Single-nucleotide base excision repair DNA polymerase activity in C. elegans in the absence of DNA polymerase β

The base excision DNA repair (BER) pathway known to occur in Caenorhabditis elegans has not been well characterized. Even less is known about the DNA polymerase (pol) requirement for the gap-filling step during BER. We now report on characterization of in vitro uracil-DNA initiated BER in C. elegans. The results revealed single-nucleotide (SN) gap-filling DNA polymerase activity and complete BER. The gap-filling polymerase activity was not due to a DNA polymerase β (pol β) homolog, or to another X-family polymerase, since computer-based sequence analyses of the C. elegans genome failed to show a match for a pol β-like gene or other X-family polymerases. Activity gel analysis confirmed the absence of pol β in the C. elegans extract. BER gap-filling polymerase activity was partially inhibited by both dideoxynucleotide and aphidicolin. The results are consistent with a combination of both replicative polymerase(s) and lesion bypass/BER polymerase pol θ contributing to the BER gap-filling synthesis. Involvement of pol θ was confirmed in experiments with extract from pol θ null animals. The presence of the SN BER in C. elegans is supported by these results, despite the absence of a pol β-like enzyme or other X-family polymerase

Public Health Risks in Urban Slums : Findings of the Qualitative 'Healthy Kitchens Healthy Cities' Study in Kathmandu, Nepal

BACKGROUND: Communities in urban slums face multiple risks to their health. These are shaped by intermediary and structural determinants. Gaining a clear understanding of these determinants is a prerequisite for developing interventions to reduce the health consequences of urban poverty. With 828 million people living in slum conditions, the need to find ways to reduce risks to health has never been greater. In many low income settings, the kitchen is the epicentre of activities and behaviours which either undermine or enhance health. METHODS: We used qualitative methods of semi-structured interviews, observation and participatory workshops in two slum areas in Kathmandu, Nepal to gain women's perspectives on the health risks they faced in and around their kitchens. Twenty one women were interviewed and four participatory workshops with a total of 69 women were held. The women took photographs of their kitchens to trigger discussions. FINDINGS: The main health conditions identified by the women were respiratory disease, gastrointestinal disease and burn injuries. Women clearly understood intermediary (psychosocial, material and behavioural) determinants to these health conditions such as poor ventilation, cooking on open fires, over-crowding, lack of adequate child supervision. Women articulated the stress they experienced and clearly linked this to health conditions such as heart disease and uptake of smoking. They were also able to identify protective factors, particularly social capital. Subsequent analysis highlighted how female headed-households and those with disabilities had to contend with greater risks to health. CONCLUSIONS: Women living in slums are very aware of the intermediary determinants-material, behavioural and psycho-social, that increase their vulnerability to ill health. They are also able to identify protective factors, particularly social capital. It is only by understanding the determinants at all levels, not just the behavioural, that we will be able to identify appropriate interventions

Drosophila DNA polymerase theta utilizes both helicase-like and polymerase domains during microhomology-mediated end joining and interstrand crosslink repair

Double strand breaks (DSBs) and interstrand crosslinks (ICLs) are toxic DNA lesions that can be repaired through multiple pathways, some of which involve shared proteins. One of these proteins, DNA Polymerase theta (Pol theta), coordinates a mutagenic DSB repair pathway named microhomology-mediated end joining (MMEJ) and is also a critical component for bypass or repair of ICLs in several organisms. Pol theta contains both polymerase and helicase-like domains that are tethered by an unstructured central region. While the role of the polymerase domain in promoting MMEJ has been studied extensively both in vitro and in vivo, a function for the helicase-like domain, which possesses DNA-dependent ATPase activity, remains unclear. Here, we utilize genetic and biochemical analyses to examine the roles of the helicase-like and polymerase domains of Drosophila Pol theta. We demonstrate an absolute requirement for both polymerase and ATPase activities during ICL repair in vivo. However, similar to mammalian systems, polymerase activity, but not ATPase activity, is required for ionizing radiation-induced DSB repair. Using a site-specific break repair assay, we show that overall end-joining efficiency is not affected in ATPase-dead mutants, but there is a significant decrease in templated insertion events. In vitro, Pol theta can efficiently bypass a model unhooked nitrogen mustard crosslink and promote DNA synthesis following microhomology annealing, although ATPase activity is not required for these functions. Together, our data illustrate the functional importance of the helicase-like domain of Pol theta and suggest that its tethering to the polymerase domain is important for its multiple functions in DNA repair and damage tolerance

Urban agriculture, dietary diversity and child health in a sample of Tanzanian town folk

