X‑ray crystal structure of rac-[Ru(phen)2dppz]2+ with d(ATGCAT)2 shows enantiomer orientations and water ordering

We report an atomic resolution X-ray crystal structure containing both enantiomers of rac-[Ru(phen)2dppz]2+ with the d-(ATGCAT)2 DNA duplex (phen = phenanthroline; dppz = dipyridophenazine). The first example of any enantiomeric pair crystallized with a DNA duplex shows different orientations of the Λ and Δ binding sites, separated by a clearly defined structured water monolayer. Job plots show that the same species is present in solution. Each enantiomer is bound at a TG/CA step and shows intercalation from the minor groove. One water molecule is directly located on one phenazine N atom in the Δ-enantiomer only.

Observations of the eruption of the Sarychev volcano and simulations using the HadGEM2 climate model

In June 2009 the Sarychev volcano located in the Kuril Islands to the northeast of Japan erupted explosively, injecting ash and an estimated 1.2 ± 0.2 Tg of sulfur dioxide into the upper troposphere and lower stratosphere, making it arguably one of the 10 largest stratospheric injections in the last 50 years. During the period immediately after the eruption, we show that the sulfur dioxide (SO2) cloud was clearly detected by retrievals developed for the Infrared Atmospheric Sounding Interferometer (IASI) satellite instrument and that the resultant stratospheric sulfate aerosol was detected by the Optical Spectrograph and Infrared Imaging System (OSIRIS) limb sounder and CALIPSO lidar. Additional surface‐based instrumentation allows assessment of the impact of the eruption on the stratospheric aerosol optical depth. We use a nudged version of the HadGEM2 climate model to investigate how well this state‐of‐the‐science climate model can replicate the distributions of SO2 and sulfate aerosol. The model simulations and OSIRIS measurements suggest that in the Northern Hemisphere the stratospheric aerosol optical depth was enhanced by around a factor of 3 (0.01 at 550 nm), with resultant impacts upon the radiation budget. The simulations indicate that, in the Northern Hemisphere for July 2009, the magnitude of the mean radiative impact from the volcanic aerosols is more than 60% of the direct radiative forcing of all anthropogenic aerosols put together. While the cooling induced by the eruption will likely not be detectable in the observational record, the combination of modeling and measurements would provide an ideal framework for simulating future larger volcanic eruptions.

Six new loci associated with body mass index highlight a neuronal influence on body weight regulation

Common variants at only two loci, FTO and MC4R, have been reproducibly associated with body mass index (BMI) in humans. To identify additional loci, we conducted meta-analysis of 15 genome-wide association studies for BMI (n > 32,000) and followed up top signals in 14 additional cohorts (n > 59,000). We strongly confirm FTO and MC4R and identify six additional loci (P < 5 x 10(-8)): TMEM18, KCTD15, GNPDA2, SH2B1, MTCH2 and NEGR1 (where a 45-kb deletion polymorphism is a candidate causal variant). Several of the likely causal genes are highly expressed or known to act in the central nervous system (CNS), emphasizing, as in rare monogenic forms of obesity, the role of the CNS in predisposition to obesity.

Evidence of increased net ecosystem productivity associated with a longer vegetated season in a deciduous forest in south-central Indiana, USA

Observations of net ecosystem exchange (NEE) of carbon and its biophysical drivers have been collected at the AmeriFlux site in the Morgan-Monroe State Forest (MMSF) in Indiana, USA since 1998. Thus, this is one of the few deciduous forest sites in the world, where a decadal analysis on net ecosystem productivity (NEP) trends is possible. Despite the large interannual variability in NEP, the observations show a significant increase in forest productivity over the past 10 years (by an annual increment of about 10 g C m−2 yr−1). There is evidence that this trend can be explained by longer vegetative seasons, caused by extension of the vegetative activity in the fall. Both phenological and flux observations indicate that the vegetative season extended later in the fall with an increase in length of about 3 days yr−1 for the past 10 years. However, these changes are responsible for only 50% of the total annual gain in forest productivity in the past decade. A negative trend in air and soil temperature during the winter months may explain an equivalent increase in NEP through a decrease in ecosystem respiration.

