bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of simvastatin‐induced structural and functional alterations in the molecules of kidney brush border membrane by ATR‐FTIR spectroscopy and chemometric approaches
Authors: Severcan Feride , Gocmen Semire Uzun , Ozek Nihal Simsek , Severcan Mete 
Published: June 2021

Simvastatin, lipophilic statin, is the most commonly used drugs to treat hyperlipidaemia. Recent studies reported that they have both adverse and beneficial effects on kidney. However these results are contradictory. In this study, the aim was to investigate the effects of simvastatin on concentration, structure and function of molecules of kidney brush border membrane (BBM) by Attenuated Total Reflectance‐Fourier Transform Infrared (ATR‐FTIR) spectroscopy and chemometric analysis.During 30 days, control and simvastatin treated rats were taken serum physiologic and 50 mg/kg/day simvastatin intragastrically, respectively. Simvastatin‐induced changes in the structure and function of molecules in kidney BBM were determined from the frequency, area and width analysis of spectral bands. Based on these alterations, cluster and principal component analysis (PCA) were applied to discriminate these groups. Moreover, artificial neural network (ANN) analysis was used to determine the secondary structure alterations in proteinsSpectral analysis indicated a decrease in the amount of saturated and unsaturated lipids and proteins with simvastatin treatment. Control and simvastatin groups were successfully distinguished. A significant decrease in beta sheet and increase in random coil content were observed in simvastatin treated group. This study was supported by BAP‐08–11‐DPT‐2011K121010.
S1P1 Receptor Regulation by Phosphorylation
Authors: Bazúa‐Valenti Silvana , Morquecho‐León Marco. A , Romero‐Ávila M. Teresa , García‐Sáinz J. Adolfo 
Published: June 2021

Sphingosine‐1‐phosphate (S1P) is a bioactive molecule that has been implicated in regulating cellular processes. S1P exerts its extracellular effects as a ligand of a GPCR family. S1P1 receptors are coupled to heterotrimeric Gi/o proteins. The importance of S1P and its receptor S1P1 in multiple cellular and physiological processes (vascular tone, permeability, angiogenesis, lymphocyte egress) makes them and their regulation, an interesting pharmacological target. It has been demonstrated that S1P1 activation by its natural ligand and the activation of PKC by phorbol myristate acetate leads to receptor phosphorylation and internalization. However, little is known about the identity of the kinases involved in this process. The primary objective of this study is to characterize the molecular processes that lead to receptor phosphorylation and identify the PKC isoform/s implicated.A human prostate cancer cell line stably expressing the S1P1 fused to the Green Fluorescence Protein was used for this work. We conducted functional analysis by measuring intracellular calcium mobilization in the presence or absence of PMA and distinct PKC selective inhibitors for the different isoforms. S1P1‐PKC interaction in the course of stimulation with PMA was analyzed by co‐immunoprecipitation. Our results indicate that of two isoforms participate in the PMA‐mediated desensitization, PKC α and to a lesser extent PKC β.
Arrestin‐3 binding to JNK1alpha1/JNK2alpha2: modulation of JNK1 and JNK2 activity via scaffolding
Authors: Kook Seunghyi , Zhan Xuanzhi , Kaoud Tamer S , Dalby Kevin N , Gurevich Vsevolod V , Gurevich Eugenia V 
Published: June 2021

Non‐visual arrestins scaffold mitogen‐activated protein kinase (MAPK) cascades, bringing together three components of MAPK signaling modules. The c‐Jun N‐terminal kinases (JNKs) are members of MAPK family and three JNKs isoforms (JNK1, JNK2, and JNK3) have been identified. JNK1 and JNK2 are ubiquitously expressed, whereas JNK3 is expressed mainly in testes and neuronal tissues. Arrestin‐3 isoform has been shown to enhance JNK3 activity by scaffolding JNK3 with upstream kinases. However, it has not been documented whether arrestin‐3 can modulate the activity of JNK1 and JNK2 isoforms. Using purified proteins we found that arrestin‐3 directly binds JNK1α1 and JNK2α2. Reconstitution of JNK1α1 or JNK2α2 signaling module with either MKK4 or MKK7 in the presence of different arrestin‐3 concentrations showed that arrestin‐3 acts as scaffold, facilitating JNK1α1 and JNK2α2 phosphorylation at optimal concentration. Arrestin‐3 also enhanced phosphorylation of endogenous JNK1 and 2 isoforms when upstream kinases MKK4 or MKK7 were overexpressed together with arrestin‐3 in COS‐7 cells. Thus, the data suggest that arrestin‐3 also modulates JNK1 and JNK2 activity in non‐neuronal cells acting as a scaffold for these JNK isoforms and upstream kinases.Support: NIH Grants NS065868 and DA030103 (EVG), GM077561, GM081756, and EY011500 (VVG), GM059802 and Welch Foundation Grant F‐1390 (KND).
Protein kinase C mutations in cancer
Authors: Antal Corina E. , Kang Emily , Newton Alexandra C. 
Published: June 2021

