Three-Dimensional Structure of CAP-Gly Domain of Mammalian Dynactin Determined by Magic Angle Spinning NMR Spectroscopy: Conformational Plasticity and Interactions with End-Binding Protein EB1

Microtubules and their associated proteins play important roles in vesicle and organelle transport, cell motility and cell division. Perturbation of these processes by mutation typically gives rise to severe pathological conditions. In our efforts to obtain atomic information on microtubule-associated protein/microtubule interactions with the goal to understand mechanisms that might potentially assist in the development of treatments for these diseases, we have determined the three-dimensional structure of CAP-Gly (cytoskeleton-associated protein, glycine-rich) domain of mammalian dynactin by magic angle spinning NMR spectroscopy. We observe two conformations in the β2 strand encompassing residues T43-V44-A45, residues that are adjacent to the disease-associated mutation, G59S. Upon binding of CAP-Gly to microtubule plus-end tracking protein EB1, the CAP-Gly shifts to a single conformer. We find extensive chemical shift perturbations in several stretches of residues of CAP-Gly upon binding to EB1, from which we define accurately the CAP-Gly/EB1 binding interface. We also observe that the loop regions may exhibit unique flexibility, especially in the GKNDG motif, which participates in the microtubule binding. This study in conjunction with our previous reports suggests that conformational plasticity is an intrinsic property of CAP-Gly likely due to its unusually high loop content and may be required for its biological functions.     

The Four Canonical TPR Subunits of Human APC/C Form Related Homo-Dimeric Structures and Stack in Parallel to Form a TPR Suprahelix

The anaphase-promoting complex or cyclosome (APC/C) is a large E3 RING-cullin ubiquitin ligase composed of between 14 and 15 individual proteins. A striking feature of the APC/C is that only four proteins are involved in directly recognizing target proteins and catalyzing the assembly of a polyubiquitin chain. All other subunits, which account for > 80% of the mass of the APC/C, provide scaffolding functions. A major proportion of these scaffolding subunits are structurally related. In metazoans, there are four canonical tetratricopeptide repeat (TPR) proteins that form homo-dimers (Apc3/Cdc27, Apc6/Cdc16, Apc7 and Apc8/Cdc23). Here, we describe the crystal structure of the N-terminal homo-dimerization domain of Schizosaccharomyces pombe Cdc23 (Cdc23^Nterm). Cdc23^Nterm is composed of seven contiguous TPR motifs that self-associate through a related mechanism to those of Cdc16 and Cdc27. Using the Cdc23^Nterm structure, we generated a model of full-length Cdc23. The resultant “V”-shaped molecule docks into the Cdc23-assigned density of the human APC/C structure determined using negative stain electron microscopy (EM). Based on sequence conservation, we propose that Apc7 forms a homo-dimeric structure equivalent to those of Cdc16, Cdc23 and Cdc27. The model is consistent with the Apc7-assigned density of the human APC/C EM structure. The four canonical homo-dimeric TPR proteins of human APC/C stack in parallel on one side of the complex. Remarkably, the uniform relative packing of neighboring TPR proteins generates a novel left-handed suprahelical TPR assembly. This finding has implications for understanding the assembly of other TPR-containing multimeric complexes.     

黑龙江省野生东北虎调查管理信息系统的构建

文章以黑龙江省野生东北虎（Panthera tigris altaica）野外调查数据为基础,利用地理信息系统技术、计算机技术与野生动物资源调查管理技术,构建了黑龙江省野生东北虎调查管理信息系统。主要运用面向对象程序设计语言C#和ArcGIS Engine嵌入式组件技术以及SQL Server数据库技术,设计并构建东北虎调查管理系统,实现了对野生东北虎调查数据的图形可视化操作管理。同时,结合研究区域内的自然因素和人文因素对调查资源进行动态的空间分析,及时准确地反映出东北虎的种群数量和空间变化规律,并制作出相应的分类专题图及野外分布信息统计图表等。该管理信息系统将有助于野生东北虎种群及栖息地调查数据与资料的科学管理,对于推动我国野生东北虎就地保护和科学管理具有重要意义。     

Albinism in phylogenetically and geographically distinct populations of Astyanax cavefish arises through the same loss-of-function Oca2 allele

The Mexican tetra, Astyanax mexicanus, comprises 29 populations of cave-adapted fish distributed across a vast karst region in northeastern Mexico. These populations have a complex evolutionary history, having descended from ‘old'' and ‘young'' ancestral surface-dwelling stocks that invaded the region ∼6.7 and ∼2.8 MYa, respectively. This study investigates a set of captive, pigmented Astyanax cavefish collected from the Micos cave locality in 1970, in which albinism appeared over the past two decades. We combined novel coloration analyses, coding sequence comparisons and mRNA expression level studies to investigate the origin of albinism in captive-bred Micos cavefish. We discovered that albino Micos cavefish harbor two copies of a loss-of-function ocular and cutaneous albinism type II (Oca2) allele previously identified in the geographically distant Pachón cave population. This result suggests that phylogenetically young Micos cavefish and phylogenetically old Pachón cave fish inherited this Oca2 allele from the ancestral surface-dwelling taxon. This likely resulted from the presence of the loss-of-function Oca2 haplotype in the ‘young'' ancestral surface-dwelling stock that colonized the Micos cave and also introgressed into the ancient Pachón cave population. The appearance of albinism in captive Micos cavefish, caused by the same loss-of-function allele present in Pachón cavefish, implies that geographically and phylogenetically distinct cave populations can evolve the same troglomorphic phenotype from standing genetic variation present in the ancestral taxon.     

