bluuebunny/crossref_metadata_2025_split huggingface dataset:
Push‐pull thermoregulatory control by raphé‐projecting preoptic neurons?
Authors: Tanaka Mutsumi , McKinley Michael Joseph , McAllen Robin Michael 
Published: June 2021

Cutaneous vasoconstriction is tonically regulated by preoptic neurons (Tanaka et al 2009, Am J. Physiol 296, R1248‐57) via a pathway that relays synaptically in the medullary raphé but not in the dorsomedial hypothalamus (Rathner et al 2008, Am J. Physiol 295, R343‐54). We sought to identify the preoptic neurons responsible for this function in 28 urethane‐anesthetized rats (1–1.5g/kg, i.v.). Extracellular unit recordings were made from 40 preoptic neurons that were antidromically activated by electrical stimulation in the medullary raphé. The neurons’ ongoing activity was measured during episodes where trunk skin and core temperatures were manipulated by passing cold or warm water through a jacket around the animal's trunk. Frontal EEG was recorded at the same time. Seventeen preoptic‐raphé neurons were unresponsive to temperature, and a further four cells gave responses that were secondary to changes in EEG state. Seven preoptic‐raphé neurons behaved as expected for neurons regulating cutaneous vasonstriction: they were tonically active in warm conditions but were inhibited by cooling the trunk skin. Unexpectedly, twelve preoptic‐raphé neurons were activated by cooling the trunk skin. Both ‘warm’ and ‘cold’ preoptic neurons thus project directly to the medullary raphé, and we speculate that both contribute to the control of cutaneous vasoconstriction.Supported by NHMRC
Role of PPARα in the regulation of glutathione metabolism
Authors: Guelzim Najoua , Huneau Jean‐François , Tomé Daniel , Hermier Dominique 
Published: June 2021

Glutathione (GSH) derives from cysteine and plays a key role in redox status. GSH synthesis is determined by the availability of cysteine (from the diet or derived from methionine) and by the activity of rate limiting enzyme glutamyl‐cysteine synthase (GCS). Because PPARα has been shown to regulate the secondary metabolism of certain amino acids, GSH synthesis from cysteine was explored in fasted wild‐type (WT) and PPARα‐null (KO) male mice, fed on a semi synthetic standard diet. The concentration of plasma amino acids and of hepatic thiols was measured. Activity and mRNA levels of GCS were determined in the liver.Plasma cysteine concentration was identical in both groups, whereas that of methionine was 18% higher in KO mice. Hepatic GSH concentration was 40% higher in KO mice, whereas other thiols (cysteine, homocysteine and cysteinylglycine) were not affected. GCS activity of KO mice was 16% higher for specific activity and 52% higher for total hepatic activity.In contrast, PPARα deficiency did not affect GCS mRNA level. In conclusion, PPARα deficiency enhanced hepatic GSH storage, probably through an increased synthesis from cysteine. Thus, PPARα may influence the redox status by regulating cysteine metabolism. However, the absence of transcriptional regulation of GCS suggests a more complex control of GSH synthesis. Research support: Valorex & GLN (France).
Signal Transducer and Activator of Transcription 5 in Enterocytes Promotes Intestinal Mucosal Wound Healing by Regulation of Epithelial Tight Junction Assembly
Authors: Han Xiaonan , Gilbert Shila 
Published: June 2021

MethodsWe generated intestinal epithelial‐specific STAT5 knock out mice (STAT5 IEC KO) using cre‐mediated recombination to delete stat5 locus in IEC. STAT5 IEC KO mice were then treated with 3 % dextran sodium sulfate (DSS) either for seven days or for five days followed by 5 days of water. STAT5 IEC KO mice also exposed to NSAIDs chow for two weeks. We significantly knocked down GM‐CSF signaling and STAT5 expression in Caco‐2 and HT‐29 monolayer.ResultsSTAT5 IEC KO mice revealed an increased para‐cellular permeability and bacterial translocation in mesenteric lymph nude. STAT5 IEC KO mice were more susceptible to NSAIDs‐induced ileitis and DSS‐induced colitis, precluding mucosal healing after stopping DSS administration compared to littermate control mice (STAT5 IEC WT). Intestinal epithelial cells (IEC) monolayer exhibited a hyperpermeability under either GM‐CSF signaling or STAT5 knocking down; phosphoserine‐MLC was elevated and tight junction (TJ) assembly was disrupted in either IEC monolayer with STAT5 knock down or STAT5‐depleted IEC.ConclusionSTAT5 signaling in enterocytes is required for maintaining intestinal mucosal barrier function and promotes intestinal mucosal wound healing. Targeting on the activity of STAT5 signaling in enterocytes may be a novel therapeutic approach for treating intestinal barrier dysfunction in the sepsis and inflammatory bowel disease. This work was supported by Crohns and Colitis Foundation of America (XH), CCHMC Trustee Award (XH) and NIH clinical and translational research award KL2 (RR026315, XH).
Scaling in the primate masticatory apparatus
Authors: Holmes Megan A , Ruff Christopher B , Deleon Valerie B , Brown Kirsten M , Frohlich Bruno 
Published: June 2021