Protein kinase C (PKC) levels are aberrant in diverse cancers and over 160 mutations in PKC have been identified in human cancers. Here we characterized PKC mutations identified in human cancers to investigate whether PKCs function as oncogenes or tumor suppressors or whether their function is isozyme and/or context dependent. Live‐cell imaging was used to determine how these mutations affect PKC translocation, subcellular localization, and activity. Cell‐based assays were used to determine how PKC mutations alter proliferation, apoptosis, migration, and anchorageindependent growth. Of 30 mutations we examined thus far, 14 of them reduced or completely abolished PKC activity, while only 1 increased it. These mutations reside within the diacylglycerol‐binding C1 domain, the Ca2+‐binding C2 domain, or the kinase domain, within both conventional and novel PKCs. The inactivating mutations ablate activity by either impeding Ca2+ or diacylglycerol binding, or by yielding a misfolded kinase. These results suggest that PKC can act as a tumor suppressor. Understanding whether mutations are activating or inactivating in specific cancers would allow us to determine whether therapeutic strategies should target ways to inactivate or activate PKC in the respective cancers.This work was supported by GM43154 to ACN and DGE1144086 and T32 GM007752 to CEA.
Investigations into the role of Lantibiotic Cyclase‐like (LanCL) proteins in mammals
Authors: Zeng Min , Chen Jie , van der Donk Wilfred 
Published: June 2021

Lantibiotics are a group of antibiotics that are ribosomally synthesized and posttranslationally modified peptides. Lantibiotic cyclase (LanC) catalyzes the Michael addition reaction of the thiol group in cysteines to the α, β‐unsaturated carbonyl in dehydrated amino acids in the precursor peptides, generating the macrocyclic structures of lantibiotics.Interestingly, in eukaryotes, which do not produce lantibiotics, homologs of LanC widely exist. LanC‐like (LanCL) proteins have highly conserved sequences as well as the Zn2+ ligands and active site residues that are also found in LanC. However, the function of these proteins and the underlying mechanisms are largely unknown. In the current study, we discovered a novel function of LanCL2 in the regulation of Akt phosphorylation and insulin signaling in mammalian cells and propose a possible mechanism of this regulation. Our discoveries suggest the functional significance of LanC‐like proteins in mammals.
Automated analysis of Ca2+ mobilization in the cornea under hypoxia
Authors: Lee Albert , Derricks Kelsey , Trinkaus‐Randall Vickery 
Published: June 2021

Previously, our lab demonstrated that ATP release upon injury induces Ca2+ mobilization in corneal epithelial cells via purinergic signaling. This mobilization was shown to be critical for the promotion of corneal wound repair. Most recently, we demonstrated that glutamatergic and purinergic receptors modulate communication between corneal epithelia and its innervating neurons by eliciting a complex bimodal Ca2+ wave upon injury. In this study, our goal was to examine changes in Ca2+ mobilization caused by hypoxia during corneal wound repair.Ca2+ mobilization was analyzed by an algorithm using MATLAB. When epithelial cells were treated with neuronal wound media, hypoxia decreased both Ca2+ mobilization and subsequent cluster formation. There was a reduction in the amount of ATP present in both primary trigeminal rat neurons and human corneal limbal epithelial cells (HCLEs). Hypoxia reduced response to agonists specific to P2Y by 45% and to P2X receptors by 64%. Wound closure was impaired and the phosphorylation of paxillin was decreased.Our results demonstrated that hypoxia impairs cell‐cell communication upon injury, which correlated with changes in the purinergic signaling pathway. Our automated Ca2+ mobilization analysis showed a reduction in nucleotide‐induced Ca2+ mobilization and a decrease in cluster formation under hypoxia.
The Effect of Phosphatidylinositol 4,5‐bisphosphate Depletion on the Internalization of G Protein‐coupled Receptors
Authors: Tóth Dániel J , Tóth József T , Tallósy Bernadett , Hunyady László , Várnai Péter 
Published: June 2021

