Miracle-dz/UniFAR-FTUs huggingface dataset:
Differential Local Connectivity and Neuroinflammation Profiles in the Medial Prefrontal Cortex and Hippocampus in the Valproic Acid Rat Model of Autism

Autism spectrum disorders (ASD) are a group of developmental disabilities characterized by impaired social interaction, communication deficit and repetitive and stereotyped behaviors. Neuroinflammation and synaptic alterations in several brain areas have been suggested to contribute to the physiopathology of ASD. Although the limbic system plays an important role in the functions found impaired in ASD, reports on these areas are scarce and results controversial. In the present study we searched in the medial prefrontal cortex (mPFC) and hippocampus of rats exposed to the valproic acid (VPA) model of ASD for early structural and molecular changes, coincident in time with the behavioral alterations. After confirming delayed growth and maturation in VPA rats, we were able to detect decreased exploratory activity and social interaction at an early time point (postnatal day 35). In mPFC, although typical cortical column organization was preserved in VPA animals, we found that interneuronal space was wider than in controls. Hippocampal CA3 (cornu ammonis 3) pyramidal layer and the granular layer of the dentate gyrus both showed a disorganized spatial arrangement in VPA animals. Neuronal alterations were accompanied with increased tomato lectin and glial fibrillary acidic protein (GFAP) immunostainings both in the mPFC and hippocampus. In the latter region, the increased GFAP immunoreactivity was CA3 specific. At the synaptic level, while mPFC from VPA animals showed increased synaptophysin (SYN) immunostaining, a SYN deficit was found in all hippocampal subfields. Additionally, both the mPFC and the hippocampus of VPA rats showed increased neuronal cell adhesion molecule (NCAM) immunostaining together with decreased levels of its polysialylated form (PSA-NCAM). Interestingly, these changes were more robust in the CA3 hippocampal subfield. Our results indicate that exploratory and social deficits correlate with region-dependent neuronal disorganization and reactive gliosis in the mPFC and hippocampus of VPA rats. While microgliosis is spread in these two limbic areas, astrogliosis, although extended in the mPFC, is circumscribed to the CA3 hippocampal subfield. Our work indicates that neuroinflammation and synaptic alterations do coexist in VPA rats, making this model suitable for studying novel aspects of neuron-glia interactions. Moreover, it suggests that the mPFC and hippocampus might behave differently in the context of the local hyperconnectivity and synaptic hypotheses of autism.
Ticks (Acari: Ixodidae) Infesting Wild Birds in an Atlantic Forest Area in the State of São Paulo, Brazil, with Isolation of Rickettsia from the Tick Amblyomma longirostre

Abstract During field work in Nazaré Paulista, state of São Paulo, Brazil, we found 13 (56.5%) of 23 birds (mostly Passeriformes) to be infested by 28 larvae and 1 nymph of Amblyomma spp. Two larvae were reared to the adult stage, being taxonomically identified as Amblyomma parkeri Fonseca and Aragão, whereas five larvae and one nymph were identified as Amblyomma longirostre Koch. All six A. longirostre specimens were shown to be infected by rickettsia, as demonstrated by polymerase chain reaction (PCR) targeting two rickettsial genes (gltA and ompA) or isolation of rickettsia in cell culture from one of the ticks. This isolate was designated as strain AL, which was established in Vero cell culture and was molecularly characterized by DNA sequencing fragments of the rickettsial genes gltA, htrA, ompA, and ompB. Phylogenetic analyses inferred from ompA and ompB partial sequences showed a high degree of similarity of strain AL with Rickettsia sp. strain ARANHA, previously detected by PCR in A. longirostre ticks from Rondônia, northern Brazil. We conclude that strain AL is a new rickettsia genotype belonging to the same species of strain ARANHA, which are closely related to Candidatus ’R. amblyommii’. Further studies should elucidate if strains AL and ARANHA are different strains of Candidatus ’R. amblyommii’ or are a new species.
Ecological conditions during winter affect sexual selection and breeding in a migratory bird

