A viral strategy for targeting and manipulating interneurons across vertebrate species

A fundamental impediment to understanding the brain is the availability of inexpensive and robust methods for targeting and manipulating specific neuronal populations. The need to overcome this barrier is pressing because there are considerable anatomical, physiological, cognitive and behavioral differences between mice and higher mammalian species in which it is difficult to specifically target and manipulate genetically defined functional cell types. In particular, it is unclear the degree to which insights from mouse models can shed light on the neural mechanisms that mediate cognitive functions in higher species, including humans. Here we describe a novel recombinant adeno-associated virus that restricts gene expression to GABAergic interneurons within the telencephalon. We demonstrate that the viral expression is specific and robust, allowing for morphological visualization, activity monitoring and functional manipulation of interneurons in both mice and non-genetically tractable species, thus opening the possibility to study GABAergic function in virtually any vertebrate species.National Institutes of Health (U.S.) (Grant MH071679)National Institutes of Health (U.S.) (Grant NS08297)National Institutes of Health (U.S.) (Grant NS074972)National Institutes of Health (U.S.) (Grant MH095147)National Institutes of Health (U.S.) (Grant MH066912)National Institutes of Health (U.S.) (Grant EY022577)National Institutes of Health (U.S.) (Grant MH063912

Особенности планировки и застройки научно-технологических парков в условиях провинций Шаньси и Ганьсу в Китайской Народной Республике

Creation and development of scientific and technological parks in the People's Republic of China is used as a means of activating areas in need of socio-economic development, for example such territories as along the New Silk Road in Shanxi and Gansu provinces. Five types of basic planning models recommended for creation of scientific and technological parks of different functional profiles have been developed in the paper. Model A comprises scientific and technological parks with a compact layout (area of less than 2 square kilometers) located in the peripheral zones of large cities built into the city's infrastructure and they do not have practically reserves for territorial development. The model is recommended for creation of educational and scientific parks and high-tech parks. Model B comprises scientific and technological parks of medium size (area of their territory – 2–10 square kilometers) located in the nearest suburbs of large cities (up to 10 km) and these parks partially use urban infrastructure having the possibility for territorial development. The model is recommended for creation parks of industrial-logistics, high technology, light industry, precision engineering. Model C comprises scientific and technological parks of medium size (area of 10–20 square kilometers) located in the suburbs of large cities (up to 30 km), geographically and infra-structurally interconnected with international airports. The model is recommended for creating parks of high-tech, precision engineering, biochemistry that produce products which are economically expedient to be transported by airplanes (smart phones, optical fiber equipment, other high-tech devices, cosmetics, medicines, etc.). Model D comprises scientific and technological park of medium size (area of 10–20 square kilometers) located in the suburbs of large cities (up to 30 km) along transport and communication corridors of national and regional importance with its own infrastructure and territorial development opportunities. The model is recommended for creation of parks in construction industry, transport engineering, bio- and agro-technologies. Model E comprises large-scale scientific and technological parks (with area of more than 20 square kilometers) located in inter-settlement territories along transport and communication corridors of international and national importance with its own infrastructure and territorial development opportunities. The model is recommended for creation of parks for chemical industry, heavy and transport engineering. The paper has made it possible to identify common types of functionalplanning zones formed on the territory of scientific and technological parks and it provides recommendations on their correlation. Analysis of the layout for existing and projected scientific and technological parks has allowed to develop characteristic schemes of their planning organization: band, compact, dispersed.Создание и развитие научно-технологических парков в Китайской Народной Республике используется как средство активизации районов, нуждающихся в социально-экономическом развитии, например, таких, как территории вдоль Нового шелкового пути в провинциях Шаньси и Ганьсу. Разработаны пять типов базовых планировочных моделей, рекомендуемых для создания научно-технологических парков разного функционального профиля. Модель А – научно-технологические парки с компактной планировкой (площадь территории менее 2 кв. км), размещаемые в периферийных зонах больших городов, встроенные в инфраструктуру города, практически не имеющие резервов для территориального развития. Модель рекомендуется для образовательно-научных парков, парков высоких технологий. Модель Б – научно-технологические парки средней величины (площадь территории 2–10 кв. км), размещаемые в ближайших пригородах больших городов (до 10 км), частично использующие городскую инфраструктуру, имеющие возможность территориального развития. Модель рекомендуется для парков производственно-логистических, высоких технологий, легкой промышленности, точного машиностроения. Модель В – научно-технологические парки средней величины (площадь территории 10–20 кв. км), размещаемые в пригородных зонах больших городов (до 30 км), территориально и инфраструктурно взаимосвязанные с международными аэропортами. Модель рекомендуется для парков высоких технологий, точного машиностроения, биохимии, производящих продукцию, которую экономически целесообразно перевозить на самолетах (смартфоны, оптико-волоконная техника и иные высокотехничные устройства, косметика, лекарства и др.). Модель Г – научно-технологические парки средней величины (площадь территории 10–20 кв. км), размещаемые в пригородных зонах больших городов (до 30 км) вдоль транспортно-коммуникационных коридоров национального и регионального значения, имеющие собственную инфраструктуру и возможность территориального развития. Модель рекомендуется для парков строительной индустрии, транспортного машиностроения, био- и агротехнологий. Модель Д – научно-технологические парки большой величины (площадь территории более 20 кв. км), размещаемые на межселенных территориях, вдоль транспортно-коммуникационных коридоров международного и национального значения, имеющие собственную инфраструктуру и возможность территориального развития. Модель рекомендуется для парков химической промышленности, тяжелого, транспортного машиностроения. Выявлены характерные типы функционально-планировочных зон, формируемых на территории научно-технологических парков, и даны рекомендации по их соотношению. Анализ планировки существующих и проектируемых научно-технологических парков позволил разработать характерные схемы их планировочной организации: полосовую, компактную, рассредоточенную

