Fungal horizons: the Asilomar Fungal Genetics Conference 2007.

This meeting report covers advances presented at the 2007 Asilomar Fungal Genetics Conference that expand our understanding of fungal biology and the myriad ways in which studies of organisms in this ubiquitous and successful kingdom of life advance an understanding of conserved biological principles.     

重组腺相关病毒2型转导人外周血单核细胞来源树突状细胞的研究

To find out the infection efficiency of recombinant adeno-as sociated virus 2-mediated exogenou s genes in human peripheral blood monocyte-derived dendritic cells(D Cs),the process of transfection wa s investigated by FITC-labeled rAA V2,and observed under confocal mic roscope.Newly separated dendritic cells were tranfected by rAAV2-luc and rAAV2-GFP at different MOI,and transfection efficiency were detec ted by luminometer for rAAV2-luc a nd flow cytometry for rAAV2-GFP.Th e results were elucidated in four different assay systems:(1)60min w as needed for rAAV2 to bind on den dritic cells,and got into cells in the following 10min;(2)the express ion of luc could be detected at th e MOI as low as 1×10~5v.g/cell,and the expression plateau was reached by the MOI of 10~6～10~7v.g/cell,furt her increase of MOI had no functio n on expression level;(3)transgene expression was detected after 48h, and maintained a higher expression level from 96h to 240h after infec tion;(4)7days postinfection of rAA V2-GFP,5%～18% dendritic cells were GFP positive. These data suggest th at rAAV2 vector can efficiently in fect monocyte-derived dendritic ce lls and mediate exogenous gene exp ression,and that the application o f rAAV2 as vector may be useful fo r gene transfer to dendritic cells in ex vivo immunotherapy.     

Window traps and direct observations record similar arthropod flower visitor assemblages in two mass flowering crops

Understanding the role of unmanaged arthropod flower visitors as crop pollinators is critical if robust and reliable long‐term alternatives are to be found for honey bee pollination. However, data on pollinator assemblages can be scant. Field observation of crop flower visitors is a common data collection technique but it can be inadequate for species identification and is labour‐intensive if used across many sites. Trapping may reduce this problem, but trap performance and sampling consistency over long distances (sites separated by >100 km) are rarely examined. Window traps were designed to collect flower‐visiting arthropods from peak‐flowering onion (Allium cepa) and pak choi (Brassica rapa var. chinensis) fields across several regions throughout New Zealand. Trap efficacy was evaluated by comparing trapped samples with observations of flower visiting arthropods during the same trapping period, from dawn (6:00 to 7:00 hours) through to dusk (20:00–21:00 hours) at the same locations. Similar types of larger arthropods (length ≥3 mm) were observed and trapped within both crops, with the hymenopteran genera Apidae, Colletidae and Halictidae and the dipteran families Syrphidae, Calliphoridae, Anthomyiidae, Stratiomyidae, Sarcophagidae, Bibionidae, Tachinidae and Muscidae the most commonly recorded. The total counts of these taxa across fields were strongly correlated between the two methods; however, the ratio of trapped to observed individuals could vary greatly between taxa. Trapping allowed more arthropods to be identified to the species level and also helped record more small arthropods (body length <3 mm) when compared with observation. Window traps can be effective for assessing the relative diversity of flower visitor assemblages and the abundance of specific taxa in specific cropping systems at the regional scale, but variation in trap efficiency between arthropod taxa must be assessed for a true measure of assemblage composition.     

Community mental health care in the Asia‐Pacific region: using current best‐practice models to inform future policy

