bluuebunny/crossref_metadata_2025 huggingface dataset:
Caregivers’ Behavioral Skills Associated with Preschool Children Consumption of Sugar‐Sweetened Beverages (SSBs)
Authors: Lora Karina , Wakefield Dorothy , Ferris Ann
Published: June 2021

Study tested hypothesis that caregivers with greater behavioral skills (BS) to limit consumption of SSBs would report their children consume fewer SSBs. Caregivers of 3–5 y old children (n=462) provided demographics, a home inventory of beverages including child daily consumption of SSBs, and an Information‐Motivation‐Behavioral Skills (IMB) measure of child consumption of SSBs (IMB‐mCSSBs). BS, a component of the IMB model, was based on 10 items of the IMB‐mCSSBs measure. Chi‐square analyses tested association of BS tertiles (High: greater BS) with child's daily total ounces consumed of SSBs (flavored milk, fluid and powdered juice drinks (JD), iced tea, energy drinks, soda), and with JD alone. Mean total child consumption of SSBs was10.4±15.01 oz/day. By BS tertiles, 29% of caregivers in the low tertile, vs.19% and 18% in the middle and high tertiles respectively, allowed their child to drink >;16oz/day of SSBs (P<.05). For consumption of juice drinks specifically, the same pattern emerged. Age was related to BS grouping, with older caregivers more represented in the high BS group vs. low BS group (37% aged 45–54 in high BS group vs. 25% in low). Being an African‐American caregiver was associated with higher child consumption of total SSBs and JD. Children consumed less SSBs when their caregivers have greater skills and efficacy to manage consumption of these beverages. Funding: USDA/NRI 2008–55215‐19071
A Qualitative Investigation of How Parents Determine Fullness in their Preschool Children
Authors: Goodell L. Suzanne , Antono Amanda C. , Daniel Joylyn C. , Walker Samantha L. , Johnson Susan L. , Power Thomas G. , Hughes Sheryl O.
Published: June 2021

Parental inability to recognize fullness in their children and their encouragement to eat beyond satiety may contribute to overconsumption and excessive weight gain at an early age. To investigate if and how parents determine fullness in their preschool children, researchers conducted 17 focus groups with African American and Hispanic parents of 3–5 year olds from low‐income families (total participants = 103) in Washington, Texas & Colorado. Applying principles of grounded theory to analyze transcripts, researchers discovered that parents determined fullness in their child through a series of events, often triggered by their child stating or signaling that they are full. However, regardless of their child's statement of fullness, parents ultimately used the amount of food left on their child's plate to determine if their child had “eaten enough”, which to parents equated to fullness. Parents reported modifying their expectations of children's consumption and how they determined fullness in their children based on a myriad of factors, including previous experiences and daily circumstances. Ultimately, the vast majority of parents did not believe their child had the skills to adequately self‐regulate intake and determine their own fullness. Outcomes of this study will be used in the development of educational interventions for parents, emphasizing internal and external cues to hunger and fullness.
Post diagnosis diet quality and colorectal cancer survival
Authors: Kashambwa Rutendo , Chiuve Stephanie , Meyerhardt Jeffrey , Sato Kaori , Hu Frank , Fung Teresa
Published: June 2021

Diet quality has shown to influence colorectal cancer (CRC) risk, however, its association with CRC survival is unknown. Therefore, we prospectively assessed the association between dietary quality scores, dietary patterns and survival among 1628 women and 532 men diagnosed with stages 1 to 3 CRC. Post diagnosis diet information was collected via a food frequency questionnaire administered at least 6 months after diagnosis to avoid diet change due to active treatment. We computed scores for the Alternate Healthy Eating Index (AHEI) 2010, alternate Mediterranean Diet score (aMED) and Dietary Approaches to Stop Hypertension score (DASH) and derived two dietary patterns, Western and Prudent, by principal component analysis for each individual. In up to 14 years of follow‐up, we documented 485 deaths in women and 256 in men. After adjusting for potential confounders, women with higher AHEI2010 or aMED scores had a significantly better overall survival (RR comparing extreme quintiles of AHEI‐2010 = 0.66, 95% CI 0.49 – 0.91, p trend = 0.001; aMED = 0.79, 95% CI 0.58 – 1.07, p trend = 0.03). However, these scores had no association with CRC survival. In men, there was no clear association between diet quality scores and survival. Prudent or Western pattern were not associated with survival in women or men. In conclusion, a higher AHEI2010 or aMed score may be associated with better overall survival after CRC diagnosis in women.
Endothelium exposed to atheroprone flow promotes monocyte transmigration and specification
Authors: Turjman Alexis , Edelman Elazer R , García‐Cardeña Guillermo
Published: June 2021

Atherosclerosis and its consequences, myocardial infarction and stroke continue to be the leading cause of mortality worldwide. Despite recent progress in our understanding of the initiation and progression of atherosclerosis, there is an increasing need to identify novel signaling pathways with potential therapeutic targeting. One of the earliest events in atherogenesis is endothelial dysfunction triggered by disturbed flow characteristic of atherosclerosis susceptible regions. This event is followed by monocyte transmigration and differentiation into macrophages. To mechanistically dissect the contribution of atheroprone flow on the endothelial cell phenotype and monocyte transmigration and specification, we have developed a novel in vitro model in which endothelial cells (EC) are seeded on a collagen gel and exposed to athero‐prone and ‐protective shear stress waveforms. Using this model, we have demonstrated that atheroprone but not atheroprotective flow promotes monocyte recruitment via a Krüppel Like Factor‐2‐dependent pathway. Furthermore, we have documented that transmigrated monocytes under atheroprone flow polarize toward a pro‐inflammatory phenotype as measured by gene expression of a set of pro‐inflammatory markers. This work supports the hypothesis that the hemodynamic environment promotes EC‐monocyte interactions, which are a key determinant of macrophage polarization.
Role of Elp1 in neural crest cell migration, differentiation and target tissue innervation in Familial Dysautonomia
Authors: Jackson Marisa Z. , Gruner Katherine A. , Tourtellotte Warren G.
Published: June 2021

