bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neutrophil gelatinase‐associated lipocalin in rats with myocardial infarction: expression in the brain related to depression? (728.13)
Authors: Gouweleeuw Leonie , Liu Hui , Eisel Ulrich , Schoemaker Regien 
Published: June 2021

Heart failure increases the risk to develop depression, which worsens prognosis. Plasma Neutrophil Gelatinase‐Associated Lipocalin (NGAL), associated with heart failure as well as with depression, is found increased in cardiomyocytes weeks after myocardial infarction (MI) in rats. This study was aimed to investigate the role of NGAL in depressive symptoms in MI rats.Male Wistar rats were subjected to coronary artery ligation (MI) or sham surgery. Three weeks later, depressive symptoms were obtained from the open field test. Plasma levels of NGAL were measured with Elisa, and NGAL expression in the brain was obtained using immunohistochemistry.Plasma NGAL levels were increased related to infarct size (r=0.78, p=0.013, N=9). NGAL expression in the paraventricular nucleus of the hypothalamus was increased in MI compared to sham rats (45±7 vs 26±3 NGAL+ cells per high power field), irrespective of plasma NGAL levels. The increased number of NGAL positive cells in the paraventricular nucleus of the hypothalamus was negatively correlated to exploratory behavior in the open field (r=‐0.77, p=0.006). A decrease in exploratory behavior in the open field can be considered a sign of depressive behavior.Data indicate that while circulating NGAL may rather represent severity of heart failure, locally expressed NGAL in the brain may be associated with depressive symptoms after myocardial infarction in rats.
Innovative therapies in psychiatric medicine (728.14)
Authors: Cartier Earnestine , Cartier William , Tulp Orien , Einstein George 
Published: June 2021

To determine the effectiveness of innovative approaches on behavioural medicine outcomes, a long term two phase study was developed involving using clinical records review and associated parameters in a long term in‐patient population. Phase I of the research has taken 5 years (Psychological Aspect). The second ongoing phase, which will last a duration of 2 years, will consist of medical‐lab testing, bio‐markers, nutritional guidance and usage of pharmaceuticals. Within our research, we wondered what was missing in the treatment of the mentally ill. Phase one of our research has been within the correctional system. The United States and the world at this time are being overwhelmed with mentally ill Offenders. We all must remember, before these individuals became offenders they may have been in our school systems, walking the streets, everywhere within our infrastructure. In this phase of our research we will demonstrate that each case study has presented evidence that each individual was able to exercise some “Independent” control over his/her stressors within society by being taught how to correctly “manage” their own behavior. Phase two of our research, will be outside of the correctional system. We hope to prove again, that utilizing of this form of therapy, along with a group of researchers, researching critical diseases, that there will be measurable metabolic and behavioural changes that will favourably enhance the rehabilitative process.Grant Funding Source: Institutional Resources
Effects of stress on CRH, CRH‐R1, CRH‐R2 expressions and anxiety‐related behaviors (728.16)
Authors: Eraslan Evren , Akyazi Ibrahim , Ergül Ekiz Elif , Matur Erdal 
Published: June 2021

The effects of noise stress on brain corticotrophin‐releasing hormone (CRH), CRH receptors 1and 2 (CRH‐R1, CRH‐R2) mRNA levels and anxiety related behaviors in rats have been investigated.Rats, which were divided into 4 groups consisting of 8 animals each, were used for gene expression analyses. Basal Level Group (BSG) was sacrificed without exposing to stress. Other groups were exposed to 4 hour long, 100 dB white noise stress every day. Acute Stress Group (ASG) was sacrificed after 30 min stress application. Subacute Stress Group (SSG) and Chronic Stress Group (KSG) were sacrificed at day 16 and at day 31 respectively, 24 hours after stress application. Expression profiles of CRH, CRH‐R1, and CRH‐R2 in amygdala and hypothalamus were analysed by quantitative RT‐ PCR.The same stress procedure was applied to the experimental group of behavior test. Effects of stress on anxiety‐related behaviors were investigated in defensive withdrawal test. Control and experimental rats were tested on 29th and 30th of the stress application days.CRH and CRH‐R1 mRNA levels increased in amygdala and hypothalamus of KSG animals comparing to those of control. In amygdala mRNA levels of CRH‐R1 in ASG animals and CRH‐R2 in ASG, SSG and KSG decreased. In hypothalamus, CRH‐R2 mRNA levels in SSG decreased. In the defensive withdrawal test, latency to exit the closed chamber decreased in stressed group.Chronic white noise stress causes delayed CRF system activation observed as CRH and CRH‐R1 mRNA expression increases in brain . As anxiety related behaviors were measured before this delayed activation, anxiolytic effect observed in stressed animals may be related to decreased CRH‐R2 mRNA levels in amygdala and also the type of the stressor.Grant Funding Source: This work was supported by Research Fund of Istanbul University (No:4963)
Recurrent laryngeal nerve morphometry in short‐term experimental diabetes (728.21)
Authors: Mendes Vânia Alice , Silva Greice Anne , Castania Jaci , Salgado Helio , Fazan Valéria Paula 
Published: June 2021

