bluuebunny/crossref_metadata_2025 huggingface dataset:
Multivariate analyses of morphological traits in indigenous chicken populations of Metekel zone, Northwestern Ethiopia
Authors: Getachew Fasil , Abegaz Solomon , Assefa Abraham , Misganaw Manaye , Emshaw Yibrehu , Hailu Abebe , Tessema Misikire , Okore Cleopas
Published: January 2017

An exploratory survey to phenotypically characterize indigenous chicken populations was carried out in Metekel zone of Northwestern Ethiopia in April 2013. A total of 69 males and 244 females were sampled to record their qualitative and quantitative traits. Eight quantitative and 16 qualitative variables were measured. Sampling included three districts representing different agroecological zones. Coefficient of variation for quantitative variables ranged from 6.38 to 52.37 percent in male sample populations and 4.59–21.4 percent in females. The chi-square tests for plumage colour of the neck, ear lobe colour and skeletal variant type were highly significant (χ2< 0.05). The correct classification percentage from discriminant analysis was 93.73 and 98.41 percent for male and female sample populations, respectively, indicating the homogeneity of the chicken populations within districts. The stepwise discriminant analysis identified five variables for male and three variables for female sample populations, which had the highest discriminating power. Canonical analyses showed that differences in body measurements between indigenous chicken populations were highly significant (P <0.0001). The results obtained from on-farm performance evaluation indicated that the average age at first lay of hens, number of chicks weaned and mean number of eggs laid per bird per year were 5.5 months, 6.5, 50.1, respectively. This information will constitute the basis for further characterization and development of conservation strategies for indigenous chicken populations of Northwestern Ethiopia.
Dairy production systems and the adoption of genetic and breeding technologies in Tanzania, Kenya, India and Nicaragua
Authors: Ojango J.M.K. , Wasike C.B. , Enahoro D.K. , Okeyo A.M.
Published: January 2017

Development of the livestock industry and its role in poverty alleviation in developing countries depends on how adaptive the production systems are to changing global environmental and economic trends. This paper characterizes dairy production systems in India, Tanzania, Kenya and Nicaragua, and describes the genetic and breeding technologies that hold promise for the advancement of global development goals. The dairy value chain has been prioritized for development under the CGIAR research programme on Livestock and Fish in Tanzania (East Africa), India (South Asia) and Nicaragua (Latin America), while ILRI is involved in research on dairy development in Kenya. In all the countries, a large number of smallholder farmers operating mixed crop–livestock production systems play a significant role in dairy production. In Tanzania, Kenya and Nicaragua, milk is predominantly produced by cattle of genotypes that differ both across countries and among production systems within the same country. In India, buffaloes contribute to a larger proportion of the national milk than cattle. Information on productivity per animal and on optimal genotypes to utilize within the smallholder production systems of all the countries is however limited. Crossbreeding and artificial insemination were identified as the most widely utilized breeding and reproductive technologies. Only in Kenya is there a national organization conducting livestock recording and monitoring productivity, however, the proportion of the dairy cattle population enrolled in the recording system is small (<2.5 percent). In all the countries, enhanced and adequately planned use of breeding and reproductive technologies, complemented with the relevant infrastructure, is needed to sustainably increase dairy productivity. The capacities of actors in the dairy value chain need to be developed in order to properly implement and manage improvements.
Mitochondrial DNA hypervariable region 1 diversity in Nigerian goats
Authors: Okpeku Moses , Peters Sunday O. , Imumorin Ikhide G. , Caires Kyle C. , Sharma Varun K. , Wheto Mathew , Tamang Rakesh , Adenaike Adeyemi S. , Ozoje Michael O. , Thangaraj Kumarasamy
Published: January 2017

Goats make up the largest group of ruminant livestock in Nigeria and are strategic in bridging animal protein supply gap and improving the economy of rural households. The hypervariable region 1 (HVR1) of the caprine mitochondrial genome was investigated to better understand genetic diversity important for improving selection for animal breeding and conservation programs. We sequenced and analysed the mitochondrial DNA (mtDNA) HVR1 in 291 unrelated indigenous Nigerian goats (West African Dwarf (WAD), Red Sokoto (RSO) and Sahel (SAH)), randomly sampled from around the country, and compared them with the HVR1 sequences of 336 Indian goats and 12 other sequences in five different species in the genusCapra(C. falconeri, C. ibex nubiana, C. aegagrus, C. cylindricornisandC. sibirica). A total of 139 polymorphic sites from 291 individuals were captured in 204 haplotypes. Within and among population variations were 77.25 and 22.74 percent, respectively. Nigerian goats showed high genetic diversity (0.87) and high FST values, and separate from Indian goats and other wild species. Haplogroups in WAD separates it from RSO and SAH concomitant with a different demographic history. Clear genetic structure was found among Nigerian goat breeds with appreciable variation in mtDNA HVR1 region. This study grouped Nigerian goat breeds into two major groups suggesting two different demographic origins for Northern and Southern breeds. High genetic admixing denotes different maternal origins and in contrast to evidence from goats from Levant and Central Asia, where goats were originally domesticated.
Multivariate analysis for morphological traits of the Hamra goat population in two regions of Morocco
Authors: Hilal B. , El Otmani S. , Chentouf M. , Boujenane I.
Published: January 2017