Populations of migratory birds have undergone marked declines, although the causes and mechanisms remain unknown. Because environmental effects on population dynamics are mediated by the effects of ecological factors on individuals, understanding changes in individual phenotypes in response to ecological conditions is key to understanding population trends. We show that breeding individuals of a declining population of trans–Saharan migratory barn swallows, Hirundo rustica, were affected by environmental conditions, as estimated from the normalized difference vegetation index (NDVI), reflecting primary production, in their winter quarters. The breeding dates of the same individuals in consecutive breeding seasons were advanced and clutch sizes were larger after winters with high NDVI in the winter quarters. Feather moult was also affected by winter conditions, with consequences for male sexual attractiveness. Length of tail ornament was positively correlated with NDVI during the previous winter, and males with large tail ornaments reproduced earlier and had larger clutches. The mean annual breeding date of the population was earlier and breeding success was increased after favourable winters, but this result was mainly determined by a single winter with very low NDVI. Thus, ecological conditions in Africa influence individual performance and productivity in a barn swallow population.
Demonstration of rare protein in the outer membrane of Treponema pallidum subsp. pallidum by freeze-fracture analysis

The surface of Treponema pallidum subsp. pallidum (T. pallidum), the etiologic agent of syphilis, appears antigenically inert and lacks detectable protein, as judged by immunocytochemical and biochemical techniques commonly used to identify the outer membrane (OM) constituents of gram-negative bacteria. We examined T. pallidum by freeze-fracture electron microscopy to visualize the architecture of its OM. Treponema phagedenis biotype Reiter (T. phagedenis Reiter), a nonpathogenic host-associated treponeme, and Spirochaeta aurantia, a free-living spirochete, were studied similarly. Few intramembranous particles interrupted the smooth convex and concave fracture faces of the OM of T. pallidum, demonstrating that the OM of this organism is an unusual, nearly naked lipid bilayer. In contrast, the concave fracture face of the OM of S. aurantia was densely covered with particles, indicating the presence of abundant integral membrane proteins, a feature shared by typical gram-negative organisms. The concentration of particles in the OM concave fracture face of T. phagedenis Reiter was intermediate between those of T. pallidum and S. aurantia. Similar to typical gram-negative bacteria, the OM convex fracture faces of the three spirochetes contained relatively few particles. The unique molecular architecture of the OM of T. pallidum can explain the puzzling in vitro properties of the surface of the organism and may reflect a specific adaptation by which treponemes evade the host immune response.
Racial Disparities in Incarceration Increase Acceptance of Punitive Policies

During the past few decades, punitive crime policies have led to explosive growth in the United States prison population. Such policies have contributed to unprecedented incarceration rates for Blacks in particular. In this article, we consider an unexamined relationship between racial disparities and policy reform. Rather than treating racial disparities as an outcome to be measured, we exposed people to real and extreme racial disparities and observed how this drove their support for harsh criminal-justice policies. In two experiments, we manipulated the racial composition of prisons: When the penal institution was represented as “more Black,” people were more concerned about crime and expressed greater acceptance of punitive policies than when the penal institution was represented as “less Black. ” Exposure to extreme racial disparities, then, can lead people to support the very policies that produce those disparities, thus perpetuating a vicious cycle.
Protein Kinase C Activation Stimulates the Phosphorylation and Internalization of the sst2A Somatostatin Receptor*

