bluuebunny/crossref_metadata_2025 huggingface dataset:
Incubation of C2C12 myotubes with the phopholipase D (PLD) inhibitor 1‐butanol ablates contraction‐induced but not leucine‐induced signaling to p70 S6 kinase (S6K1) via phosphatidic acid (PA)
Authors: Atherton Philip James , Loughna Paul , Hill Derek Samuel , Rankin Debbie , Rennie Michael
Published: June 2021

Signaling through mammalian target of rapamycin complex 1 (mTORC1) regulates muscle protein synthesis (MPS) responses to amino acids (AA) (particularly leucine, (Leu)) and contraction via mechanisms independent of upstream insulin signaling (e.g. phosphoinositide 3‐kinase). Recently, it was shown that PLD‐dependent production of the lipid 2nd‐messenger PA (which binds and relieves inhibition of mTORC1 by FK506‐binding protein 12, thus activating mTORC1) is necessary for signaling to S6K1 after eccentric contractions. We hypothesized that, similarly, Leu‐induced increases in S6K1 signaling might also be PA‐dependent. Murine C2C12 myotubes were contracted for 30 min (1 or 4 Hz, 20 V, 24 ms pulses) or incubated with 1 mM Leu (n=6) in the presence/absence of 0.25 % 1‐butanol, a potent inhibitor of PA production by PLD. Phosphorylation of S6K1Thr389 was measured by immunoblotting. Increased phosphorylation of S6K1 with 4 Hz stimulation exceeded that with 1 Hz (+53 vs. +33%; P<0.05), but was ablated by 1‐butanol at both 1 and 4 Hz. Conversely, the increase in S6K1 phosphorylation caused by Leu (+33%; P<0.01) was unaffected by 1‐butanol (+31%; P<0.01), which also did not alter basal S6K1 phosphorylation. Thus, whereas contraction requires PA for signaling to S6K1, Leu regulates mTORC1 signaling separately, perhaps explaining why AA and contraction synergistically stimulate MPS. Support: BBSRC, RCUK, EXGENESIS

Grant Funding Source: Physiology (APS)
Situational analysis of infant and young child nutrition (IYCN) activities in six countries of the African Sahel demonstrates that most IYCN policies, and related training materials & programs, are consistent with international guidelines, but substantial gaps exist in program coverage and effective monitoring & evaluation (M&E)
Authors: Wuehler Sara E , Hess Sonja Y , Brown Kenneth H
Published: June 2021

Background & objectives

Due to limited or no progress toward reducing <5 mortality and malnutrition, an alliance of international agencies joined to “Reposition children's right to adequate nutrition in the Sahel”, starting with an analysis of IYCN activities: national policies, training materials, programs, and M&E, compared with international recommendations.

Methods

Key informants conducting IYCN‐related activities in Burkina Faso, Chad, Mali, Mauritania, Niger & Senegal were interviewed, and >500 documents were reviewed & compared with internationally recommended policies on: optimal breastfeeding & complementary feeding (CF) practices, prevention of micronutrient deficiencies, prevention of mother‐to‐child transmission of HIV (PMTCT), management of acute malnutrition (AM), & food security.

Results

Most IYCN policies & related training materials are consistent with international guidelines. Neglected topics include specific CF recommendations, zinc in diarrhea management, PMTCT & screening for AM. Programs target high‐risk populations, but few reach national coverage or are adapted to research into local barriers & beliefs. Most M&E activities do not permit identification of effective program components.

Conclusions

The IYCN foundation is set, but greater resources & capacity building are needed to enhance & expand program activities and M&E.

Support: FAO, HKI, MI, UNICEF, WFP
Influence of garlic and ginger compared to aspirin on diabetic indicators in STZ‐induced diabetic rats
Authors: Thomson Martha , Al‐Qattan Khaled , Al‐Houli Mouna , Divya J.S. , Al‐Hassan Jassim , Al‐Sawan Shorooq , Ali Muslim
Published: June 2021

The hypoglycemic effects of aqueous extracts of raw ginger (Zingiber officinale) and garlic (Allium savitum) in comparison to aspirin were studied in diabetic rats. Diabetes was induced by IP injection of streptozotocin and a fasting blood sugar >300 mg/dl indicated diabetes. Diabetic rats were divided into 4 groups: control, garlic‐treated, ginger‐treated and aspirin‐treated. Garlic and ginger extracts and aspirin were administered daily for 8 weeks. Blood glucose and serum creatinine, cholesterol and triglycerides were significantly elevated in diabetic control rats, and significantly lowered by both ginger and garlic treatments. Aspirin treatment of diabetic rats significantly decreased serum triglyceride and cholesterol levels but not blood glucose levels. Serum protein decreased significantly in diabetic compared to normal rats, with ginger and garlic treatment resulting in nearly normal serum protein levels. Urine creatinine and protein were elevated in diabetic rats, and significantly decreased by garlic and ginger but not aspirin. Diabetic rats lost weight, and increased water and food intake as well as urine output compared to normal. Ginger‐treated rats had a modest weight gain and decreased food and water intake and urine output, while garlic‐treated rats had a slight weight gain and decreased urine output. Aspirin treatment resulted in no change in urine protein and creatinine, body weight, water and food intake and urine output. Thus, garlic and ginger treatments were useful in ameliorating the negative progress of diabetes in STZ‐induced diabetic rats, while aspirin had limited effects.