The recurrent laryngeal nerve (RLN) is responsible for the innervation of most laryngeal muscles, including the vocal muscle. Reports on vocal cord palsy in diabetic patients are increasing in the literature but, to the best of our knowledge, there are no reports on the morphology of the RLN in human or experimental models of diabetes. In the present study, male Wistar rats received a single intravenous streptozotocin (STZ) injection in order to induce diabetes while control rats received vehicle. The diabetic state was confirmed by the high glycemic levels on the 3rd day after STZ injection. On the 15th day after the injections, rats were anesthetized for arterial pressure (AP) and heart rate (HR) recordings, prior to RLN removal. Proximal and distal segments of the right and left RLN were prepared for light microscopy morphometry, by means of a computer software. Both the AP and HR were reduced in the diabetic group, attaining significant difference on the HR values. Fascicle morphometry parameters were not different between groups. Myelinated fiber morphometry showed smaller axonal area and diameter on diabetic animals’ nerves, attaining significance on the distal left segments. Average G ratio values were normal (0.6) in controls with a tendency to smaller values in the diabetic group. These results suggest the presence of axonal atrophy on the RLN of diabetic rats, that show early in the STZ experimental model.Grant Funding Source: Supported by FAPESP, CAPES, CNPq and FAEPA.
Vagus nerve morphology in elderly spontaneously hypertensive rats (728.23)
Authors: Silva Letícia , Castania Jaci , Salgado Helio , Fazan Valéria Paula 
Published: June 2021

Aging affects peripheral nerve function and regeneration in experimental models but few literature reports deal with animals aged one year or more. The vagus nerve is an important branch of the efferent arm of the baroreflex heading to the heart. In adult spontaneously hypertensive rats (SHR), the vagus nerve morphology was compared between genders [1] and no differences were found. However, the effects of aging associated to hypertension were not yet investigated for this nerve. Male SHR aged 20 and 50 weeks had their arterial pressure (AP) and heart rate (HR) recorded by a computerized system. The rats were then systemically perfused with a fixative solution and had their cervical vagi nerves prepared for light microscopy. Proximal and distal segments of the left and right vagi nerves were evaluated for morphometric parameters including fascicle area and diameter. Comparisons were made between sides and segments on the same age as well as between ages. Differences were considered significant when p<0.05. SHR aged 50 weeks were heavier than 20‐week old animals, with no differences on the AP and HR averages. Body weight differences were followed by fascicular area and diameter results, as 50‐week old animals have larger vagus nerve fascicles compared to 20‐week old animals. Also, 50‐week old animals presented a clear reduction of the number of endoneural vessels compared to younger animals. This results deserves further investigations. Our data provide a morphological basis for further studies involving functional investigations of the efferent arm of the baroreflex in hypertension associated with ageing.[1] Alcântara et al. Brain Res 1197:170, 2008.Grant Funding Source: FAPESP, CAPES, CNPq and FAEPA
Abnormalities in BDNF/TrkB/PI3K signaling pathways in autism (728.3)
Authors: Fahnestock Margaret , Nicolini Chiara 
Published: June 2021

