bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiomyocyte β2‐Adrenergic Receptor Plays A Protective Role in Cardiac Fibrosis
Authors: Zhu Chaoqun , Deng Bingqing , Zhang Yu , Wang Ying , Xu Bing , Xiang Yang Kevin 
Published: April 2020

BackgroundChronic stimulation of β adrenergic receptor (βAR) has been implicated in cardiac remodeling including hypertrophy and fibrosis associated with heart failure. Previous studies indicate a role of β2AR on inhibiting collagen production in cultured cardiac fibroblasts, however, our recent studies show that global deletion of β2AR prevent cardiac fibrosis in diabetic cardiomyopathy. Therefore, this study aims to determine the specific role of cardiomyocyte β2AR in cardiac function and the development of cardiac fibrosis in vivo.Methods2‐month old male β2AR flox/flox (f/f) mice (n=10) and cardiomyocyte‐specific knockout of β2AR (CKO) mice (n=10) were fed with either normal chow (NC), or high fat diet (HFD) for 6 months to induce obesity and diabetes. Echocardiography was performed using a Vevo 2100 imaging system from VisualSonics. Biochemistry and histological analyses were performed on heart tissues. Real‐time PCR was performed for mRNA expression examination.ResultsWhile cardiac function was normal at 2‐month old CKO mice, a significant decrease in cardiac contractility was observed in CKO mice compared to f/f mice at 8‐month old age (EF%: CKO 48.43 ± 1.314 vs. f/f 52.69 ± 0.8270, p<0.05). Moreover, HFD feeding exacerbated cardiac dysfunction in CKO mice when compared to f/f mice (EF%: CKO 42.93 ± 0.69 vs. f/f 46.79 ± 0.76, p<0.001). CKO mice also exhibited diastolic dysfunction (IVRT: CKO 20.23 ± 0.30 vs. f/f 16.83 ± 0.23, p<0.0001), which was exacerbated after HFD feeding (IVRT, CKO 24.75 ± 0.50 vs. f/f 19.94 ± 0.45, p<0.0001). The observed cardiac dysfunction was associated with severe cardiac fibrosis in 8‐month old CKO mice, and HFD feeding leads to further exacerbation in cardiac fibrosis. Cardiac fibrosis was validated with elevated protein expression of connective tissue growth factor (CTGF), and significant upregulations of mRNA expression of CTGF, α smooth muscle actin (α‐SMA), and collagen 1 in CKO HFD mice.ConclusionsThis study elucidates that cardiomyocyte β2AR is essential to maintain normal cardiac function and plays a protective role against the development of cardiac fibrosis in aging and HFD feeding in vivo.Support or Funding InformationNIH HL113413, HL147264, VABX002900
The cardiovascular response to ambient temperature changes within the human thermoneutral zone
Authors: Ugland Nora , Lin Aihua , Bergersen Tone Kristin , Andersen Marian Berge , Holme Nathalie Linn , Zilakos Ilias , Elstad Maja 
Published: April 2020

