Neuroblast lineage-specific origin of the neurons of the Drosophila larval olfactory system

The complete neuronal repertoire of the central brain of Drosophila originates from only approximately 100 pairs of neural stem cells, or neuroblasts. Each neuroblast produces a highly stereotyped lineage of neurons which innervate specific compartments of the brain. Neuroblasts undergo two rounds of mitotic activity: embryonic divisions produce lineages of primary neurons that build the larval nervous system; after a brief quiescence, the neuroblasts go through a second round of divisions in larval stage to produce secondary neurons which are integrated into the adult nervous system. Here we investigate the lineages that are associated with the larval antennal lobe, one of the most widely studied neuronal systems in fly. We find that the same five neuroblasts responsible for the adult antennal lobe also produce the antennal lobe of the larval brain. However, there are notable differences in the composition of larval (primary) lineages and their adult (secondary) counterparts. Significantly, in the adult, two lineages (lNB/BAlc and adNB/BAmv3) produce uniglomerular projection neurons connecting the antennal lobe with the mushroom body and lateral horn; another lineage, vNB/BAla1, generates multiglomerular neurons reaching the lateral horn directly. lNB/BAlc, as well as a fourth lineage, vlNB/BAla2, generate a diversity of local interneurons. We describe a fifth, previously unknown lineage, BAlp4, which connects the posterior part of the antennal lobe and the neighboring tritocerebrum (gustatory center) with a higher brain center located adjacent to the mushroom body. In the larva, only one of these lineages, adNB/BAmv3, generates all uniglomerular projection neurons. Also as in the adult, lNB/BAlc and vlNB/BAla2 produce local interneurons which, in terms of diversity in architecture and transmitter expression, resemble their adult counterparts. In addition, lineages lNB/BAlc and vNB/BAla1, as well as the newly described BAlp4, form numerous types of projection neurons which along the same major axon pathways (antennal tracts) used by the antennal projection neurons, but which form connections that include regions outside the “classical” olfactory circuit triad antennal lobe-mushroom body-lateral horn. Our work will benefit functional studies of the larval olfactory circuit, and shed light on the relationship between larval and adult neurons.     

Patterns of variability are consistent across signal types in the treefrog Dendropsophus ebraccatus

Animal signal characteristics vary at multiple levels, and this variation can be related to the selective forces acting on signal structure. However, the effectiveness of selection acting on any one signal type may depend on selective forces acting on the same characteristics in other signal types, particularly if the signals share a common physical production mechanism. In anurans, signal variability has been related to the potential for various forms of selection by female choice on the characteristics of male advertisement calls. The significance of variability in the characteristics of another vocalization type, the aggressive call, is less well understood. In the present stiudy, within‐ and between‐male variability was measured in several characteristics of both advertisement and aggressive calls in the treefrog Dendropsophus ebraccatus. Many characteristics of both call types were repeatable within males. Fine‐temporal and spectral characteristics generally had low variation within males, whereas gross‐temporal characteristics were more variable. Unexpectedly, there were strong correlations between both measures of variability and mean values of the call characteristics of advertisement and aggressive calls. Thus, despite potentially conflicting selection pressures acting on advertisement and aggressive calls, the characteristics of individuals' calls were consistent across these two signal types. The potential forces responsible for consistency across call types are discussed, including morphological constraints and behavioural syndromes that act across different signalling contexts. In general, it is argued that measurements of variability made across multiple signal types, as in the present study, can provide important insights into the evolution of signal structure in organisms with complex signal repertoires. © 2013 The Linnean Society of London, Biological Journal of the Linnean Society, 2013, 109 , 131–145.     

Meal replacements and fibre supplement as a strategy for weight loss. Proprietary PGX® meal replacement and PGX® fibre supplement in addition to a calorie-restricted diet to achieve weight loss in a clinical setting

Meal replacements and viscous soluble fibre represent safe and sustainable aids for weight loss. Our purpose was to determine if PGX® meal replacements and PGX^® fibre complex in combination with a calorie-restricted diet would aid in weight loss in a clinical setting. Fifty-two overweight and obese participants (49 women, 3 men; average age 47.1 years) with a mean body mass index (BMI) of 33.8 ± 6.4 kg/m² consumed 57 g of proprietary PGX® meal replacement product at breakfast and another 57 g at lunch for 12 weeks. In addition to the meal replacements, they were also asked to consume 5 g/day of PGX® fibre in the form of granules, powder or capsules together with 250 mlwater. A registered dietician recommended low-fat, low-glycaemic-index foods for snacks and the dinner menus such that each volunteer was consuming a total of 1200 kcal/day. All participants (n = 52) lost a significant amount of weight from baseline (?4.69 ± 3.73 kg), which was further reflected in the reductions in their waist (?7.11 ± 6.35 cm) and hip circumference (?5.59 ± 3.58 cm) over the 12-week study (p < 0.0001). BMI scores (n = 51) were reduced by 1.6 ± 1.4 kg/m². The use of PGX® meal replacements and PGX^® fibre along with a controlled dietary caloric intake is of benefit for short-term weight loss.     

