Miracle-dz/UniFAR-FTUs huggingface dataset:
Resetting the Dynamic Range of Hypothalamic‐Pituitary‐Adrenal Axis Stress Responses Through Pregnancy

The hypothalamic‐pituitary‐adrenal (HPA) axis plays a key role in the neuroendocrine response to stress. Dynamic changes in HPA axis regulation and hence HPA responsivity occur over the lifetime of an animal. This article focuses on two extremes of the spectrum. The first occurs naturally during pregnancy when stress responses are dampened. The second, at the opposite end of the scale, occurs in offspring of mothers who were exposed to stress during pregnancy and display exaggerated HPA axis stress responses. Reduced glucocorticoid output in response to stress in pregnancy may have important consequences for conserving energy supply to the foetus(es), in modulating immune system adaptations and in protecting against adverse foetal programming by glucocorticoids. Understanding the mechanisms underpinning this adaptation in pregnancy may provide insights for manipulating HPA axis responsiveness in later life, particularly in the context of resetting HPA axis hyperactivity associated with prenatal stress exposure, which may underlie several major pathologies, including cardiovascular disease, diabetes mellitus type 2, obesity, cognitive decline and mood disorders.
Ayurvedic approach towards Cerebral Palsy

Cerebral Palsy is the leading cause of childhood disability affecting function and development. Its prevalence is approximately 1.5-2 cases per 1000 live births. Its incidence has not changed in the last more than 4 decades, despite significant advances in the medical care of neonates. Nearly 15-20 % of total physically handicapped children suffer from Cerebral Palsy. It is a condition which cripples the child during the course of growth and development. Based on its Lakshanas , the chief Dosha involved in Cerebral Palsy is identified as Vata , hence Nidana-panchaka are evolved accordingly and this disorder can be managed on the line of treatment of Vata Vyadhi .
GPR39, a Receptor of the Ghrelin Receptor Family, Plays a Role in the Regulation of Glucose Homeostasis in a Mouse Model of Early Onset Diet‐Induced Obesity

GPR39, which may function as a Zn2+ sensor, is a member of the G protein‐coupled receptor family that also includes the receptor for the hunger hormone ghrelin. The down‐regulation of GPR39 mRNA in adipose tissue of obese type 2 diabetic patients suggests that GPR39 may contribute to the pathogenesis of the disease. The present study aimed to investigate the role of GPR39 in the regulation of energy balance and glucose homeostasis in wild‐type (GPR39+/+) and GPR39 knockout mice (GPR39−/−) with obesity‐related type 2 diabetes. GPR39 mRNA levels in adipose tissue of fasted GPR39+/+ mice fed a high‐fat diet (HFD) for 30 weeks were reduced and correlated positively with blood glucose levels. Body weight, fat percentage and energy intake were increased in the HFD group but did not differ between both genotypes. Within the HFD group, blood glucose levels were lower in GPR39−/− than in GPR39+/+ mice, despite significant reductions in prandial plasma insulin levels. The latter may not be a result of changes in β‐cell hyperplasia because immunohistochemical staining of pancreata of mice on a HFD showed no differences between genotypes. The lower blood glucose levels may involve alterations in insulin sensitivity as revealed by glucose tolerance tests and respiratory quotient measurements that showed a preference of obese GPR39−/− mice for the use of carbohydrates as metabolic fuel. The increase in plasma ghrelin levels in GPR39−/− mice fed a HFD may contribute to the alterations in glucose homeostasis, whereas changes in gastric emptying or intestinal Zn2+ absorption are not involved. The results obtained in the present study suggest that GPR39 plays a role in the pathogenesis of obesity‐related type 2 diabetes by affecting the regulation of glucose homeostasis.
Developmental changes in neuromagnetic rhythms and network synchrony in autism

There is gathering consensus that altered connectivity is a hallmark of the autistic brain. This includes atypical neural oscillations and their coordination across brain regions, which are understood to mediate information processing and integration. It remains unclear whether and how connectivity in various neurophysiological frequency ranges develops atypically in autism spectrum disorder (ASD).
Nutritional Status Based on Anthropometry of Tribal Preschool Children in Paschim Medinipur District of West Bengal, India

