Amino acid transporter SLC38A5 is a tumor promoter and a novel therapeutic target for pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) cells have a great demand for nutrients in the form of sugars, amino acids, and lipids. Particularly, amino acids are critical for cancer growth and, as intermediates, connect glucose, lipid and nucleotide metabolism. PDAC cells meet these requirements by upregulating selective amino acid transporters. Here we show that SLC38A5 (SN2/SNAT5), a neutral amino acid transporter is highly upregulated and functional in PDAC cells. Using CRISPR/Cas9-mediated knockout of SLC38A5, we show its tumor promoting role in an in vitro cell line model as well as in a subcutaneous xenograft mouse model. Using metabolomics and RNA sequencing, we show significant reduction in many amino acid substrates of SLC38A5 as well as OXPHOS inactivation in response to SLC38A5 deletion. Experimental validation demonstrates inhibition of mTORC1, glycolysis and mitochondrial respiration in KO cells, suggesting a serious metabolic crisis associated with SLC38A5 deletion. Since many SLC38A5 substrates are activators of mTORC1 as well as TCA cycle intermediates/precursors, we speculate amino acid insufficiency as a possible link between SLC38A5 deletion and inactivation of mTORC1, glycolysis and mitochondrial respiration, and the underlying mechanism for PDAC attenuation. Overall, we show that SLC38A5 promotes PDAC, thereby identifying a novel, hitherto unknown, therapeutic target for PDAC.

The psychometric properties of the Depression Anxiety Stress Scale-21 (DASS-21) Bangla version.

The Bangla version of the Depression Anxiety Stress Scale-21 (DASS-21-BV) draws huge attention among the researchers to assess the mental health status in various situations among the Bangladeshi adults. Since no published research article to date has assessed the psychometric properties of the scale (Bangla version), this study (n = 980 Bangladeshi adults) aimed to assess the psychometric characteristics of this scale utilizing both classical test theory (CTT) and item response theory (IRT) approaches. Item analysis results (item-total correlations in CTT and slope coefficients of the graded response model in IRT) suggested that items had satisfactory discrimination indices. The confirmatory factor analysis results supported the three-factor correlated model of the DASS-21-BV. This scale had good internal consistency reliabilities (alpha, omega, Rho coefficient, etc.) in both approaches. Additionally, multigroup confirmatory factor analysis results suggested strict invariance of this scale between males and females. Although the convergent and divergent validity of the DASS-21-BV were not assessed in this study, it was still proposed as a psychometrically sound tool to assess depression, anxiety, and stress in the non-clinical sample Bangladesh.

Replication analysis of the COVID-19 Worry Scale.

Efforts and focus regarding the COVID-19 pandemic have largely been centered around physical health. However, mental health is equally as critical-as such, psychological impacts can resonate adversely during and following the pandemic. This study examined a sample of 729 Bangladeshi people and aimed to assess the psychological impact of the pandemic. Through this replication analysis, the results supported the validation and reliability of the COVID-19 Worry Scale on a Bangladeshi population. The validation of another COVID-19 mental health measure can help determine who is mentally affected by the pandemic and the extent of COVID-19's psychological impact.

Adaptation of the Bangla Version of the COVID-19 Anxiety Scale.

The Coronavirus Anxiety Scale (CAS) is among the first few published screening tools for assessing dysfunctional anxiety induced by the current COVID-19 pandemic. The CAS was translated into the Bangla language following the International Test Commission's guidelines for this adaptation study and placed in an online survey (N = 737, with a mean age of 26.55 (SD = 7.166 years) to assess the psychometric properties of the Bangla version of the scale. Results suggested that all items had a good item discrimination index and single-factor structure with good factor loadings. The CAS Bangla version was found to have good internal consistency reliabilities, test-retest reliability, and composite reliability (≥ 0.7). The measurement invariance suggested invariances across age groups and gender. The CAS Bangla version showed a high correlation to the anxiety subscale of the short form of the Depression Anxiety Stress Scale (DASS-21) and a moderate correlation to the depression subscale of the DASS-21 and the COVID-19 Worry Scale. This validation of a Bangla CAS scale would be helpful for mental health practitioners to assess pandemic anxiety among the Bangladeshi people.

Mental Health Status, Anxiety, and Depression Levels of Bangladeshi University Students During the COVID-19 Pandemic.

The current COVID-19 pandemic has affected people of all ages across the world both physically and psychologically. Understanding COVID-19's impact on university students' mental health status in Bangladesh has been limited, yet is a necessary population to study, since they are particularly vulnerable to stress and mental health issues. This study assessed anxiety, depressive symptoms, and mental health status among university students in Bangladesh. The Generalized Anxiety Disorder-7, Center for Epidemiological Studies Depression Revised Scale, and Mental Health Inventory-5 were translated into Bangla and administered to university students (N = 874) online. In total, 40% of the participants had moderate to severe anxiety, 72% had depressive symptoms and 53% had moderate to poor mental health status. Moreover, path analysis showed worrying about COVID-19 and knowledge about the virus predicted anxiety and moderate to poor mental health status; knowledge and belief about COVID-19's severity in Bangladesh predicted depressive symptoms. Thus, revealing that mental health issues were high and COVID-19 worry predicted psychopathology symptoms among Bangladeshi university students. Overall, these results, examining students' mental health during COVID-19, in April 2020, can be helpful to compare how students have adjusted over the pandemic's progression.

In silico analysis of deleterious SNPs of human MTUS1 gene and their impacts on subsequent protein structure and function.

The mitochondrial tumor suppressor 1 (MTUS1) gene acts as a crucial tumor suppressor by inhibiting growth and proliferation of eukaryotic cells including tumor cell lines. Down regulation of MTUS1 gene has been implicated in a wide range of cancers as well as various human diseases. Alteration through nsSNPs can potentially damage the structure and/or function of the protein. As characterization of functional SNPs in such disease linked genes is a major challenge, it is feasible to analyze putative functional SNPs prior to performing larger population studies. Hence, in this in silico study we differentiated the potentially harmful nsSNPs of the MTUS1 gene from the neutral ones by using various sequence and structure based bioinformatic tools. In a total of 215 nsSNPs, 9 were found to be most likely to exert deleterious effect using 7 prediction tools. From which, 5nsSNPs (S1259L, E960K, P503T, L1084V and L1143Q) were selected as potentially damaging due to their presence in the highly conserved region and ability to decrease protein stability. In fact, 2 nsSNPs (S1259L and E960K) among these 5 were found to be individually associated with two distinctive cancers named Stomach adenocarcinoma and Uterine corpus endometrial carcinoma. As this is the first comprehensive study analyzing the functional nsSNPs of MTUS1, the results of the current study would certainly be helpful in future prospects concerning large population-based studies as well as drug discovery, especially developing individualized medicine.