bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pyruvate‐enriched Ringer's resuscitation bolsters cytoprotective defenses in reperfused hindlimb in the setting of hemorrhagic shock
Authors: Flaherty Devin C , Hoxha Besim , Sun Jie , Simecka Jerry W , Olivencia‐Yurvati Albert H , Mallet Robert T 
Published: June 2021

HypothesisResuscitation with Ringer's solution containing pyruvate, an antioxidant and anti‐inflammatory metabolite, may mitigate hindlimb ischemia‐reperfusion injury in the setting of hemorrhagic shock.MethodsIsoflurane‐anesthetized male goats were hemorrhaged to lower mean arterial pressure (MAP) to c. 50 mmHg, then the right femoral artery and vein were occluded for 90 min. Lactate‐ (LR) or pyruvate‐fortified Ringer's solution (PR) was infused iv (10 ml/min) from 30 min occlusion until 30 min after release of occlusion. At 4 h post‐occlusion, gastrocnemius was biopsied for analyses of antioxidative enzymes (spectrophotometry) and pro‐ and anti‐apoptotic proteins (actin‐normalized immunoblot). Results [*P < 0.05 vs. sham; †P < 0.05 vs. LR]: At 4 h post‐occlusion, MAP (mm Hg) was better maintained following PR (64 ± 6 †) than LR (44 ± 4). PR increased activities (mU/g) of antioxidant enzymes glutathione reductase (Sham 4.1 ± 0.2, LR 6.9 ± 0.7*, PR 9.8 ± 1.0* †) and glutathione peroxidase (Sham 11.3 ± 2.7, LR 14.0 ± 0.9, PR 17.4 ± 1.2* †). PR also stabilized muscle contents of the antiapoptotic protein Bcl‐XL (Sham 1.95 ± 0.02, LR 1.25 ± 0.12*, PR 1.77 ± 0.15 †) and the ratio of uncleaved (i.e., inactive)/cleaved (i.e., pro‐apoptotic) poly‐ADP ribose polymerase (PARP) (Sham 3.53 ± 0.57, LR 2.27 ± 0.23*, PR 3.90 ± 0.44 †).ConclusionsRelative to conventional LR, resuscitation with PR more effectively stabilized MAP, bolstered the ischemic hindlimb's antioxidant and anti‐apoptotic phenotype. Funding: U.S. Dept. of Defense
The effects of prenatal lipopolysaccharide on cardiac function
Authors: Han Bing , Huang Hong , Schanbacher Brandon L , Bauer John A , Giannone Peter J 
Published: June 2021

Low birth weight has been strongly associated with cardiovascular disease in adulthood. The first report of poor maternal nutrition being associated with cardiovascular disorders in offspring was from Dr. David Barker who showed that people had an increased risk of death from cardiovascular disease if they were small at birth. There is also substantial evidence that maternal infection/inflammation are likely contributors to low birth weight. We tested the hypothesis that prenatal exposure of lipopolysaccharide (LPS) decreases cardiac function in adulthood.Pregnant C57BL/6J mice were treated with a single dose of LPS (2 ug/mouse) i.p. or vehicle at gestation E16. Basal cardiac performance and responses to stress (isoproterenol, 2.5 mg/kg, ip) were determined in male offspring at 8 weeks with echocardiogram. Offspring were sacrificed and cardiac tissues were collected.Compared with the control group, offspring of LPS‐treated dam had slower growth rate (body weight at 8w: 22.1±1.3 vs. 24.6±2.1g, p<0.05) with decreased cardiac output (CO, 21.8±3.9 vs. 25.7±2.1 ml/min, p<0.05), signifying an impaired cardiac contractility. In addition, offspring with prenatal LPS exposure seemed to have less increase of CO after stress test, suggesting a decreased cardiac reserve.Our data suggest that prenatal inflammation has long term effects on cardiac function. Further mechanistic studies are undergoing.
Role of Rh (rhesus) complex in K‐Cl cotransport (KCC) regulation in red blood cells (RBCs) of Rh and Rh‐associated glycoprotein (RhAg) knockout (KO) mice
Authors: Lauf Peter K. , Adragna Norma C. , Goossens Dominique , Cartron Jean‐Pierre 
Published: June 2021

