bluuebunny/crossref_metadata_2025 huggingface dataset:
The basis of clinicopathological heterogeneity in TDP-43 proteinopathy
Authors: Kawakami Ito , Arai Tetsuaki , Hasegawa Masato
Published: September 2019

Transactive response DNA-binding protein 43 kDa (TDP-43) was identified as a major disease-associated component in the brain of patients with amyotrophic lateral sclerosis (ALS), as well as the largest subset of patients with frontotemporal lobar degeneration with ubiquitinated inclusions (FTLD-U), which characteristically exhibits cytoplasmic inclusions that are positive for ubiquitin but negative for tau and α-synuclein. TDP-43 pathology occurs in distinct brain regions, involves disparate brain networks, and features accumulation of misfolded proteins in various cell types and in different neuroanatomical regions. The clinical phenotypes of ALS and FTLD-TDP (FTLD with abnormal intracellular accumulations of TDP-43) correlate with characteristic distribution patterns of the underlying pathology across specific brain regions with disease progression. Recent studies support the idea that pathological protein spreads from neuron to neuron via axonal transport in a hierarchical manner. However, little is known to date about the basis of the selective cellular and regional vulnerability, although the information would have important implications for the development of targeted and personalized therapies. Here, we aim to summarize recent advances in the neuropathology, genetics and animal models of TDP-43 proteinopathy, and their relationship to clinical phenotypes for the underlying selective neuronal and regional susceptibilities. Finally, we attempt to integrate these findings into the emerging picture of TDP-43 proteinopathy, and to highlight key issues for future therapy and research.
Peripheral inflammatory markers and clinical correlations in patients with frontotemporal lobar degeneration with and without the C9orf72 repeat expansion
Authors: Katisko Kasper , Solje Eino , Korhonen Paula , Jääskeläinen Olli , Loppi Sanna , Hartikainen Päivi , Koivisto Anne M. , Kontkanen Aleksi , Korhonen Ville E. , Helisalmi Seppo , Malm Tarja , Herukka Sanna-Kaisa , Remes Anne M. , Haapasalo Annakaisa
Published: September 2019

In this study, our aim was to evaluate potential peripheral inflammatory changes in frontotemporal lobar degeneration (FTLD) patients carrying or not the C9orf72 repeat expansion. To this end, levels of several inflammatory markers (MCP-1, RANTES, IL-10, IL-17A, IL-12p, IFN-γ, IL-1β, IL-8, and hs-CRP) and blood cells counts in plasma and/or serum of FTLD patients (N = 98) with or without the C9orf72 repeat expansion were analyzed. In addition, we evaluated whether the analyzed peripheral inflammatory markers correlated with disease progression or distinct clinical phenotypes under the heterogenous FTLD spectrum. Elevated levels of pro-inflammatory RANTES or MCP-1 and decreased levels of anti-inflammatory IL-10 were found to associate with Parkinsonism and a more rapid disease progression, indicated by longitudinal measurements of either MMSE or ADCS-ADL decline. These findings were observed in the total cohort in general, whereas the C9orf72 repeat expansion carriers showed only slight differences in IL-10 and hemoglobin levels compared to non-carriers. Furthermore, these C9orf72 repeat expansion-associated differences were observed mostly in male subjects. The females in general showed elevated levels of several pro-inflammatory markers compared to males regardless of the C9orf72 genotype. Our study suggests that pro-inflammatory changes observed in the early symptomatic phase of FTLD are associated with distinct clinical profiles and a more rapid disease progression, and that the C9orf72 repeat expansion and gender may also affect the inflammatory profile in FTLD.
Geothermisches Nutzungspotenzial der Buntsandstein- und Keuperaquifere im Nordosten Bayerns mit Fokus auf tiefe Aquiferspeicher
Authors: Kunkel Cindy , Agemar Thorsten , Stober Ingrid
Published: September 2019

Die mitteltiefen und tiefen geothermischen Ressourcen in Deutschland sind begrenzt auf Mittel- und Niedrigenthalpiesysteme. Diese werden vorwiegend für balneologische Anwendungen, Fern- und Raumwärme, sowie an zurzeit neun Standorten auch zur Stromgewinnung genutzt. Diese Studie befasst sich mit den gespannten Aquiferen im Nordosten Bayerns, die sowohl für die Balneologie als auch zur Energiespeicherung genutzt werden können.

Auf Grundlage neu ausgewerteter Daten aus Pumptests und Förderdaten wurden die Durchlässigkeitsbeiwerte und Transmissivitäten der beiden Hauptaquifere Keuper und Buntsandstein mit einer großflächigen Verbreitung für mitteltiefe und tiefe geothermische Anwendungen ab 100 m auskartiert. Zudem fließen Temperaturabschätzungen sowie Angaben über die Tiefenlage der beiden Festgesteinsaquifere (Keuper 100 bis 650 m, Buntsandstein 100 bis 1400 m) mit ein. Die Ergebnisse werden in Form von Karten zur Verteilung von Durchlässigkeitsbeiwerten, Transmissivitäten und den Temperaturabschätzungen dargestellt und in das geothermische Informationssystem GeotIS (https://www.geotis.de) integriert.