Regulation of synaptic growth and maturation by a synapse-associated E3 ubiquitin ligase at the neuromuscular junction

The ubiquitin–proteasome pathway has been implicated in synaptic development and plasticity. However, mechanisms by which ubiquitination contributes to precise and dynamic control of synaptic development and plasticity are poorly understood. We have identified a PDZ domain containing RING finger 3 (PDZRN3) as a synapse-associated E3 ubiquitin ligase and have demonstrated that it regulates the surface expression of muscle-specific receptor tyrosine kinase (MuSK), the key organizer of postsynaptic development at the mammalian neuromuscular junction. PDZRN3 binds to MuSK and promotes its ubiquitination. Regulation of cell surface levels of MuSK by PDZRN3 requires the ubiquitin ligase domain and is mediated by accelerated endocytosis. Gain- and loss-of-function studies in cultured myotubes show that regulation of MuSK by PDZRN3 plays an important role in MuSK-mediated nicotinic acetylcholine receptor clustering. Furthermore, overexpression of PDZRN3 in skeletal muscle of transgenic mice perturbs the growth and maturation of the neuromuscular junction. These results identify a synapse-associated E3 ubiquitin ligase as an important regulator of MuSK signaling

Impacts of Abnormal Heating of Tibetan Plateau on Rossby Wave Activity and Hazards Related to Snow and Ice in South China

In January 2008, extreme freezing rain struck South China. At the same time, the Tibetan Plateau (TP) was experiencing pronounced surface heating. The characteristics of this extreme weather and its linkage to the TP surface heating anomaly were analyzed in this paper. The results show that (1) anomalous heating of the TP helps to form and sustain the Siberian blocking high, which is important for persistent southward flow of dry and cold Siberian air; (2) TP heating helps the moisture flux move more north and strengthens the southerly wind above 850 hPa; (3) there are two Rossby wave trains at 500 hPa and the layers above it (at about 20∘N–40∘N). Correlation analysis reveals that TP heating anomalies are closely associated with these Rossby wave trains; (4) the Rossby wave propagates downstream from the TP to South China in the mid and high layers of the atmosphere when the TP changes swiftly from a heat sink to a heat source. This implies that anomalous heating of the TP may stimulate the Rossby wave train to propagate downward in midlatitudes

Epidemic Spreading with Heterogeneous Awareness on Human Networks

The spontaneous awareness behavioral responses of individuals have a significant impact on epidemic spreading. In this paper, a modified Susceptible-Alert-Infected-Susceptible (SAIS) epidemic model with heterogeneous awareness is presented to study epidemic spreading in human networks and the impact of heterogeneous awareness on epidemic dynamics. In this model, when susceptible individuals receive awareness information about the presence of epidemic from their infected neighbor nodes, they will become alert individuals with heterogeneous awareness rate. Theoretical analysis and numerical simulations show that heterogeneous awareness can enhance the epidemic threshold with certain conditions and reduce the scale of virus outbreaks compared with no awareness. What is more, for the same awareness parameter, it also shows that heterogeneous awareness can slow effectively the spreading size and does not delay the arrival time of epidemic spreading peak compared with homogeneous awareness

Maternal diabetes up-regulates NOX2 and enhances myocardial ischaemia/reperfusion injury in adult offspring

Offspring of diabetic mothers are at risk of cardiovascular diseases in adulthood. However, the underlying molecular mechanisms are not clear. We hypothesize that prenatal exposure to maternal diabetes up-regulates myocardial NOX2 expression and enhances ischaemia/reperfusion (I/R) injury in the adult offspring. Maternal diabetes was induced in C57BL/6 mice by streptozotocin. Glucose-tolerant adult offspring of diabetic mothers and normal controls were subjected to myocardial I/R injury. Vascular endothelial growth factor (VEGF) expression, ROS generation, myocardial apoptosis and infarct size were assessed. The VEGF-Akt (protein kinase B)-mammalian target of rapamycin (mTOR)-NOX2 signalling pathway was also studied in cultured cardiomyocytes in response to high glucose level. In the hearts of adult offspring from diabetic mothers, increases were observed in VEGF expression, NOX2 protein levels and both Akt and mTOR phosphorylation levels as compared to the offspring of control mothers. After I/R, ROS generation, myocardial apoptosis and infarct size were all significantly higher in the offspring of diabetic mothers relative to offspring of control mothers, and these differences were diminished by in vivo treatment with the NADPH oxidase inhibitor apocynin. In cultured cardiomyocytes, high glucose increased mTOR phosphorylation, which was inhibited by the PI3 kinase inhibitor LY294002. Notably, high glucose-induced NOX2 protein expression and ROS production were inhibited by rapamycin. In conclusion, maternal diabetes promotes VEGF-Akt-mTOR-NOX2 signalling and enhances myocardial I/R injury in the adult offspring. Increased ROS production from NOX2 is a possible molecular mechanism responsible for developmental origins of cardiovascular disease in offspring of diabetic mothers