Phosphatidylinositol 4,5‐bisphosphate (PtdInsP2) has been shown to be critical for many endocytic processes including the internalization of G protein‐coupled receptors (GPCRs). Our aim in this study was to compare the effect of different plasma membrane PtdInsP2 depletion methods on GPCR internalization.We used bioluminescence resonance energy transfer (BRET) to follow the internalization of the luciferase‐tagged β2 adrenergic receptor (β2AR) in HEK 293 cells. To reduce PtdInsP2 levels, we applied either the rapamycin‐inducible recruitment of a 5‐phosphatase domain to the plasma membrane, or a truncated form of type 1 angiotensin receptor (AT1R) which activates phospholipase Cβ. We determined the rate of PtdInsP2 degradation using the PH domain of phospholipase Cδ1 which binds PtdInsP2 specifically, and found it to be comparable for the two depletion methods. While PtdInsP2 depletion by our rapamycin‐based system inhibited the internalization of β2AR, PtdInsP2 depletion by AT1R had no effect on it, measured by the same method.Our data suggest that the effect of plasma membrane PtdInsP2 depletion on the internalization of β2AR can be different depending on the method by which the lipid is degraded. Further investigation is needed to determine whether this discrepancy is due to degradation of distinct PtdInsP2 pools of the plasma membrane or other factors are responsible for it.Support: OTKA K105006
High blood pressure and arterial stiffness are not associated with low bone mass
Authors: Johnson Sarah A. , Figueroa Arturo , Navaei Negin , Wong Alexei , Kalfon Roy , Elam Marcus , Payton Mark , Arjmandi Bahram H. 
Published: June 2021

Hypertension (HTN), arterial stiffness and osteoporosis have common etiologies and their occurrence increases dramatically after menopause. HTN and arterial stiffness have been shown to be inversely associated with bone mass. The objective of this cross‐sectional study was to examine the degree to which bone mineral density (BMD), bone mineral content (BMC) and percent body fat (PBF) are influenced by high blood pressure (BP) and arterial stiffness in 38 postmenopausal women with pre‐ and stage 1‐HTN. Systolic and diastolic BP were evaluated using resting brachial BP and arterial stiffness was assessed using carotid‐femoral pulse wave velocity (cfPWV) and right brachial‐ankle pulse wave velocity (RbaPWV). BMD, BMC and PBF were measured using dual‐energy X‐ray absorptiometry (DXA). Pearson correlation coefficients were used to determine the relationship between variables of interest. Systolic BP, diastolic BP and cfPWV were not correlated with BMD (P = 0.98, 0.55, and 0.63, respectively), BMC (P = 0.77, 0.94, and 0.47, respectively) or PBF (P = 0.44, 0.88, and 0.35, respectively). RbaPWV was not correlated with right leg BMD (P = 0.79) or right leg BMC (P = 0.39). There was a strong negative correlation between RbaPWV and PBF (r = − 0.45, P = 0.004). These findings do not suggest that there is a link between high BP, arterial stiffness and bone mass but do suggest a link between body fat and systemic arterial stiffness.Grant Funding Source: Internal Funding
Are physical activity and food insecurity associated with depressive feelings in U.S. adults?
Authors: McNeill Meghan , Venci Brittany Jeanne , Park Sohyun , Lee Seung‐Yeon 
Published: June 2021

We examined associations between depressive feelings and food security while controlling for physical activity (PA) in a nationally representative sample using the 2011 National Health Interview Survey data for 29,981 U.S. adults (≥18 years). Multivariable logistic regression was used to estimate adjusted odds ratio (OR) and 95% confidence interval (CI) for associations between food security and having depressive feelings after controlling for sociodemographic and lifestyle factors. Food security scale was used to define food secure (score 0–2), low food secure (3–5), and very low food secure (6–10). About 87% were food secure, 6.6% were low food secure and 5.2% were very low food secure. Regardless of PA status, both low and very low food secure adults had higher odds of having each of 6 depressive feelings compared to physically active, food secure adults. For example, very low food secure, physically inactive adults had higher odds for feeling sad (OR=3.40, 95% CI=2.75, 4.20), nervous (OR=2.47, 95% CI=1.98, 3.07), restless/fidgety (OR=3.00, 95% CI=2.36, 3.82), hopeless (OR=3.28, 95% CI=2.62, 4.09), everything was an effort (OR=3.13, 95% CI=2.51, 3.89), and worthless (OR=3.68, 95% CI=2.86, 4.75) than physically active, food secure adults. Although the directionality of our associations is unknown, our findings suggest that food insecure, physically inactive adults tend to have more depressive feelings.Grant Funding Source: None
Why have NCDs received so little attention in Nigeria?
Authors: Adeyemi Olutayo , Pelletier David L. , Devine Carol M. , Pinstrup‐Andersen Per , Stoltzfus Rebecca J. 
Published: June 2021

