bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intermittent hypoxia (IH) causes greater insulin resistance than chronic hypoxia (CH) in lean mice
Authors: O'Donnell Christopher Paul , Strollo Hilary C , Romano Lia C , Skalka Kristy , Rosa Taylor C , Stefanovski Darko , Bergman Richard N , Garcia‐Ocana Adolfo , Alonso Laura C 
Published: June 2021

INTRODUCTIONSleep apnea is characterized by IH and is associated with metabolic dysfunction. We developed the first frequently sampled intravenous glucose tolerance test (FSIVGTT) in conscious mice to examine the effects of IH and CH on glucose disposal.METHODSAdult male C57BL/6J mice with chronic femoral artery and venous catheters were exposed to seven hours of either IH (nadir inspired oxygen 5‐6% at 60 cycles hr−1) or CH (constant 10% FIO2). Control groups were exposed to either intermittent air (IA) or were unhandled (UH). A FSIVGTT was performed by rapidly sampling arterial blood for glucose (and insulin) at (‐10), (0), (1), (2), 3, (4), 5, 6, (8), 10, (12), 14, (16), 18, (20), 25, (30), 40, 50, (60), (90), and (120) min after a bolus injection of i.v. glucose (1 g/kg). Data analysis was performed in collaboration with the Bergman group at USC utilizing the previously validated Minimal Model program.RESULTSCompared with the UH and IA groups, the IH group demonstrated a decrease in glucose effectiveness (Sg), and marked decreases in insulin sensitivity (SI) and the Disposition Index (DI) for glucose. The CH group also showed a decrease in Sg, but SI and DI were not as impaired compared to IH. * p<0.05 vs UH/IA control; # p<0.05 IH vs CH.CONCLUSIONIH is a unique paradigm of hypoxic stress that specifically induces insulin resistance and impairs the disposition of glucose into the peripheral tissues.Supported by NHBL063767
Hypoxia and zinc induced changes in the contractile machinery of isolated rat pulmonary microvascular endothelial cells (RPMVECs)
Authors: Bernal Paula Jimena , Watkins Simon Charles , St Croix Claudette Marie 
Published: June 2021

Our recent data suggest that hypoxic induced increases in NO biosynthesis result in increases in intracellular free zinc that in turn contribute to vasoconstriction of small, non‐muscularized intra‐acinar arteries (<50 um). In order to understand the cellular changes behind this contractile behavior, we examined actin‐myosin dynamics and focal adhesion changes in isolated rat pulmonary microvascular endothelial cells (RPMVEC) in response to 30 minutes of hypoxia or exogenously applied zinc. Immunocytochemistry and confocal analysis showed that contraction in response to either 2% oxygen or zinc, were accompanied by increases in actin‐myosin interactions; stress fiber formation; and recruitment of focal adhesion proteins to cell‐matrix contacts. Live cell imaging of GFP tagged proteins provided real‐time information about the strengthening and alignment of actin stress fibers while total internal reflection (TIRF) imaging showed recruitment of paxillin, talin and zyxin to focal adhesions. These data suggest that the reorganization of cytoskeletal and focal adhesion proteins in response to hypoxia or zinc may be responsible for the force induction and cell stability necessary to elicit an active contractile response in pulmonary endothelium.Funded by NIH HL 081421 (CMS)
Redox‐switch modulation of human SSADH by dynamic catalytic loop
Authors: Kim Kyung‐Jin , Kim Yeon‐Gil , Kim Yeon‐Gil 
Published: June 2021

Succinic semialdehyde dehydrogenase (SSADH) is involved in the final degradation step of the inhibitory neurotransmitter gamma‐aminobutyric acid (GABA) by converting succinic semialdehyde (SSA) to succinic acid in the mitochondrial matrix. SSADH deficiency, a rare autosomal recessive disease, exhibits variable clinical phenotypes, including psychomotor retardation, language delay, behavior disturbance, and convulsions. Here we present crystal structures of both oxidized and reduced forms of human SSADH. Interestingly, the structures show that the catalytic loop of the enzyme undergoes large structural changes depending on the redox status of the environment, which is mediated by a reversible disulfide bond formation between a catalytic Cys340 and an adjacent Cys342 residues located on the loop. Subsequent in vivo and in vitro studies reveal that the ¡(r)dynamic catalytic loop¡ confers a response to reactive oxygen species (ROS) and changes in redox status, indicating that the redox‐switch modulation could be a physiological control mechanism of human SSADH. Structural basis for the substrate specificity of the enzyme and the impact of known missense point mutations associated with the disease pathogenesis are presented as well.This work was funded by 21C Frontier Microbial Genomics and Application Center Program, Ministry of Education, Science and Technology (MEST), Republic of Korea.γ
Dipyridamole Enhancement of Diabetic Ischemia Induced Angiogenesis
Authors: Branch Billy Glynn , Greber Eric , Pattillo Christopher , Kevil Christopher 
Published: June 2021

