Evaluation of satellite based indices for gross primary production estimates in a sparse savanna in the Sudan

One of the more frequently applied methods for integrating controls on primary production through satellite data is the Light Use Efficiency (LUE) approach. Satellite indices such as the Normalized Difference Vegetation Index (NDVI), Enhanced Vegetation Index (EVI) and the Shortwave Infrared Water Stress Index (SIWSI) have previously shown promise as predictors of primary production in several different environments. In this study, we evaluate NDVI, EVI and SIWSI derived from the Moderate Resolution Imaging Spectroradiometer (MODIS) satellite sensor against in-situ measurements from central Sudan in order to asses their applicability in LUE-based primary production modeling within a water limited environment. Results show a strong correlation between vegetation indices and gross primary production (GPP), demonstrating the significance of vegetation indices for deriving information on primary production with relatively high accuracy at similar areas. Evaluation of SIWSI however, reveal that the fraction of vegetation apparently is to low for the index to provide accurate information on canopy water content, indicating that the use of SIWSI as a predictor of water stress in satellite data-driven primary production modeling in similar semi-arid ecosystems is limited

Controlling the Oxidation of Magnetic and Electrically Conductive Solid-Solution Iron-Rhodium Nanoparticles Synthesized by Laser Ablation in Liquids

This study focuses on the synthesis of FeRh nanoparticles via pulsed laser ablation in liquid and on controlling the oxidation of the synthesized nanoparticles. Formation of monomodal γ-FeRh nanoparticles was confirmed by transmission electron microscopy (TEM) and their composition confirmed by atom probe tomography (APT). For these particles, three major contributors to oxidation were analysed: (1) dissolved oxygen in the organic solvents, (2) the bound oxygen in the solvent and (3) oxygen in the atmosphere above the solvent. The decrease of oxidation for optimized ablation conditions was confirmed through energy-dispersive X-ray (EDX) and Mössbauer spectroscopy. Furthermore, the time dependence of oxidation was monitored for dried FeRh nanoparticles powders using ferromagnetic resonance spectroscopy (FMR). By magnetophoretic separation, B2-FeRh nanoparticles could be extracted from the solution and characteristic differences of nanostrand formation between γ-FeRh and B2-FeRh nanoparticles were observed

Efficacy and safety of the anti-IL-12/23 p40 monoclonal antibody, ustekinumab, in patients with active psoriatic arthritis despite conventional non-biological and biological anti-tumour necrosis factor therapy: 6-month and 1-year results of the phase 3, multicentre, double-blind, placebo-controlled, randomised PSUMMIT 2 trial

Objective: Assess ustekinumab efficacy (week 24/week 52) and safety (week 16/week 24/week 60) in patients with active psoriatic arthritis (PsA) despite treatment with conventional and/or biological anti-tumour necrosis factor (TNF) agents. Methods: In this phase 3, multicentre, placebo-controlled trial, 312 adults with active PsA were randomised (stratified by site, weight (≤100 kg/>100 kg), methotrexate use) to ustekinumab 45 mg or 90 mg at week 0, week 4, q12 weeks or placebo at week 0, week 4, week 16 and crossover to ustekinumab 45 mg at week 24, week 28 and week 40. At week 16, patients with <5% improvement in tender/swollen joint counts entered blinded early escape (placebo→45 mg, 45 mg→90 mg, 90 mg→90 mg). The primary endpoint was ≥20% improvement in American College of Rheumatology (ACR20) criteria at week 24. Secondary endpoints included week 24 Health Assessment Questionnaire-Disability Index (HAQ-DI) improvement, ACR50, ACR70 and ≥75% improvement in Psoriasis Area and Severity Index (PASI75). Efficacy was assessed in all patients, anti-TNF-naïve (n=132) patients and anti-TNF-experienced (n=180) patients. Results: More ustekinumab-treated (43.8% combined) than placebo-treated (20.2%) patients achieved ACR20 at week 24 (p<0.001). Significant treatment differences were observed for week 24 HAQ-DI improvement (p<0.001), ACR50 (p≤0.05) and PASI75 (p<0.001); all benefits were sustained through week 52. Among patients previously treated with ≥1 TNF inhibitor, sustained ustekinumab efficacy was also observed (week 24 combined vs placebo: ACR20 35.6% vs 14.5%, PASI75 47.1% vs 2.0%, median HAQ-DI change −0.13 vs 0.0; week 52 ustekinumab-treated: ACR20 38.9%, PASI75 43.4%, median HAQ-DI change −0.13). No unexpected adverse events were observed through week 60. Conclusions: The interleukin-12/23 inhibitor ustekinumab (45/90 mg q12 weeks) yielded significant and sustained improvements in PsA signs/symptoms in a diverse population of patients with active PsA, including anti-TNF-experienced PsA patients

