CD11b+ bone marrow-derived monocytes are the major leukocyte subset responsible for retinal capillary leukostasis in experimental diabetes in mouse and express high levels of CCR5 in the circulation

We investigated the phenotype of cells involved in leukostasis in the early stages of streptozotocin-induced diabetes in mice by direct observation and by adoptive transfer of calcein-AM-labeled bone marrow-derived leukocytes from syngeneic mice. Retinal whole mounts, confocal microscopy, and flow cytometry ex vivo and scanning laser ophthalmoscopy in vivo were used. Leukostasis in vivo and ex vivo in retinal capillaries was increased after 2 weeks of diabetes (Hb A(1c), 14.2 ± 1.2) when either donor or recipient mice were diabetic. Maximum leukostasis occurred when both donor and recipient were diabetic. CD11b(+), but not Gr1(+), cells were preferentially entrapped in retinal vessels (fivefold increase compared with nondiabetic mice). In diabetic mice, circulating CD11b(+) cells expressed high levels of CCR5 (P = 0.04), whereas spleen (P = 0.0001) and retinal (P = 0.05) cells expressed increased levels of the fractalkine chemokine receptor. Rosuvastatin treatment prevented leukostasis when both recipient and donor were treated but not when donor mice only were treated. This effect was blocked by treatment with mevalonate. We conclude that leukostasis in early diabetic retinopathy involves activated CCR5(+)CD11b(+) myeloid cells (presumed monocytes). However, leukostasis also requires diabetes-induced changes in the endothelium, because statin therapy prevented leukostasis only when recipient mice were treated. The up-regulation of the HMG-CoA reductase pathway in the endothelium is the major metabolic dysregulation promoting leukostasis.

Baseline Soil Variation Is a Major Factor in Arsenic Accumulation in Bengal Delta Paddy Rice

Factors responsible for paddy soil arsenic accumulation in the tubewell irrigated systems of the Bengal Delta were investigated. Baseline (i.e., nonirrigated) and paddy soils were collected from 30 field systems across Bangladesh. For each field, soil sampled at dry season (Boro) harvest i.e., the crop cycle irrigated with tubewell water, was collected along a 90 m transect away from the tubewell irrigation source. Baseline soil arsenic levels ranged from 0.8 to 21. mg/kg, with lower values found on the Pliestocene Terrace around Gazipur (average, 1.6 +/- 0.2 mg/kg), and higher levels found in Holecene sediment tracts of Jessore and Faridpur (average, 6.6 +/- 1.0 mg/kg). Two independent approaches were used to assess the extent of arsenic build-up in irrigated paddy soils. First, arsenic build-up in paddy soil at the end of dry season production (irrigated - baseline soil arsenic) was regressed against number of years irrigated and tubewell arsenic concentration. Years of irrigation was not significant (P 0.711), indicating no year-on-year arsenic build-up, whereas tubewell As concentration was significant (P = 0.008). The second approach was analysis of irrigated soils for 20 fields over 2 successive years. For nine of the fields there was a significant (P <0.05) decrease in soil arsenic from year 1 to 2, one field had a significant increase, whereas there was no change for the remaining 10. Over the dry season irrigation cycle, soil arsenic built-up in soils at a rate dependent on irrigation tubewell water, 35* (tubewell water concentration in mg/kg, mg/L). Grain arsenic rises steeply at low soil/shoot arsenic levels, plateauing out at concentratations. Baseline soil arsenic at Faridpur sites corresponded to grain arsenic levels at the start of this saturation phase. Therefore, variation in baseline levels of soil arsenic leads to a large range in grain arsenic. Where sites have high baseline soil arsenic, further additional arsenic from irrigation water only leads to a gradual increase in grain arsenic concentration.