An ca. 80 % aller 243 untersuchten Lokalitäten lassen die vorhandenen Daten darauf schließen, dass die Aquifere für eine geothermische Nutzung geeignet sind. Beim Keuper liegen sogar über 90 % der 155 Transmissivitätswerte im Bereich für eine entsprechende Nutzung des Untergrundes. Die neu erstellten Karten ersetzen aber keine Machbarkeitsstudie für Geothermieprojekte, da eine detaillierte geologische Vorerkundung unabdingbar für die Planung einer geothermischen Untergrundnutzung ist.
Statement for gastroesophageal reflux disease after peroral endoscopic myotomy from an international multicenter experience
Authors: Inoue Haruhiro , Shiwaku Hironari , Kobayashi Yasutoshi , Chiu Philip W. Y. , Hawes Robert H. , Neuhaus Horst , Costamagna Guido , Stavropoulos Stavros N. , Fukami Norio , Seewald Stefan , Onimaru Manabu , Minami Hitomi , Tanaka Shinwa , Shimamura Yuto , Santi Esperanza Grace , Grimes Kevin , Tajiri Hisao
Published: September 2019

It has been 10 years since peroral endoscopic myotomy (POEM) was reported for the first time, and POEM has currently become the standard treatment for achalasia and related disorders globally because it is less invasive and has a higher curative effect than conventional therapeutic methods. However, there are limited studies comparing the long-term outcomes of POEM with those of conventional therapeutic methods, particularly in the occurrence of gastroesophageal reflux disease (GERD) after therapy. With this background, we held a consensus meeting to discuss the pathophysiology and management of GERD after POEM based on published papers and experiences of each expert and to discuss the prevention of GERD and dealing with anti-acid drug refractory GERD. This meeting was held on April 27, 2018 in Tokyo to establish statements and finalize the recommendations using the modified Delphi method. This manuscript presents eight statements regarding GERD after POEM.
Conceptual confusion in the chemistry curriculum: exemplifying the problematic nature of representing chemical concepts as target knowledge
Authors: Taber Keith S.
Published: September 2019

This paper considers the nature of a curriculum as presented in formal curriculum documents, and the inherent difficulties of representing formal disciplinary knowledge in a prescription for teaching and learning. The general points are illustrated by examining aspects of a specific example, taken from the chemistry subject content included in the science programmes of study that are part of the National Curriculum in England (an official document published by the UK government). In particular, it is suggested that some statements in the official curriculum document are problematic if we expect a curriculum to represent canonical disciplinary knowledge in an unambiguous and authentic manner. The paper examines the example of the requirement for English school children to be taught that chemical reactions take place in only three different ways (i.e., proton transfer; electron transfer; electron sharing) and considers how this might be interpreted in terms of canonical chemistry and within the wider context of other curriculum statements, in order to make sense of neutralisation and precipitation reactions. It is argued that although target knowledge that is set out as the focus of teaching and learning cannot be identical to disciplinary knowledge, the English National Curriculum offers a representation of chemistry which distorts and confuses canonical ideas. It is suggested that the process of representing the disciplinary knowledge of chemistry as curriculum specifications is worthy of more scholarly attention.
Thermography assessment of spastic lower limb in patients after cerebral stroke undergoing rehabilitation
Authors: Nowak Iga , Mraz Maciej , Mraz Małgorzata
Published: September 2019

Stroke contributes to disability in adulthood. The assessment of the degree of spasticity is one of the basic methods of patient examination after stroke and is used for monitoring rehabilitative outcomes; however, no optimal scale for the unambiguous assessment of spasticity exists. Our study aimed to assess the usefulness of thermography in measuring the effects of rehabilitation in stroke patients’ spastic hemiparesis. In this prospective, single-center study, 40 stroke patients with a mean age of 60.6 ± 5.5 years were enrolled. All suffered from hemiparesis. Surface temperature of the shank was assessed with infrared thermography; degree of independence with the Barthel Index; and muscle tone with the Modified Ashworth Scale. A comparison of temperature between the spastic and non-spastic posterior part of the shank was conducted. Temperature changes, severity of spasticity, and gait pattern were evaluated and compared at baseline and after 6 weeks of rehabilitation. All patients completed a rehabilitation program. The baseline temperature in the spastic extremity was significantly lower than in the normal extremity (mean temperature 28.93 °C vs 30.20 °C; p = 0.0001). After rehabilitation, the temperature in the spastic extremity increased significantly; however, the significant difference between the two extremities persisted (mean temperature 29.76 °C vs 30.54 °C; p = 0.0001). After rehabilitation, spasticity in affected extremity decreased significantly (p > 0.001). Additionally, an improvement in gait pattern was observed. We conclude that thermography proved to be useful in the assessment of rehabilitation effects in stroke patients with spastic hemiparesis; thus, it can be considered an additional tool for determining impaired muscle tone in patients with spasticity.
No deterioration in health-related quality of life in patients with axial spondyloarthritis followed for 5 years in ordinary outpatient clinics in the biological treatment era
Authors: Rohde Gudrun , Berg Kari Hansen , Pripp Are Hugo , Prøven Anne , Haugeberg Glenn
Published: September 2019

Background

Axial spondyloarthritis (ax-SpA) causes pain, fatigue, stiffness, loss of physical function and impaired health-related quality of life (HRQOL).

Aims

The study aimed to explore the changes in HRQOL over 5 years in patients with ax-SpA and to identify baseline predictors associated with changes in HRQOL assessed using three HRQOL measures.

Methods

Demographic, disease, medication and HRQOL data were collected at baseline and at 5-year follow-up. HRQOL was assessed using SF-6D, 15D and SF-36. Analyses involved McNemar, independent paired t tests and multiple regression.