A highly conserved germline point mutation located in the donor splice site of intron 20 of the human Elp1 gene leads to loss of its encoded protein and causes familial dysautonomia (FD; Riley‐Day Syndrome; hereditary sensory and autonomic neuropathy, type 3; HSAN3), an autosomal recessive disease characterized by severe and progressive sympathetic and sensory neuron loss. The protein encoded by elp1 is required for development beyond mid‐gestation and it is part of the transcriptional elongator multi‐protein complex, but its functional role in disease pathogenesis remains poorly understood. To examine the role of elp1 in sympathetic and sensory neuron development, we generated conditional elp1 knockout mice and we used Wnt1‐Cre transgenic mice to ablate elp1 in neural crest (NC) cells, a highly migratory population of cells which gives rise to sympathetic, sensory and enteric neurons during development. Loss of elp1 in NC cells showed no impairment in their migration, but there was a significant impact on post‐migratory sensory and sympathetic neuron survival and target tissue innervation. In vitro studies using elp1‐deficient neurons showed that it has a profound impact on growth factor‐induced neurite outgrowth but no role in neuron survival. These results indicate that FD is not caused by impaired neuronal migration but rather, neuron death resulting from ineffective target tissue innervation.
GROWTH HORMONE ADMINISTRATION ALTERS PROTEIN EXPRESSION IN SKELETAL MUSCLE OF RATS WITH AORTIC STENOSIS‐INDUCED HEART FAILURE
Authors: Lima Aline Regina Ruiz , Damatto Ricardo Luiz , Pagan Luana Urbano , Bonomo Camila , Cezar Marcelo Diarcádia Mariano , Guizoni Daniele Mendes , Martinez Paula Felippe , Gomes Mariana Janini , Okoshi Katashi , Okoshi Marina Politi
Published: June 2021

In this study we evaluated the effects of growth hormone (GH) administration on protein expression of myostatin, follistatin, and the myogenic regulatory factors in skeletal muscle of rats with ascending aortic stenosis‐induced heart failure.

Methods

Male Wistar rats were subjected to thoracotomy to induce aortic stenosis (AS). After developing tachypnea/labored respiration, rats were subjected to echocardiogram and assigned to three groups (n=8): Sham, AS, and AS treated with GH (AS‐GH, 2 mg/kg/day) for 14 days. After treatment, rats were subjected to echocardiogram and euthanatized. Protein expression was evaluated by Western‐blot.

Statistical analysis

Anova and Tukey.

Results

Before GH treatment, cardiac parameters did not differ between AS and AS‐GH groups. GH preserved body weight. Right ventricular weight/BW ratio and left ventricular posterior wall thickness were higher in both AS groups than Sham. MyoD was higher in AS than Sham and similar between AS‐GH and Sham (Sham 1.0±1.3; AS 1.7±1.4; AS‐GH 1.2±1.2 arbitrary units). MRF4 expression was higher in AS‐GH than Sham (Sham 1.0±0.7; AS 1.6±0.4; AS‐GH 3.1±1.6 arbitrary units). Myostatin, follistatin, and myogenin expression did not differ between groups.

Conclusion

Growth hormone increases MRF4 and normalizes MyoD expression in skeletal muscle of heart failure rats. Myostatin/follistatin pathway is not changed in this experimental model.
Muscle RING Finger‐1 (MuRF1) inhibits insulin‐like growth factor‐1 (IGF‐1)‐dependent cardiomyocyte hypertrophy by reducing Akt nuclear activity
Authors: Wadosky Kristine M. , Hite Rebecca L. , Willis Monte S.
Published: June 2021

Previous studies in our laboratory have demonstrated that MuRF1 inhibits cardiomyocyte growth in pathological hypertrophy by inhibiting specific nuclear transcription factors. To further define MuRF1's role in regulating other types of hypertrophy, we investigated MuRF1's role in the development of exercise‐induced physiologic hypertrophy, acting through the IGF‐1 signaling pathway. The cardiomyocyte‐derived HL‐1 cell line was treated with 10nM of IGF‐1 after MuRF1 expression was increased or transiently knocked down using adenovirus constructs. MuRF1 knockdown elicited an exaggerated IGF‐1‐dependent increase in cell area (49.6%) compared to control adenovirus (30.1%), normalized to vehicle controls. Conversely, increased MuRF1 expression completely inhibited IGF‐1‐dependent growth. Since IGF‐1 signaling converges on the kinase Akt, we determined if IGF‐1‐stimulated cell growth with MuRF1 knockdown was accompanied by enhanced Akt signaling. Decreasing MuRF1 significantly increased active Akt localization in the nucleus, along with evidence of increased nuclear‐specific Akt activity‐increased nuclear phospho‐forkhead box protein O‐1 (FOXO1) and decreased prostaglandin D2 synthase (PDGS) expression. These findings suggest that MuRF1 inhibits IGF‐1‐dependent Akt nuclear localization and activity, identifying a novel mechanism of regulating physiologic cardiac hypertrophy.
Role of Renin Angiotensin System inhibitors on Toll‐like receptors expression in cardiac hypertrophy induced by renal ischemia/reperfusion
Authors: Abrahão Mariana , Carneiro‐Ramos Marcela Sorelli
Published: June 2021

Objective

The heart is a target organ of many regulatory systems that modulates heart trophism, such as cardiac renin‐angiotensin system (RAS). Literature data confirm the direct relationship between inflammatory responses, Toll‐Like receptors (TLR) and many cardiovascular diseases. This work aims to investigate the role of RAS inhibitors on TLR expression in a cardiac hypertrophy model induced by renal ischemia/reperfusion.