The study was supported by KFAS grant # 2007‐1302‐04.
Ground beef from corn‐fed cattle provides greater health benefits than ground beef from pasture‐fed cattle
Authors: Gilmore Linda Anne , Walzem Rosemary L. , Crouse Stephen F. , Smith Stephen B.
Published: June 2021

We proposed that, compared to ground beef enriched in saturated fatty acids (SFA) and trans‐fatty acids (pasture‐fed), ground beef enriched with monounsaturated fatty acids (MUFA; corn‐fed) would increase high density lipoprotein cholesterol (HDL‐C). Twenty‐seven men were allotted to three treatment groups to rotate through three ground beef patty preparations (24% total fat). Participants consumed five, 114‐g patties per week for 5 wk and then rotated to the other ground beef types for a total of three phases. Ground beef patties were produced from pasture‐fed steers (MUFA:SFA = 0.71), from corn‐fed, short‐fed steers (MUFA:SFA = 0.83), and from corn‐fed, long‐fed steers (MUFA:SFA = 1.10). The high‐MUFA ground beef increased HDL‐C over initial values (P = 0.03), and there was a linear relationship between ground beef MUFA:SFA and the change in HDL‐C (r = 0.23, P < 0.05). Type of ground beef had no effect on plasma oleic acid, but there was a negative correlation between plasma oleic acid and HDL‐C (r = −0.25, P < 0.01). Thus, consumption of high‐oleic acid ground beef can increase HDL‐C. Supported by a grant from the National Cattlemen's Beef Association.
The postprandial response to a high fat meal: Effects of processed tomatoes on markers of inflammation and endothelial function in overweight men and women
Authors: Burton‐Freeman Britt Marie , Cao Yumei , Giordano Rose , Edirisinghe Indika , Kris‐Etherton Penny , Kappagoda Tissa
Published: June 2021

Postprandial hyperlipidemia is associated with oxidative stress and elevated markers of inflammation and endothelial dysfunction. Tomato products contain appreciable levels of antioxidant nutrients and nutrient like compounds with potential for modulating oxidative‐/meal‐ induced inflammatory status and protecting the endothelium. We hypothesized that tomato paste added to a high fat meal known to induce hyperlipidemia would reduce the concomitant postprandial inflammation. Twenty‐three men and women (41.7 ± 12.8 y, 29.5 ± 3.6 kg/m2) completed 2 postprandial (pp) tests after run‐in (3 wk of low tomato diet). Each test included consuming 1 of 2 pp meals; a high fat meal with (TOM) or without (Pbo) tomato paste (90 g). IL‐6, TNF‐α, and cellular adhesion molecules (ICAM and VCAM) were measured at 0, 3 and 6h. Test meals had a statistically marginal impact on IL‐6 (2.6 ± 0.2 vs 2.2 ± 0.2, p=0.08, respectively) and TNF‐α (2.1 ± 0.1 vs 2.0 ± 0.1, p=0.10, respectively); however, inclusion of BMI in the model revealed a significant interaction of BMI with meal showing a benefit of tomato that was most apparent in overweight individuals (p<0.05). ICAM and VCAM responses varied by test meals and BMI: TOM attenuated VCAM in obese people only. Consuming antioxidant‐rich foods with meals helps to modulate meal‐induced postprandial inflammation. Study sponsored by the Tomato Products Wellness Council.
Effects of protein intake on energy‐restriction‐induced changes in lipid‐lipoprotein profile, glycemic control, resting energy expenditure, and appetite in overweight men
Authors: Tang Minghua , Armstrong Cheryl LH , Mattes Richard D , Leidy Heather J , Campbell Wayne W
Published: June 2021

Purpose

To assess the effects of dietary protein (pro) on diet‐induced changes in indices of metabolic health.

Methods

For 12 wk, overweight men (BMI 25.0–39.9 kg/m2), aged 24–75 y, consumed a 750 kcal/d energy deficit diet with 25% energy as fat, and either 15% pro (normal pro, NP, n = 21) and 60% CHO, or 25% pro (higher pro, HP, n = 22) and 50% CHO. The NP diet excluded striated tissue and eggs; the HP diet had 15% pro from eggs and 25% pro from lean pork. Pre and post‐study, fasting blood was taken; body composition, blood pressure (BP), and resting energy expenditure (REE) were measured; and daily appetite was assessed.

Results

Reductions over time (p<0.05) in the NP and HP groups included: weight 10 and 9%; fat mass 21 and 20%; lean body mass (LBM) 5 and 3%; cholesterol 18 and 22%; HDL 9 and 9%; LDL 19 and 20%; triacylglycerol 30 and 42%; insulin 3.7 ± 1.4 and 5.4 ± 1.2 μU/mL; HOMA 0.9 ± 0.2 and 1.4 ± 0.2; systolic:diastolic BP 8:6 and 7:8%; and REE 260 ± 112 and 97 ± 78 kcal/d. Diet did not influence these responses, except ΔLBM was greater in NP vs. HP (time × group, p<0.05). ΔREE was predicted by ΔLBM (R2 = 0.21). Daily desire to eat ratings decreased in both groups, but hunger decreased in HP only.

Conclusion

Overweight men can successfully improve indices of metabolic health after weight loss when consuming a normal protein vegetarian or higher protein omnivorous diet.

Support: Natl Pork Brd; Am Egg Brd‐Egg Nutr Ctr; Purdue Ingest Behav Res Ctr.

