Functional constraints of the Cu,Zn superoxide dismutase in species of the Drosophila melanogaster subgroup and phylogenetic analysis

The phylogenetic relationships among the Drosophila melanogaster subgroup species were analyzed using approximately 1550-nucleotide-long sequences of the Cu,Zn SOD gene. Phylogenetic analysis was performed using separately the whole region and the intron sequences of the gene. The resulting phylogenetic trees reveal virtually the same topology, separating the species into distinct clusters. The inferred topology generally agrees with previously proposed classifications based on morphological and molecular data. The amino acid sequences of the Cu,Zn SOD of the D. melanogaster subgroup species reveal a high-conservation pattern. Only 3.9% of the total amino acid sites are variable, and none affects the major structural elements. Comparison of the Drosophila Cu,Zn SOD amino acid sequences with the Cu,Zn SOD of Bos taurus and Xenopus laevis (whose three-dimensional structure has been elucidated) reveals conservation of all the protein's functionally important amino acids and no substitutions that dramatically change the charge or the polarity of the amino acids.     

From plots to islands: species diversity at different scales

Aim To investigate how plant diversity of whole islands (‘gamma’) is related to alpha and beta diversity patterns among sampling plots within each island, thus exploring aspects of diversity patterns across scales. Location Nineteen islands of the Aegean Sea, Greece. Methods Plant species were recorded at both the whole‐island scale and in small 100 m² plots on each island. Mean plot species richness was considered as a measure of alpha diversity, and six indices of the ‘variation’‐type beta diversity were also applied. In addition, we partitioned beta diversity into a ‘nestedness’ and a ‘replacement’ component, using the total species richness recorded in all plots of each island as a measure of ‘gamma’ diversity. We also applied 10 species–area models to predict the total observed richness of each island from accumulated plot species richness. Results Mean alpha diversity was not significantly correlated with the overall island species richness or island area. The range of plot species richness for each island was significantly correlated with both overall species richness and area. Alpha diversity was not correlated with most indices of beta diversity. The majority of beta diversity indices were correlated with whole‐island species richness, and this was also true for the ‘replacement’ component of beta diversity. The rational function model provided the best prediction of observed island species richness, with Monod’s and the exponential models following closely. Inaccuracy of predictions was positively correlated with the number of plots and with most indices of beta diversity. Main conclusions Diversity at the broader scale (whole islands) is shaped mainly by variation among small local samples (beta diversity), while local alpha diversity is not a good predictor of species diversity at broader scales. In this system, all results support the crucial role of habitat diversity in determining the species–area relationship.     

Differential encoding in prefrontal cortex projection neuron classes across cognitive tasks

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The beaded intermediate filaments and their potential functions in eye lens

The elongated fiber cells of the eye lens contain a unique cytoskeletal system, the beaded chain filaments (BFs). The BFs had been morphologically identified more than two decades ago, but the precise identity of their subunit molecules remained unknown. Recently, use of recombinant DNA approaches, refined morphological and immunochemical studies and experiments with mutant mice have allowed the molecular dissection of these structures and provided clues about their potential functins. The BFs represent a highly specialized network of intermediate filaments (IFs) juxtaposed to the plasma membrane. They are obligate heteropolymers composed of two lens-specific polypeptides, filensin and phakinin. In this review we discuss the properties, molecular interactions and in situ arrangement of these two proteins, and comment on their potential roles during lens development.     

A review of phylogeographic analyses of animal taxa from the Aegean and surrounding regions

We provide a review and synthesis of key findings in phylogeographic research on terrestrial animals in the Aegean archipelago (Greece) and surrounding regions (Greek mainland, southern Balkans and Asia Minor). A critical review of more than 100 phylogeographic articles on 76 animal genera (30 invertebrates and 46 vertebrates) that have been published so far for the region leads to the recognition of three types of distribution patterns: old ‘colonizers’ diversified in the Aegean before the formation of the mid‐Aegean Trench (MAT – i.e. before 9 Mya), post‐MAT colonizers that arrived to the Aegean in late Miocene and Pliocene and new colonizers that inhabited the region in the Pleistocene or even the Holocene. Several problems, mainly regarding the use of calibration points and/or molecular clock rates for clade chronology, have been identified in many analyses. Despite the large amount of phylogeographic work concerning the Aegean and surrounding regions, many groups remain unstudied (especially invertebrates, micro‐organisms, fungi and plants), and many issues still remain unresolved. The relative roles of extinction, speciation, dispersal and vicariance, as well as the effects of adaptive and non‐adaptive components of diversification, need further analyses with modern tools that can provide deeper insights. A more detailed reconstruction of the palaeogeography of the region is also of prime importance. The critical views presented herein may prove useful also for the evaluation of similar work in other regions.     