Methods

C57bl/6 young, male mice (n=72) were treated with Losartan (Los ‐ 10 mg/kg/day) or Enalapril (Ena ‐ 40 mg/kg/day) for 5 days before or after surgery, and kept under observation for 12, 15 or 20 days to investigate the role of TLR in cardiac hypertrophy, evaluated by morphologic parameters and gene expression.

Results

Our model was able to induce cardiac hypertrophy in 12d mice that was prevented and reversed with Los and Ena administration based on ANF/α‐actin gene expression. TLR gene expression was evaluated in animal treated with Los and Ena, that were able to reduce TLR mRNA levels in 15d and 20d mice, respectively.

Conclusion

Taken together our data suggest an important role for local RAS as a modulator of cardiac hypertrophy through regulation of TLR expression. Financial Support: FAPESP and UFABC.
Disfunction of endosome prevents developing alcoholic fatty liver disease via inhibition of TLR4, TLR7, and TLR9 signaling pathways
Authors: Matsumoto Hiroshi , Okazaki Shunichiro , Katada Ryuichi
Published: June 2021

The pathogenesis of alcoholic fatty liver disease has never been established. It has been that TLR‐signaling pathway plays an important role in the development. What primes TLR‐signaling pathway and any prevention remains unclear. Endosome includes TLR4, TLR7 and TLR9, which may contribute to innate immune response in macrophage. We hypothesized that disturbance of endosome reduces alcoholic fatty liver disease. To clarify the hypothesis, we evaluated fatty liver injury in alcohol‐fed rats after treatment with endosome inhibitors. Male Wistar rats were fed with Lieber‐DeCarli alcohol liquid diet for 4 weeks. Omeprazole or lansoprazole, endosome inhibitors, was treated to alcohol liquid diet‐fed rats. Immunohistochemical staining for TLR4, TLR7 and TLR9 was performed in formalin‐fixed, paraffin‐embedded liver sections. ER stress markers were analyzed by quantitative realtime PCR. Alcohol feeding caused expression of TLR4, TLR7 and TLR9 and accumulation of ER stress. Inhibition of endosome results in reduction of fatty liver change, especially lipid droplets inflammation in hepatocytes and no staining for TLR7 and TLR9. However, accumulation of ER stress was not changed by inhibition of proton pump. Therefore, chronic alcohol consumption causes developing fatty liver disease via TLR7 and TLR9, which expression can be reduced by inhibition of endosome.
Study approaches, study methods, academic success, and recall of anatomical learning
Authors: Ward Peter Jason
Published: June 2021

The purpose of this research was to investigate how students learn and recall anatomical knowledge. A group of medical students was assessed with the ASSIST instrument to categorize their approaches to study. Each group's performance on four outcomes (anatomy grade, cumulative grades at end of 1st and 2nd year, COMLEX exam) was compared by ANOVA. For all outcomes, strategic approaches were associated with high performance and surface approaches with poor performance. Subsequently, I investigated how students used available study methods and how this impacted long term recall. Students completed an open‐ended questionnaire about how they studied and responses were coded using grounded theory to find emergent themes. An anatomy assessment was administered six months after the course to find high and low‐recall cohorts in the class. Factors associated with effective recall were the ability to abstract information from multiple sources and willingness to recreate content in detail. Poor recall was associated with repetitive study and stopping at familiarity. In conclusion, Surface approaches to study must be discouraged through deliberate course design. Effective recall of anatomy is connected with an awareness of assessment and the ability to build understanding from the details and not just the big picture.

Grant Funding Source: N/A
Autophagy, metabolic syndrome, and heart surgery
Authors: Mentzer Robert M , Jahania Salik M , Sengstock David , Vaitkevicius Peter , Andres Allen , Ito Bruce R , Gottlieb Roberta A
Published: June 2021

Myocardial stress has been linked to induction of autophagy. Rodent and porcine models of metabolic syndrome exhibit impaired autophagy and may explain loss of cardioprotection. To test the hypothesis that cardiac stress is associated with upregulation of autophagy in humans, autophagic flux was measured in 12 patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). Right atrial tissue (200–400 mg) was excised during atrial cannulation, before initiation of CPB and aortic cross‐clamping, and again after removal of cross‐clamp and weaning from CPB. Autophagy proteins Beclin‐1, Atg5–12, and p62 were analyzed by Western blot. Heart surgery was associated with significant decreases in cardiac levels of Beclin‐1, Atg5–12, and p62, indicating robust autophagic flux. The magnitude of change was correlated with calculated mortality/morbidity (M/M) risk scores extracted from patient medical records using the Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database. There was a significant inverse relationship between the change in p62 and risk score. This is the first time that upregulation of autophagic flux has been linked to better outcomes after heart surgery. Strategies designed to upregulate flux during conditions of cardiac stress may have therapeutic utility and represent a new approach to patients with ischemic heart disease and metabolic syndrome in which autophagy is impaired.

