bluuebunny/crossref_metadata_2025 huggingface dataset:
Exemplary Reading Teachers’ Use of Instructional Scaffolds With Emergent Bilinguals: How Knowledge and Context Shape Their Choices
Authors: Johnson Erika Moore
Published: September 2018

Instructional scaffolding—the use of resources, structures, and verbal interaction to help students do challenging academic work—is known to be essential for effective English language reading instruction for emergent bilinguals (EBs; Goldenberg,; Walqui,). Yet little systematic research examines the scaffolds that teachers use. Drawing on scholarship about teacher cognition (Ben‐Peretz,) and instructional scaffolding (van Lier,), this study analyzes how six middle school teachers, all nominated as exemplary, chose and used scaffolds during English language reading instruction. Data include video recordings of 60 reading lessons and 18 interviews. The researcher analyzed which scaffolds teachers used and how they explained their choices. AsEBs read and discussed texts, teachers used a wide range of planned scaffolds (materials, structures, and routines) and interactional scaffolds (in‐the‐moment supports for language and content). Drawing on both formal and practical knowledge (Elbaz,), they chose scaffolds that effectively provided comprehensible input, opportunities for language production and interaction, or support for reading development. The instructional context—class composition, available materials and equipment, and professional support—mediated teachers’ choice and use of scaffolds. Findings inform teacher educators, school leaders, and researchers who seek to improve the scaffolding practice of preservice and in‐service teachers working withEBs.
Re: Maternal hemodynamics in normal pregnancy and in pregnancy affected by pre‐eclampsia. D. Stott, O. Nzelu, K. H.Nicolaides and N. A. Kametas. Ultrasound Obstet Gynecol 2018; 52: 359–364.
Authors: Khalil A.
Published: September 2018

Linked Comment: Ultrasound Obstet Gynecol 2018; 52: 359–364
Re: Cerebroplacental ratio thresholds measured within 2 weeks before birth and risk of Cesarean section for intrapartum fetal compromise and adverse neonatal outcome. L. N. Bligh, A. A. Alsolai, R. M. Greer and S. Kumar. Ultrasound Obstet Gynecol 2018; 52: 340–346.
Authors: Figueras F.
Published: September 2018

Linked Comment: Ultrasound Obstet Gynecol 2018; 52: 340–346
The evolving role of zoological parks and aquariums in migratory bird conservation
Authors: Hutchins Michael , Marra Peter P. , Diebold Ed , Kreger Michael D. , Sheppard Christine , Hallager Sara , Lynch Colleen
Published: September 2018

As threats to migratory birds in the Western Hemisphere, including North America, intensify and bird populations decline, there is a growing interest among zoo biologists in the conservation and management of these taxa. The purpose of this article is to explore the role that Association of Zoos and Aquariums (AZA)‐accredited zoos and aquariums either are playing or could play in the conservation and management of migratory birds. Topics explored include: (1) Public education and advocacy; (2) Captive breeding and reintroduction; (3) In situ conservation; (4) Tracking and monitoring; (5) Research/technology development; and (6) Sustainability/green practices; and (7) Partnerships. Zoos and aquariums could play an important role in increasing the public's access to understanding migratory birds and the threats they face, ultimately helping to protect these remarkable species.
What Exactly is Meant by “Loss of Domain” for Ventral Hernia? Systematic Review of Definitions
Authors: Parker S. G. , Halligan S. , Blackburn S. , Plumb A. A. O. , Archer L. , Mallett S. , Windsor A. C. J.
Published: September 2018

Large ventral hernias are a significant surgical challenge. “Loss of domain” (LOD) expresses the relationship between hernia and abdominal volume, and is used to predict operative difficulty and success. This systematic review assessed whether different definitions of LOD are used in the literature. The PubMed database was searched for articles reporting large hernia repairs that explicitly described LOD. Two reviewers screened citations and extracted data from selected articles, focusing on the definitions used for LOD, study demographics, study design, and reporting surgical specialty. One hundred and seven articles were identified, 93 full‐texts examined, and 77 were included in the systematic review. Sixty‐seven articles were from the primary literature, and 10 articles were from the secondary literature. Twenty‐eight articles (36%) gave a written definition for loss of domain. These varied and divided into six broad groupings; four described the loss of the right of domain, six described abdominal strap muscle contraction, five described the “second abdomen”, five describing large irreducible hernias. Six gave miscellaneous definitions. Two articles gave multiple definitions. Twenty articles (26%) gave volumetric definitions; eight used the Tanaka method [hernia sac volume (HSV)/abdominal cavity volume] and five used the Sabbagh method [(HSV)/total peritoneal volume]. The definitions used for loss of domain were not dependent on the reporting specialty. Our systematic review revealed that multiple definitions of loss of domain are being used. These vary and are not interchangeable. Expert consensus on this matter is necessary to standardise this important concept for hernia surgeons.
Investigating the genetic diversity and differentiation patterns in the Penstemon scariosus species complex under different sample sizes using AFLPs and SSRs
Authors: Rodríguez-Peña Rosa A. , Johnson Robert L. , Johnson Leigh A. , Anderson Chris D. , Ricks Nathan J. , Farley Kevin M. , Robbins Matthew D. , Wolfe Andrea D. , Stevens Mikel R.
Published: September 2018