IntroductionThe human temperature control within the thermoneutral zone (TNZ) depends on the regulation of skin blood flow to hands and feet (acral skin)
[1]. The acral skin blood flow is regulated by absolute level and fluctuations in arterio‐venous anastomoses’ vasculature resistance. We hypothesized that a change in ambient temperature would not affect the hemodynamic responses within the TNZ in healthy humans.MethodsTwenty‐four young healthy human subjects were exposed to three ambient temperatures (20°C, 26°C and 32°C) while supine and lightly dressed in a climate chamber. Each temperature plateau lasted for 40 minutes. The protocol either started at 20°C or 32°C, with a subsequent increase or decrease in temperature, respectively, and the order was randomized. Beat‐by‐beat blood flux from both index fingers and the left forearm were recorded simultaneously by laser Doppler flowmetry (DRT4, Moor Instruments, Devon, UK), together with heart rate (HR, from ECG). Non‐invasive finger arterial blood pressure (Finometer, Finapres Medical System, Netherlands; calibrated at each temperature plateau) was recorded continuously from the right middle finger, providing mean arterial pressure (MAP) and estimated beat‐to‐beat cardiac stroke volume (SV). The medians and their corresponding 95% confidence intervals were calculated by Hodges‐Lehmann’s estimates. Wilcoxon signed rank sum test for paired samples tested differences between states.Preliminary resultsIncreasing ambient temperature from 20°C to 32°C caused a five‐fold increase in left fingertip flux (p<0.003) while left forearm flux doubled (p<0.008). The fluctuations in the bilateral fingertip flux were maximum correlated at 26°C (>0.82) and significantly higher than the correlation at 32°C (0.73, p<0.01 as compared to 26°C). The hemodynamic variables changed significantly within the TNZ. MAP decreased from 74 (70,77) mmHg at 20°C to 64 (60,68) mmHg at 32°C (p<0.0001). SV decreased from 102 (93, 113) ml at 20°C to 97 (86, 106) ml at 32°C (p<0.0004). HR increased minimally from 20°C (56 bpm (52, 59) to 32°C (58 bpm (56, 61) (p=0.01).ConclusionsThe marked changes in acral skin blood flow within TNZ affected the central hemodynamic variables, with the vasodilation reflected in MAP decrease coinciding with an increase in ambient temperature. HR and SV showed minimal changes within TNZ.Support or Funding InformationThe Research Council of Norway (grant no: 230354)
Supracristal Plane: Is it an accurate predictor of the aortic bifurcation or the caval confluence?
Authors: Pather Nalini 
Published: April 2020

An accurate knowledge of surface anatomy and anatomical planes are imperative to clinical practice. Traditionally anatomical planes are based on cadaveric studies. Radiological imaging creates an opportunity to re‐assess our current knowledge of surface anatomy. One commonly used landmark is the supracristal plane that can also be used to locate the position for needle insertion in the lumbar puncture. This study aimed to assess the location of the supracristal plane in relation to vertebral levels using Computed Tomography (CT) and to determine the structures located at this plane.Materials and MethodsAdult CT scans (n=191, mean age, 52 years; 59% male) in the supine position were analysed to determine the vertebral level of the supracristal plane, aortic bifurcation, inferior vena cava confluence and umbilicus. The incidence of these structures at each vertebral level was correlated with sex and age. Scans (n=31) with distorting pathology and an absence of consensus amongst reporters was excluded.ResultsThe supracristal plane, aortic bifurcation, IVC confluence and umbilicus were most frequently located at L4/5 intervertebral disc (47.5%), lower third of the L4 vertebra (38.1%), lower third of the L5 vertebra (30%) and at the level of the L4 vertebra (28.7%). In only 13% of patients was the aortic bifurcation located at the supracristal plane. Lumabrisation and sacralisation was present in 2 and 3 patients, respectively.ConclusionModern imaging has enabled an evidence‐based prediction of the location of abdominal organs in different populations. It is imperative that this information is assimilated and incorporated in surgical anatomy education.
Effect of MED28 on epithelial‐mesenchymal transition in human colorectal cancer cells
Authors: Li Po-Chen , Hsieh Nien-Tsu , Chang Yu-Tsen , Lee Ming-Fen 
Published: April 2020