Grant Funding Source:supported by an NIH Grant (NIH 2 R01 HL034579–23 and 5R01 AG033283)
Glycerolipid intermediates alter insulin signaling
Authors: Coleman Rosalind , Zhang Chongben , Cooper Daniel E. , Iping Joyce , Eaton James , Klett Eric , Harris Thurl E.
Published: June 2021

Excess synthesis and storage of triacylglycerol (TAG) underlie much of the pathophysiology of major chronic disorders, including obesity, the metabolic syndrome, and diabetes. We previously showed that phosphatidic acid (PA) synthesized via glycerol‐3‐P acyltransferase‐1 (GPAT1) inhibits mTORC2 activity by decreasing the rictor ‐ mTOR association, thereby down‐regulating insulin action. To determine whether other GPAT isoforms signal similarly, we over‐expressed GPAT3 and GPAT4 in primary mouse hepatocytes. No effect was observed with GPAT3, but GPAT4 over‐expression impaired insulin‐suppressed gluconeogenesis and insulin‐stimulated glycogen synthesis. Impaired hepatic glucose homeostasis was coupled to the inhibition of insulin‐stimulated phosphorylation of Akt‐S473 and ‐ T308. GPAT4 over‐expression inhibited mTORC2 activity and decreased the association of mTOR and rictor, but had no effect on mTORC1/S6K1 or on the IRS1/PI3K pathway. Lipid profiles of mouse hepatocytes over‐expressing GPAT4 showed significant increases in the cellular content of PA and diacylglycerol, without changes in lysoPA. Among the PA species identified, 16:0–16:0 PA increased most. These data demonstrate critical links between nutrient excess, GPAT‐1 and ‐4 mediated TAG synthesis, and hepatic insulin resistance. Support: USDA 2010–65200‐20354 & NIH DK56598, K08‐DK090141, T32HD057824, UNC NORC DK056350
Loss of tumor necrosis factor‐alpha diminishes indicators of colonic Wnt‐signaling activation induced by obesity
Authors: Liu Zhenhua , Kim Susan , Pfalzer Anna C. , Mason Joel B
Published: June 2021

Epidemiological studies implicate obesity as an important risk factor for colorectal cancer (CRC). However, the mechanism(s) responsible for this effect remains unclear. Our prior study suggested that the molecular mechanism might consist of obesity‐induced upregulation of tumor necrosis factor alpha (TNF‐α) and thereby the Wnt‐signaling. In the present study, a TNF‐α knockout mouse was utilized to further establish the seminal role of TNF‐α in mediating this phenomenon. The results show that the TNF‐α−/− mouse is responsive to high‐fat diet‐induced obesity, as measured by body weight and magnetic resonance imaging of body fat (p<0.05), although the magnitude of obesity was attenuated by TNF‐α deletion (p<0.05). Colonic TNF‐α expression was abolished by the genetic deletion of TNF‐α in both lean and obese mice (p<0.01). The increase of TNF‐α expression induced by obesity was significant in male mice (p<0.05), but not significant in female mice. Obesity‐promoted over‐expression of Axin2, a readout of the Wnt pathway, was diminished by TNF‐α deletion (p<0.05). Colonic epithelial proliferation (Ki‐67), which is partly under the control of Wnt signaling, was also decreased by the blockade of TNF‐α in obese mice. These results demonstrate that TNF‐α plays a substantial role in regulating Wnt‐signaling in the colonic epithelium due to obesity.
Successful use of case studies in an online physiology course
Authors: Knabb Maureen , Casotti Giovanni
Published: June 2021

As institutions respond to the need for greater flexibility in access to higher education, there has been increasing emphasis in offering distance education courses. To address this need, an online graduate course in physiology using case studies was offered at WCU. Topics in both animal and human physiology were organized as modules that contained a case study with questions, a pre‐recorded online lecture, and 3 research journal articles. We followed best practices for teaching and learning in distance education including preparation of materials before the course starting date, a discussion board for responding to pre‐ and post case discussion questions, and prompt reply to student queries. For exams, students generated their own questions based on unfamiliar cases and developed their own case study for the final project. Although only 20% of students had previously taken an online course, all students would recommend this course to others. Formative assessment indicated that students found cases interesting, informative, and presented at the appropriate level. Most students said that the online course took them more time; they learned more content and used the primary literature more than a traditional class. Our results indicate that a well‐organized physiology course using a case study format is a very effective model for online learning.
Evo‐devo: Evidence of developmental plasticity in the shape of the talo‐crural joint in response to substrate use.
Authors: Turley Kevin , Frost Stephen R.
Published: June 2021

Is plasticity in joint shape observed with different substrate use? The current study examines the appositional articular morphology (AAM) of the talo‐crural joint across catarrhine primates.

Matched tibiae and tali from 245 adults and 163 subadults from 6 hominoid and 6 cercopithecoid taxa (H. sapiens, G. gorilla, P. troglodytes, P. paniscus, Pongo spp., Hylobatidae, M. fascicularis, M. mulatta, M. thibetana, P. hamadryas, C. guereza, N. larvatus) were studied. Sixteen tibial and 15 talar landmarks were placed on laser surface scans of the articular surfaces using Landmark Editor software. Generalized Procrustes analysis, principal component analysis, multivariate regression and singular warps analysis were used to examine joint shape.

Adult terrestrial taxa have features that provide flexibility and stability on horizontally placed irregular surfaces of different textures, while adult arboreal taxa medially placed curvilinear surfaces with irregular surface movement.

Evidence of developmental plasticity due to substrate preference was observed. Adult articular shape sorted by substrate preference across superfamily reflecting differences in use, and when the AAM subsets were examined, subadults of both arboreal and terrestrial forms are similar, and there was little change between subadults and adults in arboreal taxa, but significant change between subadults and adults of terrestrial forms.

Funding provided in part by NSF BCS0452539, and the University of Oregon, and funding to the CPRC by NIH Grant No. P40 RR003640.

