The Extreme Male Brain Theory of Autism and the Potential Adverse Effects for Boys and Girls with Autism

Autism, typically described as a spectrum neurodevelopmental disorder characterized by impairments in verbal ability and social reciprocity as well as obsessive or repetitious behaviours, is currently thought to markedly affect more males than females. Not surprisingly, this encourages a gendered understanding of the Autism Spectrum. Simon Baron-Cohen, a prominent authority in the field of autism research, characterizes the male brain type as biased toward systemizing. In contrast, the female brain type is understood to be biased toward empathizing. Since persons with autism are characterized as hyper-systemizers and hypo-empathizers, Baron-Cohen suggests that, whether they are male or female, most possess an “extreme male brain profile.” We argue that Baron-Cohen is misled by an unpersuasive gendering of certain capacities or aptitudes in the human population. Moreover, we suggest that this may inadvertently favour boys in diagnosing children with Autism Spectrum Disorders. If this is correct, it could also have rather serious consequences for treatment and services for girls (and women) on the Autism Spectrum.     

Molecular characterization of a novel UT-A urea transporter isoform (UT-A5) in testis

Urea movement across plasmamembranes is modulated by specialized transporter proteins that areproducts of two genes, termed UT-A and UT-B. These proteins play keyroles in the urinary concentrating mechanism and fluid homeostasis. Wehave isolated and characterized a 1.4-kb cDNA from testes encoding anew isoform (UT-A5) belonging to the UT-A transporter family. Forcomparison, we also isolated a 2.0-kb cDNA from mouse kidneyinner medulla encoding the mouse UT-A3 homologue. The UT-A5 cDNAhas a putative open reading frame encoding a 323-amino acidprotein, making UT-A5 the smallest UT-A family member in terms ofmolecular size. Its putative topology is of particular interest,because it calls into question earlier models of UT-A transporterstructure. Expression of UT-A5 cRNA in Xenopus oocytesmediates phloretin-inhibitable urea uptake and does not translocatewater. The distribution of UT-A5 mRNA is restricted to the peritubularmyoid cells forming the outermost layer of the seminiferous tubuleswithin the testes and is not detected in kidney. UT-A5 mRNA levels arecoordinated with the stage of testes development and increase 15 dayspostpartum, commensurate with the start of seminiferous tubule fluid movement.

     

Dispersal and natural enemies interact to drive spatial synchrony and decrease stability in patchy populations

Spatial synchrony is widespread in natural populations but the mechanisms that underpin it are not yet fully understood. Two key biotic drivers of spatial synchrony have been identified: dispersal and trophic interactions (e.g. natural enemies). We used spatially structured, patchy bacterial populations to show that although increased dispersal always enhanced spatial synchrony of fluctuations in bacterial abundance, this effect was far stronger in the presence of a bacteriophage parasite. Bacteriophages drove strong within patch fluctuations in bacterial abundance that became phase locked through dispersal. Furthermore, the way in which stability, measured as constancy, responded to increasing dispersal was qualitatively different depending on whether parasites were present or not. Patch-level constancy decreased with dispersal in the presence of parasites, whereas dispersal increased patch-level constancy in the absence of parasites. Population-level constancy also decreased with dispersal in the presence of parasites, but was unaffected by dispersal in the absence of parasites. These contrasting patterns were likely due to the different role played by dispersal in the presence and absence of parasites, synchronizing dynamics in the former case and averaging stochastic fluctuations in the latter. Taken together, our findings suggest that dispersal and natural enemies can interact to drive spatially synchronous population fluctuations that decrease stability at both the patch and population level.     

Lake Tanganyika—A 'Melting Pot' of Ancient and Young Cichlid Lineages (Teleostei: Cichlidae)?