Results

In the 240 (women 31%, men 69%) ax-SpA patients assessed (mean age 46 years), measures reflecting disease activity decreased and co-morbidities increased, and more patients were treated with biologic drugs during follow-up. No deterioration in HRQOL was observed between baseline and 5-year follow-up; indeed, there was a significant increase in SF-6D and SF-36 PCS scores. Improvement in HRQOL measured by SF-6D was associated with younger age, higher education, low Bath Ankylosing Spondylitis (BAS) Activity Index (BASDAI), high BAS Patient Global Score and high C-reactive protein; improvement in SF-36 PCS was associated with younger age, higher education, low BASDAI and no use of biological treatment at baseline.

Conclusion

Our ax-SpA outpatient clinic patients, with more patients treated with biologic drugs during the 5-year follow-up, did not deteriorate in HRQOL. In fact, the physical dimension in HRQOL improved over the years, as did measures reflecting disease activity. Our study adds evidence to the importance of suppressing inflammation to maintain and improve HRQOL in ax-SpA patients.
Toolpath Interpolation and Smoothing for Computer Numerical Control Machining of Freeform Surfaces: A Review
Authors: Zhong Wen-Bin , Luo Xi-Chun , Chang Wen-Long , Cai Yu-Kui , Ding Fei , Liu Hai-Tao , Sun Ya-Zhou
Published: September 2019

Driven by the ever increasing demand in function integration, more and more next generation high value-added products, such as head-up displays, solar concentrators and intra-ocular-lens, etc., are designed to possess freeform (i.e., non-rotational symmetric) surfaces. The toolpath, composed of high density of short linear and circular segments, is generally used in computer numerical control (CNC) systems to machine those products. However, the discontinuity between toolpath segments leads to high-frequency fluctuation of feedrate and acceleration, which will decrease the machining efficiency and product surface finish. Driven by the ever-increasing need for high-speed high-precision machining of those products, many novel toolpath interpolation and smoothing approaches have been proposed in both academia and industry, aiming to alleviate the issues caused by the conventional toolpath representation and interpolation methods. This paper provides a comprehensive review of the state-of-the-art toolpath interpolation and smoothing approaches with systematic classifications. The advantages and disadvantages of these approaches are discussed. Possible future research directions are also offered.
Differences in Aceria tosichella population responses to wheat resistance genes and wheat virus transmission
Authors: Khalaf Luaay , Chuang Wen-Po , Aguirre-Rojas L. M. , Klein Peter , Michael Smith C.
Published: September 2019

Severe winter wheat yield losses due to infestations of wheat curl mite,Aceria tosichellaKeifer, and mite-transmitted viruses occur in wheat production areas of the United States and Canada. Mite infestation alone causes stunted, chlorotic plants in susceptible wheat varieties, and mites transmitWheat Streak Mosaic(WSMV),High Plains Wheat Mosaic(HPWMoV), andTriticum Mosaic Virus(TriMV). Wheat curl mites were collected from 25 sites in Kansas, Missouri, Nebraska, Texas, North Dakota, and South Dakota in 2014 and 2015. At each site, mite virulence was determined to wheat plants harboring theCmc2-,Cmc3-, orCmc4mite resistance gene; orCmc4plus theWsm2WSMV resistance gene. Mites collected from 92%, 36%, and 24% of sites were virulent to susceptible Jagger wheat plants (noCmc),Cmc2, andCmc3,respectively. The mega-population consisting of all 25 mite sub-populations was avirulent to 80% of plants containingCmc4 + Wsm2orCmc4. WSMV, HPWMoV, or TriMV was present in mites at 76%, 16%, and 8% of the 25 sites, respectively. Our results will enable breeders to increase the efficiency of wheat production by releasing wheat varieties containing wheat curl mite resistance genes that reduce wheat yield losses.
Teaching strategies to foster techno-mathematical literacies in an innovative mathematics course for future engineers
Authors: van der Wal Nathalie J. , Bakker Arthur , Drijvers Paul
Published: September 2019

The workplace practices of engineers have changed due to the ubiquity of digital technology. So-called techno-mathematical literacies (TmL), seen as a domain specification of 21st-century skills, are essential for future engineers. How these TmL can be fostered in their education, however, is still unclear. To address this issue, we conducted a design study in which we developed a course in applied mathematics for higher technical professional education with TmL as central learning goals. This paper describes the design and implementation of the course in a first design cycle with 59 chemistry students. We focus on the teaching strategies that the lecturer used to stimulate the development of students’ TmL. In classroom discussions, in the so-called feedback hours on which students’ collaborative work on TmL was centered, context-based cases were discussed. Results include didactical, process, and inquiry-based learning strategies used by the lecturer.
Liquid biopsy in oncology: a consensus statement of the Spanish Society of Pathology and the Spanish Society of Medical Oncology
Authors: Remon J. , García-Campelo R. , de Álava E. , Vera R. , Rodríguez-Peralto J. L. , Rodríguez-Lescure Á. , Bellosillo B. , Garrido P. , Rojo F. , Álvarez-Alegret R.
Published: September 2019

