Nanopore sequencing reveals that DNA replication compartmentalisation dictates genome stability and instability in Trypanosoma brucei.

The Trypanosoma brucei genome is structurally complex. Eleven megabase-sized chromosomes each comprise a transcribed core flanked by silent subtelomeres, housing thousands of Variant Surface Glycoprotein (VSG) genes. Additionally, hundreds of sub-megabase chromosomes contain 177 bp repeats of unknown function, and VSG transcription sites localise to many telomeres.

Familial and Bullying Victimisation: The Impact of Early Adversity Within the Home and Peer Settings on Late Adolescence and Adult Psychopathology.

Background: Awareness of adverse childhood experiences and their impact on adult psychopathology primarily focuses on adversities within the home. There is limited insight into the impact of adversities across peer environments.

Objective: This study investigates 19 items related to adverse experiences across the home, school and peer environments and their relationship to 12-month and lifetime psychopathology.

ADHD Comorbidity Structure and Impairment: Results of the WHO World Mental Health Surveys International College Student Project (WMH-ICS).

Objective: To examine the prevalence of ADHD and the association of comorbid disorders, and multivariate disorder classes with role impairment in college students.

Method: About 15,991 freshmen (24 colleges, 9 countries, WMH-ICS) (response rate = 45.6%) completed online WMH-CIDI-SC surveys for 6-month ADHD and six 12-month DSM-IV disorders.

Variations in the oral microbiome are associated with depression in young adults.

A growing body of evidence supports an important role for alterations in the brain-gut-microbiome axis in the aetiology of depression and other psychiatric disorders. The potential role of the oral microbiome in mental health has received little attention, even though it is one of the most diverse microbiomes in the body and oral dysbiosis has been linked to systemic diseases with an underlying inflammatory aetiology. This study examines the structure and composition of the salivary microbiome for the first time in young adults who met the DSM-IV criteria for depression (n = 40) and matched controls (n = 43) using 16S rRNA gene-based next generation sequencing.

Genome duplication in relies on persistent subtelomeric DNA replication.

DNA replication is needed to duplicate a cell's genome in S phase and segregate it during cell division. Previous work in detected DNA replication initiation at just a single region in each chromosome, an organisation predicted to be insufficient for complete genome duplication within S phase. Here, we show that acetylated histone H3 (AcH3), base J and a kinetochore factor co-localise in each chromosome at only a single locus, which corresponds with previously mapped DNA replication initiation regions and is demarcated by localised G/T skew and G4 patterns.

Conditional knockout of RAD51-related genes in Leishmania major reveals a critical role for homologous recombination during genome replication.

Homologous recombination (HR) has an intimate relationship with genome replication, both during repair of DNA lesions that might prevent DNA synthesis and in tackling stalls to the replication fork. Recent studies led us to ask if HR might have a more central role in replicating the genome of Leishmania, a eukaryotic parasite. Conflicting evidence has emerged regarding whether or not HR genes are essential, and genome-wide mapping has provided evidence for an unorthodox organisation of DNA replication initiation sites, termed origins.

Methylome profiling of young adults with depression supports a link with immune response and psoriasis.

Background: Currently the leading cause of global disability, clinical depression is a heterogeneous condition characterised by low mood, anhedonia and cognitive impairments. Its growing incidence among young people, often co-occurring with self-harm, is of particular concern. We recently reported very high rates of depression among first year university students in Northern Ireland, with over 25% meeting the clinical criteria, based on DSM IV.

Mental health, behavioural problems and treatment seeking among students commencing university in Northern Ireland.

Mental health and behavioural problems are common among students commencing university. University life can be stressful and problems often exacerbate during their course of study, while others develop disorders for the first time. The WHO World Mental Health Surveys International College Student Project aims to conduct longitudinal research to examine and monitor student mental health and wellbeing.

Mapping replication dynamics in Trypanosoma brucei reveals a link with telomere transcription and antigenic variation.

Survival of Trypanosoma brucei depends upon switches in its protective Variant Surface Glycoprotein (VSG) coat by antigenic variation. VSG switching occurs by frequent homologous recombination, which is thought to require locus-specific initiation. Here, we show that a RecQ helicase, RECQ2, acts to repair DNA breaks, including in the telomeric site of VSG expression.

Interactions among Trypanosoma brucei RAD51 paralogues in DNA repair and antigenic variation.

Homologous recombination in Trypanosoma brucei is used for moving variant surface glycoprotein (VSG) genes into expression sites during immune evasion by antigenic variation. A major route for such VSG switching is gene conversion reactions in which RAD51, a universally conserved recombinase, catalyses homology-directed strand exchange. In any eukaryote, RAD51-directed strand exchange in vivo is mediated by further factors, including RAD51-related proteins termed Rad51 paralogues.

Context-dependent intergenerational effects: the interaction between past and present environments and its effect on population dynamics.

Intergenerational effects arise when parents' actions influence the reproduction and survival of their offspring and possibly later descendants. Models suggest that intergenerational effects have important implications for both population dynamical patterns and the evolution of life-history traits. However, these will depend on the nature and duration of intergenerational effects.

How effective are maternal effects at having effects?

The well studied trade-off between offspring size and offspring number assumes that offspring fitness increases with increasing per-offspring investment. Where mothers differ genetically or exhibit plastic variation in reproductive effort, there can be variation in per capita investment in offspring, and via this trade-off, variation in fecundity. Variation in per capita investment will affect juvenile performance directly--a classical maternal effect--while variation in fecundity will also affect offspring performance by altering the offsprings' competitive environment.

Changes in maternal investment in eggs can affect population dynamics.

The way that mothers provision their offspring can have important consequences for their offspring's performance throughout life. Models suggest that maternally induced variation in life histories may have large population dynamical effects, even perhaps driving cycles such as those seen in forest Lepidoptera. The evidence for large maternal influences on population dynamics is unconvincing, principally because of the difficulty of conducting experiments at both the individual and population level.

Age and size at maturity: sex, environmental variability and developmental thresholds.

In most organisms, transitions between different life-history stages occur later and at smaller sizes as growth conditions deteriorate. Day and Rowe recently proposed that this pattern could be explained by the existence of developmental thresholds (minimum sizes or levels of condition below which transitions are unable to proceed). The developmental-threshold model predicts that the reaction norm of age and size at maturity will rotate in an anticlockwise manner from positive to a shallow negative slope if: (i) initial body size or condition is reduced; and/or (ii) some individuals encounter poor growth conditions at increasingly early developmental stages.

Talkin' 'bout my generation: environmental variability and cohort effects.

In variable environments, it is probable that environmental conditions in the past can influence demographic performance now. Cohort effects occur when these delayed life-history effects are synchronized among groups of individuals in a population. Here we show how plasticity in density-dependent demographic traits throughout the life cycle can lead to cohort effects and that there can be substantial population dynamic consequences of these effects.