Habitat fragmentation due to anthropogenic activities is the major cause of biodiversity loss. Endemic and narrowly distributed species are the most susceptible to habitat degradation. Penstemon scariosus is one of many species whose natural habitat is vulnerable to industrialization. All varieties of P. scariosus (P. scariosus var. albifluvis, P. scariosus var. cyanomontanus, P. scariosus var. garrettii, P. scariosus var. scariosus) have small distribution ranges, but only P. scariosus var. albifluvis is being considered for listing under the Endangered Species Act. We used eight microsatellites or simple sequence repeats (SSRs) loci and two amplified fragment length polymorphism (AFLP) primer combinations to investigate the population genetic structure and diversity of P. scariosus varieties. Moreover, we compared the utility of the two marker systems in conservation genetics and estimated an appropriate sample size in population genetic studies. Genetic differentiation among populations based on Fst ranged from low to moderate (Fst = 0.056–0.157) and from moderate to high when estimated with Des (Des = 0.15–0.32). Also, AMOVA analysis shows that most of the genetic variation is within populations. Inbreeding coefficients (Fis) were high in all varieties (0.20–0.56). The Bayesian analysis, STRUCTURE, identified three clusters from SSR data and four clusters from AFLPs. Clusters were not consistent between marker systems and did not represent the current taxonomy. MEMGENE revealed that a high proportion of the genetic variation is due to geographic distance (R2 = 0.38, P = 0.001). Comparing the genetic measurements from AFLPs and SSRs, we found that AFLP results were more accurate than SSR results across sample size when populations were larger than 25 individuals. As sample size decreases, the estimates become less stable in both AFLP and SSR datasets. Finally, this study provides insight into the population genetic structure of these varieties, which could be used in conservation efforts.
User Acceptability of Whole Exome Reproductive Carrier Testing for Consanguineous Couples in Australia
Authors: Josephi‐Taylor Sarah , Barlow‐Stewart Kristine , Selvanathan Arthavan , Roscioli Tony , Bittles Alan , Meiser Bettina , Worgan Lisa , Rajagopalan Sulekha , Colley Alison , Kirk Edwin P.
Published: September 2018

The study aimed to explore with consanguineous couples in Australia the acceptability and perceived utility of whole exome reproductive carrier screening for autosomal recessive and X‐linked recessive conditions. Semi‐structured interviews with 21 consanguineous couples were conducted prior to the offer of screening. Interviews were coded, and thematic analysis was informed by an inductive approach. Three major themes were identified: experiences and attitudes of Australian consanguineous couples, childhood genetic conditions and beliefs, and the perceived utility of genomic screening. All but one couple had previously sought genetic advice, and a large majority of couples were aware of childhood conditions within their family or community. Thirteen couples perceived consanguinity as increasing the risk of having affected children. Nine spoke of premarital screening programs routinely conducted in their countries of origin. All supported the concept and availability of genomic reproductive carrier screening. Hypothetically, if found to be carriers of a severe childhood disorder, 13 couples reported they would test a pregnancy, and 12 of whom would consider termination of pregnancy or pre‐implantation genetic diagnosis. Four couples would not test a pregnancy and two were unsure. A majority of couples would communicate potential at‐risk status to family members, although there were some caveats. Fourteen couples chose to have exome screening and reported that they would utilize the results with the goal of preventing childhood conditions. Of these couples, nine (64%) had an affected child but were aware that testing may reveal they were at risk for a child with a different condition and five (71%) without an affected child. While from diverse ethnic and backgrounds, all couples practiced a religion and all but one couple were recruited from the same clinical genetics unit, with a likely higher genetic literacy and bias towards accepting genetic testing. However, the choice made by all couples was reportedly made with consideration of their personal values, their current family situation, and exome testing issues, including fear of incidental findings and concerns about test reliability.
Introduction
Authors: Doherty Gareth
Published: September 2018

These short contributions from scholars and practitioners of architecture and the environment in the Arabian Peninsula, offer a variety of viewpoints on the future of the region's built environment. While each piece offers its own perspective, there is a clear consensus among the authors that the design of the future built environment needs to be more environmentally sensitive and human focused. Such a human focus encompasses individuals and the collective, local citizens and foreign-born residents, visitors and workers.
Identifying a Local in Gulf Cities
Authors: Reisz Todd
Published: September 2018

Depending upon how you approach the matter, it is either humdrum or complicated to ask an architect how he would improve the Gulf region's built environment. Humdrum, because that is what architects do every day: say how they can improve what was done poorly before them. Complicated, because there's a frustrating modern history of experts coming to the Gulf to do just that. In the Arab Gulf countries, architecture is most often assumed to result from imported expertise, certified and purchased abroad. The foundation of that assumption rests in the late colonial British management of Gulf cities. Colonial officers, most often referred to as political agents or political residents, harnessed the built environment to visually convey the bureaucratic order that the British government was instituting where it had suppressed it in the decades before. Modern architecture served as a sleight of optics to foster economic improvement and political stability. It was less style, more content. Literally, the contents of the building: medical machines, cadastral maps, canned foods, air conditioning. In this way, the architect was perceived as a herald and packager of promised technological improvements from afar. And, in many ways, he or she still is perceived as such. And that's a problem worth touching upon.
GEOLOGIES OF ERASURE: SINKHOLES, SCIENCE, AND SETTLER COLONIALISM AT THE DEAD SEA
Authors: Popperl Simone
Published: September 2018

