relevant information about protein function. Each group builds a portfolio of information about the enzyme that includes multiple sequence alignments, structures, catalytic mechanism, inhibition and regulation, and connection to a metabolic pathway. They also find information about medical or socio‐economic relevance. The assigned enzymes can be chosen based on various criteria but are typically from pathways that are distinct from, but can be connected to those covered in lecture. Students complete the exercises outside of lecture and present their findings to class in short oral presentations.
A Cat among the Wolves: An attempt to reveal the identity of a felid‐like humerus misidentified as Canis dirus from Rancho La Brea
Authors: Koper Lindsey
Published: June 2021

There have been many kinds of animals found at Rancho La Brea located in Los Angeles, California; both carnivore and herbivore alike. The most common species found in the tar pits are the predators of the area such as Canis dirus (Dire wolf), Smilodon fatalis (saber‐tooth cat), and Canis latrans (American coyote). Other large carnivores that are not as common but still prevalent include Panthera atrox (American lion), Puma concolor (mountain lion), Panthera onca (jaguar), and Arctodus simus (short‐faced bear). Multitudes of these fossil specimens have been excavated from Hancock Park since the 1870s, and the University of California, Berkeley, was the first institution to house these fossils. Since these early dig operations in the 1900s, University of California, Berekely has traded fossil specimens with other large institutions, including the Field Museum of Natural History located in Chicago, Illinois. It was during a recent visit to the Field Museum to study the La Brea specimens in the Geology collection, that I found a misidentified limb bone. The bone is a humerus which was labeled Aenocyon dirus (Canis dirus). This humerus shows some characteristics that hint toward it belonging to a felid of some kind rather than a large canid. The most likely taxa include Panthera onca and Puma concolor.

Grant Funding Source: Nothern Illinois University
Variant fibulocalcaneus muscles of the ankle: Photographic evidence and clinical significance
Authors: Lambert H Wayne , Atsas Stavros , Fox Jacob N , Dodson Sean C , Daney Blake T
Published: June 2021

Anomalous fibulocalcaneus muscles have gained recent attention in the clinical literature. During 207 cadaveric leg dissections, novel variants of three fibulocalcaneus muscles associated with the ankle joint were identified: 1) fibularis quartus, 2) fibulocalcaneus internus, and 3) anterior fibulocalcaneus. Approximately 20% of dissected limbs contained a fibularis quartus, including several rare muscle variants, including a fibulocuboideus and a novel fibulocalcaneocuboideus. One fibulocalcaneus internus was identified, which led to the first gross anatomical case report since 1914 and the first photograph of this rare muscle. Seven examples of the anterior fibulocalcaneus, a novel muscle first reported in 2010, were identified with bilateral presentation in three cadavers. Photographic evidence of these variant fibulocalcaneus muscles will be presented, and the clinical significance of these variant muscles will be discussed. Biometric and radiologic studies of these muscles are ongoing. Radiologists and clinicians should be aware of these muscles when embarking in diagnosis and imaging interpretation, especially when chronic ankle pain is involved.
Positive selection on mitochondrial M7 lineages among the Gelong people in Hainan
Authors: Li Dongna , Yang Kun , Jin Li , Li Hui , Consortium Genographic
Published: June 2021

Selections on human mitochondrial variations are difficult to examine. In this study, we found possible signs of selection on mitochondrial M7 lineages among the Gelong people who migrated from Guizhou to Hainan throughout the last 1000 years. The genetic structure of the Gelong people shows an obvious sex‐biased population admixture pattern with only 4.9% paternal contribution but 30.7% maternal contribution from indigenous Hlai people. According to frequency spectrum tests for deviation from neutrality and mismatch tests of demographic expansion, part of the maternal mitochondrial M7 lineages among the Gelong came from the Hlai had spread quickly and therefore might have undergone positive selection. In the future, whole mitochondrial genome sequencing might reveal the functional advantage of the M7 lineages.

The research was supported by the National Natural Science Foundation of China (30860124), Natural Science Foundation of Hainan (061014)

Grant Funding Source : the research was supported by the National Natural Science Foundation of China (30860124,), Natural Science Foundation of Hainan (061014)
Midline Angular Relationships between the Hard Palate and Cribriform Plate: Implications for Surgical Access to the Pituitary Fossa
Authors: Golubovskaya Yevgeniya , Lawson William , Fisher Juliya , Pagano Anthony S , Caceres Noel , Marquez Samuel
Published: June 2021

Understanding of the regional anatomy and craniometric landmarks surrounding the pituitary fossa are of important use in locating the pituitary gland during endoscopic sinus surgery and in preventing complications that may arise from damage to the adjacent structures. One important anatomical relationship cited in most anatomical textbooks is that the cribriform plate is parallel to the hard palate in the midline plane. However, the cribriform plate appears inferoposteriorly oriented and the hard palate is posterosuperiorly oriented in midsagittal and parasagittal views. To better assess their orientation, we quantified the angle made by the intersection of two chords between; 1) the anterior nasal spine (ANS) and posterior nasal spine (PNS) and 2) the anterior‐ and posterior‐ midline points on the cribriform plate (ACP, PCP). In a sample of 15 bisected cadaveric heads metal rods were used to approximate the extents of the two chords. The bisected heads were photographed with the rods in place and the photographs were analyzed in the computer program Image J where the angle of intersection between the ANS‐PNS and ACP‐PCP chords was calculated. Results show that the chords are oriented an average of 7.35 degrees from each other with a range between 4 and 15 degrees. ENT surgeons must be aware of these angular relationships to ensure proper and safe access to the pituitary gland during transsphenoidal hypophysectomy.