Mammalian Mediator complex plays an important role in transcriptional activation by bridging RNA polymerase II and transcriptional machinery. Multiple Mediator subunits have been implicated in human diseases including cancer development. Our laboratory has previously reported that MED28, a Mediator subunit, mediates Wnt/β‐catenin signaling and promotes cell growth in human colorectal cancer (CRC) cells. The objective of the current study is to investigate the effect of MED28 on epithelial‐mesenchymal transition in CRC in addition to cell growth. Suppression of MED28 attenuated the expression of several mesenchymal biomarkers including vimentin and transcription factors Snail and Slug, but increased the expression of E‐cadherin, an epithelial biomarker; however, overexpression of MED28 reversed the reciprocal change of epithelial and mesenchymal biomarkers. The underlying molecular mechanism is currently under investigation. Our data indicate that MED28 modulates the development of epithelial‐mesenchymal transition in human CRC cells, further reinforcing the significance of MED28 in the progression of malignancy in CRC.Support or Funding InformationThis work was supported by the grant MOST 106‐2320‐B‐039‐062‐MY3 to M‐F Lee.
Natural and synthetic glycan arrays for probing interactions of the innate and adaptive immune system with zwitterionic oligosaccharides
Authors: Wilson Iain B. H. , Eckmair Barbara , Yan Shi , Hykollari Alba , Paschinger Katharina 
Published: April 2020

Invertebrate glycans are often ‘foreign’ to mammals, but many invertebrates are parasites which also immunomodulate the responses of the host, while invertebrate cell lines are potential ‘cell factories’ for production of secreted glycoprotein biopharmaceuticals. However, if we wish to investigate the innate or adaptive immune response of mammals to invertebrate glycoconjugates, a methodological hurdle is that most glycan arrays primarily focus on mammalian structures and not on those from other species. We are addressing this gap in the glycobiological toolbox by preparing arrays of either natural glycans from invertebrates or synthetic glycoconjugates displaying invertebrate glyco‐epitopes. To date we have printed (i) the neutral and anionic pools of N‐glycans from honeybee royal jelly, (ii) the native and hydrofluoric acid‐treated neutral pools of N‐glycans from the canine heartworm, (iii) fractions of N‐glycans from the canine heartworm, (iii) mono‐ and disaccharides modified with zwitterionic phosphoethanolamine or phosphorylcholine and (iv) fucosylated and non‐fucosylated forms of chitobiose and LacdiNAc. These pools, fractions or compounds were probed with various lectins, pentraxins or antibodies. We show that human serum amyloid P binds glycans derived from royal jelly (the food for honeybee queens, but also used as a beauty product), while human C‐reactive protein (CRP) interacts with the glycans of the canine heartworm (a mosquito‐borne parasite). On the other hand, short phosphorylcholine‐modified glycoconjugates are recognized not only by CRP, but by IgG and IgM in the sera of some nematode‐infected animals. Not only are such arrays complementary to current resources, but they have high potential to yield new insights into the glycan‐mediated interactions of invertebrates with mammals.Support or Funding InformationThis work was supported by the Austrian Science Fund (FWF) by grants to I.B.H.W., S.Y., A.H. and K.P.
Mixed Effects Of Active Immunization Against Aß In An Alzheimer Mouse Model
Authors: Oberman Klaske , Hoogerhout Peter , Gouweleeuw Leonie , Eisel Ulrich L.M. , van Riet Elly , Schoemaker Regien G. 
Published: April 2020

