bluuebunny/crossref_metadata_2025 huggingface dataset:
A seismically induced onshore surge deposit at the KPg boundary, North Dakota
Authors: DePalma Robert A. , Smit Jan , Burnham David A. , Kuiper Klaudia , Manning Phillip L. , Oleinik Anton , Larson Peter , Maurrasse Florentin J. , Vellekoop Johan , Richards Mark A. , Gurche Loren , Alvarez Walter
Published: April 2019

Significance

The Chicxulub impact played a crucial role in the Cretaceous–Paleogene extinction. However the earliest postimpact effects, critical to fully decode the profound influence on Earth’s biota, are poorly understood due to a lack of high-temporal-resolution contemporaneous deposits. The Tanis site, which preserves a rapidly deposited, ejecta-bearing bed in the Hell Creek Formation, helps to resolve that long-standing deficit. Emplaced immediately (minutes to hours) after impact, Tanis provides a postimpact “snapshot,” including ejecta accretion and faunal mass death, advancing our understanding of the immediate effects of the Chicxulub impact. Moreover, we demonstrate that the depositional event, calculated to have coincided with the arrival of seismic waves from Chicxulub, likely resulted from a seismically coupled local seiche.
Underwater ritual offerings in the Island of the Sun and the formation of the Tiwanaku state
Authors: Delaere Christophe , Capriles José M. , Stanish Charles
Published: April 2019

Significance

Ritual and religion are significant factors in primary or archaic state formation. These beliefs and practices not only legitimize these new political organizations in their ability to control supernatural forces, but also incentivize intragroup cooperation by punishing freeloading and rewarding cooperative behavior. Recent archaeological excavations from an underwater ceremonial location near the Island of the Sun in Lake Titicaca have revealed the remarkable constituent elements of repetitive rituals practiced by the Tiwanaku state between the 8th and 10th centuries CE. Evidence of animal sacrifice and high-value offerings of vessels, gold, shells, and lapidary stones on a strategically located reef illustrates how power was consolidated in one of the earliest Andean states.
The effect of frequency on learners’ ability to recall the forms of deliberately learned L2 multiword expressions
Authors: Lindstromberg Seth , Eyckmans June
Published: April 2019

In incidental learning, open class vocabulary items with high or relatively high objective frequency in input are comparatively likely to be acquired. However, many single words and most multiword expressions (MWEs) occur infrequently in authentic input. It has therefore been argued that learners of school age or older can benefit from episodes of instructed or self-managed deliberate (or intentional) L2 vocabulary learning, especially when L2 is learned in an EFL environment and most especially when productive knowledge is the goal. A relevant question is whether the objective frequency of vocabulary items is an important factor in production-oriented deliberate L2 vocabulary learning. We report three small-scale interim meta-analyses addressing this question with regard to two-word English Adj-Noun and Noun-Noun expressions. The data derive from 8 original studies involving 406 learners and 139 different MWEs. Our results suggest that objective frequency has a weak, possibly negative effect in the deliberate learning of MWE forms.
Statistical knowledge and training in second language acquisition
Authors: Gonulal Talip
Published: April 2019

The present study investigated second language acquisition (SLA) doctoral students’ statistical training and knowledge of statistics. One hundred and twenty SLA doctoral students in North America took a comprehensive statistics survey, and 16 of them participated in follow-up interviews. The results showed that doctoral students were well trained in basic descriptive statistics, while their training in inferential statistics, particularly advanced statistics, was limited. When looking at their statistical knowledge, the results indicated that SLA doctoral students were good at understanding descriptive and inferential statistics, but they found it hard to interpret statistical analyses related to inferential statistics that are commonly encountered in SLA research. Several suggestions directed toward improving statistical literacy in SLA were provided.
PAK2 links cell survival to mechanotransduction and metabolism
Authors: Campbell Hannah K. , Salvi Alicia M. , O’Brien Timothy , Superfine Richard , DeMali Kris A.
Published: April 2019

