A SxIP motif interaction at the microtubule plus end is important for processive retrograde axonal transport

The retrograde transport of endosomes within axons proceeds with remarkable uniformity despite having to navigate a discontinuous microtubule network. The mechanisms through which this navigation is achieved remain elusive. In this report, we demonstrate that access of SxIP motif proteins, such as BPAG1n4, to the microtubule plus end is important for the maintenance of processive and sustained retrograde transport along the axon. Disruption of this interaction at the microtubule plus end significantly increases endosome stalling. Our study thus provides strong insight into the role of plus-end-binding proteins in the processive navigation of cargo within the axon.     

An Holistic Approach to the Management of Information Systems Development—A View Using a Soft Systems Approach and Multiple Viewpoints

This paper argues that only a systems-based approach to information systems development is likely to cover all the recognized problem issues reported in the literature. It is then shown that software development can be characterized by the structure of the Soft Systems Methodology, so that this methodology acts as a metaphor for the process of information systems development. The structure of this methodology can be seen at lower levels of the development process, and so the model generated here is seen as recursive. Further, information systems development is seen as an unstructured business problem that can be characterized by the Multiple Viewpoint approach. The connections between this approach and the methodology are identified. Finally, the unifying link between these approaches and all forms of action research is identified.     

Mutations in the gene encoding GlyT2 (SLC6A5) define a presynaptic component of human startle disease

Hyperekplexia is a human neurological disorder characterized by an excessive startle response and is typically caused by missense and nonsense mutations in the gene encoding the inhibitory glycine receptor (GlyR) alpha1 subunit (GLRA1). Genetic heterogeneity has been confirmed in rare sporadic cases, with mutations affecting other postsynaptic glycinergic proteins including the GlyR beta subunit (GLRB), gephyrin (GPHN) and RhoGEF collybistin (ARHGEF9). However, many individuals diagnosed with sporadic hyperekplexia do not carry mutations in these genes. Here we show that missense, nonsense and frameshift mutations in SLC6A5 (ref. 8), encoding the presynaptic glycine transporter 2 (GlyT2), also cause hyperekplexia. Individuals with mutations in SLC6A5 present with hypertonia, an exaggerated startle response to tactile or acoustic stimuli, and life-threatening neonatal apnea episodes. SLC6A5 mutations result in defective subcellular GlyT2 localization, decreased glycine uptake or both, with selected mutations affecting predicted glycine and Na+ binding sites.     

Bacteria adhesion and biofilms on surfaces

Bacterial adhesion has become a significant problem in industry and in the domicile, and much research has been done for deeper understanding of the processes involved. A generic biological model of bacterial adhesion and population growth called the bacterial biofilm growth cycle, has been described and modified many times. The biofilm growth cycle encompasses bacterial adhesion at all levels, starting with the initial physical attraction of bacteria to a substrate, and ending with the eventual liberation of cell clusters from the biofilm matrix. When describing bacterial adhesion one is simply describing one or more stages of biofilm development, neglecting the fact that the population may not reach maturity. This article provides an overview of bacterial adhesion, cites examples of how bacterial adhesion affects industry and summarises methods and instrumentation used to improve our understanding of the adhesive properties of bacteria.     