The Rh blood group is a macromolecular complex of protein subunits (D and CE), RhAG, a NH3/CO2 gas transporter (PNAS 101:17222,2004; FASEB J 22;1,2008), and accessory proteins (ICAM‐4/LW, CD47 and GPB). In the mild hemolytic human Rhnull disorder, the Rh complex is absent/severely deficient. Altered K fluxes have been found in Rhnull RBC (Blood 48: 457, 1976). A double blind study on male (m) or female (f) wild type (WT), and Rh−/− and Rhag−/− KO mice (Transf Clin Biol 13:164,2006) studied: Total, ouabain (O)‐sensitive Na/K pump, O‐insensitive+bumetanide (B)‐sensitive Na‐K‐2Cl cotransport (NKCC), and O‐ and B‐insensitive KCC ± the thiol alkylant N‐ethylmaleimide (NEM), staurosporine (STP, a kinase inhibitor) and Mg removal by A23187.Results1) Total, Na/K pump, NKCC and basal KCC influx were not different between groups. 2) NEM activated KCC by >100 % (p<0.001) in both m/f Rh−/− and RhAg−/−, compared to WT. KCC activation by both STP, and Mg depletion (except for m Rh−/−), was similar in m Rh−/−, m/f Rhag−/− RBCs and WT.ConclusionThiol modification reveals a Rh‐complex role in KCC regulation, i.e. via protein phosphorylation or protein/protein interactions. However, unlike in human Rhnull RBCs, Na/K pump and passive K‐"leak" fluxes were normal, an apparent difference in the Rh complex‐K transport association between mice and man. Support in part by a WSU School of Medicine Grant.
The Phenotypes and Models Portal at RGD: a new interactive tool for physiologists linking genotype to phenotype and disease
Authors: Munzenmaier Diane H. , Dwinell Melinda , Nigam Rajni , Shimoyama Mary , Jacob Howard J. 
Published: June 2021

AimThe Rat Genome Database (RGD) has been developing tools and resources to aid investigators in the integration of genomic and phenomic data derived from rat research for the past 10 years. Recently, a new Phenotypes and Models Portal has been developed. Designed to be an entryway into RGD for physiologists, it allows access to phenotype data and disease model information for biomedical investigators doing rat research.MethodsRGD has always contained valuable information for physiologists, though the focus has been primarily on genomic data, making it somewhat challenging for physiologists to navigate. This portal provides new types of phenotype data, as well as different ways to access existing data in RGD, allowing extraction of data relevant to an investigator's research interests by specific organ system function or identification of suitable rat models for specific diseases. The Phenotypes branch provides access to phenotype data for cardiovascular, pulmonary, blood, biochemistry, renal, vascular measurements and general morphological results. The Strains and Models branch houses strain information, includes strain "medical records" and links to genotype and phenotype data.ConclusionThe Phenotypes and Models Portal promises to be an effective means to access and retrieve physiological data and disease model information for researchers using the rat as a model to study physiology and disease.
Comparison of sex hormones in ischemic‐reperfusion injury in isolated rat hearts
Authors: Balonan Lino , Das Rapti , Ho Susan , Wong Tak Ming 
Published: June 2021