Grant Funding Source: American Egg Board, National Pork Board
Curcumin Inhibits IFN‐γ Signaling in Colonic Epithelial Cells
Authors: Midura‐Kiela Monica T , Larmonier Claire B , Laubitz Daniel , Ghishan Fayez K , Kiela Pawel R
Published: June 2021

IFN‐γ is a proinflammatory cytokine with profound effects on colonic epithelial cells. Elevated IFN‐γ disrupts the epithelial barrier function, prevents epithelial cell migration and wound healing, and primes IEC cells to express MHC class II molecules and to serve as non‐professional antigen presenting cells (APC). In this report we demonstrate that curcumin inhibits IFN‐γ signaling in colonic epithelial T‐84 and YAMC cells. Curcumin significantly inhibited IFN‐γ induced GAS element‐driven luciferase activity. IFN‐γ dramatically stimulated expression of MHCII genes, HLA‐DRα and HLA‐DPα1, while curcumin dose‐dependently prevented this increase. Curcumin inhibited IFN‐γ stimulated expression of CII TA, a master regulator of MHCII class genes. EMSA analysis showed curcumin‐mediated inhibition of STAT‐1 binding to both GAS and ISRE cis‐elements. Immunofluorescence studies demonstrated that curcumin inhibited IFN‐γ‐stimulated nuclear translocation of Stat‐1. IFN‐γ induced and JAK‐dependent phosphorylation of Stat‐1 at Tyr701, a residue critical in Stat‐1 dimerization and nuclear translocation, was also inhibited. In summary, curcumin acts as a potent inhibitor of Jak‐Stat signaling pathway in the colonic epithelial cells, a phenomenon which may partially account for the beneficial effects of curcumin in experimental colitis as well as in human IBD.

Grant support: 5R01DK067286 (P.R.K.)
Regulation of STAT3 pathway by cPLA2α and PPARδ
Authors: Han Chang , Li Guiying , Huang Shuo , Wu Tong
Published: June 2021

Cytosolic phospholipase A2α (cPLA2α) is a rate‐limiting key enzyme that releases arachidonic acid (AA) from membrane phospholipid. This study shows a novel role of cPLA2α for activation of peroxisome proliferator‐activated receptor‐δ (PPARδ) and STAT3 in the nuclei. Overexpression of cPLA2α in human hepatocellular carcinoma cells (Hep3B) induced the binding of PPARδ to STAT3 response element through the release of transcriptional repressor Bcl‐6 and increased STAT3 reporter activity as determined by luciferease reporter activity assay. These effects are significantly inhibited by the cPLA2α siRNA and specific inhibitors (AACOCF3 and Pyrrolidine) as well as by siRNA knockdown of PPARδ. Overexpression of PPARδ or treatment with the selective PPARδ ligand, GW501516, also increased PPARdelta binding to STAT3 response element and increased STAT3 reporter activity. Addition of GW501516 to nuclear extracts induced a comparable degree of PPARδ binding to STAT3 response element. Moreover, overexpression of PPARδ or treatment with GW501516 upregulated the expression of Stat3 and its downstream anti‐apoptotic molecules including Mcl‐1, Survivin and Bcl‐XL. These results reveal a novel interaction linking cPLA2α, PPARδ and STAT3 signaling pathways in human hepatocellular carcinoma cells.
Pigment epithelium‐derived factor (PEDF) protects neurons from oxidant injury by activation of extracellular signal‐regulated kinase (ERK) 1/2 and induction of Bcl‐2
Authors: Sanchez Alma , Grammas Paula
Published: June 2021

Oxidative stress is an important trigger in the chain of events leading to neuronal death. Mitigating oxidative‐induced damage is critical to preserving neuronal function in injury and disease. Studies show that PEDF imparts protection for retinal neurons and recently also for cerebral cortical cultures. The mechanisms underlying its protective effects have not been elucidated. The current study aims to determine the mechanisms contributing to the neuroprotective effect of PEDF in cortical neurons. Cultured primary neurons are exposed to increasing doses of H2O2 and PEDF with or without an ERK 1/2 inhibitor (U0126) or PI‐3K/Akt inhibitor (LY294002). Levels of the anti‐apoptotic protein Bcl‐2 and phosphorylated ERK1/2, as well as cell survival are determined. H2O2 treatment decreases neuron survival and release of PEDF. Exogenous PEDF induces a dose‐dependent increase in Bcl‐2 and neuronal survival. PEDF pre‐treatment prevents the H2O2‐mediated decrease in cell survival and this effect is blocked by both U0126 and LY294002. PEDF pre‐treatment also prevents the H2O2‐induced decrease in Bcl‐2 which is blocked by U0126 but not by LY294002. These results demonstrate that PEDF protection against H2O2 ‐induced injury is mediated by ERK1/2 induction of Bcl‐2 and suggest that PEDF can protect neurons from oxidative stress. This work was supported, in part, by grants from the NIH (AG15964, AG020569 and AG028367).
Mild acidosis delays neutrophil apoptosis
Authors: El Kebir Driss , Jozsef Levente , Pan Wanling , Wang Lili , Filep Janos G.
Published: June 2021

Emerging evidence indicates that local acidosis associated with infection and inflammation triggers innate and adaptive immunity. Activation of infiltrating neutrophils contributes to transient drop in pH. We investigated the impact of extracellular acidosis on neutrophil apoptosis, a critical determinant of the outcome of the inflammatory responses. Culture of human isolated neutrophils under mild acidosis (pH 6.0–7.0) resulted in concurrent activation of the ERK and PI3‐kinase/Akt signaling pathways, leading to phosphorylation of the pro‐apoptotic protein BAD at Ser112 and Ser136, respectively and prevention of the degradation of Mcl‐1. Consequently, extracellular acidosis prevented disruption of mitochondrial transmembrane potential and translocation of cytochrome c to the cytosol from the mitochondria. Acidosis produced similar delay in apoptosis that could be achieved with LPS. Pharmacological inhibition of either ERK or phosphatidylinositol 3‐kinase partially reversed the anti‐apoptotic action of acidosis. Our results identify mild acidosis as a survival signal for neutrophils by suppressing the constitutive apoptotic machinery and suggest that transient decreases in local pH could contribute to prolongation and amplification of inflammation. (Supported by CIHR MOP‐97742).
Epigenetic regulation of gene expression
Authors: McKnight Robert Allen
Published: June 2021

