Identification of a mechanism of photoprotective energy dissipation in higher plants

Under conditions of excess sunlight the efficient light-harvesting antenna found in the chloroplast membranes of plants is rapidly and reversibly switched into a photoprotected quenched state in which potentially harmful absorbed energy is dissipated as heat, a process measured as the non-photochemical quenching of chlorophyll fluorescence or qE. Although the biological significance of qE is established, the molecular mechanisms involved are not. LHCII, the main light-harvesting complex, has an inbuilt capability to undergo transformation into a dissipative state by conformational change and it was suggested that this provides a molecular basis for qE, but it is not known if such events occur in vivo or how energy is dissipated in this state. The transition into the dissipative state is associated with a twist in the configuration of the LHCII-bound carotenoid neoxanthin, identified using resonance Raman spectroscopy. Applying this technique to study isolated chloroplasts and whole leaves, we show here that the same change in neoxanthin configuration occurs in vivo, to an extent consistent with the magnitude of energy dissipation. Femtosecond transient absorption spectroscopy, performed on purified LHCII in the dissipative state, shows that energy is transferred from chlorophyll a to a low-lying carotenoid excited state, identified as one of the two luteins (lutein 1) in LHCII. Hence, it is experimentally demonstrated that a change in conformation of LHCII occurs in vivo, which opens a channel for energy dissipation by transfer to a bound carotenoid. We suggest that this is the principal mechanism of photoprotection.     

Analysis of Plasmodium falciparum diversity in natural infections by deep sequencing

Malaria elimination strategies require surveillance of the parasite population for genetic changes that demand a public health response, such as new forms of drug resistance. Here we describe methods for the large-scale analysis of genetic variation in Plasmodium falciparum by deep sequencing of parasite DNA obtained from the blood of patients with malaria, either directly or after short-term culture. Analysis of 86,158 exonic single nucleotide polymorphisms that passed genotyping quality control in 227 samples from Africa, Asia and Oceania provides genome-wide estimates of allele frequency distribution, population structure and linkage disequilibrium. By comparing the genetic diversity of individual infections with that of the local parasite population, we derive a metric of within-host diversity that is related to the level of inbreeding in the population. An open-access web application has been established for the exploration of regional differences in allele frequency and of highly differentiated loci in the P.?falciparum genome.     

An Optimal Algorithm To Recognize Robinsonian Dissimilarities

A dissimilarity D on a finite set S is said to be Robinsonian if S can be totally ordered in such a way that, for every i < j < k, D (i, j) ≤ D (i, k) and D (j, k) ≤ D (i, k). Intuitively, D is Robinsonian if S can be represented by points on a line. Recognizing Robinsonian dissimilarities has many applications in seriation and classification. In this paper, we present an optimal O (n ²) algorithm to recognize Robinsonian dissimilarities, where n is the cardinal of S. Our result improves the already known algorithms.     

三维血管介入手术模拟方法

针对血管内介入手术模拟建模与碰撞消除方法存在的不足,提出了一种多体-双层的导管/导丝组合体模型及基于几何分析和旋转角传播的快速碰撞消除方法,并开发了一个实时的三维介入手术模拟系统,模拟导管/导丝在实际血管中的运动行为.该多体-双层模型由若干分段组成,每一分段代表了一段导丝、导管或两者兼有的组合体,导丝和导管的半径定义不同,材料属性不同,但每一分段长度相同.模型的运动通过碰撞检测和消除加以引导,抵达目标位置后对该模型施加松弛过程使其状态与实际状态更加吻合.实验结果表明,导管/导丝模型的运动状态与给定的材料参数密切相关,模拟可以达到实时的要求,方法可靠有效,有望应用于临床.     

