Pakistan is vulnerable to climate change, and extreme climatic conditions are threatening food security. This study examines the effects of climate change (e.g., maximum temperature, minimum temperature, rainfall, relative humidity, and the sunshine) on the major crops of Pakistan (e.g., wheat, rice, maize, and sugarcane). The methods of feasible generalized least square (FGLS) and heteroscedasticity and autocorrelation (HAC) consistent standard error were employed using time series data for the period 1989 to 2015. The results of the study reveal that maximum temperature adversely affects wheat production, while the effect of minimum temperature is positive and significant for all crops. Rainfall effect towards the yield of a selected crop is negative, except for wheat. To cope with and mitigate the adverse effects of climate change, there is a need for the development of heat- and drought-resistant high-yielding varieties to ensure food security in the country.

The intensity of the total choline (tCho) signal in spectroscopic images of tumors is spatially heterogeneous. The likewise heterogeneous physiologic tumor microenvironment may contribute to this heterogeneity. We therefore investigated the relationship between hypoxia, choline metabolites, and choline kinase (Chk) in a human prostate cancer model. Human PC-3 prostate cancer cells were engineered to express enhanced green fluorescent protein (EGFP) under hypoxic conditions. These PC-3-5HRE-EGFP cells were characterized in culture and as tumors transplanted in mice using 1 H magnetic resonance spectroscopy (MRS) and MRS imaging (MRSI) combined with EGFP fluorescence microscopy and imaging. Hypoxic EGFP-fluorescing tumor regions colocalized with regions of high tCho in combined MRSI and optical imaging studies. Cellular phosphocholine (PC) and tCho concentrations as well as Chk expression levels significantly increased following exposure of PC-3 cells to hypoxia. A putative promoter region located 5 ¶ of the translation start site of the human chk-a gene was cloned and luciferase (Luc)-based reporter vector constructs were generated. Luc reporter assays provided evidence that some of the putative hypoxia response elements (HRE) within this putative chk-a promoter region functioned in vitro. Chromatin immunoprecipitation assays using an antibody against hypoxia-inducible factor (HIF)-1A showed that HIF-1 can directly bind this region of the endogenous chk-a promoter in hypoxic PC-3-5HRE-EGFP cells. These data suggest that HIF-1 activation of HREs within the putative chk-a promoter region can increase Chk-A expression within hypoxic environments, consequently increasing cellular PC and tCho levels within these environments. [Cancer Res 2008;68(1):172-80]

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Multiple factors including long-term treatment with tamoxifen are involved in the development of selective estrogen receptor (ER) modulator resistance in ERα-positive breast cancer. Many underlying molecular events that confer resistance are known but a unifying theme is yet to be revealed. In this report, we provide evidence that HOXB7 overexpression renders MCF-7 cells resistant to tamoxifen via cross-talk between receptor tyrosine kinases and ERα signaling. HOXB7 is an ERα-responsive gene. Extended treatment of MCF-7 cells with tamoxifen resulted in progressively increasing levels of HOXB7 expression, along with EGFR and EGFR ligands. Up-regulation of EGFR occurs through direct binding of HOXB7 to the EGFR promoter, enhancing transcriptional activity. Finally, higher expression levels of HOXB7 in the tumor significantly correlated with poorer disease-free survival in ERα-positive patients with breast cancer on adjuvant tamoxifen monotherapy. These studies suggest that HOXB7 acts as a key regulator, orchestrating a major group of target molecules in the oncogenic hierarchy. Functional antagonism of HOXB7 could circumvent tamoxifen resistance.