Bcl-XL Inhibits Membrane Permeabilization by Competing with Bax

Although Bcl-XL and Bax are structurally similar, activated Bax forms large oligomers that permeabilize the outer mitochondrial membrane, thereby committing cells to apoptosis, whereas Bcl-XL inhibits this process. Two different models of Bcl-XL function have been proposed. In one, Bcl-XL binds to an activator, thereby preventing Bax activation. In the other, Bcl-XL binds directly to activated Bax. It has been difficult to sort out which interaction is important in cells, as all three proteins are present simultaneously. We examined the mechanism of Bax activation by tBid and its inhibition by Bcl-XL using full-length recombinant proteins and measuring permeabilization of liposomes and mitochondria in vitro. Our results demonstrate that Bcl-XL and Bax are functionally similar. Neither protein bound to membranes alone. However, the addition of tBid recruited molar excesses of either protein to membranes, indicating that tBid activates both pro- and antiapoptotic members of the Bcl-2 family. Bcl-XL competes with Bax for the activation of soluble, monomeric Bax through interaction with membranes, tBid, or t-Bid-activated Bax, thereby inhibiting Bax binding to membranes, oligomerization, and membrane permeabilization. Experiments in which individual interactions were abolished by mutagenesis indicate that both Bcl-XL–tBid and Bcl-XL–Bax binding contribute to the antiapoptotic function of Bcl-XL. By out-competing Bax for the interactions leading to membrane permeabilization, Bcl-XL ties up both tBid and Bax in nonproductive interactions and inhibits Bax binding to membranes. We propose that because Bcl-XL does not oligomerize it functions like a dominant-negative Bax in the membrane permeabilization process

Nitrogen as a threat to European water quality

Anthropogenic increase of nitrogen in water poses direct threats to human health and aquatic ecosystems. High nitrogen concentrations in drinking water are dangerous for human health. In aquatic ecosystems the nitrogen enrichment contributes to eutrophication, which is responsible for toxic algal blooms, water anoxia, fish kills and habitat and biodiversity loss. Nitrogen concentrations in European rivers, lakes, aquifers and coastal waters are generally high in many regions. In addition, nitrogen is probably accumulating in groundwaters, reducing the future reliability of the resource. In Europe, nitrogen pressures on water are wide spread, resulting in elevated costs. About 40% of the European population would potentially be exposed to high nitrates values in drinking water if adequate treatment was not in place, and a large proportion of European aquatic ecosystems is eutrophicated or at risk of eutrophication. Even under favourable land use scenarios the nitrogen export to European waters and seas is likely to remain significant in the near future. The effects of climate change on nitrogen export to waters are still unsure. Policy tools are available within the European Union and under international conventions to mitigate against nitrogen pollution in water, but their full implementation has not yet been achieved throughout Europe. In many cases a delay in the water quality response to implementation of management measures have been observed, due to historical nitrogen accumulation in soils, sediments or aquifers or to inadequate design of the mitigation plans. The issue of pollution swapping between environmental compartments has appeared as an important element to be considered by both the scientific and policy prospective. To support the sustainable management of water resources, positive effects could be obtained implementing existing policy tools, improving the integration in sectoral policies and promoting the interactions between science and policy.JRC.DDG.H.5-Rural, water and ecosystem resource

Young solid Earth researchers of the world unite!