The goal of this study was to characterize the Hamra goat population and to determine if Hamra goats of Beni Arouss and Rommani regions belong to the same population. Eleven morphometric traits of 157 Hamra animals (94 from Beni Arouss and 63 from Rommani) were used for this study. Overall, heart girth, body length, height at withers (HaW), height at rump (HS), chest depth (ChD), pelvis width (PW), chest width (CW), cannon circumference, head length (HeL), head width (HeW) and horn length (HL) of Hamra goats averaged 81.3, 61.5, 64.8, 65.3, 40.9, 19.3, 20.2, 9.67, 28.0, 26.3 and 23.4 cm, respectively. The effect of region was significant only on HaW, PW, HeL, HeW and HL, indicating certain homogeneity among goats of the two regions. Moreover, the inter region variance component ranged from 0 percent (absence of variability) for HS, CW, ChD and ChD to 18.5 percent for HeL, suggesting that the variability of body measurements between Beni Arouss and Rommani regions is very low. The factor analysis revealed four factors, which accounted for 73.5 percent of the total variance. The most discriminant variables between the two populations were HeL, HeW, PW and CW. The Mahalanobis distance between the two populations was 1.197, suggesting that there was genetic exchange between the two populations. The discriminant analysis showed that 80.9 percent of Rommani and 50.0 percent of Beni Arouss individuals were classified into their respective population. Results obtained will help in developing improvement and preservation strategies for the Hamra goat population.
Morphometric, productive and reproductive traits of indigenous goose of Bangladesh
Authors: Islam M.F. , Mia M.M. , Rahman M.A. , Bhowmik N.
Published: January 2017

The study was aimed to identify, characterize and describe the phenotypic variation of indigenous goose populations in Bangladesh. The research was conducted at Sylhet Sadar Upazilla in Sylhet district and encompassed about 141 geese (74 brown type and 67 white type). Least Square Mean ± SE of body length, wing span, shank length, beak length and head length of mature indigenous goose were 73.47 ± 0.95, 134.53 ± 1.38, 9.27 ± 0.09, 8.88 ± 0.10 and 6.42 ± 0.02 cm, respectively. Males were significantly (p< 0.01) higher than their female counterparts for all morphometric traits but no significant differences (p> 0.05) were found between two types. The body weight of indigenous goose at day old, 2-week, 1-month, 2-month and 10-month of age were 95.45 ± 0.88, 148.59 ± 1.55, 407.34 ± 7.27 gm, 1.19 ± 0.03 kg and 3.65 ± 0.06 kg, respectively. Males were significantly (p< 0.01) heavier than females in all age groups except day old gosling but no significant difference (p> 0.05) were observed for body weights between two types of goose. Egg weight, egg length, egg width, incubation period, clutch size, number of eggs in a breeding season and age at first egg were 131.85 ± 1.70 gm, 7.40 ± 0.02 cm, 5.22 ± 0.02 cm, 30.30 ± 0.07 days, 7.42 ± 0.08, 20.52 ± 0.38 and 313.22 ± 3.03 days, respectively. The number of eggs in a breeding season of brown type were significantly (p< 0.05) higher than that of white type goose. This study provides a bench mark for the morphometric traits and performance of goose in Bangladesh.
«Triple Antikoagulation – Triple Threat»
Authors: Santos Lopes Bruno , Steffel Jan
Published: January 2017

Zusammenfassung. Im klinischen Alltag sind Patienten, welche eine sogenannte «Triple Antikoagulation» benötigen häufig. Hierunter versteht man die gleichzeitige Dauerantikoagulation (zumeist aufgrund eines nicht-valvulären Vorhofflimmerns) in Kombination mit einer vorübergehenden dualen Thrombozytenaggregationshemmung (meistens im Rahmen einer koronaren Herzkrankheit/ACS und Stenting). Da die Triple Antikoagulation mit einem stark erhöhten Blutungsrisiko assoziiert ist, muss eine sorgfältige Risikostratifizierung von Fall zu Fall vorgenommen werden. Die Dauer der Triple Antikoagulation richtet sich nach einer individuellen Risiko-Nutzen Abwägung. Neueste Daten legen nahe, dass eine kürzere Triple Antikoagulation zu einem besseren Gesamtoutcome für die Patienten führt – insbesondere durch die Reduktion der Blutungskomplikationen (bis zu > 50 % relative Risikoreduktion über 12 Monate). Die neuen oralen Antikoagulantien (oder «Nicht Vitamin-K abhängigen Oralen Antikoagulantien», DOACs) sind in der modernen Behandlung des nicht-valvulären Vorhofflimmerns Standardtherapie. Obgleich speziell ausgelegte Studien zur Verwendung der DOACs im Rahmen der Triple Therapie noch fehlen, können sie hierfür in der klinischen Praxis verwendet werden. Bei Hochrisikopatienten hinsichtlich Blutungskomplikationen – oder bei absoluter Kontraindikation – stellt der interventionelle Vorhofohrverschluss eine valide Alternative zur oralen Antikoagulation dar.
Thrombophilieabklärung
Authors: Angelillo-Scherrer Anne , Nagler Michael
Published: January 2017

Zusammenfassung. Thrombophilien sind hereditäre oder erworbene Krankheitszustände, welche das Risiko für Thromboembolien erhöhen. Eine Thrombophilieabklärung wird häufig bei Patienten mit venösen Thromboembolien (VTE) sowie bei deren Angehörigen durchgeführt. Über deren Durchführung besteht allerdings keine Einigkeit, da die Ergebnisse mehrheitlich keinen Einfluss auf die Behandlung der Patienten haben. Im vorliegenden Artikel diskutieren wir die Thrombophilieabklärung in den folgenden klinische Situationen: bei provozierter bzw. nicht provozierter VTE, bei Angehörigen von Patienten mit VTE, oder bei weiblichen Verwandten von Patienten mit VTE, welche die Einnahme von Östrogenen oder eine Schwangerschaft planen. Wir stellen weiterhin eine Checkliste der zu testenden Laborparameter und den Zeitpunkt der Abklärung vor. In den meisten Fällen ist keine labormässige Abklärung empfohlen. Die Thrombophilieabklärung sollte sehr selektiv durchgeführt werden und nur, wenn sich die gewonnenen Informationen auf wichtige Entscheidungen des Patienten auswirken und die möglichen Risiken aufwiegen. Manchmal ist das Wissen um eine Thrombophilie für den Patienten wichtig, um ein Krankheitsereignis verarbeiten zu können. Eine kompetente Beratung vor der Laboruntersuchung und eine fachgerechte Interpretation der Ergebnisse sind zwingend gefordert. Eine Thrombophilieabklärung sollte nicht im Akutstadium einer VTE oder während der ersten 3 Monate einer Antikoagulation durchgeführt werden.
Modulation of carotid strain by statin therapy in atherosclerosis patients
Authors: Schaefer Christian Alexander , Blatzheim Anna Katharina , Passon Sebastian Gorgonius , Pausewang Kristin Solveig , Schahab Nadjib , Nickenig Georg , Skowasch Dirk , Schueler Robert , Hammerstingl Christoph , Pingel Simon
Published: January 2017