Scientists who study Dead Sea sinkholes come to know them in particular ways (as generalized hydrogeoloic phenomena, symptoms of a regional environmental crisis, or divine retribution) and at particular scales (from the distant orbit of Earth observation satellites, from digitally altered aerial photographs, and occasionally from the inside). Using ethnographic data gathered between 2012 and 2015 in the occupied Palestinian territories (oPt), Israel, and Jordan, I compare how groups and individuals study, think, and learn about Dead Sea sinkholes. The way hydrogeologic knowledge about these sinkholes is gathered and circulated helps define land around the Dead Sea as territory to be colonized. These scientific processes can nullify Palestinian claims to the Dead Sea, eliminate Palestinian people from Dead Sea landscapes, and marginalize Bedouin opposition to Jordanian government policies. I suggest that attention to “geologies of erasure” helps scholars to understand the scientific and political impacts of settler colonialisms on the collection of knowledge about changing natural environments in the Middle East and beyond.
Population dynamics of the crabHepatus pudibundus(Herbst, 1785) (Decapoda, Aethridae) on the southern coast of São Paulo state, Brazil
Authors: Miazaki Lizandra Fernandes , Simões Sabrina Morilhas , Castilho Antonio Leão , Costa Rogério Caetano
Published: September 2018

The present study investigated the population dynamics ofHepatus pudibundusin the Cananéia region, in southern São Paulo state, Brazil, focusing on population structure, growth parameters, longevity, sex ratio, reproduction and recruitment juvenile period. Sampling was performed monthly at seven stations from July 2012 to June 2014, using a shrimp fishing boat. A total of 1650 specimens were collected: 551 males and 1099 females. The males were larger than females. Reproductive females were captured throughout the study period and juveniles were captured in most months. Both of these demographic categories were positively correlated with temperature. Growth parameters showed differences between sexes: CW∞= 78.91 mm,k= 0.0066 day−1,t0= 0.0965 for males and CW∞= 69.71 mm,k= 0.0053 day−1,t0= −0.2404 for females. Longevity was estimated at 1.91 and 2.40 years for males and females, respectively. The findings provide a greater understanding of the life cycle in this species. Additionally, since trawl nets are not selective, this study also provides information for better trawl fishery management, addressing not only the target shrimp but also the by-catch species.
Regulator constants of integral representations of finite groups
Authors: TORZEWSKI ALEX
Published: September 2018

Let G be a finite group and p be a prime. We investigate isomorphism invariants of $\mathbb{Z}_p$[G]-lattices whose extension of scalars to $\mathbb{Q}_p$ is self-dual, called regulator constants. These were originally introduced by Dokchitser–Dokchitser in the context of elliptic curves. Regulator constants canonically yield a pairing between the space of Brauer relations for G and the subspace of the representation ring for which regulator constants are defined. For all G, we show that this pairing is never identically zero. For formal reasons, this pairing will, in general, have non-trivial kernel. But, if G has cyclic Sylow p-subgroups and we restrict to considering permutation lattices, then we show that the pairing is non-degenerate modulo the formal kernel. Using this we can show that, for certain groups, including dihedral groups of order 2p for p odd, the isomorphism class of any $\mathbb{Z}_p$[G]-lattice whose extension of scalars to $\mathbb{Q}_p$ is self-dual, is determined by its regulator constants, its extension of scalars to $\mathbb{Q}_p$, and a cohomological invariant of Yakovlev.
A datalog-based computational model for coordination-free, data-parallel systems
Authors: INTERLANDI MATTEO , TANCA LETIZIA
Published: September 2018

Cloud computingrefers to maximizing efficiency by sharing computational and storage resources, whiledata-parallel systemsexploit the resources available in the cloud to perform parallel transformations over large amounts of data. In the same line, considerable emphasis has been recently given to two apparently disjoint research topics:data-parallel, andeventually consistent, distributedsystems.Declarative networkinghas been recently proposed to ease the task of programming in the cloud, by allowing the programmer to express only the desired result and leave the implementation details to the responsibility of the run-time system. In this context, we deem it appropriate to propose a study on alogic-programming-based computational modelfor eventually consistent, data-parallel systems, the keystone of which is provided by the recent finding that the class of programs that can be computed in an eventually consistent, coordination-free way is that ofmonotonic programs. This principle is called Consistency and Logical Monotonicity (CALM) and has been proven by Amelootet al.for distributed, asynchronous settings. We advocate that CALM should be employed as a basic theoretical tool also for data-parallel systems, wherein computation usually proceeds synchronously in rounds and where communication is assumed to be reliable. We deem this problem relevant and interesting, especially for what concernsparallel dataflow optimizations. Nowadays, we are in fact witnessing an increasing concern about understanding which properties distinguish synchronous from asynchronous parallel processing, and when the latter can replace the former. It is general opinion that coordination-freedom can be seen as a major discriminant factor. In this work, we make the case that the current form of CALM does not hold in general for data-parallel systems, and show how, using novel techniques, the satisfiability of the CALM principle can still be obtained although just for the subclass of programs calledconnected monotonic queries. We complete the study with considerations on the relationships between our model and the one employed by Amelootet al., showing that our techniques subsume the latter when the synchronization constraints imposed on the system are loosened.
2018 AGU Union Medal, Award, and Prize Recipients Announced
Authors: Davidson Eric , Holmes Mary
Published: September 2018

The world’s largest organization of Earth and space scientists honors 33 exceptional individuals.
Catchment Drainage Network Scaling Laws Found Experimentally in Overland Flow Morphologies
Authors: Cheraghi Mohsen , Rinaldo Andrea , Sander Graham C. , Perona Paolo , Barry D. A.
Published: September 2018

