👤 Q Hanif

Treatment options for the Triple-Negative Breast Cancer (TNBC) subtype remain limited and the outcome for patients with advanced TNBC is very poor. The standard of care is chemotherapy, but approximately 50% of tumors develop resistance. We performed gene expression profiling of 58 TNBC tumor samples by microarray, comparing chemosensitive with chemoresistant tumors, which revealed that one of the top upregulated genes was TGFβ2. A connectivity mapping bioinformatics analysis predicted that the SRC inhibitor Dasatinib was a potential pharmacological inhibitor of chemoresistant TNBCs. Claudin-low TNBC cell lines were selected to represent poor-outcome, chemoresistant TNBC, for in vitro experiments and in vivo models. In vitro, we identified a signaling axis linking SRC, AKT and ERK2, which in turn upregulated the stability of the transcription factors, Slug and Snail. Slug was shown to repress TGFβ2-antisense 1 to promote TGFβ2 signaling, upregulating cell survival via apoptosis and DNA-damage responses. Additionally, an orthotopic allograft in vivo model demonstrated that the SRC inhibitor Dasatinib reduced tumor growth as a single agent, and enhanced responses to the TNBC mainstay drug, Epirubicin. Targeting the SRC-Slug-TGFβ2 axis may therefore lead to better treatment options and improve patient outcomes in this highly aggressive subpopulation of TNBCs. Show less

Foetal akinesia deformation sequence (FADS) represents a group of disorders resulting from absent or diminished in utero foetal mobility. The aetiology is multifactorial, including genetic, environmental, maternal, and foetal causes. The absence of foetal movements leading to multiple joint contractures, pulmonary hypoplasia, and intrauterine growth restriction are the key features of foetal akinesia deformation sequence. Herein we describe the case of a 30-year-old gravida 4 (para 2+1) who came for foetal ultrasound at 28 weeks of gestation due to decreased foetal movements. Ultrasound showed features of FADS with fixed flexed position of foetal limbs, pulmonary hypoplasia, polyhydramnios, and intrauterine growth restriction. The timely use of ultrasound enables early detection of these cases and aids in appropriate counselling and management. Show less

Fuzhong buffalo, a native breed of Guangxi Zhuang Autonomous Region, is traditionally used as a draft animal to provide farm power in the rice cultivation. In addition, the Fuzhong buffalo also prepared for the bullfighting festival organized by the locals. The detection of the selective signatures in its genome can help in elucidating the selection mechanisms in its stamina and muscle development of a draft animal. In this study, we analyzed 27 whole genomes of buffalo (including 15 Fuzhong buffalo genomes and 12 published buffalo genomes from Upper Yangtze region). The ZHp, ZFst, π-Ratio, and XP-EHH statistics were used to identify the candidate signatures of positive selection in Fuzhong buffalo. Our results detected a set of candidate genes involving in the pathways and GO terms associated with the response to exercise (e.g., ALDOA, STAT3, AKT2, EIF4E2, CACNA2D2, TCF4, CDH2), immunity (e.g., PTPN22, NKX2-3, PIK3R1, ITK, TMEM173), nervous system (e.g., PTPN21, ROBO1, HOMER1, MAGI2, SLC1A3, NRG3, SNAP47, CTNNA2, ADGRL3). In addition, we also identified several genes related to production and growth traits (e.g., PHLPP1, PRKN, MACF1, UCN3, RALGAPA1, PHKB, PKD1L). Our results depicted several pathways, GO terms, and candidate genes to be associated with response to exercise, immunity, nervous system, and growth traits. The selective sweep analysis of the Fuzhong buffalo demonstrated positive selection pressure on potential target genes involved in behavior, immunity, and growth traits, etc. Our findings provided a valuable resource for future research on buffalo breeding and an insight into the mechanisms of artificial selection. Show less

Ketosis (KET) is one common metabolic disorder that occurs mainly in early lactation and affects the dairy industry with significant economic losses. Cows with ketosis have lower milk yield and reproductive performance and greater risk of other periparturient diseases. As a metabolic disease, the pathogenesis of KET is multifactorial. To better understand the genetic background of KET, a genome-wide association study was performed using the Illumina BovineSNP50 BeadChip. Single-step genomic BLUP methodology was used to incorporate genomic data into a threshold-liability model. Results of the GWAS are reported as the proportion of variance explained by 20-SNP windows. Six genomic regions on Bos taurus autosomes 10, 13, 14 and 25 showed association with KET. Most interestingly, several candidate genes, including previously reported genes (BMP4, HNF4A and APOBR) and newly identified genes (SOCS4, GCH1, ATG14, RGS6, CYP7A1 and MAPK3), are involved in insulin metabolism or lipid metabolism, implicating the contribution of energy-metabolism-associated genes to the genetic basis of KET. Our results provide new information about the underlying biology and molecular mechanisms associated with KET. Future studies that combine genomic variation analysis and functional gene information may help elucidate the biology of KET. Show less