Role for substance p-based nociceptive signaling in progenitor cell activation and angiogenesis during ischemia in mice and in human subjects

Our data highlight the role of SP in reparative neovascularization. Nociceptive signaling may represent a novel target of regenerative medicine.

Mechanisms of motivation-cognition interaction: challenges and opportunities

There has been a recent rejuvenation of interest in studies of motivation-cognition interactions arising from many different areas of psychology and neuroscience. The current issue of Cognitive, Affective, and Behavioral Neuroscience provides a sampling of some of the latest research from a number of these different areas. In this introductory paper, we provide an overview of the current state of the field, in terms of key research developments and candidate neural mechanisms receiving focused investigation as potential sources of motivation-cognition interaction. However, our primary goal is conceptual: to highlight the distinct perspectives taken by different research areas in terms of how motivation is defined, the relevant dimensions and dissociations that are emphasized, and the theoretical questions being targeted. Together, these distinctions present both challenges and opportunities for efforts aiming towards a more unified and cross-disciplinary approach. We identify a set of pressing research questions calling out for this sort of cross-disciplinary approach, with the explicit goal of encouraging integrative and collaborative investigations directed towards them.

Schwann cells can be reprogrammed to multipotency by culture

Adult neural crest related-stem cells persist in adulthood, making them an ideal and easily accessible source of multipotent cells for potential clinical use. Recently, we reported the presence of neural crest-related stem cells within adult palatal ridges, thus raising the question of their localization in their endogenous niche. Using immunocytochemistry, reverse transcription-polymerase chain reaction, and correlative fluorescence and transmission electron microscopy, we identified myelinating Schwann cells within palatal ridges as a putative neural crest stem cell source. Palatal Schwann cells expressed nestin, p75(NTR), and S100. Correlative fluorescence and transmission electron microscopy revealed the exclusive nestin expression within myelinating Schwann cells. Palatal neural crest stem cells and nestin-positive Schwann cells isolated from adult sciatic nerves were able to grow under serum-free conditions as neurospheres in presence of FGF-2 and EGF. Spheres of palatal and sciatic origin showed overlapping expression pattern of neural crest stem cell and Schwann cell markers. Expression of the pluripotency factors Sox2, Klf4, c-Myc, Oct4, the NF-κB subunits p65, p50, and the NF-κB-inhibitor IκB-β were up-regulated in conventionally cultivated sciatic nerve Schwann cells and in neurosphere cultures. Finally, neurospheres of palatal and sciatic origin were able to differentiate into ectodermal, mesodermal, and endodermal cell types emphasizing their multipotency. Taken together, we show that nestin-positive myelinating Schwann cells can be reprogrammed into multipotent adult neural crest stem cells under appropriate culture conditions.

Methods for the modulation and analysis of NF-κB-dependent adult neurogenesis

The hippocampus plays a pivotal role in the formation and consolidation of episodic memories, and in spatial orientation. Historically, the adult hippocampus has been viewed as a very static anatomical region of the mammalian brain. However, recent findings have demonstrated that the dentate gyrus of the hippocampus is an area of tremendous plasticity in adults, involving not only modifications of existing neuronal circuits, but also adult neurogenesis. This plasticity is regulated by complex transcriptional networks, in which the transcription factor NF-κB plays a prominent role. To study and manipulate adult neurogenesis, a transgenic mouse model for forebrain-specific neuronal inhibition of NF-κB activity can be used. In this study, methods are described for the analysis of NF-κB-dependent neurogenesis, including its structural aspects, neuronal apoptosis and progenitor proliferation, and cognitive significance, which was specifically assessed via a dentate gyrus (DG)-dependent behavioral test, the spatial pattern separation-Barnes maze (SPS-BM). The SPS-BM protocol could be simply adapted for use with other transgenic animal models designed to assess the influence of particular genes on adult hippocampal neurogenesis. Furthermore, SPS-BM could be used in other experimental settings aimed at investigating and manipulating DG-dependent learning, for example, using pharmacological agents.