Noncommunicable diseases (NCDs) in low and middle income countries (LMICs) increase illness, death and poverty, overburden health systems, and may retard progress on undernutrition and infectious diseases through resource competition. Global authorities have urged that “a sound and explicit government policy” is vital for tackling NCDs in LMICs; yet, policy actors’ views concerning NCDs in these countries have not been studied. This research examined the state of NCD policy and the views of policy actors in Nigeria, which is ranked fifth among LMICs in terms of mortality due to NCDs. Methods included document analysis and semi‐structured interviews with 34 key Nigerian policy actors. Interview results were compared with established factors that shape political priority.The Nigerian health ministry has had a NCD policy unit since 1989 and there has been significant policy rhetoric about NCDs. However, there is no formal policy or serious action on NCDs. Factors contributing to this neglect of NCDs include the biological/social characteristics of NCDs, lack of bureaucratic or political champions, lack of a broadly‐based, effective NCD coalition and, until recently, limited attention by the international community.Research support: Cornell University: Division of Nutritional Sciences; Mario Einaudi Center for International Studies. First Presbyterian Church in Ithaca International Hunger Student Grant
The components of metabolic syndrome in relation to weight status in South Indians
Authors: Must Aviva , Thanikachalam Mohan , Begum Mubeen , Vijayakumar Harivanza , Chui Ken , Chomitz Virginia , Bermudez Odilia , Thanikachalam Sadagopan 
Published: June 2021

Asian populations have elevated risk for obesity‐related morbidity such as metabolic syndrome (MS). MS, defined as the presence of 3 of 5 cardiovascular and anthropometric indicators, may overlook differences in its components relative to modifiable antecedents, such as weight. A population‐based cross‐sectional survey in 8042 (44% M, 56% F) South Indians collected detailed physicals and biochemical assays via standard protocols. MS components were defined based on the modified National Cholesterol Education Program Adult Treatment Panel (ATPIII) criteria for Asians. BMI categories were <18.5, 18.5–23, 23–25, 25–30, and 30+.11% M and 7% F were underweight (BMI<18.5); prevalence of BMI>;23 was 56% M and 70% F; with 6% M and 16% F with BMI >;30. MS components were prevalent across all weight groups BMI >;18.5, with ranges 27 to 59% M and 18 to 80% F. Compared to normal weight (BMI 18.5–23), after adjusting for smoking (males only) and age, prevalence ratios (PRs) for triglycerides, high density lipoproteins, elevated blood pressure/hypertension, and fasting plasma glucose/diabetes showed patterns of increasing risk across BMI categories, with PRs of 1.3 to 1.7 M and 1.2 to 2.1 F in the BMI 30+ category. Results were similar for waist circumference categories. Overall, the risk gradient is less apparent than observed in western populations, likely due to the high prevalence of these risk factors in normal weight groups.
Prospective analysis of the formulation of country‐level plans of a regional health partnership
Authors: Gonzalez Wendy , Frongillo Edward A , Thrasher James F 
Published: June 2021

