bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anomalous pattern of the cerebral arterial circle, associated with an aneurysm: a case report (543.12)
Authors: Enache Alexandra , Zahoi Delia , Sztika Dorina , Baderca Flavia , Daescu Ecaterina 
Published: June 2021

The cerebral arterial circle plays a crucial role in the blood circulation within the cortical area. Its’ morphological variability and potential for the formation of aneurysms are well documented and constitute significant mortality risks.Within the Forensic Medicine Department, several anomalies within the area were identified during the autopsy of a 29 year old male. The observations included anomalous origins of the arteries constituting the cerebral circle (anterior and posterior parts), left/right vascular asymmetry and the presence of an aneurysm which had ruptured spontaneously and was identified as the cause of death.On the anterior part of the circle, both cerebral arteries originate from the left internal carotid artery, through a 2cm common trunk. The 0.3‐0.4cm saccular aneurysm was located at the bifurcation of this trunk. The right anterior cerebral artery anastomosed with the the middle homolateral cerebral artery through a 4.5cm long and 0.2cm in diameter branch. On the posterior part of the circle, agenesis of the right posterior communicating artery was highlighted.Through their effect on hemodynamics, morphological anomalies in vessels such as those identified in this case may constitute causal factors in the development of aneurysms.
Difference between hemoglobin‐based oxygen carrier and non‐oxygen carrying plasma expander on cardiac function during hemorrhagic shock resuscitation (545.1)
Authors: Ao‐ieong Eilleen , Cabrales Pedro 
Published: June 2021

Study aimed to establish the role of acellular hemoglobin (Hb) based oxygen carrier on cardiac function during anemia. Anesthetized Golden Syrian hamsters under mechanical ventilation with air were hemorrhage 30% of the animal’s blood volume followed by equal volume resuscitation with polymerized albumin (pHSA), or polymerized Hb (pHb, Hemopure, OPK Biotech, Boston, MS). Blood oxygen saturation of >90% was maintained throughout experiment. Cardiac function was assessed through the use of a miniaturized conductance catheter inserted into the left ventricle with continuous pressure‐volume readings. All groups had an increase in stroke work, cardiac output, and ejection fraction compared to baseline. The ratio between dP/dtmax and end diastolic volume, an index of contractility, recovered to 94±33% from baseline for the pHSA, and decreased to 55± 13% from baseline for pHb one hour after resuscitation. To further elucidate the difference in contractility, the intrinsic effects of oxygenation will be investigated by the histology of hypoxic tissue using pimonidazole staining. Hemorrhage and resuscitation resulted in an increased in cardiac function for both treatments.Grant Funding Source: NIH R01 HL52684, R01 HL064395 and R01 HL062318 and ARMY: W81XWH‐11‐2‐0012
Rapid vasodilation in response to passive leg movement with age: the role of nitric oxide and the impact of perfusion pressure (546.6)
Authors: Groot H , Trinity Joel , Layec Gwenael , Rossman Matthew , Ives Stephen , Richardson Russell 
Published: June 2021

We sought to elucidate the contribution of NO, with and without posture‐induced increases in femoral perfusion pressure (FPP), on the rapid (first 7 sec) vasodilatory response to passive leg movement (PLM) with age. PLM was performed in 8 young (24±1 yrs) and 7 old (75±3 yrs) healthy males, with (blk) and without (ctrl) NO synthase (NOS) inhibition, in both the supine and upright‐seated posture. Peripheral hemodynamic responses were determined with Doppler ultrasound. In the supine posture, NOS inhibition had no effect on the rapid vasodilation (leg vascular conductance slope/time) in either the young (ctrl: 0.78 ± 0.10; blk: 0.71 ± 0.16 ml/min/mmHg/sec; p>0.05) or on the already attenuated response in the old (ctrl: 0.25 ± 0.06; blk: 0.33 ± 0.07 ml/min/mmHg/sec; p>0.05). However, in the upright‐seated posture, which similarly increased FPP in both groups (~7mmHg), NOS inhibition significantly attenuated the posture‐induced augmentation of rapid vasodilation in the young (ctrl: 1.25 ± 0.23; blk: 0.74 ± 0.11 ml/min/mmHg/sec; p<0.05), with no effect in the old (ctrl: 0.38 ± 0.05; blk: 0.26 ± 0.05 ml/min/mmHg/sec; p>0.05). PLM‐induced rapid vasodilation in the supine posture is NO‐independent and this response is attenuated with age. In the young, elevated FPP increases the role of NO in this rapid vasodilatory response, but has no effect in the old, likely due to decreased NO bioavailability in this population.Grant Funding Source: VA Merit Grant E6910R and PPG Grant
Early myocardial changes in experimental chick model of hypoplastic left heart syndrome (547.10)
Authors: Pesevski Zivorad , Kockova Radka , Buffinton Christine , Hedgeland Mark , Svatunkova Jarmila , Sedmera David 
Published: June 2021

