Synthetic biology aims to design de novo biological systems and reengineer existing ones. These efforts have mostly focused on transcriptional circuits, with reengineering of signaling circuits hampered by limited understanding of their systems dynamics and experimental challenges. Bacterial two-component signaling systems offer a rich diversity of sensory systems that are built around a core phosphotransfer reaction between histidine kinases and their output response regulator proteins, and thus are a good target for reengineering through synthetic biology. Here, we explore the signal-response relationship arising from a specific motif found in two-component signaling. In this motif, a single histidine kinase (HK) phosphotransfers reversibly to two separate output response regulator (RR) proteins. We show that, under the experimentally observed parameters from bacteria and yeast, this motif not only allows rapid signal termination, whereby one of the RRs acts as a phosphate sink towards the other RR (i.e. the output RR), but also implements a sigmoidal signal-response relationship. We identify two mathematical conditions on system parameters that are necessary for sigmoidal signal-response relationships and define key parameters that control threshold levels and sensitivity of the signal-response curve. We confirm these findings experimentally, by in vitro reconstitution of the one HK-two RR motif found in the Sinorhizobium meliloti chemotaxis pathway and measuring the resulting signal-response curve. We find that the level of sigmoidality in this system can be experimentally controlled by the presence of the sink RR, and also through an auxiliary protein that is shown to bind to the HK (yielding Hill coefficients of above 7). These findings show that the one HK-two RR motif allows bacteria and yeast to implement tunable switch-like signal processing and provides an ideal basis for developing threshold devices for synthetic biology applications.

Bacteria sense and respond to their environment through signaling cascades generally referred to as two-component signaling networks. These networks comprise histidine kinases and their cognate response regulators. Histidine kinases have a number of biochemical activities: ATP binding, autophosphorylation, the ability to act as a phosphodonor for their response regulators, and in many cases the ability to catalyze the hydrolytic dephosphorylation of their response regulator. Here, we explore the functional role of “split kinases” where the ATP binding and phosphotransfer activities of a conventional histidine kinase are split onto two distinct proteins that form a complex. We find that this unusual configuration can enable ultrasensitivity and bistability in the signal-response relationship of the resulting system. These dynamics are displayed under a wide parameter range but only when specific biochemical requirements are met. We experimentally show that one of these requirements, namely segregation of the phosphatase activity predominantly onto the free form of one of the proteins making up the split kinase, is met in Rhodobacter sphaeroides. These findings indicate split kinases as a bacterial alternative for enabling ultrasensitivity and bistability in signaling networks. Genomic analyses reveal that up 1.7% of all identified histidine kinases have the potential to be split and bifunctional.

The COVID-19 pandemic left impact on domestic violence, sexual assault and increases the pandemic related rape cases in Bangladesh. The present study aimed to give an overview COVID-19 related rape cases so that awareness can be created among public in the outbreak. Three English and Bangla online news portals were selected purposively to include in the study and news of „Rape Case‟ were searched. Search was conducted by the word “rape news”. After removal of the repetitions news, we select ten news that reported detailed rape cases during the country wide lockdown. From ten rape cases, age of victim ranges from 8-23, the victim of eight rape cases were below 18 years (In some cases the age of the victim were not mentioned). In addition, there were five incidents of gang rape, one rape attempts and among ten cases seven of the rape were general types. Additionally, the majority of rape cases occurred at rural areas. Women of all ages are at risk of rape during the pandemic and particular attention should be given to rural areas, as most cases of rape are registered there. Public awareness about rape would be effective to report in due time with preserving the evidence of crime. CBMJ 2021 January: vol. 10 no. 01 P: 43-49

The genetic contribution in stroke onset depends on the stroke subtypes. Understanding the genetic mechanism may influence the future direction in stroke management. There is complex interplay of genetic and environmental factors for any stroke event. Very small proportion of stroke is attributable to mendelian disorders. Stroke may also manifest as part of a syndromic disease in the form of single gene multisystem disorder. But there is no direct contribution of genetic polymorphism in conventional stroke subtypes. Specific genetic loci increase the suspectibility to development of hypertension, diabetes, dyslipideamia or influence the coagulation pathway or chance of atheroma formation and embolism. While chr9p21 locus or PITX2 and ZFHX3 are related to cardioemetabolic, HDAC9, TSPAN2 and 9p21 locus are responsible for the large vessel occlusion. On the otherhand, genome-wide significant locus on chromosome 1q22 the APOE locus are found to have significant association with intracerebral hemorrhage. But the direct pathophysiologic relationship of genetic plymorphirsm may be linked to onset of sub arachnoid hemorrhage. MMP-3, endothelial nitric oxide synthase (eNOS), tumor necrosis factor (TNF)-α, VCAM-1 etc have been found to be responsible for intracranial aneurysm formation, growth and risk of rupture. Journal of National Institute of Neurosciences Bangladesh, January 2021, Vol. 7, No. 1, pp. 75-86