A theory of Plasma Membrane Calcium Pump stimulation and activity

The ATP-driven Plasma Membrane Calcium pump or Ca(2+)-ATPase (PMCA) is characterized by a high affinity to calcium and a low transport rate compared to other transmembrane calcium transport proteins. It plays a crucial role for calcium extrusion from cells. Calmodulin is an intracellular calcium buffering protein which is capable in its Ca(2+) liganded form of stimulating the PMCA by increasing both the affinity to calcium and the maximum calcium transport rate. We introduce a new model of this stimulation process and derive analytical expressions for experimental observables in order to determine the model parameters on the basis of specific experiments. We furthermore develop a model for the pumping activity. The pumping description resolves the seeming contradiction of the Ca(2+):ATP stoichiometry of 1:1 during a translocation step and the observation that the pump binds two calcium ions at the intracellular site. The combination of the calcium pumping and the stimulation model correctly describes PMCA function. We find that the processes of calmodulin-calcium complex attachment to the pump and of stimulation have to be separated. Other PMCA properties are discussed in the framework of the model. The presented model can serve as a tool for calcium dynamics simulations and provides the possibility to characterize different pump isoforms by different type-specific parameter sets.Comment: 24 pages, 6 figure

Serological and Behavioral Survey on HIV/AIDS among prisoners in Nouakchott (Mauritania)

Abstract In Mauritania, epidemiological data estimatenational HIV prevalence to less than 1%. Our study is thefirst joint survey on HIV/AIDS conducted among prisonersin Mauritania. It is a cross-sectional survey with anonymityand informed consent. The study covered a sample of296 prisoners enrolled in a population of 706 prisoners heldin Nouakchott. The sex ratio was 14.6. The refusal rate ofblood sample was 4.7%. HIV prevalence in the sample was3.9%. 53.37% of prisoners knew the concept of seropositivitybut only 7.4% had a perfect knowledge of the ways ofHIV transmission untainted by false beliefs. The results showedthat 99% of prisoners knew that the condom is a meansof protection against HIV infection, but they also showedmany false beliefs about protection against HIV in the majorityof prisoners. Indeed, 98.49% of respondents said protectthemselves by avoiding sex with strangers and 94.97% ofthem thought that sex with girls or virgins are a protectionagainst HIV. Nearly one quarter of the prisoners did not havea good perception of risk of contracting HIV in prisonalthough homosexual relations between prisoners have beenreported. This study showed that prisoners in Mauritania area vulnerable group to HIV because the prevalence of HIV inthis group was higher than the national prevalence and thissub-population was unfamiliar with the disease and adoptrisk behaviors

Supporting Engagement and Floor Control in Hybrid Meetings

Remote participants in hybrid meetings often have problems to follow what is going on in the (physical) meeting room they are connected with. This paper describes a videoconferencing system for participation in hybrid meetings. The system has been developed as a research vehicle to see how technology based on automatic real-time recognition of conversational behavior in meetings can be used to improve engagement and floor control by remote participants. The system uses modules for online speech recognition, real-time visual focus of attention as well as a module that signals who is being addressed by the speaker. A built-in keyword spotter allows an automatic meeting assistant to call the remote participant’s attention when a topic of interest is raised, pointing at the transcription of the fragment to help him catch-up

TRIO loss of function is associated with mild intellectual disability and affects dendritic branching and synapse function

Recently, we marked TRIO for the first time as a candidate gene for intellectual disability (ID). Across diverse vertebrate species, TRIO is a well-conserved Rho GTPase regulator that is highly expressed in the developing brain. However, little is known about the specific events regulated by TRIO during brain development and its clinical impact in humans when mutated. Routine clinical diagnostic testing identified an intragenic de novo deletion of TRIO in a boy with ID. Targeted sequencing of this gene in over 2300 individuals with ID, identified three additional truncating mutations. All index cases had mild to borderline ID combined with behavioral problems consisting of autistic, hyperactive and/or aggressive behavior. Studies in dissociated rat hippocampal neurons demonstrated the enhancement of dendritic formation by suppressing endogenous TRIO, and similarly decreasing endogenous TRIO in organotypic hippocampal brain slices significantly increased synaptic strength by increasing functional synapses. Together, our findings provide new mechanistic insight into how genetic deficits in TRIO can lead to early neuronal network formation by directly affecting both neurite outgrowth and synapse development