Oligomeric Coiled-Coil Adhesin YadA Is a Double-Edged Sword

Yersinia adhesin A (YadA) is an essential virulence factor for the food-borne pathogens Yersinia enterocolitica and Yersinia pseudotuberculosis. Suprisingly, it is a pseudogene in Yersinia pestis. Even more intriguing, the introduction of a functional yadA gene in Y. pestis EV76 was shown to correlate with a decrease in virulence in a mouse model. Here, we report that wild type (wt) Y. enterocolitica E40, as well as YadA-deprived E40 induced the synthesis of neutrophil extracellular traps (NETs) upon contact with neutrophils, but only YadA-expressing Y. enterocolitica adhered to NETs and were killed. As binding seemed to be a prerequisite for killing, we searched for YadA-binding substrates and detected the presence of collagen within NETs. E40 bacteria expressing V98D,N99A mutant YadA with a severely reduced ability to bind collagen were found to be more resistant to killing, suggesting that collagen binding contributes significantly to sensitivity to NETs. Wt Y. pestis EV76 were resistant to killing by NETs, while recombinant EV76 expressing YadA from either Y. pseudotuberculosis or Y. enterocolitica were sensitive to killing by NETs, outlining the importance of YadA for susceptibility to NET-dependent killing. Recombinant EV76 endowed with YadA from Y. enterocolitica were also less virulent for the mouse than wt EV76, as shown before. In addition, EV76 carrying wt YadA were less virulent for the mouse than EV76 expressing YadAV98D,N99A. The observation that YadA makes Yersinia sensitive to NETs provides an explanation as for why evolution selected for the inactivation of yadA in the flea-borne Y. pestis and clarifies an old enigma. Since YadA imposes the same cost to the food-borne Yersinia but was nevertheless conserved by evolution, this observation also illustrates the duality of some virulence functions

Geographical variation in rates of surgical treatment for female stress urinary incontinence in England: a national cohort study.

OBJECTIVE: To examine geographic variation in use of surgery for female stress urinary incontinence (SUI), mainly midurethral mesh tape insertions, in the English National Health Service (NHS). DESIGN: National cohort study. SETTING: NHS hospitals. PARTICIPANTS: 27 997 women aged 20 years or older who had a first SUI surgery in an English NHS Hospital between April 2013 and March 2016 and a diagnosis of SUI at the same time as the procedure. METHODS: Multilevel Poisson regression was used to adjust for geographic differences in age, ethnicity, prevalence of long-term illness and socioeconomic deprivation. PRIMARY OUTCOME MEASURE: Rate of surgery for SUI per 100 000 women/year at two geographic levels: Clinical Commissioning Group (CCG; n=209) and Sustainability and Transformation Partnership (STP; n=44). RESULTS: The rate of surgery for SUI was 40 procedures per 100 000 women/year. Risk-adjusted rates ranged from 20 to 106 procedures per 100 000 women/year across CCGs and 24 to 69 procedures per 100 000 women/year across the STP areas. These regional differences were only partially explained by demographic characteristics as adjustment reduced variance of surgery rates by 16% among the CCGs and 35% among the STPs. CONCLUSIONS: Substantial geographic variation exists in the use of surgery for female SUI in the English NHS, suggesting that women in some areas are more likely to be treated compared with women with the same condition in other areas. The variation reflects differences in how national guidelines are being interpreted in the context of the ongoing debate about the safety of SUI surgery

Palbociclib in combination with aromatase inhibitors in patients ≥ 75 years with oestrogen receptor-positive, human epidermal growth factor receptor 2 negative advanced breast cancer : a real-world multicentre UK study