The sst2A receptor is expressed in the endocrine, gastrointestinal, and neuronal systems as well as in many hormone-sensitive tumors. This receptor is rapidly internalized and phosphorylated in growth hormone-R2 pituitary cells following somatostatin binding (Hipkin, R. W., Friedman, J., Clark, R. B., Eppler, C. M., and Schonbrunn, A. (1997) J. Biol. Chem. 272, 13869–13876). The protein kinase C (PKC) activator, phorbol 12-myristate 13-acetate (PMA), also stimulates sst2A phosphorylation. Here we examine the mechanisms and consequences of PMA and agonist-induced sst2A phosphorylation. Like somatostatin, both PMA and bombesin increased sst2A receptor phosphorylation within 2 min. The PKC inhibitor GF109203X blocked PMA- and bombesin- stimulated sst2A phosphorylation, whereas stimulation by the somatostatin analog SMS 201–995 was unaffected. Agonist and PMA each stimulated phosphorylation in two receptor domains, the third intracellular loop and the C-terminal tail. Functionally, PMA dramatically increased the internalization of the sst2A receptor-ligand complex. This PMA stimulation was blocked by GF109203X, whereas basal internalization was unaffected. However, neither basal nor PMA-stimulated internalization was altered by pertussis toxin, whereas both were blocked by hypertonic sucrose. Therefore PKC activation and agonist binding stimulate sst2A phosphorylation by distinct mechanisms, and PKC potentiates internalization of the sst2A receptor via clathrin-coated pits. Thus, hormonal stimulation of PKC-coupled receptors may provide a mechanism for regulating the inhibitory actions of somatostatin in target tissue.
Ventricular fibrillation in the Wolff-Parkinson-White syndrome.

Ventricular fibrillation (VF) is a well-known but rare complication of the Wolff-Parkinson-White syndrome (WPW). Clinical and electrophysiological data of 23 patients with spontaneous VF were compared with data from 100 consecutive patients with WPW without VF but with symptomatic supraventricular tachycardia. The 23 patients were collected in a multicentre retrospective study in seven European centres. VF occurred in only one patient who was receiving antiarrhythmic drugs, and was the first manifestation of the syndrome in six. No significant differences were found between those with VF and without VF in age, complaints of palpitations, syncope, and presence of structural heart disease. The retrograde effective refractory period of the accessory pathway, the atrial refractory period and the fastest atrial pacing rate with 1:1 anterograde conduction over the accessory pathway were similar in both groups. Significant differences were found for sex, permanent pre-excitation on the electrocardiogram, type of documented supraventricular tachyarrhythmias, shortest RR interval less than or equal to 220 ms during spontaneous atrial fibrillation (AF), inducibility of supraventricular tachycardias, ventricular effective refractory period less than or equal to 190 ms, mean shortest RR interval during induced AF less than or equal to 180 ms and presence of multiple accessory pathways. (ABSTRACT TRUNCATED AT 250 WORDS)
The Impact of the Baby’s Congenital Malformation on the Mother’s Psychological Well-Being: An Empirical Contribution on the Clubfoot

Background: Empirical findings show that the child’s illness can interfere with parental well-being and with the construction of a well-functioning effective relationship between the child and his/her caregivers. In line with these findings, the present study aims at investigating the negative impact of the baby’s diagnosis of clubfoot on the mother and the protective function of social support; moreover, the study aims at implementing, as a pilot experience, an intervention protocol directed to the same sample of mothers, providing emotional and informational support. Methods: A sample of 34 mothers was recruited within the first 3 months of the baby’s life, including 2 groups: a clinical one, with 17 mothers of babies diagnosed with clubfoot, and a control one, with 17 mothers of healthy full-term babies. The participants completed the following instruments in 1 session: the Beck Depression Inventory-II, the Rapid Stress Assessment questionnaire, the Brief COPE, and the Multidimensional Scale of Perceived Social Support. Results: The results show that the mothers in the clinical group, compared with those in the control group, reported more stress and depressive symptoms in reaction to the birth of their baby. Moreover, they displayed a pattern of coping strategies different from those of control mothers and coherent with the meaning of having a baby with a malformation. Lastly, the group condition (clinical vs. control) significantly moderated the association of social support with stress and depression. Conclusions: These preliminary findings highlight the negative impact that the congenital malformation of clubfoot can have on mothers’ psychological well-being and the protective role of social support. Moreover, the positive feedback from the mothers receiving emotional and informational support confirms the importance of implementing intervention protocols in the hospital unit directed to parents of babies with a congenital malformation.
Suppression of non-small cell lung tumor development by the let-7 microRNA family