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95272/1/eost14667.pd

Раціональність як реляційність: синтетична єдність відмінностей в трансцендентальному просторі границі

У статті висвітлюються проблеми «постсучасної» раціональності, визначальною характеристикою котрої покладається іманентна пограничність. Відношення та Іншість розглядаються як визначальні предикати раціональності, які в класичній парадигмі імплікують принципи рефлексійності, конструктивності, співмірності. Корелятами означених принципів у постструктуралістській раціональності визначаються повторність (ітеративність), фрагментарність, подвоєння, розрізняння. Конгруентність класичної та постсучасної раціональності зумовлена еквівалентністю понять трансцендентальності та пограничності. Синтетична єдність (розбіжність та зв'язок) з її специфікацією принципами пов’язання та розрізняння, визначається через медіативну функцію судження, структура якого фундується параметрами реляційності.В статье освещаются проблемы «постсовременной» рациональности, определяющей характеристикой которой полагается имманентная пограничность. Отношение и Другость рассматриваются как определяющие предикаты рациональности, которые имплицируют принципы рефлексивности, конструктивности, соразмерности в классической парадигме. Коррелятами обозначенных принципов в постструктуралистской рациональности являются повторность (итеративность), фрагментарность, удвоение, различание. Конгруэнтность классической и постсоврменной рациональности обусловлена эквивалентностью понятий трансцендентальности и пограничности. Синтетическое единств (различие и связь) с его спецификацией в позициях увязывания и различания, определяется через медиативную функцию суждения, структура которого фундируется параметрами реляционности.The paper illuminates some problems of the post-contemporary rationality that possesses the immanent borderness as its distinctive feature. The Relationality and the Anotherness are investigaled as the common predicates of rationality that implicate the “classical” principles of reflexity, constructiveness, proportionality. The main principles of the poststructuralistic rationality correlating with the classical ones are recurrence (iterativity), doubleness, fragmentariness, differance. The congruence of the classical rationality and the post-contemporary one is caused by the equivalency of the concepts “transcendentality” and “borderness”. The synthetical unity (relation between deviation and connection) with its specification by the linking and the differance principles is determined by the mediative function of the assertion that is structured by the relationality parameters

Active vitamin D (1,25-dihydroxyvitamin D) and bone health in middle-aged and elderly men: the European male aging study (EMAS)

<p>Context: There is little information on the potential impact of serum 1,25-dihydroxyvitamin D [1,25(OH)2D] on bone health including turnover.</p> <p>Objective: The objective of the study was to determine the influence of 1,25(OH)2D and 25-hydroxyvitamin D [25(OH)D] on bone health in middle-aged and older European men.</p> <p>Design, Setting, and Participants: Men aged 40–79 years were recruited from population registers in 8 European centers. Subjects completed questionnaires that included questions concerning lifestyle and were invited to attend for quantitative ultrasound (QUS) of the heel, assessment of height and weight, and a fasting blood sample from which 1,25(OH)2D, 25(OH)D, and PTH were measured. 1,25(OH)2D was measured using liquid chromatography tandem mass spectrometry. Bone markers serum N-terminal propeptide of type 1 procollagen (P1NP) and crosslinks (β-cTX) were also measured. Dual-energy x-ray absorptiometry (DXA) of the hip and lumbar spine was performed in 2 centers.</p> <p>Main Outcome Measure(s): QUS of the heel, bone markers P1NP and β-cTX, and DXA of the hip and lumbar spine were measured.</p> <p>Results: A total of 2783 men, mean age 60.0 years (SD 11.0) were included in the analysis. After adjustment for age and center, 1,25(OH)2D was positively associated with 25(OH)D but not with PTH. 25(OH)D was negatively associated with PTH. After adjustment for age, center, height, weight, lifestyle factors, and season, 1,25(OH)2D was associated negatively with QUS and DXA parameters and associated positively with β-cTX. 1,25(OH)2D was not correlated with P1NP. 25(OH)D was positively associated with the QUS and DXA parameters but not related to either bone turnover marker. Subjects with both high 1,25(OH)2D (upper tertile) and low 25(OH)D (lower tertile) had the lowest QUS and DXA parameters and the highest β-cTX levels.</p> <p>Conclusions: Serum 1,25(OH)2D is associated with higher bone turnover and poorer bone health despite being positively related to 25(OH)D. A combination of high 1,25(OH)2D and low 25(OH)D is associated with the poorest bone health.</p&gt