To compare potential protective effects of testosterone and estrogen on myocardium, we exposed isolated rat hearts to 30 minutes of ischemia followed by 120 minutes of reperfusion. One group of rats served as normal controls (sham). The experimental group underwent either bilateral orchidectomy (Gx) or ovariectomy (Ovx). After one week post‐surgery, each group was further divided, and received either a 60‐day release implant containing testosterone (Gx+T; Ovx+T) or 17 β‐estradiol (Ovx+E; Gx+E). There was no statistically significant difference in the infarct size among these groups of rats.However, when noradrenaline (10−7M) was administered during the ischemic period, the infarct size was significantly greater in both the Gx (50.66 ± 1.80) and Ovx (52.03 ± 2.36) groups than in sham cohorts (38.63 ± 1.88 and 44.09 ± 1.68, respectively). Hormone replacement in these groups significantly reduced the infarct size to levels comparable to the corresponding sham groups (Gx: 42.06 ± 1.81 versus 38.63 ± 1.88 following testosterone treatment and 42.11 ± 1.51 versus 38.63 ± 1.88 following estrogen treatment; Ovx: 41.3 ± 2.185 versus 44.09 ± 1.68 with estrogen and 43.73 ± 1.66 with testosterone).Our results suggest testosterone imparts cardioprotection and plays an important role in determining the extent of cardiac injury in response to adrenergic stimulation during myocardial ischemia.
Osteological analysis of nonhuman remains: understanding the growth and developmental patterns of post‐crania
Authors: Lee Rosanna , Macsiaz Rachael , Hong Simon , Caceres Noel , Márquez Samuel 
Published: June 2021

Osteological analyses of human and nonhuman bones are essential in the forensic assessment of unknown commingled remains. T. Dale Stewart was one of the first to recognize the resemblance between human and nonhuman remains when he reported the similarity between human and North American black bear tarsal bones, reinforcing the importance and difficulty of discerning human from nonhuman bones. We report findings on commingled skeletal remains uncovered from a construction site in New York City. Preliminary assessment of the bones narrowed them to a cow distal femur, a deer fibula and a pig humerus. Further analysis of the cow femur showed a flattened plateau on the anterior surface, characteristic of a sub‐adult cow. In addition, it lacked the sloped trochlea apparent in adult femurs. At the joint surface, four condylar‐like bony projections were present, consistent with the removed epiphysis of a sub‐adult. A comparison of the characteristic anatomy of found bones with bones from the terrestrial mammalian collection representing 7 genera and 9 species from the Division of Mammalogy at the American Museum of Natural History confirmed our analysis. Our study demonstrates that knowledge of the origin of bones, as well as the developmental stages of the specimens, is critical towards the assessment of unknown remains for a just resolution and sound testimony in medical and legal investigations.Grant Funding SourceDo not have funding
An Anatomically Informed Approach to Transcutaneous Injection Laryngoplasty
Authors: Pearson Bill , Noordzij Pieter 
Published: June 2021

Injection larygoplasty medializes deinnervated vocal folds (VFs) by introducing bulking material into the thyroarytenoid muscle. Transcutaneous larygoplasty is preferable to a transoral approach in certain compromised patients, but accessing the VFs with this approach is a challenge for the inexperienced clinician. A geometric approach to consistently and accurately guide the needle to various locations along the VF was developed using cross sectional anatomy software. Pigment was injected into the VF guided by this approach without visualization in 4 female and 3 male cadavers. The vocal folds were then dissected and results recorded. Injections were effective in 11 of 12 tries when VF lengths were within the standard deviation of the mean and in abduction.Grant Funding Sourcen/a
Inhibition of Ras‐expressing Keratinocytes by De‐epidermized Dermis
Authors: Andrews Capri Michele , Vaughan Melville B. 
Published: June 2021

Cancer cells secrete matrix‐digesting enzymes allowing invasion and migration to other locations. Ras cells secrete similar enzymes, but their targets may be different than basement membranes. Our previous research showed that ras keratinocytes, when plated on a dermal layer, invade prior to basement membrane formation, and then appear to stop. Therefore, it can be determined if the basement membrane is a factor crucial in inhibiting invasion. To test this hypothesis, ras‐overexpressing keratinocytes were plated on de‐epidermized dermis (DED), consisting of a dermal compartment and a basement membrane. Plating on the dermis‐side was used as a basement membrane‐negative control. The tissues were fixed at 1, 7, 14, and 21 days for both frozen and paraffin sections. Invasion of keratinocytes was expected in the dermis‐side samples due to the absence of a basement membrane. Surprisingly, no invasion occurred in either condition until the 21‐day mark, where a correlation between invasion and the degradation of the basement membrane became evident. Epidermal differentiation, previously shown to be randomized in the earlier model, will be assessed to determine whether the environment can instruct cells.Grant Funding SourceResearch, Creative, and Scholarly Activities Grant
Twist and E47 regulate Snail promoter activity in palatogenesis
Authors: YU Wenli , Serrano Maria , Svoboda Kathy 
Published: June 2021