A growing body of evidence suggests that environmentally induced epigenetic modifications may play an important role in a fetal basis of adult disease susceptibility. Our laboratory focuses on the effects of intrauterine growth restriction (IUGR) on DNA methylation, histone covalent modification, nucleosome positioning and RNA splicing. In order to gain insight into the mechanisms affecting epigenetic regulation, we examine the effects of IUGR on highly epigenetically regulated genes that utilize multiple promoters and alternative splicing as well as CpG island genes and metastable epialleles. The different characteristics of each of these categories of genes, provides the opportunity to look at specific aspects of epigenetic regulation. Evidence will be presented demonstrating how an altered in utero environment can affect epigenetic regulation of gene expression.
Comparative placentation: reasons for diversity and phylogenetic fit
Authors: Enders Allen C
Published: June 2021

Although there are common features in placental structure, such as short diffusion distances between vascular systems in late pregnancy, there is great morphological variation both in definitive placental structure and in the way placentas develop. In species with a long gestation period and precocial young, placentas with more intervening layers, which tend to reduce fetal to maternal cell exchanges, are an obvious advantage. In other instances, there are no apparent advantages in different placental structures. Several factors favor development of diversity in placental morphology. 1. The extraembryonic membranes of one organism, the conceptus, must develop in the uterus of another organism. 2. Early conditions for the developing conceptus are anaerobic whereas later efficient aerobic conditions are essential for continued growth of the fetus. 3. There are potentially two partially sequential placentas, the yolk sac and the chorioallantoic placenta. Despite these factors favoring various methods of forming the definitive placenta, the placental type is consistent within families, but less consistent at the order and superorder levels. The consistency within families suggests that the basic classification of mammals was reasonably accurate even before genomics, and that divergence in placental structure accompanied the initial divergence of different mammalian groups.
Ubiquitin and Autophagy Networks
Authors: Dikic Ivan
Published: June 2021

Ubiquitin is a small modifier that labels proteins in a highly specific manner. Initially, ubiquitination was described as the process of tagging proteins for degradation in the proteasome, a giant protein complex responsible for the breakdown of the majority of intracellular proteins. We have recently described Rpn13 as a novel ubiquitin receptor at the proteasome, which recruits ubiquitinated substrates and deubiquitinating enzyme Uch37 to the proteasome, thus co‐ordinating balance between recognition and disassembly of ubiquitinated substrates at the proteasome.

Removal of harmful protein aggregates, damaged organelles and microbes is mediated by autophagy, a process by which the cell sequesters cytosolic cargo and delivers it for degradation by the lysosome. The involvement of ubiquitin in selective autophagy is becoming more evident. Identification of autophagy receptors, e.g. p62 and NBR1, which simultaneously bind both ubiquitin and autophagy‐specific ubiquitin‐like modifiers, LC3/GABARAP, has provided a molecular link between ubiquitination and autophagy. The molecular details of selective autophagy suitable for clearance of various cargoes, ranging from ubiquitinated protein aggregates to membrane‐bound organelles and microbes will be discussed.
REGULATION OF DIACYLGLYCEROL KINASE THETA
Authors: Raben Daniel M , Tu‐Sekine Becky J
Published: June 2021

Diacylglycerol (DAG) and phosphatidic acid are important signaling molecules involved in numerous signaling pathways. The diacylglycerol kinases (DGKs) are particularly poised to regulate the cellular levels of these two lipids. Although interest in these enzymes is increasing, information regarding their regulation at a molecular level is scarce, particularly information pertaining to the enzymology of these enzymes. We recently showed that DGK‐θ behaves a “quasi‐scooter” given its sensitivity to both the bulk (total) and surface concentration of substrate. Additionally, stimulation of the cultured fibroblasts expressing this enzyme leads to an increase in the apparent Km (Kmapp) which was decreased in response to an increase in the bulk substrate (DOG, dioleylglycerol) concentration. Further progress on understanding the mammalian DGKs at a molecular level have been hindered in large part by the paucity of purified DGKs with significant catalytic activity. To this end, we have purified DGK‐θ to apparent homogeneity. Interestingly, the activity of purified DGK‐θ is extremely weak. Interestingly, addition of certain proteins results in a dramatic increase in its activity in vitro. Studies designed to characterize these activating proteins and their effects on the enzymology of DGK‐θ are in progress. One of the major challenges of this research will be to identify the physiologically relevant activating protein(s) and work is in progress to accomplish this goal.
Calcitonin and glucocorticoids – a novel approach to anti‐inflammatory co‐therapy
Authors: Al‐Kashi Adam , Perretti Mauro , Gilligan James , Mehta Nozer
Published: June 2021

Rheumatoid arthritis (RA) is a common autoimmune disease characterised by progressive joint destruction and extra‐articular manifestations. Glucocorticoids (GCs) are important anti‐inflammatory agents yet have serious adverse effects, including osteoporosis via enhanced bone resorption. Calcitonin (CT), on the other hand, inhibits bone resorption. Here we investigate the combination of sub‐therapeutic GC and calcitonin (CT) in rat collagen‐induced arthritis (CIA), a model of RA. Rats (female Lewis, 160g) immunised i.d. with bovine collagen‐II and FCA adjuvant on day 0, develop hind paw swelling from day 11. Daily treatments were given i.p. from day 11. Body weight, paw volume and clinical score were recorded up to day 18, when blood and paws were taken for analysis. GC 30 μg/kg reduced swelling and clinical scores by 80% (n=25, P<0.01). CT 1.0 μg/kg alone did not inhibit CIA, but combined with sub‐therapeutic 7.5 ug/kg GC, gave efficacy comparable to the four‐fold higher GC dose. Co‐therapy also reduced bone resorption marker CTX‐I (54%; n=14 p<0.05), and neutrophil chemoattractant CXCL5 (64%; n=14 p<0.05). Steroid dose reduction together with the osteoprotection affords a promising new outlook for the management of chronic inflammatory diseases.
Teaching pharmacology and pharmacovigilance in an integrated medical curriculum
Authors: Faingold Carl L. , Dunaway George A.
Published: June 2021