Grant Funding Source: University of Oregon
Interchangeable potential varies among mesothelial cell populations in the embryo
Authors: Thomason Rebecca Taylor , Winters Nichelle I , Bader David M
Published: June 2021

Mesothelium is an epithelial sheet that covers coelomic organs and is involved in development of the vascular system. In the developing heart, the proepicardium (PE), migrates over the heart forming the epicardium, and undergoes epithelial‐mesenchymal transition (EMT) to contribute cells to the coronary blood vessels. The gut mesothelium also serves as a major source of vascular smooth muscle cells for the gut tube in development. We hypothesize that heart and gut mesothelial cell populations possess an interchangeable potential in coelomic organs. First, we characterized avian mesothelial cells using histological and molecular techniques to determine the cell types present at time of transplant. In addition, mesothelial cells were cultured to investigate the differentiative properties the mesothelial isolates. To test the interchangeable potential of mesothelial cells, we used the chick‐quail chimera system, transplanting quail PE and epicardial cells into the peritoneal cavity of a chick embryo and quail gut mesothelial cells into chick pericardial cavities. Our findings have revealed that all mesothelia have the potential to migrate into organs in the analogous coelomic cavity. However, PE and epicardial cells did not incorporate into the endogenous gut mesothelium and retained epithelial characteristics. Alternatively, gut mesothelial cells incorporated into the endogenous epicardium and contributed vascular smooth muscle cells, fibroblasts, and myofibroblasts to the heart. Taken together, our current data suggest a limited developmental potential between heart and gut mesothelial cell populations.
The Role of PI3K/AKT Signaling in the Development of Ciona intestinalis
Authors: Evans‐Anderson Heather J. , Tucker James , Intwala Arti
Published: June 2021

In vertebrates, the regulation of cardiac myocyte proliferation has been attributed to FoxO transcription factors, which are mediated by PI3K/AKT signaling. The aim of this study was to identify the effects of altered PI3K/AKT signaling on heart development in Ciona intestinalis. We hypothesized that altered PI3K/AKT signaling would disrupt Ciona heart formation due to reduced proliferation of cardiac myocytes. In order to determine the developmental impact of altered PI3K/AKT signaling, Ciona larvae were generated via timed in vitro fertilization and then treated with drugs to specifically alter PI3K/AKT signaling. Ciona larvae were treated with drugs during the period of morphogenesis, which encompasses heart formation. Preliminary results show altered heart morphogenesis and delayed development in Ciona juveniles treated with the PI3K‐specific inhibitor in comparison to those treated with the other drugs or non‐treated controls. In addition, the size of hearts in Ciona juveniles treated with an AKT‐specific inhibitor was significantly reduced. Furthermore, increased expression of ciFoxO was observed in juveniles treated with AKT‐specific inhibitor. Future directions include the use of real time RT‐PCR to assay ciFoxO transcriptional activity and the utilization of immunohistochemistry to detect proliferation and apoptosis rates in the hearts of treated Ciona.
Ultrastructural analysis of neurons, glia and capillaries in the peri‐infarct zone of an ischemic stroke
Authors: Nahirney Patrick C , Reeson Patrick , Brown Craig E
Published: June 2021

Stroke is a serious condition that can drastically affect sensation, mobility and/or cognitive function. The peri‐infarct zone (or penumbra) is a hypo‐perfused region that, if re‐perfused, can regain function. To better understand this zone, mice were subjected to photothrombotic stroke in the forelimb somatosensory cortex (SSC) and allowed to recover for three days. Mice were then perfused and the SSC processed for light and electron microscopy. Infarcts appeared as swollen pale regions of the SSC that ranged in volume from 2–3mm3. Three zones were identified: the necrotic ischemic core, edematous, and structurally‐intact zones. In the necrotic zone, scattered erythrocytes, macrophages, neutrophils and eosinophils occupied the degenerating neuropil. The edematous zone (~100μm wide, adjacent to necrotic zone) exhibited swollen axons/dendrites 1–5μm wide, enlarged pyramidal neurons, glycogen‐filled astrocytes and capillaries with thickened and vacuolated endothelium. The intact zone (~200μm wide) contained dilated vessels surrounded by astrocytes with vast glycogen deposits. Excitatory and inhibitory synapses appeared structurally normal but reduced in number in the latter two zones. Understanding the cellular effects that occur in this zone will permit a more directed approach to therapies designed to reverse this damage. Supported by CIHR (CB), Heart & Stroke Foundation (CB) and NSERC (PN).
Activation of the glucocorticoid receptor by dexamethasone enhances BHV‐1 productive infection
Authors: Ahlers Trent , Jones Clinton , Sinani Devis
Published: June 2021

Sensory neurons in trigeminal ganglia are the primary site for bovine herpes virus‐1 (BHV‐1) latency. Following stress, glucocorticoid levels increase leading to reactivation of BHV‐1 from latency. An IV injection of the synthetic glucocorticoid dexamethasone (DEX) to latently infected calves consistently induces reactivation. A recent study showed that DEX treatment stimulates expression of host cell genes which indirectly leads to activation of lytic cycle viral genes and enhanced productive infection. DEX functions primarily by agonizing the glucocorticoid receptor (GR). The BHV‐1 genome contains numerous GR consensus sequences suggesting that DEX‐activated GR can directly transactivate viral genes. This study investigated the effect of DEX and GR on BHV‐1 productive infection in vitro. When GR was over expressed in the absence of DEX, the effect on BHV‐1 productive infection was insignificant. In the presence of DEX, GR over expression enhanced productive infection 3‐fold. These studies suggest that DEX‐activated GR stimulates reactivation from latency by activating cellular transcription factors and/or signaling pathways. Conversely, DEX may directly stimulate reactivation from latency by binding to viral promoters and inducing lytic cycle viral gene expression in a small subset of latently infected neurons. This publication was funded by NIH grant 5P20RR016469 and NIGMS grant 8P20GM103427.
The Wnt/β‐catenin/TCF‐4 pathway upregulates HMGA1 expression in colon cancer
Authors: Sumter Takita Felder , Bush Bethany , Brock Ashton , Deng Jiayue , Nelson Ronald
Published: June 2021