The proportion of cancer patients with tumours that harbour a potentially targetable genomic alteration is growing considerably. The diagnosis of these genomic alterations can lead to tailored treatment at the onset of disease or on progression and to obtaining additional predictive information on immunotherapy efficacy. However, in up to 25% of cases, the initial tissue biopsy is inadequate for precision oncology and, in many cases, tumour genomic profiling at progression is not possible due to technical limitations of obtaining new tumour tissue specimens. Efficient diagnostic alternatives are therefore required for molecular stratification, which includes liquid biopsy. This technique enables the evaluation of the tumour genomic profile dynamically and captures intra-patient genomic heterogeneity as well. To date, there are several diagnostic techniques available for use in liquid biopsy, each one of them with different precision and performance levels. The objective of this consensus statement of the Spanish Society of Pathology and the Spanish Society of Medical Oncology is to evaluate the viability and effectiveness of the different methodological approaches in liquid biopsy in cancer patients and the potential application of this method to current clinical practice. The experts contributing to this consensus statement agree that, according to current evidence, liquid biopsy is an acceptable alternative to tumour tissue biopsy for the study of biomarkers in various clinical settings. It is therefore important to standardise pre-analytical and analytical procedures, to ensure reproducibility and generate structured and accessible clinical reports. It is essential to appoint multidisciplinary tumour molecular boards to oversee these processes and to enable the most suitable therapeutic decisions for each patient according to the genomic profile.
An economic analysis of the proposed Dhaka–Chittagong Expressway in Bangladesh with the viewpoint of GHG emission reduction
Authors: Uddin Md. Zia , Mizunoya Takeshi
Published: September 2019

Frequent road intersections in Dhaka–Chittagong National Highway (NH1), the major transport corridor of Bangladesh, significantly reduce the level of service of the corridor and eventually leads to inefficient fuel economy and excessive greenhouse gas (GHG) emission. In spite of upgrading NH1 into a four-lane highway, major road intersections reduce vehicle speed and increase congestion time and eventually burn fuel. Fuel expenses during this lost time cover no distance but increase vehicular emission within the vicinity of road and contribute to roadside temperature. Besides, the transport sector’s energy demand in Bangladesh is supported mostly by imported fuel that drains out foreign currency and inhibits GDP growth. Against the backdrop, the Government of Bangladesh is proposing to construct a four-lane expressway. The paper attempts to estimate the fuel loss savings, GHG emission reduction and economic benefit of constructing Dhaka–Chittagong Expressway. As the construction of the expressway paved a way for an increment of traffic growth by 10%, the study infers that the average lost time because of 36 intersections for a projected annual average daily traffic of 27,334 vehicles/day (in 2022). In addition to that, the fuel loss savings for various vehicle classes affect economic growth and the ensuing idling emission of EFI and MFI engines contributes to transport sector pollution. The study intends to expedite the fact that Dhaka–Chittagong Expressway would not only replace road interventions that reduce travel time cost, expenditures regarding vehicle operating and accident but also contributes cardinally to economic emancipation of the country. The estimated Benefit–Cost Ratio (BCR) was 1.23, net present value was 762.34 Million USD) and Economic Internal Rate of return was 18.27% of the proposed project.
Perspective: Clinical relevance of the dichotomous classification of Alzheimer's disease biomarkers: Should there be a “gray zone”?
Authors: McRae‐McKee Kevin , Udeh‐Momoh Chinedu T. , Price Geraint , Bajaj Sumali , de Jager Celeste A. , Scott David , Hadjichrysanthou Christoforos , McNaughton Emily , Bracoud Luc , Ahmadi‐Abhari Sara , de Wolf Frank , Anderson Roy M. , Middleton Lefkos T. ,   Alzheimer's Disease Neuroimaging Initiative
Published: September 2019

The 2018 National Institute on Aging and the Alzheimer's Association (NIA‐AA) research framework recently redefined Alzheimer's disease (AD) as a biological construct, based on in vivo biomarkers reflecting key neuropathologic features. Combinations of normal/abnormal levels of three biomarker categories, based on single thresholds, form the AD signature profile that defines the biological disease state as a continuum, independent of clinical symptomatology. While single thresholds may be useful in defining the biological signature profile, we provide evidence that their use in studies with cognitive outcomes merits further consideration. Using data from the Alzheimer's Disease Neuroimaging Initiative with a focus on cortical amyloid binding, we discuss the limitations of applying the biological definition of disease status as a tool to define the increased likelihood of the onset of the Alzheimer's clinical syndrome and the effects that this may have on trial study design. We also suggest potential research objectives going forward and what the related data requirements would be.
‘A Perfect Contradiction is Mysterious for the Clever and for Fools Alike’: Did Hegel Contradict Aristotle?
Authors: Inwood Michael
Published: September 2019

Aristotle argued that there are no true statements of the form . In his lectures on history of philosophy Hegel does not challenge this view and in his Science of Logic expresses admiration for Aristotle's rebuttal of Zeno of Elea's attempt to find such contradictions in his paradoxes of motion. Yet more than once in his logics Hegel insists that everything is contradictory. I approach this problem from two directions. First, Widerspruch often means, and is understood by Hegel to mean, ‘opposition’ rather than ‘contradiction’ in the strict logical sense. Thus Catullus's simultaneous love and hatred of Clodia is a contradiction, but not an Aristotelian, or formal logical, contradiction. I defuse Hegel's occasional suggestions of Aristotelian contradictions in motion and time. Second, I exploit Hegel's tacit rejection of Aristotle's official bivalence account of truth and falsity, in favour of the view that truth is approached by successive improvements in our inevitably imperfect attempts to attain it. In this respect Hegel's procedure is similar to that of Aristotle himself, who characteristically constructs his own view of metaphysics, physics, ethics, etc., from the imperfect, but not flatly false, opinions of his predecessors. ‘The truth is the whole’, that is, the whole sequence of our attempts to reach it.
A new echimyid genus (Rodentia, Caviomorpha) in Central Argentina: uncovered diversity of a Brazilian group of mammals in the Pleistocene
Authors: Candela Adriana M. , Cenizo Marcos , Tassara Daniel , Rasia Luciano L. , Robinet Céline , Muñoz Nahuel A. , Valenzuela Carola Cañón , Pardiñas Ulyses F. J.
Published: September 2019