The relation of the X-ray B-factor to protein dynamics: insights from recent dynamic solid-state NMR data

In addressing the potential use of B-factors derived from X-ray scattering data of proteins for the understanding the (functional) dynamics of proteins, we present a comparison of B-factors of five different proteins (SH3 domain, Crh, GB1, ubiquitin and thioredoxin) with data from recent solid-state nuclear magnetic resonance experiments reflecting true (rotational) dynamics on well-defined timescales. Apart from trivial correlations involving mobile loop regions and chain termini, we find no significant correlation of B-factors with the dynamic data on any of the investigated timescales, concluding that there is no unique and general correlation of B-factors with the internal reorientational dynamics of proteins.     

Multipotent neural stem cells generate glial cells of the central complex through transit amplifying intermediate progenitors in Drosophila brain development

The neural stem cells that give rise to the neural lineages of the brain can generate their progeny directly or through transit amplifying intermediate neural progenitor cells (INPs). The INP-producing neural stem cells in Drosophila are called type II neuroblasts, and their neural progeny innervate the central complex, a prominent integrative brain center. Here we use genetic lineage tracing and clonal analysis to show that the INPs of these type II neuroblast lineages give rise to glial cells as well as neurons during postembryonic brain development. Our data indicate that two main types of INP lineages are generated, namely mixed neuronal/glial lineages and neuronal lineages. Genetic loss-of-function and gain-of-function experiments show that the gcm gene is necessary and sufficient for gliogenesis in these lineages. The INP-derived glial cells, like the INP-derived neuronal cells, make major contributions to the central complex. In postembryonic development, these INP-derived glial cells surround the entire developing central complex neuropile, and once the major compartments of the central complex are formed, they also delimit each of these compartments. During this process, the number of these glial cells in the central complex is increased markedly through local proliferation based on glial cell mitosis. Taken together, these findings uncover a novel and complex form of neurogliogenesis in Drosophila involving transit amplifying intermediate progenitors. Moreover, they indicate that type II neuroblasts are remarkably multipotent neural stem cells that can generate both the neuronal and the glial progeny that make major contributions to one and the same complex brain structure.     

Chytrid epidemics may increase genetic diversity of a diatom spring-bloom

Contrary to expectation, populations of clonal organisms are often genetically highly diverse. In phytoplankton, this diversity is maintained throughout periods of high population growth (that is, blooms), even though competitive exclusion among genotypes should hypothetically lead to the dominance of a few superior genotypes. Genotype-specific parasitism may be one mechanism that helps maintain such high-genotypic diversity of clonal organisms. Here, we present a comparison of population genetic similarity by estimating the beta-dispersion among genotypes of early and peak bloom populations of the diatom Asterionella formosa for three spring-blooms under high or low parasite pressure. The Asterionella population showed greater beta-dispersion at peak bloom than early bloom in the 2 years with high parasite pressure, whereas the within group dispersion did not change under low parasite pressure. Our findings support that high prevalence parasitism can promote genetic diversification of natural populations of clonal hosts.     

A New Class of Small Molecule Inhibitor of BMP Signaling

Growth factor signaling pathways are tightly regulated by phosphorylation and include many important kinase targets of interest for drug discovery. Small molecule inhibitors of the bone morphogenetic protein (BMP) receptor kinase ALK2 (ACVR1) are needed urgently to treat the progressively debilitating musculoskeletal disease fibrodysplasia ossificans progressiva (FOP). Dorsomorphin analogues, first identified in zebrafish, remain the only BMP inhibitor chemotype reported to date. By screening an assay panel of 250 recombinant human kinases we identified a highly selective 2-aminopyridine-based inhibitor {"type":"entrez-nucleotide","attrs":{"text":"K02288","term_id":"191391"}}K02288 with in vitro activity against ALK2 at low nanomolar concentrations similar to the current lead compound LDN-193189. {"type":"entrez-nucleotide","attrs":{"text":"K02288","term_id":"191391"}}K02288 specifically inhibited the BMP-induced Smad pathway without affecting TGF-β signaling and induced dorsalization of zebrafish embryos. Comparison of the crystal structures of ALK2 with {"type":"entrez-nucleotide","attrs":{"text":"K02288","term_id":"191391"}}K02288 and LDN-193189 revealed additional contacts in the {"type":"entrez-nucleotide","attrs":{"text":"K02288","term_id":"191391"}}K02288 complex affording improved shape complementarity and identified the exposed phenol group for further optimization of pharmacokinetics. The discovery of a new chemical series provides an independent pharmacological tool to investigate BMP signaling and offers multiple opportunities for pre-clinical development.     

Reorienting in Virtual 3D Environments: Do Adult Humans Use Principal Axes,Medial Axes or Local Geometry?

Studies have shown that animals, including humans, use the geometric properties of environments to orient. It has been proposed that orientation is accomplished primarily by encoding the principal axes (i.e., global geometry) of an environment. However, recent research has shown that animals use local information such as wall length and corner angles as well as local shape parameters (i.e., medial axes) to orient. The goal of the current study was to determine whether adult humans reorient according to global geometry based on principal axes or whether reliance is on local geometry such as wall length and sense information or medial axes. Using a virtual environment task, participants were trained to select a response box located at one of two geometrically identical corners within a featureless rectangular-shaped environment. Participants were subsequently tested in a transformed L-shaped environment that allowed for a dissociation of strategies based on principal axes, medial axes and local geometry. Results showed that participants relied primarily on a medial axes strategy to reorient in the L-shaped test environment. Importantly, the search behaviour of participants could not be explained by a principal axes-based strategy.