Accumulation of gold nanoparticles in Brassic juncea

Enzymatic digestion is proposed as a method for concentrating gold nanoparticles produced in plants. The mild conditions of digestion are used in order to avoid an increase in the gold particle size, which would occur with a high-temperature process, so that material suitable for catalysis may be produced. Gold nanoparticles of a 5-50-nm diameter, as revealed by transmission electron microscopy (TEM), at concentrations 760 and 1120 ppm Au, were produced within Brassica juncea grown on soil with 22-48 mg Au kg(-1). X-ray absorption near edge spectroscopy (XANES) reveals that the plant contained approximately equal quantities of Au in the metallic (Au0) and oxidized (Au+1) states. Enzymatic digestion dissolved 55-60 wt% of the plant matter. Due to the loss of the soluble gold fraction, no significant increase in the total concentration of gold in the samples was observed. However, it is likely that the concentration of the gold nanoparticles increased by a factor of two. To obtain a gold concentration suitable for catalytic reactions, around 95 wt% of the starting dry biomass would need to be solubilized or removed, which has not yet been achieved.     

Expression of Ca2+-permeable two-pore channels rescues NAADP signalling in TPC-deficient cells

The second messenger NAADP triggers Ca²⁺ release from endo-lysosomes. Although two-pore channels (TPCs) have been proposed to be regulated by NAADP, recent studies have challenged this. By generating the first mouse line with demonstrable absence of both Tpcn1 and Tpcn2 expression (Tpcn1/2^−/−), we show that the loss of endogenous TPCs abolished NAADP-dependent Ca²⁺ responses as assessed by single-cell Ca²⁺ imaging or patch-clamp of single endo-lysosomes. In contrast, currents stimulated by PI(3,5)P₂ were only partially dependent on TPCs. In Tpcn1/2^−/− cells, NAADP sensitivity was restored by re-expressing wild-type TPCs, but not by mutant versions with impaired Ca²⁺-permeability, nor by TRPML1. Another mouse line formerly reported as TPC-null likely expresses truncated TPCs, but we now show that these truncated proteins still support NAADP-induced Ca²⁺ release. High-affinity [³²P]NAADP binding still occurs in Tpcn1/2^−/− tissue, suggesting that NAADP regulation is conferred by an accessory protein. Altogether, our data establish TPCs as Ca²⁺-permeable channels indispensable for NAADP signalling.     

Increasing variation in taxonomic distinctness reveals clusters of specialists in the deep sea

Changes in biodiversity with latitude or along a given environmental gradient have been described in many studies, including for marine ecosystems. Currently there is no scientific consensus, however, regarding macroecological patterns of diversity vs depth. Here, we describe variation in the biodiversity of fishes along a depth gradient from 0 to 2000 m in the region of the Norfolk Ridge and Lord Howe Rise (Western Pacific), using data obtained during the NORFANZ voyage. We modelled α diversity (richness), β diversity (using Jaccard's coefficient), evenness, taxonomic distinctness and taxonomic resemblances among fish communities. Although α diversity did not change appreciably with depth, β diversity decreased significantly in deeper strata. Both taxonomic resemblances and Jaccard similarities diminished with depth, indicating convergence in community structure. In addition, average taxonomic distinctness showed no clear pattern with depth, but taxonomic trees constructed among species within deeper samples had more variable path‐lengths than those in shallower samples. The presence of taxonomically distinct clusters of highly related species at depth indicates specialised niches that have developed in a relatively extreme (dark, pressurized) yet stable environment. We propose that reduced β diversity and increased variation in taxonomic distinctness might serve as indicators of ecological communities living in harsh environments – a hypothesis that should be tested in other systems, such as deserts, high altitudes or latitudes.     

Surface-templated fibril growth of peptide fragments from the shaft domain of the adenovirus fibre protein

Here we present a study of five analogues of a fragment from the shaft domain of the adenovirus fibre protein that readily form fibrils under a range of conditions. Using atomic force microscopy the fibrillisation of these peptides at the liquid/solid interface utilizing ordered crystalline substrates has been investigated. Our results demonstrate that the assembly pathway at the liquid/solid interface enables only the formation of truncated fibrillar structures, which align along the substrate's underlying atomic lattice during growth. Furthermore, that the concentration and volume of solution applied can be used to directly control the density of fibrillar coverage at the surface.     