Solution‐Processed Hydrogen Molybdenum Bronzes as Highly Conductive Anode Interlayers in Efficient Organic Photovoltaics

Highly efficient and stable organic photovoltaic (OPV) cells are demonstrated by incorporating solution‐processed hydrogen molybdenum bronzes as anode interlayers. The bronzes are synthesized using a sol‐gel method with the critical step being the partial oxide reduction/hydrogenation using an alcohol‐based solvent. Their composition, stoichiometry, and electronic properties strongly correlate with the annealing process to which the films are subjected after spin coating. Hydrogen molybdenum bronzes with moderate degree of reduction are found to be highly advantageous when used as anode interlayers in OPVs, as they maintain a high work function similar to the fully stoichiometric metal oxide, whereas they exhibit a high density of occupied gap states, which are beneficial for charge transport. Enhanced short‐circuit current, open‐circuit voltage and, fill factor, relative to reference devices incorporating either PEDOT‐PSS or a solution processed stoichiometric molybdenum oxide, are obtained for a variety of bulk heterojunction mixtures based on different polymeric donors and fullerene acceptors. In particular, high power conversion efficiencies are obtained in devices that employed the s‐H_xMoO_2.75 as the hole extraction layer.     

A phase IIA randomized clinical trial of a multiclade HIV-1 DNA prime followed by a multiclade rAd5 HIV-1 vaccine boost in healthy adults (HVTN204)

Background

The safety and immunogenicity of a vaccine regimen consisting of a 6-plasmid HIV-1 DNA prime (envA, envB, envC, gagB, polB, nefB) boosted by a recombinant adenovirus serotype-5 (rAd5) HIV-1 with matching inserts was evaluated in HIV-seronegative participants from South Africa, United States, Latin America and the Caribbean.

Methods

480 participants were evenly randomized to receive either: DNA (4 mg IM by Biojector) at 0, 1 and 2 months, followed by rAd5 (10¹⁰ PU IM by needle/syringe) at 6 months; or placebo. Participants were monitored for reactogenicity and adverse events throughout the 12-month study. Peak and duration of HIV-specific humoral and cellular immune responses were evaluated after the prime and boost.

Results

The vaccine was well tolerated and safe. T-cell responses, detected by interferon-γ (IFN-γ) ELISpot to global potential T-cell epitopes (PTEs) were observed in 70.8% (136/192) of vaccine recipients overall, most frequently to Gag (54.7%) and to Env (54.2%). In U.S. vaccine recipients T-cell responses were less frequent in Ad5 sero-positive versus sero-negative vaccine recipients (62.5% versus 85.7% respectively, p = 0.035). The frequency of HIV-specific CD4+ and CD8+ T-cell responses detected by intracellular cytokine staining were similar (41.8% and 47.2% respectively) and most secreted ≥2 cytokines. The vaccine induced a high frequency (83.7%–94.6%) of binding antibody responses to consensus Group M, and Clades A, B and C gp140 Env oligomers. Antibody responses to Gag were elicited in 46% of vaccine recipients.

Conclusion

The vaccine regimen was well-tolerated and induced polyfunctional CD4+ and CD8+ T-cells and multi-clade anti-Env binding antibodies.

