A single-nucleotide polymorphism in a Plasmodium berghei ApiAP2 transcription factor alters the development of host immunity

The acquisition of malaria immunity is both remarkably slow and unpredictable. At present, we know little about the malaria parasite genes that influence the host\u27s ability to mount a protective immune response. Here, we show that a single-nucleotide polymorphism (SNP) resulting in a single amino acid change (S to F) in an ApiAP2 transcription factor in the rodent malaria parasit

Personalized structural biology reveals the molecular mechanisms underlying heterogeneous epileptic phenotypes caused by de novo KCNC2 variants

Whole-exome sequencing (WES) in the clinic has identified several rare monogenic developmental and epileptic encephalopathies (DEE) caused by ion channel variants. However, WES often fails to provide actionable insight for rare diseases, such as DEEs, due to the challenges of interpreting variants of unknown significance (VUS). Here, we describe a personalized structural biology (PSB) approach that leverages recent innovations in the analysis of protein 3D structures to address this challenge. We illustrate this approach in an Undiagnosed Diseases Network (UDN) individual with DEE symptoms and

Qualitatively understanding patients' and health professionals' experiences of the BRECONDA breast reconstruction decision aid

Copyright © 2016 John Wiley & Sons, Ltd. Objective: Women diagnosed with breast cancer or ductal carcinoma in situ and those with a genetic susceptibility to developing this disease face the challenging decision of whether or not to undergo breast reconstruction following mastectomy. As part of a large randomized controlled trial, this qualitative study examined women's experiences of using the Breast RECONstruction Decision Aid (BRECONDA) and health professionals' feedback regarding the impact of this resource on patients' knowledge and decision making about breast reconstruction. Method: Semistructured interviews were conducted with women who accessed the BRECONDA intervention (N=36) and with their healthcare providers (N=6). All interviews were transcribed verbatim and subjected to thematic analysis by 3 independent coders. Results: Participants reported an overall positive impression, with all interviewees endorsing this decision aid as a useful resource for women considering reconstructive surgery. Thematic analysis of patient interviews revealed 4 themes: overall impressions and aesthetics; personal relevance and utility; introducing BRECONDA; and advantages and suggested improvements. Analysis of health professionals' interviews also revealed 4 themes: need for BRECONDA, impact of BRECONDA, potential difficulties that may arise in using the decision aid, and recommending BRECONDA to patients. Patients indicated that they derived benefit from this resource at all stages of their decision-making process, with the greatest perceived benefit being for those early in their breast reconstruction journey. Conclusion: These findings support the use of BRECONDA as an adjunct to clinical consultation and other information sources

Epigallocatechin-3-gallate, a prototypic chemopreventative agent for protection against cisplatin-based ototoxicity

AbstractCisplatin-induced ototoxicity is one of the major factors limiting cisplatin chemotherapy. Ototoxicity results from damage to outer hair cells (OHCs) and other regions of the cochlea. At the cellular level, cisplatin increases reactive oxygen species (ROS) leading to cochlear inflammation and apoptosis. Thus, ideal otoprotective drugs should target oxidative stress and inflammatory mechanisms without interfering with cisplatin's chemotherapeutic efficacy. In this study, we show that epigallocatechin-3-gallate (EGCG) is a prototypic agent exhibiting these properties of an effect otoprotective agent. Rats administered oral EGCG demonstrate reduced cisplatin-induced hearing loss, reduced loss of OHCs in the basal region of the cochlea and reduced oxidative stress and apoptotic markers. EGCG also protected against the loss of ribbon synapses associated with inner hair cells and Na+/K+ ATPase α1 in the stria vascularis and spiral ligament. In vitro studies showed that EGCG reduced cisplatin-induced ROS generation and ERK1/2 and signal transducer and activator of transcription-1 (STAT1) activity, but preserved the activity of STAT3 and Bcl-xL. The increase in STAT3/STAT1 ratio appears critical for mediating its otoprotection. EGCG did not alter cisplatin-induced apoptosis of human-derived cancer cells or cisplatin antitumor efficacy in a xenograft tumor model in mice because of its inability to rescue the downregulation of STAT3 in these cells. These data suggest that EGCG is an ideal otoprotective agent for treating cisplatin-induced hearing loss without compromising its antitumor efficacy.</jats:p

Al Ain Oases Mapping Project: Qattārah Oasis, past and present (poster)

The Al Ain Oases Mapping Project is a collaboration between the Abu Dhabi Tourism and Culture Authority and Zayed University. It aims to document the present oasis landscape and identify surviving historic components, while at the same time engaging Emirati students with their heritage and building capacity for archaeology in the UAE. The project utilizes a non-intrusive field-walking methodology suitable for a class of undergraduate students. It further draws on the students\u27 community links and bilingualism to contact former residents of the oasis villages and undertake oral history interviews. The first season\u27s work focused on Qattārah Oasis and contributes to the established programme of works there; future seasons will expand the survey to neighbouring Jīmī Oasis and the other oases of al-\u27Ayn. The results will inform continued archaeological exploration of the oases by TCA

