bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunoregulation by the neurohypophysis
Authors: Quintanar‐Stephano Andrés , Villalobos Criseida , Arroyo Karla , Organista Alejandro , Tinajero Manuel , Chavira Roberto , Ventura Javier , Muñóz Martín , Campos Rafael , Reyna Humberto , Kovacs Kalman , Berczi Istvan 
Published: June 2021

The role of the neurohypophysial hormones on immunoregulation has not been completely elucidated. To obtain a deeper insight, groups of Lewis rats were subjected to sham operation (SHAM), anterior (AL) or neurointermediate pituitary lobectomy (NIL) or total hypophysectomy (HYPX) and immunized for adjuvant induced arthritis (AIA) or experimental autoimmune encephalomyelitis (EAE). Intact control groups were included for reference. Groups were sacrificed 15 days postimmunization. Serum levels of PRL, ACTH and AVP, and spleenic ILs mRNA expression and macrophages number were assessed. In the AIA experiment, SHAM animals showed normal PRL, ACTH and AVP serum levels, increased expression of ILs 1 and 12, no changes in the remaining ILs, and significant increase in macrophages number. In the AL rats, normal AVP and low PRL and ACTH serum levels occurred. Except TNFα, ILs‐1,‐2,‐6,‐10,‐12, INFγ and macrophages number were significantly increased. In NIL rats, low AVP and normal PRL and ACTH levels occurred, and no alterations in ILs expression and macrophages number were found. In HYPX animals, low PRL, ACTH and AVP were apparent, while ILs‐1 and ‐12 and macrophages number were significantly increased. In general, similar results were obtained in EAE groups. The results indicate that immune responses can occur in absence of the pituitary gland and that AVP is an important immunoregulator.Supported by UAA and CONACYT. México
Courses in modeling transport and metabolism in cardiovascular and respiratory systems
Authors: Raymond Gary M. , Butterworth Erik A. , Bassingthwaighte James B. 
Published: June 2021

Quantitative analysis is essential to integrate knowledge systematically from genome through molecular and cell biology to understand how organs and organisms function. On June 14–18, 2010 and August 23–27, 2010, the National Simulation Resource in the Department of Bioengineering, University of Washington, Seattle, is giving modeling courses on transport, pharmacokinetics and metabolism in cardiovascular and respiratory systems for clinical and research scientists. The focus is on approaches to data analysis, on using mathematical models for precisely defining hypotheses, designing experiments and evaluating the fitting of models to data. Participants are encouraged to bring data and models for group discussion. Starting with computer models from www.physiome.org/Models, participants will develop new models using standard tools including JSim, a simulation system for building and analyzing quantitative models. JSim runs on PC, Mac, and Linux platforms and is free and downloadable from www.physiome.org/jsim/download/.(Supported by NIH T15 HL088516.)
Essential roles of zinc finger factor epiprofin in tooth development
Authors: Nakamura Takashi , Yuasa Kenji , Jimenez Lucia , Unda Fernando , Koyama Eiki , Fukumoto Satoshi , Yamada Yoshihiko 
Published: June 2021

The precise reciprocal interaction between the dental epithelium and dental mesenchyme during tooth development is essential to the formation of teeth that are functional in shape and size. Epiprofin (Epfn), a transcription factor belonging to the Sp family, regulates dental epithelial cell proliferation and differentiation into ameloblasts. Epfn deficiency results in the formation of an excess number of teeth. To study the mechanism of epiprofin functions in tooth morphogenesis, we have used Epfn‐transfection in cell culture and K5‐Epfn‐transgenic mice, which expressed Epfn under the control of the epithelial cell‐specific promoter, keratin 5 (K5‐Epfn). Transient expression of Epfn stimulated the proliferation of dental epithelial progenitor cell line SF2, while stable expression of Epfn blocked cell growth and elevated the expression of ameloblast marker genes such as ameloblastin. We found that K5‐Epfn mice had fewer molars and developed an ectopic enamel layer in the incisors. Thus, the tooth phenotypes are opposite in Epfn‐deficient and K5‐Epfn mice. In K5‐Epfn mice, both proliferation and differentiation of the dental epithelium were accelerated. Taken together, these results suggest that Epfn functions to maintain the balance of dental epithelial cell proliferation and cytodifferentiation in tooth development.Grant Funding Source: Intramural Program of the NIDCR, NIH, and the Ministry of Education, Culture, Sports, Science and Technology of Japan
Developing Animal Models to Study Paranasal Sinus Function
Authors: McCullough Stephen Andrew , Reidenberg Joy S. , Laitman Jeffrey T. 
Published: June 2021