High Mobility Group A1 (HMGA1) encodes proteins that act as mediators in viral integration, modification of chromatin structure, neoplastic transformation, and metastatic progression. Because HMGA1 is overexpressed in most cancers and has transcriptional relationships with several Wnt‐responsive genes, we explored the involvement of HMGA1 in Wnt/β‐catenin/TCF‐4 signaling. In adenomatous polyposis coli (APCMin/+) mice, we observed significant upregulation of HMGA1 mRNA and protein in intestinal tumors when compared to normal intestinal mucosa. Conversely, restoration of Wnt signaling by zinc‐induction of wt‐APC resulted in HMGA1 downregulation in HT‐29 cells. Because APC mutations are associated with mobilization of the β‐catenin/TCF‐4 transcriptional complex and subsequent activation of downstream oncogenic targets, we analyzed the 5′‐flanking sequence of HMGA1 putative TCF‐4 binding elements (TBEs). We identified two functional that specifically bind the β‐ catenin/TCF‐4 complex in vitro and in vivo identifying HMGA1 as an immediate target of the β‐catenin/TCF‐4 signaling pathway in colon cancer. Collectively, these findings strongly implicate Wnt/β‐catenin/TCF‐4 signaling in regulating HMGA1 to further expand the extensive regulatory network affected by Wnt/β‐ catenin/TCF‐4 signaling.
mTOR complex 2 phosphorylates IGF2 mRNA binding protein1 cotranslationally to promote IGF2 production and the proliferation of mouse embryonic fibroblasts
Authors: Dai Ning , Avruch Joe
Published: June 2021

Lack of IGF2 in the mouse results in diminished embryonic growth due to diminished cell proliferation. Herein we show that mouse embryonic fibroblasts lacking the RNA binding protein IMP1 have defective splicing and translation of IGF2 mRNAs, markedly reduced IGF2 polypeptide production and diminished proliferation. The proliferation of the IMP1 null fibroblasts can be restored to wildtype levels by IGF2 in vitro or by reexpression of IMP1, which corrects the defects in IGF2 RNA splicing and translation. The ability of IMP1 to correct these defects is dependent on IMP1 phosphorylation at Ser181, which is catalyzed cotranslationally by mTOR complex 2. Phosphorylation strongly enhances IMP1 binding to the IGF2 leader 3 5′UTR, which is absolutely required to enable IGF2‐leader 3‐mRNA translational initiation by internal ribosomal entry. These findings uncover a new mechanism by which mTOR regulates organismal growth, by promoting IGF2 production in the mouse embryo through mTOR complex 2‐ catalyzed cotranslational IMP1/IMP3 phosphorylation. Inasmuch as TOR Complex 2 is activated by association with ribosomes, the present results indicate that mTORC2‐catalyzed cotranslational protein phosphorylation is a core function of this complex.
Public Health Model for Mitigation of Antimicrobial Resistance
Authors: Kannan Subburaj , Martinez Juan
Published: June 2021

Antibiotic resistance complicates medical treatment and frequently results in longer and more serious illness, and even death in some instances. According to the Centers for Disease Control and Prevention, 99,000 people die each year in the U.S. of hospital‐acquired infectious diseases. Medical practice involving Poly pharmacy, Hospice care, nosocomial infections, health care facilities housing chronically ill patients and use of disproportionate quantities of antibiotics on cattle to boost revenue from the Agro Industry have been shown as sources of antimicrobial resistance. Primary care physicians in private practice, health care facilities, long term critical care, and geriatric care facilities, the agriculture and livestock industries, are of potential risk factors. Also, farming communities with low literacy or illiterate migrant workers, oil rig workers, health care workers, and workers who are in constant contact with the general public (especially those in the retail industry), and transportation workers are potential targets groups and considered as “AT RISK” group. Public awareness campaigns, which attempt to educate the general public, can provide strict guidelines to eliminate antibiotic recycling and antimicrobial optimization. These are potential avenues in preventing the evolution of Antimicrobial Resistance.
Effects of 4‐phenylbutyric acid on the process and development of cerebrum injury in diabetic rats: regulation of endoplasmic reticulum stress inflammatory response
Authors: Wang zhouguang , Zhang Hongyu , Shi Hongxue , Xiao Jian
Published: June 2021

Background

Inflammation may contribute to the pathogenesis of diabetic nephropathy (DN) and inflammatory response plays an important role in diabetic cerebrum injury, although the precise regulatory mechanism is still unclear. Recent reports have shown that 4‐phenylbutyric acid (4‐PBA) can suppress endoplasmic reticulum (ER) stress. We therefore hypothesized that 4‐PBA could provide neuroprotection through the suppression of ER stress inflammatory response in DN rats.

Methods and Results

Male SD rats were randomly divided into three groups: a normal control group, a streptozotocin and high fat diet‐induced DN model group, and a DN plus 4‐PBA (1g/kg) treatment group. In diabetic animals, elevated ER stress markers, GRP78, ATF‐4, XBP‐1, CHOP and the expression of p‐eIF, p‐JNK in the cerebral cortex were increased; TNF‐¦Á and IL‐6 levels were increased and NF‐kappaB signal pathway was activated; In cultured hippocampus neurons, high glucose induced a time‐dependent increase of ER stress and inflammatory factor production. In contrast, alleviation of ER stress by 4‐PBA or blockade of JNK activity attenuated inflammatory gene expression induced by high glucose, 4‐PBA also inhibit neuron cell apoptosis in vitro and in vivo.