The scaling relation between the drainage area and stream length (Hack's law), along with exceedance probabilities of drainage area, discharge, and upstream flow network length, is well known for channelized fluvial regions. We report here on a laboratory experiment on an eroding unconsolidated sediment for which no channeling occurred. Laser scanning was used to capture the morphological evolution of the sediment. High‐intensity, spatially nonuniform rainfall ensured that the morphology changed substantially over the 16‐hr experiment. Based on the surface scans and precipitation distribution, overland flow was estimated with the D8 algorithm, which outputs a flow network that was analyzed statistically. The above‐mentioned scaling and exceedance probability relationships for this overland flow network are the same as those found for large‐scale catchments and for laboratory experiments with observable channels. In addition, the scaling laws were temporally invariant, even though the network dynamically changed over the course of experiment.
Pitch Angle Scattering and Loss of Radiation Belt Electrons in Broadband Electromagnetic Waves
Authors: Chaston C. C. , Bonnell J. W. , Halford A. J. , Reeves G. D. , Baker D. N. , Kletzing C. A. , Wygant J. R.
Published: September 2018

A magnetic conjunction between Van Allen Probes spacecraft and the Balloon Array for Radiation‐belt Relativistic Electron Losses (BARREL) reveals the simultaneous occurrence of broadband Alfvénic fluctuations and multi‐timescale modulation of enhanced atmospheric X‐ray bremsstrahlung emission. The properties of the Alfvénic fluctuations are used to build a model for pitch angle scattering in the outer radiation belt on electron gyro‐radii scale field structures. It is shown that this scattering may lead to the transport of electrons into the loss cone over an energy range from hundreds of keV to multi‐MeV on diffusive timescales on the order of hours. This process may account for modulation of atmospheric X‐ray fluxes observed from balloons and constitute a significant loss process for the radiation belts.
Dynamics of Eddy Generation in the Central Bay of Bengal
Authors: Cheng Xuhua , McCreary Julian P. , Qiu Bo , Qi Yiquan , Du Yan , Chen Xiao
Published: September 2018

Eddy activity in the central Bay of Bengal (BoB) is revealed using satellite observations and hydrographic data. Altimetric data show that eddies are generated near the eastern boundary, propagate southwestward, and have periods predominantly in the 30‐ to 120‐day band. Temperature profiles from the Research Moored Array for African‐Asian‐Australian Monsoon Analysis and Prediction (RAMA) buoy at 90°E, 15°N, have their highest amplitude in the depth range of the thermocline, indicating that the eddies are associated with a vertical motion of the thermocline (a first‐baroclinic‐mode response). To investigate the cause of the eddies, we obtained a suite of solutions to nonlinear and linear versions of a 1½‐layer (reduced‐gravity) model. They demonstrate that equatorial wind forcing, Myanmar bump and Andaman Island, and nonlinearity are all essential for eddy formation. Among the nonlinear terms, the advection terms are the primary cause.
Changes in Global Tropospheric OH Expected as a Result of Climate Change Over the Last Several Decades
Authors: Nicely Julie M. , Canty Timothy P. , Manyin Michael , Oman Luke D. , Salawitch Ross J. , Steenrod Stephen D. , Strahan Susan E. , Strode Sarah A.
Published: September 2018

The oxidizing capacity of the troposphere is controlled primarily by the abundance of hydroxyl radical (OH). The global mean concentration of tropospheric OH, [OH]TROP (the burden of OH in the global troposphere appropriate for calculating the lifetime of methane) inferred from measurements of methyl chloroform has remained relatively constant during the past several decades despite rising levels of methane that should have led to a decline. Here we examine other factors that may have affected [OH]TROP such as the changing values of stratospheric ozone, rising tropospheric H2O, varying burden of NOx (=NO+NO2), rising temperatures, and widening of the climatological tropics due to expansion of the Hadley cell. Our analysis suggests the positive trends in [OH]TROP due to H2O, NOx, and overhead O3, and tropical expansion are large enough (Δ [OH]TROP = +0.95 ± 0.18%/decade) to counter almost all of the expected decrease in [OH]TROP due to rising methane (Δ [OH]TROP = −1.01 ± 0.05%/decade) over the period 1980 to 2015, while variations in temperature contribute almost no trend (Δ [OH]TROP = −0.02 ± 0.02%/decade) in [OH]TROP. The approximated impact of Hadley cell expansion on [OH]TROP is also a small but not insignificant factor partially responsible for the steadiness of tropospheric oxidizing capacity over the past several decades, which free‐running models likely do not capture.
Individual and combined effects of acute delta-9-tetrahydrocannabinol and cannabidiol on psychotomimetic symptoms and memory function
Authors: Morgan Celia J. A. , Freeman Tom P. , Hindocha Chandni , Schafer Grainne , Gardner Chelsea , Curran H. Valerie
Published: September 2018

The main active ingredient in cannabis, delta-9-tetrahydrocannabinol (THC), can acutely induce psychotic symptoms and impair episodic and working memory. Another major constituent, cannabidiol (CBD), may attenuate these effects. This study aimed to determine the effects of THC and CBD, both alone and in combination on psychotic symptoms and memory function. A randomised, double-blind crossover design compared the effects of (i) placebo, (ii) THC 8 mg, (iii) CBD 16 mg and (iv) THC 8 mg + CBD 16 mg administered by inhalation through a vaporiser. Using an experimental medicine approach to predict treatment sensitivity, we selected 48 cannabis users from the community on the basis of (1) schizotypal personality questionnaire scores (low, high) and (2) frequency of cannabis use (light, heavy). The Brief Psychiatric Rating Scale (BPRS), Psychotomimetic States Inventory (PSI), immediate and delayed prose recall (episodic memory), 1- and 2-back (working memory) were assessed on each day. Results indicated that THC increased overall scores on the PSI, negative symptoms on BPRS, and robustly impaired episodic and working memory. Co-administration of CBD did not attenuate these effects. CBD alone reduced PSI scores in light users only. At a ratio of 2:1, CBD does not attenuate the acute psychotic and memory impairing effects of vaporised THC. Frequent cannabis users may show a blunted anti- psychotic response to CBD, which is of concern due to the high rates of cannabis use disorders in patients with schizophrenia.
CD69 enhances immunosuppressive function of regulatory T-cells and attenuates colitis by prompting IL-10 production
Authors: Yu Lei , Yang Fei , Zhang Fanghui , Guo Danfeng , Li Ling , Wang Xian , Liang Tingbo , Wang Jianli , Cai Zhijian , Jin Hongchuan
Published: September 2018

