bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural basis of substrate specificity in porcine RNase 4
Authors: Liang Shutian , Acharya K. Ravi 
Published: January 2016

RNase 4, a member of the RNase A superfamily with substrate preference for uridine, has roles in host defence, angiogenesis and neurodegenerative diseases. It also exhibits the highest interspecies amino acid sequence similarity amongst RNase A family members. However, compared to other members of the RNase A family, including eosinophil‐derived neurotoxin, eosinophil cationic protein and angiogenin, little is known about the molecular basis of substrate specificity in RNase 4. Here we report high to medium resolution structures of native porcine RNase 4 (PL3), a ‘substrate‐specificity’ determining mutant D80A and their respective complexes with deoxyuridine 5′‐monophosphate (dUMP) and deoxycytidine 5′‐monophosphate (dCMP). These structures provide insight into the structural basis of the uridine versus cytosine substrate specificity in RNase 4: in the D80A mutant (D80A•dCMP), the side chain of Arg101 is positioned further away from the substrate‐binding pocket due to the loss of the Asp80 side chain, reducing the repulsion force on the less favoured dCMP from Arg101 and allowing the ligand to occupy the binding pocket. This can also explain the observation that the ligand in the D80A•dCMP complex is stabilized only by a small number of hydrogen bonds. Compared to the previously reported structure of the human RNase 4•2′‐deoxyuridine 3′‐phosphate complex, the structure of PL3•dUMP complex shows additional hydrogen bonds between the ligand and the protein. In addition, the interaction between Arg101 and the dUMP ligand is absent. These observed differences are probably the result of the flexibility and different ‘positioning’ of the phosphate group among the mononucleotide ligands.DatabaseThe atomic coordinates and structure factors for PL3 (5AR6), D80A (5ARJ), PL3∙dUMP (5ARK) and D80A∙dCMP (5ARL) complexes have been deposited with the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ, USA (http://www.rcsb.org/).
Kinetic and structural characterization of amyloid‐β peptide hydrolysis by human angiotensin‐1‐converting enzyme
Authors: Larmuth Kate M. , Masuyer Geoffrey , Douglas Ross G. , Schwager Sylva L. , Acharya K. Ravi , Sturrock Edward D. 
Published: January 2016

Angiotensin‐1‐converting enzyme (ACE), a zinc metallopeptidase, consists of two homologous catalytic domains (N and C) with different substrate specificities. Here we report kinetic parameters of five different forms of human ACE with various amyloid beta (Aβ) substrates together with high resolution crystal structures of the N‐domain in complex with Aβ fragments. For the physiological Aβ(1–16) peptide, a novel ACE cleavage site was found at His14‐Gln15. Furthermore, Aβ(1–16) was preferentially cleaved by the individual N‐domain; however, the presence of an inactive C‐domain in full‐length somatic ACE (sACE) greatly reduced enzyme activity and affected apparent selectivity. Two fluorogenic substrates, Aβ(4–10)Q and Aβ(4–10)Y, underwent endoproteolytic cleavage at the Asp7‐Ser8 bond with all ACE constructs showing greater catalytic efficiency for Aβ(4–10)Y. Surprisingly, in contrast to Aβ(1–16) and Aβ(4–10)Q, sACE showed positive domain cooperativity and the double C‐domain (CC‐sACE) construct no cooperativity towards Aβ(4–10)Y. The structures of the Aβ peptide–ACE complexes revealed a common mode of peptide binding for both domains which principally targets the C‐terminal P2′ position to the S2′ pocket and recognizes the main chain of the P1′ peptide. It is likely that N‐domain selectivity for the amyloid peptide is conferred through the N‐domain specific S2′ residue Thr358. Additionally, the N‐domain can accommodate larger substrates through movement of the N‐terminal helices, as suggested by the disorder of the hinge region in the crystal structures. Our findings are important for the design of domain selective inhibitors as the differences in domain selectivity are more pronounced with the truncated domains compared to the more physiological full‐length forms.DatabaseThe atomic coordinates and structure factors for N‐domain ACE with Aβ peptides 4–10 (5AM8), 10–16 (5AM9), 1–16 (5AMA), 35–42 (5AMB) and (4–10)Y (5AMC) complexes have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ, USA (http://www.rcsb.org/).
Land cover change and carbon emissions over 100 years in an African biodiversity hotspot
Authors: Willcock Simon , Phillips Oliver L. , Platts Philip J. , Swetnam Ruth D. , Balmford Andrew , Burgess Neil D. , Ahrends Antje , Bayliss Julian , Doggart Nike , Doody Kathryn , Fanning Eibleis , Green Jonathan M. H. , Hall Jaclyn , Howell Kim L. , Lovett Jon C. , Marchant Rob , Marshall Andrew R. , Mbilinyi Boniface , Munishi Pantaleon K. T. , Owen Nisha , Topp‐Jorgensen Elmer J. , Lewis Simon L. 
Published: January 2016