PurposeSnail is a key transcription factor in EMT (epithelial‐mesenchymal transition). Twist and E‐47 are bHLH (basic helix‐loop‐helix) transcription factors, which binds to E‐boxes and induce EMT. Several E‐boxes were present in Snail promoter region. Previously we showed downregulation Twist or Snail blocked EMT in palatogenesis. The objective of this study is to explore the interactions between these transcription factors and examine if Twist and E47 regulate Snail expression.Methods1.7K, 1.5K, 1.0K, 0.5k Snail promter‐luciferase constructs were co‐transfected with Twist, E47 overexpressing plasmids in MDCK cells. SV40‐Renilla luciferase plasmid was transfected to control the efficiency of transfection. Expression of Firefly and Renilla luciferases were analyzed 24h post‐transfection. Dual‐luciferase reporter assay was used to measure ‐ promoter activity according to the manufacturer's instructions.ResultsIn MDCK cells, Twist and E47 were required for different promoter fragment activation. Twist activated the 1.7K promoter to 12.5 fold and E47 activated the 1.0K promoter to 9 fold over controls. When cells overexpressed both Twist and E47, the 1.0K promoter activity increased to 10 fold.ConclusionTwist and E47 may be the upstream factors that regulate Snail expression by binding to the Snail promoter to induce EMT.Grant Funding SourceMarch of Dime
The molecular basis for transmission of human prion strains
Authors: Giles Kurt , Patel Smita , De Nicola Gian , Korth Carston , Lemus Azucena , DeArmond Stephen , Prusiner Stanley B 
Published: June 2021

Human prion diseases, such as Creutzfeldt‐Jakob disease (CJD), can occur in different "strains" which are characterized by their clinical onset, and by biochemical and neuropathological hallmarks of the post mortem brain. Human prion strain type is dramatically influenced by the M/V polymorphism at residue 129, with homozygous individuals much more likely to develop disease.We report a series of novel transgenic (Tg) mouse lines expressing various chimeras of mouse and human prion protein (PrP), which were inoculated with either of the two most common strains of sporadic (s) CJD, termed MM1 and VV2, or with the variant (v) CJD strain. The differential susceptibility for each strain allows a molecular dissection of the amino acid residues that influence strain propagation.One Tg line was susceptibility to sCJD(MM1) prions in less than 80 days, and defined six human PrP residues in the central region of the molecule that are essential for strain transmission. Conversely, for the sCJD(VV2) strain, transmission is regulated by residues in the terminal regions of the PrP sequence. Modification of strain characteristics on transmission of sCJD(VV2) and vCJD strains, also allowed us to formulate a general set of rules governing strain transformation.
CD36 Mediates a Pro‐inflammatory Signaling Loop in Fat and Contributes to Insulin Resistance
Authors: Kennedy David J , Silverstein Roy L , Febbraio Maria 
Published: June 2021

