Analysis of the genome of the New Zealand giant collembolan (Holacanthella duospinosa) sheds light on hexapod evolution

Background: The New Zealand collembolan genus Holacanthella contains the largest species of springtails (Collembola) in the world. Using Illumina technology we have sequenced and assembled a draft genome and transcriptome from Holacanthella duospinosa (Salmon). We have used this annotated assembly to investigate the genetic basis of a range of traits critical to the evolution of the Hexapoda, the phylogenetic position of H. duospinosa and potential horizontal gene transfer events. Results: Our genome assembly was ~375 Mbp in size with a scaffold N50 of ~230 Kbp and sequencing coverage of ~180×. DNA elements, LTRs and simple repeats and LINEs formed the largest components and SINEs were very rare. Phylogenomics (370,877 amino acids) placed H. duospinosa within the Neanuridae. We recovered orthologs of the conserved sex determination genes thought to play a role in sex determination. Analysis of CpG content suggested the absence of DNA methylation, and consistent with this we were unable to detect orthologs of the DNA methyltransferase enzymes. The small subunit rRNA gene contained a possible retrotransposon. The Hox gene complex was broken over two scaffolds. For chemosensory ability, at least 15 and 18 ionotropic glutamate and gustatory receptors were identified, respectively. However, we were unable to identify any odorant receptors or their obligate co-receptor Orco. Twenty-three chitinase-like genes were identified from the assembly. Members of this multigene family may play roles in the digestion of fungal cell walls, a common food source for these saproxylic organisms. We also detected 59 and 96 genes that blasted to bacteria and fungi, respectively, but were located on scaffolds that otherwise contained arthropod genes. Conclusions: The genome of H. duospinosa contains some unusual features including a Hox complex broken over two scaffolds, in a different manner to other arthropod species, a lack of odorant receptor genes and an apparent lack of environmentally responsive DNA methylation, unlike many other arthropods. Our detection of candidate horizontal gene transfer candidates confirms that this phenomenon is occurring across Collembola. These findings allow us to narrow down the regions of the arthropod phylogeny where key innovations have occurred that have facilitated the evolutionary success of Hexapoda

Modeling the dynamics of glacial cycles

This article is concerned with the dynamics of glacial cycles observed in the geological record of the Pleistocene Epoch. It focuses on a conceptual model proposed by Maasch and Saltzman [J. Geophys. Res.,95, D2 (1990), pp. 1955-1963], which is based on physical arguments and emphasizes the role of atmospheric CO2 in the generation and persistence of periodic orbits (limit cycles). The model consists of three ordinary differential equations with four parameters for the anomalies of the total global ice mass, the atmospheric CO2 concentration, and the volume of the North Atlantic Deep Water (NADW). In this article, it is shown that a simplified two-dimensional symmetric version displays many of the essential features of the full model, including equilibrium states, limit cycles, their basic bifurcations, and a Bogdanov-Takens point that serves as an organizing center for the local and global dynamics. Also, symmetry breaking splits the Bogdanov-Takens point into two, with different local dynamics in their neighborhoods

Early cranial ultrasound findings among infants with neonatal encephalopathy in Uganda: an observational study.

BACKGROUND: In sub-Saharan Africa, the timing and nature of brain injury and their relation to mortality in neonatal encephalopathy (NE) are unknown. We evaluated cranial ultrasound (cUS) scans from term Ugandan infants with and without NE for evidence of brain injury. METHODS: Infants were recruited from a national referral hospital in Kampala. Cases (184) had NE and controls (100) were systematically selected unaffected term infants. All had cUS scans <36 h reported blind to NE status. RESULTS: Scans were performed at median age 11.5 (interquartile range (IQR): 5.2-20.2) and 8.4 (IQR: 3.6-13.5) hours, in cases and controls respectively. None had established antepartum injury. Major evolving injury was reported in 21.2% of the cases vs. 1.0% controls (P < 0.001). White matter injury was not significantly associated with bacteremia in encephalopathic infants (odds ratios (OR): 3.06 (95% confidence interval (CI): 0.98-9.60). Major cUS abnormality significantly increased the risk of neonatal death (case fatality 53.9% with brain injury vs. 25.9% without; OR: 3.34 (95% CI: 1.61-6.95)). CONCLUSION: In this low-resource setting, there was no evidence of established antepartum insult, but a high proportion of encephalopathic infants had evidence of major recent and evolving brain injury on early cUS imaging, suggesting prolonged or severe acute exposure to hypoxia-ischemia (HI). Early abnormalities were a significant predictor of death