This study describes anatomic and volumetric differences of paranasal sinuses (PS) as a first step in developing in vivo models for PS function. Three species were used (N=4/ea): rats, Rattus norvegicus; guinea pigs, Cavia porcellus; and rabbits, Oryctolagus cuniculus.Methods includedpostmortem dissection of each maxillary sinus (MS); measurement of hard palate length (HPL) to standardize for splanchnocranial differences; and measurement of MS volume (MSV) by filling with 70% ethanol after lateral wall perforation with a syringe.Anatomic results1) rat MS ostium is identifiable upon nasal septum removal, while in guinea pigs and rabbits, MS ostia are covered by the middle concha; 2) MS of rats and rabbits have thin lateral walls, and are easily accessible upon syringe perforation, whereas the guinea pig MS is considerably smaller with a thicker lateral wall, making entry more difficult.Volumetric results1) MSV correlates with HPL (r2=0.7307, N=3/species) across species; 2) species vary in mean MSV/HPL ratio significantly (p<0.0001) as expected from splanchnocranial differences.DiscussionAlthough differences exist, each species can model PS function depending on the approach. Data suggest MSV is related to cranial size and, by extension, physiologic demand of the animal. This phase provides foundation for selecting models to test hypotheses of PS function and implication in disease.Grant Funding Source: Mount Sinai Research Fellowship
Influence of different types of diets and a protocol of aerobic exercise on the mechanical properties of bones
Authors: Okubo Rodrigo , Leonardi Daphne Santoro , Fernandes Cleverson Rodrigues , Falcai Maurício José , Frajacomo Fernando Tadeu Trevisan , Fazan Valéria Paula , Shimano Antônio Carlos , Volpon José Batista , Jordão Alceu Afonso , Garcia Sérgio Britto 
Published: June 2021

The purpose of this study was to evaluate the effects of different types of diets and the swimming exercise in tibias of rats. This study was approved by Ethical Committee in Animals Experiment. Sixty three‐month‐old male Wistar rats were randomly assigned to six groups (n=10): (G1) control AIN‐93 diet sedentary, (G2) control AIN‐93 diet aerobic training, (G3) high‐fat diet sedentary, (G4) high‐fat diet aerobic training, (G5) high‐fat‐protein diet sedentary, (G6) high‐fat‐protein diet aerobic training. Control diet is AIN‐93. The total caloric values of control, high‐fat and high‐fat‐protein diet is respectively 394.8 kcal, 609.8 Kcal, 609.8 Kcal for 100g of diet. Physical exercise consisted of swimming on a large aquarium. Rats swam 5 days a week, 60 minutes, during 8 weeks. Tibias were dissected and tested in a universal testing machine. Data were analyzed using specific tests; level of significance was set at 5%. Mean values of maximum load for groups: G1 (40.5±5.6)N, G2 (44.8±7.4)N, G3 (64.2±4.1)N, G4 (53.3±9.4)N, G5 (48.5±10.8)N and G6 (47.4±7.1)N. Data from our study suggest that a diet programs may influence bone resistance however changing its body weight.Grant Funding Source: FAPESP
Bears May Maintain Bone Strength During Hibernation by Reducing Osteoblast Response to Apoptosis
Authors: Bradford Rachel Marie , Gray Sarah , Heiden David , Henriksen Kim , Gundberg Caren , Tsai Chung‐Jui , Donahue Seth 
Published: June 2021

Despite annual periods of disuse lasting up to 6 months (hibernation), black bears (Ursus americanus) maintain bone mechanical strength throughout life. Our objective is to determine the mechanism responsible for this maintenance.METHODSSerum from 6 captive black bears was collected every 10 days from the fall active (October) through the spring active season (April), fully encompassing hibernation. Osteoblasts were cultured in 2% bear serum, and cell responses were quantified.RESULTSCompared to active seasons, hibernation serum exhibited a 57% decrease in bone specific alkaline phosphatase (p<0.0001) and a 29% decrease in Tartrate Resistant Acid Phosphatase (p<0.0001). Compared to osteoblasts cultured in active serum, those cultured in hibernation serum exhibited reduced gene expression of CyclinD1 (p=0.0244) and had 36% less caspase‐3/7 activity after serum starvation (p<0.0001). The caspase response (R2adj=0.34) and CyclinD1 expression (R2adj=0.32) were negatively and positively correlated to serum creatinine, respectively.CONCLUSIONSerum markers suggest a decrease in bone turnover during hibernation. Furthermore, serum from hibernating bears seems to decrease osteoblast apoptosis.
Non‐myeloablative autologous HSCT for relapsing remitting multiple sclerosis (RRMS) and new onset type 1 diabetes mellitus (TIDM)
Authors: Burt Richard 
Published: June 2021

