Gene transfer of RANTES elicits autoimmune renal injury in MRL-Faslpr mice

Infiltrating macrophages and T cells are instrumental in autoimmune kidney destruction of MRL-Faslpr mice. We report that the β-chemokine RANTES, a chemoattractant for macrophages and T cells, is up-regulated in the MRL-Faslpr kidney prior to injury, but not normal kidneys (MRL-++, C3H-++) and increases with progressive injury. Furthermore, we establish an association between RANTES expression in the kidney and renal damage using a gene transfer approach. Tubular epithelial cells genetically modified to secrete RANTES infused under the renal capsule incites interstitial nephritis in MRL-Faslpr, but not MRL-++ or C3H-++ mice. RANTES recruits predominantly macrophages (Mø) and CD4+ and CD8+ T cells. In contrast, gene transfer of CSF-1, another molecule up-regulated simultaneously with RANTES in MRL-Faslpr kidneys, promotes the influx of Mø, CD4+ T cells and the unique double-negative (DN) T cells (CD4-,CD8-), which are prominent in diseased MRL-Faslpr kidneys. Thus, RANTES and CSF-1 recruit distinct T cell populations into the MRL-Faslpr kidney. In addition, delivery of RANTES and CSF-1 into the kidney of MRL-Faslpr mice causes an additive increase in pathology. We suggest that the complementary recruitment of T cell populations by RANTES (CD4, CD8) and CSF-1 (CD4, DN) promotes autoimmune nephritis in MRL-Faslpr mice

Characteristics of drug users who do or do not have care of their children

Aims - To compare the relative frequency of eight indicators of problem drug use and potentially adverse social circumstances in drug using parents and non-parents and to explore whether a profile based on these characteristics differs according to whether or not dependent children live with their drug-using parent. Design – The study utilises a 5-year national UK treatment monitoring system dataset. Sample – 61,425 users with, and 105,473 without dependent children accessing drug treatment services in England and Wales between January 1996 and December 2000. Measurements – Information about parenthood and children’s residence was routinely collected. Drug use and social circumstance indicators were daily heroin use, daily alcohol use, regular stimulant use, sharing of injecting equipment, living with another user, living alone, unstable accommodation, and criminal justice referral. Findings – There were clear differences between drug using parents according to where children live. Parents with children at home and non-parents showed fewer of the indicators than parents with children in care or elsewhere. Sixty-five percent of parents with none of the indicators lived with their children, compared to only 28% of those with three indicators and 9% of those with six or more indicators. Parents with children in care or living elsewhere showed the highest prevalence for each individual indicator. Conclusions – Drug using parents demonstrate a range of potentially unfavourable drug use behaviours and social circumstances but those whose children live with them use drugs less frequently and live in more favourable conditions than those whose children live elsewhere. Protective factors may operate in family situations while severe drug use and adverse social circumstances may result in a breakdown of family structures

IL-34 mediates acute kidney injury and worsens subsequent chronic kidney disease

Macrophages (Mø) are integral in ischemia/reperfusion injury–incited (I/R-incited) acute kidney injury (AKI) that leads to fibrosis and chronic kidney disease (CKD). IL-34 and CSF-1 share a receptor (c-FMS), and both cytokines mediate Mø survival and proliferation but also have distinct features. CSF-1 is central to kidney repair and destruction. We tested the hypothesis that IL-34–dependent, Mø-mediated mechanisms promote persistent ischemia-incited AKI that worsens subsequent CKD. In renal I/R, the time-related magnitude of Mø-mediated AKI and subsequent CKD were markedly reduced in IL-34–deficient mice compared with controls. IL-34, c-FMS, and a second IL-34 receptor, protein-tyrosine phosphatase ζ (PTP-ζ) were upregulated in the kidney after I/R. IL-34 was generated by tubular epithelial cells (TECs) and promoted Mø-mediated TEC destruction during AKI that worsened subsequent CKD via 2 distinct mechanisms: enhanced intrarenal Mø proliferation and elevated BM myeloid cell proliferation, which increases circulating monocytes that are drawn into the kidney by chemokines. CSF-1 expression in TECs did not compensate for IL-34 deficiency. In patients, kidney transplants subject to I/R expressed IL-34, c-FMS, and PTP−ζ in TECs during AKI that increased with advancing injury. Moreover, IL-34 expression increased, along with more enduring ischemia in donor kidneys. In conclusion, IL-34-dependent, Mø-mediated, CSF-1 nonredundant mechanisms promote persistent ischemia-incited AKI that worsens subsequent CKD

Religious practices among Islamic immigrants: Moroccan and Turkish men in Belgium