Scaling patterns within the primate masticatory complex have been the focus of a number of comparative and evolutionary studies. The aim of this study was to further elucidate the mechanical factors influencing the scaling of primate mandibular strength and molar area. It is hypothesized that cross‐sectional strength properties of the mandibular corpus will scale isometrically to estimated mandibular bending moments (size) and that both M1 and M2 occlusal area will scale with isometry to both strength properties and bite force estimates. Computed tomography scans of adult Macaca (n=18) and Papio (n=16) were used to collect mandibular bending rigidity (Ix, Iy) and strength (Zx, Zy) properties. Molar area was calculated at the dento‐enamel junction. Genera were chosen for divergent body size, similar diet and close phylogenetic association.Results indicate that when mandibular strength properties are compared to size indices both macaques and baboons scale with mechanical isometry. In contrast, molar area displays negative allometric trends in relation to strength properties and estimated bite force. This is most likely the result of diverse selective pressures acting on different elements of the masticatory complex. While mandibular cortical bone and cross‐sectional areas are highly responsive to functional demands and adapt to rapid changes in size, molar area is more genetically constrained.
Role of PS Product Inhibition in Accumulation of Phosphatidylserine (PS) in Neuronal Membranes
Authors: Kimura Atsuko Kakio , Kim Hee‐Yong 
Published: June 2021

PS is a major membrane component in mammalian tissues. Neuronal tissues are highly enriched with docosahexaenoic acid (DHA, 22:6n‐3) and PS in comparison to non‐neuronal tissues. Such concentration of DHA and PS is known to be important for proper neuronal functions. In mammalian cells, PS synthase (PSS) 1 and 2 catalyze PS synthetic activity, which is inhibited by the product PS through the feedback mechanism. We have previously found that DHA containing PS species (DHA‐PS) highly accumulates in neuronal membranes mainly due to the substrate preference in PS synthesis towards DHA phospholipid species. To understand the biochemical mechanisms underlying enrichment of PS in neuronal membranes, we hypothesized that fatty acyl composition‐dependent product inhibition in PS synthesis also plays a role in PS accumulation. We found that DHA‐PS has weaker inhibitory effect compared to oleic acid (OA, 18:1n‐9) containing PS species (OA‐PS) when tested with mouse liver microsomes. Consistently, DHA‐PS inhibited PSS activity less effectively than OA‐PS when flag‐PSS2 were expressed in mammalian cells, successfully immuno‐purified, and subsequently used as an enzyme source. DHA‐PS as a weaker inhibitor of PSS together with the high specificity towards DHA‐PS synthesis may contribute to the high PS accumulation in neuronal membranes.Intramural Program of National Institutes of Health
I'm a PC (Pyruvate Carboxylase)…and diabetes was not my idea!
Authors: Andera‐Cato S , Arnold A. , Bach S. , Faught A. , Frisch E. , Her A. , Keller A. , Kennedy E. , Martin T. , McMurray D. , Mitch C. , Orozco C. , Rice C. , Roberts B. , Rodgers A. , Sauer A. , Schulman A. , Suggs A. , Surfus K. , Tucker S. , Wray T. , Vogt G. , St. Maurice M. 
Published: June 2021