Conclusion

4‐PBA exerts a marked neuroprotective effect possibly due to modulating ER stress and related inflammatory response.
Inflammatory markers associated with osteoarthritis after destabilization surgery in mice with and without Receptor for Advanced Glycation End Products (RAGE)
Authors: Larkin D. Justin , Kartchner Jeffrey Z. , Hollis Weston R. , Doxey Alexander S. , Jackson Gregory G. , Wilhelm Spencer K. , Peterson Danielle M. , Chavez Elizabeth M. , Rees Jeffrey L. , Haynie Scott S. , Draper Christian S. , Reynolds Paul R. , Kooyman David L.
Published: June 2021

It has been shown that HtrA1, Ddr‐2 and Mmp‐13 are reliable biomarkers for osteoarthritis (OA), yet the exact mechanism for the upregulation of HtrA‐1 is not known. Some have shown that chondrocyte hypertrophy is associated with early indicators of inflammation including TFG‐β and the Receptor for Advanced Glycation End products (RAGE). The objective of this research is to examine the effects of TFG‐β and RAGE on the progression of osteoarthritis. Samples of wild type (WT) and RAGE knockout (KO) were assayed for Mmp‐13, Ddr‐2, HtrA‐1 and TGF‐β, and evaluated for cartilage degradation four weeks after a knee destabilization procedure. We observed consistent positive staining for Mmp‐13, Ddr‐2, and HtrA‐1 in both WT and RAGE KO mice with late OA, while TGF‐β staining was only positive in samples with early OA. Despite similar IHC staining profiles, RAGE KO mice exhibited significantly less cartilage degradation as compared to WT mice. In subsequent analyses, RAGE KO mice exhibited more chondrocytes and a lower percentage of cells staining positive for OA biomarkers. From our results, we hypothesize that TGF‐β is involved in the upregulation of HtrA‐1 and is subsequently inhibited by HtrA‐1, and further that the chondroprotection in RAGE KO samples is due to a decreased presence of Mmp‐13 and HtrA‐1 and consequent protection against cell death. This research has been supported by FAMRI and BYU MEG grants.
PLGA nanoparticles loaded with antitumoral drug as a Drug Delivery System
Authors: Dias Diego Juscelino Santos , Joanitti Graziella A , Silva Luciano P , Lunardi Claure N , Gomes Anderson J
Published: June 2021

Chlorambucil (CHB) is an anticancer agent used in conventional treatment of a variety of cancers, particularly in chronic lymphocyte leukemia and autoimmune disease. This use is restricted because undesirable side effects. To overcome this situation CHB was encapsulated in nanoparticles (NPs) of poly(D,L‐lactide‐co‐glycolide) acid (PLGA) using the double emulsion technique. CHB‐NP were evaluated in relation to parameters such as drug encapsulation efficiency using 10 mg CHB (93,10±0,71%), release profile (79% in 24 h), particle size (285,50±46,85 nm), zeta potential (−17,00±0,42 mV) and also physical chemistry properties of CHB‐NP were recorded (FT‐IR and UV‐vis absorptions, emission of fluorescence TGA/DTA and DSC). The spherical morphology of the NPs was analyzed through SEM. Cytotoxicity of CHB‐NP were studied in two different cells line: NIH‐3T3(64.5%) and MCF7 (64.8%) by MTT assay. DDS produced in this work showed to be a promising way to improve bioavailability, to reduce adverse effects and could be more potent agent than free CHB. Financial support: CNPq, CAPES, FAPDF, FINATEC, DPP‐UnB
Obesity polymorphisms identified in genome‐wide association studies interact with n‐3 polyunsaturated fatty acid intake and modify genetic associations with adiposity phenotypes in Yup'ik people
Authors: Lemas Dominick Joseph , Klimentidis Yann C. , Wiener Howard H. , O'Brien Diane M. , Hopkins Scarlett , Allison David B. , Fernandez Jose R. , Tiwari Hemant K. , Boyer Bert B.
Published: June 2021

n‐3 polyunsaturated fatty acids (n‐3 PUFAs) have anti‐obesity effects that may modulate risk of obesity, in part, through interactions with genetic factors. Genome‐wide association studies (GWAS) have identified genetic variants associated with BMI; however the extent to which these variants influence adiposity through interactions with n‐3 PUFAs is unknown. We evaluated 10 obesity GWAS SNPs for associations with adiposity phenotypes in a cross‐sectional sample of Yup'ik people (n=1073) and evaluated whether genetic associations with obesity were modulated by n‐3 PUFA intake. n‐3 PUFAs intake was estimated using nitrogen stable isotope ratios (δ15N) of red blood cells and genotype‐phenotype analyses were tested in linear models accounting for familial correlations. FTO was positively associated with percent body fat and ETV5 was negatively associated with hip and thigh circumference. A genetic risk score (GRS) was positively associated with adiposity. GRS interactions with n‐3 PUFAs modified the association with adiposity and accounted for more than twice the phenotypic variation (~1–2%), relative to GRS associations alone. GRS interactions with n‐3 PUFA intake potentiated the risk of fat accumulation among individuals with high obesity GRS. These data suggest the anti‐obesity effects of n‐ 3 PUFAs among Yup'ik people, in part, may be dependent upon an individual's genetic predisposition to obesity.
Deregulation of the non‐canonical pathway in triple‐negative breast cancer
Authors: Borg Jean‐Paul , Belotti Edwige , Daulat Avais , Lembo Frederique , Bertucci Francois , Charafe‐Jauffret Emmanuelle , Birnbaum Daniel
Published: June 2021

Planar cell polarity (PCP) is controlled by a non‐canonical Wnt pathway. It organizes the polarization of many epithelial tissues and organs within the plane, and drives cell migration and cell intercalation of non‐epithelial cells such as mesenchymal cells. Loss of function of PCP genes can lead to severe neural tube defects in animal models and human. Little is known about the role of PCP genes in tumor growth and dissemination.