Dissecting the genomic complexity underlying medulloblastoma

Medulloblastoma is an aggressively growing tumour, arising in the cerebellum or medulla/brain stem. It is the most common malignant brain tumour in children, and shows tremendous biological and clinical heterogeneity. Despite recent treatment advances, approximately 40% of children experience tumour recurrence, and 30% will die from their disease. Those who survive often have a significantly reduced quality of life. Four tumour subgroups with distinct clinical, biological and genetic profiles are currently identified. WNT tumours, showing activated wingless pathway signalling, carry a favourable prognosis under current treatment regimens. SHH tumours show hedgehog pathway activation, and have an intermediate prognosis. Group 3 and 4 tumours are molecularly less well characterized, and also present the greatest clinical challenges. The full repertoire of genetic events driving this distinction, however, remains unclear. Here we describe an integrative deep-sequencing analysis of 125 tumour-normal pairs, conducted as part of the International Cancer Genome Consortium (ICGC) PedBrain Tumor Project. Tetraploidy was identified as a frequent early event in Group 3 and 4 tumours, and a positive correlation between patient age and mutation rate was observed. Several recurrent mutations were identified, both in known medulloblastoma-related genes (CTNNB1, PTCH1, MLL2, SMARCA4) and in genes not previously linked to this tumour (DDX3X, CTDNEP1, KDM6A, TBR1), often in subgroup-specific patterns. RNA sequencing confirmed these alterations, and revealed the expression of what are, to our knowledge, the first medulloblastoma fusion genes identified. Chromatin modifiers were frequently altered across all subgroups. These findings enhance our understanding of the genomic complexity and heterogeneity underlying medulloblastoma, and provide several potential targets for new therapeutics, especially for Group 3 and 4 patients.     

Geological and chronological evidence of Indo-Chinese strike-slip movement in the Altyn Tagh fault zone

A set of granitic and amphibole mylonite are exposed in the Altyn Tagh fault zone. The preliminary study shows that these rocks are the product of the syntectonic anatexis in the process of the left-lat- eral strike-slip shear, and are the result of the ductile transpression. There are two types of zircon sorted from the mylonite formed with synshear anatexis. Among them, one is the anatectic long columnar zircon and another is the residual metamorphic sub-rounded columnar zircon. Two groups of age for single zircon measured by ion microprobe (SHRIMP) are obtained: one is 461-547 Ma for the sub-rounded columnar residual metamorphic zircon, and the other is 239-244 Ma for the long-columnar anatectic zircon. This type of zircon is directionally spread in rock, and the long axis direction of its crystal is identical to that of stretching lineation, representing the direction of tectonic stress in the process of the strike-slip. 40Ar-39Ar age of the directional growth hornblende in the same mylonite sample measured is 223-226 Ma. The above geological and chronological data prove that the syntectonic anatexis occurred during Indo-Chinese Epoch, showing that the strong strike-slip movement occurred in the Altyn Tagh fault zone at least as early as Indo-Chinese Epoch.     

神经生理学家艾伦·霍奇金(1914～1998)

1998年12月20日去世的艾伦·霍奇金（AlanHodgkin）是本世纪最伟大的神经生理学家之一。在一个极有应用前景的领域中，他和个赫克斯利（AudrewHuxley）合作，通过解释神经冲动的起因，为大部分现代神经科学奠定了基础。他们的工作不仅仅在于阐明种经冲动的爆炸“起火”和冲动沿着神经轴突（神经纤维）的传导，同时也打开了一个所谓‘海子通道”的全新的科学领域——即嵌入在每个细胞的细胞膜表面的一个亚微观孔道，它们调节离子的通过，并控制由大批细胞组成的程序。1939年7月，霍奇金和赫克斯利（一位25岁，一位对岁）成功地测量了神经细…     

The trophic fingerprint of marine fisheries

Biodiversity indicators provide a vital window on the state of the planet, guiding policy development and management. The most widely adopted marine indicator is mean trophic level (MTL) from catches, intended to detect shifts from high-trophic-level predators to low-trophic-level invertebrates and plankton-feeders. This indicator underpins reported trends in human impacts, declining when predators collapse ("fishing down marine food webs") and when low-trophic-level fisheries expand ("fishing through marine food webs"). The assumption is that catch MTL measures changes in ecosystem MTL and biodiversity. Here we combine model predictions with global assessments of MTL from catches, trawl surveys and fisheries stock assessments and find that catch MTL does not reliably predict changes in marine ecosystems. Instead, catch MTL trends often diverge from ecosystem MTL trends obtained from surveys and assessments. In contrast to previous findings of rapid declines in catch MTL, we observe recent increases in catch, survey and assessment MTL. However, catches from most trophic levels are rising, which can intensify fishery collapses even when MTL trends are stable or increasing. To detect fishing impacts on marine biodiversity, we recommend greater efforts to measure true abundance trends for marine species, especially those most vulnerable to fishing.