A long history of research focused on the East Africa cichlid radiations (EAR) revealed discrepancies between mtDNA and nuclear phylogenies, suggesting that interspecific hybridisation may have been significant during the radiation of these fishes. The approximately 250 cichlid species of Lake Tanganyika have their roots in a monophyletic African cichlid assemblage, but controversies remain about the precise phylogenetic origin and placement of different lineages and consequently about L. Tanganyika colonization scenarios. 3312 AFLP loci and the mitochondrial ND2 gene were genotyped for 91 species representing almost all major lacustrine and riverine haplotilapiine east African cichlid lineages with a focus on L. Tanganyika endemics. Explicitly testing for the possibility of ancient hybridisation events, a comprehensive phylogenetic network hypothesis is proposed for the origin and diversification of L. Tanganyika cichlids. Inference of discordant phylogenetic signal strongly suggests that the genomes of two endemic L. Tanganyika tribes, Eretmodini and Tropheini, are composed of an ancient mixture of riverine and lacustrine lineages. For the first time a strong monophyly signal of all non-haplochromine mouthbrooding species endemic to L. Tanganyika (“ancient mouthbrooders”) was detected. Further, in the genomes of early diverging L. Tanganyika endemics Trematocarini, Bathybatini, Hemibatini and Boulengerochromis genetic components of other lineages belonging to the East African Radiation appear to be present. In combination with recent palaeo-geological results showing that tectonic activity in the L. Tanganyika region resulted in highly dynamic and heterogeneous landscape evolution over the Neogene and Pleistocene, the novel phylogenetic data render a single lacustrine basin as the geographical cradle of the endemic L. Tanganyika cichlid lineages unlikely. Instead a scenario of a pre-rift origin of several independent L. Tanganyika precursor lineages which diversified in ancient rivers and precursor lakes and then amalgamated in the extant L. Tanganyika basin is put forward as an alternative: the ''melting pot Tanganyika'' hypothesis.     

What Mutagenesis Can and Cannot Reveal About Allostery

Allosteric regulation of protein function is recognized to be widespread throughout biology; however, knowledge of allosteric mechanisms, the molecular changes within a protein that couple one binding site to another, is limited. Although mutagenesis is often used to probe allosteric mechanisms, we consider herein what the outcome of a mutagenesis study truly reveals about an allosteric mechanism. Arguably, the best way to evaluate the effects of a mutation on allostery is to monitor the allosteric coupling constant (Q_ax), a ratio of the substrate binding constants in the absence versus presence of an allosteric effector. A range of substitutions at a given residue position in a protein can reveal when a particular substitution causes gain-of-function, which addresses a key challenge in interpreting mutation-dependent changes in the magnitude of Q_ax. Thus, whole-protein mutagenesis studies offer an acceptable means of identifying residues that contribute to an allosteric mechanism. With this focus on monitoring Q_ax, and keeping in mind the equilibrium nature of allostery, we consider alternative possibilities for what an allosteric mechanism might be. We conclude that different possible mechanisms (rotation-of-solid-domains, movement of secondary structure, side-chain repacking, changes in dynamics, etc.) will result in different findings in whole-protein mutagenesis studies.     

Intradermal delivery of IL-12 naked DNA induces systemic NK cell activation and Th1 response in vivo that is independent of endogenous IL-12 production.

In this study four murine IL-12 naked DNA expression plasmids (pIL-12), containing both the p35 and p40 subunits, were shown to induce systemic biological effects in vivo after intradermal injection. Three of the four IL-12 expression vectors augmented NK activity and induced expression of the IFN-gamma and IFN-gamma-inducible Mig genes. Both IL-12 p70 heterodimer and IFN-gamma proteins were documented in the serum within 24 h after intradermal injection of the pIL-12o- plasmid, which also induced the highest level of NK activity in the spleen and liver among the IL-12 constructs. Interestingly, both p40 mRNA expression at the injection site and serum protein levels followed a biphasic pattern of expression, with peaks on days 1 and 5. Subsequent studies revealed that the ability of intradermally injected pIL-12o- to augment NK lytic activity was prevented by administration of a neutralizing anti-IL-12 mAb. Finally, injection of the pIL-12o- into BALB/c IL-12 p40-/- mice also resulted in a biphasic pattern of IL-12 p70 appearance in the serum, and induced IFN-gamma protein and activated NK lytic activity in liver and spleen. These results demonstrate that injection of delivered naked DNA encoding the IL-12 gene mediates the biphasic systemic production of IL-12-inducible genes and augments the cytotoxic function of NK cells in lymphoid and parenchymal organs as a direct result of transgene expression. The results also suggest that these naked DNA plasmids may be useful adjuvants for vaccines against infectious and neoplastic diseases.     

