ARHGEF9 regulates melanoma morphogenesis in environments with diverse geometry and elasticity by promoting filopodial-driven adhesion.

Rho GTP Exchange Factors (RhoGEFs) and Rho GTPase Activating Proteins (RhoGAPs) are large families of molecules that regulate shape determination in all eukaryotes. In pathologies such as melanoma, RhoGEF and RhoGAP activity underpins the ability of cells to invade tissues of varying elasticity. To identify RhoGEFs and RhoGAPs that regulate melanoma cell shape on soft and/or stiff materials, we performed genetic screens, in tandem with single-cell quantitative morphological analysis. We show that ARHGEF9/Collybistin (Cb) is essential for cell shape determination on both soft and stiff materials, and in cells embedded in 3D soft hydrogel. ARHGEF9 is required for melanoma cells to invade 3D matrices. Depletion of ARHGEF9 results in loss of tension at focal adhesions decreased cell-wide contractility, and the inability to stabilize protrusions. Taken together we show that ARHGEF9 promotes the formation of actin-rich filopodia, which serves to establish and stabilize adhesions and determine melanoma cell shape

Reduced Affective Biasing of Instrumental Action With tDCS Over the Prefrontal Cortex

AbstractBackgroundInstrumental action is well known to be vulnerable to affective value. Excessive transfer of affective value to instrumental action is thought to contribute to psychiatric disorders. The brain region most commonly implicated in overriding such affective biasing of instrumental action is the prefrontal cortex.ObjectiveThe aim of the present study was to reduce affective biasing of instrumental action using transcranial direct current stimulation (tDCS) in young healthy human volunteers.MethodsIn a double-blind, randomized between-group design, 120 participants received anodal, cathodal and sham tDCS while at the same time (online) performing a task that assessed affective biasing of instrumental action. We placed tDCS electrodes over the anterior part of the prefrontal cortex based on evidence from brain stimulation work demonstrating the role of this brain region in controlling affective biasing of instrumental action.ResultsWe showed that prefrontal tDCS reduced affective biasing of instrumental action. Specifically, prefrontal tDCS reduced the degree to which aversive (versus appetitive) cues potentiated instrumental avoidance and suppressed instrumental approach. Contrary to our hypothesis, this effect was seen for cathodal tDCS rather than anodal tDCS.ConclusionThe results demonstrate the potential utility of prefrontal tDCS as a tool for reducing affective biasing of instrumental behavior, thus opening avenues for interventional research on psychiatric disorders that implicate excessive transfer of affective value

Comorbidities between tuberculosis and common mental disorders: A scoping review of epidemiological patterns and person-centred care interventions from low-to-middle income and BRICS countries

Background : There is increasing evidence that the substantial global burden of disease for tuberculosis unfolds in concert with dimensions of common mental disorders. Person-centred care holds much promise to ameliorate these comorbidities in low-tomiddle income countries and emerging economies. Towards this end, this paper aimed to review 1) the nature and extent of tuberculosis and common mental disorder comorbidity and 2) person-centred tuberculosis care in low-to-middle income countries and emerging economies. Main text : A scoping review was conducted of English-language studies published from 2000-2019 in peer-reviewed and grey literature, using established guidelines, for each of the study objectives. Four broad tuberculosis/mental disorder comorbidities were described in the literature, namely alcohol use and tuberculosis, depression and tuberculosis, anxiety and tuberculosis, and general mental health and tuberculosis. Rates of comorbidity varied widely across countries for depression, anxiety, alcohol use and general mental health. Alcohol use and tuberculosis were significantly related, especially in the context of poverty. The initial tuberculosis diagnostic episode had substantial socio-psychological effects on service users. While men tended to report higher rates of alcohol use and treatment default, women in general had worse mental health outcomes. Older age and a history of mental illness were also associated with pronounced tuberculosis and mental disorder comorbidity. Person-centred tuberculosis care interventions were almost absent, with only one study from Nepal identified. Conclusions : There is an emerging body of evidence describing the nature and extent of tuberculosis and mental disorders comorbidity in low-to-middle income countries. Despite the potential of person-centred interventions, evidence is limited. This review highlights a pronounced need to address psychosocial comorbidities with TB in LMICs, where models of person-centred TB care in routine care platforms may yield promising outcomes

Early detection of ultra high risk for psychosis in a Norwegian catchment area: The two year follow-up of the prevention of psychosis study

Objectives: Most individuals experience a relatively long period of sub-clinical psychotic like symptoms, known as the ultra high risk (UHR) or at risk mental states (ARMS), prior to a first episode of psychosis. Approximately 95% of individuals who will later develop psychosis are not referred to specialized clinical services and assessed during the UHR phase. The study aimed to investigate whether a systematic early detection program, modeled after the successful early detection of psychosis program TIPS, would improve the detection of help-seeking UHR individuals. The secondary aim was to examine the rates and predictors of conversion to psychosis after 2 years. Method: The overall study design was a prospective (2012–2018), follow- up study of individuals fulfilling UHR inclusion criteria as assessed by the structural interview for prodromal syndromes (SIPS). Help-seeking UHR individuals were recruited through systematic early detection strategies in a Norwegian catchment area and treated in the public mental health services. Results: In the study period 141 UHR help-seeking individuals were identified. This averages an incidence of 7 per 100,000 people per year. The baseline assessment was completed by 99 of these and the 2 year psychosis conversion rate was 20%. A linear mixed-model regression analysis found that the significant predictors of conversion were the course of positive (0.038) and negative symptoms (0.017). Age was also a significant predictor and showed an interaction with female gender ( \u3c 0.000). Conclusion: We managed to detect a proportion of UHR individuals in the upper range of the expected prediction by the population statistics and further case enrichment would improve this rate. Negative symptoms were significant predictors. As a risk factor for adverse functional outcomes and social marginalization, this could offer opportunities for earlier psychosocial intervention

