Diversity considerations in HIV-1 vaccine selection

Globally, human immunodeficiency virus-type 1 (HIV-1) is extraordinarily variable, and this diversity poses a major obstacle to AIDS vaccine development. Currently, candidate vaccines are derived from isolates, with the hope that they will be sufficiently cross-reactive to protect against circulating viruses. This may be overly optimistic, however, given that HIV-1 envelope proteins can differ in more than 30% of their amino acids. To contend with the diversity, country-specific vaccines are being considered, but evolutionary relationships may be more useful than regional considerations. Consensus or ancestor sequences could be used in vaccine design to minimize the genetic differences between vaccine strains and contemporary isolates, effectively reducing the extent of diversity by half.     

White fat progenitor cells reside in the adipose vasculature

White adipose (fat) tissues regulate metabolism, reproduction, and life span. Adipocytes form throughout life, with the most marked expansion of the lineage occurring during the postnatal period. Adipocytes develop in coordination with the vasculature, but the identity and location of white adipocyte progenitor cells in vivo are unknown. We used genetically marked mice to isolate proliferating and renewing adipogenic progenitors. We found that most adipocytes descend from a pool of these proliferating progenitors that are already committed, either prenatally or early in postnatal life. These progenitors reside in the mural cell compartment of the adipose vasculature, but not in the vasculature of other tissues. Thus, the adipose vasculature appears to function as a progenitor niche and may provide signals for adipocyte development.     

Anterior cingulate conflict monitoring and adjustments in control

Conflict monitoring by the anterior cingulate cortex (ACC) has been posited to signal a need for greater cognitive control, producing neural and behavioral adjustments. However, the very occurrence of behavioral adjustments after conflict has been questioned, along with suggestions that there is no direct evidence of ACC conflict-related activity predicting subsequent neural or behavioral adjustments in control. Using the Stroop color-naming task and controlling for repetition effects, we demonstrate that ACC conflict-related activity predicts both greater prefrontal cortex activity and adjustments in behavior, supporting a role of ACC conflict monitoring in the engagement of cognitive control.     

Endocannabinoid hydrolysis generates brain prostaglandins that promote neuroinflammation

Phospholipase A(2)(PLA(2)) enzymes are considered the primary source of arachidonic acid for cyclooxygenase (COX)-mediated biosynthesis of prostaglandins. Here, we show that a distinct pathway exists in brain, where monoacylglycerol lipase (MAGL) hydrolyzes the endocannabinoid 2-arachidonoylglycerol to generate a major arachidonate precursor pool for neuroinflammatory prostaglandins. MAGL-disrupted animals show neuroprotection in a parkinsonian mouse model. These animals are spared the hemorrhaging caused by COX inhibitors in the gut, where prostaglandins are instead regulated by cytosolic PLA(2). These findings identify MAGL as a distinct metabolic node that couples endocannabinoid to prostaglandin signaling networks in the nervous system and suggest that inhibition of this enzyme may be a new and potentially safer way to suppress the proinflammatory cascades that underlie neurodegenerative disorders.     

Climate data challenges in the 21st century

Climate data are dramatically increasing in volume and complexity, just as the users of these data in the scientific community and the public are rapidly increasing in number. A new paradigm of more open, user-friendly data access is needed to ensure that society can reduce vulnerability to climate variability and change, while at the same time exploiting opportunities that will occur.     

Toward inherently secure and resilient societies

Recent years have seen a number of challenges to social stability and order, ranging from terrorist attacks and natural disasters to epidemics such as AIDS and SARS. Such challenges have generated specific policy responses, such as enhanced security at transportation hubs and planned deployment of a global tsunami detection network. However, the range of challenges and the practical impossibility of adequately addressing each in turn argue for adoption of a more comprehensive systems perspective. This should be based on the principle of enhancing social and economic resiliency as well as meeting security and emergency response needs and, to the extent possible, developing and implementing dual-use technologies that offer societal benefits even if anticipated disasters never occur.