Abstract. Background: The beneficial effect of statin therapy on the progress of atherosclerotic disease has been demonstrated by numerous studies. Vascular strain imaging is an arising method to evaluate arterial stiffness. Our study examined whether an influence of statin therapy on the vessel wall could be detected by vascular strain imaging. Patients and methods: 88 patients with recently detected atherosclerosis underwent an angiological examination including ankle-brachial index (ABI), pulse wave index (PWI), central puls ewave velocity and duplex ultrasound. Captures for vascular strain analysis were taken in B-mode during ultrasound examination of the common carotid artery and evaluated using a workstation equipped with a speckle tracking based software. A statin therapy was recommended and after six months a follow-up examination took place. Meanwhile, the non-adherence of a group of patients (N = 18) lead to a possibility to observe statin effects on the vascular strain. Results: In the statin non-adherent group the ABI decreased significantly to a still non-pathological level (1.2 ± 0.2 vs. 1.0 ± 0.2; p = 0.016) whereas it stagnated in the adherent group (1.0 ± 0.2 vs. 1.0 ± 0.2; p = 0.383). The PWI did not differ in the non-adherent group (180.5 ± 71.9 vs. 164.4 ± 75.8; p = 0.436) but under statin therapy it decreased significantly (261.8 ± 238.6 vs. 196.4 ± 137.4; p = 0.016). In comparison to the adherent group (4.2 ± 2.0 vs. 4.0 ± 1.8; p = 0.548) under statin therapy the radial strain decreased significantly in the non-adherent group (4.7 ± 2.0 vs. 3.3 ± 1.1; p = 0.014). Conclusions: Our findings reveal a beneficial influence of statin therapy on the arterial wall detected by vascular strain analysis.
Carotid endarterectomy following thrombolysis for acute ischaemic stroke
Authors: Ahmed Naz , Kelleher Damian , Madan Manmohan , Sochart Sarita , Antoniou George A.
Published: January 2017

Abstract. Background: Insufficient evidence exists to support the safety of carotid endarterectomy (CEA) following intravenous thrombolysis (IVT) for acute ischaemic stroke. Our study aimed to report a single-centre experience of patients treated over a five-year period. Patients and methods: Departmental computerised databases were interrogated to identify patients who suffered an ischaemic stroke and subsequently underwent thrombolysis followed by CEA. Mortality and stroke within 30 days of surgery were defined as the primary outcome end points. Results: Over a five-year period, 177 out of a total of 679 carotid endarterectomies (26 %) were performed in patients presenting with acute ischaemic stroke. Twenty-five patients (14 %) received IVT prior to CEA in the form of alteplase. Sixty percent of patients were male with a mean age of 68 years. Sixteen patients (64 %) underwent CEA within 14 days of IVT and the median interval between thrombolysis and CEA was 7.5 days (range, 3–50 days). One female patient died of a further intraoperative stroke within 30 days of surgery, yielding a mortality rate of 4 %. Two patients (8 %) suffered from cardiac complications postoperatively resulting in a short high dependency unit stay. Another two patients (8 %) developed local wound complications, which were managed conservatively without the need for re-operation. The median hospital length of stay was 4.5 days (range, 1–33 days). Conclusions: Our experience indicates that CEA post-thrombolysis has a low incidence of mortality. Further high quality evidence is required before CEA can be routinely recommended following IVT for acute ischaemic stroke.
Implementation des Trainingsprogrammes Kalkulie in der Grundschule
Authors: Müller Alexander , Fritz-Stratmann Annemarie
Published: January 2017

Zusammenfassung. Viele Studien belegen die Wirksamkeit von Trainings- und Förderprogrammen unter spezifischen kontrollierten Bedingungen. Eine seit längerem bemängelte Forschungslücke besteht in der oft nicht bewiesenen Effektivität dieser Programme an dem Ort, für den sie eigentlich konzipiert wurden, die Schule, bzw. das unterrichtliche Handeln. In der hier vorliegenden Studie geht es um die Implementation des Trainingsprogrammes Kalkulie. Geplant ist ein Implementationszeitraum von drei Jahren, beteiligt sind zwei Grundschulen mit je zwei Klassen und zwei Kontrollschulen. An dieser Stelle wird über die Ergebnisse der Implementation nach einem Jahr berichtet. Die Effekte der Implementation werden anhand zweier unterschiedlicher Transferstrategien erfasst: die „partizipative Strategie“ nimmt die individuelle Umsetzung der Konzeption vor Ort, ihrer Weiterentwicklung und optimierenden Maßnahmen in den Blick, die evidenzbasierte Strategie die Veränderungen in den Schülerleistungen. Es zeigt sich, dass vor allem im ersten Jahr der Implementation partizipative Transferstrategien in den Fokus treten. Schulen beschäftigen sich vorrangig mit schulorganisatorischen Maßnahmen und Weiterbildungen der Lehrkräfte. Steigerungen in den Schülerleistungen sind nur für einen Teil der Schülerinnen und Schüler nachweisbar.
Dyskalkulie bei Erwachsenen in drei Fallbeschreibungen
Authors: Mueller Adelheid , Moeller Korbinian
Published: January 2017