We describe a new extinct spiny rat,Proclinodontomys dondasin. gen. n. sp. (Rodentia, Caviomorpha, Echimyidae), represented by a noteworthy preserved skull and mandible from the early-middle Pleistocene outcrops at the coastal cliffs of SE Buenos Aires Province (Central Argentina). Phylogenetic analyses allow us to propose that the new species described here and the already knownEurzygomatomys mordax(Winge) represent a new genus closely related to the livingEuryzygomatomys spinosusandClyomys laticeps. The new genus differs fromEuryzygomatomysandClyomysby having much more procumbent upper incisors, a more developed fossa for the M. temporalis, more flared and laterally expanded zygomatic arches, frontal less markedly expanded posteriorly, jugals much deeper anteriorly than posteriorly, with the dorsal border descending more abruptly posteriorly, smaller orbital cavity, and external auditory meatus relatively smaller and slanted upward and backward. Several features of the new species reflect a higher degree of adaptation to semifossorial habits than those ofE.spinosus. The origin of the semifossorial ecomorphotype within echimyids may have been triggered by the expansion of relatively open and arid environments that arose near the Miocene-Pliocene boundary. The record of this new echimyid in Central Argentina indicates that during the early-middle Pleistocene, the southern limit of the geographic range of extinct representatives of the Brazilian lineage of semifossorial echimyids extended farther south than that of their living members.

UUID:http://zoobank.org/c30ec1fe-4352-4867-a02f-e0d45c884bfe
Effect of high-fat diet on peripheral blood mononuclear cells and adipose tissue in early stages of diet-induced weight gain
Authors: Lowry Jake E. , Tumurbaatar Batbayar , D’Agostino Claudia , Main Erika , Wright Traver J. , Dillon Edgar L. , Saito Tais B. , Porter Craig , Andersen Clark R. , Brining Douglas L. , Endsley Janice J. , Sheffield-Moore Melinda , Volpi Elena , Fang Rong , Abate Nicola , Tuvdendorj Demidmaa R.
Published: September 2019

Subcutaneous adipose tissue (scAT) and peripheral blood mononuclear cells (PBMC) play a significant role in obesity-associated systemic low-grade inflammation. High-fat diet (HFD) is known to induce inflammatory changes in both scAT and PBMC. However, the time course of the effect of HFD on these systems is still unknown. The aim of the present study was to determine the time course of the effect of HFD on PBMC and scAT. New Zealand white rabbits were fed HFD for 5 or 10 weeks (i.e. HFD-5 and HFD-10) or regular chow (i.e. control (CNT)-5 and CNT-10). Thereafter, metabolic and inflammatory parameters of PBMC and scAT were quantified. HFD induced hyperfattyacidaemia in HFD-5 and HFD-10 groups, with the development of insulin resistance in HFD-10, while no changes were observed in scAT lipid metabolism and inflammatory status. HFD activated the inflammatory pathways in PBMC of HFD-5 group and induced modified autophagy in that of HFD-10. The rate of fat oxidation in PBMC was directly associated with the expression of inflammatory markers and tended to inversely associate with autophagosome formation markers in PBMC. HFD affected systemic substrate metabolism, and the metabolic, inflammatory and autophagy pathways in PBMC in the absence of metabolic and inflammatory changes in scAT. Dietary approaches or interventions to avert HFD-induced changes in PBMC could be essential to prevent metabolic and inflammatory complications of obesity and promote healthier living.
In vivoantimalarial activity and pharmacokinetics of artelinic acid-choline derivative liposomes in rodents
Authors: Duan Shuai , Wang Ruili , Wang Rongrong , Tang Jiaqi , Xiao Xiaoyang , Li Ning , Guo Wenju , Yang Qingshan , Ren Guolian , Zhang Shuqiu
Published: September 2019

It is urgent to develop new antimalarial drugs with good therapeutic effects to address the emergence of drug resistance. Here, the artelinic acid-choline derivative (AD) was synthesized by dehydration reaction and esterification reaction, aimed to avoid the emergence of drug resistance by synergistic effect of artemisinins and choline derivative, which could compete with choline for rate-limiting enzymes in the phosphatidylcholine (PC) biosynthetic pathway. AD was formulated into liposomes (ADLs) by the thin-film hydration method. Efficacy of ADLs was evaluated by Peters 4-day suppression test. The suppression percentage againstPlasmodium yoeliiBY265 (PyBY265) in ADLs group was higher than those of positive control groups (dihydroartemisinin liposomes,P< 0.05) and other control groups (P⩽ 0.05) at the doses of 4.4, 8.8, 17.6µmol (kg·d)−1, respectively. The negative conversion fraction, recrudescence fraction and survival fraction of ADLs group were superior to other control groups. Pharmacokinetics in rats after intravenous injection suggested that ADLs exhibited higher exposure levels (indexed by area under concentration-time curve) than that of AD solution, artelinic acid liposomes or artelinic acid solution (P< 0.01). Taken together, ADLs exhibited promising antimalarial efficacy and pharmacokinetic characteristics.
A review on toxoplasmosis in humans and animals from Egypt
Authors: Abbas I. E. , Villena I. , Dubey J. P.
Published: September 2019