Six-month exercise training program to treat post-thrombotic syndrome: a randomized controlled two-centre trial

Background

Exercise training may have the potential to improve post-thrombotic syndrome, a frequent, chronic complication of deep venous thrombosis. We conducted a randomized controlled two-centre pilot trial to assess the feasibility of a multicentre-based evaluation of a six-month exercise training program to treat post-thrombotic syndrome and to obtain preliminary data on the effectiveness of such a program.

Methods

Patients were randomized to receive exercise training (a six-month trainer-supervised program) or control treatment (an education session with monthly phone follow-ups). Levels of eligibility, consent, adherence and retention were used as indicators of study feasibility. Primary outcomes were change from baseline to six months in venous disease-specific quality of life (as measured using the Venous Insufficiency Epidemiological and Economic Study Quality of Life [VEINES-QOL] questionnaire) and severity of post-thrombotic syndrome (as measured by scores on the Villalta scale) in the exercise training group versus the control group, assessed by t tests. Secondary outcomes were change in generic quality of life (as measured using the Short-Form Health Survey-36 [SF-36] questionnaire), category of severity of post-thrombotic syndrome, leg strength, leg flexibility and time on treadmill.

Results

Of 95 patients with post-thrombotic syndrome, 69 were eligible, 43 consented and were randomized, and 39 completed the study. Exercise training was associated with improvement in VEINES-QOL scores (exercise training mean change 6.0, standard deviation [SD] 5.1 v. control mean change 1.4, SD 7.2; difference 4.6, 95% CI 0.54 to 8.7; p = 0.027) and improvement in scores on the Villalta scale (exercise training mean change −3.6, SD 3.7 v. control mean change −1.6, SD 4.3; difference −2.0, 95% CI −4.6 to 0.6; p = 0.14). Most secondary outcomes also showed greater improvement in the exercise training group.

Interpretation

Exercise training may improve post-thrombotic syndrome. It would be feasible to definitively evaluate exercise training as a treatment for post-thrombotic syndrome in a large multicentre trial.Chronic post-thrombotic syndrome develops in up to one-half of patients with deep venous thrombosis and is associated with varying combinations of leg pain, heaviness, swelling, edema, hyperpigmentation and varicose collateral veins. In severe instances, lipodermatosclerosis and venous ulcers occur.¹ Patients with post-thrombotic syndrome have substantially impaired quality of life.^2,3 Given that effective treatments are lacking, new approaches to managing post-thrombotic syndrome are needed.⁴Exercise training is an effective treatment for arterial claudication^5,6 and may also improve post-thrombotic syndrome.⁷ Potential mechanisms include improved endurance resulting from increased aerobic capacity, reduced muscular effort from improved strength, reduced swelling and discomfort via improved function of the calf muscle pump and improved muscu-loskeletal function via increased flexibility of ankle and knee joints.^8,9We performed a pilot trial to obtain data on the effectiveness of exercise training to treat post-thrombotic syndrome and to assess the feasibility of performing a multicentre study to address this question.     

1H-imidazo[4,5-c]pyridine-4-carbonitrile as cathepsin S inhibitors: separation of desired cellular activity from undesired tissue accumulation through optimization of basic nitrogen pka

Based on the theoretical understanding of the in vivo lysosomotropism, by adjusting the pk_a of basic nitrogen containing cathepsin S inhibitors, a set of compounds with pk_a 6-8 were identified to have excellent cell based Lip10 activity, yet avoiding undesired sequestration in spleen.     