The reporting of child sexual abuse (CSA) and physician-patient sexual relationships (PPSR) are currently the focus of professional, legal and media attention in several countries. This paper briefly reviews mental health policies on these issues and reports on a WPA survey of them. While the WPA Madrid Declaration permits breaching confidentiality for mandatory reporting of CSA and clearly prohibits PPSR, it is not known how or to what extent these policies are implemented in WPA Member Societies’ countries. It is also not known whether policies or laws exist on these topics nationally or to what extent psychiatrists and the public are aware of them. Representatives of WPA Member Societies were e-mailed a survey about issues pertaining to CSA and PPSR. Fifty-one percent of 109 countries replied. All reporting countries had laws or policies regarding the reporting of CSA, but this was often voluntary (63%) and without protection for reporting psychiatrists either by law (29%) or by Member Societies (27%). A substantial number of psychiatric leaders did not know the law (27%) or their Society’s policy (11%) on these matters. With respect to PPSR, some reporting countries lacked laws or policies about PPSR with current (17%) or past (56%) patients. Fewer than half of responding representatives believed that their Society’s members or the public were well informed about the laws and policies pertaining to CSA or PPSR. There is clearly a wide range of laws, policies and practices about CSA and PPSR in WPA Member Societies’ countries. There is a need in some countries for laws or supplemental policies to facilitate the protection of vulnerable child and adult patients through clear, mandatory reporting policies for CSA and PPSR. Mechanisms to protect and support reporting psychiatrists should also be developed where they do not already exist. There is also a need in some countries to develop strategies to improve the education of psychiatrists, trainees, and the public on these issues.The Asia-Pacific region has close to half of the estimated 450 million people affected by mental illness globally 1.Based on international mental health care benchmarks, many Western health systems have established contemporary health policy and guidelines which include the provision of mental health care in the community. However, the delivery of quality and appropriate community mental health care remains an ongoing challenge for countries of both high and low socio-economic level. Difficulties and obstacles in implementation of comprehensive community service models include inadequate funding, availability of trained mental health workforce, integration with primary care services and community agencies, and collaboration between public and private health systems 2 - 3. As community mental health service system depends on sufficient workforce for service delivery, the critical shortage of adequately trained mental health staff continues to impede the progress of mental health reform.In response to such global trends, many countries in the Asia-Pacific region have begun to establish mental health policy and guidelines to move from institutional care to community mental health services. While these reforms are supported by recommendations from the World Health Organization (WHO) governing bodies, such as the Western Pacific Regional Mental Health Strategy 4, social, economic and cultural factors in Asia-Pacific countries often do not allow ready translation of Western community mental health models of care. Governments and service providers commonly face challenges in the development and implementation of locally appropriate community mental health care and services. Additionally, it would be unrealistic or undesirable to produce rigid recommendations for a singular community mental health care model, due to the diversity across the Asia-Pacific region. Hence, for constructive change to occur in the region, innovative, culturally appropriate and economically sustainable pathways for community treatment models need to be explored, developed and shared. Community mental health service reform appears to be gaining momentum in this region, despite the obstacles. Valuable lessons and inspiration for further development can be gained from both the successes and difficulties in reforming mental health systems and practices in the region.An emerging network of representatives from governments, peak bodies and key organizations is emerging in the Asia-Pacific region to build supportive relationships in order to facilitate the implementation of locally appropriate policy frameworks for community mental health service reform. The network is supported by the Asia-Pacific Community Mental Health Development (APCMHD) project, which involves 14 countries/regions in the Asia-Pacific region. Initiated in collaboration with the WHO Western Pacific Regional Office, the APCMHD project is led by Asia-Australia Mental Health, a consortium of the University of Melbourne Department of Psychiatry and Asialink, and St. Vincent’s Health, which is a part of the WHO Collaborating Centre for Mental Health (Melbourne). The project, which brought many key mental health organizations to work collaboratively, is consistent with the WHO Global Action Programme for Mental Health 5.The project aims are to promote best practice in community mental health care through exchange of knowledge and practical experience in the Asia-Pacific region. The key outcome is the documentation of the current status, strengths and needs of community mental health services in the region, in the hope to translate current understanding into practical changes in the future.     

Apolipoproteins and amyloid fibril formation in atherosclerosis

Amyloid fibrils arise from the aggregation of misfolded proteins into highly-ordered structures. The accumulation of these fibrils along with some non-fibrillar constituents within amyloid plaques is associated with the pathogenesis of several human degenerative diseases. A number of plasma apolipoproteins, including apolipoprotein (apo) A-I, apoA-II, apoC-II and apoE are implicated in amyloid formation or influence amyloid formation by other proteins. We review present knowledge of amyloid formation by apolipoproteins in disease, with particular focus on atherosclerosis. Further insights into the molecular mechanisms underlying their amyloidogenic propensity are obtained from in vitro studies which describe factors affecting apolipoprotein amyloid fibril formation and interactions. Additionally, we outline the evidence that amyloid fibril formation by apolipoproteins might play a role in the development and progression of atherosclerosis, and highlight possible molecular mechanisms that could contribute to the pathogenesis of this disease.     