Too little or too much force can trigger cell death, yet factors that ensure the survival of cells remain largely unknown. Here, we demonstrate that E-cadherin responds to force by recruiting and activating p21-activated protein kinase 2 (PAK2) to allow cells to stiffen, metabolize, and survive. Interestingly, PAK2 activation and its control of the apoptotic response are specific for the amplitude of force applied. Specifically, under low amplitudes of physiological force, PAK2 is protected from proteolysis, thereby ensuring cell survival. In contrast, under higher amplitudes of physiological force, PAK2 is left unprotected and stimulates apoptosis, an effect that is prevented by cleavage-resistant forms of the protein. Finally, we demonstrate that PAK2 protection is conferred by direct binding of AMPK. Thus, PAK2 mediates the survival of cells under force. These findings reveal an unexpected paradigm for how mechanotransduction, metabolism, and cell survival are linked.
Thyrotropin aggravates atherosclerosis by promoting macrophage inflammation in plaques
Authors: Yang Chongbo , Lu Ming , Chen Wenbin , He Zhao , Hou Xu , Feng Mei , Zhang Hongjia , Bo Tao , Zhou Xiaoming , Yu Yong , Zhang Haiqing , Zhao Meng , Wang Laicheng , Yu Chunxiao , Gao Ling , Jiang Wenjian , Zhang Qunye , Zhao Jiajun
Published: April 2019

Subclinical hypothyroidism is associated with cardiovascular diseases, yet the underlying mechanism remains largely unknown. Herein, in a common population (n = 1,103), TSH level was found to be independently correlated with both carotid plaque prevalence and intima-media thickness. Consistently, TSH receptor ablation in ApoE−/− mice attenuated atherogenesis, accompanied by decreased vascular inflammation and macrophage burden in atherosclerotic plaques. These results were also observed in myeloid-specific Tshr-deficient ApoE−/− mice, which indicated macrophages to be a critical target of the proinflammatory and atherogenic effects of TSH. In vitro experiments further revealed that TSH activated MAPKs (ERK1/2, p38α, and JNK) and IκB/p65 pathways in macrophages and increased inflammatory cytokine production and their recruitment of monocytes. Thus, the present study has elucidated the new mechanisms by which TSH, as an independent risk factor of atherosclerosis, aggravates vascular inflammation and contributes to atherogenesis.
Modelling public health improvements as a result of air pollution control policies in the UK over four decades—1970 to 2010
Authors: Carnell E , Vieno M , Vardoulakis S , Beck R , Heaviside C , Tomlinson S , Dragosits U , Heal MR , Reis S
Published: April 2019

In much of the industrialised world, policy interventions to address the challenges of wide-spread air pollution as resulting from development and economic progress in the 2nd half of the 20th century have overall led to reductions in air pollution levels and related health effects since the 1970s. While overall improvements towards reducing health effects from ambient air pollution are recorded, comprehensive and consistent assessments of the long-term impact of policy interventions are still scarce. In this paper, we conduct a model assessment over a 40 year period of air pollution in the UK. In order to correct for the short and longer term variability of meteorological factors contributing to trends in ambient concentrations of priority air pollutants (nitrogen dioxide, sulphur dioxide, fine particulate matter and ozone), we use a fixed meteorological year for all model simulations. Hence, the modelled changes in air pollutant concentrations and related health effects are solely a function of the changes in emissions since 1970. These changes in emissions are primarily driven by policy interventions, ranging from phasing out of specific fuels or substances, to regulating the use of chemicals and driving the development of cleaner, more efficient technologies. Over the 40 year period, UK attributable mortality due to exposure to PM2.5 and NO2 have declined by 56% and 44% respectively, while ozone attributable respiratory mortality increased by 17% over the same period (however, with a slight decrease by 14% between 2000 and 2010).
The effects of climate extremes on global agricultural yields
Authors: Vogel Elisabeth , Donat Markus G , Alexander Lisa V , Meinshausen Malte , Ray Deepak K , Karoly David , Meinshausen Nicolai , Frieler Katja
Published: April 2019