Many microRNAs (miRNAs) target mRNAs involved in processes aberrant in tumorigenesis, such as proliferation, survival, and differentiation. In particular, the let-7 miRNA family has been proposed to function in tumor suppression, because reduced expression of let-7 family members is common in non-small cell lung cancer (NSCLC). Here, we show that let-7 functionally inhibits non-small cell tumor development. Ectopic expression of let-7g in K-RasG12D-expressing murine lung cancer cells induced both cell cycle arrest and cell death. In tumor xenografts, we observed significant growth reduction of both murine and human non-small cell lung tumors when overexpression of let-7g was induced from lentiviral vectors. In let-7g expressing tumors, reductions in Ras family and HMGA2 protein levels were detected. Importantly, let-7g-mediated tumor suppression was more potent in lung cancer cell lines harboring oncogenic K-Ras mutations than in lines with other mutations. Ectopic expression of K-RasG12D largely rescued let-7g mediated tumor suppression, whereas ectopic expression of HMGA2 was less effective. Finally, in an autochthonous model of NSCLC in the mouse, let-7g expression substantially reduced lung tumor burden.
Application of Cell-Based Therapies in Facial Transplantation

Abstract The main purpose of cellular therapy application in face transplantation is the continuous need for the development of new strategies that would eliminate the use of toxic immunosuppressive protocols. Cellular therapy in transplantation can significantly benefit allograft survival and shorten healing time. Cells used for a therapeutic purpose are isolated mostly from bone marrow and adipose tissues. They have the ability to proliferate and differentiate in the transplanted tissue and have immunomodulatory activity. Most of the cellular therapies such as T-regulatory, dendritic, and chimeric cells are still in the experimental stage. Molecular characterization of these cells and the mechanism of their participation in allograft acceptance and rejection are not well established and will contribute to the future of modern transplantology.
Solubilization and stabilization of bacteriophage MS2 in organic solvents

Several techniques were examined for the solubilization of bacteriophage MS2 in organic solvents. Direct extraction of the MS2 from an aqueous phase into isooctane containing 2 mM AOT, a proven approach for the organic solubilization of many proteins, was not successful. However, predried samples of MS2 were solubilized through the direct addition of organic solvents containing 500 mM AOT. As an alternative procedure, reverse micelles containing aqueous solutions of MS2 were prepared in isooctane using AOT, dehydrated through solvent evaporation and azeotropic drying, and resolubilized in a solvent of choice. The structure and microenvironment of organic‐solubilized MS2 were investigated by UV absorbance, the fluorescence emission of an attached solvatochromatic dye, tryptophan fluorescence, and atomic force microscopy, all of which contributed evidence for a fully assembled capsid in the organic solvent. The solubilized MS2 was derivatized with stearic acid in chloroform, illustrating that bioconjugation reactions can be performed on organic‐solubilized capsids using reagents that are completely insoluble in water. Furthermore, the organic‐solubilized phage remained infectious after heating at 90°C for 20 min, whereas phage in aqueous buffer or dried with nitrogen were nonviable following the heat treatment protocol. The extended range of available chemical modifications and the enhanced thermal stability of the organic‐solubilized capsids bodes well for the formulation of storage‐stable vaccines predicated on reactions in or exposure to organic media. Biotechnol. Bioeng. 2007;97: 224–234. © 2006 Wiley Periodicals, Inc.
State-level structural sexual stigma and HIV prevention in a national online sample of HIV-uninfected MSM in the United States