Zusammenfassung. Das Thema Dyskalkulie/Rechenstörung und damit verbundene Probleme in der numerischen Entwicklung von Kindern rückt inzwischen immer mehr in den Fokus von Forschung und Bildungspraxis. Demgegenüber sind die Folgen einer Rechenstörung im Erwachsenenalter bislang nur wenig erforscht. Dementsprechend fehlen oft nicht nur diagnostische Verfahren, sondern auch evaluierte Therapieansätze. In einem ersten Blick auf Auswirkungen von Dyskalkulie im Erwachsenenalter werden im vorliegenden Artikel drei Einzelfälle beschrieben. Dabei wird deutlich, dass die Probleme der betroffenen im Umgang mit numerisch-mathematischen Inhalten nicht nur die Schullaufbahn massiv beeinflussten, sondern auch darüber hinaus bei der Berufswahl, aber auch im alltäglichen Leben zu erheblichen Schwierigkeiten führten. Über die inhaltliche Problematik hinaus zeigt sich auch, dass das wiederholte Erleben von Misserfolg, Versagen und Hilflosigkeit im Umgang mit numerisch-mathematischen Zusammenhängen auch zu nicht zu vernachlässigenden psychischen Belastungen führte. Zusammenfassend lässt sich sagen, dass in den beschriebenen Einzelfällen die vorhandene Rechenstörung das Leben der betroffenen in den verschiedensten Bereichen prägte.
Redox potential as a master variable controlling pathways of metal reduction by Geobacter sulfurreducens
Authors: Levar Caleb E , Hoffman Colleen L , Dunshee Aubrey J , Toner Brandy M , Bond Daniel R
Published: January 2017

Geobacter sulfurreducens uses at least two different pathways to transport electrons out of the inner membrane quinone pool before reducing acceptors beyond the outer membrane. When growing on electrodes poised at oxidizing potentials, the CbcL-dependent pathway operates at or below redox potentials of –0.10 V vs the standard hydrogen electrode, whereas the ImcH-dependent pathway operates only above this value. Here, we provide evidence that G. sulfurreducens also requires different electron transfer proteins for reduction of a wide range of Fe(III)- and Mn(IV)-(oxyhydr)oxides, and must transition from a high- to low-potential pathway during reduction of commonly studied soluble and insoluble metal electron acceptors. Freshly precipitated Fe(III)-(oxyhydr)oxides could not be reduced by mutants lacking the high-potential pathway. Aging these minerals by autoclaving did not change their powder X-ray diffraction pattern, but restored reduction by mutants lacking the high-potential pathway. Mutants lacking the low-potential, CbcL-dependent pathway had higher growth yields with both soluble and insoluble Fe(III). Together, these data suggest that the ImcH-dependent pathway exists to harvest additional energy when conditions permit, and CbcL switches on to allow respiration closer to thermodynamic equilibrium conditions. With evidence of multiple pathways within a single organism, the study of extracellular respiration should consider not only the crystal structure or solubility of a mineral electron acceptor, but rather the redox potential, as this variable determines the energetic reward affecting reduction rates, extents, and final microbial growth yields in the environment.
Patterns of bacterial diversity in the marine planktonic particulate matter continuum
Authors: Mestre Mireia , Borrull Encarna , Sala M Montserrat , Gasol Josep M
Published: January 2017

Depending on their relationship with the pelagic particulate matter, planktonic prokaryotes have traditionally been classified into two types of communities: free-living (FL) or attached (ATT) to particles, and are generally separated using only one pore-size filter in a differential filtration. Nonetheless, particulate matter in the oceans appears in a continuum of sizes. Here we separated this continuum into six discrete size-fractions, from 0.2 to 200 μm, and described the prokaryotes associated to each of them. Each size-fraction presented different bacterial communities, with a range of 23–42% of unique (OTUs) in each size-fraction, supporting the idea that they contained distinct types of particles. An increase in richness was observed from the smallest to the largest size-fractions, suggesting that increasingly larger particles contributed new niches. Our results show that a multiple size-fractionation provides a more exhaustive description of the bacterial diversity and community structure than the use of only one filter. In addition, and based on our results, we propose an alternative to the dichotomy of FL or ATT lifestyles, in which we differentiate the taxonomic groups with preference for the smaller fractions, those that do not show preferences for small or large fractions, and those that preferentially appear in larger fractions.
Therapeutic microparticles functionalized with biomimetic cardiac stem cell membranes and secretome
Authors: Tang Junnan , Shen Deliang , Caranasos Thomas George , Wang Zegen , Vandergriff Adam C. , Allen Tyler A. , Hensley Michael Taylor , Dinh Phuong-Uyen , Cores Jhon , Li Tao-Sheng , Zhang Jinying , Kan Quancheng , Cheng Ke
Published: January 2017

Stem cell therapy represents a promising strategy in regenerative medicine. However, cells need to be carefully preserved and processed before usage. In addition, cell transplantation carries immunogenicity and/or tumourigenicity risks. Mounting lines of evidence indicate that stem cells exert their beneficial effects mainly through secretion (of regenerative factors) and membrane-based cell–cell interaction with the injured cells. Here, we fabricate a synthetic cell-mimicking microparticle (CMMP) that recapitulates stem cell functions in tissue repair. CMMPs carry similar secreted proteins and membranes as genuine cardiac stem cells do. In a mouse model of myocardial infarction, injection of CMMPs leads to the preservation of viable myocardium and augmentation of cardiac functions similar to cardiac stem cell therapy. CMMPs (derived from human cells) do not stimulate T-cell infiltration in immuno-competent mice. In conclusion, CMMPs act as ‘synthetic stem cells’ which mimic the paracrine and biointerfacing activities of natural stem cells in therapeutic cardiac regeneration.
Ti3C2 MXene co-catalyst on metal sulfide photo-absorbers for enhanced visible-light photocatalytic hydrogen production
Authors: Ran Jingrun , Gao Guoping , Li Fa-Tang , Ma Tian-Yi , Du Aijun , Qiao Shi-Zhang
Published: January 2017