Foxp3+regulatory T cells (Tregs) can inhibit immune responses and maintain immune tolerance by secreting immunosuppressive TGF-β1 and IL-10. However, the efficiency of Tregs become the major obstacle to their use for immunotherapy. In this study, we investigated the relevance of the C-type lectin receptor CD69 to the suppressive function. Compared to CD4+Foxp3+CD69−Tregs (CD69−Tregs), CD4+Foxp3+CD69+Tregs (CD69+Tregs) displayed stronger ability to maintain immune tolerance. CD69+Tregs expressed higher levels of suppression-associated markers such as CTLA-4, ICOS, CD38 and GITR, and secreted higher levels of IL-10 but not TGF-β1. CD69+Tregs fromIl10+/+rather thanIl10−/−mice significantly inhibit the proliferation of CD4+T cells. CD69 over-expression stimulated higher levels of IL-10 and c-Maf expression, which was compromised by silencing of STAT3 or STAT5. In addition, the direct interaction of STAT3 with the c-Maf promoter was detected in cells with CD69 over-expression. Moreover, adoptive transfer of CD69+Tregs but not CD69−Tregs or CD69+Tregs deficient in IL-10 dramatically prevented the development of inflammatory bowel disease (IBD) in mice. Taken together, CD69 is important to the suppressive function of Tregs by promoting IL-10 production. CD69+Tregs have the potential to develop new therapeutic approach for autoimmune diseases like IBD.
Evidence for Regulation of Hemoglobin Metabolism and Intracellular Ionic Flux by the Plasmodium falciparum Chloroquine Resistance Transporter
Authors: Lee Andrew H. , Dhingra Satish K. , Lewis Ian A. , Singh Maneesh K. , Siriwardana Amila , Dalal Seema , Rubiano Kelly , Klein Matthias S. , Baska Katelynn S. , Krishna Sanjeev , Klemba Michael , Roepe Paul D. , Llinás Manuel , Garcia Celia R. S. , Fidock David A.
Published: September 2018

Plasmodium falciparum multidrug resistance constitutes a major obstacle to the global malaria elimination campaign. Specific mutations in the Plasmodium falciparum chloroquine resistance transporter (PfCRT) mediate resistance to the 4-aminoquinoline drug chloroquine and impact parasite susceptibility to several partner agents used in current artemisinin-based combination therapies, including amodiaquine. By examining gene-edited parasites, we report that the ability of the wide-spread Dd2 PfCRT isoform to mediate chloroquine and amodiaquine resistance is substantially reduced by the addition of the PfCRT L272F mutation, which arose under blasticidin selection. We also provide evidence that L272F confers a significant fitness cost to asexual blood stage parasites. Studies with amino acid-restricted media identify this mutant as a methionine auxotroph. Metabolomic analysis also reveals an accumulation of short, hemoglobin-derived peptides in the Dd2 + L272F and Dd2 isoforms, compared with parasites expressing wild-type PfCRT. Physiologic studies with the ionophores monensin and nigericin support an impact of PfCRT isoforms on Ca2+ release, with substantially reduced Ca2+ levels observed in Dd2 + L272F parasites. Our data reveal a central role for PfCRT in regulating hemoglobin catabolism, amino acid availability, and ionic balance in P. falciparum, in addition to its role in determining parasite susceptibility to heme-binding 4-aminoquinoline drugs.
Electrophysiological Correlates of Blast-Wave Induced Cerebellar Injury
Authors: Ordek Gokhan , Asan Ahmet S. , Cetinkaya Esma , Skotak Maciej , Kakulavarapu Venkata R. , Chandra Namas , Sahin Mesut
Published: September 2018

Understanding the mechanisms underlying traumatic neural injury and the sequelae of events in the acute phase is important for deciding on the best window of therapeutic intervention. We hypothesized that evoked potentials (EP) recorded from the cerebellar cortex can detect mild levels of neural trauma and provide a qualitative assessment tool for progression of cerebellar injury in time. The cerebellar local field potentials evoked by a mechanical tap on the hand and collected with chronically implanted micro-ECoG arrays on the rat cerebellar cortex demonstrated substantial changes both in amplitude and timing as a result of blast-wave induced injury. The results revealed that the largest EP changes occurred within the first day of injury, and partial recoveries were observed from day-1 to day-3, followed by a period of gradual improvements (day-7 to day-14). The mossy fiber (MF) and climbing fiber (CF) mediated components of the EPs were affected differentially. The behavioral tests (ladder rung walking) and immunohistological analysis (calbindin and caspase-3) did not reveal any detectable changes at these blast pressures that are typically considered as mild (100–130 kPa). The results demonstrate the sensitivity of the electrophysiological method and its use as a tool to monitor the progression of cerebellar injuries in longitudinal animal studies.
Particular CSF sphingolipid patterns identify iNPH and AD patients
Authors: Torretta Enrica , Arosio Beatrice , Barbacini Pietro , Casati Martina , Capitanio Daniele , Mancuso Roberta , Mari Daniela , Cesari Matteo , Clerici Mario , Gelfi Cecilia
Published: September 2018

