Low Variation in the Polymorphic Clock Gene Poly-Q Region Despite Population Genetic Structure across Barn Swallow (Hirundo rustica) Populations

Recent studies of several species have reported a latitudinal cline in the circadian clock gene, Clock, which influences rhythms in both physiology and behavior. Latitudinal variation in this gene may hence reflect local adaptation to seasonal variation. In some bird populations, there is also an among-individual association between Clock poly-Q genotype and clutch initiation date and incubation period. We examined Clock poly-Q allele variation in the Barn Swallow (Hirundo rustica), a species with a cosmopolitan geographic distribution and considerable variation in life-history traits that may be influenced by the circadian clock. We genotyped Barn Swallows from five populations (from three subspecies) and compared variation at the Clock locus to that at microsatellite loci and mitochondrial DNA (mtDNA). We found very low variation in the Clock poly-Q region, as >96% of individuals were homozygous, and the two other alleles at this locus were globally rare. Genetic differentiation based on the Clock poly-Q locus was not correlated with genetic differentiation based on either microsatellite loci or mtDNA sequences. Our results show that high diversity in Clock poly-Q is not general across avian species. The low Clock variation in the background of heterogeneity in microsatellite and mtDNA loci in Barn Swallows may be an outcome of stabilizing selection on the Clock locus

Deciphering Proteomic Signatures of Early Diapause in Nasonia

Insect diapause is an alternative life-history strategy used to increase longevity and survival in harsh environmental conditions. Even though some aspects of diapause are well investigated, broader scale studies that elucidate the global metabolic adjustments required for this remarkable trait, are rare. In order to better understand the metabolic changes during early insect diapause, we used a shotgun proteomics approach on early diapausing and non-diapausing larvae of the recently sequenced hymenopteran model organism Nasonia vitripennis. Our results deliver insights into the molecular underpinnings of diapause in Nasonia and corroborate previously reported diapause-associated features for invertebrates, such as a diapause-dependent abundance change for heat shock and storage proteins. Furthermore, we observed a diapause-dependent switch in enzymes involved in glycerol synthesis and a vastly changed capacity for protein synthesis and degradation. The abundance of structural proteins and proteins involved in protein synthesis decreased with increasing diapause duration, while the abundance of proteins likely involved in diapause maintenance (e.g. ferritins) increased. Only few potentially diapause-specific proteins were identified suggesting that diapause in Nasonia relies to a large extent on a modulation of pre-existing pathways. Studying a diapause syndrome on a proteomic level rather than isolated pathways or physiological networks, has proven to be an efficient and successful avenue to understand molecular mechanisms involved in diapause

A novel approach of homozygous haplotype sharing identifies candidate genes in autism spectrum disorder

Autism spectrum disorder (ASD) is a highly heritable disorder of complex and heterogeneous aetiology. It is primarily characterized by altered cognitive ability including impaired language and communication skills and fundamental deficits in social reciprocity. Despite some notable successes in neuropsychiatric genetics, overall, the high heritability of ASD (~90%) remains poorly explained by common genetic risk variants. However, recent studies suggest that rare genomic variation, in particular copy number variation, may account for a significant proportion of the genetic basis of ASD. We present a large scale analysis to identify candidate genes which may contain low-frequency recessive variation contributing to ASD while taking into account the potential contribution of population differences to the genetic heterogeneity of ASD. Our strategy, homozygous haplotype (HH) mapping, aims to detect homozygous segments of identical haplotype structure that are shared at a higher frequency amongst ASD patients compared to parental controls. The analysis was performed on 1,402 Autism Genome Project trios genotyped for 1 million single nucleotide polymorphisms (SNPs). We identified 25 known and 1,218 novel ASD candidate genes in the discovery analysis including CADM2, ABHD14A, CHRFAM7A, GRIK2, GRM3, EPHA3, FGF10, KCND2, PDZK1, IMMP2L and FOXP2. Furthermore, 10 of the previously reported ASD genes and 300 of the novel candidates identified in the discovery analysis were replicated in an independent sample of 1,182 trios. Our results demonstrate that regions of HH are significantly enriched for previously reported ASD candidate genes and the observed association is independent of gene size (odds ratio 2.10). Our findings highlight the applicability of HH mapping in complex disorders such as ASD and offer an alternative approach to the analysis of genome-wide association data