Reducing malnutrition, which contributes to more than one third of all deaths in children under age 5, is currently an urgent global priority. Global Health Partnerships (GHPs) work together with country partners in the formulation of action plans that address pressing health challenges such as malnutrition. Formulation of country action plans is often a contentious process. The successful formulation of an action plan occurs when the process pursues goals of feasibility, alignment, and ownership. We prospectively examined the formulation of two country‐level action plans of a regional health partnership in Latin America, and assessed whether these three goals were pursued. Data were collected using participant observation of key events; semi‐structured, in‐depth interviews with involved actors; and document review. We found that, although a GHP can promote feasibility, ownership, and alignment, the country context is a key determinant of whether these goals can be reached. Lack of nutrition plans and aims, weak leadership of the Ministry of Health, and an upcoming political transition were factors that prevented attainment of these three goals. By recognizing that a complex context can delay or impede the attainment of these goals, GHPs can be responsive to the country‐specific challenges, devise appropriate procedures to address them, and adapt expectations to the context.Grant Funding Source: None
A Study of the Effects of the Delivery System on the Efficacy of the Probiotic Bifidobacterium animalis subsp. lactis BB‐12 in Mediating Colonic Transit Time and Improving Immune Function
Authors: Holligan Simone , Roberts Robert F. , Kris‐Etherton Penny M. , Fleming Jennifer A. , Ba Zhaoyong , Polizzano Kimberley E. , Furumoto Emily J. , Rogers Connie J. 
Published: June 2021

Probiotics are functional ingredients that may act independently of the matrix used to deliver them to the human host. In this controlled, crossover, free‐living study we are evaluating the efficacy of the probiotic bacterium Bifidobacterium animalis subsp. lactis BB‐12 (B. lactis), delivered in a yogurt smoothie (organism added before or after fermentation), or as a supplement (tablet), by assessing colonic transit time (CTT) and markers of immune function. B. lactis is given at a dose of log 10± 0.5 CFUs/day. Treatment periods are 4 weeks long, followed each by a 2‐week washout period. Participants include healthy adults (Age: 18–40 years; BMI: 20–35 kg/m2) with a baseline CRP level of < 2.0 mg/dl. Mean CTT was 33.2 ± 12.8 hours at baseline as determined using the SmartPill® (N = 6). Phenotyping of peripheral blood mononuclear cells by flow cytometry showed that, at baseline, participants had 67.0% T cells (with 43.5% CD4 and 20.5% CD8), 9.8% CD19+/HLA‐DR+ B cells, 0.87% CD11c+/HLA‐DR+/CD123+ dendritic cells, 6.0% CD15+/CD11b+ granulocytes, 9.8% CD14+/HLA‐DR+ monocytes, and 7.6% CD56+/CD3− NK cells, on average (N = 3). Mean NK cell cytotoxicity was 9.5% ± 11.36% (range 0 – 29.81% cytotoxicity at 100:1 E: T ratio) at baseline (N = 6). Post‐treatment changes in CTT and immune function from baseline will be determined to elucidate whether B. lactis and the vehicle used for its delivery influences its performance.Grant Funding Source: The Dairy Research Institute
Effects of unsaturated fatty acids (USFA) on human gut microbiome profile in a subset of canola oil multicenter intervention trial (COMIT)
Authors: Pu Shuaihua , Khazanehei Hamidreza R , Krause Denis O , West Sheila G , Kris‐Etherton Penny M , Jenkins David J , Lamarche Benoît , Jones Peter J , Khafipour Ehsan 
Published: June 2021

The effects of USFA treatments on gut microbiome profile were studied in 25 subjects (13 obese, 9 overweight, 3 normal) in a double‐blinded randomized crossover study consisting of five 30 d periods. Treatments included 60 g of canola oil (63% MUFA, 20% LA, 10% ALA), high oleic canola oil (72% MUFA, 15% LA, 2% ALA), high oleic canola/DHA oil (64% MUFA, 13% LA, 6% DHA), corn/safflower oil (18% MUFA, 69% LA) and flax/safflower oil (18% MUFA, 38% LA, 32% ALA). Stool samples were collected at the end of each period. DNA was extracted and amplified for pyrosequencing. Sequences were edited and taxonomically classified using mothur software and Silva database. Categorical data were analyzed using GLIMMIX of SAS and PLS‐DA of SIMCA. A total of 17 phyla and 195 genera were identified. The USFA treatments did not affect microbiome at the phylum level. However, obese participants had a higher proportion of Firmicutes to Bacteroidetes than overweight or normal groups (P<0.05). At the genus level, three MUFA diets increased Clostridiales, Parabacteroides, Prevotella, and Turicibacter's population. Anaerostipes, Coprobacillus, and Faecalibacterium population were greater in high oleic canola oil compared to that in high oleic canola/DHA oil. Data suggest that obesity was associated with the decline in Bacteroidetes while USFA consumption only affected the microbiome at the genus level.Grant Funding Source: ARDI