Scalable and sustainable solar hydrogen production through photocatalytic water splitting requires highly active and stable earth-abundant co-catalysts to replace expensive and rare platinum. Here we employ density functional theory calculations to direct atomic-level exploration, design and fabrication of a MXene material, Ti3C2 nanoparticles, as a highly efficient co-catalyst. Ti3C2 nanoparticles are rationally integrated with cadmium sulfide via a hydrothermal strategy to induce a super high visible-light photocatalytic hydrogen production activity of 14,342 μmol h−1g−1 and an apparent quantum efficiency of 40.1% at 420 nm. This high performance arises from the favourable Fermi level position, electrical conductivity and hydrogen evolution capacity of Ti3C2 nanoparticles. Furthermore, Ti3C2 nanoparticles also serve as an efficient co-catalyst on ZnS or ZnxCd1−xS. This work demonstrates the potential of earth-abundant MXene family materials to construct numerous high performance and low-cost photocatalysts/photoelectrodes.
Properties of the exotic metastable ST12 germanium allotrope
Authors: Zhao Zhisheng , Zhang Haidong , Kim Duck Young , Hu Wentao , Bullock Emma S. , Strobel Timothy A.
Published: January 2017

The optical and electronic properties of semiconducting materials are of great importance to a vast range of contemporary technologies. Diamond-cubic germanium is a well-known semiconductor, although other ‘exotic’ forms may possess distinct properties. In particular, there is currently no consensus for the band gap and electronic structure of ST12-Ge (tP12, P43212) due to experimental limitations in sample preparation and varying theoretical predictions. Here we report clear experimental and theoretical evidence for the intrinsic properties of ST12-Ge, including the first optical measurements on bulk samples. Phase-pure bulk samples of ST12-Ge were synthesized, and the structure and purity were verified using powder X-ray diffraction, transmission electron microscopy, Raman and wavelength/energy dispersive X-ray spectroscopy. Optical measurements indicate that ST12-Ge is a semiconductor with an indirect band gap of 0.59 eV and a direct optical transition at 0.74 eV, which is in good agreement with electrical transport measurements and our first-principles calculations.
Cannabinoid CB2 receptor ligand profiling reveals biased signalling and off-target activity
Authors: Soethoudt Marjolein , Grether Uwe , Fingerle Jürgen , Grim Travis W. , Fezza Filomena , de Petrocellis Luciano , Ullmer Christoph , Rothenhäusler Benno , Perret Camille , van Gils Noortje , Finlay David , MacDonald Christa , Chicca Andrea , Gens Marianela Dalghi , Stuart Jordyn , de Vries Henk , Mastrangelo Nicolina , Xia Lizi , Alachouzos Georgios , Baggelaar Marc P. , Martella Andrea , Mock Elliot D. , Deng Hui , Heitman Laura H. , Connor Mark , Di Marzo Vincenzo , Gertsch Jürg , Lichtman Aron H. , Maccarrone Mauro , Pacher Pal , Glass Michelle , van der Stelt Mario
Published: January 2017

The cannabinoid CB2 receptor (CB2R) represents a promising therapeutic target for various forms of tissue injury and inflammatory diseases. Although numerous compounds have been developed and widely used to target CB2R, their selectivity, molecular mode of action and pharmacokinetic properties have been poorly characterized. Here we report the most extensive characterization of the molecular pharmacology of the most widely used CB2R ligands to date. In a collaborative effort between multiple academic and industry laboratories, we identify marked differences in the ability of certain agonists to activate distinct signalling pathways and to cause off-target effects. We reach a consensus that HU910, HU308 and JWH133 are the recommended selective CB2R agonists to study the role of CB2R in biological and disease processes. We believe that our unique approach would be highly suitable for the characterization of other therapeutic targets in drug discovery research.
Small RNA zippers lock miRNA molecules and block miRNA function in mammalian cells
Authors: Meng Lingyu , Liu Cuicui , Lü Jinhui , Zhao Qian , Deng Shengqiong , Wang Guangxue , Qiao Jing , Zhang Chuyi , Zhen Lixiao , Lu Ying , Li Wenshu , Zhang Yuzhen , Pestell Richard G. , Fan Huiming , Chen Yi-Han , Liu Zhongmin , Yu Zuoren
Published: January 2017

MicroRNAs (miRNAs) loss-of-function phenotypes are mainly induced by chemically modified antisense oligonucleotides. Here we develop an alternative inhibitor for miRNAs, termed ‘small RNA zipper’. It is designed to connect miRNA molecules end to end, forming a DNA–RNA duplex through a complementary interaction with high affinity, high specificity and high stability. Two miRNAs, miR-221 and miR-17, are tested in human breast cancer cell lines, demonstrating the 70∼90% knockdown of miRNA levels by 30–50 nM small RNA zippers. The miR-221 zipper shows capability in rescuing the expression of target genes of miR-221 and reversing the oncogenic function of miR-221 in breast cancer cells. In addition, we demonstrate that the miR-221 zipper attenuates doxorubicin resistance with higher efficiency than anti-miR-221 in human breast cancer cells. Taken together, small RNA zippers are a miRNA inhibitor, which can be used to induce miRNA loss-of-function phenotypes and validate miRNA target genes.
A niobium and tantalum co-doped perovskite cathode for solid oxide fuel cells operating below 500 °C
Authors: Li Mengran , Zhao Mingwen , Li Feng , Zhou Wei , Peterson Vanessa K. , Xu Xiaoyong , Shao Zongping , Gentle Ian , Zhu Zhonghua
Published: January 2017