Since Aß plaques and cognitive function are often not related in Alzheimers disease (AD), attention has shifted towards the neurotoxic soluble oligomeric Aß as the culprit in AD. Accordingly, INTRAVAC developed a concept vaccine that is specifically directed towards these misfolded Aß molecules. A previous study indicated protection against Aß‐induced neuronal damage in vaccinated mice. The aim of this study is to investigate the effects of the vaccine in a mouse model for AD.MethodsAs model for AD, J20 mice, overexpressing the human Amyloid Precursor Protein were used. AD phenotype of J20 mice was evaluated at 6 months of age. The vaccine consisted of 3 cyclic Aß peptides, conjugated to tetanus toxoid with proper adjuvants. Mock control consisted of tetanus toxoid +adjuvants. Mice were vaccinated or mock treated at 2,3 and 4 months of age, while behavior and plaque formation were evaluated at 6, 9 and 12 months of age.ResultsAD phenotype of J20 mice was confirmed by significant decline in cognitive performance, as well as the presence of plaques. Vaccinated mice showed significant improvement of working memory at 12 months compared to mock, as tested as correct alternations in Y‐maze exploration; 59.2±1.3 vs 56.1±1.6%. However, spatial learning (AUC learning curve: 858±±29 vs758±43s) and memory (number of platform crossings: 0.47±0.19 vs 1.04±0.39), measured in the Morris Water Maze, appeared deteriorated at 12 months. Plaque load, measured as number times size, increased with age, but was even slightly higher in vaccinated compared to mock mice at 12 months;9356±1200 vs 8155±1142 pixels). Antibody response showed significant titers for the cyclic peptides, but insignificant levels for Aß.ConclusionCognitive decline and plaque formation in 6 months old J20 mice provide a relevant model for AD to test effects of vaccination against oligomeric Aß. Although vaccination at young ages improved working memory at 12 months, spatial learning and memory rather deteriorated, and plaque formation was not reduced. The lack of antibody response to Aß suggests that behavioral effects are mediated by mechanisms other than Aß reduction.Support or Funding InformationStudies are partly funded by INTRAVACC, the Netherlands
Understanding Brain/Face Integration from Neuropsychiatric Disorders
Authors: Martínez-Abadías Neus , Hostalet Noemí , Gonzàlez Rubèn , González Alejandro , Sevillano Xavier , Canales Rodríguez Erick J. , Salvador Raymond , Pomarol-Clotet Edith , Fatjó-Vilas Mar 
Published: April 2020

Understanding how genetic and environmental variation alter the integrated development of the face and the brain has important implications for medicine and human evolution. Neuropsychiatric disorders offer an ideal model for investigating the association between facial and brain phenotypes with their underlying genotype. Schizophrenia (SZ) and Bipolar Disorder (BD) are severe psychiatric disorders caused by pathological processes occurring early in neurodevelopment. Disruptions in signaling pathways that are common to brain and face development may explain why these disorders are associated with abnormalities of brain structure and a high prevalence of minor facial dysmorphologies. We assessed facial shape with its neuroanatomical and genetic correlates in a sample with magnetic resonances and genetic data available for 188 subjects (75 healthy controls, 67 SZ and 46 BP patients). Geometric Morphometrics revealed that facial shape variation assessed from 3D facial reconstructions significantly differentiated between SZ/BP patients and controls with moderate accuracy (60–65%). ANOVA tests detected a significant association between facial shape and specific measures of the brain superior frontal regions (thickness, volume and area), whereas the explained facial shape variation increased from 1% to 4.8% in SZ and 6.5% in BD when we included in the model the interaction between a SNP in GLI3 gene and these brain measures. We conclude that facial shape may be considered as an indirect marker of deviances in brain development, and GLI3 as a modulator of brain‐face relationships; probably due to the key role of this gene in the Shh signaling pathway regulating brain and face development.Support or Funding InformationMinisterio de Ciencia, Innovación y Universidades, Proyectos I+D+i «Retos Investigación» RTI2018‐097845‐J‐I00; 2017SGR1630; 2017SGR1271; CD16/00264.
Effects Of J147 On Post‐Operative Cognitive Dysfunction
Authors: Oberman Klaske , Villafranca Ernest , Schoemaker Regien G. 
Published: April 2020