Integrated medical curricula pose a challenge to teaching pharmacology effectively. This contributes to a significant educational deficit, since insufficient drug knowledge is a key factor in major drug‐related public health problems. Adverse drug‐related events (ADRs) are estimated to be the 5th leading cause of in‐patient deaths in the U.S. Drug overdose is the 2nd leading cause of accidental death and is also a common method of suicide. These public health problems indicate the need for improved physician knowledge of drug toxicities and ADRs and emphasize the value of education on pharmacovigilance, which is defined as the epidemiologic study of drug‐related adverse events. Pharmacovigilance has lacked emphasis in U.S. Medical Schools where the term is unrecognized, although ADRs, toxicity, and drug interactions are covered. The integrated 2nd year medical curriculum at SIUSM emphasizes the learning of pharmacology stressing pharmacovigilance. This involves presenting the ABCs of Pharmacology (A: pharmacodynamics; B: pharmacokinetics; and C: pharmacovigilance) and includes web‐based instructional modules (WIMs) that list objectives and resources on 84 drug classes, referencing textbooks that emphasize pharmacovigilance (1) and parallel national pharmacology knowledge objectives.
Thoracic‐pulmonary mechanic model for the comprehension of lung ventilation and water seal chest drainage
Authors: Soto‐Saucedo Ana Cristina , Gómez‐Gallardo‐O'Leary Jorge A , Almanza‐Huante Emmanuel , Castillo‐Hernández Luis , Quintanar‐Stephano Andrés
Published: June 2021

The thoracic‐pulmonary mechanic model (TPMM) is a teaching tool used to better understand the changes in pulmonary and intrapleural pressures during thoracic respiratory movements. Here, we used the model to explain how the intrapleural pressures during the respiratory movements coupled to water seal chest drainage (WSCD) results in an effective solution for pneumo and hydrothorax. Pressures were measured by using equipment and computational MP150 AcqKnowledge software from Biopac Systems Inc. Table shows the pulmonary and intrapleural pressures in basal, pneumothorax and hydrothorax conditions and in solved pneumo and hydrothorax conditions. In conclusion, the TPMM‐WSCD model is useful to understand the physics of the pulmonary ventilation and the principles of the WSCD.

Pulmonary pressure (mmHg)
Intrapleural pressure (mmHg)

TPMM‐WSCD Basal conditions (no breath)
0.50
−4.40

Pneumothorax
0.51
0.28

Pneumothorax solved
0.48
−4.21

Hydrothorax
0.48
2.61

Hydrothorax solved
0.47
−7.11

Supported by UAA. México
Calibrated peer review: The application of statistical concepts to a biological research question
Authors: Dasgupta Annwesa , Neroorkar Samiksha , Gundlach Ellen , Pelaez Nancy
Published: June 2021

This project used Calibrated Peer Review™ (CPR) for Teaching Experimental, Ethical, and Quantitative (TEEQ) Biology in a freshman biology course to help students connect what they learn in lecture to both current and historical research endeavors. The innovation is to introduce reading primary literature and writing about statistical skills in a way that is allied to student interests in biology. CPR is a Web‐based program that enables frequent writing assignments even in large classes with limited instructional resources. In fact, CPR can reduce the time an instructor spends reading and assessing student writing. This study examines improvements in student's ability to (1) identify the treatments in a biological experiment; (2) present a completely randomized design to address the research question of interest; (3) describe the benefit of limiting sources of variability; and (4) describe the limitations to the scope of inference for the biologist. Responses to an AP Statistics item used as a measure show that a series of CPR assignments produced a very high frequency of students with knowledge about use of experimental, quantitative, and statistical applications to a biological research question. Funded by NSF DUE/CCLI #0837229.
Team‐based learning: using case studies and team exams to integrate physiological concepts
Authors: DeRuisseau Lara Roberts
Published: June 2021

Team‐based learning (TBL) was initiated in the first semester of a year‐long undergraduate anatomy and physiology course with the objective of improving integration between physiological systems. An additional goal was for students to understand principles as opposed to merely memorizing facts. Heterogeneous teams were formed the first week of class. Team exams and team case studies comprised 15% of the course grade. Exams were administered every 2 weeks. Following each exam, a new packet of notes was provided for the next module. There were 5 class periods between exams: the first 3 were devoted to a case study(s) applying the recently tested material and 2 were spent lecturing on the most difficult new material. The next exam consisted of 15 questions of new material and 5 questions based on the case study, but were more in‐depth. The students completed the exam individually and then completed the exact same exam with their teammates using the Immediate Feedback Assessment Technique® which allowed multiple attempts (partial credit) at each question until the correct answer was determined. At the mid‐term, 97% of students preferred having team exams. This teaching method has resulted in more engaged students, not only during team exams and cases, but also during lecture. TBL appears to be an efficient tool for increasing integration across physiological systems in the undergraduate classroom.
Assessment of Hepatic Steatosis and Fibrosis in Embalmed Cadavers
Authors: Kwong Allison J , Chu Edward , Mak Ki M
Published: June 2021