KLHL3 mutations cause familial hyperkalemic hypertension by impairing ion transport in the distal nephron

Familial hyperkalemic hypertension (FHHt) is a Mendelian form of arterial hypertension that is partially explained by mutations in WNK1 and WNK4 that lead to increased activity of the Na(+)-Cl(-) cotransporter (NCC) in the distal nephron. Using combined linkage analysis and whole-exome sequencing in two families, we identified KLHL3 as a third gene responsible for FHHt. Direct sequencing of 43 other affected individuals revealed 11 additional missense mutations that were associated with heterogeneous phenotypes and diverse modes of inheritance. Polymorphisms at KLHL3 were not associated with blood pressure. The KLHL3 protein belongs to the BTB-BACK-kelch family of actin-binding proteins that recruit substrates for Cullin3-based ubiquitin ligase complexes. KLHL3 is coexpressed with NCC and downregulates NCC expression at the cell surface. Our study establishes a role for KLHL3 as a new member of the complex signaling pathway regulating ion homeostasis in the distal nephron and indirectly blood pressure.     

Genetic evidence that oxidative derivatives of retinoic acid are not involved in retinoid signaling during mouse development

Retinoic acid, the active derivative of vitamin A (retinol), is a hormonal signaling molecule that acts in developing and adult tissues. The Cyp26a1 (cytochrome p450, 26) protein metabolizes retinoic acid into more polar hydroxylated and oxidized derivatives. Whether some of these derivatives are biologically active metabolites has been debated. Cyp26a1(-/-) mouse fetuses have lethal morphogenetic phenotypes mimicking those generated by excess retinoic acid administration, indicating that human CYP26A1 may be essential in controlling retinoic acid levels during development. This hypothesis suggests that the Cyp26a1(-/-) phenotype could be rescued under conditions in which embryonic retinoic acid levels are decreased. We show that Cyp26a1(-/-) mice are phenotypically rescued by heterozygous disruption of Aldh1a2 (also known as Raldh2), which encodes a retinaldehyde dehydrogenase responsible for the synthesis of retinoic acid during early embryonic development. Aldh1a2 haploinsufficiency prevents the appearance of spina bifida and rescues the development of posterior structures (sacral/caudal vertebrae, hindgut, urogenital tract), while partly preventing cervical vertebral transformations and hindbrain pattern alterations in Cyp26a1(-/-) mice. Thus, some of these double-mutant mice can reach adulthood. This study is the first report of a mutation acting as a dominant suppressor of a lethal morphogenetic mutation in mammals. We provide genetic evidence that ALDH1A2 and CYP26A1 activities concurrently establish local embryonic retinoic acid levels that must be finely tuned to allow posterior organ development and to prevent spina bifida.     

Gamma-band synchronization in visual cortex predicts speed of change detection

Our capacity to process and respond behaviourally to multiple incoming stimuli is very limited. To optimize the use of this limited capacity, attentional mechanisms give priority to behaviourally relevant stimuli at the expense of irrelevant distractors. In visual areas, attended stimuli induce enhanced responses and an improved synchronization of rhythmic neuronal activity in the gamma frequency band (40-70 Hz). Both effects probably improve the neuronal signalling of attended stimuli within and among brain areas. Attention also results in improved behavioural performance and shortened reaction times. However, it is not known how reaction times are related to either response strength or gamma-band synchronization in visual areas. Here we show that behavioural response times to a stimulus change can be predicted specifically by the degree of gamma-band synchronization among those neurons in monkey visual area V4 that are activated by the behaviourally relevant stimulus. When there are two visual stimuli and monkeys have to detect a change in one stimulus while ignoring the other, their reactions are fastest when the relevant stimulus induces strong gamma-band synchronization before and after the change in stimulus. This enhanced gamma-band synchronization is also followed by shorter neuronal response latencies on the fast trials. Conversely, the monkeys' reactions are slowest when gamma-band synchronization is high in response to the irrelevant distractor. Thus, enhanced neuronal gamma-band synchronization and shortened neuronal response latencies to an attended stimulus seem to have direct effects on visually triggered behaviour, reflecting an early neuronal correlate of efficient visuo-motor integration.