Hypoplastic left heart syndrome (HLHS) is a complex congenital heart defect in which the left ventricle of the heart is critically underdeveloped and unable to effectively supply blood to the body. Early reloading of the hypoplastic left ventricle can induce its growth and maturation and lead to rescue. To analyze the early changes during development of HLHS, we used an experimental chick model of left atrial ligation (LAL). Fertilized eggs were incubated at 37.5 °C. Partial ligation of the left atrium of chick embryonic hearts was performed at the ED4. At ED6, we performed ultrasound biomicroscopy examination of control and ligated hearts, followed by confocal microscopy 3D reconstruction of the left ventricle. Only those LAL hearts with clear phenotype, defined as apex‐forming right ventricle, were included in the quantitative evaluation. The hypoplastic left ventricle was significantly smaller in cross‐section with a total tissue volume less than half that of matched controls. In ovo analysis of circumferential strain from ultrasound showed no difference between the control and LAL group. This data indicate that although there is a clear morphological phenotype at this stage, the myocardial performance is still within normal limits, strengthening the point of early, possibly fetal, intervention for HLHS.Grant Funding Source: Supported by PRVOUK‐P35/LF1/5, RVO: 67985823, GACR P302/11/1308, and Bucknell University PUR grant
In vivo two‐photon microscopy for imaging leukocytes in atherosclerotic plaques (547.16)
Authors: McArdle Sara , Koltsova Ekaterna , Ley Klaus 
Published: June 2021

Atherosclerosis is characterized by chronic inflammation of the walls of large and medium arteries that have been infiltrated by macrophages, dendritic cells (DCs), T cells, and other leukocytes. Disease progression is determined in part by a variety of cell functions that are regulated by the cell’s motility, including recruitment, transmigration, egress, phagocytosis, and interaction between multiple cell types. In vivo imaging is necessary to better understand leukocyte activity during atherosclerosis within the native plaque microenvironment.Two‐photon microscopy is emerging as a valuable tool to image live, fluorescent cells in explants or certain organs in vivo. However, new technical challenges are introduced when imaging tissues that move within the body, such as arteries, which expand with every heart beat. In‐frame and between‐frame motion cause still images to be distorted and movies to appear unsteady, making cell tracking infeasible.We engineered an integrated hardware and software system for in vivo two‐photon imaging of large arteries. To ensure that the artery is in the same position for every picture, a trigger mechanism was constructed which links image acquisition to the mouse’s heartbeat via pulse oximetry. To minimize distortions, a method was developed to acquire only a fraction of a frame during each heart beat and then stitch the resulting small strips together to form a larger frame. A custom stage was built to precisely position the mouse under the microscope objective in 3 dimensions in coordination with the trigger mechanism. The resulting 3D movies will be used to track cell motion. This system can be used to study multiple questions involving cell motility in vivo, including leukocyte recruitment from blood, antigen presentation, phagocytosis, chemokine function, and the role of cell subsets in disease progression.Grant Funding Source: Supported By the AHA (11PRE7580009), HHMI (56005681), and NHLBI (T32HL007089‐35)
Activation of TGF‐β mediated SMAD pathway induces cardiac fibrosis in mice carrying targeted disruption of guanylyl cyclase/natriuretic peptide receptor‐A gene (547.17)
Authors: Subramanian Umadevi , Gogulamudi Venkateswara , Chen David , Pandey Kailash 
Published: June 2021