BackgroundPeripheral Artery Disease and critical limb ischemia affect millions of Americans with an alarming increase in diabetics. There is a need for therapeutic restoration of vascular function in those affected by these diseases. We studied the hypothesis that dipyridamole could be used for angiogenic preconditioning due to its relationship with eNOS expression and activation in various tissue sites.MethodsHind limb ligations were performed in dipyridamole and control db/db diabetic mice. Serial laser Doppler blood flow measurements were taken on days 0, 3, 5, and 7. CD31, DAPI, and Ki67 immunofluorescent staining was used to evaluate vascular densities and active endothelial cell proliferation. Tissue and blood nitrite measurements were collected to confirm a rise in nitrite levels after treatment.ResultsOur experiment showed that dipyridamole significantly increased blood flow and vascular density. Blood flow levels were returned to 98.4±4.1% of pre‐ligation blood flow by day 7 in the dipyridamole dosed mice as compared to 58.2±4.5% at day 7 in the control mice. Immunofluorescent staining values were significantly increased in the ischemic limbs of dipyridamole dosed mice as compared to control mice showing that dipyridamole selectively increases ischemic hind limb vascular density and endothelial cell proliferation. Tissue nitrite levels were significantly elevated in dipyridamole dosed mice as compared to control mice.ConclusionOur results show that dipyridamole has great potential as a preconditioning and angiogenesis stimulating agent in diabetic chronic ischemia.
Seasonal variation in vitamin D status in healthy young adults of different ancestry in the Toronto area
Authors: Gozdzik Agnes , Barta Jodi , Wu HongYu , Cole David , Vieth Reinhold , Whiting Susan , Parra Esteban 
Published: June 2021

This study examined seasonal variation in serum 25(OH)D concentrations in young adults of different ancestry. 237 subjects participated in the study. Dietary intake, anthropometric measurements, skin pigmentation, UVR exposure and serum 25(OH)D levels were measured in late summer and winter in the Toronto area.Mean late summer serum 25(OH)D concentration was 49.7 nmol/L for the full sample. However, concentrations were lower for those of East Asian and South Asian ancestry than those of European ancestry (44.6, 33.9 and 71.7 nmol/l, respectively). During late summer, serum 25(OH)D levels were influenced by skin pigmentation (p<0.001), vitamin D intake (p<0.001) and the amount of time spent outdoors at peak UVR hours (p=0.003).Mean winter serum 25(OH)D concentration was 35.4 nmol/L. Again, mean concentrations were lower in those of East Asian and South Asian ancestry compared to those of European ancestry (28.1, 26.5 and 51.6 nmol/l, respectively). Total vitamin D intake (p<0.001) and summer serum 25(OH)D levels (p<0.001) had significant effects on wintertime vitamin D status.The low 25(OH)D levels observed during the winter, and also during the late summer for many young adults is of public health concern. Our data indicates that vitamin D intake is insufficient to maintain adequate levels of vitamin D throughout the year, particularly in individuals of non‐European ancestry.NSERC, ERA and Wenner‐Gren
Population attributable risk and population attributable risk percentage for high methylmalonic acid in the post‐folic acid fortification period in the US
Authors: Vanegas Sally M , Kafai Mohammad R , Ganji Vijay 
Published: June 2021