Breathing Metal–Organic Framework Based on Flexible Inorganic Building Units

Five novel bismuth carboxylate coordination polymers were synthesized from biphenyl-3,4\u2032,5-tricarboxylic acid (H3BPT) and [1,1\u2032:4\u2032,1\u2032\u2032]terphenyl-3,3\u2032\u2032,5,5\u2032\u2032-tetracarboxylic acid (H4TPTC). One of the phases, [Bi(BPT)]\ub72MeOH (denoted SU-100, as synthesized), is the first example, to the best of our knowledge, of a reversibly flexible bismuth-based metal\u2013organic framework. The material exhibits continuous changes to its unit cell parameters and pore shape depending on the solvent it is immersed in and the dryness of the sample. Typically, in breathing carboxylate-based MOFs, flexibility occurs through tilting of the organic linkers without significantly altering the coordination environment around the cation. In contrast to this, the continuous breathing mechanism in SU-100 involves significant changes to bond angles within the Bi2O12 inorganic building unit (IBU). The flexibility of the IBU of SU-100 reflects the nondiscrete coordination geometry of the bismuth cation. A disproportionate increase in the solvent accessible void volume was observed when compared to the expansion of the unit cell volume of SU-100. Additionally, activated SU-100 (SU-100-HT) exhibits a large increase in unit cell volume, yet has the smallest void volume of all the studied samples

Gene expression profiles in rat brain disclose CNS signature genes and regional patterns of functional specialisation

Background: The mammalian brain is divided into distinct regions with structural and neurophysiological differences. As a result, gene expression is likely to vary between regions in relation to their cellular composition and neuronal function. In order to improve our knowledge and understanding of regional patterns of gene expression in the CNS, we have generated a global map of gene expression in selected regions of the adult rat brain (frontomedial-, temporal- and occipital cortex, hippocampus, striatum and cerebellum; both right and left sides) as well as in three major non-neural tissues (spleen, liver and kidney) using the Applied Biosystems Rat Genome Survey Microarray. Results: By unsupervised hierarchical clustering, we found that the transcriptome within a region was highly conserved among individual rats and that there were no systematic differences between the two hemispheres (right versus left side). Further, we identified distinct sets of genes showing significant regional enrichment. Functional annotation of each of these gene sets clearly reflected several important physiological features of the region in question, including synaptic transmission within the cortex, neurogenesis in hippocampus and G-protein-mediated signalling in striatum. In addition, we were able to reveal potentially new regional features, such as mRNA transcription- and neurogenesis-annotated activities in cerebellum and differential use of glutamate signalling between regions. Finally, we determined a set of 'CNSsignature' genes that uncover characteristics of several common neuronal processes in the CNS, with marked overrepresentation of specific features of synaptic transmission, ion transport and cell communication, as well as numerous novel unclassified genes. Conclusion: We have generated a global map of gene expression in the rat brain and used this to determine functional processes and pathways that have a regional preference or ubiquitous distribution within the CNS, respectively. The existence of shared specialised neuronal activities in CNS is interesting in a context of potential functional redundancy, and future studies should further explore the overall characteristics of CNS-specific versus region-specific gene profiles in the brain

Pola Gaya Hidup dalam Keuangan Keluarga (Studi Kasus:unit Kerja Institusi Pendidikan Swasta di Bandung)

This research was conducted to discover lifestyle patterns in family finances. This research was conducted in a private educational institution in Bandung. Data collection technique used in this research is survey technique with questionnaires and the data analysis technique that used in this study is descriptive analysis. It has been found that the lifestyle patterns of employees at one of private educational institution in Bandung generally still have a good patterns. This is proved by the monetary sequences of their revenues and expenses. Also, the priority selection of their needs and wants in fulfilling their life style is still in control. From this research, it is known generally the respondents already have their own house, vehicles, and mobile communication devices like hand phone. The purchasing frequency of hand phone in average is less than 2 times per year. Moreover, the respondents have already had a habit of saving/investing and buying insurance. To fill their spare time, respondents prefer to gather with their family, go to mall with frequency of 1-4 times per month and do exercise. But, the problem that needs to be taken care of is how to handle their credit cards/loans because a lot of respondents have routine spending of paying credit card installment/loans. From this research, it is also found that there is still a lack of awareness for making simple bookkeeping of their revenues and expenses. Therefore to make them family finances literate, they need to follow a counseling and training on family finances. Even, they are suggested to follow the counseling and training with their family members