AbstractAgricultural expansion has resulted in both land use and land cover change (LULCC) across the tropics. However, the spatial and temporal patterns of such change and their resulting impacts are poorly understood, particularly for the presatellite era. Here, we quantify the LULCC history across the 33.9 million ha watershed of Tanzania's Eastern Arc Mountains, using geo‐referenced and digitized historical land cover maps (dated 1908, 1923, 1949 and 2000). Our time series from this biodiversity hotspot shows that forest and savanna area both declined, by 74% (2.8 million ha) and 10% (2.9 million ha), respectively, between 1908 and 2000. This vegetation was replaced by a fivefold increase in cropland, from 1.2 million ha to 6.7 million ha. This LULCC implies a committed release of 0.9 Pg C (95% CI: 0.4–1.5) across the watershed for the same period, equivalent to 0.3 Mg C ha−1 yr−1. This is at least threefold higher than previous estimates from global models for the same study area. We then used the LULCC data from before and after protected area creation, as well as from areas where no protection was established, to analyse the effectiveness of legal protection on land cover change despite the underlying spatial variation in protected areas. We found that, between 1949 and 2000, forest expanded within legally protected areas, resulting in carbon uptake of 4.8 (3.8–5.7) Mg C ha−1, compared to a committed loss of 11.9 (7.2–16.6) Mg C ha−1 within areas lacking such protection. Furthermore, for nine protected areas where LULCC data are available prior to and following establishment, we show that protection reduces deforestation rates by 150% relative to unprotected portions of the watershed. Our results highlight that considerable LULCC occurred prior to the satellite era, thus other data sources are required to better understand long‐term land cover trends in the tropics.
Modelling the introduction and spread of non‐native species: international trade and climate change drive ragweed invasion
Authors: Chapman Daniel S. , Makra László , Albertini Roberto , Bonini Maira , Páldy Anna , Rodinkova Victoria , Šikoparija Branko , Weryszko‐Chmielewska Elżbieta , Bullock James M. 
Published: January 2016

AbstractBiological invasions are a major driver of global change, for which models can attribute causes, assess impacts and guide management. However, invasion models typically focus on spread from known introduction points or non‐native distributions and ignore the transport processes by which species arrive. Here, we developed a simulation model to understand and describe plant invasion at a continental scale, integrating repeated transport through trade pathways, unintentional release events and the population dynamics and local anthropogenic dispersal that drive subsequent spread. We used the model to simulate the invasion of Europe by common ragweed (Ambrosia artemisiifolia), a globally invasive plant that causes serious harm as an aeroallergen and crop weed. Simulations starting in 1950 accurately reproduced ragweed's current distribution, including the presence of records in climatically unsuitable areas as a result of repeated introduction. Furthermore, the model outputs were strongly correlated with spatial and temporal patterns of ragweed pollen concentrations, which are fully independent of the calibration data. The model suggests that recent trends for warmer summers and increased volumes of international trade have accelerated the ragweed invasion. For the latter, long distance dispersal because of trade within the invaded continent is highlighted as a key invasion process, in addition to import from the native range. Biosecurity simulations, whereby transport through trade pathways is halted, showed that effective control is only achieved by early action targeting all relevant pathways. We conclude that invasion models would benefit from integrating introduction processes (transport and release) with spread dynamics, to better represent propagule pressure from native sources as well as mechanisms for long‐distance dispersal within invaded continents. Ultimately, such integration may facilitate better prediction of spatial and temporal variation in invasion risk and provide useful guidance for management strategies to reduce the impacts of invasion.
Water for small‐scale biogas digesters in sub‐Saharan Africa
Authors: Bansal Vamini , Tumwesige Vianney , Smith Jo U. 
Published: January 2016