Miro1 Regulates Activity-Driven Positioning of Mitochondria within Astrocytic Processes Apposed to Synapses to Regulate Intracellular Calcium Signaling

It is fast emerging that maintaining mitochondrial function is important for regulating astrocyte function, although the specific mechanisms that govern astrocyte mitochondrial trafficking and positioning remain poorly understood. The mitochondrial Rho-GTPase 1 protein (Miro1) regulates mitochondrial trafficking and detachment from the microtubule transport network to control activity-dependent mitochondrial positioning in neurons. However, whether Miro proteins are important for regulating signaling-dependent mitochondrial dynamics in astrocytic processes remains unclear. Using live-cell confocal microscopy of rat organotypic hippocampal slices, we find that enhancing neuronal activity induces transient mitochondrial remodeling in astrocytes, with a concomitant, transient reduction in mitochondrial trafficking, mediated by elevations in intracellular Ca(2+). Stimulating neuronal activity also induced mitochondrial confinement within astrocytic processes in close proximity to synapses. Furthermore, we show that the Ca(2+)-sensing EF-hand domains of Miro1 are important for regulating mitochondrial trafficking in astrocytes and required for activity-driven mitochondrial confinement near synapses. Additionally, activity-dependent mitochondrial positioning by Miro1 reciprocally regulates the levels of intracellular Ca(2+) in astrocytic processes. Thus, the regulation of intracellular Ca(2+) signaling, dependent on Miro1-mediated mitochondrial positioning, could have important consequences for astrocyte Ca(2+) wave propagation, gliotransmission, and ultimately neuronal function

A simple mooring modification reduces impacts on seagrass meadows

AbstractMoorings can have a detrimental impact on seagrass, fragmenting the meadows, resulting in the habitat degradation. To reduce contact of the moorings with the seabed we attached small floats along the chain of a traditional swing mooring and monitored the ecological impacts of this modified mooring, with reference to a standard swing mooring, in a seagrass meadow under high tidal influence. After three years, seagrass density surrounding the modified mooring was over twice as high as that of the standard mooring, with blade length surrounding the modified mooring also found to exceed that of the standard mooring. Seagrass-associated epifaunal species richness was twice as high surrounding the modified mooring compared to the standard mooring. Sediment composition was considerably finer at the modified mooring, indicative of increased disturbance surrounding the standard mooring. A simple modification to existing swing moorings can mitigate some of the impacts of moorings on seagrass meadows, whilst accommodating for tidal fluctuations. The scale of the differences observed between the mooring types demonstrates the susceptibility of seagrass meadows to damage from swing moorings. Given the ecological importance of these habitats, it is crucial that action is taken to reduce further degradation, such as that demonstrated here.</jats:p

Neuronal activity mediated regulation of glutamate transporter GLT-1 surface diffusion in rat astrocytes in dissociated and slice cultures.

The astrocytic GLT-1 (or EAAT2) is the major glutamate transporter for clearing synaptic glutamate. While the diffusion dynamics of neurotransmitter receptors at the neuronal surface are well understood, far less is known regarding the surface trafficking of transporters in subcellular domains of the astrocyte membrane. Here, we have used live-cell imaging to study the mechanisms regulating GLT-1 surface diffusion in astrocytes in dissociated and brain slice cultures. Using GFP-time lapse imaging, we show that GLT-1 forms stable clusters that are dispersed rapidly and reversibly upon glutamate treatment in a transporter activity-dependent manner. Fluorescence recovery after photobleaching and single particle tracking using quantum dots revealed that clustered GLT-1 is more stable than diffuse GLT-1 and that glutamate increases GLT-1 surface diffusion in the astrocyte membrane. Interestingly, the two main GLT-1 isoforms expressed in the brain, GLT-1a and GLT-1b, are both found to be stabilized opposed to synapses under basal conditions, with GLT-1b more so. GLT-1 surface mobility is increased in proximity to activated synapses and alterations of neuronal activity can bidirectionally modulate the dynamics of both GLT-1 isoforms. Altogether, these data reveal that astrocytic GLT-1 surface mobility, via its transport activity, is modulated during neuronal firing, which may be a key process for shaping glutamate clearance and glutamatergic synaptic transmission

The Red Sea under the Caliphal Dynasties, c. 639–1171

Students of world history will be familiar with the Red Sea as a strategic communications corridor linking the Mediterranean to the Indian Ocean. This paper examines the Red Sea region between the seventh and twelfth centuries, when it was ruled by a succession of Islamic caliphal dynasties, namely, the Umayyads, ʿAbbāsids, and Fāṭimids. It first sets out a sketch of the political history of the Red Sea and its constituent hinterland polities, including particularly Egypt, Sudan, al‐Ḥijāz, and Yemen, drawing attention to episodes and processes in which the Red Sea was significant. A section on Africa and Arabia explores the Red Sea as a zone of economic and social interaction; another section deals with the historic shift of Indian Ocean trade from the ʿAbbāsid Persian Gulf to the Fāṭimid Red Sea. Finally, the impact of the Red Sea on its constituent hinterland polities and the wider sweep of Islamic history is considered