Objectives There is a paucity of data on nutritional status among tribal preschool children. Therefore a study was conducted to determine the nutritional status based on anthropometry among rural preschool children. Methods A community based cross sectional study was conducted during July-August 2009 in a village of Paschim Medinipur district, West Bengal, India. Nutritional status was determined based on weight-for-age, height-for-age and weight-for-height and mid upper arm circumference-for-age z-scores method. Prevalence of undernutrition was defined as Z-score <-2.0 SD from the new WHO reference standards. Results A total of 65 Munda and Oraon children aged 13-60 months were included in the present study. Overall, the prevalence of underweight, stunting and wasting was 61.5 %,38.5% and 55.4%, respectively. The prevalence of undernutrition was 56.9% based on MUAC, of whom, 44.6% and 12.3% children was moderately and severely undernourished, respectively. It was observed that the MUAC had good agreement (Kappa=0.84) with underweight, followed by moderate agreement with wasting (Kappa=0.53). While poor agreement was found with stunting (Kappa=0.28). Conclusion According to WHO criteria for severity of malnutrition, the overall prevalence of stunting was high while underweight and wasting were very high, indicating a critical situation.
Guanine Nucleotide Exchange Factor αPIX Leads to Activation of the Rac 1 GTPase/Glycogen Phosphorylase Pathway in Interleukin (IL)-2-stimulated T Cells

Background: Rac 1 GTPase mediates glycogen phosphorylase activation and controls IL-2-stimulated T cell proliferation. Results: PKCθ activates αPIX by serine phosphorylation and now this Rho-GEF activates Rac 1. Conclusion: IL-2-stimulated T cells migration and proliferation require the involvement of the PKCθ/αPIX/Rac 1/PYGM pathway. Significance: This new signaling cascade may be a viable therapeutic target to block the inflammatory response mediated by T cells. Recently, we have reported that the active form of Rac 1 GTPase binds to the glycogen phosphorylase muscle isoform (PYGM) and modulates its enzymatic activity leading to T cell proliferation. In the lymphoid system, Rac 1 and in general other small GTPases of the Rho family participate in the signaling cascades that are activated after engagement of the T cell antigen receptor. However, little is known about the IL-2-dependent Rac 1 activator molecules. For the first time, a signaling pathway leading to the activation of Rac 1/PYGM in response to IL-2-stimulated T cell proliferation is described. More specifically, αPIX, a known guanine nucleotide exchange factor for the small GTPases of the Rho family, preferentially Rac 1, mediates PYGM activation in Kit 225 T cells stimulated with IL-2. Using directed mutagenesis, phosphorylation of αPIX Rho-GEF serines 225 and 488 is required for activation of the Rac 1/PYGM pathway. IL-2-stimulated serine phosphorylation was corroborated in Kit 225 T cells cultures. A parallel pharmacological and genetic approach identified PKCθ as the serine/threonine kinase responsible for αPIX serine phosphorylation. The phosphorylated state of αPIX was required to activate first Rac 1 and subsequently PYGM. These results demonstrate that the IL-2 receptor activation, among other early events, leads to activation of PKCθ. To activate Rac 1 and consequently PYGM, PKCθ phosphorylates αPIX in T cells. The biological significance of this PKCθ/αPIX/Rac 1 GTPase/PYGM signaling pathway seems to be the control of different cellular responses such as migration and proliferation.
Deoxycytidine and Deoxythymidine Treatment for Thymidine Kinase 2 Deficiency

Thymidine kinase 2 (TK2), a critical enzyme in the mitochondrial pyrimidine salvage pathway, is essential for mitochondrial DNA (mtDNA) maintenance. Mutations in the nuclear gene, TK2, cause TK2 deficiency, which manifests predominantly in children as myopathy with mtDNA depletion. Molecular bypass therapy with the TK2 products, deoxycytidine monophosphate (dCMP) and deoxythymidine monophosphate (dTMP), prolongs the life span of Tk2‐deficient (Tk2–/–) mice by 2‐ to 3‐fold. Because we observed rapid catabolism of the deoxynucleoside monophosphates to deoxythymidine (dT) and deoxycytidine (dC), we hypothesized that: (1) deoxynucleosides might be the major active agents and (2) inhibition of deoxycytidine deamination might enhance dTMP+dCMP therapy.
Tumor Necrosis Factor (TNF) Receptor-associated Factor (TRAF)-interacting Protein (TRIP) Negatively Regulates the TRAF2 Ubiquitin-dependent Pathway by Suppressing the TRAF2-Sphingosine 1-Phosphate (S1P) Interaction*