AbstractBiogas could provide a more sustainable energy source than wood fuels for rural households in sub‐Saharan African. However, functioning of biogas digesters can be limited in areas of low water availability. The water required is approximately 50 dm3 day−1 for each cow and 10 dm3 day−1 for each pig providing manure to the digester, or 25 (±6) dm3 day−1 for each person in the household, using a digester volume of 1.3 (±0.3) m3 capita−1. Here, we consider the potential of domestic water recycling, rainwater harvesting, and aquaculture to supply the water needed for digestion in different countries of sub‐Saharan Africa. Domestic water recycling was found to be important in every country but was usually insufficient to meet the requirements of the digester, with households in 72% of countries need to collect additional water. Rooftop rainwater harvesting also has an important role, iron roofs being more effective than thatched roofs at collecting water. However, even with an iron roof, the size of roof commonly found in sub‐Saharan Africa (15 to 40 m2) is too small to collect sufficient water, requiring an extra area (in m2) for each person of (R/100) (where R is the rainfall in mm). If there is a local market for fish, stocking a pond with tilapia, fed on plankton growing on bioslurry from the digester, could provide an important source of additional income and hold the water required by the digester. In areas where rainfall is low and seasonal, the fishpond might be stocked only in the rainy season, allowing the pond to be covered during the dry period to reduce evaporation. If evaporative losses (E in mm) exceed rainfall, an extra catchment area is needed to maintain the water level in the pond, equivalent to approximately (1.5 × ((E−R)/R)) m2 for each person in the household.
Eomesodermin promotes interferon‐γ expression and binds to multiple conserved noncoding sequences across the Ifng locus in mouse thymoma cell lines
Authors: Fukuoka Natsuki , Harada Misuzu , Nishida Ai , Ito Yuko , Shiota Hideki , Kataoka Takao 
Published: January 2016

The T‐box transcription factors T‐bet and eomesodermin (Eomes) have been shown to regulate the lineage‐specific expression of interferon‐γ (IFN‐γ). However, in contrast to T‐bet, the role of Eomes in the expression of IFN‐γ remains unclear. In this study, we investigated the Eomes‐dependent expression of IFN‐γ in the mouse thymoma BW5147 and EL4 cells, which do not express T‐bet or Eomes. The ectopic expression of Eomes induced BW5147 and EL4 cells to produce IFN‐γ in response to phorbol 12‐myristate 13‐acetate (PMA) and ionomycin (IM). In BW5147 cells, Eomes augmented luciferase activity driven by the Ifng promoter encoding from –2500 to +113 bp; however, it was not increased by a stimulation with PMA and IM. A chromatin immunoprecipitation assay showed that Eomes bound to the Ifng promoter and conserved noncoding sequence (CNS) –22 kb across the Ifng locus with high efficacy in BW5147 cells. Moreover, Eomes increased permissive histone modifications in the Ifng promoter and multiple CNSs. The stimulation with PMA and IM greatly augmented Eomes binding to CNS–54, CNS–34, CNS+19 and CNS+30, which was inhibited by FK506. These results indicated that Eomes bound to the Ifng promoter and multiple CNSs in stimulation‐dependent and stimulation‐independent manners.
Diagnosis of pheochromocytoma in a hemodialysis patient through measurement of plasma catecholamines
Authors: Vantomme Bram , Donck Jan , van Hooland Simon , Wauters Anne , De Clippele Marc , Neirynck Valerie , Huysman Frédérique 
Published: January 2016

AbstractWe report the case of a patient on chronic hemodialysis treatment with paroxysms of severe arterial hypertension accompanied by tachycardia, pallor, sweating and tremor. Measurement of plasma catecholamines revealed norepinephrine level of 4625 pg/mL (reference range 191–225 pg/mL), epinephrine level of 1035 pg/mL (58–76 pg/mL) and dopamine level of 148 pg/mL (50–100 pg/mL). MRI showed a left adrenal mass of 2 cm. After the patient was started on an alpha‐1 adrenergic receptor blocker, she underwent a left adrenalectomy. Anatomopathological examination confirmed the diagnosis of pheochromocytoma. Although urinary testing is not possible in anuric hemodialysis patients, diagnosis of pheochromocytoma can be made through measurement of plasma free metanephrines and/or plasma catecholamines.
Increased prevalence of eosinophilia in a hemodialysis population: Longitudinal and case control studies
Authors: Hildebrand Sarah , Corbett Richard , Duncan Neill , Ashby Damien 
Published: January 2016