Cortical connectivity and spine abnormalities may account for clinical features of autism. BDNF, a key spine regulator, exhibits altered isoform balance in autism. Here, we investigated whether BDNF receptors and their signaling pathways are disrupted in post‐mortem fusiform gyrus from subjects with autism compared to controls and in the valproic acid (VPA)‐induced rat model of autism.Protein levels were examined by Western blot in 11 autism vs 13 control subjects and in lateral temporal neocortices of VPA rats vs controls. Reduced TrkB, PI3K, Akt, mTOR, phospho‐mTOR, p70S6K, eIF4B and PSD‐95 and a trend towards increased truncated TrkB and p75NTR, but no changes in 4E‐BP1 or eIF4E, were found in autism subjects versus controls. Similar deficits were observed in VPA rats, although total and phospho‐4E‐BP1 were decreased in these rats.These findings suggest imbalances in BDNF/TrkB/PI3K and proBDNF/p75NTR signaling in autism which could lead to spine defects. Reduced Akt‐mTOR protein and signaling, suggesting spine protein synthesis deficits, were observed in both autism and VPA rats, despite minor differences in down‐regulated signaling cascades. The resulting spine defects might lead to loss of excitatory synapses/decreased PSD‐95 in autism. Reduced excitatory synapses might perturb cortical circuitry, contributing to autism’s cognitive and behavioral deficits.
Lower extremity skin temperature and intramuscular response to whole body vibration (731.6)
Authors: Crossley Kent , Denning W. , Rigby Justin , Feland J. 
Published: June 2021

Previously established research has shown that whole body vibration (WBV) is effective at increasing intramuscular temperature (IMT) of the medial gastrocnemius (MG) at 26Hz. A “reaction” of itching and redness to WBV has been noted in prior research, but is not reported in all subjects. The purpose of this study was to determine if WBV affects skin and MG IMT differently in those exhibiting this reaction vs those with no reaction when performing a standard static semi‐squat WBV protocol. 60 subjects were screened, 10 exhibited a reaction; 6 had no reaction. Subjects completed two 5x60s bouts of WBV (26Hz, 4mm amplitude) on an oscillating platform with 15s rest between bouts. Skin and IMT were taken pre, mid (after 5 min vibration), and post 10 min of vibration. There was no difference in starting temperatures for skin or MG IMT. No significant change in skin or MG IMT of the non‐reactive group. Reactive group had significant increases in skin temperature (pre‐mid p<.0001, 2.32°C; pre‐post p<.0001, 2.57°C) and MG IMT (pre‐mid p<.0001, 1.5°C, mid‐post p<.004, 0.95°C, pre‐post p<.0001, 2.46°C). In conclusion, WBV exerts its effects upon reactive and non‐reactive groups differently. This difference could be due to histamine release due to WBV. Future research should be conducted to determine how WBV affects skin and muscle temperature or blood flow response.Grant Funding Source: None
Plasma rich platelet use in experimental burn model of second and third degrees (734.4)
Authors: Monte‐Alto‐Costa Andrea , Venter Neil , Santos Jeanine , Marques Ruy 
Published: June 2021

Plasma rick platelet (PRP) is a concentrated of platelets, that releases growth factors to stimulate healing. This study evaluates the effects of PRP on an experimental burn model. Wister rats were divided into 2 groups: second (SD) and third (TD) degrees burn; in each group, 8 animals were treated with PRP and 8 animals were not treated. Burn area was measured weekly until day 21, when animals were killed and samples collected. Sections were stained with hematoxylin and eosin and immunostained for CD68 and α‐smooth muscle actin. Hydroxyproline levels were determined by biochemical method. At day 21, wounds areas in SD where significantly smaller in the PRP treated animals. The density of inflammatory cells, CD68 positive macrophages, and blood vessels was greater in the control group of SD. In this study we showed that PRP treatment was able to improve the healing of second degree burns but not of the third degree burns.Grant Funding Source: Supported by: FAPERJ, CNPq and CAPES
Blockade of the opioid growth factor receptor with naltrexone enhances wound repair in type 2 db/db mice (734.5)
Authors: Immonen Jessica , Zagon Ian , McLaughlin Patricia 
Published: June 2021