Scavenger receptor CD36 recognizes ligands generated in pro‐atherogenic hyperlipidemic (PA‐HL) states, including oxidized LDL (oxLDL). Systemic levels of oxLDL are highly associated with insulin resistance (IR). We hypothesized that CD36 ligands generated in PA‐HL states disrupt insulin signaling in adipocytes via CD36‐dependent signaling.CD36+ and CD36− mice were fed a high‐fat diet for 8 weeks and examined for markers of IR. Compared to CD36+, CD36− mice had improved glucose tolerance and both decreased JNK and inhibitory IRS‐1 serine phosphorylation in adipose tissue. Further, macrophages from CD36− mice demonstrated decreased production of ROS and proinflammatory cytokines, and increased arginase activity compared to cells from CD36+ mice.L1 adipocytes treated with oxLDL showed time and dose dependent increases in CD36, activated JNK, inhibitory IRS‐1 serine phosphorylation, and adipocyte lypolysis with decreased glucose uptake. Pre‐incubation with either a CD36 mAb or JNK inhibitor attenuated these changes. In addition, adipocytes co‐cultured with transwell separation from CD36− macrophages showed both decreased JNK and inhibitory IRS‐1 serine phosphorylation compared to those co‐cultured with CD36+ macrophages.These data suggest a CD36‐dependent paracrine loop between adipocytes and macrophages that facilitates chronic inflammation in adipose and underlies IR common to PA‐HL states.
The Protein Structure Initiative Structural Genomics Knowledgebase
Authors: Gabanyi Margaret , Westbrook John , Tao Wendy , Shah Raship , Kouranov Andrei , Schwede Torsten , Arnold Konstantin , Kiefer Florian , Bordoli Lorenza , Podvinec Michael , Kopp Jurgen , Adams Paul , Carter Lester , Minor Wladek , Nair Rajesh , La Baer Joshua , Berman Helen M. 
Published: June 2021

The Protein Structure Initiative (PSI) has produced more than 3300 protein structures in a high throughput manner. In order to achieve this, new technologies for all aspects of the structure determination and analysis pipeline have been developed. The strategies used for target selection by PSI centers have resulted in the structural determination of many novel sequences, and an increase in the structural coverage of protein families.The PSI Structural Genomics Knowledgebase (PSI SGKB) gives centralized access to the structures, annotations, models, protein production protocols, materials and technologies catalyzed by the PSI efforts. In collaboration with the Nature Publishing Group, the PSI SGKB expanded to become the Structural Genomics Gateway that provides a research library, editorials about new research advances and technologies, news, and an events calendar to present a broader view of structural biology and structural genomics. A description of how this resource can be used for enabling biological research will be given.The PSI SGKB is funded by the NIGMS.
Characteristics of short gel filtration columns for rapid screening of aggregates and impurities
Authors: Heijbel Anna , Salomonson Inger , Zuo Jinyu , Carlsson Marianne , Lundstrom Fredrik 
Published: June 2021

Gel filtration (GF) is a gentle technique suitable for the study of aggregation and purity of a target protein. GF, however, is often time consuming and can also be held up due to the expense of sample and buffers. A new, small (3 ml) column format packed with Superdex(tm) 75 and Superdex 200 has been developed for rapid and reliable gel filtration enabling analyses in less than 6 min using only 4 µl of sample.Results illustrating the resolution of a standard protein mixture, sensitivity, flow rate properties and influence of system dead volumes upon resolution will be shown. The short gel filtration columns will also be compared to the longer Superdex 75 and 200 10/300 GL columns.
Determining The Role of Subcellular Localization of Heterotrimeric G Protein βγ Subunits in a Trans Golgi Network‐To‐Plasma Membrane Vesicle Formation Pathway
Authors: Irannejad Roshanak , Wedegaertner Philip B 
Published: June 2021