Mice carrying targeted‐disruption of the natriuretic peptide receptor‐A (GC‐A/NPRA) gene (Npr1) have demonstrated cardiac hypertrophy with increased collagen deposition and fibrosis. The objective of this study was to determine the mechanisms regulating the development of fibrosis in Npr1 gene‐disrupted mice hearts. The Npr1 null mutant (Npr1‐/‐, 0‐copy), heterozygous (Npr1+/‐, 1‐copy), and wild‐type (Npr1+/+, 2‐copy) mice were orally administered with transforming growth factor‐β1 receptor inhibitor GW788388 (2 mg/kg/day) for 28 days, and the hearts were isolated and used for quantification of fibrotic markers using real time quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR) and Western blot analyses. Npr1‐/‐ null mutant mice showed 6‐fold induction of fibrosis in the hearts compared to wild‐type controls. Moreover, the expression of fibrotic markers such as connective tissue growth factor (CTGF), α‐smooth muscle actin (α‐SMA) and TGF‐βRI, TGF‐βRII and SMAD proteins were upregulated in Npr1‐/‐ mice hearts compared with age‐matched wild‐type controls. Whereas, treatment with TGF‐β inhibitor, GW788388, significantly prevented the cardiac fibrosis and potentially down‐regulated the expression of fibrotic markers and SMAD proteins in Npr1‐/‐ mice hearts. The results of the present study suggest that, induction of cardiac fibrosis in Npr1‐/‐ gene‐disrupted mice is majorly through TGF‐β mediated SMAD‐dependent pathway.Grant Funding Source: NIH
Risk factors and characteristics of lesions of the cardiovascular system in young aged patients with psoriasis (547.2)
Authors: Batpenova Gulnar , Kazieva Aliya , Pshembaeva Saule , Sadykova Gulnaz 
Published: June 2021

To study lipid metabolism,as well as the identification of risk factors,the characteristics of the cardiovascular system lesions in young aged patients with psoriasis.It was found in clinical and epidemiological study that among patients with psoriasis most men were ‐ 61.1%, women ‐ 38.9%. Mean age ‐ 46,4±2,3years. In the study of the spectrum the concomitant somatic pathology in adult patients 61.3% was identified with underlying diseases. In patients with severe psoriasis concomitant diseases were observed in 78.4% of patients, that is 1.3 times higher than in patients with psoriasis vulgaris and exudative. Lipid profile were as follows: hypercholesterolemia was diagnosed in 39.5% patients,74.4% patients, LDL cholesterol was above normal. Values of triglycerides (TG) averaged 1,82±0,15 mmol/l. In carrying out the cluster analysis between lipid profile and the main clinical and laboratory parameters in patients with psoriasis, revealed strong correlation rates (p<0.001) HDL with disease duration (r=‐0,95),with the affected area (r=‐0,83).In a study of the cardiovascular system in patients with psoriasis most often ‐ in 70% of cases met various cardiac arrhythmias. Signs of connective tissue dysplasia, namely, small malformations of the heart were detected in 25.6% patients. Hypertension was diagnosed in 9.3%, signs of peripheral atherosclerosis‐6.9% of the patients, ischemic heart disease‐4.7%.
Insulin suppresses ischemia/reperfusion‐induced myocardial injury via inhibiting mitochondrial JNK translocation (547.20)
Authors: Xu Jie , Qin Xinghua , Zhang Xing , Yang Lu , Xing Yuan , Gao Feng 
Published: June 2021

Objective: Insulin exerts cardioprotective effect against ischemia/reperfusion (I/R) injury, but the underlying mechanism is unclear. This study aimed to examine the role of mitochondria in insulin‐induced cardioprotection against myocardial I/R injury.Methods: Adult male rats were subjected to 30 min of myocardial ischemia and 2 h of reperfusion. Rats randomly received vehicle, insulin, and Tat‐SabKIM1 administered 5 min before reperfusion. Incidence of myocardial apoptosis was determined by TUNEL. JNK from the extractions of mitochondria, cytosol/nucleus, and whole cell was detected by Western blot.Results: Myocardial I/R produced significant myocardial apoptosis, both mitochondrial and cytosolic/nuclear JNK activation and myocardial infarction (n=6, P<0.05). Importantly, we found JNK translocation from mitochondria to cytosol/nucleus together with cytochrome c release following myocardial I/R, which were blunted by insulin treatment. Inhibiting JNK translocation to mitochondria with Tat‐SabKIM1, a retro‐inverso peptide which disrupting the JNK interaction with mitochondria, not only decreased mitochondrial JNK activation but also exerted cardioprotective effect as evidenced by reduced myocardial apoptosis (10.2±1.3% vs. 16.0±1.2%, P<0.05) and myocardial infarct size (15.9±2.1% vs. 23.7±1.5%, P<0.05) after myocardial I/R.Conclusion: These data show that insulin exerts mitochondrial protective action via disrupting JNK translocation to mitochondria and thus inhibiting cytochrome c release, which contributes to insulin‐elicited cardioprotection against I/R injury.Key words: insulin, ischemia/reperfusion injury, JNK signaling, mitochondria, cardioprotectionGrant Funding Source: supported by grants from the National Basic Research Program of China (No. 2013CB531204)
Heart rate variability and cardiac function in heart failure rats treated with allogeneic mesenchymal stem cells (547.21)
Authors: Morais Sharon , Lataro Renata , Silva Carlos Alberto , Oliveira Luciano , Carvalho Eduardo , Simões Marcus Vinicius , Meirelles Lindolfo , da Silva Luiz Eduardo , Salgado Hélio , Fazan Rubens 
Published: June 2021