Exploring the Transcriptome of Atlantic Salmon (Salmo salar) Skin, a Major Defense Organ

The skin of fish is the first line of defense against pathogens and parasites. The skin transcriptome of the Atlantic salmon is poorly characterized, and currently only 2,089 expressed sequence tags (ESTs) out of a total of half a million sequences are generated from skin-derived cDNA libraries. The primary aim of this study was to enhance the transcriptomic knowledge of salmon skin by using next-generation sequencing (NGS) technology, namely the Roche-454 platform. An equimolar mixture of high-quality RNA from skin and epidermal samples of salmon reared in either freshwater or seawater was used for 454-sequencing. This technique yielded over 600,000 reads, which were assembled into 34,696 isotigs using Newbler. Of these isotigs, 12 % had not been sequenced in Atlantic salmon, hence representing previously unreported salmon mRNAs that can potentially be skin-specific. Many full-length genes have been acquired, representing numerous biological processes. Mucin proteins are the main structural component of mucus and we examined in greater detail the sequences we obtained for these genes. Several isotigs exhibited homology to mammalian mucins (MUC2, MUC5AC and MUC5B). Mucin mRNAs are generally > 10 kbp and contain large repetitive units, which pose a challenge towards full-length sequence discovery. To date, we have not unearthed any full-length salmon mucin genes with this dataset, but have both N- and C-terminal regions of a mucin type 5. This highlights the fact that, while NGS is indeed a formidable tool for sequence data mining of non-model species, it must be complemented with additional experimental and bioinformatic work to characterize some mRNA sequences with complex features.

Psychosocial and academic characteristics of extremely low birth weight (<or =800 g) adolescents who are free of major impairment compared with term-born control subjects

To compare academic and cognitive ability, attention, attitudes, and behavior of extremely low birth weight (ELBW) adolescents who are free of major impairments at 17 years of age with term-born control subjects.

RNAi screen identifies Jarid1b as a major regulator of mouse HSC activity

Histone methylation is a dynamic and reversible process proposed to directly impact on stem cell fate. The Jumonji (JmjC) domain-containing family of demethylases comprises 27 members which can demethylate mono-, di- and tri-methylated lysine residues of histone (or non-histone) targets. To evaluate their role in regulation of hematopoietic stem cell (HSC) behaviour we performed a RNAi-based screen and found that demethylases JARID1B (H3K4) and JHDM1F (H3K9) play opposing roles in regulation of HSC activity. Decrease in Jarid1b levels correlated with an in vitro expansion of HSC with preserved long term in vivo lympho-myeloid differentiation potential. Jarid1b knockdown was associated with an increase in expression levels of 5’ Hoxa cluster genes and CxCl5 , and reduced levels of Pu.1, Egr1 and Cav1. shRNA against Jhdmlf, in contrast, impaired hematopoietic reconstitution of bone marrow cells. Together, our studies identified Jarid1b as a negative, and Jhdmlf as a positive regulator of HSC activity.

No major schizophrenia locus detected on chromosome 1q in a large multicenter sample

Reports of substantial evidence for genetic linkage of schizophrenia to chromosome 1q were evaluated by genotyping 16 DNA markers across 107 centimorgans of this chromosome in a multicenter sample of 779 informative schizophrenia pedigrees. No significant evidence was observed for such linkage, nor for heterogeneity in allele sharing among the eight individual samples. Separate analyses of European-origin families, recessive models of inheritance, and families with larger numbers of affected cases also failed to produce significant evidence for linkage. If schizophrenia susceptibility genes are present on chromosome 1q, their population-wide genetic effects are likely to be small.

Smoking is a major cause of premature death worldwide

Question. How many deaths were attributable to smoking in 2000 worldwide? Study design. Statistical extrapolation of epidemiological and clinical data. Main results. In the year 2000, about 12% of adults died prematurely from smoking (estimated 4.83 million uncertainty range 3.94-5.93 million). Leading causes of death attributable to smoking were cardiovascular diseases (1.69 million deaths), chronic obstructive pulmonary disease (0.97 million deaths) and lung cancer (0.85 million deaths; 71% of lung cancers were smoking related). Smoking related deaths in men were about 3 times more common than women in industrial countries, and about 7 times more common in developing countries. Authors' conclusions. Smoking was a major cause of death worldwide in 2000. © 2004 Elsevier Ltd. All rights reserved.