Idiopathic normal pressure hydrocephalus (iNPH) is characterized by reversible neurological symptoms due to an impairment in cerebrospinal fluid (CSF) clearance. In these patients, cognitive functions are severely impaired, with a scenario similar to Alzheimer’s disease (AD), making the differential diagnosis difficult and highlighting the need of new markers. We analyzed the composition of sphingolipids (SLs) in serum, by combining a single phase extraction with a high-performance thin-layer chromatography (HPTLC) primuline-profiling, and, in CSF, by MALDI profiling and LC-MS. Ceramides and sphingomyelins (SMs) were similar in serum of iNPH and AD patients compared to healthy controls, whereas, in CSF, MALDI profiling indicated that: 1) SM C24:1 is significantly decreased in AD compared to iNPH patients and controls (Kruskal-Wallis p-value < 0.00001); 2) phosphatidylcholine (PC) 36:2 is increased in iNPH patients (p-value < 0.001). LC-MS identified an increasing trend of Cer C24:0 and of a set of SMs in patients with AD, a significant decrease of sphingosine-1-phosphate (S1P) (t-test p-value 0.0325) and an increase of glucosylceramide (GlcCer) C24:0 (p-value 0.0037) in AD compared to iNPH patients. In conclusion CSF PC 36:2, SM C24:1, S1P, and GlcCer can contribute to improve the differential diagnosis of patients with iNPH or AD and foster preventive therapeutic strategies in the early phase of the disease.
Tranexamic acid in primary total knee arthroplasty without tourniquet: a randomized, controlled trial of oral versus intravenous versus topical administration
Authors: Wang Duan , Wang Hao-Yang , Cao Chang , Li Ling-Li , Meng Wei-Kun , Pei Fu-Xing , Li De-Hua , Zhou Zong-Ke , Zeng Wei-Nan
Published: September 2018

Abundant literature confirms that intravenous (IV) and intra-articular (IA) administration of tranexamic acid (TXA) reduces blood loss in total knee arthroplasty (TKA). Oral formulations of TXA exhibit profound cost-saving benefits. However, comparisons of the clinical efficacy among three different modalities of TXA administration have not been previously investigated in the setting of TKA with no closed suction drain and tourniquet. A total of 180 patients undergoing TKA were randomized to receive 2-g oral TXA 2 hours preoperatively, 20-mg/kg IV TXA 5 minutes prior to incision, or 2-g IA TXA. The primary outcome was 72-hour blood loss. Secondary outcomes were reductions in hemoglobin, the rate of transfusions, and adverse events. No significant differences were identified with regard to the mean 72-hour blood loss among the three groups (1003 mL in oral group, 1108 mL in IV group, and 1059 mL in IA group, respectively). Similarly, hemoglobin reduction was equivalent among the groups. Only one patient in IV group exhibited deep venous thrombosis. No difference was identified regarding transfusion rates. Oral TXA results in similar blood loss in TKA, with a profound cost-saving benefit, compared with the IA and IV formulations.
Fluorescently Labelled Silica Coated Gold Nanoparticles as Fiducial Markers for Correlative Light and Electron Microscopy
Authors: Fokkema Jantina , Fermie Job , Liv Nalan , van den Heuvel Dave J. , Konings Tom O. M. , Blab Gerhard A. , Meijerink Andries , Klumperman Judith , Gerritsen Hans C.
Published: September 2018

In this work, gold nanoparticles coated with a fluorescently labelled (rhodamine B) silica shell are presented as fiducial markers for correlative light and electron microscopy (CLEM). The synthesis of the particles is optimized to obtain homogeneous, spherical core-shell particles of arbitrary size. Next, particles labelled with different fluorophore densities are characterized to determine under which conditions bright and (photo)stable particles can be obtained. 2 and 3D CLEM examples are presented where optimized particles are used for correlation. In the 2D example, fiducials are added to a cryosection of cells whereas in the 3D example cells are imaged after endocytosis of the fiducials. Both examples demonstrate that the particles are clearly visible in both modalities and can be used for correlation. Additionally, the recognizable core-shell structure of the fiducials proves to be very powerful in electron microscopy: it makes it possible to irrefutably identify the particles and makes it easy to accurately determine the center of the fiducials.
Effect of present versus previous smoking on non-invasive haemodynamics
Authors: Choudhary Manoj Kumar , Eräranta Arttu , Tikkakoski Antti J. , Bouquin Heidi , Hautaniemi Elina J. , Kähönen Mika , Sipilä Kalle , Mustonen Jukka , Pörsti Ilkka
Published: September 2018

We examined cardiovascular function in 637 volunteers (19–72 years) without antihypertensive medication in never smokers (n = 365), present smokers (n = 81) and previous smokers (n = 191, median abstinence 10 years). Haemodynamics during passive head-up tilt were recorded using whole-body impedance cardiography and radial pulse wave analysis. Results were adjusted for age, sex, body mass index, LDL cholesterol and alcohol use. Systolic and diastolic blood pressure, heart rate, and pulse wave velocity were not different between the groups. Supine aortic reflection times did not differ, while upright values were shorter in present versus previous smokers (p = 0.04). Heart rate adjusted augmentation index was increased in the supine position in present smokers versus controls (p = 0.045), and in present (p < 0.001) and previous (p = 0.031) smokers versus controls in the upright position. Supine and upright cardiac output was higher (p ≤ 0.016) and systemic vascular resistance lower (p ≤ 0.001) in present versus previous smokers. In spite of the long abstinence, in the upright position previous smokers had lower cardiac output (p = 0.032) and higher systemic vascular resistance (p = 0.014) than never smokers. In the absence of differences in blood pressure and arterial stiffness, present smokers presented with hyperdynamic circulation and enhanced wave reflection compared with previous smokers.
Trans-abdominal in vivo placental vessel occlusion using High Intensity Focused Ultrasound
Authors: Shaw Caroline J. , Rivens Ian , Civale John , Botting Kimberley J. , ter Haar Gail , Giussani Dino A. , Lees Christoph C.
Published: September 2018