AbstractEosinophilia is commonly found in patients with clinical reactions to the hemodialysis circuit. With modern membranes, such reactions have become less common, but they may be under diagnosed in patients with subtle symptoms, in whom the presence of eosinophilia is an important diagnostic feature. Two case reports are presented, along with a hemodialysis study of the frequency and clinical associations of eosinophilia. In three hemodialysis facilities, all current hemodialysis patients with persistent eosinophilia (greater than 1 × 109/L for 3 months) were identified. Control patients without eosinophilia (less than 0.5 × 109/L for 3 months) matched for age, gender, and ethnicity were identified from the same facilities. A historical cohort of patients, dialyzing at the same facilities 5 years ago, was screened for the presence of persistent eosinophilia. From 510 patients, 24 cases of persistent eosinophilia were identified (4.7%). The median eosinophil count was 1.75 × 109/L (range 1.1–7.5 × 109/L). The prevalence in a historical cohort 5 years previously was significantly less at 1.5% (P = 0.046). Compared to controls, patients with eosinophilia were more likely to be on an angiotensin converting enzyme inhibitor (41.7% vs. 12.5%, P = 0.049), had a lower C‐reactive protein (10 vs. 24 mg/L, P = 0.02) and were more likely to be using a fistula for access (P = 0.049). Over the following 12 months, there was no difference in the mean number of hospital admission days between cases and controls (7.6 vs. 11.5 days, P = 0.54), and no difference in mortality over 29 months (25.0% vs. 29.2%, P = 1.00). Eosinophilia remains not uncommon in hemodialysis patients, and in most cases reflects allergy to components of the dialysis circuit, which is usually subclinical. The overall prognosis for asymptomatic patients appears to be favourable.
Current evidence for the diagnostic value of gadoxetic acid‐enhanced magnetic resonance imaging for liver metastasis
Authors: Tsurusaki Masakatsu , Sofue Keitaro , Murakami Takamichi 
Published: January 2016

A variety of imaging techniques, including ultrasonography (US), multidetector computed tomography (MDCT), magnetic resonance imaging (MRI) and positron emission tomography combined with CT scan (PET/CT), are available for diagnosis and treatment planning in liver metastasis. Contrast‐enhanced MDCT is a relatively non‐invasive, widely available and standardized method for hepatic work‐up. Gadoxetic acid (gadolinium‐ethoxybenzyl‐diethylenetriamine pentaacetic acid; EOB Primovist®]) is a recently developed liver‐specific hepatobiliary MR contrast agent that offers both dynamic imaging as well as liver‐specific static hepatocyte imaging, referred to as the hepatobiliary phase. Following contrast injection, this technique reveals dynamic vascular phases (arterial, portal venous and delayed phases), in addition to the hepatobiliary phase upon uptake by functional hepatocytes. The overall sensitivity of gadoxetic acid‐enhanced MRI was significantly higher than that of contrast‐enhanced CT. Specifically, the higher sensitivity of gadoxetic acid‐enhanced MRI was observed in lesions smaller than 1 cm in diameter. Gadoxetic acid‐enhanced MRI is considered an extremely useful tool for the diagnosis of liver metastases. Future studies will focus on diagnostic algorithms involving combinations of modalities such as MRI, MDCT and/or 18F‐fluorodeoxyglucose PET/CT, which may impact the treatment plan for these patients.
Caries‐preventive self‐care for children. Consistent oral health messages to the public?
Authors: Løken SY , Wang NJ , Wigen TI 
Published: January 2016