Background Breast cancer incidence increases with age and real-world data is essential to guide prescribing practices in the older population. The aim of this study was to collect large scale real-world data on tolerability and efficacy of palbociclib + AI in the first line treatment of ER+/HER2-advanced breast cancer in those aged ≥75 years. Methods 14 cancer centres participated in this national UK retrospective study. Patients aged ≥75 years treated with palbociclib + AI in the first line setting were identified. Data included baseline demographics, disease characteristics, toxicities, dose reductions and delays, treatment response and survival data. Multivariable Cox regression was used to assess independent predictors of PFS, OS and toxicities. Results 276 patients met the eligibility criteria. The incidence of febrile neutropenia was low (2.2%). The clinical benefit rate was 87%. 50.7% of patients had dose reductions and 59.3% had dose delays. The 12- and 24- month PFS rates were 75.9% and 64.9%, respectively. The 12- and 24- month OS rates were 85.1% and 74.0%, respectively. Multivariable analysis identified PS, Age-adjusted Charlson Comorbidity Index (ACCI) and number of metastatic sites to be independent predictors of PFS. Dose reductions and delays were not associated with adverse survival outcomes. Baseline ACCI was an independent predictor of development and severity of neutropenia. Conclusion Palbociclib is an effective therapy in the real-world older population and is well-tolerated with low levels of clinically significant toxicities. The use of geriatric and frailty assessments can help guide decision making in these patients

Seasonal variation of carbon fluxes in a sparse savanna in semi arid Sudan

<p>Abstract</p> <p>Background</p> <p>Large spatial, seasonal and annual variability of major drivers of the carbon cycle (precipitation, temperature, fire regime and nutrient availability) are common in the Sahel region. This causes large variability in net ecosystem exchange and in vegetation productivity, the subsistence basis for a major part of the rural population in Sahel. This study compares the 2005 dry and wet season fluxes of CO₂for a grass land/sparse savanna site in semi arid Sudan and relates these fluxes to water availability and incoming photosynthetic photon flux density (PPFD). Data from this site could complement the current sparse observation network in Africa, a continent where climatic change could significantly impact the future and which constitute a weak link in our understanding of the global carbon cycle.</p> <p>Results</p> <p>The dry season (represented by Julian day 35–46, February 2005) was characterized by low soil moisture availability, low evapotranspiration and a high vapor pressure deficit. The mean daily NEE (net ecosystem exchange, Eq. 1) was -14.7 mmol d^-1for the 12 day period (negative numbers denote sinks, i.e. flux from the atmosphere to the biosphere). The water use efficiency (WUE) was 1.6 mmol CO₂mol H₂O^-1and the light use efficiency (LUE) was 0.95 mmol CO₂mol PPFD^-1. Photosynthesis is a weak, but linear function of PPFD. The wet season (represented by Julian day 266–273, September 2005) was, compared to the dry season, characterized by slightly higher soil moisture availability, higher evapotranspiration and a slightly lower vapor pressure deficit. The mean daily NEE was -152 mmol d^-1for the 8 day period. The WUE was lower, 0.97 mmol CO₂mol H₂O^-1and the LUE was higher, 7.2 <it>μ</it>mol CO₂mmol PPFD^-1during the wet season compared to the dry season. During the wet season photosynthesis increases with PPFD to about 1600 <it>μ</it>mol m^-2s^-1and then levels off.</p> <p>Conclusion</p> <p>Based on data collected during two short periods, the studied ecosystem was a sink of carbon both during the dry and wet season 2005. The small sink during the dry season is surprising and similar dry season sinks have not to our knowledge been reported from other similar savanna ecosystems and could have potential management implications for agroforestry. A strong response of NEE versus small changes in plant available soil water content was found. Collection and analysis of flux data for several consecutive years including variations in precipitation, available soil moisture and labile soil carbon are needed for understanding the year to year variation of the carbon budget of this grass land/sparse savanna site in semi arid Sudan.</p