Population attributable risk and population attributable risk percentage for methylmalonicacidemia in the post‐folic acid fortification period in the USSerum methylmalonic acid (MMA) is a sensitive marker of cobalamin status. We investigated population attributable risk (PAR) and population attributable risk percentage (PAR%) for high serum MMA (>350 nmol/L) using the data from 3 cross‐sectional National Health and Nutrition Examination Survey cycles (1999‐2004) conducted in the post‐folic acid fortification period on US residents (n=18569). PAR%s for high MMA were 24.8% for non‐Hispanic white [prevalence, 3.4%; odds ratio (OR), 1.6; P<0.0001)], 40.5% for =60 y old persons (prevalence, 8.3%; OR, 4.0; P<0.0001), 11.8% for nonsupplement users (prevalence, 3.5%; OR, 1.82; P<0.0001), 13.3% for serum creatinine =130 ?mol/L (prevalence, 34.1%; OR, 12.6; P<0.0001), and 16.2% for serum cobalamin concentration <148 pmol/L (prevalence, 27.6%; OR, 13.5; P<0.0001). In the post‐folic acid fortification period, old age, white race, nonsupplement usage, kidney dysfunction, and cobalamin deficiency significantly contribute to PAR and PAR% of high MMA in the US. By improving serum cobalamin concentrations ³148 pmol/L, the incidence of high MMA would be reduced by »16%. This amounts to a reduction of 5 new cases per 1000 people (PAR=0.005) of high MMA in the US. This is an important finding in light of calls for cofortification of folic acid fortified cereals and cereal products with cobalamin.
Chronic endometritis: How many plasma cells does it take to make the diagnosis?
Authors: Hartman Sarah K. , Symons Wendy A. , Yeh I‐Tien 
Published: June 2021

3–10% of endometrial biopsies are said to show histologic evidence of chronic endometritis. In this study we correlate the # of plasma cells by H&E to the # of plasma cells by CD138 IHC in endometrial biopsies.Methods100 endometrial biopsies were selected, excluding specimens with limited material, cancer and menstrual phase. H&Es were reviewed, and the # of plasma cells/10 hpfs were recorded. Additional sections were stained with CD138 antibody (clone B‐A38; Cell Marque, Rocklin, CA). Hot spots of CD138+ cells were recorded as the #/10 hpfs. Histologic findings near the CD138+ cells were also recorded.ResultsPlasma cells were identified in 29 cases by H&E alone (ave. 2.1, range 1–12) and 90 cases were + for plasma cells by CD138 (ave. 13.9 plasma cells, range 1–190). Of the 29 cases with plasma cells on H&E, CD138 highlighted an average of 24.3, with a minimum of 1. 71 biopsies lacked plasma cells on initial H&E review, but averaged 7.7 plasma cells by CD138. Often, the endometrial stroma contains scattered lymphocytes or mild edema, but lacked the spindled stroma typically associated with chronic endometritis.ConclusionsBy careful exam on H&E, >1 plasma cells were seen in 29% vs. 90% of endometrial bxs by CD138. These cases include diagnoses of gland‐stromal dyssynchrony, disordered proliferative endometria, and endometrial hyperplasias. The presence of CD138+ plasma cells may not equate to chronic endometritis.
Claudin‐4 promotes repair and barrier function in lung epithelia
Authors: Rokkam Deepti , Hirsch Jan , Ho Gwen , Griffin Chris , LaFemina Michael J , Frank James A 
Published: June 2021

Claudin‐4 is a transmembrane protein important in paracellular sealing at tight junctions. Recent studies have found that claudin‐4 is specifically induced during epithelial repair and higher claudin‐4 expression levels are associated with intact barrier function in injured human lungs. In this study, claudin‐4 expression and trafficking were examined in primary rat alveolar type 2 cells and human bronchial epithelial cells in a scratch wound migration assay. To determine the role of claudin‐4 in migration, cell morphology, actin distribution and focal adhesions were examined. To discover claudin‐4 binding partners, coimmunoprecipitates were evaluated by mass spectrometry. Induction of claudin‐4 during repair was conserved in alveolar and bronchial epithelia and knockdown of claudin‐4 slowed migration. EGFR and JNK signaling were required for claudin‐4 expression. During repair, claudin‐4 was trafficked to the leading edge of migrating cells where it appeared to influence actin nucleation and lamellipodia formation. Novel protein‐protein interactions with claudin‐4 may provide clues to the role of this protein in collective migration. The combined effects of claudin‐4 on tight junction sealing and epithelial repair potentially explain the positive correlation between claudin‐4 expression levels and epithelial barrier function in human lungs.Funded by NIH/NHLBI HL88440, HL88440S2
Undergraduate student‐led cadaveric dissection: an interdisciplinary approach to connecting pathological findings to health conditions
Authors: Drennan Rachel , Goatley Lee , Muff Jaclyn , Scavuzzo Raghela , Young Whitney , Zidon Terese 
Published: June 2021