Human cadavers used for teaching Anatomy are embalmed in a fluid (75% ethanol, 20% propylene glycol, 2% phenol, 2% formalin, 1% sodium acetate) that is not routinely used in histological fixation. This study assessed quality of tissue preservation and incidence of steatosis and fibrosis, two significant liver diseases, in embalmed livers. Livers from 34 cadavers (age 64–100 yrs) with diverse causes of death were embedded in paraffin, sectioned and stained with H&E for histology, Sirius red for collagen and á‐smooth muscle actin (á‐SMA) antibody for hepatic stellate cells (HSCs) and myofibroblasts. Tissue preservation was graded as good in 12 livers, fair in 12 and poor in 10. Despite these variations, steatosis was seen in 12 livers, central vein fibrosis in 21, perisinusoidal fibrosis in 25, portal tract fibrosis in 16, fibrous septa in 12, bridging septa in 10 and cirrhosis in 1. Eleven livers had lobular inflammation and 14 had portal inflammation. Tumors were noted in 3 livers. Only 3 livers showed minimal change. á‐SMA immunostaining revealed HSCs in the space of Disse and myofibroblasts in central veins, portal tracts and septa, consistent with their fibrogenic role. Conclusions: Embalmed livers provide valuable tissue for histopathology. Steatosis and fibrosis are prevalent in the elderly; though not indicated as the primary cause of death, this pathology may have exacerbated the health of this population.

Grant Funding Source: Mount Sinai School of Medicine
Histochemical and Immunohistochemical Staining for Markers of Fibrosis in Embalmed Cadavers
Authors: Mak Ki M , Chu Edward , Kwong Allison J
Published: June 2021

Liver fibrosis is a significant liver disease, but its incidence in the elderly is not known. Embalmed cadavers used for teaching human anatomy provide liver tissue for analysis of fibrosis in this population. Livers from 32 cadavers (age 64–100 yrs) with diverse causes of death were embedded in paraffin, sectioned and stained for markers of fibrosis: Sirius red stain for collagen, resorcin fuchsin and van Gieson stains for elastin and collagen, and á‐smooth muscle actin (á‐SMA) antibody, followed by Sirius red, for á‐SMA expression by hepatic stellate cells (HSCs) and myofibroblasts. As determined by collagen staining and morphometry, central vein fibrosis was seen in 21 livers, perisinusoidal fibrosis in 25, portal tract fibrosis in 16, short and long fibrous septa in 12, bridging septa (portal‐portal, portal‐central, central‐central) in 10 and cirrhosis in 1. Only 3 livers showed minimal change. Although absent in the space of Disse, elastic fibers co‐distributed with collagen in the portal tracts, septa, central veins and walls of blood vessels. á‐SMA‐stained HSCs localized to collagen fibers in the space of Disse, while myofibroblasts were found with collagen and elastin in portal tracts, septa and central veins, consistent with their role in fibrogenesis. Conclusions: Liver fibrosis, from early to late stages, is prevalent in older adults, and this pathology may have exacerbated the health of this population.
Hepatopancreaticobiliary pathology in the PCK model of ARPKD
Authors: Mason Stephen Bruce , Eggleston‐Gulyas Tracy , Lai Xianyin , Witzmann Frank A. , Gattone Vincent H.
Published: June 2021

Autosomal Recessive Polycystic Kidney Disease (ARPKD) results in renal and hepatic fibrocystic pathology. This study evaluated hepatobiliary pathology in PCK rats, an orthologous model of slowly progressive ARPKD. Male and female rats were evaluated from 4–35 weeks, quantifying organ growth, serology, bile flow rates, histology, Microfil organ casts and bile proteomics. PCK hepatofibrocystic disease is progressive (liver weight as % of body weight and hepatic fibrocystic volume), which after 18 weeks was more severe in females vs. males. A retrograde Microfil cast of hepatopancreaticobiliary ducts demonstrated widespread fusiform bile duct cysts. Pancreatic ducts open into the grossly dilated common hepatic duct. Bile flow rate for 12–15 week and 25 week PCK rats was greater than that seen in normal 15 week rats. The bile proteome from females using 2D gels identified significant differences. MS/MS protein identification of 32 spots found overexpressed proteins (triacylglycerol lipase, pancreatic amylase, chymotrypsinogen B and apolipoprotein A‐1) and numerous albumin fragments, i.e., pancreatic enzymes and fragmented proteins. Biliary pathology and proteomic findings suggest that the grossly dilated hepatic duct cause choledochal sphincter incompetence. The reflux of pancreatic enzymes into the biliary tree might exacerbate the hepatobiliary fibrosis and could also occur in human ARPKD.

Grant Funding Source: NIH
Morphology of longissimus thoracis and its clinical applications
Authors: Kumka Myroslava , Truszkowski Stephen R
Published: June 2021

Current interest in understanding of spinal mechanics, etiology of back pain, and increased use of complex musculoskeletal models require detailed knowledge of the morphology of Longissimus Thoracis (LT) muscle.

Methods

This study utilized 28 embalmed cadavers using traditional anatomical dissections.

Results

Direct connections between LT and thoracic facet fibrous capsules were not found. Superior tendinous attachment of LT was at T2 vertebra in all specimens. At T2, T5 and T8 the LT medial tendons attached at the lateral third of the inferior margin of the transverse processes, whereas lateral tendons were found between the angle and tubercle of the ribs. Myofascial continuity of LT to posterior cervical musculature was found in all specimens. Lateral branches of the dorsal primary rami of the thoracic spinal nerves coursed through the muscle substance of LT in 31.5% of the identified nerves.