BackgroundPostoperative cognitive dysfunction (POCD) is a major complication in patients undergoing surgery. The inflammatory response necessary for wound healing seems derailed and is reflected in the brain as neuroinflammation and consequently cognitive decline. J147 has anti‐dementia and anti‐aging effects that may be attributed to anti‐inflammatory properties.Aiminvestigate effects of J147 treatment in an animal model for POCD.Materials and MethodsMale Wistar rats (n=60; ±350g) were randomly divided over 1. non‐surgery; 2. control surgery; 3. surgery + acute J147 (20 mg/kg) and 4. surgery + chronic J147 (30 mg/kg/day). Acutely treated rats received one single oral administration of J147 before surgery, chronically treated rats received oral J147 through their food during the whole experiment. Behavioral testing consisted of an Open Field test (OF), Novel Object and Novel Location Recognition test (NOR/NLR) and the Morris Water Maze (MWM) to assess exploratory behavior, object memory, spatial learning and memory, and cognitive flexibility, resp. Two weeks after surgery, rats were sacrificed, and blood and brain tissue is collected for later analyses of (neuro)inflammation.ResultsAll rats survived surgery and were subjected to behavioral testing. The OF showed that chronic treated animals payed significant more visits to the center (12.6±1.5 vs 9.7±1.4 in control surgery), at similar distance moved. No difference in spatial learning capacity, reflected in the learning curve of the MWM test, was seen between the groups. Platform crossings in the MWM indicated that chronic treatment can restore the spatial memory deficits caused by surgery (1.6±0.2 vs 1.0±0.1). NOR test did not discriminate between groups. In NLR, control surgery rats performed at chance level (60±5 vs 50%), whereas performance in chronic treated rats significantly increased above chance level; 70±6%. For the acute treated group no significant differences were seen compared to the control surgery group in all the tests.ConclusionOur data indicate that chronic J147, but not acute J147 prevents cognitive impairment following abdominal surgery in our POCD model. Therefore, chronic J147 treatment could provide a promising novel therapeutic approach in POCD in patients. To study the underlying mechanism of (neuro) inflammation, plasma cytokines levels and microglia activation in the brain will be determined.Support or Funding InformationThe study is supported by funding from ABREXA
Influence of Incubation Temperature on Chicks Ventilation and Oxygen Consumption
Authors: Rocha Aline Cristina Gonçales , da Silva Welex Cândido , Bícego Kênia Cardoso , Gargaglioni Luciane Helena 
Published: April 2020

The first third of the incubation is determinant for the embryonic development and the temperature is considered one of the most important factors that can affect the quality and the survival rate of the embryos. The aim of this study was to evaluate the effect of changes in the temperature of incubation (36 °C‐cold; 37.5 °C‐thermoneutral and 39 °C‐hot) during the first 5 days on ventilation (VE) body temperature (Tb) and oxygen consumption (VO2) of 2 days old broiler males (M) and females (F) in basal conditions and under exposition to hypoxia (10% O2) or hypercapnia (7% CO2). No difference among groups was observed during room air conditions. Under hypercapnia, the VE of females exposed to cold incubation was lower compared to other treatments (P =0.0402 compared to control and P= value=0.0193 compared to hot), as well as the respiratory frequency (fR) when compared with hot treatment (P =0.0387), but not to the control situation (P = 0.1109). VO2 of females during CO2 exposure was higher in 36 °C group compared with other groups (P = 0.0004 compared to control; P =0.0078 compared to hot). VE and of control males was lower when compared to hot (P = 0.0344) and VT of the same group was lower than cold (P‐value=0.0171) and hot (P =0.0324) treatments. There was no difference in fR and VO2 among groups. Hypoxia promoted a higher VE (P = 0.0439) and VT (P =0.0041) in cold exposed females compared to hot. VO2 was higher (P = 0.0290) as well when compared to 37.5 °C group. No difference was observed in respiratory responses of males exposed to hypoxia. Therefore, temperature of incubation can affect the ventilation in young broiler chickens under hypercapnic and hypoxic conditions in a sex‐dependent manner.Support or Funding InformationFAPESP, CNPq and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior ‐ Brasil (CAPES) ‐ Finance Code 00
Saturated Fatty Acid‐Enriched Diet Affect Liver Transcriptional Response of Anti‐oxidant Genes of Perinatal Undernourished Rats
Authors: Costa-Silva João H. , Simões-Alves Aiany C. , Fernandes Mariana P. , Leandro Carol G. , Pirola Luciano , Morio Béatrice 
Published: April 2020