Grant Funding Source : AAA
To Assess and compare the standing lumbar curve in relation to the two chair designs used at the School of Physiotherapy in Jamaica
Authors: singh keerti , Myrie carolyn , martin sharmila roopchand
Published: June 2021

Objective

To determine which of the two chair designs at School of Physiotherapy (UWI Mona) most approximates the normal degree of standing lumbar curve.

Design and Methods

A non‐equivalent control group experimental study design was used in which 34 of the 61 subjects participated. The degree of lumbar curvature of each subjects was measured in standing and sitting in a standard desk arm chair. The lumbar curvature was measured using a flexible ruler moulded to the spine of each each subject. The landmarks of the lumbar curve from the second sacral spinous process to the third lumbar spinous process were palpated and marked with skin pencil. The corresponding landmarks of the lumbar curve were marked on the flexible ruler. The flexible ruler was used and moulded to the skin overlying these spinous processes. The curve from the ruler was traced on paper. The degrees of lumbar curvature were calculated.

Results

Neither of the two chair designs ( the standard chair or the desk‐arm chair design) provided correct sitting posture. However, the standard chair design yielded the better lordotic curve.

Conclusions

Provision should be made for correct sitting posture to prevent possible back injury of future physical thrapists.

Grant Funding Source : University of West Indies
Embryology of the Anomalous Left Vertebral Artery and its Implications in Neck Surgery
Authors: Vasan Nagaswami , Vasan Cheryl , Varricchio Paolo , DeFouw David
Published: June 2021

Anomalous branches of the aortic arch (AA) occur frequently but are poorly explained. In an 82‐year old Caucasian male cadaver who died of coronary artery disease with severe aortic stenosis, the left vertebral artery (LVA) originated from the AA between the common carotid and subclavian arteries. The prevertebral part of LVA was also tortuous, narrower and entered the C5 transverse foramen. The right vertebral artery (RVA) from the right subclavian was wider than the left suggesting compensation to the cerebral circulation. Respectively, the inner and outer diameters of LVA were 2.5and 3.6 mm and of RVA were 5.6 and 6.0 mm. Prevalence of LVA arising from AA was reported at 2.4–5.8% of cadaveric specimens. An anomalous LVA may be asymptomatic; however, it is important in neck and supraaortic arch vascular surgery and in other noninvasive neck procedures. Embryologically, VA is formed by development of longitudinal anastomoses linking the cervical intersegmental arteries. These intersegmental arteries regress except the seventh, which becomes the proximal subclavian artery, the point of origin of the adult VA. When LVA arises from AA proximal to the subclavian artery, the 6th dorsal intersegmental artery might have persisted. (Supported by the Department of Cell Biology and Molecular Medicine).
External Laryngeal Morphology: Gender differences
Authors: Bee Mary Tracy , Diven Allison , Kalnasy Kevin , Koetters Emily , Ottenbreit Mark
Published: June 2021

The larynx is an important part of the respiratory system and has great clinical relevance. While many medical procedures involve manipulation or accessing different areas of the larynx, few studies quantify the distances within and between these cartilaginous structures. Our study investigated the size and distance of the hyoid bone, thyroid cartilage and cricoid cartilage and the distances between these structures on human cadavers (n=37). Surprisingly, a significant difference in the size of the cartilaginous structures was not identified in most parameters between genders (p=0.318). However, the distances of the fibrous gaps that lie between the hyoid bone the cartilaginous structures were higher in females than males (p<0.05). Knowledge of this variability has a significant impact on clinical processes like tracheostomies and cricothyrotomies of different genders.
Musculocutaneous nerve transit through a supernumerary head of the biceps brachii: implications for lateral antebrachial cutaneous and musculocutaneous nerve entrapments, diagnosis, and treatment
Authors: Miller Joseph M. A. , Trelease Robert
Published: June 2021

The lateral antebrachial cutaneous nerve (LACN) can be entrapped by the biceps tendon or bicipital aponeurosis at the cubital fossa, and the musculocutaneous nerve (MCN) can be compressed as it penetrates the coracobrachialis. Either condition can result in pain in the anterolateral elbow region and dysesthesia of the lateral forearm. These entrapment syndromes are treated either conservatively or by surgical decompression of the LACN by incision or resection of the biceps tendon or bicipital aponeurosis. We describe an unusual anatomical variation of a musculocutaneous nerve that penetrates a third head of the biceps brachii before continuing as the lateral antebrachial cutaneous nerve. Compression of the MCN by such a supernumerary biceps head could result in a pattern of symptoms similar to LACN entrapment at the elbow or MCN entrapment at the shoulder. Given that the frequency of supernumerary biceps heads has been reported to be as high as 12% in the general population, this etiology should be considered by clinicians in the differential diagnosis and treatment of these entrapment syndromes.
Hypertrophy of the Subclavius Muscle Accompanied by Atrophy of the Pectoralis Muscles Post‐mastectomy
Authors: Carey Fred , Jones Beth Moody
Published: June 2021

