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Isolation stress is a major risk factor for neuropsychiatric disorders such as depressive and anxiety disorders. However, the molecular mechanisms underlying isolation-induced neuropsychiatric disorders remain elusive. In the present study, we investigated the subcellular mechanisms by which long-term isolation elicits depression and anxiety-related behaviors in mice. First, we found that long-term isolation induced depression-related behaviors in the forced swimming test (FST) and the sucrose preference test, as well as anxiety-related behaviors in the elevated zero maze test (EZMT) and the open field test. Next, we showed that intracentral amygdala (CeA) injection of oxytocin (OXT), but not intracerebroventricular injection, attenuated isolation-induced depression and anxiety-related behaviors via oxytocin receptor (OXTR), not vasopressin-1a receptor (V1aR), in the FST and EZMT, respectively. Quantitative real-time polymerase chain reaction analysis revealed that after 5 weeks of isolation, mRNA transcription of OXTR in the CeA, but not that of V1aR, significantly decreased, whereas OXT and vasopressin mRNA transcription in the paraventricular nucleus of hypothalamus did not change significantly. Whole-cell patch clamping of acute brain slices demonstrated that the frequency of miniature inhibitory postsynaptic currents (mIPSCs) in CeA neurons, but not their amplitude, was lower in isolated mice than in group-housed mice. Notably, OXT treatment increased the mIPSC frequency in the CeA neurons, but to a lesser extent in the case of isolated mice than in that of group-housed mice via OXTR. Taken together, our findings suggest that long-term isolation down-regulates OXTR mRNA transcription and diminishes OXT-induced inhibitory synaptic transmission in the CeA and may contribute to the development of depression and anxiety-related behaviors in isolated mice through the enhancement of CeA activity.

In a previous study, we have shown that human neural stem cells (hNSCs) transplanted in brain of mouse intracerebral hemorrhage (ICH) stroke model selectively migrate to the ICH lesion and induce behavioral recovery. However, low survival rate of grafted hNSCs in the brain precludes long-term therapeutic effect. We hypothesized that hNSCs overexpressing Akt1 transplanted into the lesion site could provide long-term improved survival of hNSCs, and behavioral recovery in mouse ICH model. F3 hNSC was genetically modified with a mouse Akt1 gene using a retroviral vector. F3 hNSCs expressing Akt1 were found to be highly resistant to H(2)O(2)-induced cytotoxicity in vitro. Following transplantation in ICH mouse brain, F3.Akt1 hNSCs induced behavioral improvement and significantly increased cell survival (50-100% increase) at 2 and 8 weeks post-transplantation as compared to parental F3 hNSCs. Brain transplantation of hNSCs overexpressing Akt1 in ICH animals provided functional recovery, and survival and differentiation of grafted hNSCs. These results indicate that the F3.Akt1 human NSCs should be a great value as a cellular source for the cellular therapy in animal models of human neurological disorders including ICH.

Ornithodoros turicata is a veterinary and medically important argasid tick that is recognized as a vector of the relapsing fever spirochete Borrelia turicatae and African swine fever virus. Historic collections of O. turicata have been recorded from Latin America to the southern United States. However, the geographic distribution of this vector is poorly understood in relation to environmental variables, their hosts, and consequently the pathogens they transmit. Localities of O. turicata were generated by performing literature searches, evaluating records from the United States National Tick Collection and the Symbiota Collections of Arthropods Network, and by conducting field studies. Maximum entropy species distribution modeling (Maxent) was used to predict the current distribution of O. turicata. Vertebrate host diversity and GIS analyses of their distributions were used to ascertain the area of shared occupancy of both the hosts and vector. Our results predicted previously unrecognized regions of the United States with habitat that may maintain O. turicata and could guide future surveillance efforts for a tick capable of transmitting high-consequence pathogens to human and animal populations.

Borrelia turicatae is a causative agent of tick-borne relapsing fever (TBRF) in the subtropics and tropics of the United States and Latin America. Historically, B . turicatae was thought to be maintained in enzootic cycles in rural areas. However, there is growing evidence that suggests the pathogen has established endemic foci in densely populated regions of Texas. With the growth of homelessness in the state and human activity in city parks, it was important to implement field collection efforts to identify areas where B . turicatae and its vector circulate. Between 2017 and 2020 we collected Ornithodoros turicata ticks in suburban and urban areas including public and private parks and recreational spaces. Ticks were fed on naïve mice and spirochetes were isolated from the blood. Multilocus sequence typing (MLST) was performed on eight newly obtained isolates and included previously reported sequences. The four chromosomal loci targeted for MLST were 16S ribosomal RNA ( rrs ), flagellin B ( flaB ), DNA gyrase B ( gyrB ), and the intergenic spacer (IGS). Given the complexity of Borrelia genomes, plasmid diversity was also evaluated. These studies indicate that the IGS locus segregates B . turicatae into four genomic types and plasmid diversity is extensive between isolates. Furthermore, B . turicatae and its vector have established endemic foci in parks and recreational areas in densely populated settings of Texas.

Background Ornithodoros turicata is an important vector of both human and veterinary pathogens. One primary concern is the global spread of African swine fever virus and the risk of its re-emergence in the Americas through potential transmission by O . turicata to domestic pigs and feral swine. Moreover, in Texas, African warthogs were introduced into the state for hunting purposes and evidence exists that they are reproducing and have spread to three counties in the state. Consequently, it is imperative to develop strategies to evaluate exposure of feral pigs and African warthogs to O. turicata. Results We report the development of an animal model to evaluate serological responses of pigs to O. turicata salivary proteins after three exposures to tick feeding. Serological responses were assessed for ~ 120 days by enzyme-linked immunosorbent assay and immunoblotting using salivary gland extracts from O. turicata. Conclusions Our findings indicate that domestic pigs seroconverted to O. turicata salivary antigens that is foundational toward the development of a diagnostic assay to improve soft tick surveillance efforts.

