Novel role of PKR in inflammasome activation and HMGB1 release

The inflammasome regulates the release of caspase activation-dependent cytokines, including interleukin (IL)-1β, IL-18 and high-mobility group box 1 (HMGB1). By studying HMGB1 release mechanisms, here we identify a role for double-stranded RNA-dependent protein kinase (PKR, also known as EIF2AK2) in inflammasome activation. Exposure of macrophages to inflammasome agonists induced PKR autophosphorylation. PKR inactivation by genetic deletion or pharmacological inhibition severely impaired inflammasome activation in response to double-stranded RNA, ATP, monosodium urate, adjuvant aluminium, rotenone, live Escherichia coli, anthrax lethal toxin, DNA transfection and Salmonella typhimurium infection. PKR deficiency significantly inhibited the secretion of IL-1β, IL-18 and HMGB1 in E. coli-induced peritonitis. PKR physically interacts with several inflammasome components, including NOD-like receptor (NLR) family pyrin domain-containing 3 (NLRP3), NLRP1, NLR family CARD domain-containing protein 4 (NLRC4), absent in melanoma 2 (AIM2), and broadly regulates inflammasome activation. PKR autophosphorylation in a cell-free system with recombinant NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC, also known as PYCARD) and pro-caspase-1 reconstitutes inflammasome activity. These results show a crucial role for PKR in inflammasome activation, and indicate that it should be possible to pharmacologically target this molecule to treat inflammation.     

Reach and grasp by people with tetraplegia using a neurally controlled robotic arm

Paralysis following spinal cord injury, brainstem stroke, amyotrophic lateral sclerosis and other disorders can disconnect the brain from the body, eliminating the ability to perform volitional movements. A neural interface system could restore mobility and independence for people with paralysis by translating neuronal activity directly into control signals for assistive devices. We have previously shown that people with long-standing tetraplegia can use a neural interface system to move and click a computer cursor and to control physical devices. Able-bodied monkeys have used a neural interface system to control a robotic arm, but it is unknown whether people with profound upper extremity paralysis or limb loss could use cortical neuronal ensemble signals to direct useful arm actions. Here we demonstrate the ability of two people with long-standing tetraplegia to use neural interface system-based control of a robotic arm to perform three-dimensional reach and grasp movements. Participants controlled the arm and hand over a broad space without explicit training, using signals decoded from a small, local population of motor cortex (MI) neurons recorded from a 96-channel microelectrode array. One of the study participants, implanted with the sensor 5?years earlier, also used a robotic arm to drink coffee from a bottle. Although robotic reach and grasp actions were not as fast or accurate as those of an able-bodied person, our results demonstrate the feasibility for people with tetraplegia, years after injury to the central nervous system, to recreate useful multidimensional control of complex devices directly from a small sample of neural signals.     

常规公交乘客对车内拥挤的感知阻抗的调查方法与模型

采用SP(stated preference)与RP(revealed preference)相结合的调查方法,在分析得出车内拥挤程度分级阈值的基础上,通过Binary Logit模型分析得出不同车内拥挤程度下乘客出行选择行为效用函数,计算得到乘客出行时间价值,建立车内拥挤程度与时间价值的函数关系,进而将车内拥挤转化为时间,给出车内拥挤的乘客感知阻抗模型.     

Transient pulsed radio emission from a magnetar

Anomalous X-ray pulsars (AXPs) are slowly rotating neutron stars with very bright and highly variable X-ray emission that are believed to be powered by ultra-strong magnetic fields of >10(14) G, according to the 'magnetar' model. The radio pulsations that have been observed from more than 1,700 neutron stars with weaker magnetic fields have never been detected from any of the dozen known magnetars. The X-ray pulsar XTE J1810-197 was revealed (in 2003) as the first AXP with transient emission when its luminosity increased 100-fold from the quiescent level; a coincident radio source of unknown origin was detected one year later. Here we show that XTE J1810-197 emits bright, narrow, highly linearly polarized radio pulses, observed at every rotation, thereby establishing that magnetars can be radio pulsars. There is no evidence of radio emission before the 2003 X-ray outburst (unlike ordinary pulsars, which emit radio pulses all the time), and the flux varies from day to day. The flux at all radio frequencies is approximately equal--and at >20 GHz XTE J1810-197 is currently the brightest neutron star known. These observations link magnetars to ordinary radio pulsars, rule out alternative accretion models for AXPs, and provide a new window into the coronae of magnetars.     

Abdominal obesity and metabolic syndrome

Metabolic syndrome is associated with abdominal obesity, blood lipid disorders, inflammation, insulin resistance or full-blown diabetes, and increased risk of developing cardiovascular disease. Proposed criteria for identifying patients with metabolic syndrome have contributed greatly to preventive medicine, but the value of metabolic syndrome as a scientific concept remains controversial. The presence of metabolic syndrome alone cannot predict global cardiovascular disease risk. But abdominal obesity - the most prevalent manifestation of metabolic syndrome - is a marker of 'dysfunctional adipose tissue', and is of central importance in clinical diagnosis. Better risk assessment algorithms are needed to quantify diabetes and cardiovascular disease risk on a global scale.     

Gamma-ray bursts: huge explosion in the early Universe

Long gamma-ray bursts (GRBs) are bright flashes of high-energy photons that can last for tens of minutes; they are generally associated with galaxies that have a high rate of star formation and probably arise from the collapsing cores of massive stars, which produce highly relativistic jets (collapsar model). Here we describe gamma- and X-ray observations of the most distant GRB ever observed (GRB 050904): its redshift (z) of 6.29 means that this explosion happened 12.8 billion years ago, corresponding to a time when the Universe was just 890 million years old, close to the reionization era. This means that not only did stars form in this short period of time after the Big Bang, but also that enough time had elapsed for them to evolve and collapse into black holes.