The present paper summarizes prevalence, epidemiology and clinical disease of naturalToxoplasma gondiiinfections in humans and animals from Egypt. The current situation of toxoplasmosis in Egypt is confusing. There is no central laboratory or group of researchers actively investigating toxoplasmosis in humans or animals, and no reports on the national level are available. Based on various serological tests and convenience samples,T. gondiiinfections appear highly prevalent in humans and animals from Egypt. Living circumstances in Egypt favour the transmission ofT. gondii. Up to 95% of domestic cats, the key host ofT. gondii, are infected withT. gondii; they are abundant in rural and suburban areas, spreadingT. gondiioocysts. Many women have been tested in maternity clinics, most with no definitive diagnosis.Toxoplasma gondiiDNA and IgM antibodies have been found in blood samples of blood donors. Clinical toxoplasmosis in humans from Egypt needs further investigations using definitive procedures. Reports on congenital toxoplasmosis are conflicting and some reports are alarming. Although there are many serological surveys forT. gondiiin animals, data on clinical infections are lacking. Here, we critically review the status of toxoplasmosis in Egypt, which should be useful to biologist, public health workers, veterinarians and physicians.
A TAXONOMIC REVISION OF BEGONIA VEITCHII (BEGONIACEAE)
Authors: Tebbitt M. C. , Reynel C. , Limachi L. Huaylla , Martín C. M.
Published: September 2019

A taxonomic revision of Begonia veitchii Hook.f. is presented. Two taxa are newly recognised as synonyms of Begonia veitchii: B. baumannii Lemoine and B. clarkei Hook.f. Addditionally, two infraspecific taxa are newly described and illustrated: Begonia veitchii var. machupicchuensis Tebbitt, which is endemic to the Cusco Department of Peru, and B. veitchii var. lanatifolia Tebbitt, which is endemic to Chuquisaca Department, Bolivia. Begonia veitchii, as well as four taxa recognised as synonyms of B. veitchii – B. baumannii, B. rosaeflora Hook.f., B. coriacea A.DC. and B. clarkei – are lectotypified. A key, descriptions, distribution map and illustrations are provided for all the recognised infraspecific taxa of Begonia veitchii.
Five Tips for a Successful API
Authors: Dale Robert
Published: September 2019

It’s now remarkably easy to release to the world a cloud-based application programming interface (API) that provides some software function as a service. As a consequence, the cloud API space has become very densely populated, so that even if a particular API offers a service whose potential value is considerable, there are many other factors that play a role in determining whether or not that API will be commercially successful. If you’re thinking about entering the API marketplace with your latest and greatest idea, this post offers some entirely subjective advice on how you might increase the chances of your offering not being lost in all the noise.
Micro-analytical Evidence of Copper-Based Pigment and Fungal Contamination of Medieval Mural Paintings in Beram, Croatia
Authors: Zubin Ferri Tea , Pustijanac Emina , Kovačić Ines , Bilić Josipa
Published: September 2019

The aim of the present study was to map the painting materials, degradation processes, and biological features present on the mural painting in the church of St. Mary in Beram (Croatia) to study their possible interaction and produce information helping the preservation of this valuable painting. The research was conducted on micro samples of painting materials taken from different sites along the painting and the characterization of the present fungal species was carried out. The painting samples, together with observable patinas and degradation products, were studied by optical microscopy (OM), scanning electron microscopy, energy-dispersive spectroscopy (SEM/EDS), Fourier-Transform Infrared spectroscopy, and powder X-ray diffraction. Fungal diversity was studied using cultivation methods followed by OM and SEM analyses in addition to molecular analysis. The results contribute to the characterization of the original painting materials, successively added materials and occurred interventions, to the understanding of degradation progressions and fungal biotransformation processes. A mineral, cumengite, a copper-based pigment extremely rarely used in art, was found. Its occurrence together with barium sulfate, gypsum, and calcium oxalate possibly produced by microbiological activity was studied and information was added regarding the composition of painting materials in St. Mary church mural cycle.
Expression changes in theTaNAC2andTaNAC69-1transcription factors in drought stress tolerant and susceptible accessions ofTriticum boeoticum
Authors: Nazari Maryam , Goharrizi Kiarash Jamshidi , Moosavi Sayyed Saeed , Maleki Mahmood
Published: September 2019

Triticum boeoticumis a valuable gene source for tolerance to drought stress. In order to study the effect of drought stress on this plant, and to understand its adaptive mechanisms at the molecular level, 10 accessions ofT. boeoticumwere evaluated under non- and drought stress conditions. Evaluation of 31 different phenological, morpho-physiological and root-related traits showed that there were significant differences between accessions. Using the bi-plot resulting from the PCA, the studied traits and accessions were separated in different groups. The most tolerant (B5) and susceptible (B6) accessions to drought stress were identified, so these accessions were used for assessment of changes in theTaNAC2andTaNAC69-1transcription factors (TFs) expression. The results showed that in the most tolerant and susceptible accessions,TaNAC2andTaNAC69-1expression levels increased between non-stress and stress conditions significantly, but the increased level of these two genes expression in the most tolerant accession was much higher than the most susceptible accession. According to the obtained results,T. boeoticumcan be a suitable and promising gene source for improving modern wheat. In addition, the results of TFs expression could improve our understanding about the complex mechanisms associated with drought tolerance in wheat, especially wild wheat.
Indigenous Knowledge Puts Industrial Pollution in Perspective
Authors: Burke Ty
Published: September 2019

A 3-year project documents how climate change is affecting the sequestration of decades-old mining by-products in Canadian lakes.
Sociodemographic Outcomes From an Urban Pediatric Obesity Program
Authors: Andorko Nicole D. , Getzoff Elizabeth A. , Gelfand Kenneth , Demeule Michelle , Scheimann Ann O.
Published: September 2019