A screen led us to identify Vangl2, a PCP receptor, as a molecule overexpressed at the genomic, transcriptomic and protein levels in poor prognosis triple negative breast cancers. Using cultured breast cancer cells, we show that Vangl2 is implicated in tumorigenicity and cell migration, and triggers a non‐canonical Wnt‐JNK pathway. Implication of Vangl2 in tumor growth was confirmed in xenograft assays in nude mice. Through a combinatory two‐hybrid/proteomic approach, we further discovered Vangl2 PDZ partners including Scribble and Dishevelled. Interaction with Scribble, but not Dishevelled, is required for cell migration of cancer cells. Our work reveals a novel implication for PCP proteins in triple negative breast cancer.
Effect of medical advice for diet on diabetes self‐management and glycemic control for Haitian and African Americans with type 2 diabetes
Authors: Dixon Zisca , Exebio Joel C , Vaccaro Joan A , Zarini Gustavo G , Huffman Fatma G
Published: June 2021

Objective

The purpose was to assess dietary advice with diabetes self‐management and glycemic control by ethnicity.

Methods

Cross‐sectional analysis of 254 Blacks with type 2 diabetes (Haitian Americans=129; African Americans=125) recruited from Miami‐Dade and Broward Counties, Florida by community outreach. Sociodemographics, anthropometrics and blood samples were collected after informed consent.

Results

Dietary advice and behavior dependent on ethnicity. The combined model ethnicity by ‘given advice to follow a diet’ was not significant, so separate logistic regression analyses were conducted for each ethnicity. Haitian Americans given advice ‘to follow a diet’ were more likely to ‘use food groups’ than not [OR=3.27(1.32, 8.00) p=.007]. A one unit increase in diabetes self‐management score decreased the odds ratio point estimate of having less than optimal glycemic control (A1C >; 7.2%) by a factor of 0.94 in African Americans (p=.009).

Conclusions

These results suggest that medical advice for diet plans may not be communicated effectively to some race/ethnicities. Studies of diet management specific to Black ethnicities are recommended. Funding was by an NIH/NIDDK grant.
A Simple, non‐Destructive Method for Bromide Analysis in Plasma for Field Body Composition Studies
Authors: Kehayias Christopher Erkki , Kempf Kari G , Roto Anna V , Kehayias Joseph J
Published: June 2021

Objective

Expansion of extracellular water (ECW) space serves as a measure of muscle loss, cachexia or inflammation. It is used to monitor frailty, depletion of muscle mass, and the efficacy of nutritional interventions. ECW is measured by bromide dilution, where a known amount of NaBr is administered and a plasma (or urine) sample is analyzed, after equilibrium, by instrumental neutron activation analysis (INAA) or high‐performance liquid chromatography (HPLC). The objective of this work is to develop an alternative, automated method of analysis that does not require the complexity of INAA or HPLC.

Method

We tested a non‐destructive energy dispersive X‐ray fluorescent (XRF) device which uses a Cd‐109 radioactive source, a miniature (25 mm2), electronically cooled, high resolution (<150 eV) silicon detector and a microprocessor‐controlled sample‐positioning system to obtain X‐ray spectra from plasma samples. The method requires no sample preparation and preserves 100% of each specimen.

Results

Sensitivity: 0.1ug/cc, reproducibility for Br in plasma or urine <0.8%, accuracy <1.0%. Validated against INAA (R2=0.994).

Conclusion

The method can be used in the field for repeated measurements. The lack of sample preparation eliminates the opportunity for bromide loss due to filtering. Being non‐destructive, XRF allows for full preservation of the specimen. Support: USDA contr. 51000–071
A systematic review of the effects of sodium reduction on glucose levels
Authors: PATEL SHEENA , COBB PAUL , SAYDAH SHARON , ZHANG XUANPING , DE JESUS JANET , COGSWELL MARY
Published: June 2021

OBJECTIVE

Assess effects of sodium reduction on glucose levels.

METHODS

We systematically searched The Cochrane Library, MEDLINE, EMBASE, CINAHL, and Web of Science through July 2012. We initially included randomized and non‐randomized intervention trials comparing ≥2 sodium intake levels and examining ≥1 measure of glucose levels.

RESULTS

Of 2920 abstracts screened, 37 trials (1402 participants) evaluated the effects of sodium intake on glucose levels. Participants were 10–79 years old, primarily healthy or with hypertension. Metaanalysis of 10 randomized, cross‐over trials with ≥7 day interventions, >;80% follow‐up, and intent‐to‐treat analysis of follow‐up fasting glucose concentrations, showed that fasting glucose did not differ by sodium intake (N=299, mean difference, mmol/L: 0.04; 95% confidence interval −0.07,0.14) and heterogeneity was not significant (I2=0%, P=1.0) in the random effects model. Among these studies, mean excretion for the lowest sodium reduction group ranged from 280–2875 mg/d (weighted mean=713 mg/d) versus 2171–6859 mg/d (weighted mean= 5723 mg/d) for the other group.

CONCLUSION

Our meta‐analysis of randomized, cross‐over trials, with fasting glucose and low risk of bias, suggests ≥7 day sodium reduction (weighted mean ‐5010 mg/d) does not affect fasting glucose. Variation in methods precluded meta‐analysis of other glucose measures.