IL-22 Protects against Tissue Damage during Cutaneous Leishmaniasis

Cutaneous leishmaniasis is a disease characterized by ulcerating skin lesions, the resolution of which requires an effective, but regulated, immune response that limits parasite growth without causing permanent tissue damage. While mechanisms that control the parasites have been well studied, the factors regulating immunopathologic responses are less well understood. IL-22, a member of the IL-10 family of cytokines, can contribute to wound healing, but in other instances promotes pathology. Here we investigated the role of IL-22 during leishmania infection, and found that IL-22 limits leishmania-induced pathology when a certain threshold of damage is induced by a high dose of parasites. Il22 ^-/- mice developed more severe disease than wild-type mice, with significantly more pathology at the site of infection, and in some cases permanent loss of tissue. The increased inflammation was not due to an increased parasite burden, but rather was associated with the loss of a wound healing phenotype in keratinocytes. Taken together, these studies demonstrate that during cutaneous leishmaniasis, IL-22 can play a previously unappreciated role in controlling leishmania-induced immunopathology.     

Fetal microchimerism in kidney biopsies of lupus nephritis patients may be associated with a beneficial effect

IntroductionMicrochimeric male fetal cells (MFCs) have been associated with systemic lupus erythematosus, and published studies have further correlated MFC with lupus nephritis (LN). In the present study, we evaluated the frequency of MFC in the renal tissue of patients with LN.MethodsTwenty-seven renal biopsies were evaluated: Fourteen were from women with clinical and laboratory findings of LN, and thirteen were from controls. Genomic DNA was extracted from kidney biopsies, and the male fetal DNA was quantified using real-time quantitative polymerase chain reactions for the detection of specific Y chromosome sequences.ResultsMFCs were detected in 9 (64%) of 14 of patients with LN, whereas no MFCs were found in the control group (P = 0.0006). No differences in pregnancy history were found between patients with LN and the control group. Significantly higher amounts of MFCs were found in patients with LN with serum creatinine ≤1.5 mg/dl. Furthermore, women with MFCs had significantly better renal function at the time of biopsy (P = 0.03). In contrast, patients with LN without MFCs presented with more severe forms of glomerulonephritis (World Health Organization class IV = 60% and class V = 40%).ConclusionsOur data indicate a high prevalence of MFCs in renal biopsy specimens from women with LN, suggesting a role for MFCs in the etiology of LN. The present report also provides some evidence that MFCs could have a beneficial effect in this disease.

Electronic supplementary material

The online version of this article (doi:10.1186/s13075-015-0615-4) contains supplementary material, which is available to authorized users.     

The skin microbiome

The skin is the human body's largest organ, colonized by a diverse milieu of microorganisms, most of which are harmless or even beneficial to their host. Colonization is driven by the ecology of the skin surface, which is highly variable depending on topographical location, endogenous host factors and exogenous environmental factors. The cutaneous innate and adaptive immune responses can modulate the skin microbiota, but the microbiota also functions in educating the immune system. The development of molecular methods to identify microorganisms has led to an emerging view of the resident skin bacteria as highly diverse and variable. An enhanced understanding of the skin microbiome is necessary to gain insight into microbial involvement in human skin disorders and to enable novel promicrobial and antimicrobial therapeutic approaches for their treatment.     

Pyrazole-based arylalkyne Cathepsin S inhibitors. Part III: Modification of P4 region

Novel classes of tetrahydropyrido-pyrazole thioether amines and arylalkynes that display potency against human Cathepsin S have been previously reported. Here, key pharmacophoric elements of these two classes are merged, and SAR investigations of the P4 region are described, in conjunction with re-optimization of the P5 and P1/P1′/P3 regions. Identification of meta-substituted arylalkynes with good potency and improved solubility is described.     