AbstractBackgroundRecommendations regarding caries‐preventive self‐care for children are provided by several health authorities.ObjectiveTo investigate recommendations given to the public regarding children's caries‐preventive self‐care by Norwegian dentists, dental hygienists, dental nurses and public health nurses.MethodsQuestionnaires were sent by e‐mail and answered by 808 of 1132 persons who provide oral preventive promotion to children in dental services and health centres. The preventive advice was obtained through questions about the preferred preventive methods, fluoride recommendations and sources of knowledge on which the personnel based the advice about caries prevention in children. The responses were analysed using logistic regression.ResultsThe majority (59–71%) in all professions judged oral hygiene education to be the most important caries‐preventive method. Most personnel (84–98%) recommended all children to use fluoride toothpaste, and half of all personnel (53%) recommended fluoride lozenges for 50% or more of children. Multivariate analysis showed that dental nurses recommended lozenges to more children than dentists (OR 2.5, 95% CI 1.7–3.7), while health nurses recommended lozenges to fewer children than dentists (OR 0.5, 95% CI 0.3–0.8). The most important source of knowledge reported by dental personnel was professional education, while health nurses relied on information from dental personnel.ConclusionsHealth professions’ recommendations regarding caries‐preventive self‐care for children were mainly similar, although variation existed both between and within professions. Collaboration between professions and awareness of the evidence base for preventive oral care may improve the consistency of information given by health professionals to the public.
High prevalence of metabolic syndrome in patients with psoriasis in Lebanon: a prospective study
Authors: Itani Salam , Arabi Asma , Harb Dana , Hamzeh Diana , Kibbi Abdul‐Ghani 
Published: January 2016

AbstractBackgroundPsoriasis is a chronic inflammatory disease that affects not only the skin but also other organs as well. Genetic factors play an important role in individual predisposition. Lately, a positive association has been confirmed between psoriasis and metabolic syndrome (MBS), in western as well as in Middle Eastern countries.AimAssess the prevalence of MBS in Lebanese patients with psoriasis and the differential effect according to types and disease severity.MethodsThis was a case‐control study including 150 psoriasis patients and 150 age‐ and gender‐matched controls admitted to the dermatology clinics at the American University of Beirut‐Medical Center, a tertiary care center in Beirut. Psoriasis severity was assessed by the Psoriasis Area Severity Index (PASI). Blood samples were collected from fasting subjects and tested for glucose, HDL cholesterol, triglycerides, and C‐reactive protein (CRP). Multivariate binary logistic regression models were built to assess the relationship between MBS and psoriasis, after adjustment for smoking as a possible confounding variable.ResultsPatients with psoriasis were two times more likely to have MBS as compared to controls (35.3% vs 18.0%, P < 0.001) with an odds ratio (OR) of 2.4. All components of MBS were more prevalent in psoriasis patients than in controls. PASI score was greater in patients with MBS than those without MBS (10.5 ± 11.5 vs. 7.0 ± 8.1, P = 0.05). MBS prevalence tended to be higher in the inverse type than in others (52.2% versus 32.3%; P = 0.06) and in patients with nail pitting versus those without (45.3% vs. 28.2%; P = 0.03).ConclusionsThis was the first study to assess the prevalence of MBS in Lebanese subjects with psoriasis and, to our knowledge, the first study that showed a higher likelihood of MBS in patients with inverse psoriasis and with nail pitting.
Spectrum of mucocutaneous manifestations in an Asian cohort of patients with leukemia
Authors: Aggarwal Saurabh , Malhotra Pankaj , Dogra Sunil , Vinay Keshavamurthy , Kanwar Amrinder J. , Saikia Uma N. 
Published: January 2016

AbstractBackgroundLiterature on cutaneous manifestations of leukemia is limited.ObjectiveTo determine the pattern of mucocutaneous manifestations in adult Asian patients with leukemia and to establish their relation with the leukemia type.Subjects and methodsAfter previous consent, 196 consecutively registered patients with leukemia aged ≥18 years were recruited. All patients were prospectively followed for 3 months to evaluate the patterns of mucocutaneous involvement. The mucocutaneous manifestations were categorized into specific lesions with leukemic infiltration and non‐specific lesions.ResultsSeventy‐nine (40.3%) of 196 (males 128 and females 68) recruited patients showed one or more mucocutaneous manifestations. The total number of complaints observed was 87 with mean number of dermatoses per patient being 0.44. Specific manifestations (leukemia cutis) were present in six (3.06%) and nonspecific mucocutaneous manifestations in 73 (37.2%, reactive dermatoses n = 21 and infections n = 52). Cutaneous viral infections were significantly associated with acute lymphoblastic leukemia (P < 0.005). Antiviral prophylaxis with acyclovir significantly reduced the incidence of varicella‐zoster infection (P = 0.016).ConclusionCutaneous manifestations are common in Asian patients with leukemia, and a thorough cutaneous examination will aid in their management.