Broad clinical phenotypes associated with TAR-DNA binding protein (TARDBP) mutations in amyotrophic lateral sclerosis

The finding of TDP-43 as a major component of ubiquitinated protein inclusions in amyotrophic lateral sclerosis (ALS) has led to the identification of 30 mutations in the transactive response-DNA binding protein (TARDBP) gene, encoding TDP-43. All but one are in exon 6, which encodes the glycine-rich domain. The aim of this study was to determine the frequency of TARDBP mutations in a large cohort of motor neurone disease patients from Northern England (42 non-superoxide dismutase 1 (SOD1) familial ALS (FALS), nine ALS-frontotemporal dementia, 474 sporadic ALS (SALS), 45 progressive muscular atrophy cases). We identified four mutations, two of which were novel, in two familial (FALS) and two sporadic (SALS) cases, giving a frequency of TARDBP mutations in non-SOD1 FALS of 5% and SALS of 0.4%. Analysis of clinical data identified that patients had typical ALS, with limb or bulbar onset, and showed considerable variation in age of onset and rapidity of disease course. However, all cases had an absence of clinically overt cognitive dysfunction

A fresh look at the evolution and diversification of photochemical reaction centers

In this review, I reexamine the origin and diversification of photochemical reaction centers based on the known phylogenetic relations of the core subunits, and with the aid of sequence and structural alignments. I show, for example, that the protein folds at the C-terminus of the D1 and D2 subunits of Photosystem II, which are essential for the coordination of the water-oxidizing complex, were already in place in the most ancestral Type II reaction center subunit. I then evaluate the evolution of reaction centers in the context of the rise and expansion of the different groups of bacteria based on recent large-scale phylogenetic analyses. I find that the Heliobacteriaceae family of Firmicutes appears to be the earliest branching of the known groups of phototrophic bacteria; however, the origin of photochemical reaction centers and chlorophyll synthesis cannot be placed in this group. Moreover, it becomes evident that the Acidobacteria and the Proteobacteria shared a more recent common phototrophic ancestor, and this is also likely for the Chloroflexi and the Cyanobacteria. Finally, I argue that the discrepancies among the phylogenies of the reaction center proteins, chlorophyll synthesis enzymes, and the species tree of bacteria are best explained if both types of photochemical reaction centers evolved before the diversification of the known phyla of phototrophic bacteria. The primordial phototrophic ancestor must have had both Type I and Type II reaction centers

Atypical disengagement from faces and its modulation by the control of eye fixation in children with Autism Spectrum Disorder

By using the gap overlap task, we investigated disengagement from faces and objects in children (9–17 years old) with and without autism spectrum disorder (ASD) and its neurophysiological correlates. In typically developing (TD) children, faces elicited larger gap effect, an index of attentional engagement, and larger saccade-related event-related potentials (ERPs), compared to objects. In children with ASD, by contrast, neither gap effect nor ERPs differ between faces and objects. Follow-up experiments demonstrated that instructed fixation on the eyes induces larger gap effect for faces in children with ASD, whereas instructed fixation on the mouth can disrupt larger gap effect in TD children. These results suggest a critical role of eye fixation on attentional engagement to faces in both groups

Abstract Reasoning and Friendship in High Functioning Preadolescents with Autism Spectrum Disorders