NIH estimates that 23 million Americans have diabetes, and 6.2 million are undiagnosed. If untreated, diabetes can cause complications, including heart disease and neuropathy. Type two diabetes patients cannot regulate glucose due to insulin resistance or deficiency. Pyruvate carboxylase (PC) plays an important role in insulin release from pancreatic β cells. Abnormal PC activity has been correlated with type two diabetes. PC is a dimer of dimers, each monomer a single chain with four domains: N‐terminal biotin carboxylase (BC), central carboxyltransferase (CT), C‐terminal biotin carboxyl carrier protein (BCCP), and allosteric domains. PC catalyzes the conversion of pyruvate to oxaloacetate (OAA). The process begins when biotin is carboxylated at the BC active site. The BCCP domain transfers the carboxybiotin to an active site in the CT domain. OAA is formed at the CT domain by adding a carboxyl group to pyruvate. Researchers concluded that the BCCP domain swings between active sites on opposite chains, instead of sites on the same chain. The Brown Deer SMART Team (Students Modeling A Research Topic), in collaboration with MSOE, built a model of PC using 3D printing technology illustrating this movement of the BCCP domain. Current research is focused on increasing PC activity through controlling a binding site in the allosteric domain, which may increase insulin production.Supported by a grant from NIH‐NCRR‐SEPA.
Tissue injury by microbeam irradiation depends on the stage of vascular maturation
Authors: Sabatasso Sara , Laissue Jean Albert , Hlushchuk Ruslan , Bräuer‐Krisch Elke , Bravin Alberto , Blattmann Hans , Djonov Valentin 
Published: June 2021

PurposeThe aim of this study is to explore the effects of Microbeam Radiation (MR) on vascular biology using the chick chorio‐allantoic membrane (CAM).MethodsCAMs were irradiated with multiple planar synchrotron X‐ray beams at doses between 100 and 300 Gy and were evaluated morphologically and in vivo at days 8 and 12.ResultsIn vivo monitoring and morphological investigations of day 8 CAM immature vasculature 6 hr after MR revealed a near total destruction of the capillary plexus within the beams’ width. Surprisingly, arteries and veins were not affected. Conversely, at day 12, only well defined lesions in the microvasculature (mature ones, covered by pericytes) were observed.After 300 Gy MR, TEM revealed enlargement of the interendothelial cell junctions which could explain the oedema, the microvessels along the beam path showed signs of disruption and apoptosis. The remaining vasculature recovered rapidly and CAM regained its normal thickness. Between 1 hr and 6 hr no additional morphological changes were observed.Conclusions
The effects of MR are most likely mediated by capillary damage.
The vascular toxicity of MR depends on the stage of capillary maturation: the immature vessels are much more vulnerable than the mature ones.
The physiological effects of MR appear within a short time, the most important structural alterations being present between 15 and 60 minutes after irradiation.
Signalling pathway of prostate‐specific membrane antigen implicates different types of detergent‐resistant membranes
Authors: Schmidt Sonja , Heine Martin , Naim Hassan Y. 
Published: June 2021

Prostate‐specific membrane antigen (PSMA) is a surface protein overexpressed in prostate cancer and neovasculature of further tumours. It is therefore one of the most promising biomarkers in diagnosis and treatment of prostate cancer.PSMA is associated with detergent‐resistant membranes (DRMs). The mature form of PSMA is mainly insoluble in Lubrol WX, but does not associate with Triton X‐100 DRMs.Recently we could demonstrate that cross‐linking of cell surface PSMA with specific antibodies activates different signalling cascades like the MAPK‐pathway. Here we show that internalization of PSMA is increased after antibody binding and this leads to redistribution of PSMA to Triton X‐100 DRMs in a time‐dependent manner.Our results propose an essential role for different DRM types in the signalling pathways involving PSMA.
Characterization of two synthetic ligands of peroxisome proliferator‐activated receptor γ (PPARγ) by cofactor recruitment, site‐directed mutagenesis and structure analysis
Authors: Crestani Maurizio , Mitro Nico , Gilardi Federica , Scotti Elena , Pochetti Giorgio , Lavecchia Antonio , Novellino Ettore , Fracchiolla Giuseppe , Laghezza Antonio , Tortorella Paolo , Aschi Massimiliano , Mazza Fernando , Montanari Roberta , Loiodice Fulvio 
Published: June 2021

In this study we report the behavior of two PPAR enantiomeric ligands (R‐1 and S‐1). Cell‐based reporter assays indicate that both enantiomers are dual PPARα/γ ligands, being R‐1 a full agonist of PPARα and γ and S‐1 a partial agonist of PPARγ. 3D‐structure analysis of the PPARγ ligand binding domain in the complex with the two ligands shows that the suboptimal conformation of helix 12 in the PPARγ/S‐1 complex is the consequence of a steric hindrance between the ethyl group of the ligand and the Q286 in helix 3. Site‐directed mutagenesis confirms that Q286 is a key residue in determining the activity of different ligands. By using FRET assays, we found that the coactivators SRC‐1, PGC‐1α, RIP140, TIF‐2 are recruited by R‐1, S‐1 and rosiglitazone with similar EC50, whereas CBP affinity is higher in the presence of rosiglitazone. Conversely, only S‐1 allows the association of the corepressor N‐CoR to PPARγ as opposed to rosiglitazone and R‐1, providing a functional explanation to the partial agonist behavior of S‐1. ChIP assays confirmed that S‐1 enhances the association of N‐CoR to PPARγ target promoters in the native chromatin context, whereas rosiglitazone and R‐1 recruit less N‐CoR. Altogether, our results provide a rationale for the distinct behavior of different PPAR ligands.Supported by CARIPLO Foundation, Harvard‐Armenise Foundation
ELEMENTAL IMAGING OF HUMAN EMBRYONIC STEM CELLS
Authors: Finney Lydia , Wolford Janet , Jin Qiaoling , Chishti Yasmin , Ward Jesse , Vogt Stefan , Chen Liaohai 
Published: June 2021