Musculoskeletal impairments of the upper extremity following mastectomy are well documented, although the cause of these impairments is not always known. In this case study, asymmetry of the shoulder girdle musculature was found during anterior chest wall dissection of a female cadaver with a history of a left mastectomy at age 45 (age at death: 96). The left pectoralis major and minor muscles were markedly smaller than the contralateral pectoralis muscles, while the converse was apparent for the subclavius muscles (i.e. left larger than right).

In situ measurements of the depth of the bellies of the subclavius muscles at distances of 5 and 7 cm from the sternoclavicular joint demonstrated that the left subclavius depth was nearly twice that of the right (at 5 cm: R=5mm, L=10mm; at 7 cm: R=8mm, L=15 mm). Measurements of the length and wet weight of the muscles confirmed both the increased size and mass of the left subclavius (length: R=8.5 cm, L=10.5 cm; weight: R=1.2 g, L=3.3 g).

The pattern of atrophy of the pectoralis muscles suggests that the medial pectoral nerve was damaged during surgery or during post‐operative treatment. How this led to the apparent hypertrophy of the left subclavius muscle is unclear. It is possible that because of the atrophy and associated weakness of the left pectoralis muscles, the left subclavius muscle took on a greater role in shoulder girdle stabilization, increasing in size and mass over time.
Radiofrequency reduces fibrosis in experimental tendon lesions
Authors: Akamatsu Flávia , Teodoro Walcy , Saleh Samir , Andrade Mauro , Jacomo Alfredo Luiz
Published: June 2021

BACKGROUND

Calcaneous tendon injuries are commonly seen as consequences of sports trauma. Ideal management should provide rapid healing so early mobilization can avoid tissue adhesions. Radiofrequency (RF) produces heat by molecular friction caused by polarity changes and its therapeutic use aims reduction of the local inflammatory response. We investigated the action of the RF on the fibrosis produced after experimental lesions of the calcaneous tendon in rats.

METHODS AND MATERIAL

Thirty adult male Wistar rats weighing 250 to 300 g were surgically submitted to bilateral partial transverse section of the calcaneous tendon. The right tendon was treated with RF whereas the left tendon served as control. On the third postoperative day, the rats were divided into three experimental groups consisting of ten rats each which were treated with monopolar RF (Tonederm™) adjusted to 650 kHz and 1–2w, for two minutes twice a week, until they were sacrificed on the 7th, 14th and 28th days, respectively. Tendons were weighed and histological specimens were studied for inflammatory cell content and fibrosis was evaluated by hidroxyprolin content.

RESULTS

No difference was observed concerning inflammatory cells in all groups, but significant reduction in collagen content on day 14 was related to RF treatment, as well as tendon weight as compared to controls.

CONCLUSION

RF treatment can reduce fibrosis in experimental tendons injuries healing and clinical studies may include RF among the therapeutic tools in tendinous lesion management.
Brain volume of the newly‐discovered species Rhynchocyon udzugwensis (Mammalia: Afrotheria: Macroscelidea): implications for brain‐body allometry within Afrotheria
Authors: Kaufman Jason A. , Turner Gregory H. , Holroyd Patricia A. , Rovero Francesco , Grossman Ari
Published: June 2021

The Gray‐faced Sengi (Rhynchocyon udzugwensis) is a newly‐discovered species of Sengi (Elephant‐Shrew) and is the largest known extant representative of the order Macroscelidea. The discovery of R. udzugwensis provides an opportunity to investigate the allometric scaling relationship between brain size and body size within the superorder Afrotheria. We performed a 3D spin echo magnetic resonance imaging (MRI) scan on a preserved adult specimen of R. udzugwensis using a 7‐Tesla high‐field MR imaging system. The brain was manually segmented and its volume was compiled into a dataset containing previously‐published allometric data on 29 other species of insectivore‐grade mammals including representatives of Afrotheria, Soricomorpha and Erinaceomorpha. Results of log‐linear regression confirm a strong correlation between brain size and body size among all taxa. Post‐hoc tests indicate a grade‐shift between Macroscelidea and other members of Afrotheria, Soricomorpha and Erinaceomorpha: the Macroscelidea have larger positive brain‐size residuals. As a group, the Macroscelidea have larger brains for a given body size than that observed for the other insectivores. Further research incorporating Hyracoidea, Proboscidea, and Sirenia are necessary for a more‐complete understanding of brain allometry in Afrotheria compared to other Eutherian mammals.

This research was supported by an intramural grant from Midwestern University.