A cadaveric anatomical dissection was completed by five Westminster College undergraduate students with the objective to analyze anatomical abnormalities in order to compile a complete report of pathological findings. Abnormalities were identified through observation, histological preparation, and examination of aberrant tissues that may indicate possible health conditions at time of death. Preliminary pathological findings include enlargement of the thyroid gland (length=6.8 cm, width=4.6 cm), abnormal growth on the exterior surface of the superior vena cava (length=3.1 cm, width=1.6 cm), bronchopulmonary lymph nodes with anthracotic pigmentation, a papillary process present on the liver, numerous dense polyps on the descending colon, sigmoid colon and rectum, and uterine irregularities. Further histological analysis of the listed abnormalities was performed to identify the severity of disease(s) at the time of death. In addition to dissection, students documented personal experiences through journaling and participated in educational seminars to enhance their understanding and appreciation for human anatomy.Grant Funding Source: Westminster College
Male‐male combat drives bite force evolution in the absence of mastication
Authors: Jones Katrina Elizabeth , Ruff Christopher B 
Published: June 2021

Bite force production is often cited as a key influence on the anatomical evolution of the mammal jaw. However, most research focuses on mastication and food processing as the driving force for the evolution of large bite forces in terrestrial mammals. Pinnipeds (seals, sea lions and walruses) have lost the ability to masticate as an adaptation to marine feeding and instead use their jaws for a wide range of other behavior, including prey capture and male‐male combat in certain polygynous species. This study investigates the influence of male fighting on the jaw morphology of a mammal whose postcrania are entirely specialized for swimming. We measured cortical thickness of males and females of two polygynous (n=14) and three monogamous (n=19) species, from a wide taxonomic range. Section modulus of the corpus was calculated using a hollow beam model and bite force estimated by scaling by jaw length. We find that polygynous species that exhibit male combat (harem‐defense polygyny) produce significantly larger theoretical bite forces than females of the same species and males and females of monogamous species, including those with different feeding specializations. This indicates that male‐male combat is the most important influence on bite force evolution in pinnipeds and is a major contributor to variation in mandibular anatomy.Grant Funding Source: n/a
Muscles Underlying the Elevation of the Hyolaryngeal Complex
Authors: Pearson William G. , Langmore Susan E , Yu Lou B , Zumwalt Ann C 
Published: June 2021

IntroductionA critical event in the pharyngeal phase of swallowing is the elevation of the hyolaryngeal complex opening the upper esophageal sphincter. Current swallowing theory assigns this function to the suprahyoid (mylohyoid, geniohyoid, digastrics, and stylohyoid) and thyrohyoid muscles. The role of the long pharyngeal muscles (stylopharyngeus, palatopharyngeus, and salpingopharyngeus) that insert into the thyroid cartilage and distal pharynx is uninvestigated in humans. This study uses a cadaver model to document the structural properties of muscles to analyze their potential for elevating the hyolaryngeal complex.MethodsMeasurements to determine physiological cross‐sectional areas (PCSAs) of suprahyoid, thyrohyoid and long pharyngeal muscles were taken from hemisected head and neck formalin‐fixed cadaver specimens (n = 14). Coordinates of muscle attachment sites and PCSAs were used to calculate unit force vectors representing the relative maximum tetanic tension muscles in the superior direction. Force vectors of muscle samples were compared by an analysis of variance to evaluate their potential for force in elevating the hyolaryngeal complex.ResultsAn ANOVA with Tukey HSD post hoc analysis of unit force vectors in the superior direction showed the following results: suprahyoid (1.54±0.34 cm2) > long pharyngeal (.74±0.20 cm2) (p<.01), and long pharyngeal > thyrohyoid (.49±0.17 cm2) (p<.05).DiscussionThe morphology of these muscles suggests that while the suprahyoid muscles have the most potential for force in elevating the hyolaryngeal complex, the long pharyngeal muscles contribute significantly more to UES opening than the thyrohyoid. If verified by physiological data, this data would add to the current understanding of swallowing.Grant Funding Source: n/a
Screening for additives that stabilize enzymes at higher temperatures
Authors: Coleman Jack , Dai Lijun , Patton Wayne F 
Published: June 2021