Environmental correlates of annual survival differ between two ecologically similar and congeneric owls

Understanding how survival is affected by the environment is essential to gain insight into population dynamics and the evolution of life‐history traits as well as to identify environmental selection pressures. However, we still have little understanding of the relative effect of different environmental factors and their interactions on demographic traits and population dynamics. Here we used two long‐term, individual‐based datasets on Tawny Owl Strix aluco (1981–2010) and Ural Owl S. uralensis (1986–2010) to undertake capture‐mark‐recapture analysis of annual survival of adult females in response to three biologically meaningful environmental variables and their two‐way interactions. Despite the similar ecology of these two species, their survival was associated with different and uncorrelated environmental drivers. The main correlate of Tawny Owl survival was an inverse association with snow depth (winter severity). For Ural Owl, high food (vole) abundance improved survival during years with deep snow, but was less important during years with little snow. In addition, Ural Owl survival was strongly density‐dependent, whereas Tawny Owl survival was not. Our findings advise caution in extrapolating demographic inferences from one species to another, even when they are very closely related and ecologically similar. Analyses including only one or few potential environmental drivers of a species' survival may lead to incomplete conclusions because survival may be affected by several factors and their interactions.     

New tools for the investigations of Neuro-AIDS at a molecular level: The potential role of data-mining

Cognitive impairment represents the most significant and devastating neurological complication associated with HIV infection. Despite recent advances in our knowledge of the clinical features, pathogenesis, and molecular aspects of HIV-related dementia, current diagnostic strategies are associated with significant limitations. It has been suggested that the use of some biomarkers may assist researchers and clinicians in predicting the onset of the disease process and in evaluating the effects of new therapies. However, the large number of chemicals and metabolic pathways involved in the pathogenesis of neurodegeneration, warrants the development of novel approaches to integrate this huge amount of data. The contribution of theoretical disciplines, such as bioinformatics and data-mining, may be useful for testing new hypotheses in diagnosis and patient-centered treatment interventions.     

The effectiveness of post-contact defenses in a prey with no pre-contact detection

Most empirical and theoretical papers on prey–predator interactions are for animals with long-range detection, animals that can detect and react to predators long before these touch the prey. Heavy-bodied and chemically defended harvestmen (Arachnida, Opiliones) are an exception to this general pattern and rely on contact to detect arthropod predators. We examined the interactions between the Brazilian wandering spider Ctenus ornatus with harvestmen (Mischonyx cuspidatus) or control prey (Gryllus sp. and M. cuspidatus immature, both with soft integuments). Considering a prey–predator system in which fleeing from or reacting to a predator at a distance is not possible, we predicted both a high survival value of near-range defense mechanisms and that mortality would be higher in the absence of such defense mechanisms. We also expected the predator to behave differently when interacting with harvestmen or with a control prey without such defense mechanisms. Our results from laboratory experiments partially matched our predictions: First of all, histological sections showed that the integument of adult harvestmen is thicker than that of immature harvestmen and that of crickets. Adult harvestmen were less preyed upon than the control prey; the heavy armature increases the survival rate but the secretions from the scent glands do not. The predator did behave differently when attacking harvestmen compared to crickets. Despite the large size difference between predator and harvestmen, the protection provided by the armature allowed some of the harvestmen to survive encounters without pre-contact detection, thus greatly reducing the reliance on long-range detection to survive encounters with predators. Harvestmen call for theoretical and empirical work on prey–predator interactions that take into account the possibility that prey may not detect the predator before contact is established.     

CHANGES IN CLICK SOURCE LEVELS WITH DISTANCE TO TARGETS: STUDIES OF FREE-RANGING WHITE-BEAKED DOLPHINS LAGENORHYNCHUS ALBIROSTRIS AND CAPTIVE HARBOUR PORPOISES PHOCOENA PHOCOENA

ABSTRACT

Probably all odontocetes use echolocation for spatial orientation and detection of prey. We used a four hydrophone “Y” array to record the high frequency clicks from free-ranging White-beaked Dolphins Lagenorhynchus albirostris and captive Harbour Porpoises Phocoena phocoena. From the recordings we calculated distances to the animals and source levels of the clicks. The recordings from White-beaked Dolphins were made in Iceland and those from Harbour Porpoises at Fjord & Baelt, Kerteminde, Denmark during prey capture. We used stringent criteria to determine which clicks could be defined as being on the acoustic axis. Two dolphin and nine porpoise click series could be used to track individual animals, which presumably focused on the array hydrophones or a fish right in front of the array. The apparent source levels of clicks in the individual tracks increased with range. One individual White-beaked Dolphin and three Harbour Porpoises regulate their output signal level to nearly compensate for one-way transmission loss while approaching a target. The other dolphin regulated the output differently. For most of the recordings the sound level at the target remains nearly constant and the echo level at the animal increases as it closes on the target.