Differential lipid dependence of function of bacterial sodium channel homologues

The lipid bilayer is important for maintaining the integrity of cellular compartments and plays a vital role in maintaining the hydrophobic/charged interactions necessary for structure, conformational flexibility and function. Despite the intimate relationship between ion channels and the membranes in which they are embedded, challenges resulting from the dynamic and complex nature of cellular membranes have limited our ability to address the functional role of these interactions. To directly assess lipid dependence of activity, we examined channel function ofthree purified bacterial sodium channel orthologues (NaChBac, NavMs, and NavSp) by cumulative 22Na+ uptake into proteoliposomes containing a 3:1 ratio of POPE and another glycerophospholipid (POPC, POPG, POPS, Cardiolipin (CL), POPA, or PI). We observed a unique lipid dependence for each homologue tested. Common to each was a low level of activity above background (uptake into protein free liposomes) when the second lipid was a zwitterionic lipid such as POPE and POPC. Maximal activity for full-length NaChBac and NavMs proteins was observed in POPE + POPG liposomes. On the other hand, full-length NavSp channels possessed a different lipid dependence, with maximal activity in liposomes containing POPE + PI. No strong lipid dependence was observed for pore-only constructs of NavMs or NavSp, that lacked the S1-S4 segments, suggesting that the lipid dependence of sodium channels may arise from their abilities to affect the voltage-sensing domains. The effect may be maximized by specific lipid-protein interactions that are uniquely favourable in each homologue, giving rise to differing lipid dependences

The role of apoptosis in the development of AGM hematopoietic stem cells revealed by Bcl-2 overexpression

Apoptosis is an essential process in embryonic tissue remodeling and adult tissue homeostasis. Within the adult hematopoietic system, it allows for tight regulation of hematopoietic cell subsets. Previously, it was shown that B-cell leukemia 2 (Bcl-2) overexpression in the adult increases the viability and activity of hematopoietic cells under normal and/or stressful conditions. However, a role for apoptosis in the embryonic hematopoietic system has not yet been established. Since the first hematopoietic stem cells (HSCs) are generated within the aortagonad-mesonephros (AGM; an actively remodeling tissue) region beginning at embryonic day 10.5, we examined this tissue for expression of apoptosis-related genes and ongoing apoptosis. Here, we show expression of several proapoptotic and antiapoptotic genes in the AGM. We also generated transgenic mice overexpressing Bcl-2 under the control of the transcriptional regulatory elements of the HSC marker stem cell antigen-1 (Sca-1), to test for the role of cell survival in the regulation of AGM HSCs. We provide evidence for increased numbers and viability of Sca-1(+) cells in the AGM and subdissected midgestation aortas, the site where HSCs are localized. Most important, our in vivo transplantation data show that Bcl-2 overexpression increases AGM and fetal liver HSC activity, strongly suggesting that apoptosis plays a role in HSC development

Мультипарадигмальний підхід до аналізу феномену нігілізму

У статті розглянуто нігілізм як неоднозначне й поліморфне поняття. Досліджено різні підходи до тлумачення та розв’язання питань, пов’язаних із нігілізмом. Розкрито людиномірність нігілізму в контексті відстеження варіативного смислового навантаження феномену. Встановлено, що нігілізм потрібно позиціонувати як спосіб пробудження людського духу, заперечення деструктивного конформізму й відсутності опору (пасивний песимізм).В статье рассмотрен нигилизм как неоднозначное и полиморфное понятие. Исследованы различные подходы к толкованию и решению вопросов, связанных с нигилизмом. Раскрыта человекомерность нигилизма в контексте отслеживания вариативной смысловой нагрузки феномена. Установлено, что нигилизм нужно позиционировать как способ пробуждения человеческого духа, отрицание деструктивного конформизма и отсутствия сопротивления (пассивный пессимизм).Nihilism is considered as ambiguous and polymorphic concept. Different approaches to the interpretation and solution of issues associated with nihilism are investigated. Human measurement of nihilism in the context of tracking meaning of varied semantic capacity of the phenomenon is revealed. It is determined that nihilism must be positioned as a way of awakening of the human spirit, denial of destructive conformism and absence of resistance (passive pessimism)

Anthropogenic Space Weather

Anthropogenic effects on the space environment started in the late 19th century and reached their peak in the 1960s when high-altitude nuclear explosions were carried out by the USA and the Soviet Union. These explosions created artificial radiation belts near Earth that resulted in major damages to several satellites. Another, unexpected impact of the high-altitude nuclear tests was the electromagnetic pulse (EMP) that can have devastating effects over a large geographic area (as large as the continental United States). Other anthropogenic impacts on the space environment include chemical release ex- periments, high-frequency wave heating of the ionosphere and the interaction of VLF waves with the radiation belts. This paper reviews the fundamental physical process behind these phenomena and discusses the observations of their impacts.Comment: 71 pages, 35 figure

Distribution and population size of Hieracium stenolepiforme, Cheddar Hawkweed (Asteraceae).

The distribution and population size of Hieracium stenolepiforme (Pugsley) P. D. Sell & C. West, Cheddar Hawkweed (Asteraceae) has been assessed. It is endemic to Cheddar Gorge and the adjacent Black Rock Nature Reserve, Somerset, England (vice-county 6, North Somerset). Historical records show that it has been recorded in Cheddar Gorge and at Black Rock but has declined. On 11 June 2000, 52 plants were counted in the main gorge and 5 plants at Black Rock; on 14 June 2016, 59 plants were recorded in Cheddar Gorge but none at Black Rock. Hieracium stenolepiforme is IUCN (2001) threat status ‘Critically Endangered’

Measurement of the light orbital angular momentum spectrum using an optical geometric transformation

We recently demonstrated a new method to efficiently analyse the orbital angular momentum (OAM) states of light by application of an optical geometric transformation (Berkhout et al 2010 Phys. Rev. Lett. 105 153601). Here we study the performance of such a system to measure the change in the observed OAM spectrum, as the input beam is misaligned with respect to the analyser. We present modelled and experimental results which show that our reformatting approach does correctly measure the OAM spectrum for lateral and tilt misalignment of the input beam

The T1-tetramerization domain of Kv1.2 rescues expression and preserves function of a truncated NaChBac Sodium Channel

Cytoplasmic domains frequently promote functional assembly of multimeric ion channels. To investigate structural determinants of this process, we generated the ‘T1-chimera’ construct of the NaChBac sodium channel by truncating the C-terminal domain and splicing the T1-tetramerisation domain of the Kv1.2 channel to the N-terminus. Purified T1-chimera channels were tetrameric, conducted Na+ when reconstituted into proteliposomes and were blocked by the drug mibefradil. Both the T1-chimera and full-length NaChBac had comparable expression in the membrane whereas a NaChBac mutant lacking a cytoplasmic domain had greatly-reduced membranal expression. Our findings support a model whereby bringing the transmembrane regions into close proximity enables their tetramerization. This phenomemon is found with other channels and thus our findings substantiate this as a common assembly mechanism. Nazzareno ‡, Andrew J. Miles2 ‡, Andrew M. Powl2, Colin G. Nichols3, B.A. Wallace2, Andrias O. O’Reilly4