Pre-clinically, High Intensity Focused Ultrasound (HIFU) has been shown to safely and effectively occlude placental blood vessels in the acute setting, when applied through the uterus. However, further development of the technique to overcome the technical challenges of targeting and occluding blood vessels through intact skin remains essential to translation into human studies. So too does the assessment of fetal wellbeing following this procedure, and demonstration of the persistence of vascular occlusion. At 115 ± 10 d gestational age (term~147 days) 12 pregnant sheep were exposed to HIFU (n = 6), or to a sham (n = 6) therapy through intact abdominal skin (1.66 MHz, 5 s duration,in situISPTA1.3–4.4 kW.cm−2). Treatment success was defined as undetectable colour Doppler signal in the target placental vessel following HIFU exposures. Pregnancies were monitored for 21 days using diagnostic ultrasound from one day before HIFU exposure until term, when post-mortem examination was performed. Placental vessels were examined histologically for evidence of persistent vascular occlusion. HIFU occluded 31/34 (91%) of placental vessels targeted, with persistent vascular occlusion evident on histological examination 20 days after treatment. The mean diameter of occluded vessels was 1.4 mm (range 0.3–3.3 mm). All pregnancies survived until post mortem without evidence of significant maternal or fetal iatrogenic harm, preterm labour, maternal or fetal haemorrhage or infection. Three of six ewes exposed to HIFU experienced abdominal skin burns, which healed without intervention within 21 days. Mean fetal weight, fetal growth velocity and other measures of fetal biometry were not affected by exposure to HIFU. Fetal Doppler studies indicated a transient increase in the umbilical artery pulsatility index (PI) and a decrease in middle cerebral artery PI as a result of general anaesthesia, which was not different between sham and treatment groups. We report the first successful application of fully non-invasive HIFU for occlusion of placental blood flow in a pregnant sheep model, with a low risk of significant complications. This proof of concept study demonstrates the potential of this technique for clinical translation.
Antiviral innate immune response in non-myeloid cells is augmented by chloride ions via an increase in intracellular hypochlorous acid levels
Authors: Ramalingam Sandeep , Cai Baiyi , Wong Junsheng , Twomey Matthew , Chen Rui , Fu Rebecca M. , Boote Toby , McCaughan Hugh , Griffiths Samantha J. , Haas Jürgen G.
Published: September 2018

Phagocytes destroy ingested microbes by producing hypochlorous acid (HOCl) from chloride ions (Cl−) and hydrogen peroxide within phagolysosomes, using the enzyme myeloperoxidase. HOCl, the active ingredient in bleach, has antibacterial/antiviral properties. As myeloperoxidase is needed for HOCl production, non-myeloid cells are considered incapable of producing HOCl. Here, we show that epithelial, fibroblast and hepatic cells have enhanced antiviral activity in the presence of increasing concentrations of sodium chloride (NaCl). Replication of enveloped/non-enveloped, DNA (herpes simplex virus-1, murine gammaherpesvirus 68) and RNA (respiratory syncytial virus, influenza A virus, human coronavirus 229E, coxsackievirus B3) viruses are inhibited in a dose-dependent manner. Whilst treatment with sodium channel inhibitors did not prevent NaCl-mediated virus inhibition, a chloride channel inhibitor reversed inhibition by NaCl, suggesting intracellular chloride is required for antiviral activity. Inhibition is also reversed in the presence of 4-aminobenzoic hydrazide, a myeloperoxidase inhibitor, suggesting epithelial cells have a peroxidase to convert Cl− to HOCl. A significant increase in intracellular HOCl production is seen early in infection. These data suggest that non-myeloid cells possess an innate antiviral mechanism dependent on the availability of Cl− to produce HOCl. Antiviral activity against a broad range of viral infections can be augmented by increasing availability of NaCl.
Tuning electronic properties of transition-metal dichalcogenides via defect charge
Authors: Aghajanian Martik , Mostofi Arash A. , Lischner Johannes
Published: September 2018

Defect engineering is a promising route for controlling the electronic properties of monolayer transition-metal dichalcogenide (TMD) materials. Here, we demonstrate that the electronic structure of MoS2 depends sensitively on the defect charge, both its sign and magnitude. In particular, we study shallow bound states induced by charged defects using large-scale tight-binding simulations with screened defect potentials and observe qualitative changes in the orbital character of the lowest lying impurity states as function of the impurity charge. To gain further insights, we analyze the competition of impurity states originating from different valleys of the TMD band structure using effective mass theory and find that impurity state binding energies are controlled by the effective mass of the corresponding valley, but with significant deviations from hydrogenic behaviour due to unconventional screening of the defect potential.
Phylogenetic evidence for independent origins of GDF1 and GDF3 genes in anurans and mammals
Authors: Opazo Juan C. , Zavala Kattina
Published: September 2018

