Number Of Biochemical Activities Research Articles

Psychomotor functions at various weeks of chronic renal failure in rats.

In chronic renal failure there is a gradual retention of substances in the tissues and body fluids, called as uremic retention toxins, which can bring about a number of biochemical activities in the body. Chronic renal insufficiency also leads to progressive behavioural conflict. Uremic toxins can affect both the central and the peripheral nervous system. Uremic encephalopathy is also associated with problems in cognition and memory. To study the psychomotor functional disorders in rats with progressive chronic renal failure surgical nephrectomy was done by resection method. The animals were grouped into two control groups, Sham control (SC) and normal control (NC) and two uremic groups, moderate uremia (GM) and severe uremia (GS). Psychomotor analysis was done by passive avoidance and open field in these animals at 4, 8, 12, and 16weeks. After the incubation period, the nephrectomised groups (GM and GS) showed significant changes in exploratory, locomotor and emotional behaviour when compared to the controls (NC and SC). Psychomotor changes involve poor cognition, reduced memory, reduced locomotor activity and decreased exploratory drive and emotional disturbance like increased fear during the initial stages. During the later stages a restless behaviour was noticed, associated with diminished fear.

Split Histidine Kinases Enable Ultrasensitivity and Bistability in Two-Component Signaling Networks

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.

Detection of Aberrant 2′‐5′ Linkages in RNA by Anion Exchange

Formation of aberrant 2'-5' linkages can unintentionally occur in chemical synthesis of RNA. These linkages may arise by phosphoryl migration during deprotection, release, or subsequent steps during manufacture of therapeutic RNA. Their presence has been linked to a number of biochemical activities, so their potential for contribution to "off-target" effects is significant. Assaying for their presence, to ensure safe and effective therapeutic activity, is not straightforward. Since these linkages do not alter the RNA mass or the ionic or hydrophobic character of the product, confirmation of their presence or absence is not readily addressable by conventional chromatographic, electrophoretic, or mass spectrometric techniques. Since 2'-5' linkages are known to alter RNA solution conformation, they may also alter stationary phase interactions. A method for identifying the presence of these aberrant linkages by pellicular anion-exchange HPLC is presented in this unit.

Mechanism and history of evolution of symbiotic HIV strains into lethal pandemic strains: The key event may have been a 1927 trial of pamaquine in Leopoldville (Kinshasa), Congo

In previous papers, I have rejected both the zoonosis and the serial transfer hypotheses of the origin and evolution of the current lethal pandemic strains of HIV. The hypothesis that fits the critical observations is that all the human and nonhuman primate species in central Africa (an area of hyper-endemic malaria) have shared (through inter-species transfers) a "primate T-cell retrovirus" (PTRV), which has adapted to each host species. This retrovirus is believed to assist primate T-cells attack the liver stage of the malaria infection. Each geographic region has a dominant primate host and a characteristic virus. Starting in 1955 and continuing into the late 1970s, chloroquine was provided by the WHO and used for prophylaxis against malaria. Chloroquine has a number of biochemical activities but two of the most important are blocking transcription of cellular genes and proviruses activated by NF-kappaB and blocking the glycosylation of surface proteins on viruses and cells. Concurrent with the development of resistance of the malaria parasite to chloroquine, HIV strains were quickly selected, which have enhanced transcription rates (by inclusion of multiple kappaB binding sites in their long terminal repeats by recombination) and enhanced infectivity (fusogenicity) (most likely by mutations in multiple viral genes that regulate glycosylation of Env). There also may have been mutations that enhanced activation of NF-kappaB in the host cell. These changes in the retrovirus genome were not manifest in effects of the HIV strains as long as the hosts were under the influence of chloroquine. But, when the virus infects people who are not protected by chloroquine, the virus multiplies more rapidly and is more communicable. Fortunately, most of these strains (i.e., HIV-2 groups, and HIV-1 O and HIV-1 N) self-regulate (i.e., infected cells kill infected cells) well enough that viral loads remain subdued and bystander cells of the immune system are not excessively attrited. In the case of HIV-1 group M, however, there is more going on. Following the work of Korber et al. on the phylogenetics of HIV-1 groups M, I reach the conclusion that the major subgroups giving rise to the worldwide pandemic, were founded in a 1927 clinical trial of pamaquine (plasmoquine) in Leopoldville (Kinshasa). This drug is much more toxic that chloroquine and appears to have strongly selected for resistance to apoptosis in infected cells, which allows these subgroups to attrite bystander cells leading to AIDS.