Trophic macrophages in development and disease

Specialized phagocytes are found in the most primitive multicellular organisms. Their roles in homeostasis and in distinguishing self from non-self have evolved with the complexity of organisms and their immune systems. Equally important, but often overlooked, are the roles of macrophages in tissue development. As discussed in this Review, these include functions in branching morphogenesis, neuronal patterning, angiogenesis, bone morphogenesis and the generation of adipose tissue. In each case, macrophage depletion impairs the formation of the tissue and compromises its function. I argue that in several diseases, the unrestrained acquisition of these developmental macrophage functions exacerbates pathology. For example, macrophages enhance tumour progression and metastasis by affecting tumour-cell migration and invasion, as well as angiogenesis

HCN and HCO+ images of the Orion Bar photodissociation region

The Orion Bar is an ideal astrophysical laboratory for studying photodissociation regions because of its nearly edge-on orientation in the observer's line of sight. High angular resolution (similar to 9") maps of the Orion Bar in the J = 1-0 emission lines of HCO+ and HCN have been made by combining single-dish millimeter observations with interferometric data. This mapping technique provides both large-scale structural information and high resolution. The new maps show that HCO+ and HCN have globally similar spatial distributions in the Orion Bar. Both molecular species show the same clumpy NE to SW bar seen by previous observers in molecular line emission from the Orion Bar. However, our maps show HCN emission to be more confined to the bar structure and to clump cores than HCO+ emission. We do a crosscut comparison of our full-synthesis maps with previously published observations of the Orion Bar in: (1) the rotational transitions of (CO)-C-12 J = 1-0, (CO)-C-13 J = 1-0, CN N = 3-2, and CS J = 7-6; (2) the UV-pumped rovibrational transition of H-2 at 2.122 mu m; (3) 3.3 mu m emission attributed to the aromatic C-H bond stretching of polycyclic aromatic hydrocarbons (PAH); and (4) the atomic finestructure transitions of C I (609 mu m), O I (63 mu m), and C II (158 mu m). The crosscuts show the same chemical stratification seen by previous observers as expected from an edge-on photodissociation region. In:addition, we see that the HCN peak profile is relatively narrow and symmetrical compared to the broader asymmetrical HCO+ peak. We argue that this difference in peak shape supports a previously published suggestion that HCO+ production is enhanced in warm gas at the surface of the photodissociation region. We explain these observations using a nonhomogeneous photodissociation region model to which we have added nitrogen chemistry and the thermal chemical effects of polycyclic aromatic hydrocarbons. Instead of using a homogeneous model, we follow more recent models employing two components because the clumpiness seen in all the recent observations suggests at least two density components in the Orion Bar. From our model calculations, we have found that a ridge of dense clumps (3 x 10(6) cm(-3)) embedded in a lower density interclump medium (5 x 10(4) cm(-3)) explains our observations very well. Although some of the observations (e.g., emissions from H-2, CO, O I, C I and C II) arise from the interclump medium, we show that HCN and HCO+ J = 1-0 emission must come from a ridge of dense clumps near the ionization front. This result agrees with the findings of previous observers, who have suggested the presence of dense clumps in the Orion Bar

A Phase II/III, randomized, double-masked, vehicle-controlled, dose-ranging study of the safety and efficacy of OTX-101 in the treatment of dry eye disease [Corrigendum]

Tauber J, Schechter BA, Bacharach J, et al. Clin Ophthalmol. 2018;12:1921–1929.On page 1927, “Safety and tolerability assessments” section, third paragraph, first sentence should read from “Fifteen subjects exited the study due to AEs: 5 subjects (3.3%) in the OTX-101 0.09% group, 4 subjects (2.6%) in the OTX-101 0.09% group, and 6 subjects (3.9%) in the vehicle group.” to “Fifteen subjects exited the study due to AEs: 5 subjects (3.3%) in the OTX-101 0.09% group, 4 subjects (2.6%) in the OTX-101 0.05% group, and 6 subjects (3.9%) in the vehicle group.”Read the original articlePrevious corrigendum has been publishe