Objective: Pediatric weight management programs are plagued by insufficient changes in standardized body mass index (zBMI), disproportionately impacting racial minorities. Treatment outcomes of a pediatric weight management program with a large and diverse baseline sample were evaluated. Demographic and socioeconomic predictors of change in zBMI after 1 year were examined separately to identify characteristics contributing to treatment outcomes. It was hypothesized that socioeconomic disparities would account for lower zBMI outcomes above and beyond demographic factors. Method: Data were collected from 1,784 youth at baseline ( n = 271 at 12 months; age M = 11.89 years, SD = 3.15). Information on zBMI, demographics (sex, race, age, mother’s body mass index [BMI]) and socioeconomic status (SES; health insurance, number parents in home) were collected at baseline and 12 months post intervention. Results: After 1 year, average change in zBMI was −0.12 ( SD = 0.21). Linear hierarchical regression analysis assessed if SES factors predicted change in zBMI after 12 months above and beyond demographic factors. Demographics were entered in Block 1, and SES factors in Block 2. The final model significantly accounted for 14.2% of variance in change in zBMI ( p < .000). Examining blocks separately indicated SES variables did not significantly add to the model beyond demographic variables, contributing to less than 1.0% of the variance. Unique predictors included age, and mother’s BMI. Conclusions: Participation in the program was associated with decreases in zBMI for youth who completed the year of treatment and follow-ups. Factors related to age and family had the largest association with weight loss. SES factors were not related to change in zBMI beyond demographic factors.

Implications for Impact Statement

Examination of the differential impact of demographic and socioeconomic (SES) factors on 12-month weight loss outcomes of a diverse, and urban pediatric weight management program indicated SES was not associated with weight loss above and beyond demographic variables. Youth under the age of 8 had the best weight loss outcomes, whereas those with mothers who reported high BMI at baseline saw the least improvement. Findings highlighted the importance of creating flexible programs that tailor pediatric weight loss interventions to be age-appropriate and inclusive to all members of the family.
Dedifferentiation process driven by radiotherapy-induced HMGB1/TLR2/YAP/HIF-1α signaling enhances pancreatic cancer stemness
Authors: Zhang Lirong , Shi Hui , Chen Hongbo , Gong Aihua , Liu Yanfang , Song Lian , Xu Xuewen , You Tao , Fan Xin , Wang Dongqing , Cheng Fang , Zhu Haitao
Published: September 2019

Differentiated cancer cells reacquiring stem cell traits following radiotherapy may enrich cancer stem cells and accelerate tumor recurrence and metastasis. We are interested in the mechanistic role of dying cells-derived HMGB1 in CD133− pancreatic cancer cells dedifferentiation following radiotherapy. We firstly confirmed that X-ray irradiation induced differentiation of CD133− pancreatic cancer cells, from either sorted from patient samples or established cell lines, into cancer stem-like cells (iCSCs). Using an in vitro coculture model, X-ray irradiation induced dying cells to release HMGB1, which further promoted CD133− pancreatic cancer cells regaining stem cell traits, such as higher sphere forming ability and expressed higher level of stemness-related genes and proteins. Inhibiting the expression and activity of HMGB1 attenuated the dedifferentiation stimulating effect of irradiated, dying cells on C133− pancreatic cancer cells in vitro and in PDX models. Mechanistically, HMGB1 binding with TLR2 receptor functions in a paracrine manner to affect CD133− pancreatic cancer cells dedifferentiation via activating Hippo-YAP pathway and HIF-1α expression in oxygen independent manner in vitro and in vivo. We conclude that X-ray irradiation induces CD133− pancreatic cancer cell dedifferentiation into a CSC phenotype, and inhibiting HMGB1 may be a strategy to prevent CSC enrichment and further pancreatic carcinoma relapse.
Mechanically controlled reversible photoluminescence response in all-inorganic flexible transparent ferroelectric/mica heterostructures
Authors: Zheng Ming , Sun Hailing , Kwok K. W.
Published: September 2019

The ability to reversibly control the luminescent properties of functional materials with diverse external stimuli, such as an electric field, strain, and temperature, is crucial for designing high-performance optical devices. Here, we demonstrate that a purely mechanical strain in a flexible mica substrate triggered by bending can be used to dramatically modify the photoluminescence response of a Pr-doped Ba0.85Ca0.15Ti0.9Zr0.1O3epitaxial thin film in a stable and repeatable manner with a large gauge factor of up to 6853. The strong dependence of the photoluminescence performance on the mechanical bending arises from strain-induced variations in the lattice symmetry of the host film and the local crystal field around the Pr3+. In particular, because of the nature of mica, the film structure exhibits excellent antifatigue characteristics after 104bending cycles as well as high optical transparency in the range of 450–780 nm. This study provides a viable route for exploring the correlation between structural symmetry and photoluminescence in ferroelectric thin-film systems and offers new possibilities for developing all-inorganic, reconfigurable, transparent and flexible light sources, photodetectors, and wearable sensors.
Soybean antiviral immunity conferred by dsRNase targets the viral replication complex
Authors: Ishibashi Kazuhiro , Saruta Masayasu , Shimizu Takehiko , Shu Miao , Anai Toyoaki , Komatsu Kunihiko , Yamada Naohiro , Katayose Yuichi , Ishikawa Masayuki , Ishimoto Masao , Kaga Akito
Published: September 2019