Conclusion

Our findings suggest that the LT does not have direct attachments to the fibrous capsules of thoracic facets, a point that should be considered in experimental models of thoracic facet joint structure. Continuity between the LT muscle and posterior cervical musculature suggests a mechanism of myofascial pain or mechanical dysfunction of these muscles. Perforation of LT by the lateral branches of the thoracic spinal nerves may provide a mechanism for neurogenic back pain associated with LT hypertonicity.
Relationship of brachial artery blood flow rate and muscle activity in the anterior flexor compartment of the arm: A test of asymmetry
Authors: Vilnits Yefim , Barry Christin , Parnes Gregory , Pagano Anthony , Marquez Samuel
Published: June 2021

During strenuous activity, the human body must provide an adequate supply of oxygen to active muscles. Apart from a general upswing of blood flow to the muscles moderated by the sympathetic nervous system, the body appears to have a mechanism for directing blood flow to the specific acting muscles. This quantitative study documents blood flow rate (BFR) to muscles in need of oxygen by employing a mixed sex sample (n=20) of individuals between the ages of 22 to 25. Subjects performed a preset number of biceps curls (flexing the elbow against resistance) with one arm only. Left‐handed and right‐handed curls were split evenly among the participants. Increases in BFR were measured through ultrasound of the brachial artery just proximal to the elbow. Results showed a general increase in BFR in both arms with a substantially higher percent increase in the weight‐bearing arm. The average percent increase of BFR in the weight‐bearing arm was 130.5% with a standard deviation (sd) of 31.4% and a standard error (se) of 9.9%. The average percent increase of BFR of the non‐weight bearing arm was 47.1% (sd=53.4%, se=16.9%). These preliminary findings suggest an asymmetrical blood delivery increase favoring the active muscles. BFR increases are likely influenced by local muscle activity in a dynamic functional relationship.
Correlation between hard and soft tissue dimensions of the human foot
Authors: Narvaez Francisco Alberto , Cardona Jessica , Pagano Anthony Santino , Marquez Samuel
Published: June 2021

During locomotion, the metatarsals create a sturdy lever for forward thrust while affording flexibility in stance phase. However, their exposure to impact with the substrate during touchdown of the foot renders the metatarsals a common site for traumatic foot injuries. The greater lengths of the metatarsals relative to other foot bones may exacerbate this condition. Thus a strong correlation of total foot length with the respective lengths of metatarsals (MT's) I, II, and III may suggest a relationship between foot length and risk of metatarsal injury. It is hypothesized that the metatarsal of the greatest length will show the strongest correlation with total foot length. This study examined 48 feet from 24 donor bodies. Measurements were collected by all authors and averaged to reduce inter‐observer error. Both left and right feet were measured and the mean of the two was used to control for asymmetry. MT II was longer than MT's I and III but the length of MT I had a higher correlation coefficient with total foot length than did the lengths of MT II or III. All correlations were positive but none were significant (p>.05). The greater correlation between total foot length and first metatarsal length may be related to the medial transmission of weight during stance phase. While the high p value could be a product of unaccounted variation in tarsal and digit length, these factors warrant further investigation.

Grant Funding Source: AAA
Geometric morphometric investigation of size and shape in prosimian molar morphology: incorporating phylogeny into allometric analyses
Authors: St Clair Elizabeth , Boyer Doug , Baab Karen , Perry Jonathan
Published: June 2021

Previous published statistical analyses of allometric variation in primate molar form have not included phylogenetic information. Some primate clades and dietary groups differ in average body size; thus, observed associations between size and morphological variation might be due to evolutionary history and/or diet. We examined 3D μCT generated surfaces of mandibular second molars of 26 prosimian taxa (n=69) to test if shape variation is correlated with size variation taking phylogeny into account. We positioned 41 landmarks and semilandmarks on cusps and crests. After superimposition via generalized Procrustes analysis, principal components (PC) analysis was used to explore shape variation. Species means were then calculated for the first 10 PCs. In a phylogeny‐free least squares analysis, PC1 (37.7% of the variance) and PC3 (12.0%) were significantly correlated with tooth size (= ln centroid size). In a Phylogenetic Generalized Least Squares analysis, only PC3 had a statistically significant relationship with tooth size (R2 = .2496, p<0.05). This result suggests that some resemblances in molar shape among taxa of similar tooth size may reflect shared phylogenetic history rather than size‐required constraints on shape. Phylogenetic relationships should be considered in future analyses of allometric variation in the dentition.

Grant Funding Source: American Society of Mammalogists grant to ESC, Evolving Earth Foundation Grant and NSF DIG (BCS‐062254) to DB
The jaw adductor resultant vector in primates
Authors: Perry Jonathan M. G. , Logan Rachel L.
Published: June 2021

To optimize bite force, the jaw adductor resultant force is predicted to pass directly behind the last molar, crossing the jaw at 30% of jaw length from the joint (Greaves, 2000). We estimated the location, orientation, and magnitude of the resultant in strepsirrhine and platyrrhine primates using empirical data. To estimate vector location and orientation for each muscle (temporalis, masseter, and medial pterygoid) we outlined areas of attachment on lateral images of skulls. To estimate vector magnitude for each muscle we used published data on muscle cross‐sectional area. Individual muscle vectors were summed to obtain the resultant. In all cases, the resultant passes significantly posterior to the 30% mark (mean = 21%) and posterior to the last molar. This suggests that bite forces are less than optimal and joint reaction forces are greater than optimal. However, this vector location lowers the risk of dislocating the jaw joint and increases the potential for gape. The magnitude of the resultant scales with significant negative allometry to species mean body mass. Thus larger primates might be at a disadvantage for generating bite force.