Evidence that Cd101 is an autoimmune diabetes gene in nonobese diabetic mice

We have previously proposed that sequence variation of the CD101 gene between NOD and C57BL/6 mice accounts for the protection from type 1 diabetes (T1D) provided by the insulin-dependent diabetes susceptibility region 10 (Idd10), a <1 Mb region on mouse chromosome 3. In this study, we provide further support for the hypothesis that Cd101 is Idd10 using haplotype and expression analyses of novel Idd10 congenic strains coupled to the development of a CD101 knockout mouse. Susceptibility to T1D was correlated with genotype-dependent CD101 expression on multiple cell subsets, including Foxp3(+) regulatory CD4(+) T cells, CD11c(+) dendritic cells, and Gr1(+) myeloid cells. The correlation of CD101 expression on immune cells from four independent Idd10 haplotypes with the development of T1D supports the identity of Cd101 as Idd10. Because CD101 has been associated with regulatory T and Ag presentation cell functions, our results provide a further link between immune regulation and susceptibility to T1D.     

Extracellular ATP Hydrolysis Inhibits Synaptic Transmission by Increasing pH Buffering in the Synaptic Cleft

Neuronal computations strongly depend on inhibitory interactions. One such example occurs at the first retinal synapse, where horizontal cells inhibit photoreceptors. This interaction generates the center/surround organization of bipolar cell receptive fields and is crucial for contrast enhancement. Despite its essential role in vision, the underlying synaptic mechanism has puzzled the neuroscience community for decades. Two competing hypotheses are currently considered: an ephaptic and a proton-mediated mechanism. Here we show that horizontal cells feed back to photoreceptors via an unexpected synthesis of the two. The first one is a very fast ephaptic mechanism that has no synaptic delay, making it one of the fastest inhibitory synapses known. The second one is a relatively slow (τ≈200 ms), highly intriguing mechanism. It depends on ATP release via Pannexin 1 channels located on horizontal cell dendrites invaginating the cone synaptic terminal. The ecto-ATPase NTPDase1 hydrolyses extracellular ATP to AMP, phosphate groups, and protons. The phosphate groups and protons form a pH buffer with a pKa of 7.2, which keeps the pH in the synaptic cleft relatively acidic. This inhibits the cone Ca²⁺ channels and consequently reduces the glutamate release by the cones. When horizontal cells hyperpolarize, the pannexin 1 channels decrease their conductance, the ATP release decreases, and the formation of the pH buffer reduces. The resulting alkalization in the synaptic cleft consequently increases cone glutamate release. Surprisingly, the hydrolysis of ATP instead of ATP itself mediates the synaptic modulation. Our results not only solve longstanding issues regarding horizontal cell to photoreceptor feedback, they also demonstrate a new form of synaptic modulation. Because pannexin 1 channels and ecto-ATPases are strongly expressed in the nervous system and pannexin 1 function is implicated in synaptic plasticity, we anticipate that this novel form of synaptic modulation may be a widespread phenomenon.     

Brm Inhibits the Proliferative Response of Keratinocytes and Corneal Epithelial Cells to Ultraviolet Radiation-Induced Damage

Ultraviolet radiation (UV) from sunlight is the primary cause of skin and ocular neoplasia. Brahma (BRM) is part of the SWI/SNF chromatin remodeling complex. It provides energy for rearrangement of chromatin structure. Previously we have found that human skin tumours have a hotspot mutation in BRM and that protein levels are substantially reduced. Brm−/− mice have enhanced susceptibility to photocarcinogenesis. In these experiments, Brm−/− mice, with both or a single Trp53 allele were exposed to UV for 2 or 25 weeks. In wild type mice the central cornea and stroma became atrophic with increasing time of exposure while the peripheral regions became hyperplastic, presumably as a reparative process. Brm−/−, Trp53+/−, and particularly the Brm−/− Trp53+/− mice had an exaggerated hyperplastic regeneration response in the corneal epithelium and stroma so that the central epithelial atrophy or stromal loss was reduced. UV induced hyperplasia of the epidermis and corneal epithelium, with an increase in the number of dividing cells as determined by Ki-67 expression. This response was considerably greater in both the Brm−/− Trp53+/+ and Brm−/− Trp53+/− mice indicating that Brm protects from UV-induced enhancement of cell division, even with loss of one Trp53 allele. Cell division was disorganized in Brm−/− mice. Rather than being restricted to the basement membrane region, dividing cells were also present in the suprabasal regions of both tissues. Brm appears to be a tumour suppressor gene that protects from skin and ocular photocarcinogenesis. These studies indicate that Brm protects from UV-induced hyperplastic growth in both cutaneous and corneal keratinocytes, which may contribute to the ability of Brm to protect from photocarcinogenesis.