Eukaryotic positive-strand RNA viruses replicate their genomes in membranous compartments formed in a host cell, which sequesters the dsRNA replication intermediate from antiviral immune surveillance. Here, we find that soybean has developed a way to overcome this sequestration. We report the positional cloning of the broad-spectrum soybean mosaic virus resistance gene Rsv4, which encodes an RNase H family protein with dsRNA-degrading activity. An active-site mutant of Rsv4 is incapable of inhibiting virus multiplication and is associated with an active viral RNA polymerase complex in infected cells. These results suggest that Rsv4 enters the viral replication compartment and degrades viral dsRNA. Inspired by this model, we design three plant-gene-derived dsRNases that can inhibit the multiplication of the respective target viruses. These findings suggest a method for developing crops resistant to any target positive-strand RNA virus by fusion of endogenous host genes.
Human immunoglobulin G hinge regulates agonistic anti-CD40 immunostimulatory and antitumour activities through biophysical flexibility
Authors: Liu Xiaobo , Zhao Yingjie , Shi Huan , Zhang Yan , Yin Xueying , Liu Mingdong , Zhang Huihui , He Yongning , Lu Boxun , Jin Tengchuan , Li Fubin
Published: September 2019

Human immunoglobulin G (IgG) agonistic antibodies targeting costimulatory immunoreceptors represent promising cancer immunotherapies yet to be developed. Whether, and how, human IgG hinge and Fc impact on their agonistic functions have been disputed. Here, we show that different natural human IgGs confer divergent agonistic anti-CD40 immunostimulatory and antitumour activities in FcγR-humanized mice, including inactive IgG3 and superior IgG2. This divergence is primarily due to their CH1-hinges despite all human IgGs requiring Fc-FcγR binding for optimal agonistic activities. Unexpectedly, biophysical flexibility of these CH1-hinges inversely correlates with, and can modulate, their agonistic potency. Furthermore, IgG Fcs optimized for selective FcγR binding synergize with and still require IgG hinge, selected for rigidity, to confer improved anti-CD40 immunostimulatory and antitumour activities. These findings highlight the importance of both hinge rigidity and selective FcγR binding in antibody agonistic function, and the need for newer strategies to modulate antibody agonism for improved clinical application.
Piezophototronic gated optofluidic logic computations empowering intrinsic reconfigurable switches
Authors: Purusothaman Yuvasree , Alluri Nagamalleswara Rao , Chandrasekhar Arunkumar , Venkateswaran Vivekananthan , Kim Sang-Jae
Published: September 2019

Optofluidic nano/microsystems have advanced the realization of Boolean circuits, with drastic progression to achieve extensive scale integration of desirable optoelectronics to investigate multiple logic switches. In this context, we demonstrate the optofluidic logic operations with interfacial piezophototronic effect to promote multiple operations of electronic analogues. We report an optofluidic Y-channeled logic device with tunable metal-semiconductor-metal interfaces through mechanically induced strain elements. We investigate the configuration of an OR gate in a semiconductor-piezoelectric zinc oxide nanorod-manipulated optofluidic sensor, and its direct reconfiguration to logic AND through compressive strain-induced (−1%) piezoelectric negative polarizations. The exhibited strategy in optofluidic systems implemented with piezophototronic concept enables direct-on chip working of OR and AND logic with switchable photocurrent under identical analyte. Featured smart intrinsic switching between the Boolean optoelectronic gates (OR↔AND) ultimately reduces the need for cascaded logic circuits to operate multiple logic switches on-a-chip.
Ideological differences in the expanse of the moral circle
Authors: Waytz Adam , Iyer Ravi , Young Liane , Haidt Jonathan , Graham Jesse
Published: September 2019

Do clashes between ideologies reflect policy differences or something more fundamental? The present research suggests they reflect core psychological differences such that liberals express compassion toward less structured and more encompassing entities (i.e., universalism), whereas conservatives express compassion toward more well-defined and less encompassing entities (i.e., parochialism). Here we report seven studies illustrating universalist versus parochial differences in compassion. Studies 1a-1c show that liberals, relative to conservatives, express greater moral concern toward friends relative to family, and the world relative to the nation. Studies 2a-2b demonstrate these universalist versus parochial preferences extend toward simple shapes depicted as proxies for loose versus tight social circles. Using stimuli devoid of political relevance demonstrates that the universalist-parochialist distinction does not simply reflect differing policy preferences. Studies 3a-3b indicate these universalist versus parochial tendencies extend to humans versus nonhumans more generally, demonstrating the breadth of these psychological differences.
Optical control of protein phosphatase function
Authors: Courtney Taylor M. , Deiters Alexander
Published: September 2019

Protein phosphatases are involved in embryonic development, metabolic homeostasis, stress response, cell cycle transitions, and many other essential biological mechanisms. Unlike kinases, protein phosphatases remain understudied and less characterized. Traditional genetic and biochemical methods have contributed significantly to our understanding; however, these methodologies lack precise and acute spatiotemporal control. Here, we report the development of a light-activated protein phosphatase, the dual specificity phosphatase 6 (DUSP6 or MKP3). Through genetic code expansion, MKP3 is placed under optical control via two different approaches: (i) incorporation of a caged cysteine into the active site for controlling catalytic activity and (ii) incorporation of a caged lysine into the kinase interaction motif for controlling the protein-protein interaction between the phosphatase and its substrate. Both strategies are expected to be applicable to the engineering of a wide range of light-activated phosphatases. Applying the optogenetically controlled MKP3 in conjunction with live cell reporters, we discover that ERK nuclear translocation is regulated in a graded manner in response to increasing MKP3 activity.