To investigate the relationship between cognitive and social functioning, 20 Israeli individuals with HFASD aged 8–12 and 22 age, maternal education, and receptive vocabulary–matched preadolescents with typical development (TYP) came to the lab with a close friend. Measures of abstract reasoning, friendship quality, and dyadic interaction during a play session were obtained. As hypothesized, individuals with HFASD were significantly impaired in abstract reasoning, and there were significant group differences in friend and observer reports of friendship quality. There also was consistency in reports between friends. Two factors—“relationship appearance” and “relationship quality” described positive aspects of the relationships. Disability status and age related to relationship appearance. Proband abstract reasoning was related to relationship quality

Muscle Fiber Viability, a Novel Method for the Fast Detection of Ischemic Muscle Injury in Rats

Acute lower extremity ischemia is a limb- and life-threatening clinical problem. Rapid detection of the degree of injury is crucial, however at present there are no exact diagnostic tests available to achieve this purpose. Our goal was to examine a novel technique - which has the potential to accurately assess the degree of ischemic muscle injury within a short period of time - in a clinically relevant rodent model. Male Wistar rats were exposed to 4, 6, 8 and 9 hours of bilateral lower limb ischemia induced by the occlusion of the infrarenal aorta. Additional animals underwent 8 and 9 hours of ischemia followed by 2 hours of reperfusion to examine the effects of revascularization. Muscle samples were collected from the left anterior tibial muscle for viability assessment. The degree of muscle damage (muscle fiber viability) was assessed by morphometric evaluation of NADH-tetrazolium reductase reaction on frozen sections. Right hind limbs were perfusion-fixed with paraformaldehyde and glutaraldehyde for light and electron microscopic examinations. Muscle fiber viability decreased progressively over the time of ischemia, with significant differences found between the consecutive times. High correlation was detected between the length of ischemia and the values of muscle fiber viability. After reperfusion, viability showed significant reduction in the 8-hour-ischemia and 2-hour-reperfusion group compared to the 8-hour-ischemia-only group, and decreased further after 9 hours of ischemia and 2 hours of reperfusion. Light- and electron microscopic findings correlated strongly with the values of muscle fiber viability: lesser viability values represented higher degree of ultrastructural injury while similar viability results corresponded to similar morphological injury. Muscle fiber viability was capable of accurately determining the degree of muscle injury in our rat model. Our method might therefore be useful in clinical settings in the diagnostics of acute ischemic muscle injury

Reactive community-based self-administered treatment against residual malaria transmission: study protocol for a randomized controlled trial

Background: Systematic treatment of all individuals living in the same compound of a clinical malaria case may clear asymptomatic infections and possibly reduce malaria transmission, where this is focal. High and sustained coverage is extremely important and requires active community engagement. This study explores a communitybased approach to treating malaria case contacts. Methods/design: This is a cluster-randomized trial to determine whether, in low-transmission areas, treating individuals living in the same compound of a clinical malaria case with dihydroartemisinin-piperaquine can reduce parasite carriage and thus residual malaria transmission. Treatment will be administered through the local health system with the approach of encouraging community participation designed and monitored through formative research. The trial goal is to show that this approach can reduce in intervention villages the prevalence of Plasmodium falciparum infection toward the end of the malaria transmission season. Discussion: Adherence and cooperation of the local communities are critical for the success of mass treatment campaigns aimed at reducing malaria transmission. By exploring community perceptions of the changing trends in malaria burden, existing health systems, and reaction to self-administered treatment, this study will develop and adapt a model for community engagement toward malaria elimination that is cost-effective and fits within the existing health system. Trial registration: Clinical trials.gov, NCT02878200. Registered on 25 August 2016

Patterns of neonatal hypoxic–ischaemic brain injury

Enormous progress has been made in assessing the neonatal brain, using magnetic resonance imaging (MRI). In this review, we will describe the use of MRI and proton magnetic resonance spectroscopy in detecting different patterns of brain injury in (full-term) human neonates following hypoxic–ischaemic brain injury and indicate the relevance of these findings in predicting neurodevelopmental outcome