Autologous non‐myeloablative hematopoietic stem cell transplantation (HSCT) is a method of delivering intense immune suppression. We, therefore, evaluated the safety and clinical outcome of autologous non‐myeloablative HSCT in 2 autoimmune diseases relapsing‐remitting multiple sclerosis (RRMS) failing interferon therapy and new onset Type 1 Diabetes mellitus. Peripheral blood hematopoietic stem cells (HSC) were mobilized with cyclophosphamide (2.0 g/m2) and granulocyte colony stimulating factor (10 ug/kg/day). HSCT conditioning regimen was cyclophosphamide (200 mg/kg) and rabbit anti‐thymocyte globulin (either 6 mg/kg or 4.5 mg/kg).Eligible patients with RRMS had, despite interferon beta, 2 corticosteroid treated relapses within the prior 12 months, or 1 such relapse and gadolinium enhancing lesion(s) on magnetic resonance imaging (MRI) demonstrated on an occasion distinct from the relapse. All patients are surviving, 17 patients (81%) improved by at least 1.0 or more EDSS points, and five patients (24%) relapsed but achieved another remission after further immunosuppression. After a mean of 3 years, progression‐free survival is 100%, and relapse‐free survival is 76%. Significant improvement occurred in neurologic disability determined by extended disability status scale (EDSS), neurologic rating score (NRS), paced auditory serial addition test (PASAT), and 25 foot walk, as well as quality of life as measured by the short form‐36 (SF‐36). Non‐myeloablative autologous HSCT in RRMS appears capable of reversing neurologic deficits.Eligible patients for HSCT of T1DM were diagnosed in the previous 6 weeks by clinical findings and hyperglycemia and confirmed with positive antibodies against glutamic acid decarboxylase. 23 type 1 diabetic patients (aged between 13 and 31 years) were treated. During a 7‐to 58‐month follow‐up (mean 29.8) 20 patients without previous ketoacidosis and not receiving steroids during the preparative regimen became insulin‐free; 12 patients maintained this status for 14 to 52 months (mean 31) while 8 patients relapsed and resumed insulin use at low dose (0.1 to 0.3 IU/kg). In the continuous insulin‐independent group, HbA1c levels were always <7.0%, continuous glucose monitoring was within normal levels and mean AUC of C‐peptide levels increased significantly from 225.0 ng/mL pre‐transplantation to 785.4 ng/mL at +24 months (P <0.001) and to 728.1 ng/mL at +36 months (P = 0.03). In the transient insulin‐independent group mean AUC of C‐peptide levels also increased from 148.9 ng/ml before transplantation to 546.8 ng/mL at +36 months (P = 0.001) that was sustained at + 48 months In this group, two patients regained insulin independence after treatment with sitagliptin which was associated with increase in C‐peptide levels. HSCT induces insulin and drug free remission for up to 5 years post HSCT and appears to preserve or allow regeneration of islet cell mass with maximal C‐peptide levels reached 2–3 years after HSCT.
Somatostatin modulates mast cell‐induced responses in murine spinal sensory neurons and satellite cells
Authors: Van Op den Bosch Joeri , Van Nassauw Luc , Van Marck Eric , Adriaensen Dirk , Timmermans Jean‐Pierre 
Published: June 2021

The expression of somatostatin (SOM) receptors (SSTRs) in mucosal mast cells and sensory nerve fibers suggests a modulatory effect for this peptide in the mast cell‐neuron communication. Therefore, the modulatory effects of SOM on the short‐term and long‐term effects induced by histamine (HIS) and serotonin (5‐HT) on sensory neuronal characteristics were assessed using murine spinal neuronal cultures.ELISA and live cell imaging demonstrated acute HIS‐ and 5‐HT‐induced neuronal CGRP release and calcium‐mediated activation of both neurons and non‐neuronal cells. Both of these effects were strongly reduced by preincubating the spinal cultures with SOM. Long‐term incubation of the spinal cultures with HIS and 5‐HT significantly elevated neuronal expression of substance P, CGRP and SOM as demonstrated by qPCR and quantitative analysis. Also these long‐term effects of HIS and 5‐HT were partly inhibited by chronic SOM exposure. Immunocytochemistry and RT‐PCR revealed the involvement of SSTR1 and SSTR2A in these SOM‐dependent effects.The data demonstrate an interfering effect of SOM on the mast cell‐neuron communication, implying a major role for this peptide in intestinal inflammatory responses. Since SOM affects HIS‐ and 5‐HT‐induced responses in non‐neuronal cells as well, SOM could indirectly modulate sensory neuronal characteristics through modulation of the surrounding non‐neuronal cells.
Hypoxic preconditioning by HIF‐1 accumulation not angiogenesis provides neuroprotection in rats following MCAO
Authors: Darlington Timothy Ryan , Xu Kui , LaManna Joseph C 
Published: June 2021