Undernutrition and micronutrient deficiency continue to be two of the major health burdens in less developed economies. In this study, we explore the link between urban agriculture, dietary diversity and child health, using weight-for-age and height-for-age Z-scores. The study makes use of two rounds of observational data for urban Tanzania and employs an instrumental variables estimation approach. We show that practising urban agriculture leads to the consumption of a greater variety of food items and the health status of urban children living in households practising urban agriculture significantly improves in the short and, more importantly, long term

Forme tetraplegiche

La letteratura considera tetraplegie, o tetraparesi, le paralisi cerebroli infantili caratterizzate da: interessamento equivalente di tutti e quattro gli arti, crescita somatica difficoltosa, ritardo mentale spesso importante, disturbi visivi frequenti, deficit uditivi possibili,compromissione orofacciale da paralisi pseudobulbare, con conseguenti disordini della masticazione, della deglutizione, della mimica, e del linguaggio, epilessia con crisi di difficile , leucomalcia periventricolare grave come lesione cerebrale più tipica

Condizioni per il trattamento rieducativo

Al momento di accogliere il bambino affetto da paralisi cerebrale infantile (PCI) e di stipulare con la sua famiglia il contatto terapeutico, il primo compito importante ed a volte più difficile che impegna il medico riabilitatore è rappresentato dalla necessità di trasformare e di trasferire il concetto di lesione, con quanto di oggettivo e di provato lo accompagna, nel concetto di paralisi, condizione soggettiva e potenziale il cui trattamento si rivela pieno di se, di ma, di forse e di però

Guida all'interpretazione della paralisi cerebrale infantile

L'espressione Paralisi Cerebrale Infantile definisce una "turba persistente ma non immutabile della postura e del movimento, dovuta ad una alterazione organica e non progressiva della funzione cerebrale, per cause pre - peri - post natali, prima che se ne completi la crescita e lo sviluppo"

Functional Reach and touch: how sense of movement disorders can influence Anticipatory Postural Adjustment?

Background: Sense of movement disorders (SMDs), as result of the failure of a complex multisensorial process involving the proprioceptive, visual, somaesthetic, and vestibular systems (A Berthoz 1997), are very frequent in children with cerebral palsy (CP) and negatively influence motor function- ing and postural control. The most frequent signs are: exaggerated and low threshold startle reaction, freezing posture, blinking or closing eyes, visual attention shifting, and facial grimaces. Diplegic children with SMDs show panic reactions to mild postural perturbations and are therefore unable to execute common tasks successfully, such as reaching and touching an object. Postural adjustments depend on motor reactions as well as on perception but perception has a leading role in anticipation. Objectives: We wanted to investigate how SMDs negatively influence anticipatory postural adjustments (APA). Method: A group of 14 children with diplegia were selected according to the following criteria: aged 6\u201315 years, acquired walking, no major differences at GMFCS, and no major sensorial or cognitive deficit. Eight were diagnosed positive for SMDs (according to the mentioned clinical signs), six did not have SMDs, and five normal participants matched for age were selected for the control group. The experimental setting consisted of a functional reach and touch task in the sitting position on an adjustable stool, a force platform registered the centre of pressure. A small ball target was placed at a distance of 120% of arms\u2019 length and at 45\u2da of abduction. The child sat with feet on a foot rest. The stool was set at two levels: ground and raised. Results: APAs are indicated by a backward shifting of centre of pressure with respect to the reaching direction before the start of the gesture. The presence of APAs according to group were: SMD, ground 42%, raised 36%; non-SMD ground 83%, raised 78%; controls, ground 93%, raised 93%. Discussion: The diplegic group with SMD has significantly fewer APAs than both the controls and non-SMD group. The height of the stool seems to influence APAs within the same group but we did not have enough statistical evidence (ttest). Data seem to support the hypothesis that SMDs influence negatively anticipatory postural control and this can reduce autonomy levels in action

The term diplegia should be enhanced. Part I: a new rehabilitation oriented classification of cerebral palsy

The classification systems for cerebral palsy (CP) need to be continuously updated, according to specific aims and to significant changes observed over the years in the panorama of CP. A simplification of CP categories, abandoning the use of the term diplegia, has been recently suggested. Conversely, in this paper a new proposal for classification of CP is briefly presented, where special attention is given to diplegia which is suggested to be divided into four main clinical forms, according to the patterns of walking observable in these subjects. The proposed classification was applied to a large population of 213 subjects with diplegia, among 467 cases of CP admitted to two reference centres for this disorder. The relative incidence of the four forms is reported. The adopted classification criteria, based on a primary ability of professionals working in rehabilitation, i.e. observation capacity, makes this approach simple and easy to use at all levels of the rehabilitation services for CP