Barium Bismuth Niobate Double Perovskite/Tungsten Oxide Nanosheet Photoanode for High‐Performance Photoelectrochemical Water Splitting

Recently, a new method to effectively engineer the bandgap of barium bismuth niobate (BBNO) double perovskite was reported. However, the planar electrodes based on BBNO thin films show low photocurrent densities for water oxidation owing to their poor electrical conductivity. Here, it is reported that the photoelectrochemical (PEC) activity of BBNO‐based electrodes can be dramatically enhanced by coating thin BBNO layers on tungsten oxide (WO₃) nanosheets to solve the poor conductivity issue while maintaining strong light absorption. The PEC activity of BBNO/WO₃ nanosheet photoanodes can be further enhanced by applying Co_0.8Mn_0.2O_x nanoparticles as a co‐catalyst. A photocurrent density of 6.02 mA cm^?2 at 1.23 V (vs reversible hydrogen electrode (RHE)) is obtained using three optically stacked, but electrically parallel, BBNO/WO₃ nanosheet photoanodes. The BBNO/WO₃ nanosheet photoanodes also exhibit excellent stability in a high‐pH alkaline solution; the photoanodes demonstrate negligible photocurrent density decay while under continuous PEC operation for more than 7 h. This work suggests a viable approach to improve the PEC performance of BBNO absorber‐based devices.     

Breeding season habitat associations and population declines of British Hawfinches Coccothraustes coccothraustes

Capsule At both landscape and local scales, breeding persistence in a declining Hawfinch population was greatest where broadleaved woodland cover was high, while at a fine scale, nest sites were associated with openings in the woodland canopy.

Aims To assess which components of habitat are associated with Hawfinch occupancy at landscape (10-km), local (tetrad) and fine (nest) spatial scales, during a period of population decline and range contraction.

Methods Bird Atlas 2008–11 data were used to determine areas of Hawfinch loss and persistence over 20 years. Current habitat was measured and compared to look for correlates that helped explain the differing status at both 10-km and tetrad scales. Fine scale habitat data collected at nest sites were compared with random locations to investigate within-wood nest site selection.

Results At both 10-km and tetrad scales, Hawfinch persistence is more likely where woodland cover is greater. Recent woodland management was less evident in tetrads where the species persisted. At the nest site scale, the only relationship detected was for nests to be close to canopy openings.

Conclusions Maintaining and increasing broadleaved woodland area is likely to benefit Hawfinch. Within woods, maintenance and creation of open areas may enhance nesting opportunities.     

Nest survival,causes of failure and productivity of British Hawfinches Coccothraustes coccothraustes

Capsule: Nest success rate of Hawfinches Coccothraustes coccothraustes within our study areas averaged 36% across five seasons, a level unlikely to be driving population declines and considerably higher than was suggested by recent estimates from the long-term Nest Record Scheme.

Aims: To investigate potential habitat correlates of nest success and identify nest predators from an intensive study on Hawfinches. To compare nest success and habitat of these nests with those found by Nest Record Scheme (NRS) recorders and test whether there is evidence of a decline in nest success over time from the NRS data.

Methods: Females trapped at feed sites were fitted with radio-tags and tracked back to nest sites providing a sample of nests for subsequent monitoring. Habitat measures potentially influencing survival were collected at nest sites and modelled against nest outcome. Nest success was compared with that from the long-term Nest Record Scheme. Nest cameras were deployed to identify predators.

Results: Nest success varied among years, but the mean value was not substantially lower than other Hawfinch studies or from other species with similar nesting strategies. Apparent recent declines in success suggested by Nest Record Scheme data were not evident in our study areas. Only avian species were recorded predating nests and a number of partial predations were recorded. No correlation was found between overall success for study nests and the habitat or temporal measurements collected.

Conclusions: Within our study areas, average Hawfinch nest success and productivity appeared to be sufficient to maintain local population stability though our sample size was modest and further work would be beneficial. General nest recording may have inherent biases that lead to an over-estimation of nest failure compared to those found by more structured study. Drivers of recent UK Hawfinch declines may be operating outside of the nesting season and/or in landscapes outside primary woodland.