Hypoxic preconditioning has been shown to be neuroprotective in ischemic models. We have previously reported an accumulation of HIF‐1α and its target genes at 3 days of hypoxic exposure in rats whereas at 3 weeks of exposure vascular adaptation is successfully completed. To distinguish the relative contributions from the two mechanisms to neuroprotection, we compared the effects of 3‐day and 21‐day hypoxic preconditioning on infarction of brain tissue following permanent middle cerebral artery occlusion (MCAO) in rats. Male Wistar rats were exposed to hypobaric hypoxia (0.5 ATM) for 3 or 21 days before undergoing permanent MCAO. Infarct volumes (% of contralateral hemisphere) were determined at 24 hours post‐occlusion in each rat. The 3‐day hypoxic preconditioned rats had significantly lower (ANOVA, p < 0.05) infarct volumes compared to the normoxic control animals following MCAO. Control animals (n = 7) produced an average infarct of 50 ± 4% (mean ± SEM) whereas an average infarct of only 32 ± 2% was observed in 3‐day hypoxic preconditioned rats (n = 9). The 21‐day hypoxic preconditioned rats did not show significantly decreased infarct volumes with an average of 50 ± 4% (n = 7). In conclusion, in permanent MCAO rat model the 3‐day hypoxic preconditioning appears to reduce infarct volumes compared to 21‐day hypoxic preconditioning. This suggests that the neuroprotective contribution from the accumulation of HIF‐1α and its target genes is greater than increased capillary density in the permanent focal ischemia model. Study supported by NIH grant 38632Grant Funding Source: NIH
QUALITATIVE AND QUANTITATIVE STUDY OF THE SYNAPSES IN THE HIPPOCAMPUS OF PATIENTS WITH ALZHEIMER's DISEASE
Authors: Shaibah Hassan , Elbarrany W.G. 
Published: June 2021

Human brains were obtained at postmortem examination from 5 control male individuals aged from 56 to 78 years and with no history of Alzheimer's disease (Group I). Also from 7 patients aged between 59 to 80 years and with history of Alzheimer's disease (Group II). Tissues were obtained from the same area of the hippocampus in both groups within 24 hours postmortem and processed for electron microscopic study.Two main types of synapses were encountered in the control Group I, symmetric and asymmetric synapses. The former had wide pre‐ and postsynaptic densities. The dendritic and axon terminals contained clear and dense‐cored vesicles in both types of synapses. There was no obvious difference between the width of the synaptic cleft of the two types of synapses. The mean surface density of the symmetric synapses of the control group was 990/mm2 and that of asymmetric synapses was 2164/mm2. The mean lengths of the synaptic opposition was 0.100 μm in the symmetric synapses and 0.121 μm in the asymmetric ones. In Group II with Alzheimer’ disease, vacuolations appeared within the dendrites and in the axon terminals. The myelinated nerve axons showed splitting of the lamellae of its myelin sheaths by intramyelinic vacuoles. The mean surface density of the symmetric synapses was 940/mm2 and that of asymmetric synapses was 1178/mm2. The mean length of the synaptic opposition was 0.271 μm in the symmetric synapses and 0.280 μm in the asymmetric ones.It could be concluded that the hippocampus of individuals with Alzheimer's disease showed vacuolations at the synaptic junctions and in the myelin sheaths. The number of synapses decreased in these individual with a compensatory increase in the synaptic lengths.
Inflammatory and angiogenic potential of primary and hTERT‐transduced human coronary artery endothelial cells
Authors: Baumer Yvonne , Ivanov Svetlana , Schlosshauer Burkhard 
Published: June 2021