Climate extremes, such as droughts or heat waves, can lead to harvest failures and threaten the livelihoods of agricultural producers and the food security of communities worldwide. Improving our understanding of their impacts on crop yields is crucial to enhance the resilience of the global food system. This study analyses, to our knowledge for the first time, the impacts of climate extremes on yield anomalies of maize, soybeans, rice and spring wheat at the global scale using sub-national yield data and applying a machine-learning algorithm. We find that growing season climate factors—including mean climate as well as climate extremes—explain 20%–49% of the variance of yield anomalies (the range describes the differences between crop types), with 18%–43% of the explained variance attributable to climate extremes, depending on crop type. Temperature-related extremes show a stronger association with yield anomalies than precipitation-related factors, while irrigation partly mitigates negative effects of high temperature extremes. We developed a composite indicator to identify hotspot regions that are critical for global production and particularly susceptible to the effects of climate extremes. These regions include North America for maize, spring wheat and soy production, Asia in the case of maize and rice production as well as Europe for spring wheat production. Our study highlights the importance of considering climate extremes for agricultural predictions and adaptation planning and provides an overview of critical regions that are most susceptible to variations in growing season climate and climate extremes.
Juvenile plumage whiteness is associated with the evolution of clutch size in passerines
Authors: Morales Judith , Cuervo José Javier , Moreno Juan , Soler Juan José
Published: April 2019

The offspring of many animals are conspicuous during parental dependence, despite juveniles generally suffering from high predation risk. However, to date, it is unclear whether offspring structural ornaments play a role in intrafamily communication. This is the case of conspicuous plumage in young birds, which is worn unchanged during a long period after fledging, when they still depend on their parents. If plumage color facilitates intrafamily interactions, its role should be more important in large-brooded species, where the strength of intrafamily conflict is potentially stronger. We therefore performed a comparative study in 210 passerine bird species to test whether an offspring structural trait, white plumage, evolves more frequently in lineages with larger clutches. We also explored the number of broods raised per year as another source of intrafamily conflict. First, we found that juvenile whiteness was more frequent in open-nesting species. Moreover, in agreement with our prediction, the presence of juvenile white tail/wing patches was strongly and positively associated with clutch size. This relationship was not due to the strong resemblance between offspring and adult plumage, which was controlled for in the statistical analyses. Moreover, the association remained significant after taking into account predation risk, for which there was information for a subset of species. In contrast, juvenile whiteness was not associated with the number of broods raised per year. These results may suggest that the evolution of juvenile conspicuousness is favored in species with potentially stronger intrabrood sibling conflict.
PRISMOID: a comprehensive 3D structure database for post-translational modifications and mutations with functional impact
Authors: Li Fuyi , Fan Cunshuo , Marquez-Lago Tatiana T , Leier André , Revote Jerico , Jia Cangzhi , Zhu Yan , Smith A Ian , Webb Geoffrey I , Liu Quanzhong , Wei Leyi , Li Jian , Song Jiangning
Published: April 2019

Post-translational modifications (PTMs) play very important roles in various cell signaling pathways and biological process. Due to PTMs’ extremely important roles, many major PTMs have been studied, while the functional and mechanical characterization of major PTMs is well documented in several databases. However, most currently available databases mainly focus on protein sequences, while the real 3D structures of PTMs have been largely ignored. Therefore, studies of PTMs 3D structural signatures have been severely limited by the deficiency of the data. Here, we develop PRISMOID, a novel publicly available and free 3D structure database for a wide range of PTMs. PRISMOID represents an up-to-date and interactive online knowledge base with specific focus on 3D structural contexts of PTMs sites and mutations that occur on PTMs and in the close proximity of PTM sites with functional impact. The first version of PRISMOID encompasses 17 145 non-redundant modification sites on 3919 related protein 3D structure entries pertaining to 37 different types of PTMs. Our entry web page is organized in a comprehensive manner, including detailed PTM annotation on the 3D structure and biological information in terms of mutations affecting PTMs, secondary structure features and per-residue solvent accessibility features of PTM sites, domain context, predicted natively disordered regions and sequence alignments. In addition, high-definition JavaScript packages are employed to enhance information visualization in PRISMOID. PRISMOID equips a variety of interactive and customizable search options and data browsing functions; these capabilities allow users to access data via keyword, ID and advanced options combination search in an efficient and user-friendly way. A download page is also provided to enable users to download the SQL file, computational structural features and PTM sites’ data. We anticipate PRISMOID will swiftly become an invaluable online resource, assisting both biologists and bioinformaticians to conduct experiments and develop applications supporting discovery efforts in the sequence–structural–functional relationship of PTMs and providing important insight into mutations and PTM sites interaction mechanisms. The PRISMOID database is freely accessible at http://prismoid.erc.monash.edu/. The database and web interface are implemented in MySQL, JSP, JavaScript and HTML with all major browsers supported.
IntronDB: a database for eukaryotic intron features
Authors: Wang Dapeng
Published: April 2019