Neotropical bats: estimating species diversity with DNA barcodes

DNA barcoding using the cytochrome c oxidase subunit 1 gene (COI) is frequently employed as an efficient method of species identification in animal life and may also be used to estimate species richness, particularly in understudied faunas. Despite numerous past demonstrations of the efficiency of this technique, few studies have attempted to employ DNA barcoding methodologies on a large geographic scale, particularly within tropical regions. In this study we survey current and potential species diversity using DNA barcodes with a collection of more than 9000 individuals from 163 species of Neotropical bats (order Chiroptera). This represents one of the largest surveys to employ this strategy on any animal group and is certainly the largest to date for land vertebrates. Our analysis documents the utility of this tool over great geographic distances and across extraordinarily diverse habitats. Among the 163 included species 98.8% possessed distinct sets of COI haplotypes making them easily recognizable at this locus. We detected only a single case of shared haplotypes. Intraspecific diversity in the region was high among currently recognized species (mean of 1.38%, range 0-11.79%) with respect to birds, though comparable to other bat assemblages. In 44 of 163 cases, well-supported, distinct intraspecific lineages were identified which may suggest the presence of cryptic species though mean and maximum intraspecific divergence were not good predictors of their presence. In all cases, intraspecific lineages require additional investigation using complementary molecular techniques and additional characters such as morphology and acoustic data. Our analysis provides strong support for the continued assembly of DNA barcoding libraries and ongoing taxonomic investigation of bats.     

MicroRNA signatures in tumor tissue related to angiogenesis in non-small cell lung cancer

Background

Angiogenesis is regarded as a hallmark in cancer development, and anti-angiogenic treatment is presently used in non-small cell lung cancer (NSCLC) patients. MicroRNAs (miRs) are small non-coding, endogenous, single stranded RNAs that regulate gene expression. In this study we aimed to identify significantly altered miRs related to angiogenesis in NSCLC.

Methods

From a large cohort of 335 NSCLC patients, paraffin-embedded samples from 10 patients with a short disease specific survival (DSS), 10 with a long DSS and 10 normal controls were analyzed. The miRs were quantified by microarray hybridization and selected miRs were validated by real-time qPCR. The impacts of different pathways, including angiogenesis, were evaluated by Gene Set Enrichment Analysis (GSEA) derived from Protein ANalysis THrough Evolutionary Relationship (PANTHER). One of the most interesting candidate markers, miR-155, was validated by in situ hybridization (ISH) in the total cohort (n = 335) and correlation analyses with several well-known angiogenic markers were done.

Results

128 miRs were significantly up- or down-regulated; normal versus long DSS (n = 68) and/or normal versus short DSS (n = 63) and/or long versus short DSS (n = 37). The pathway analysis indicates angiogenesis-related miRs to be involved in NSCLC. There were strong significant correlations between the array hybridization and qPCR validation data. The significantly altered angiogenesis-related miRs of high interest were miR-21, miR-106a, miR-126, miR-155, miR-182, miR-210 and miR-424. miR-155 correlated significantly with fibroblast growth factor 2 (FGF2) in the total cohort (r = 0.17, P = 0.002), though most prominent in the subgroup with nodal metastasis (r = 0.34, P<0.001).

Conclusions

Several angiogenesis-related miRs are significantly altered in NSCLC. Further studies to understand their biological functions and explore their clinical relevance are warranted.