The slow activity of cathode materials is one of the most significant barriers to realizing the operation of solid oxide fuel cells below 500 °C. Here we report a niobium and tantalum co-substituted perovskite SrCo0.8Nb0.1Ta0.1O3−δ as a cathode, which exhibits high electroactivity. This cathode has an area-specific polarization resistance as low as ∼0.16 and ∼0.68 Ω cm2 in a symmetrical cell and peak power densities of 1.2 and 0.7 W cm−2 in a Gd0.1Ce0.9O1.95-based anode-supported fuel cell at 500 and 450 °C, respectively. The high performance is attributed to an optimal balance of oxygen vacancies, ionic mobility and surface electron transfer as promoted by the synergistic effects of the niobium and tantalum. This work also points to an effective strategy in the design of cathodes for low-temperature solid oxide fuel cells.
Cell division orientation is coupled to cell–cell adhesion by the E-cadherin/LGN complex
Authors: Gloerich Martijn , Bianchini Julie M. , Siemers Kathleen A. , Cohen Daniel J. , Nelson W. James
Published: January 2017

Both cell–cell adhesion and oriented cell division play prominent roles in establishing tissue architecture, but it is unclear how they might be coordinated. Here, we demonstrate that the cell–cell adhesion protein E-cadherin functions as an instructive cue for cell division orientation. This is mediated by the evolutionarily conserved LGN/NuMA complex, which regulates cortical attachments of astral spindle microtubules. We show that LGN, which adopts a three-dimensional structure similar to cadherin-bound catenins, binds directly to the E-cadherin cytosolic tail and thereby localizes at cell–cell adhesions. On mitotic entry, NuMA is released from the nucleus and competes LGN from E-cadherin to locally form the LGN/NuMA complex. This mediates the stabilization of cortical associations of astral microtubules at cell–cell adhesions to orient the mitotic spindle. Our results show how E-cadherin instructs the assembly of the LGN/NuMA complex at cell–cell contacts, and define a mechanism that couples cell division orientation to intercellular adhesion.
Saturated palmitic acid induces myocardial inflammatory injuries through direct binding to TLR4 accessory protein MD2
Authors: Wang Yi , Qian Yuanyuan , Fang Qilu , Zhong Peng , Li Weixin , Wang Lintao , Fu Weitao , Zhang Yali , Xu Zheng , Li Xiaokun , Liang Guang
Published: January 2017

Obesity increases the risk for a number of diseases including cardiovascular diseases and type 2 diabetes. Excess saturated fatty acids (SFAs) in obesity play a significant role in cardiovascular diseases by activating innate immunity responses. However, the mechanisms by which SFAs activate the innate immune system are not fully known. Here we report that palmitic acid (PA), the most abundant circulating SFA, induces myocardial inflammatory injury through the Toll-like receptor 4 (TLR4) accessory protein MD2 in mouse and cell culture experimental models.Md2knockout mice are protected against PA- and high-fat diet-induced myocardial injury. Studies of cell surface binding, cell-free protein–protein interactions and molecular docking simulations indicate that PA directly binds to MD2, supporting a mechanism by which PA activates TLR4 and downstream inflammatory responses. We conclude that PA is a crucial contributor to obesity-associated myocardial injury, which is likely regulated via its direct binding to MD2.
Cleavage of DFNA5 by caspase-3 during apoptosis mediates progression to secondary necrotic/pyroptotic cell death
Authors: Rogers Corey , Fernandes-Alnemri Teresa , Mayes Lindsey , Alnemri Diana , Cingolani Gino , Alnemri Emad S.
Published: January 2017

Apoptosis is a genetically regulated cell suicide programme mediated by activation of the effector caspases 3, 6 and 7. If apoptotic cells are not scavenged, they progress to a lytic and inflammatory phase called secondary necrosis. The mechanism by which this occurs is unknown. Here we show that caspase-3 cleaves the GSDMD-related protein DFNA5 after Asp270 to generate a necrotic DFNA5-N fragment that targets the plasma membrane to induce secondary necrosis/pyroptosis. Cells that express DFNA5 progress to secondary necrosis, when stimulated with apoptotic triggers such as etoposide or vesicular stomatitis virus infection, but disassemble into small apoptotic bodies when DFNA5 is deleted. Our findings identify DFNA5 as a central molecule that regulates apoptotic cell disassembly and progression to secondary necrosis, and provide a molecular mechanism for secondary necrosis. Because DFNA5-induced secondary necrosis and GSDMD-induced pyroptosis are dependent on caspase activation, we propose that they are forms of programmed necrosis.
Structural characterisation of the fatty acid biosynthesis enzyme FabF from the pathogen Listeria monocytogenes
Authors: Soares da Costa Tatiana P. , Nanson Jeffrey D. , Forwood Jade K.
Published: January 2017

Development of new antimicrobial agents is required against the causative agent for listeriosis, Listeria monocytogenes, as the number of drug resistant strains continues to increase. A promising target is the β-ketoacyl-acyl carrier protein synthase FabF, which participates in the catalysis of fatty acid synthesis and elongation, and is required for the production of phospholipid membranes, lipoproteins, and lipopolysaccharides. In this study, we report the 1.35 Å crystal structure of FabF from L. monocytogenes, providing an excellent platform for the rational design of novel inhibitors. By comparing the structure of L. monocytogenes FabF with other published bacterial FabF structures in complex with known inhibitors and substrates, we highlight conformational changes within the active site, which will need to be accounted for during drug design and virtual screening studies. This high-resolution structure of FabF represents an important step in the development of new classes of antimicrobial agents targeting FabF for the treatment of listeriosis.
Protective effects of intercalated disk protein afadin on chronic pressure overload-induced myocardial damage
Authors: Zankov Dimitar P. , Shimizu Akio , Tanaka-Okamoto Miki , Miyoshi Jun , Ogita Hisakazu
Published: January 2017

