Glioblastoma is the most fatal of all primary human brain tumors with 14 months median survival. The mainstay therapy for this tumor involves temozolomide, surgery, radiotherapy and tumor treating electric field. Cancer resistance to commonly available chemotherapeutics remains a major challenge in glioblastoma patients receiving treatment and unfavorably impact their overall survival and outcome. However, the lack of progress in this area could be attributed to lack of tools to probe unbiasedly at the genome wide level the coding and non-coding elements contribution on a large scale for factors that control resistance to chemotherapeutics. Understanding the mechanisms of resistance to chemotherapeutics will enable precision medicine in the treatment of cancer patients. CRISPR Cas9a has emerged as a functional genomics tool to study at genome level the factors that control cancer resistance to drugs. Recently, we used genome wide CRISPR-Cas9a screen to identify genes responsible for glioblastoma susceptibility to etoposide. We extended our inquiry to understand genes that control glioblastoma response to temozolomide by using genome scale CRISPR. This study shows that the unbiased genome-wide loss of function approach can be applied to discover genes that influence tumor resistance to chemotherapeutics and contribute to chemoresistance in glioblastoma.

Promoters play a key role in influencing transcriptional regulation for fine-tuning the expression of genes. Heterologous promoter engineering has been a widely used concept to control the level of transcription in all model organisms. The strength of a promoter is mainly determined by its nucleotide composition. Many promoter libraries have been curated, but few have attempted to develop theoretical methods to predict the strength of promoters from their nucleotide sequence. Such theoretical methods are not only valuable in the design of promoters with specified strength but are also meaningful in understanding the mechanistic role of promoters in transcriptional regulation. In this study, we present a theoretical model to describe the relationship between promoter strength and nucleotide sequence in . We infer from our analysis that the -49-10 sequence with respect to the Transcription Start Site represents the minimal region that can be used to predict promoter strength. https://qpromoters.com/ and a standalone tool https://github.com/DevangLiya/QPromoters to quickly quantify the strength of promoters.

Reproductive disorders and infertility have become more common recently among the general population. Toxic metals are known as endocrine disruptors and as they are widespread in nature they may be linked to reproductive problems. This study was conducted as a cross-sectional study and its aim was to examine the dose-response relationship between cadmium, arsenic, mercury, chromium and nickel and serum hormone levels of testosterone (women) and estradiol and progesterone (men) using the Benchmark dose approach (BMD). Blood samples were collected from 218 women and 217 men digested in a microwave, and the levels of the tested metals were determined by atomic absorption spectrophotometry (AAS) or inductively coupled plasma-mass spectrometry (ICP-MS). Dose-response analysis was performed in PROAST software (version 70.1). The model averaging method was used to calculate the Benchmark dose interval (BMDI). A dose-response relationship has been established between all metals and hormones. The narrowest BMDI was found for the As-testosterone and Hg-testosterone. Levels estimated to produce the extra risk of testosterone serum levels disturbances of 10% were lower than median levels measured in the general population. Moreover, this research suggests the possibility of use of the BMD approach in analyzing data pool generated from extensive human-biomonitoring studies.

Diabetes mellitus (DM) is an enormous public health issue worldwide. Recent data suggest that chronic arsenic exposure is linked to the risk of developing type 1 and type 2 DM, albeit the underlying mechanisms are unclear. This review discusses the role of the immune system as a link to possibly explain some of the mechanisms of developing T1DM or T2DM associated with arsenic exposure in humans, animal models, and studies. The rationale for the hypothesis includes: (1) Arsenic is a well-recognized modulator of the immune system; (2) arsenic exposures are associated with increased risk of DM; and (3) dysregulation of the immune system is one of the hallmarks in the pathogenesis of both T1DM and T2DM. A better understanding of DM in association with immune dysregulation and arsenic exposures may help to understand how environmental exposures modulate the immune system and how these effects may impact the manifestation of disease.