Background:Stigmatizing social environments (of which ‘structural stigma’ is one component) negatively affect health-related outcomes. However, few studies have examined structural stigma related to sexual minority status as a risk factor for HIV outcomes among MSM. Methods:In August 2013, members of a large MSM social and sexual networking site in the United States completed a survey about HIV-prevention practices. A previously validated composite index provided values for state-level structural stigma, including density of same-sex couples, proportion of public high schools with Gay-Straight Alliances, state laws protecting sexual minorities, and public opinion toward homosexuality. Multivariable logistic generalized estimating equations assessed the relationship between structural stigma and condomless anal intercourse, use and awareness of antiretroviral-based HIV-prevention strategies (i.e. pre and postexposure prophylaxis, or PEP and PrEP), and comfort discussing male–male sex with primary care providers. Results:Among the 4098 HIV-uninfected MSM, lower state-level structural stigma was associated with decreased odds of condomless anal intercourse [adjusted odds ratio (aOR) 0.97 per one unit increase in structural stigma score, 95% confidence interval (CI) 0.94–0.99], increased odds of awareness of PEP (aOR 1.06, 95% CI 1.02–1.09), and PrEP (aOR 1.06, 95% CI 1.02–1.10), having taken PEP (aOR 1.15, 95% CI 1.05–1.26) and PrEP (aOR 1.21, 95% CI 1.01–1.44), and comfort discussing male–male sex with providers (aOR 1.08, 95% CI 1.05–1.11), after adjusting for social and state-level confounders. Conclusion:MSM living in more stigmatizing environments had decreased use of antiretroviral-based HIV-prevention strategies compared to those in less stigmatizing environments. Legal reforms protecting sexual minorities should be evaluated as structural interventions that could reduce HIV risk among MSM.
Nitric Oxide Modulates Reactivity to Angiotensin II in Internal Mammary Arterial Grafts in Hytertensive Patients Without Associated Risk Factors

We investigated the effects of extraendothelial nitric oxide (NO) on angiotensin II (Ang II) reactivity in internal mammary artery (IMA) rings, as well as the impact of hypertension without associated risk factors in this response. Vascular reactivity, NO levels, and resting membrane potentials were determined in hypertensive (HT) and normotensive (NT) IMA rings. Only rings with endothelial dysfunction were included. Ang II produced a dose-dependent contraction that was higher in HT rings. Response to Ang II was potentiated by Nω-nitro L-arginine methyl ester (L-NAME) in NT but not in HT rings. The antioxidant agents tempol and diphenyleneiodonium (DPI) reverted the hyperreactivity to Ang II in HT rings. Extraendothelial NO was present in both NT and HT rings. However, NT rings showed higher values. L‐NAME and S-methyl-L-thiocitrulline inhibited NO release in all cases. L-arginine reverted this inhibition. Both tempol and DPI increased NO release in both NT and HT rings. The number of vascular smooth muscle cells (VSMC) and anti-α-actin positive areas were lower in HT than in NT rings, without variations in wall thickness or wall/lumen ratio. With regard to resting membrane potential, we found in HT rings that the depolarization induced by Ang II was abolished by tempol. These findings suggest that extraendothelial NO counterregulates Ang II contractility in IMA rings; however, its action could be altered in hypertensive situations even though the patients did not have associated risk factors. We suggest two mechanisms: increased oxidative stress and a decreased ability of nNOS in VSMC to produce NO.
Regulation of Pancreatic β-Cell Regeneration in the Normoglycemic 60% Partial-Pancreatectomy Mouse

β-Cell mass is determined by a dynamic balance of proliferation, neogenesis, and apoptosis. The precise mechanisms underlying compensatory β-cell mass (BCM) homeostasis are not fully understood. To evaluate the processes that maintain normoglycemia and regulate BCM during pancreatic regeneration, C57BL/6 mice were analyzed for 15 days following 60% partial pancreatectomy (Px). BCM increased in Px mice from 2 days onwards and was ∼68% of the shams by 15 days, partly due to enhanced β-cell proliferation. A transient ∼2.8-fold increase in the prevalence of β-cell clusters/small islets at 2 days post-Px contributed substantially to BCM augmentation, followed by an increase in the number of larger islets at 15 days. To evaluate the signaling mechanisms that may regulate this compensatory growth, we examined key intermediates of the insulin signaling pathway. We found insulin receptor substrate (IRS)2 and enhanced-activated Akt immunoreactivity in islets and ducts that correlated with increased pancreatic duodenal homeobox (PDX)1 expression. In contrast, forkhead box O1 expression was decreased in islets but increased in ducts, suggesting distinct PDX1 regulatory mechanisms in these tissues. Px animals acutely administered insulin exhibited further enhancement in insulin signaling activity. These data suggest that the IRS2-Akt pathway mediates compensatory β-cell growth by activating β-cell proliferation with an increase in the number of β-cell clusters/small islets.