This study examines the religious participation of Islamic immigrants in Belgium using data from the Migration History and Social Mobility Survey collected in 1994–1996 from 2,200 men who had immigrated from Turkey and Morocco. Religious participation is measured as mosque attendance, fasting during Ramadan, and sacrificing a sheep at the Festival of Sacrifice. Results show that the religious participation of Islamic immigrants depends on both premigration and postmigration characteristics. Religious participation is higher among immigrants who: (1) attended a Koranic school in their country of origin, (2) were socialized in a religious region of their home country, (3) received little schooling, (4) currently live in an area of Belgium with a greater number of mosques, and (5) associate with a high number of co-ethnics. These results suggest that the religious participation of Islamic immigrants in Belgium is an outcome of characteristics unique to immigrants as well as processes common among the general population.

A global method for coupling transport with chemistry in heterogeneous porous media

Modeling reactive transport in porous media, using a local chemical equilibrium assumption, leads to a system of advection-diffusion PDE's coupled with algebraic equations. When solving this coupled system, the algebraic equations have to be solved at each grid point for each chemical species and at each time step. This leads to a coupled non-linear system. In this paper a global solution approach that enables to keep the software codes for transport and chemistry distinct is proposed. The method applies the Newton-Krylov framework to the formulation for reactive transport used in operator splitting. The method is formulated in terms of total mobile and total fixed concentrations and uses the chemical solver as a black box, as it only requires that on be able to solve chemical equilibrium problems (and compute derivatives), without having to know the solution method. An additional advantage of the Newton-Krylov method is that the Jacobian is only needed as an operator in a Jacobian matrix times vector product. The proposed method is tested on the MoMaS reactive transport benchmark.Comment: Computational Geosciences (2009) http://www.springerlink.com/content/933p55085742m203/?p=db14bb8c399b49979ba8389a3cae1b0f&pi=1

Low-frequency vibratory exercise reduces the risk of bone fracture more than walking: a randomized controlled trial

BACKGROUND: Whole-body vibration (WBV) is a new type of exercise that has been increasingly tested for the ability to prevent bone fractures and osteoporosis in frail people. There are two currently marketed vibrating plates: a) the whole plate oscillates up and down; b) reciprocating vertical displacements on the left and right side of a fulcrum, increasing the lateral accelerations. A few studies have shown recently the effectiveness of the up-and-down plate for increasing Bone Mineral Density (BMD) and balance; but the effectiveness of the reciprocating plate technique remains mainly unknown. The aim was to compare the effects of WBV using a reciprocating platform at frequencies lower than 20 Hz and a walking-based exercise programme on BMD and balance in post-menopausal women. METHODS: Twenty-eight physically untrained post-menopausal women were assigned at random to a WBV group or a Walking group. Both experimental programmes consisted of 3 sessions per week for 8 months. Each vibratory session included 6 bouts of 1 min (12.6 Hz in frequency and 3 cm in amplitude with 60° of knee flexion) with 1 min rest between bouts. Each walking session was 55 minutes of walking and 5 minutes of stretching. Hip and lumbar BMD (g·cm(-2)) were measured using dual-energy X-ray absorptiometry and balance was assessed by the blind flamingo test. ANOVA for repeated measurements was adjusted by baseline data, weight and age. RESULTS: After 8 months, BMD at the femoral neck in the WBV group was increased by 4.3% (P = 0.011) compared to the Walking group. In contrast, the BMD at the lumbar spine was unaltered in both groups. Balance was improved in the WBV group (29%) but not in the Walking group. CONCLUSION: The 8-month course of vibratory exercise using a reciprocating plate is feasible and is more effective than walking to improve two major determinants of bone fractures: hip BMD and balance

The <i>Castalia</i> mission to Main Belt Comet 133P/Elst-Pizarro

We describe Castalia, a proposed mission to rendezvous with a Main Belt Comet (MBC), 133P/Elst-Pizarro. MBCs are a recently discovered population of apparently icy bodies within the main asteroid belt between Mars and Jupiter, which may represent the remnants of the population which supplied the early Earth with water. Castalia will perform the first exploration of this population by characterising 133P in detail, solving the puzzle of the MBC’s activity, and making the first in situ measurements of water in the asteroid belt. In many ways a successor to ESA’s highly successful Rosetta mission, Castalia will allow direct comparison between very different classes of comet, including measuring critical isotope ratios, plasma and dust properties. It will also feature the first radar system to visit a minor body, mapping the ice in the interior. Castalia was proposed, in slightly different versions, to the ESA M4 and M5 calls within the Cosmic Vision programme. We describe the science motivation for the mission, the measurements required to achieve the scientific goals, and the proposed instrument payload and spacecraft to achieve these