Transplantation of human glial-restricted neural precursors into injured spinal cord promotes functional and sensory recovery without causing allodynia

Background aimsTraumatic injuries of the central nervous system cause damage and degeneration of specific cell populations with subsequent functional loss. Cell transplantation is a strategy to treat such injuries by replacing lost or damaged cell populations. Many kinds of cells are considered candidates for intraspinal transplantation. Human neural precursor cells (hNPC) derived from post-mortem fetal tissue are easy to isolate and expand, and are capable of producing large numbers of neuronal and glial cells. After transplantation into the nervous system, hNPC produce mature neural phenotypes and permit functional improvement in some models of neurodegenerative disease. In this study, we aimed to elucidate the therapeutic effect of different neuronal and glial progenitor populations of hNPC on locomotor and sensory functions of spinal cord-injured (SCI) ratsMethodsDifferent populations of progenitor cells were obtained from hNPC by cell sorting and neural induction, resulting in cell cultures that were NCAM⁺ A2B5⁺, NCAM⁺ A2B5^? or A2B5⁺ NG2⁺. These different cell populations were then tested for efficacy in repair of the injured spinal cord by transplantation into rats with SCIResultsThe A2B5⁺ NG2⁺ population of hNPC significantly improved locomotor and sensory (hindlimb) functional recovery of SCI rats. Importantly, no abnormal pain responses were observed in the forelimbs following transplantationConclusionsThis treatment approach can improve functional recovery after SCI without causing allodynia. Further studies will be conducted to investigate the ability of A2B5⁺ NG2⁺ cells to survive, differentiate and integrate in the injured spinal cord.     

Developmental origins of physical fitness: the Helsinki Birth Cohort Study

Background

Cardiorespiratory fitness (CRF) is a major factor influencing health and disease outcomes including all-cause mortality and cardiovascular disease. Importantly CRF is also modifiable and could therefore have a major public health impact. Early life exposures play a major role in chronic disease development. Our aim was to explore the potential prenatal and childhood origins of CRF in later life.

Methods/Principal Findings

This sub-study of the HBCS (Helsinki Birth Cohort Study) includes 606 men and women who underwent a thorough clinical examination and participated in the UKK 2-km walk test, which has been validated against a maximal exercise stress test as a measure of CRF in population studies. Data on body size at birth and growth during infancy and childhood were obtained from hospital, child welfare and school health records. Body size at birth was not associated with adult CRF. A 1 cm increase in height at 2 and 7 years was associated with 0.21 ml/kg/min (95% CI 0.02 to 0.40) and 0.16 ml/kg/min (95% CI 0.03 to 0.28) higher VO_2max, respectively. Adjustment for adult lean body mass strengthened these findings. Weight at 2 and 7 years and height at 11 years became positively associated with CRF after adult lean body mass adjustment. However, a 1 kg/m² higher BMI at 11 years was associated with −0.57 ml/kg/min (95% CI −0.91 to −0.24) lower adult VO_2max, and remained so after adjustment for adult lean body mass.

Conclusion/Significance

We did not observe any significant associations between body size at birth and CRF in later life. However, childhood growth was associated with CRF in adulthood. These findings suggest, importantly from a public point of view, that early growth may play a role in predicting adult CRF.     

Labile disulfide bonds are common at the leucocyte cell surface

Redox conditions change in events such as immune and platelet activation, and during viral infection, but the biochemical consequences are not well characterized. There is evidence that some disulfide bonds in membrane proteins are labile while others that are probably structurally important are not exposed at the protein surface. We have developed a proteomic/mass spectrometry method to screen for and identify non-structural, redox-labile disulfide bonds in leucocyte cell-surface proteins. These labile disulfide bonds are common, with several classes of proteins being identified and around 30 membrane proteins regularly identified under different reducing conditions including using enzymes such as thioredoxin. The proteins identified include integrins, receptors, transporters and cell-cell recognition proteins. In many cases, at least one cysteine residue was identified by mass spectrometry as being modified by the reduction process. In some cases, functional changes are predicted (e.g. in integrins and cytokine receptors) but the scale of molecular changes in membrane proteins observed suggests that widespread effects are likely on many different types of proteins including enzymes, adhesion proteins and transporters. The results imply that membrane protein activity is being modulated by a 'redox regulator' mechanism.