Using Africa’s protected area network to estimate the global population of a threatened and declining species: a case study of the critically endangered White-headed Vulture Trigonoceps occipitalis

The White-headed Vulture Trigonoceps occipitalis (WhV) is uncommon and largely restricted to protected areas across its range in sub-Saharan Africa. We used the World Database on Protected Areas to identify protected areas (PAs) likely to contain White-headed Vultures. Vulture occurrence on road transects in Southern, East, and West Africa was adjusted to nests per km2 using data from areas with known numbers of nests and corresponding road transect data. Nest density was used to calculate the number of WhV nests within identified PAs and from there extrapolated to estimate the global population. Across a fragmented range, 400 PAs are estimated to contain 1893 WhV nests. Eastern Africa is estimated to contain 721 nests, Central Africa 548 nests, Southern Africa 468 nests, and West Africa 156 nests. Including immature and nonbreeding birds, and accounting for data deficient PAs, the estimated global population is 5475 - 5493 birds. The identified distribution highlights are alarming: over 78% (n = 313) of identified PAs contain fewer than five nests. A further 17% (n = 68) of PAs contain 5 - 20 nests and 4% (n = 14) of identified PAs are estimated to contain >20 nests. Just 1% (n = 5) of PAs are estimated to contain >40 nests; none is located in West Africa. Whilst ranging behavior of WhVs is currently unknown, 35% of PAs large enough to hold >20 nests are isolated by more than 100 km from other PAs. Spatially discrete and unpredictable mortality events such as poisoning pose major threats to small localized vulture populations and will accelerate ongoing local extinctions. Apart from reducing the threat of poisoning events, conservation actions promoting linkages between protected areas should be pursued. Identifying potential areas for assisted re-establishment via translocation offers the potential to expand the range of this species and alleviate risk.

Discovering biomarkers for antidepressant response: protocol from the Canadian biomarker integration network in depression (CAN-BIND) and clinical characteristics of the first patient cohort

Background Major Depressive Disorder (MDD) is among the most prevalent and disabling medical conditions worldwide. Identification of clinical and biological markers (“biomarkers”) of treatment response could personalize clinical decisions and lead to better outcomes. This paper describes the aims, design, and methods of a discovery study of biomarkers in antidepressant treatment response, conducted by the Canadian Biomarker Integration Network in Depression (CAN-BIND). The CAN-BIND research program investigates and identifies biomarkers that help to predict outcomes in patients with MDD treated with antidepressant medication. The primary objective of this initial study (known as CAN-BIND-1) is to identify individual and integrated neuroimaging, electrophysiological, molecular, and clinical predictors of response to sequential antidepressant monotherapy and adjunctive therapy in MDD. Methods CAN-BIND-1 is a multisite initiative involving 6 academic health centres working collaboratively with other universities and research centres. In the 16-week protocol, patients with MDD are treated with a first-line antidepressant (escitalopram 10–20 mg/d) that, if clinically warranted after eight weeks, is augmented with an evidence-based, add-on medication (aripiprazole 2–10 mg/d). Comprehensive datasets are obtained using clinical rating scales; behavioural, dimensional, and functioning/quality of life measures; neurocognitive testing; genomic, genetic, and proteomic profiling from blood samples; combined structural and functional magnetic resonance imaging; and electroencephalography. De-identified data from all sites are aggregated within a secure neuroinformatics platform for data integration, management, storage, and analyses. Statistical analyses will include multivariate and machine-learning techniques to identify predictors, moderators, and mediators of treatment response. Discussion From June 2013 to February 2015, a cohort of 134 participants (85 outpatients with MDD and 49 healthy participants) has been evaluated at baseline. The clinical characteristics of this cohort are similar to other studies of MDD. Recruitment at all sites is ongoing to a target sample of 290 participants. CAN-BIND will identify biomarkers of treatment response in MDD through extensive clinical, molecular, and imaging assessments, in order to improve treatment practice and clinical outcomes. It will also create an innovative, robust platform and database for future research.