Type 2 diabetes (T2D) is associated with impaired cutaneous wound healing, and can result in ulceration, infection and/or amputation. More than 26 million people in the U.S. have T2D and are vulnerable to epithelial‐related complications. New therapies regulating altered diabetic pathways are needed. Topical application of the opioid receptor antagonist naltrexone (NTX) dissolved in cream reverses delayed wound closure, and enhances angiogenesis and remodeling of full‐thickness wounds in T1D rats. NTX acts though the OGF‐OGFr axis to accelerate DNA synthesis and cell proliferation, and is a potential therapy for nonhealing wounds. In this study, the genetically obese mouse model db/db and normal C57Bl/6 mice received 6 mm diameter circular wounds on their dorsum. Wounds were treated topically 3 times daily with 10‐5 M NTX, or sterile saline, dissolved in cream, and photographed every 2 days. Db/db mice receiving saline had wounds that were 11‐92% larger than those in normal mice. NTX therapy reduced residual wound size by 13‐30% between days 8 and 14 compared to diabetic, vehicle‐treated wounds. Reepithelialization and DNA synthesis, as analyzed by epithelial thickness and BrdU labeling index, were accelerated in NTX treated wounds. These data indicate that a novel opioid receptor pathway is impaired under diabetic conditions, and modulation with NTX can regulate deleterious changes in healing seen in T2D.Grant Funding Source: American Diabetes Association
Template homology determines the genetics and mechanisms of gross chromosomal rearrangements in S. cerevisiae (736.11)
Authors: Bell Sara , Putnam Christopher , Kolodner Richard 
Published: June 2021

Double strand breaks (DSBs) can lead to genome instability and cell death, and must be faithfully repaired. In Saccharomyces cerevisiae, DSBs are primarily repaired via homologous recombination (HR), which uses homologous sequence as a template for repair. Improper repair can result in gross chromosomal rearrangements (GCRs) such as translocations. Aberrant HR may occur when a template sequence with imperfect homology is used instead of completely homologous sequence. It is not known how divergent homologous sequences are selected as targets for non‐allelic HR, or which pathways suppress the formation of such GCRs. To examine this, we devised 3 separate genetic assays to detect GCRs mediated by a distinct sequence with imperfect homology to the rest of the genome. The assays differ from each other in both percent homology to their target sequences and number of potential rearrangement targets. We find that the GCR rates for these assays differ from each other as well as from existing assays. Additionally, the GCRs detected by the 3 assays exhibit diverse genetic requirements, responding differently to mutations affecting the HR pathways, HR between divergent sequences, and the DNA replication checkpoint. Finally, we characterized the products of the GCRs observed in the 3 assays. These results suggest that the homology between the recombination substrate and its rearrangement targets influences the mechanisms and genetics of GCR formation and the GCR spectrum.Grant Funding Source: NIH Grant GM26017
Reduced SHMT2 expression and serine/glycine ratio affect mtDNA (736.7)
Authors: Alonzo Judith , Stover Patrick 
Published: June 2021

Maintaining proper nucleotide balance is required to avoid genome instability, for both mitochondrial DNA (mtDNA) and nuclear DNA (nuDNA). Mitochondrial deoxynucleotide triphosphates (dNTPs) are obtained from either salvage or de novo biosynthesis pathways. De novo biosynthesis of thymidylate and purines is folate‐dependent. De novo thymidylate (dTMP) biosynthesis has been shown to occur within mitochondria for mtDNA synthesis and the nucleus for nuDNA synthesis. Disruption of nuclear de novo dTMP biosynthesis affects genome integrity and increases uracil levels in DNA.In mitochondria, de novo dTMP biosynthesis requires serine hydroxymethyltransferase 2 (SHMT2), which transfers a one‐carbon unit from serine to tetrahydrofolate (THF), producing 5,10‐methyleneTHF and glycine; 5‐10‐methyleneTHF is then utilized by thymidylate synthase to generate dTMP from dUMP. In the nucleus, SHMT expression is limiting in de novo dTMP biosynthesis, and reduced SHMT expression elevates uracil content in nuDNA. We are investigating effects of reduced SHMT2 expression and alterations in the cellular serine/glycine ratio on mtDNA content, mitochondria mass, and uracil levels in mtDNA in HeLa cells. Preliminary data indicate that reduced SHMT2 expression and serine and glycine ratio affect mtDNA content and mtDNA integrity.Grant Funding Source: Supported by NIH R37DK58144
Pathogen‐mediated regulation of small GTPases (739.9)
Authors: Neunuebel Maria , Chen Yang , Backlund Peter , Machner Matthias 
Published: June 2021