Background: TNF receptor-associated factor 2 (TRAF2) is a key adaptor molecule in the TNF receptor (TNFR) signaling pathway. Results: TRAF-interacting protein (TRIP) inhibits Lys63-linked TRAF2 ubiquitination by blocking the binding of the cofactor sphingosine 1-phosphate (S1P) to the TRAF2 RING domain. Conclusion: TRIP negatively regulates the TRAF2 ubiquitin-dependent pathway by modulating the TRAF2-S1P interaction. Significance: TRIP is an important cellular regulator of the TNFR-mediated inflammatory response. The signaling pathway downstream of TNF receptor (TNFR) is involved in the induction of a wide range of cellular processes, including cell proliferation, activation, differentiation, and apoptosis. TNFR-associated factor 2 (TRAF2) is a key adaptor molecule in TNFR signaling complexes that promotes downstream signaling cascades, such as nuclear factor-κB (NF-κB) and mitogen-activated protein kinase activation. TRAF-interacting protein (TRIP) is a known cellular binding partner of TRAF2 and inhibits TNF-induced NF-κB activation. Recent findings that TRIP plays a multifunctional role in antiviral response, cell proliferation, apoptosis, and embryonic development have increased our interest in exploring how TRIP can affect the TNFR-signaling pathway on a molecular level. In our current study, we demonstrated that TRIP is negatively involved in the TNF-induced inflammatory response through the down-regulation of proinflammatory cytokine production. Here, we demonstrated that the TRAF2-TRIP interaction inhibits Lys63-linked TRAF2 ubiquitination by inhibiting TRAF2 E3 ubiquitin (Ub) ligase activity. The TRAF2-TRIP interaction inhibited the binding of sphingosine 1-phosphate, which is a cofactor of TRAF2 E3 Ub ligase, to the TRAF2 RING domain. Finally, we demonstrated that TRIP functions as a negative regulator of proinflammatory cytokine production by inhibiting TNF-induced NF-κB activation. These results indicate that TRIP is an important cellular regulator of the TNF-induced inflammatory response.
Idiopathic erosive polyarthritis in six dogs (description of the disease and treatment with bilateral pancarpal arthrodesis)

Summary Six dogs with severe, deforming, idiopathic erosive polyarthritis (IEP) were treated with bilateral pancarpal arthrodesis using bone-plate stabilization. This type of arthropathy resembles those classified previously as canine rheumatoid arthritis and results in a progressive erosion of articular cartilage and instability of multiple joints, most notably the carpi, tarsi and digits. Arthrodesis was successful in all of the cases and resulted in a significant improvement in ambulation in all six dogs, even in the presence of continued compromise of phalangeal and tarsal joints. Idiopathic erosive polyarthritis (IEP) is a disease of unknown pathogenesis that affects multiple joints of dogs, usually of the distal limbs, and causes a symmetrical, progressive lameness. Six dogs affected with IEP were treated with bilateral pancarpal arthrodesis, resulting in improved ambulatory ability and an adequate quality of life.
Conversion of a Chaperonin GroEL-independent Protein into an Obligate Substrate*

Background: Chaperonin GroEL and GroES (GroE) assist a subset of proteins in the cell. Results: Conversion of a GroE-independent MetK into an obligate MetK occurred; GroE dependence was correlated with the propensity to form protein aggregates. Conclusion: Subtle differences, even at single point mutations, determine the GroE dependence. Significance: Buffering the aggregation-prone mutations by GroE plays a role in maintaining diversity of proteins. Chaperones assist protein folding by preventing unproductive protein aggregation in the cell. In Escherichia coli, chaperonin GroEL/GroES (GroE) is the only indispensable chaperone and is absolutely required for the de novo folding of at least ∼60 proteins. We previously found that several orthologs of the obligate GroE substrates in Ureaplasma urealyticum, which lacks the groE gene in the genome, are E. coli GroE-independent folders, despite their significant sequence identities. Here, we investigated the key features that define the GroE dependence. Chimera or random mutagenesis analyses revealed that independent multiple point mutations, and even single mutations, were sufficient to confer GroE dependence on the Ureaplasma MetK. Strikingly, the GroE dependence was well correlated with the propensity to form protein aggregates during folding. The results reveal the delicate balance between GroE dependence and independence. The function of GroE to buffering the aggregation-prone mutations plays a role in maintaining higher genetic diversity of proteins.
The Mechanoenzymatic Core of Dynamin-related Protein 1 Comprises the Minimal Machinery Required for Membrane Constriction*