Growth differentiation factors 1 (GDF1) and 3 (GDF3) are members of the transforming growth factor superfamily (TGF-β) that is involved in fundamental early-developmental processes that are conserved across vertebrates. The evolutionary history of these genes is still under debate due to ambiguous definitions of homologous relationships among vertebrates. Thus, the goal of this study was to unravel the evolution of the GDF1 and GDF3 genes of vertebrates, emphasizing the understanding of homologous relationships and their evolutionary origin. Our results revealed that the GDF1 and GDF3 genes found in anurans and mammals are the products of independent duplication events of an ancestral gene in the ancestor of each of these lineages. The main implication of this result is that the GDF1 and GDF3 genes of anurans and mammals are not 1:1 orthologs. In other words, genes that participate in fundamental processes during early development have been reinvented two independent times during the evolutionary history of tetrapods.
Low temperature synthesis of NbC/C nano-composites as visible light photoactive catalyst
Authors: Gupta Aayush , Mittal Manish , Singh Mahesh Kumar , Suib Steven L. , Pandey Om Prakash
Published: September 2018

A facile carbothermal route was adopted to obtain niobium carbide nanoparticles (NPs) embedded in carbon network from Nb2O5 to study photocatalytic behavior. Optimization of synthesis parameters to obtain single phase NbC NPs has been successfully done. The phase identification, morphology and nature of carbon were determined with the help of X-ray diffraction, transmission electron microscopy (TEM) and Raman spectroscopy. X-ray photoelectron spectroscopy (XPS) suggested the presence of multiple oxidation states of Nb associated to NbC and NbCxOy centers on the surface of NPs. Due to the presence of NbCxOy on the surface of NPs, absorption under visible region of EM spectrum has been observed by UV-visible spectroscopy. Different organic dyes (RhB, MB and MO) were used to study the effect of holding time on the photocatalytic performance of as-synthesized samples. RhB dye was found to be the most sensitive organic molecule among all the considered dyes and degraded 78% in 120 min.
Quillaja brasiliensis saponin-based nanoparticulate adjuvants are capable of triggering early immune responses
Authors: Cibulski Samuel Paulo , Rivera-Patron Mariana , Mourglia-Ettlin Gustavo , Casaravilla Cecilia , Yendo Anna Carolina Alves , Fett-Neto Arthur Germano , Chabalgoity José Alejandro , Moreno María , Roehe Paulo Michel , Silveira Fernando
Published: September 2018

Commercially available saponins are extracted from Quillaja saponaria barks, being Quil A® the most widely used. Nanoparticulate immunostimulating complexes (ISCOMs or ISCOMATRIX) formulated with these, are able to stimulate strong humoral and cellular immune responses. Recently, we formulated novel ISCOMs replacing QuilA® by QB-90 (IQB-90), a Quillaja brasiliensis leaf-extracted saponin fraction, and reported that IQB-90 improved antigen uptake, and induced systemic and mucosal antibody production, and T-cell responses. However, its mechanism of action remains unclear. In this study we provide a deeper insight into the immune stimulatory properties of QB-90 and ISCOMATRIX-like based on this fraction (IMXQB-90). We show herein that, when used as a viral vaccine adjuvant, QB-90 promotes an “immunocompetent environment”. In addition, QB-90 and IMXQB-90 induce immune-cells recruitment at draining-lymph nodes and spleen. Subsequently, we prove that QB-90 or IMXQB-90 stimulated dendritic cells secret IL-1β by mechanisms involving Caspase-1/11 and MyD88 pathways, implying canonical inflammasome activation. Finally, both formulations induce a change in the expression of cytokines and chemokines coding genes, many of which are up-regulated. Findings reported here provide important insights into the molecular and cellular mechanisms underlying the adjuvant activity of Q. brasiliensis leaf-saponins and its respective nanoparticles.
The regulation of miRNAs by reconstituted high-density lipoproteins in diabetes-impaired angiogenesis
Authors: Hourigan Samuel T. , Solly Emma L. , Nankivell Victoria A. , Ridiandries Anisyah , Weimann Benjamin M. , Henriquez Rodney , Tepper Edward R. , Zhang Jennifer Q. J. , Tsatralis Tania , Clayton Zoe E. , Vanags Laura Z. , Robertson Stacy , Nicholls Stephen J. , Ng Martin K. C. , Bursill Christina A. , Tan Joanne T. M.
Published: September 2018

Diabetic vascular complications are associated with impaired ischaemia-driven angiogenesis. We recently found that reconstituted high-density lipoproteins (rHDL) rescue diabetes-impaired angiogenesis. microRNAs (miRNAs) regulate angiogenesis and are transported within HDL to sites of injury/repair. The role of miRNAs in the rescue of diabetes-impaired angiogenesis by rHDL is unknown. Using a miRNA array, we found that rHDL inhibits hsa-miR-181c-5p expression in vitro and using a hsa-miR-181c-5p mimic and antimiR identify a novel anti-angiogenic role for miR-181c-5p. miRNA expression was tracked over time post-hindlimb ischaemic induction in diabetic mice. Early post-ischaemia when angiogenesis is important, rHDL suppressed hindlimb mmu-miR-181c-5p. mmu-miR-181c-5p was not detected in the plasma or within HDL, suggesting rHDL specifically targets mmu-miR-181c-5p at the ischaemic site. Three known angiogenic miRNAs (mmu-miR-223-3p, mmu-miR-27b-3p, mmu-miR-92a-3p) were elevated in the HDL fraction of diabetic rHDL-infused mice early post-ischaemia. This was accompanied by a decrease in plasma levels. Only mmu-miR-223-3p levels were elevated in the hindlimb 3 days post-ischaemia, indicating that rHDL regulates mmu-miR-223-3p in a time-dependent and site-specific manner. The early regulation of miRNAs, particularly miR-181c-5p, may underpin the rescue of diabetes-impaired angiogenesis by rHDL and has implications for the treatment of diabetes-related vascular complications.