In Molecular Biology, enzymes are often required that function at elevated temperatures. Enzymes produced by mesophilic organisms usually denature at elevated temperatures, followed by aggregate formation. We developed a rapid fluorescence‐based assay for assessing a range of parameters impacting the thermal stability of an enzyme. Overall, protein stability is monitored by a fluorogenic dye that selectively detects aggregated protein. Stability can be measured in the presence of different buffers, cryoprotectants and excipients. By systematically raising the temperature of the protein in solution, the temperature at which the protein aggregates (Tagg) can be determined. Using this method with Klenow DNA polymerase, we determined that trehalose significantly increases Tagg. The DNA polymerase activity of the enzyme is significantly enhanced at 50°C in the presence of trehalose under the same conditions. Low amounts of the detergents, Tween20® and Triton X‐100® (0.05%) decreased Tagg and also compromised enzyme activity, especially at elevated temperatures. T7 RNA polymerase was tested in a similar manner. Trehalose less significantly increased Tagg, and had a more modest effect on increasing enzyme activity at 42°C. The described assay facilitates screening for buffers and additives that structurally stabilize a protein of interest at elevated temperatures.This work was supported by ENZO Life Sciences.
ANTIOXIDANTS DECREASE LIPOLYSIS AND LIPID SYNTHESIS IN HUMAN DIFFERENTIATED ADIPOCYTES
Authors: Krawczyk Sarah Anne , Deeney Jude T. , Corkey Barbara E. 
Published: June 2021

OBJECTIVEReactive oxygen species (ROS) partially mediate the aberrant effects of chronic inflammatory states such as obesity. The goal of this research was to examine the effect of ROS on triglyceride synthesis and lipolysis by scavenging ROS with the antioxidant, diphenyliodonium (DPI).METHODSHuman subcutaneous preadipocytes were differentiated for 12 days into adipocytes. Cells were then treated with DPI and labeled with tritiated oleate (3H‐FA) or 32P as a tracer to assess lipid synthesis, which was detected by thin layer chromatography (TLC). Glycerol release was measured using an enzyme‐linked assay. Protein was assessed using western blot.RESULTSThere was a decrease in glycerol released into the media of cells treated with 10 μM DPI for either 1 or 4 hours, as compared to control cells under basal and forskolin‐stimulated conditions. In parallel, triglyceride (TG) synthesis was decreased with DPI treatment compared to control (for basal and stimulated conditions). A preliminary look at the PKA pathway by western blot showed no change in activation compared to control by DPI treatment.CONCLUSIONSData indicate that both 1 and 4 hour treatment with DPI decreased basal lipolysis and concomitantly decreased neutral lipid synthesis. This may be due to decreased TG synthesis, decreased lipolysis, or a decrease in turnover.
Celecoxib preserves arachidonic acid‐induced cell degeneration: implications for the anticancer effects of NSAIDs and polyunsaturated fatty acids
Authors: AMISSAH FELIX , AYUK‐TAKEM LAMBERT T , ABONYO BARACK O. , LAMANGO NAZARIUS S. 
Published: June 2021

Polyisoprenylated proteins mediate signaling, intracellular trafficking, cell proliferation, differentiation and apoptosis. Aberrant activities of such proteins as Ras and Rab families of monomeric G‐proteins are implicated in cancers. The polyisoprenylation pathway culminates in a reversible ester‐forming polyisoprenylated protein methyl transferase‐ and hydrolytic polyisoprenylated methylated protein methyl esterase (PMPMEase)‐ catalyzed reactions. Arachidonic acid (AA) was analyzed for its effects on various cancer cells and the cellular PMPMEase activity. COX‐2 metabolism of AA was explored to demonstrate the loss of inhibitory effect on PMPMEase activity in‐vitro which was restored in the presence of celecoxib. AA induced the degeneration of the cancer cells at physiologically relevant concentrations (EC50 from 1 – 24 μM). Cellular PMPMEase activity also followed a similar profile as the cell viability (IC50 6.6 – 21 μM). Addition of COX‐1 or COX‐2 to the assay mixture restored the lost PMPMEase activity in the lysates of the AA‐treated degenerating cells. Celecoxib maintained the inhibition of PMPMEase in the presence of COX‐2. These data suggest that AA, functioning through PMPMEase inhibition, may be a physiological regulator of cell growth. The results further elucidate the association between COX‐2 expression in tumors and the chemopreventive effects of PUFAs and NSAIDs.Supported by NIH/NIGMS/SCORE (GM 08111‐35) & NIH/NCRR (G12 RR0 3020).