Structural and Histone Binding Ability Characterizations of Human PWWP Domains

The PWWP domain was first identified as a structural motif of 100-130 amino acids in the WHSC1 protein and predicted to be a protein-protein interaction domain. It belongs to the Tudor domain 'Royal Family', which consists of Tudor, chromodomain, MBT and PWWP domains. While Tudor, chromodomain and MBT domains have long been known to bind methylated histones, PWWP was shown to exhibit histone binding ability only until recently.The PWWP domain has been shown to be a DNA binding domain, but sequence analysis and previous structural studies show that the PWWP domain exhibits significant similarity to other 'Royal Family' members, implying that the PWWP domain has the potential to bind histones. In order to further explore the function of the PWWP domain, we used the protein family approach to determine the crystal structures of the PWWP domains from seven different human proteins. Our fluorescence polarization binding studies show that PWWP domains have weak histone binding ability, which is also confirmed by our NMR titration experiments. Furthermore, we determined the crystal structures of the BRPF1 PWWP domain in complex with H3K36me3, and HDGF2 PWWP domain in complex with H3K79me3 and H4K20me3.PWWP proteins constitute a new family of methyl lysine histone binders. The PWWP domain consists of three motifs: a canonical β-barrel core, an insertion motif between the second and third β-strands and a C-terminal α-helix bundle. Both the canonical β-barrel core and the insertion motif are directly involved in histone binding. The PWWP domain has been previously shown to be a DNA binding domain. Therefore, the PWWP domain exhibits dual functions: binding both DNA and methyllysine histones.This article can also be viewed as an enhanced version in which the text of the article is integrated with interactive 3D representations and animated transitions. Please note that a web plugin is required to access this enhanced functionality. Instructions for the installation and use of the web plugin are available in Text S1

Effect of Carnitine and herbal mixture extract on obesity induced by high fat diet in rats

<p>Abstract</p> <p>Background</p> <p>Obesity-associated type 2 diabetes is rapidly increasing throughout the world. It is generally recognized that natural products with a long history of safety can modulate obesity.</p> <p>Aim</p> <p>To investigate the development of obesity in response to a high fat diet (HFD) and to estimate the effect of L-carnitine and an Egyptian Herbal mixture formulation (HMF) (consisting of T. chebula, Senae, rhubarb, black cumin, aniseed, fennel and licorice) on bodyweight, food intake, lipid profiles, renal, hepatic, cardiac function markers, lipid Peroxidation, and the glucose and insulin levels in blood and liver tissue in rats.</p> <p>Method</p> <p>White male albino rats weighing 80-90 gm, 60 days old. 10 rats were fed a normal basal diet (Cr), 30 rats fed a high-fat diet (HFD) for 14 weeks during the entire study. Rats of the HFD group were equally divided into 3 subgroups each one include 10 rats. The first group received HFD with no supplement (HFD), the 2^ndgroup HFD+L-carnitine and the third group received HFD+HMF. Carnitine and HMF were administered at 10^thweek (start time for treatments) for 4 weeks.</p> <p>Body weight, lipid profile & renal function (urea, uric acid creatinine) ALT & AST activities, cardiac markers, (LDH, C.K-NAC and MB) the oxidative stress marker reduced glutathione (GSH), and Malondialdehyde (MDA) catalase activity, in addition to glucose, insulin, and insulin resistance in serum & tissues were analyzed.</p> <p>Results</p> <p>Data showed that feeding HFD diet significantly increased final body weight, triglycerides (TG), total cholesterol, & LDL concentration compared with controls, while significantly decreasing HDL; meanwhile treatment with L-carnitine, or HMF significantly normalized the lipid profile.</p> <p>Serum ALT, urea, uric acid, creatinine, LDH, CK-NAC, CK-MB were significantly higher in the high fat group compared with normal controls; and administration of L-carnitine or herbal extract significantly lessened the effect of the HFD. Hyperglycemia, hyperinsulinemia, and high insulin resistance (IR) significantly increased in HFD in comparison with the control group. The treatment with L-carnitine or HMF improved the condition. HFD elevated hepatic MDA and lipid peroxidation associated with reduction in hepatic GSH and catalase activity; whereas administration of L-carnitine or herbal extract significantly ameliorated these hepatic alterations.</p> <p>Conclusion</p> <p>HFD induced obesity associated with a disturbed lipid profile, defective antioxidant stability, and high values of IR parameters; this may have implications for the progress of obesity related problems. Treatment with L-carnitine, or HMF extract improved obesity and its associated metabolic problems in different degrees. Also HMF has antioxidant, hypolipidaemic insulin sensitizing effects. Moreover HMF might be a safe combination on the organs whose functions were examined, as a way to surmount the obesity state; and it has a distinct anti-obesity effect.</p