The effect of Mesenchymal Stem Cells (MSC) on cardiac function and non‐linear dynamics of heart rate variability was evaluated after myocardial infarction (MI) in rats. MSC (N=7) or saline (N=11) were given iv to male Wistar rats 1 week after sham (N=9) or left coronary artery ligation. Infarct size, assessed by SPECT, was found similar among rats (51±1%). Cardiac function was assessed by isotopic ventriculography before and 4 weeks after MSC therapy. 5 weeks after MI the rats underwent ECG and arterial pressure recording. The infarct size was reduced by MSC (36±2% vs 48±2% saline). Left ventricular ejection fraction (LVEF) was normal in sham but lower after MI (54±3 vs 20±2%). No effect of MSC was seen in LVEF (20±4%). Interstitial collagen was increased in rats with MI (15±2% vs 10±1%), but not in MSC treated ones (11±1%). Arterial pressure and heart rate were similar among groups in conscious rats. Baroreflex sensitivity was reduced after MI (1.80±2 vs 1.10±0.1 bmp/mmHg), while MSC prevented this outcome (1.74±0.2 bpm/mmHg). QT and QTc intervals were lengthened by MI and MSC did not affect this parameter. A reduction in sample entropy (SampEn) and increase in detrended fluctuation analysis (DFA) of RR interval were observed after MI. MSC therapy did not affect SampEn but protected the DFA. In conclusion, MSC reduced MI and interstitial fibrosis in left ventricle, combined with improvement of baroreflex sensitivity and DFA.Grant Funding Source: Financial support: FAPESP, CAPES, CNPq, NIC‐USP
A viral peptide deformylase‐ribosome complex reveals mechanism of host gene expression control (558.2)
Authors: Giglione Carmela , Grzela Renata , Bron Patrick , Lai Kee Him Joséphine , Fieulaine Sonia , Nusbaum Julien , Pozza Alexandre , Bienvenut Willy , Meinnel Thierry 
Published: June 2021

All prokaryotic nascent chains must be co‐translationally deformylated to allow the further essential removal of the first methionine. This early nascent chain processing is ensured by peptide deformylases (PDFs), an enzyme shown to interact with ribosome at the exit tunnel. Recently, studies demonstrating in one hand the acquisition by different marine phages of modified version of bacterial PDF and in the other hand that also viral proteins undergo deformylation led to propose that phage PDFs could be important for viral fitness. Aside from this intriguing hypothesis, not much is known about these phage PDFs. Here, we show that most viral versions of the PDFs do not contain a C‐terminal extension previously proposed to be responsible of direct PDF binding to ribosome. Nonetheless, we show that the smallest identified phage PDF, a fully C‐terminally‐truncated PDF, is still able to bind directly to ribosome via a new dedicated ribosome‐binding domain, playing a master regulator function. Crosslinking experiments and combination of structural data of this phage PDF alone and the complex between the phage PDF and the ribosome show that the phage PDF interacts with ribosome in several distinct regions. Taking together, our findings provide basis for understanding of a previously unrecognized mechanism based on the pathogenic virus control of host viability at the level of the tunnel exit.Grant Funding Source: CNRS, ANR
Mechanism of HigB‐mediated ribosome‐dependent mRNA degradation (568.1)
Authors: Schureck Marc , Maehigashi Tatsuya , Marquez Jhomar , Dunkle Jack , Miles Stacey , Dunham Christine 
Published: June 2021