In this work, we evaluated the impact of a saturated fatty acid (SFA)‐enriched diet (HL) in the post‐weaning offspring subjected to maternal protein restriction in liver genes of redox balance and inflammatory pathway. Wistar rats were mated and during gestation and lactation, mothers received control (C) or low protein diet (LP, 8% protein). After weaning, rats received either C or HL (+59% SFA) diets up to 90 days of life. It was verified that circulating markers of lipid metabolism and liver function were not significantly altered between groups. The LP group submitted to the post‐weaning HL diet showed an increase in liver protein and lipid oxidation (p<0.01). This group also presented greater gene transcription of NF‐KB1 and TNF‐α (p<0.05) compared to controls. Liver mRNA contents of pro‐oxidant enzymes (XDH, NOX1 and RAC1) were not different between LP and controls animals. Post‐weaning HL diet did not alter the pattern of expression of SOD1, SOD2, CAT, GPX1, GPX2, UCP2 genes in LP groups, except for CAT, which was significantly higher in LP group fed HL diet compared to C (+66%, p<0.05). In protein level, CAT was lower in LP compared to control animals under both post‐weaning C and HL (p<0.05). In contrast, SOD2 protein content was twice higher in LP groups (p<0.05). However, GPX1/2 protein expression was similar between groups. Regarding transcription factors, no differences were noted in NRF2 and FOXO3 mRNA contents. However, SFA enhanced PGC1α (+207%, p<0.05) and PPARγ (+151%, p<0.05) levels in LP groups vs. C. Thus, our data suggest that SFA‐enriched diet induces oxidative stress, activation of inflammatory pathways, however without metabolic disturbance when the animals were submitted to a low protein diet during critical periods of development.Support or Funding InformationThis study was supported by FACEPE (Brazil), CNPq (Brazil) and CAPES/COFECUB (Brazil/France).
The Effect of Serum of Cerebral Small Vessel Disease Patients on Brain Endothelial Cells
Authors: Cifu' Adriana , Janes Francesco , Domenis Rossana , Fabris Martina , Curcio Francesco 
Published: April 2020

INTRODUCTIONCerebral Small Vessel Disease (CSVD) is characterized by perforating cerebral arterioles, venules and capillaries, and a consequent damage of cerebral white and deep grey matter. The pathogenesis of CSVD is unknown and could be asymptomatic in early phases. CSVD is a typical disease of elderly population and in stroke patients. However, the increasing use of MRI in last years, led to incidental findings in young people without classical vascular risk factors. To better understand the role of brain endothelium in onset of Cerebral Small Vessel Disease, we evaluated the effect of CSVD patients’ serum on human brain endothelial cells (HBEC‐5i).METHODSHBEC‐5i were treated for twenty‐four hours with 20% of serum from six CSVD patients or six age‐ and sex‐matched controls. Trypan blue exclusion method was used to evaluate proliferation rate and viability of treated cells compared to untreated cells. The effect of CSVD patients’ serum on HBEC‐5i, was evaluated by droplet digital PCR in terms of the mRNA expression of interleukins involved in inflammatory response(IL1β, IL1α, IL6, IL8, and IL10).RESULTSThe treatment with both patients’ and controls’ serum reduced the proliferation rate of cells, however no difference was observed between the two treatment. The viability, instead, was not influenced by serum treatment. The mRNA expression of pro‐inflammatory cytokines (IL1β, IL1α, IL6) was higher in HBEC‐5i treated with serum of CSVD patients compared to both untreated cells and cells treated with serum of controls. On the other hand, the mRNA expression of IL10 , an anti‐inflammatory molecule, increased only in cells treated with controls’ serum. None treatments affected the mRNA level of IL8.CONCLUSIONSIn brain endothelial cells, the serum of CSVD patients, differently from serum of controls, promotes the expression of pro‐inflammatory cytokines. These preliminary data suggest that inflammation could play a role in pathogenesis of CSVD.Support or Funding InformationThis project was supported by Grant Interreg ARTE (J22F170001005)