A single-component multidrug transporter of the major facilitator superfamily is part of a network that protects Escherichia coli from bile salt stress

Resistance to high concentrations of bile salts in the human intestinal tract is vital for the survival of enteric bacteria such as Escherichia coli. Although the tripartite AcrAB-TolC efflux system plays a significant role in this resistance, it is purported that other efflux pumps must also be involved. We provide evidence from a comprehensive suite of experiments performed at two different pH values (7.2 and 6.0) that reflect pH conditions that E. coli may encounter in human gut that MdtM, a single-component multidrug resistance transporter of the major facilitator superfamily, functions in bile salt resistance in E. coli by catalysing secondary active transport of bile salts out of the cell cytoplasm. Furthermore, assays performed on a chromosomal ΔacrB mutant transformed with multicopy plasmid encoding MdtM suggested a functional synergism between the single-component MdtM transporter and the tripartite AcrAB-TolC system that results in a multiplicative effect on resistance. Substrate binding experiments performed on purified MdtM demonstrated that the transporter binds to cholate and deoxycholate with micromolar affinity, and transport assays performed on inverted vesicles confirmed the capacity of MdtM to catalyse electrogenic bile salt/H(+) antiport.

Psychological responses after a major fatal earthquake: The effect of preitraumatic dissociation and posttraumatic stress symptoms on anxiety and depression.

Following trauma, most people with initial symptoms of stress recover, but it is important to identify those at risk for continuing difficulties so resources are allocated appropriately. There has been limited investigation of predictors of posttraumatic stress disorder following natural disasters. This study assessed psychological difficulties experienced in 101 adult treatment seekers following exposure to a significant earthquake. Peritraumatic dissociation, posttraumatic stress symptoms, anxiety, depression, and emotional support were assessed. Path analysis was used to determine whether the experience of some psychological difficulties predicted the experience of other difficulties. As hypothesized, peritraumatic dissociation was found to predict posttraumatic stress symptoms and anxiety. Posttraumatic stress symptoms then predicted anxiety and depression. Depression and anxiety were highly correlated. Contrary to expectations, emotional support was not significantly related to other psychological variables. These findings justify the provision of psychological support following a natural disaster and suggest the benefit of assessing peritraumatic dissociation and posttraumatic stress symptoms soon after the event to identify people in need of monitoring and intervention.

GWAS identifies an NAT2 acetylator status tag single nucleotide polymorphism to be a major locus for skin fluorescence

Skin fluorescence (SF) is a non-invasive marker of AGEs and is associated with the long-term complications of diabetes. SF increases with age and is also greater among individuals with diabetes. A familial correlation of SF suggests that genetics may play a role. We therefore performed parallel genome-wide association studies of SF in two cohorts.

The radiated energy budget of Chromospheric Plasma in a major solar flare deduced from multi-wavelength observations

This paper presents measurements of the energy radiated by the lower solar atmosphere, at optical, UV, and EUV wavelengths, during an X-class solar flare (SOL2011-02-15T01:56) in response to an injection of energy assumed to be in the form of nonthermal electrons. Hard X-ray observations from RHESSI were used to track the evolution of the parameters of the nonthermal electron distribution to reveal the total power contained in flare accelerated electrons. By integrating over the duration of the impulsive phase, the total energy contained in the nonthermal electrons was found to be >2 × 1031 erg. The response of the lower solar atmosphere was measured in the free–bound EUV continua of H i (Lyman), He i, and He ii, plus the emission lines of He ii at 304 Å and H i (Lyα) at 1216 Å by SDO/EVE, the UV continua at 1600 Å and 1700 Å by SDO/AIA, and the white light continuum at 4504 Å, 5550 Å, and 6684 Å, along with the Ca ii H line at 3968 Å using Hinode/SOT. The summed energy detected by these instruments amounted to ~3 × 1030 erg; about 15% of the total nonthermal energy. The Lyα line was found to dominate the measured radiative losses. Parameters of both the driving electron distribution and the resulting chromospheric response are presented in detail to encourage the numerical modeling of flare heating for this event, to determine the depth of the solar atmosphere at which these line and continuum processes originate, and the mechanism(s) responsible for their generation.