Proteus vulgaris (P. vulgaris) is a major cause of bacterial urinary tract infections. P. vulgaris grows on medical equipment, such as catheters, in an antibiotic‐resistant state known as biofilms. In biofilms, bacteria are highly adhesive and are protected from antibiotics by a self‐produced extracellular matrix of DNA, protein and polysaccharides. My goal is to elucidate the molecular mechanism of the ribosome‐dependent RNase family of toxins, which play an important, but unknown, role in biofilm formation. Host inhibition of growth B (HigB) is a member of this family and was first identified in P. vulgaris. HigB cleaves ribosome‐bound A‐site mRNA and in contrast to most toxins, HigB recognizes mRNA in a codon‐independent manner. Using microbial, structural and biochemical techniques, we are beginning to understand how HigB can recognize such a large variety of A‐site codons. Our X‐ray crystal structure of HigB in complex with the Thermus thermophilus 70S ribosome and an A‐site codon chemically modified to prevent cleavage reveals that HigB binds the A site and dramatically reorients mRNA for catalysis by two essential HigB amino acids. Biochemically, we have shown that the minimal substrate specificity for HigB is an adenosine in the A‐site wobble position. Taken together, our results indicate that the HigB toxin acts as a novel translation factor and site specifically recognizes the wobble position.Grant Funding Source: Supported by a NIH NRSA (GM108351) and BCMB graduate training grant (5T32GM8367)
Postnatal cardiac development in transgenic mice with altered expression of the DNA glycosylase Ogg1 (573.4)
Authors: Ruchko Mykhaylo , Gorodnya Olena , Rachek Lyudmila , Pastukh Viktor , Gillespie Mark 
Published: June 2021

A switch from cardiomyocyte hyperplasia to hypertrophy underlies postnatal cardiac development in rodents. Interestingly, this transition is associated with robust mitochondrial biogenesis, which, paradoxically, is accompanied by oxidative mitochondrial (mt) DNA damage and repair (Pohjoismaki et al, NAR, 2012). Whether mtDNA damage and repair are functionally linked to mitochondrial biogenesis is unknown, but previous experiments showed that controlled DNA damage and repair are important for transcription of nuclear genes (Al‐Mehdi et al, Sci Signaling, 2012). To determine if a similar mechanism could be operative in the mitochondrial genome during postnatal cardiac development, we measured oxidative damage in the mtDNA D‐loop transcriptional regulatory sequence and the coding region as a function of time in hearts derived from wild type (WT) mice, knock‐out mice deficient in the DNA glycosylase Ogg1 (KO), and in KO mice transgenically over‐expressing human OGG1 targeted to mitochondria. In comparison to WT animals, KO mice displayed higher mtDNA damage which preceded an exaggerated postnatal increase in heart‐to‐body mass ratio. Conversely, KO mice over‐expressing mitochondria‐targeted OGG1 displayed decreased mtDNA oxidation and a blunted elevation in cardiac mass relative to KO mice. These results suggest mtDNA damage and repair may be functionally linked to postnatal cardiac development.Grant Funding Source: Supported by the NIH R21HL102789, R01HL113614
Diverse topological requirements for mitochondrial transcription (573.5)
Authors: Sondheimer Neal , Zollo Ornella 
Published: June 2021

That transcription of the three human mitochondrial promoters can be recapitulated in vitro using a limited set of proteins including the mitochondrial RNA polymerase (POLRMT) and two accessory factors, mitochondrial transcription factor A (TFAM) and transcription factor B2 (TFB2M). The complete set of mechanisms that regulate promoter selection are unknown. The objective of this study was to determine whether the topological state of template DNA plays a role in promoter selection. We used a plasmid‐based system for the in vitro analysis of transcription that recapitulates features of the mtDNA to illustrate the relationship between topology and the three mitochondrial promoters and the involvement of TFAM which can bend template DNA. Both heavy‐strand promoters (HSP1 and HSP2) can be simultaneously transcribed from a circular template but increasing TFAM concentrations suppress HSP2 transcription at concentrations that result in HSP1 activation. We identified a requirement for the use of supercoiled DNA at HSP2 for transcription from circular templates which is not present for HSP1 and LSP. We conclude that the mitochondrial promoters have distinct requirements for DNA topology and TFAM dosage in vitro providing a means for the differential regulation of mitochondrial gene expression.Grant Funding Source: NIH/NICHD