Adhesive intercellular connections at cardiomyocyte intercalated disks (IDs) support contractile force and maintain structural integrity of the heart muscle. Disturbances of the proteins at IDs deteriorate cardiac function and morphology. An adaptor protein afadin, one of the components of adherens junctions, is expressed ubiquitously including IDs. At present, the precise role of afadin in cardiac physiology or disease is unknown. To explore this, we generated conditional knockout (cKO) mice with cardiomyocyte-targeted deletion of afadin. Afadin cKO mice were born according to the expected Mendelian ratio and have no detectable changes in cardiac phenotype. On the other hand, chronic pressure overload induced by transverse aortic constriction (TAC) caused systolic dysfunction, enhanced fibrogenesis and apoptosis in afadin cKO mice. Afadin deletion increased macrophage infiltration and monocyte chemoattractant protein-1 expression, and suppressed transforming growth factor (TGF) β receptor signaling early after TAC procedure. Afadin also associated with TGFβ receptor I at IDs. Pharmacological antagonist of TGFβ receptor I (SB431542) augmented mononuclear infiltration and fibrosis in the hearts of TAC-operated control mice. In conclusion, afadin is a critical molecule for cardiac protection against chronic pressure overload. The beneficial effects are likely to be a result from modulation of TGFβ receptor signaling pathways by afadin.
Correction: Corrigendum: Genetic Epidemiology of Glucose-6-Phosphate Dehydrogenase Deficiency in the Arab World
Authors: Doss C. George Priya , Alasmar Dima R. , Bux Reem I. , Sneha P. , Bakhsh Fadheela Dad , Al-Azwani Iman , El Bekay Rajaa , Zayed Hatem
Published: January 2017

Scientific Reports 6: Article number: 37284; published online: 17 November 2016; updated: 03 January 2017 The original version of this Article contained an error in the title of the paper, where “Genetic Epidemiology of Glucose-6-Phosphate Dehydrogenase Deficiency in the Arab World” was incorrectly given as “Genetic Epidemiology of Glucose-6-Dehydrogenase Deficiency in the Arab World”.
Cu2ZnSnS4/MoS2-Reduced Graphene Oxide Heterostructure: Nanoscale Interfacial Contact and Enhanced Photocatalytic Hydrogen Generation
Authors: Ha Enna , Liu Wei , Wang Luyang , Man Ho-Wing , Hu Liangsheng , Tsang Shik Chi Edman , Chan Chris Tsz-Leung , Kwok Wai-Ming , Lee Lawrence Yoon Suk , Wong Kwok-Yin
Published: January 2017

Hydrogen generation from water using noble metal-free photocatalysts presents a promising platform for renewable and sustainable energy. Copper-based chalcogenides of earth-abundant elements, especially Cu2ZnSnS4 (CZTS), have recently arisen as a low-cost and environment-friendly material for photovoltaics and photocatalysis. Herein, we report a new heterostructure consisting of CZTS nanoparticles anchored onto a MoS2-reduced graphene oxide (rGO) hybrid. Using a facile two-step method, CZTS nanoparticles were in situ grown on the surface of MoS2-rGO hybrid, which generated high density of nanoscale interfacial contact between CZTS and MoS2-rGO hybrid. The photoexcited electrons of CZTS can be readily transported to MoS2 through rGO backbone, reducing the electron-hole pair recombination. In photocatalytic hydrogen generation under visible light irradiation, the presence of MoS2-rGO hybrids enhanced the hydrogen production rate of CZTS by 320%, which can be attributed to the synergetic effect of increased charge separation by rGO and more catalytically active sites from MoS2. Furthermore, this CZTS/MoS2-rGO heterostructure showed much higher photocatalytic activity than both Au and Pt nanoparticle-decorated CZTS (Au/CZTS and Pt/CZTS) photocatalysts, indicating the MoS2-rGO hybrid is a better co-catalyst for photocatalytic hydrogen generation than the precious metal. The CZTS/MoS2-rGO system also demonstrated stable photocatalytic activity for a continuous 20 h reaction.
MiR-218 Induces Neuronal Differentiation of ASCs in a Temporally Sequential Manner with Fibroblast Growth Factor by Regulation of the Wnt Signaling Pathway
Authors: Hu Feihu , Sun Bo , Xu Peng , Zhu Yanliang , Meng Xian-Hui , Teng Gao-Jun , Xiao Zhong-Dang
Published: January 2017

Differentiation of neural lineages from mesenchymal stem cells has raised the hope of generating functional cells as seed cells for nerve tissue engineering. As important gene regulators, microRNAs (miRNAs) have been speculated to play a vital role in accelerating stem cell differentiation and repairing neuron damage. However, miRNA roles in directing differentiation of stem cells in current protocols are underexplored and the mechanisms of miRNAs as regulators of neuronal differentiation remain ambiguous. In this study, we have determined that miR-218 serves as crucial constituent regulator in neuronal differentiation of adipose stem cells (ASCs) through Wnt signaling pathway based on comprehensive annotation of miRNA sequencing data. Moreover, we have also discovered that miR-218 and Fibroblast Growth Factor-2 (FGF2) modulate neuronal differentiation in a sequential manner. These findings provide additional understanding of the mechanisms regulating stem cell neuronal differentiation as well as a new method for neural lineage differentiation of ASCs.
Randomized trial on the effects of a combined physical/cognitive training in aged MCI subjects: the Train the Brain study
Authors:   Train the Brain Consortium, Maffei L. , Picano E. , Andreassi M. G. , Angelucci A. , Baldacci F. , Baroncelli L. , Begenisic T. , Bellinvia P. F. , Berardi N. , Biagi L. , Bonaccorsi J. , Bonanni E. , Bonuccelli U. , Borghini A. , Braschi C. , Broccardi M. , Bruno R. M. , Caleo M. , Carlesi C. , Carnicelli L. , Cartoni G. , Cecchetti L. , Cenni M. C. , Ceravolo R. , Chico L. , Cintoli S. , Cioni G. , Coscia M. , Costa M. , D’Angelo G. , D’Ascanio P. , Nes M. De , Turco S. Del , Coscio E. Di , Galante M. Di , Lascio N. di , Faita F. , Falorni I. , Faraguna U. , Fenu A. , Fortunato L. , Franco R. , Gargani L. , Gargiulo R. , Ghiadoni L. , Giorgi F. S. , Iannarella R. , Iofrida C. , Kusmic C. , Limongi F. , Maestri M. , Maffei M. , Maggi S. , Mainardi M. , Mammana L. , Marabotti A. , Mariotti V. , Melissari E. , Mercuri A. , Micera S. , Molinaro S. , Narducci R. , Navarra T. , Noale M. , Pagni C. , Palumbo S. , Pasquariello R. , Pellegrini S. , Pietrini P. , Pizzorusso T. , Poli A. , Pratali L. , Retico A. , Ricciardi E. , Rota G. , Sale A. , Sbrana S. , Scabia G. , Scali M. , Scelfo D. , Sicari R. , Siciliano G. , Stea F. , Taddei S. , Tognoni G. , Tonacci A. , Tosetti M. , Turchi S. , Volpi L.
Published: January 2017