Heterotrimeric G proteins are responsible for transducing signals initiated at the plasma membrane (PM) by G protein‐coupled receptors (GPCR). However, a number of recent studies indicate that G proteins can signal at endomembranes. Gβγ subunits have been implicated in activating protein kinase D through PKCη at the Golgi membrane to initiate a pathway causing fission of PM‐destined vesicles from Trans Golgi Network (TGN). Overactivation of these signaling components cause the complete fission of the Golgi, while inhibition of some of the components of this pathway decrease TGN‐to‐PM transport of proteins. What is not clear is the intracellular location(s) where Gβγ initiates this signaling pathway. Our data indicate that constitutively targeted Golgi‐βγ, but not PM‐, ER‐ and cytosolic‐βγ, induces complete fission of Golgi as visualized by fluorescent microscopy. Moreover, rapamycin‐inducible recruitment of Gβγ to the Golgi but not PM activates the TGN‐to‐PM vesicle formation pathway. Sequestration of Gβγ with the C‐tail of GPCR kinase 2 (GRK2ct) blocks the transport of two model proteins, GFP‐tagged vesicular stomatitis virus‐G protein (GFP‐VSV‐G) and HRP‐tagged N‐terminal signal sequence (ss‐HRP). The results identify a role for endogenous Gβγ at the Golgi in regulating vesicle transport.[Supported by NIH GM56444 and AHA 0815431D]
[beta]‐Carotene content and bioaccessibility from organic and non‐organic baby meals
Authors: Aherne‐Bruce Aisling , Jiwan Marvin A , Duane Paula , O'Sullivan Laurie , O'Brien Nora M 
Published: June 2021

Research data on the nutritional benefits to babies of consuming organic foods compared with their non‐organic counterparts is scarce. The objectives of the present study were first, to determine the β‐carotene content of organic and non‐organic baby food products; and, second, to compare the bioaccessibility of β‐carotene from these foods. Carotenoid bioaccessibility (%) is defined as the proportion of ingested carotenoid(s) that are available for absorption in the gut after digestion. Three organic (A‐C) and three non‐organic (D‐F) chicken and vegetable baby foods for babies of 4+ months of age were subjected to a simulated human gastrointestinal digestion procedure. Within each group (i.e. organic or non‐organic), there were large differences in β‐carotene content. For example, β‐carotene content of the organic dinners ranged from 8.8 to 534.9 μg/100 g. Similarly, non‐organic dinner F had significantly greater amounts of β‐carotene than the other t+wo non‐organic dinners tested. There was no difference in the average β‐carotene content between the organic and non‐organic foods. β‐Carotene bioaccessibility was greater from organic dinner C (46.4%) compared with organic dinners A and B (P<0.05). On average, β‐carotene had greater % bioaccessibility (P<0.05) from the non‐organic (41.4%) than organic (30.8%) chicken and vegetable dinners. Our findings show that β‐carotene content reflected the vegetable composition of the baby meals. To conclude, the organic dinners tested were not superior to the non‐organic foods in terms of β‐carotene content and bioaccessibility.This research was funded by Science Foundation Ireland.
An elevated protein diet does not accelerate initiation and early progression of MNU‐induced breast cancer tumors in rats
Authors: Moulton Christopher John , Valentine Rudy , Wallig Matthew , Monaco Marcia , Singletary Keith , Layman Donald 
Published: June 2021

There is growing interest in identifying nutritional factors that modify risk and development of breast cancer. This study evaluated the influence of feeding low vs. high protein diets (LP vs. HP) on measures of tumor incidence. LP and HP diets consisted of 60:15:25 (carbohydrate:protein:fat as % energy) and 40:35:25, respectively. Female SD rats ~140 g were injected intraperitoneally with N‐nitroso‐N‐methylurea (MNU) at 50 mg/kg, and subsequently fed 3 times/d for 10 wk to mimic human meal patterns. Body weight, food intake and tumor appearance/growth were monitored throughout the study. At 10 wk, rats were killed; serum insulin and IGF‐1, tumor size and pathology were evaluated. Food intake did not differ between groups but final body weight was 4% greater in HP. No differences existed in fasted or post‐prandial insulin, however post‐prandial IGF‐1 was significantly greater in HP. There were no differences in tumor latency, cumulative surface area, mass or stage of histological development. Although more LP animals (56%) had tumors than HP (40%), the difference was not significant (p = 0.19). Despite elevation of IGF‐1 in HP, this study fails to demonstrate any direct effect of normal levels of dietary protein or carbohydrate to exacerbate the initiation and early progression of breast cancer tumors.Support: Illinois Council on Food and Agricultural Research