Little evidence exists on the effect of risk-reducing surgeries in young BRCA carriers with a previous history of breast cancer. We investigated the association between risk-reducing mastectomy (RRM) or risk-reducing salpingo-oophorectomy (RRSO), or both procedures, with survival outcomes in a large global cohort of young BRCA carriers with previous breast cancer. The BRCA BCY Collaboration is an international, hospital-based, retrospective cohort study, conducted at 109 centres in five continents, including women harbouring germline BRCA1, BRCA2, or both, pathogenic or likely pathogenic variants and diagnosed with stage I–III invasive breast cancer at the age of 40 years or younger between Jan 1, 2000, and Dec 31, 2020. The primary objectives of the present analysis were to determine the association between RRM or RRSO and overall survival in young BRCA carriers with breast cancer. The primary endpoint was overall survival. This study is registered with ClinicalTrials.gov, NCT03673306. Between Jan 1, 2000 and Dec 31, 2020, 5290 patients were included, of whom 3361 (63·5%) patients were BRCA1 pathogenic variant carriers, 2708 (51·2%) had node-negative, and 2421 (45·8%) hormone receptor-positive breast cancer. Of 5290 patients, 2910 (55·0%) underwent RRM, 2782 (52·6%) underwent RRSO. After a median follow-up of 8·2 years (IQR 4·7–12·8), RRM was associated with significantly better overall survival compared with no RRM (adjusted HR [aHR] 0·65, 95% CI 0·53–0·78; 20-year restricted mean overall survival time 17·89 years [95% CI 17·61–18·17] with RRM vs 16·65 years [16·38–16·92] without RRM). RRSO was also associated with significantly better overall survival compared with no RRSO (aHR 0·58, 95% CI 0·48–0·71; 20-year restricted mean overall survival time 17·73 years [95% CI 17·43–18·03] with RRSO vs 16·67 years [16·38–16·96] without RRSO). In this global cohort of BRCA carriers with previous breast cancer diagnosis at a young age, RRM and RRSO were both associated with a significant improvement in overall survival. These findings provide evidence for a tailored counselling of a unique and high-risk patient population on cancer risk management strategies. Italian Association for Cancer Research.

Improved repigmentation of generalized vitiligo in skin types IV–VI has been reported in clinical response to combined therapy with apremilast and narrowband (NB)-UVB; however, tissue responses to combined therapy versus NB-UVB monotherapy have not been elucidated. We compared the change from baseline in cellular and molecular markers in vitiligo skin after combined therapy versus NB-UVB monotherapy. We assessed lesional and nonlesional skin samples from enrolled subjects and evaluated for immune infiltrates, inflammatory, and melanogenesis-related markers which were compared across different treatment groups. Combined therapy resulted in significant reduction of CD8 + T cells and CD11c + dendritic cells, downregulation of PDE4B and Th17-related markers, and upregulation of melanogenesis markers. This study was limited to small sample size, skin types IV–VI, and high dropout rate. Our molecular findings support the clinical analysis that apremilast may potentiate NB-UVB in repigmentation of generalized vitiligo in skin types IV–VI.

Perceptual grouping has been extensively studied, but some areas are still unexplored—in particular, the figural organizations that emerge when bundles of intersecting lines are drawn. Here, we will describe some figural organizations that emerge after the superimposition of bundles of lines forming the profile of regular triangular waves. By manipulating the lines’ jaggedness and junction geometry (regular or irregular X junction) we could generate the following organizations: (a) a grid, or a figural configuration in which both the lines and closed contours are perceived, (b) a figure–ground organization composed of figures separated by portions of the background, and (c) a corrugated surface appearing as a multifaceted polyhedral shell crossed by ridges and valleys. An experiment was conducted with the aim at testing the role of the good-continuation and closure Gestalt factors. Good continuation prevails when the lines are straight or close to straightness, but its role is questionable in the appearance of a corrugated surface. This perceptual organization occurs despite the violation of the good-continuation rule and consists of a structure of such complexity so as to challenge algorithms of computer vision and stimulate a deeper understanding of the perceptual interpretation of groups of lines.

Metastasis is the main cause of cancer mortality. In this study, we investigated the effects of surfactin, a cyclic lipopeptide produced by Bacillus subtilis, on cancer metastasis in vitro and the underlying molecular mechanisms involved. Surfactin inhibited the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced invasion, migration and colony formation of human breast carcinoma cells. Western blot analysis, gelatin zymography and reverse transcription-PCR analysis revealed that matrix metalloproteinase-9 (MMP-9) expression and activation was significantly suppressed by surfactin in a dose-dependent manner. Surfactin attenuated TPA-induced nuclear translocation and activation of nuclear factor-κB (NF-κB) and activator protein-1 (AP-1). Furthermore, surfactin strongly repressed the TPA-induced phosphorylation of Akt and extra-cellular signal-regulated kinase (ERK). Treatment with specific inhibitors of Akt and ERK suppressed MMP-9 expression and activation. These results suggest that the surfactin-mediated inhibition of breast cancer cell invasion and MMP-9 expression involves the suppression of the NF-κB, AP-1, phosphatidylinositol 3-kinase (PI-3K)/Akt and the ERK signaling pathways. Thus surfactin may have potential value in therapeutic strategies for the treatment of breast cancer metastasis.