Age-related cognitive impairment and dementia are an increasing societal burden. Epidemiological studies indicate that lifestyle factors, e.g. physical, cognitive and social activities, correlate with reduced dementia risk; moreover, positive effects on cognition of physical/cognitive training have been found in cognitively unimpaired elders. Less is known about effectiveness and action mechanisms of physical/cognitive training in elders already suffering from Mild Cognitive Impairment (MCI), a population at high risk for dementia. We assessed in 113 MCI subjects aged 65–89 years, the efficacy of combined physical-cognitive training on cognitive decline, Gray Matter (GM) volume loss and Cerebral Blood Flow (CBF) in hippocampus and parahippocampal areas, and on brain-blood-oxygenation-level-dependent (BOLD) activity elicited by a cognitive task, measured by ADAS-Cog scale, Magnetic Resonance Imaging (MRI), Arterial Spin Labeling (ASL) and fMRI, respectively, before and after 7 months of training vs. usual life. Cognitive status significantly decreased in MCI-no training and significantly increased in MCI-training subjects; training increased parahippocampal CBF, but no effect on GM volume loss was evident; BOLD activity increase, indicative of neural efficiency decline, was found only in MCI-no training subjects. These results show that a non pharmacological, multicomponent intervention improves cognitive status and indicators of brain health in MCI subjects.
Magnetic Resonance Microscopy (MRM) of Single Mammalian Myofibers and Myonuclei
Authors: Lee Choong H. , Bengtsson Niclas , Chrzanowski Stephen M. , Flint Jeremy J. , Walter Glenn A. , Blackband Stephen J.
Published: January 2017

Recently, the first magnetic resonance microscopy (MRM) images at the cellular level in isolated mammalian brain tissues were obtained using microsurface coils. These methods can elucidate the cellular origins of MR signals and describe how these signals change over the course of disease progression and therapy. In this work, we explore the capability of these microimaging techniques to visualize mouse muscle fibers and their nuclei. Isolated myofibers expressing lacZ were imaged with and without a stain for β-galactosidase activity (S-Gal + ferric ammonium citrate) that produces both optical and MR contrast. We found that MRM can be used to image single myofibers with 6-μm resolution. The ability to image single myofibers will serve as a valuable tool to study MR properties attributed to healthy and myopathic cells. The ability to image nuclei tagged with MR/Optical gene markers may also find wide use in cell lineage MRI studies.
Out-of-hospital cardiac arrest risk attributable to temperature in Japan
Authors: Onozuka Daisuke , Hagihara Akihito
Published: January 2017

Several studies have estimated the associations between extreme temperatures and mortality and morbidity; however, few have investigated the attributable fraction for a wide range of temperatures on the risk of out-of-hospital cardiac arrest (OHCA). We obtained daily records of OHCA cases in the 47 Japanese prefectures between 2005 and 2014. We examined the relationship between OHCA and temperature for each prefecture using a Poisson regression model combined with a distributed lag non-linear model. The estimated prefecture-specific associations were pooled at the nationwide level using a multivariate random-effect meta-analysis. A total of 659,752 cases of OHCA of presumed-cardiac origin met the inclusion criteria. Overall, 23.93% (95% empirical confidence interval [eCI]: 20.15–26.19) of OHCA was attributable to temperature. The attributable fraction to low temperatures was 23.64% (95% eCI: 19.76–25.87), whereas that of high temperatures was 0.29% (95% eCI: 0.21–0.35). The attributable fraction for OHCA was related to moderate low temperature with an overall estimate of 21.86% (95% eCI: 18.10–24.21). Extreme temperatures were responsible for a small fraction. The majority of temperature-related OHCAs were attributable to lower temperatures. The attributable risk of extremely low and high temperatures was markedly lower than that of moderate temperatures.
High diversity of airborne fungi in the hospital environment as revealed by meta-sequencing-based microbiome analysis
Authors: Tong Xunliang , Xu Hongtao , Zou Lihui , Cai Meng , Xu Xuefeng , Zhao Zuotao , Xiao Fei , Li Yanming
Published: January 2017

Invasive fungal infections acquired in the hospital have progressively emerged as an important cause of life-threatening infection. In particular, airborne fungi in hospitals are considered critical pathogens of hospital-associated infections. To identify the causative airborne microorganisms, high-volume air samplers were utilized for collection, and species identification was performed using a culture-based method and DNA sequencing analysis with the Illumina MiSeq and HiSeq 2000 sequencing systems. Few bacteria were grown after cultivation in blood agar. However, using microbiome sequencing, the relative abundance of fungi, Archaea species, bacteria and viruses was determined. The distribution characteristics of fungi were investigated using heat map analysis of four departments, including the Respiratory Intensive Care Unit, Intensive Care Unit, Emergency Room and Outpatient Department. The prevalence of Aspergillus among fungi was the highest at the species level, approximately 17% to 61%, and the prevalence of Aspergillus fumigatus among Aspergillus species was from 34% to 50% in the four departments. Draft genomes of microorganisms isolated from the hospital environment were obtained by sequence analysis, indicating that investigation into the diversity of airborne fungi may provide reliable results for hospital infection control and surveillance.