Trial Registration:

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00125970","term_id":"NCT00125970"}}NCT00125970     

Selective genomic copy number imbalances and probability of recurrence in early-stage breast cancer

A number of studies of copy number imbalances (CNIs) in breast tumors support associations between individual CNIs and patient outcomes. However, no pattern or signature of CNIs has emerged for clinical use. We determined copy number (CN) gains and losses using high-density molecular inversion probe (MIP) arrays for 971 stage I/II breast tumors and applied a boosting strategy to fit hazards models for CN and recurrence, treating chromosomal segments in a dose-specific fashion (-1 [loss], 0 [no change] and +1 [gain]). The concordance index (C-Index) was used to compare prognostic accuracy between a training (n = 728) and test (n = 243) set and across models. Twelve novel prognostic CNIs were identified: losses at 1p12, 12q13.13, 13q12.3, 22q11, and Xp21, and gains at 2p11.1, 3q13.12, 10p11.21, 10q23.1, 11p15, 14q13.2-q13.3, and 17q21.33. In addition, seven CNIs previously implicated as prognostic markers were selected: losses at 8p22 and 16p11.2 and gains at 10p13, 11q13.5, 12p13, 20q13, and Xq28. For all breast cancers combined, the final full model including 19 CNIs, clinical covariates, and tumor marker-approximated subtypes (estrogen receptor [ER], progesterone receptor, ERBB2 amplification, and Ki67) significantly outperformed a model containing only clinical covariates and tumor subtypes (C-Index _{full model}, train[test]  =  0.72[0.71] ± 0.02 vs. C-Index _{clinical + subtype model}, train[test]  =  0.62[0.62] ± 0.02; p<10⁻⁶). In addition, the full model containing 19 CNIs significantly improved prognostication separately for ER–, HER2+, luminal B, and triple negative tumors over clinical variables alone. In summary, we show that a set of 19 CNIs discriminates risk of recurrence among early-stage breast tumors, independent of ER status. Further, our data suggest the presence of specific CNIs that promote and, in some cases, limit tumor spread.     

Elevational Gradient of Vascular Plant Species Richness and Endemism in Crete – The Effect of Post-Isolation Mountain Uplift on a Continental Island System

Understanding diversity patterns along environmental gradients and their underlying mechanisms is a major topic in current biodiversity research. In this study, we investigate for the first time elevational patterns of vascular plant species richness and endemism on a long-isolated continental island (Crete) that has experienced extensive post-isolation mountain uplift. We used all available data on distribution and elevational ranges of the Cretan plants to interpolate their presence between minimum and maximum elevations in 100-m elevational intervals, along the entire elevational gradient of Crete (0–2400 m). We evaluate the influence of elevation, area, mid-domain effect, elevational Rapoport effect and the post-isolation mountain uplift on plant species richness and endemism elevational patterns. Furthermore, we test the influence of the island condition and the post-isolation mountain uplift to the elevational range sizes of the Cretan plants, using the Peloponnese as a continental control area. Total species richness monotonically decreases with increasing elevation, while endemic species richness has a unimodal response to elevation showing a peak at mid-elevation intervals. Area alone explains a significant amount of variation in species richness along the elevational gradient. Mid-domain effect is not the underlying mechanism of the elevational gradient of plant species richness in Crete, and Rapoport''s rule only partly explains the observed patterns. Our results are largely congruent with the post-isolation uplift of the Cretan mountains and their colonization mainly by the available lowland vascular plant species, as high-elevation specialists are almost lacking from the Cretan flora. The increase in the proportion of Cretan endemics with increasing elevation can only be regarded as a result of diversification processes towards Cretan mountains (especially mid-elevation areas), supported by elevation-driven ecological isolation. Cretan plants have experienced elevational range expansion compared to the continental control area, as a result of ecological release triggered by increased species impoverishment with increasing elevation.     

Modeling spinal muscular atrophy in Drosophila links Smn to FGF signaling

Spinal muscular atrophy (SMA), a devastating neurodegenerative disorder characterized by motor neuron loss and muscle atrophy, has been linked to mutations in the Survival Motor Neuron (SMN) gene. Based on an SMA model we developed in Drosophila, which displays features that are analogous to the human pathology and vertebrate SMA models, we functionally linked the fibroblast growth factor (FGF) signaling pathway to the Drosophila homologue of SMN, Smn. Here, we characterize this relationship and demonstrate that Smn activity regulates the expression of FGF signaling components and thus FGF signaling. Furthermore, we show that alterations in FGF signaling activity are able to modify the neuromuscular junction defects caused by loss of Smn function and that muscle-specific activation of FGF is sufficient to rescue Smn-associated abnormalities.