In vascular research the use of endothelial cell (EC) lines would be desirable because of often high priced primary EC which display donor diversity. However, endothelial cell lines are often insufficiently characterized or represent irrelevant models because of cellular dedifferentiation like the reduced inflammatory response and permeability properties or deregulated protein expression. We established a human coronary artery EC line (HCAEC) by overexpression of human telomerase reverse transcriptase (hTERT). In comparative analyses we showed that primary and hTERT transduced HCAEC displayed comparable characteristics. These studies included: 1) detection of 9 endothelial and nonendothelial proteins by fluorescence‐microscopy (IF), western blot‐ and fluorescence activated cell sorting (FACS)‐analysis, 2) uptake of ac‐LDL by IF and FACS, 3) upregulation of ICAM‐1 after pro‐inflammatory stimulation, 4) analysis of changes in endothelial barrier function by measuring transendothelial electrical resistance and 5) detection of angiogenic properties by analyzing migration potential, Matrigel™ tube formation‐ and a fibroblast co‐culture‐assays. We conclude that hTERT overexpression did not alter typical endothelial characteristics. hTERT immortalized HCAEC are a valuable tool for endothelial research.Supported by the German Ministry of Education and Research (BMBF) # 01GU0727.
Does Tip60 Regulate the Cardiomyocyte Cell‐cycle?
Authors: Fisher Joseph Bernard , Kim Min‐Su , Lough John 
Published: June 2021

Tat‐Interactive Protein 60 (Tip60), a putative tumor suppressor, is a member of the MYST family of histone acetyltransferases (HATs). Tip60 function may include DNA repair, transcriptional co‐activation/repression, apoptosis, and cell‐cycle regulation. Alternative splicing of Tip60 mRNA creates α (60kD) and β (53kD) isoproteins, both of which are expressed in embryonic hearts. However, Tip60α becomes extinguished in neonatal hearts as proliferation subsides, leaving Tip60β as the sole isoprotein in adult heart. The role of Tip60 is unknown in adult cardiomyocytes, wherein we hypothesize that Tip60β maintains the G0 cell‐cycle state while promoting apoptosis. We targeted the Tip60 gene, observing that although homozygous deletion causes embryonic lethality, heterozygous deletion has no adult phenotype in the absence of stress. Therefore, two approaches, both of which induce hypertrophy, were used to stress Tip60+/− adult hearts: (i) physical stress via aortic banding and (ii) genetic stress via c‐Myc over‐expression. Both stressors caused the predicted outcomes of increased myocardial cell‐cycle activity and reduced apoptosis. These results support the hypothesis that Tip60 inhibits the cell‐cycle in adult cardiomyocytes, a possibility to be investigated using conditionally‐targeted mice that should enable reduction of Tip60β in myocardium to haploinsufficient levels.Grant Funding Source: American Heart Association; Grant Number: 0810108Z
Cocoa polyphenols inhibit sucrose hydrolysis in Caco‐2 cells
Authors: Ellam Samantha Lee , Williamson Gary 
Published: June 2021

Disaccharidase enzymes bound to the microvilli of intestinal epithelial cells are essential in the liberation of glucose from dietary carbohydrates. Glucose uptake from the lumen of the small intestine is facilitated by transporters located in the apical membrane of enterocytes; subsequent diffusion into capillary blood occurs at the basolateral surface similarly facilitated by transporters.Attenuation of enzyme and transporter activity may decrease post‐prandial blood glucose levels thereby providing a more uniform supply of glucose to the cells rather than an initial peak followed by rapid decline. This may have positive consequences not only for healthy subjects but also for individuals suffering from impaired glucose tolerance and type‐2 diabetes.Using Caco‐2 cells, passages 36 to 40, the rate of sucrose hydrolysis has been determined in the absence and presence of cocoa extracts and various polyphenols present in chocolate and cocoa. Using sucrose as the substrate, kinetic parameters were: a maximum reaction rate (Vmax) of 4.5 μmol min−1 and a Michaelis‐Menten constant (Km) of 33 mM.The addition of cocoa extract inhibited sucrose hydrolysis by Caco‐2 cells. (−)‐Epicatechin, (+)‐catechin and procyanidin B2, major components of cocoa, also diminished sucrose hydrolysis in Caco‐2 cells substantially.These results show that intestinal hydrolysis of sucrose by alpha‐glucosidase enzymes may be inhibited by cocoa polyphenols thereby reducing the rate of liberation of glucose. This would subsequently limit the uptake of glucose into the blood thereby reducing post‐prandial blood glucose levels.This work was funded by a BBSRC industrial case award to Nestlé, York UK.