Meru, Kenya has watersheds which are shared by wildlife, humans and domesticated animals.These surface waters can be contaminated by the waterborne pathogen Cryptosporidium. To quantify the seasonality and prevalence of Cryptosporidium in Meru regional surface waters, we

The bridging sheet region of the gp120 subunit of the HIV-1 Env protein interacts with the major virus coreceptors, CCR5 and CXCR4. We examined the impact of mutations in and adjacent to the bridging sheet region of an X4 tropic HIV-1 on membrane fusion and entry inhibitor susceptibility. When the V3-loop of this Env was changed so that CCR5 was used, the effects of these same mutations on CCR5 use were assayed as well. We found that coreceptor-binding site mutations had greater effects on CXCR4-mediated fusion and infection than when CCR5 was used as a coreceptor, perhaps related to differences in coreceptor affinity. The mutations also reduced use of the alternative coreceptors CCR3 and CCR8 to varying degrees, indicating that the bridging sheet region is important for the efficient utilization of both major and minor HIV coreceptors. As seen before with a primary R5 virus strain, bridging sheet mutations increased susceptibility to the CCR5 inhibitor TAK-779, which correlated with CCR5 binding efficiency. Bridging sheet mutations also conferred increased susceptibility to the CXCR4 ligand AMD-3100 in the context of the X4 tropic Env. However, these mutations had little effect on the rate of membrane fusion and little effect on susceptibility to enfuvirtide, a membrane fusion inhibitor whose activity is dependent in part on the rate of Env-mediated membrane fusion. Thus, mutations that reduce coreceptor binding and enhance susceptibility to coreceptor inhibitors can affect fusion and enfuvirtide susceptibility in an Env context-dependent manner.

Steps in the replication of HIV-1 occurring in the virus, but not the host are preferred targets of anti-retroviral therapy. Strand transfer is unique; the DNA strand being made by viral reverse transcriptase (RT) is moved from one RNA template position to another.1 Understanding the mechanism requires knowing whether the RT directly mediates the template exchange, or dissociates during the exchange, so that it occurs by polymer dynamics. Earlier work in vitro showed that the presence of an RT-trapping polymer would allow synthesis on the original or donor template, but completely block transfer and subsequent synthesis on the second or acceptor template. One interpretation is that the RT must dissociate during transfer, but an alternative is that sequestration of non-polymerizing RTs prevents polymerization-independent ribonuclease H (RNase H) cleavages of the donor template necessary for strand exchange. To resolve this ambiguity, we designed a primer-template system that allows strand transfer without RNase H activity. Using an RNase H negative mutant RT, we showed that a polymer trap still prevented strand transfer. This confirms that RT dissociates during strand transfer. The presence of HIV-1 nucleocapsid protein, which promotes strand exchange, had little effect on this outcome. Additional assays showed that both, the wild type RT and a multiple NRTI resistant HIV-1 RT, containing an extended fingers domain, which is characterized by its enhanced primer-template binding affinity, were both unable to transfer with the trapping polymer. This implies that common sequence variations among RTs are unlikely to alter the dissociation feature.

Purpose: The main objective of this study was to examine disaster mitigation measures as strategies of disaster risk preparedness in informal settlements of Nyeri town, Nyeri County, Kenya. To achieve this, the study was guided by two specific objectives: To identify the role of stakeholders in disaster management in the informal settlements of Nyeri Town and to determine the challenges encountered during disaster risk reduction initiatives in the informal settlements of Nyeri Town. Methodology: The study adopted a descriptive research design using primary data collected through a structured questionnaire. The population for this study was 384 respondents of the four settlements of Nyeri town, that is, Majengo Witemere Ngangarithi, Mathari and Ruring’u Muslim village. The study used a sample of 384 respondents that was divided proportionally between the four settlements. Findings: The study found out that, majority of the respondents [93.0%] was aware of the disasters that can affect them in their area of residents. The study further established that, majority of the residents 196 (51.0%) were aware of the existence of disaster risk reduction policies as compared to 49.0% who were not aware of any disaster risk reduction policy. The results also showed that there was a significant association between the level of education of the respondents and the level of awareness of the disaster that could affect them [X2 (3) = 14.848, p-value =0.002<0.05] and the religions of the respondents and the level of awareness of the disaster that could affect them [X2 (2) = 7.090, p-value =0.029<0.05]. The results however indicated that, there was no significant association between the level of awareness of the disaster that could affect the respondents with the area of residents, age of the respondents and their occupation as given by the p-values of 0.393, 0.485 and 0.390 respectively. The study further established that, there was a significant association between the education level of the respondents and the level of awareness of any policy rule concerning with disaster risk reduction [X2 (3) = 8.056, p-value =0.045<0.05], and the religions of the respondents and the level of awareness of any policy rule concerning with disaster risk reduction [X2 (2) = 10.031, p-value =0.007<0.05]. It was concluded that Risk assessment as a step for successful disaster reduction measures will ensure that the community members are aware of the possible hazards. National and County government should incorporate the national and international policies and guidelines in their policy. Recommendations: The Government should be keen on learning on previous disasters that have affected other informal settlements and other parts of the country by having disaster management well kwon by the communities living in informal sectors. The researcher further recommends to the scholars to consider research on Disaster risk preparedness as the strategy of counties development agenda and Social and economic potentials that the County Governments can tap in informal settlements.

Efavirenz is a non-nucleoside reverse transcriptase inhibitor used for treating HIV/AIDS. We found that polymerization activity of a reverse transcriptase (RT) with the E478Q mutation that inactivates the RNase H catalytic site is much more sensitive to efavirenz than the wild type RT, indicating that a functional RNase H attenuates the effectiveness of efavirenz. Moreover, efavirenz actually stimulated wild type RNase H binding and catalytic functions, indicating another link between efavirenz action and RNase H function. During reverse transcription in vivo, the RT that is extending the DNA primer also periodically cleaves the genomic RNA. The RNase H makes primary template cuts about 18 nucleotides from the growing DNA 3′ end and, when the RT pauses synthesis, it shifts to make secondary cuts about 9 nucleotides from the DNA 3′ end. After synthesis, RTs return to bind remaining template RNA segments at their 5′ ends, and make primary and secondary cuts, 18 and 9 nucleotides in, respectively. We found that efavirenz stimulates both 3′ and 5′-directed RNase H activity. Use of specific substrates revealed a particular acceleration of secondary cuts. Efavirenz specifically promoted binding of the RT to RNase H substrates, suggesting that it stabilizes the shifting of RTs to make the secondary cuts. We further showed that efavirenz similarly stimulates the RNase H of an RT from a patient-derived virus that is highly resistant and grows more rapidly in the presence of low concentrations of efavirenz. We suggest that for efavirenz resistant RTs, stimulated RNase H activity contributes to increased viral fitness.