New regulatory role of Znf1 in transcriptional control of pentose phosphate pathway and ATP synthesis for enhanced isobutanol and acid tolerance.

To develop a cost-effective microbial cell factory for the production of biofuels and biochemicals, an understanding of tolerant mechanisms is vital for the construction of robust host strains. Here, we characterized a new function of a key metabolic transcription factor named Znf1 and its involvement in stress response in Saccharomyces cerevisiae to enhance tolerance to advanced biofuel, isobutanol. RNA-sequencing analysis of the wild-type versus the znf1Δ deletion strains in glucose revealed a new role for transcription factor Znf1 in the pentose phosphate pathway (PPP) and energy generation. The gene expression analysis confirmed that isobutanol induces an adaptive cell response, resulting in activation of ATP1-3 and COX6 expression. These genes were Znf1 targets that belong to the electron transport chain, important to produce ATPs. Znf1 also activated PPP genes, required for the generation of key amino acids, cellular metabolites, and maintenance of NADP/NADPH redox balance. In glucose, Znf1 also mediated the upregulation of valine biosynthetic genes of the Ehrlich pathway, namely ILV3, ILV5, and ARO10, associated with the generation of key intermediates for isobutanol production. Using S. cerevisiae knockout collection strains, cells with deleted transcriptional regulatory gene ZNF1 or its targets displayed hypersensitivity to isobutanol and acid inhibitors; in contrast, overexpression of ZNF1 enhanced cell survival. Thus, the transcription factor Znf1 functions in the maintenance of energy homeostasis and redox balance at various checkpoints of yeast metabolic pathways. It ensures the rapid unwiring of gene transcription in response to toxic products/by-products generated during biofuel production. Importantly, we provide a new approach to enhance strain tolerance during the conversion of glucose to biofuels.

Prevalence of Depression and Subjective Job Stress Among Men who have Sex with Men and Transgender Community Health Workers in Pakistan.

OBJECTIVE: To determine the prevalence of depression, subjective work-related stress and associated factors among men who have sex with men and transgender people working in community-based organisations in Pakistan. STUDY DESIGN: Cross-sectional descriptive study. Place and Duration of the Study: Community-based organisations in Lahore, October 2022. METHODOLOGY: Community-based organisations were contacted and link of the study tool in the Urdu language was shared. The study tool consisted of sociodemographic questions, substance abuse history, Patient Health Questionnaire (PHQ) 9, the General Self-Efficacy Scale (GSE), and the Subjective job stress scale (SJSS). The composite score for each scale was calculated and compared. RESULTS: A total of 91 men participated in the study. Of them, 52.1% were below 30 years of age. The mean PHQ-9 score was 7.62 (range 0-27), mean GSE score was 32.38 (range 12-40), and mean SJSS score was 10.48 (4-14). While 41.7% of the participants were not depressed, 31.77% had depression of at least moderate severity. About 56.52% of the study participants had an SJSS score of more than ten showing a high level of work-related stress. CONCLUSION: There is a high frequency of depression among MSM and TG community health workers. High degree of self-efficacy may protect against depression. There is a need of developing comprehensive referral systems with psychiatric units for these community workers. KEY WORDS: Community health workers, Homosexual men, Transgender, Depression.

Filicide In Depressive Psychosis: Case Report Of An Emotionally Unstable Woman Slaughtering Her Two Children.

Filicide is the murder of a child by the parent. It is associated with various psychiatric and nonpsychiatric conditions. We herein present a case report of a filicide by an emotionally unstable mother suffering from depressive psychosis. A thirty years old woman previously treated for depression with psychotic features, having undergone electro-convulsive therapy and on oral medication three years ago was brought by the police for psychiatric assessment. She had slaughtered her two sons of 4 and 7 years of age three days ago without any guilt or remorse. She had low mood, irritability, crying spells, hopelessness and loss of sleep, appetite and sexual desires for the past six months along with the delusions of poverty and infidelity for the past two months. She was a chain smoker. Multiple deliberate self-harm and suicidal attempts were reported in the past two months. She had disturbed family life and multiple conflicts with the husband. Psychometrics revealed BDI score of 32, BPRS score of 39 and PCL-R score of 28. She was diagnosed as a case of depressive psychosis with emotionally unstable personality traits leading to impaired judgment and poor comprehension of the consequences of her actions. This case report highlights the importance of accurately and timely diagnosing and managing a mental health disorder in order to avoid the harm towards self and others.

Comparison Of Effectiveness Of Antipsychotics In Schizophrenia: Second-Generation Versus The Irstgeneration.

BACKGROUND: The choice of the antipsychotic medication is based upon the risks, benefits and the cost. There has been still a debate that which group of antipsychotics is overall better amongst the two so we planned this study with the objective to compare the efficacy of the 1st & 2nd generation antipsychotics for the treatment of schizophrenia. METHODS: This RCT was conducted at in/out patient department of Psychiatry at a tertiary care hospital of Pakistan over the time period of six months. All the patients of schizophrenia between 18-50 years of age of either gender and all the socioeconomic groups were included in the study. Each patient was assessed with the Simpson-Angus Scale (SAS) for the EPS and the Positive and Negative Syndrome Scale (PANSS) for the schizophrenia at the baseline, 6 weeks and 12 weeks after starting the designated medication. RESULTS: The mean age of the 350 patients included in the study was 34.25±16.74 years. One hundred and forty-eight (42.3%) patients were female and 202 (57.7%) were male. The overall response of 1st Generation & 2nd Generation antipsychotics was 51 (140) 36% and 135 (210) 64% respectively (p-value=0.00024). Sixty-three (45%) patients who were taking 1st Generation Antipsychotics had relapse of the disease as compared to the 29 (13.7%) patients who were taking the 2nd Generation antipsychotics. Dryness of mouth, sedation and EPS were the common side effects with the 1st generation antipsychotics while dryness of mouth, cardiac arrhythmias, and sexual dysfunction were the common side effects with the 2nd generation antipsychotics. CONCLUSIONS: This study concluded that the 2nd generation antipsychotics were superior to the 1st generation antipsychotics among the patients of schizophrenia in terms of the success rate, relapse rate and the tolerability.

Projected Increase in Hydropower Production in India under Climate Change.

Hydropower is a valuable renewable energy resource in India, which can help in climate change mitigation and meet the increasing energy demands. However, the crucial role of climate change on hydropower production in India remains unexplored. Here using the observations and model simulations, we show that seven large hydropower projects experienced a significant (p-value < 0.05) warming and a decline in precipitation and streamflow during the observed period of 1951-2007. However, all the hydropower projects are projected to experience a warmer and wetter climate in the future. Multimodel ensemble mean annual average temperature (precipitation) is projected to rise up to 6.3 ± 1.6 °C (18 ± 14.6%) in the catchments upstream of the other reservoirs by the end of the 21st century under representative concentration pathway (RCP) 8.5. Due to the projected increase in precipitation, mean annual streamflow (up to +45%) and hydropower (up to +25%) production are projected to rise under the future climate. However, significant warming (6.25 ± 1.62 °C) is projected to result in a decline in streamflow and hydropower production in May- June for snow-dominated Nathpa Jhakri and Bhakra Nangal hydropower projects. Our results provide insights into the development and planning of hydropower projects in India under the current projected future climate.