Grant Funding Source: Master of Biomedical Science Program, MWU
Efficacies of DNA and Protein‐Based Gamma‐glutamyl cysteine synthetase (γGCS) Vaccines from Leishmania donovani on the Cutaneous Lesions in Leishmania major infected Balb/c Mice
Authors: Alawa Judith Nkiruka , Nok Andrew Jonadi , Kwanashie Helen O. , Alawa Clement B.
Published: June 2021

Gamma‐glutamyl cysteine synthetase (GCS) is an enzyme that catalyses the rate limiting step in glutathione synthesis. In this study the efficacies of the DNA and protein vaccines of GCS from L. donovani was evaluated against cutaneous leishmaniasis caused by L. major. Balb/c mice immunized with plasmid containing the full gene sequence for GCS (pVAX‐GCS) or plasmid alone (pVAX) or the recombinant protein (rGCS) or PBS (control) were challenged with high dose of L. major promastigotes in the shaven rump and the degree of protection was evaluated. by lesion progression, histopathological outcome of lesions and immunological profile. Vaccination of mice with the recombinant protein resulted in protection as demonstrated in the delay in lesion expansion and accompanied by an improved histopathological outcome of the skin lesions with little tissue destruction compared to the control. Furthermore, immunological analysis of the antibody isotypes showed high levels of IgG2a compared to IgG1 which is suggestive of a TH1 immune response and also characterized by the induction of significantly high levels of gamma interferon production with little or no IL‐4 production. Vaccination with DNA plasmid or the plasmid alone did not confer any protection. These results demonstrate that the recombinant protein of γGCS from L. donovani induced cross immunoprotection with improved histopathological outcome against cutaneous leishmaniasis suggesting that it represents a good candidate for use as a vaccine.

Grant Funding Source: Carnegie Corperation/ABU Fellowship Award
Assessment of a time‐frame for postnatal changes in the aerodigestive tract during the first year of life
Authors: Raja Harish , Laitman Jeffrey T
Published: June 2021

The goal of this study is to provide the first comprehensive assessment of the timing and sequencing of developmental change in the human aerodigestive tract (ADT) during the first year of postnatal life. We hypothesize that a period of identifiable change occurs in this interval. The ADT serves as the anatomic crossroads for the functions of olfaction, breathing, swallowing, and vocalization. It undergoes anatomic restructuring marked by descent of the larynx and disengagement of the epiglottis from the soft palate. This transition period has also been associated with sudden infant death syndrome (SIDS). Although proper configuration of these structures is vital for normal function, little is known about the exact timing of events. We performed an extensive multimodal analysis of the current literature to determine whether there is a period of identifiable change within the first year. Imaging (MR, CT, US, 3D‐CT, 3D–MR) and physiologic studies were assessed as they relate to visualization and timing of ADT positional changes. Results suggest that an identifiable period of change occurs between the 2nd and 6th months based on a matrix of functional and imaging data. This period is cotemporaneous with increased frequency of SIDS, obstructive sleep apnea, and aspiration during suckling. Future research will center on developing a more robust database of normal values and establishing patterns of normal variation.

Grant Funding Source: Mount Sinai Summer Research Fellowship
A craniosynostosis‐syndrome related Fgfr2 mutation promotes early craniofacial defects in chick
Authors: Li Xin , Tropp Stephen , Marcucio Ralph
Published: June 2021

In addition to premature suture closure, patients with craniosynostosis have a variety of structural deformities in the brain and face. Whether brain and face malformations result from premature suture closure, or are caused directly by disease‐causing mutations are unknown. Gain‐of‐function mutations in Fibroblast Growth Factor Receptors (FGFRs) account for ~20% of craniosynostosis syndromes, and mice harboring a ubiquitously expressed, disease‐causing allele of FGFR2 recapitulate craniosynostosis phenotypes. To test the hypothesis that facial malformations result directly from activation of FGFR2 in the face, we introduced the human Fgfr2C278F mutant allele into chick embryos using the RCAS virus. RCAS::Fgfr2C278F particles were injected into mesenchyme adjacent to the forebrain after neural crest emigration form the neural tube was complete (stage 10). After 72 hrs embryos were harvested for analysis. Infected embryos were microcephalic, appeared to have widened faces, and had more prominent and hypertrophic nasal pits compared to controls. Consistent with FGF activation, we observed increased pErk staining. Infected embryos also had fewer proliferating cells. In conclusion, our results demonstrate that activation of the FGF pathway produces dysmorphology independent of premature suture fusion that resembles the facial phenotype of people with craniosynostosis.

Grant Funding Source: NIH
VEGF Induces Cervical Epithelial Proliferation in Mice: A Molecular and Morphological Study
Authors: Scott Kelsey M , Kephart Samantha D , Rhyne Scott B , Mowa Chishimba N
Published: June 2021

Cervical remodeling is a physiological inflammatory process associated with and possibly regulated by proliferating cervical epithelial. We have previously shown by SEM that administration of VEGF recombinant protein increases cervical epithelial folds in the cervix of pregnant and non‐pregnant rodents. In the present study, we show by SEM that VEGF blocker attenuates the epithelial folds and disfigures the epithelial cells. We also show by real time PCR that levels of PCNA, a marker for cellular proliferation, was up regulated in VEGF‐treated non‐pregnant mice versus control. The proliferating cell types were identified by histology and confocal microscopy. We conclude that VEGF plays a role in cervical remodeling, in part, by promoting proliferation of cervical epithelial cells and endothelial cells during angiogenesis.

Grant Funding Source: Appalachian State University