Legionella pneumophila is an opportunistic pathogen that infects human alveolar macrophages causing a severe pneumonia known as Legionnaire’s disease. Upon phagocytosis into the host cell, L. pneumophila efficiently avoids endolysosomal fusion and degradation, and provides an environment that is suitable for bacterial replication by translocating a vast number of effector proteins into the host cell to subvert the function of key regulatory proteins such as small GTPases. Post‐translational modification of small GTPases is emerging as a critical strategy for virulence of intracellular pathogens, including L. pneumophila. My objective was to dissect how L. pneumophila exploits the ER‐to‐Golgi vesicle transport pathway through reversible AMPylation (covalent addition of adenosine 5‐monophosphate) of Rab1, a key regulator of endoplasmic reticulum (ER)‐to‐Golgi traffic. Rab1 is recruited to the Legionella‐containing vacuole (LCV), activated, and then AMPylated by SidM. Our results show that AMPylated Rab1 is locked in the active conformation until the Legionella effector protein SidD de‐AMPylates Rab1, causing the inactivation and subsequent release of Rab1 from the LCV. AMPylation is a novel post‐translational modification in the pathogen‐host context and it is an efficient strategy to control host cellular pathways during infection by L. pneumophila as well as other intracellular bacterial pathogens.Grant Funding Source: Supported by the National Institute for Child Health nad Human Development
Resveratrol prevents p53 core domain aggregation (754.1)
Authors: Costa Danielly , Campos Nathali , Rangel Luciana , Zanphorlin Letícia , Ramos Carlos , Silva Jerson 
Published: June 2021

p53 has an essential role in preventing cancer development by inducing cell cycle arrest and/or apoptosis in response to cellular stress. Mutations in the p53 gene are described in over 50% of all human cancers. Besides the mutations, cellular aggregation of p53 can also inactivate the protein, leading to malignancy. Resveratrol, a natural polyphenol found in grapes and red wine, is able to induce p53‐dependent cell death in a variety of cell lines. Although several indirect mechanisms of p53 activation by resveratrol have been proposed, there is no evidence that this bioactive compound can interact with p53. Thus, we investigated a possible interaction between resveratrol and the p53 core domain (p53C). In addition, we tested the potential of resveratrol in preventing wild‐type and mutated p53 aggregation in vitro and in tumor cells. Experiments were performed by using fluorescence spectroscopy and fluorescence microscopy techniques. Our data suggest that an interaction between resveratrol and the wild‐type p53C does occur. We also found that resveratrol has the ability to inhibit the wild‐type p53 core domain as well as the R248Q p53 mutant to undergo in vitro aggregation. Additionally, resveratrol (50 and 100µM) reduces the formation of nuclear p53 aggregates in MDA‐MB231 human breast cancer cells. Our study provides evidence that resveratrol can directly modulate p53 and may pave the way for a better understanding of the mechanisms involved in p53 protein aggregation as a therapeutic strategy for cancer treatment.Grant Funding Source: Supported by FAPERJ, CNPq, INCT/INBEB
The effects of curcumin, ellagic acid and methionine on post‐thawed Merino rams sperm parameters (759.1)
Authors: Omur Ali , Coyan Kenan , Ozturk Caner , Gungor Sukru , Bucak Mustafa 
Published: June 2021

The aim of this study was to determine the effects of the antioxidants curcumin, ellagic acid and methionine on microscopic sperm parameters following the freeze‐thawing of Merino ram semen. Ejaculates were collected via artificial vagina from four Merino rams and microscopically evaluated and pooled at 37 ◦C. The pooled semen samples were diluted in a Tris‐based extender and separated to groups including curcumin (1, 2, 4 mM), ellagic acid (1, 2, 4 mM), methionine (1, 2, 4 mM) and no antioxidant (control). The diluted semen was slowly cooled to 5 ◦C and then the samples were frozen in liquid nitrogen vapour, plunged into liquid nitrogen (‐196ºC) for storage. Frozen straws were thawed individually at 37 ◦C for 30 s in a water bath for microscopic sperm evaluation. All of antioxidant groups led to higher percentage of sperm motility in comparison to the control group. The freezing extender supplemented with methionine (1 mM), curcumin (1 and 2 mM), ellagic acid (1 and 2 mM) led to higher percentage of sperm plasma membrane integrity when compared to the other groups (P < 0.05). Looking at the evaluation of sperm acrosome integrity, antioxidant groups led to higher percentace in comparison to the control. Methionine, curcumin and ellagic acid (1mM: 27.7±2.4, 28.0±2.1 and 26.8±2.0) groups provided more higher protective in terms of sperm mitochondrial activity when compared to the other groups (P < 0.05). Findings of this study showed that the different antioxidants (curcumin, methionine and ellagic acid) at different doses protective effects on the ram sperm parameters.Grant Funding Source: Selcuk University SCIENTIFIC RESEARCH PROJECTS COORDINATION UNIT (Project no: 09102041)