Background: Drp1 oligomerization and activity is critical for mitochondrial fission. Results: GTP hydrolysis is required for Drp1 constriction of lipid bilayers. The variable domain of Drp1 regulates self-assembly and is not required for constriction of lipid bilayers. Conclusion: The core machinery of Drp1 is sufficient to mediate lipid assembly, constriction, and disassembly. Significance: Characterization of the mechanoenzymatic properties of Drp1 advances our understanding of mitochondrial fission. Mitochondria are dynamic organelles that continually undergo cycles of fission and fusion. Dynamin-related protein 1 (Drp1), a large GTPase of the dynamin superfamily, is the main mediator of mitochondrial fission. Like prototypical dynamin, Drp1 is composed of a mechanochemical core consisting of the GTPase, middle, and GTPase effector domain regions. In place of the pleckstrin homology domain in dynamin, however, Drp1 contains an unstructured variable domain, whose function is not yet fully resolved. Here, using time-resolved EM and rigorous statistical analyses, we establish the ability of full-length Drp1 to constrict lipid bilayers through a GTP hydrolysis-dependent mechanism. We also show the variable domain limits premature Drp1 assembly in solution and promotes membrane curvature. Furthermore, the mechanochemical core of Drp1, absent of the variable domain, is sufficient to mediate GTP hydrolysis-dependent membrane constriction.
Sequential Amyloid-β Degradation by the Matrix Metalloproteases MMP-2 and MMP-9*

Background: Abnormal accumulation of Aβ in the brain is associated with neurodegeneration in Alzheimer disease. Results: Proteolytic degradation of Aβ by MMP-2/MMP-9 sequentially generates highly soluble, nontoxic, and nonfibrillogenic C-terminally truncated fragments normally present in CSF. Conclusion: The MMP-generated Aβ species likely reflects clearance mechanisms rather than active participation in the amyloidogenesis process. Significance: Matrix metalloproteases are important contributors to Aβ homeostasis. Matrix metalloproteases (MMPs) MMP-2 and MMP-9 have been implicated in the physiological catabolism of Alzheimer's amyloid-β (Aβ). Conversely, their association with vascular amyloid deposits, blood-brain barrier disruption, and hemorrhagic transformations after ischemic stroke also highlights their involvement in pathological processes. To better understand this dichotomy, recombinant human (rh) MMP-2 and MMP-9 were incubated with Aβ40 and Aβ42, and the resulting proteolytic fragments were assessed via immunoprecipitation and quantitative mass spectrometry. Both MMPs generated Aβ fragments truncated only at the C terminus, ending at positions 34, 30, and 16. Using deuterated homologues as internal standards, we observed limited and relatively slow degradation of Aβ42 by rhMMP-2, although the enzyme cleaved >80% of Aβ40 during the 1st h of incubation. rhMMP-9 was significantly less effective, particularly in degrading Aβ(1–42), although the targeted peptide bonds were identical. Using Aβ(1–34) and Aβ(1–30), we demonstrated that these peptides are also substrates for both MMPs, cleaving Aβ(1–34) to produce Aβ(1–30) first and Aβ(1–16) subsequently. Consistent with the kinetics observed with full-length Aβ, rhMMP-9 degraded only a minute fraction of Aβ(1–34) and was even less effective in producing Aβ(1–16). Further degradation of Aβ(1–16) by either MMP-2 or MMP-9 was not observed even after prolonged incubation times. Notably, all MMP-generated C-terminally truncated Aβ fragments were highly soluble and did not exhibit fibrillogenic properties or induce cytotoxicity in human cerebral microvascular endothelial or neuronal cells supporting the notion that these truncated Aβ species are associated with clearance mechanisms rather than being key elements in the fibrillogenesis process.
Exploratory Study of Animal Assisted Therapy Interventions Used by Mental Health Professionals