A critical aspect of understanding human embryonic stem cell (hESC) differentiation is regulation of protein activity. After all, it is by selectively activating and inhibiting various proteins that cells are able to proliferate and differentiate. One way Nature achieves this is by changing the availability of the metal ions that activate or inhibit existing proteins. An estimated one third of all proteins bind metal ions which play numerous critical cellular roles including as cofactors for enzymatic reactions, structural nuclei for protein folding motifs, and various signaling pathways.We are elucidating the role of metals in the dynamic cellular process of hESC differentiation at a systems level and developing analytical tools applicable to any cellular system in which metal ions play such roles. Combining existing molecular and cell biology approaches with cutting‐edge x‐ray fluorescent capabilities at the APS, we are currently investigating dynamics in metal ion distribution across stem cell colonies upon induction of differentiation, seeking a paradigm for the role of metal ions in developmental biology. We find that cellular zinc levels may serve as a biomarker of differentiation, indirectly correlating with the expression of pluripotency markers.
Targeting protein‐protein interaction networks: Structural genomics of FeS cluster assembly and human cancer biology
Authors: Montelione Gaetano T 
Published: June 2021

The NESG is one of four Large‐Scale Centers of the NIGMS Protein Structure Initiative (PSI). A key goal of the PSI is to generate 3D structures for some 5,000 proteins selected using broad biological, genomic, and bioinformatics criteria, together with targets selected from specific biological theme projects, so as to provide significant structural coverage of a large number of protein sequences in nature. The PSI also develops new methods for protein structure analysis, and proactively disseminates these technologies to the broader biological community. Our efforts span three classes of proteins: (i) selected to provide course‐grained coverage of large protein domain families; (ii) nominated in collaborations with the biomedical research community; and (iii) NESG Biomedical Theme of ‘Networks of Proteins Associated with Human Cancer and Developmental Biology’. NESG technology development emphasizes: (i) new technologies for production of proteins, (ii) new methods for protein NMR; (iii) hybrid approaches exploiting synergies of crystallography, SAX, NMR, and computational prediction, and (iv) improved methods for crystallizing proteins. This technology development is driven by our Biomedical Theme focus on human proteins, including protein complexes associated with cancer biology. The many structures, reagents, methods and technologies developed in this project provide starting points for traditional hypothesis‐driven biological research, and provide powerful, broad‐impact infrastructure for biological science and engineering.Supported by Natl. Inst. of General Medical Sciences
Pantesin, an Active Derivative of Vitamin B5, Used as a Nutritional Supplement, Significantly Lowers Cardiovascular (CV) Disease Markers in Low to Intermediate CV Risk North American Subjects: A Triple‐Blind Placebo/Diet Controlled Study
Authors: Rumberger John Arthur , Evans Mal , Napolitano Joseph J , Azumano Isao , Kamiya Toshikazu 
Published: June 2021

Serum cholesterol (C), LDL‐C, non‐HDL‐C, and apolipoprotein B (apo‐B) are well established risk markers for CV disease. The effect (and safety) of Pantesin (Daiichi Fine Chemicals) versus placebo on these risk markers was studied in 120 subjects (n=60/group) who were low to intermediate CV disease risk (NCEP ATP III) at screening. All subjects completed a 4 week diet lead‐in (TLC – Therapeutic Lifestyle Change) prior to randomization (baseline). Results for LDL‐C:

LDL‐C (mg/dL)
Screening
Baseline
4‐weeks
8‐weeks
16‐weeks

Placebo
115±26
108±25
112±28
114±29
115±27

Pantesin
112±24 (NS)
112±31 (NS)
104±27*
104±28*
108±30*

= p≤0.005
NS = non‐significant; data are mean±SD

ConclusionPantesin supplementation for 16 weeks (600 mg/d for 8 weeks then 900 mg/d for 8 weeks) significantly lowered LDL‐C as well as apo‐B (p=0.010) and non‐HDL‐C (p<0.001) over and above the effect of TLC diet alone. Pantesin was well tolerated with no differences between groups in adverse events. These results are noteworthy as prior studies have shown each 1 mg/dL reduction in LDL‐C lowers CV risk by 1%.
Identification of Peptides Derived from Azuki Bean (Vigna angularis) which Stimulate Cholecystokinin Secretion from the Enteroendocrine STC‐1 Cells
Authors: Sufian Md. Kaosar Niaz Bin , Hira Tohru , Hara Hiroshi 
Published: June 2021

ObjectivesWe found appetite‐suppressive peptides through cholecystokinin (CCK) secretion in vivo from a peptic digest of soybean β‐conglycinin. Later we found that peptic digest of dolicholin, a newly identified protein in country beans (Dolichos lablab), similar to β‐conglycinin, more potently stimulate CCK secretion from enteroendocrine cells. Our present study aimed to screen new CCK‐releasing peptides from beans that exist with homologous protein to dolicholin and to identify the active peptides therein.MethodsFive kinds of beans were hydrolyzed with pepsin and were examined for CCK‐releasing activities in the enteroendocrine cell line STC‐1.ResultsPeptones prepared from azuki bean (ABP), mung bean (Vigna radiata) and country bean containing closely homologous protein were potent to stimulate CCK secretion in the STC‐1 cells, with the highest activity by ABP. Acetonitrile soluble peptides in ABP stimulated CCK secretion, and pronase treatment abolished its activity. Average molecular size of ABP was estimated to be ~3 kDa, and fractions containing 3–5 kDa peptides showed highest CCK‐releasing activities.ConclusionsThese results indicate that peptides in ABP are potent to stimulate CCK secretion and also suggest that the CCK‐releasing peptides are derived from protein similar to dolicholin.(This research was supported by Japan Society for the Promotion of Science).
Long‐term effects of honey versus sucrose on glucose, insulin and lipid responses in mice
Authors: Jennings Tabitha , Nemoseck Tricia , Cole Sarah , Kern Mark 
Published: June 2021

We recently investigated the potential health benefits of honey as a substitute for refined sugars and demonstrated that compared to sucrose, honey may produce lower serum triglyceride, glucose and insulin concentrations over a short‐term period. Our goal was to determine the influence of honey versus sucrose on adiposity and plasma concentrations of insulin, glucose and lipids in two groups of weanling mice after a long‐term period. Eighteen male weanling ICR mice (29.7 ± 0.6 g) were equally divided into two groups and fed ad libitum one of two isoenergetic diets differing only in the carbohydrate source provided. Diets contained 20% carbohydrate (by weight of total diet) from clover honey or sucrose. After 116 days, fat pads were removed and blood was collected. No differences (p > 0.05) were found for weight gain, fat pad weights, glucose, insulin and triglycerides concentrations between honey and sucrose fed mice. Total cholesterol tended to be lower in the honey fed mice (p=.078). The results suggest that consuming honey instead of sucrose may potentially promote lower cholesterol over a long term period, but that benefits observed after shorter term feeding did not persist in growing ICR mice.Sponsored by American Heart Association
Anemia and iron deficiency prevalence in Mexican adolescents. Results from the national probabilistic survey ENSANUT 2006.
Authors: De la Cruz Góngora Vanessa , Villalpando Salvador , Gaona Berenice , Shamah Teresa , Mundo Verónica , Robledo Ricardo 
Published: June 2021

ObjectiveTo describe the anemia and iron deficiency prevalence in Mexican adolescents.MethodsNational probabilistic sample. The data of 3000 adolescents (12–19 years of age) was analyzed. Hemoglobin concentration was measured by capillary blood. Commercial kits were used to measure the serum concentrations of ferritin. Iron deficiency was defined as ferritin concentration <12 mcg/L. Iron deficiency and anemia predictors were evaluated with logistic regression models.ResultsAnemia prevalence among adolescents was 11.5%, there was no differences by sex. The national iron deficiency prevalence was 13.6%, and it was higher among women (13.38%) than men (9.28%). When stratifying by age (younger or older than 15 years of age), the iron deficiency prevalence in men declined (11.32 vs 7%) and in women increased (14.8 vs 21.9%). The odds of being anemic increased by 3 folds in iron deficient adolescents compared to the non‐deficient (p<0.001).ConclusionsAnemia and iron deficiency are still being a health problem in Mexican adolescents. The women and the adolescents from the southern zone of the country have the largest prevalence of iron deficiency.