The purpose of this study was to explore the various animal assisted interventions mental health professionals incorporate in the therapeutic treatment process, as well as the various therapeutic purposes intended with each technique. Participants were recruited from animal assisted therapy related databases. Participants included professionals who practiced in the mental health field. Thirty one participants qualified for the study. A survey was developed based on information found reviewing literature related to animal assisted therapy. Nineteen animal assisted therapy techniques and ten therapeutic intentions were identified from a review of the literature. Participants were asked to rate on a Likert scale how often they incorporated each technique in their treatment process. Additionally, participants were asked to identify which therapeutic purposes they intended with each technique. Results indicated participants incorporated a variety of animal assisted techniques for various therapeutic intentions. Results indicated seven animal assisted techniques were incorporated by more than 50% of the participants. Building rapport in the therapeutic relationship was the most common therapeutic intention reported with a variety of animal assisted techniques.
Critically Examining Black Students’ Preparation to Counsel White Clients

Abstract This study explored how Black students are prepared to counsel White clients in two predominantly White universities. Data analysis revealed five themes, which exposed Black students’ preparation experiences: (a) relevant content excluded, (b) stereotyping experienced, (c) authenticity challenged, (d) counter spaces should be included, and (e) cultural sensitivity of faculty warrants increase. The authors discuss implications of the study’s findings for educators as well as limitations and recommendations for future research. Author's Notes Correspondence addressing this article should be sent to Natoya Hill Haskins: nhaskins@uga.edu
Circadian Modulation of Osmoregulated Firing in Rat Supraoptic Nucleus Neurones

The antidiuretic hormone vasopressin (VP) promotes water reabsorption from the kidney and levels of circulating VP are normally related linearly to plasma osmolality, aiming to maintain the latter close to a predetermined set point. Interestingly, VP levels rise also in the absence of an increase in osmolality during late sleep in various mammals, including rats and humans. This circadian rhythm is functionally important because the absence of a late night VP surge results in polyuria and disrupts sleep in humans. Previous work has indicated that the VP surge may be caused by facilitation of the central processes mediating the osmotic control of VP release, and the mechanism by which this occurs was recently studied in angled slices of rat hypothalamus that preserve intact network interactions between the suprachiasmatic nucleus (SCN; the biological clock), the organum vasculosum lamina terminalis (OVLT; the central osmosensory nucleus) and the supraoptic nucleus (SON; which contains VP‐releasing neurohypophysial neurones). These studies confirmed that the electrical activity of SCN clock neurones is higher during the middle sleep period (MSP) than during the late sleep period (LSP). Moreover, they revealed that the excitation of SON neurones caused by hyperosmotic stimulation of the OVLT was greater during the LSP than during the MSP. Activation of clock neurones by repetitive electrical stimulation, or by injection of glutamate into the SCN, caused a presynaptic inhibition of glutamatergic synapses made between the axon terminals of OVLT neurones and SON neurones. Consistent with this effect, activation of clock neurones with glutamate also reduced the excitation of SON neurones caused by hyperosmotic stimulation of the OVLT. These results suggest that clock neurones in the SCN can mediate an increase in VP release through a disinhibition of excitatory synapses between the OVLT and the SON during the LSP.
Comparative pharmacological evaluation of adaptogenic activity of Holoptelea integrifolia and Withania somnifera

The present work was planned to compare adaptogenic activity of ethanolic extracts of Holoptelea integrifolia (ETHEHI 250 mg/kg and ETHEHI 500 mg/kg) with Withania somnifera (ETHEWS 100 mg/kg) using forced swimming endurance test and Chronic cold restraint stress models. Based on the results, it can be concluded that both 250mg/kg and 500mg/kg doses of ethanolic extract of Holoptelea integrifolia showed adaptogenic activity and this activity was closer to the activity of 100mg/kg of Withania somnifera. The adaptogenic activity was dose dependent in ethanolic extract of Holoptelea integrifolia. These effects may be due to the presence of tannins, saponins, alkaloids, phenolics, flavonoids in the extract of bark of Holoptelea integrifolia as flavonoids, tannins and phenolics are mainly responsible for adaptogenic activity. Adaptogens have not only specific therapeutic effects in some stress induced and stress related disorders, but will also have an impact on the quality of life of patients.