The rate and extent of unbalanced eukaryotic intron changes exhibit dynamic patterns for different lineages of species or certain functional groups of genes with varied spatio-temporal expression modes affected by selective pressure. To date, only a few key conserved splicing signals or regulatory elements have been identified in introns and little is known about the remaining intronic regions. To trace the evolutionary trajectory of spliceosomal introns from available genomes under a unified framework, we present IntronDB, which catalogs ∼50 000 000 introns from over 1000 genomes spanning the major eukaryotic clades in the tree of life. Based on the position of introns relative to coding regions, it categorizes introns into three groups, such as 5'UTR, CDS and 3'UTR and subsequently divides CDS introns into three categories, such as phase 0, phase 1 and phase 2. It provides the quality evaluation for each sequence entry and characterizes the intronic parameters including number, size, sequence composition and positioning information as well as the features for exons and genes, making possible the comparisons between introns and exons. It reports the dinucleotides around the intron boundary and displays the consensus sequence features for all introns, small introns and large introns for each genome. By incorporating the taxonomic assignment of genomes, it performs high-level or genome-wide statistical analysis for single feature and coupled features both in a single genome and across multiple genomes. It offers functionalities to browse the data from representative protein-coding transcripts and download the data from all transcripts from protein-coding genes.

Availability and implementation

http://www.nextgenbioinformatics.org/IntronDB.

Supplementary information

Supplementary data are available at Bioinformatics online.
A sequential interferon gamma directed chemotactic cellular immune response determines survival and cardiac function post-myocardial infarction
Authors: Finger Stefanie , Knorr Maike , Molitor Michael , Schüler Rebecca , Garlapati Venkata , Waisman Ari , Brandt Moritz , Münzel Thomas , Bopp Tobias , Kossmann Sabine , Karbach Susanne , Wenzel Philip
Published: April 2019

Aims

Myelomonocytic cells are critical in injury and healing post-myocardial infarction (MI). Mechanisms of regulation, however, are incompletely understood. The aim of the study was to elucidate the role of interferon gamma (IFN-γ) in the orchestrated inflammatory response in a murine model of MI.

Methods and results

MI was induced in 8- to 12-week-old male mice (C57BL/6 background) by permanent ligation of the left anterior descending (LAD) coronary artery. Lysozyme M (LysM)+ cell-depleted LysMiDTR transgenic mice displayed a reduced influx of CD45.2+/CD3−/CD11b+/Gr-1high neutrophils into infarcted myocardium 1 day post-MI compared with infarcted controls, paralleled by decreased cardiac mRNA levels of IFN-γ and tumour necrosis factor alpha (TNF-α). Mortality after MI was significantly increased in LysM+ cell-depleted mice within 28 days post-MI. To more specifically address the role of neutrophils, we depleted C57BL/6 mice with a monoclonal anti-Gr-1 antibody and found increased mortality, deteriorated cardiac function as well as decreased cardiac IFN-γ mRNA expression early after MI. Ccl2, Cxcl1, Cx3cl1, and Il12b mRNA were reduced 3 days after MI, as was the amount of CD11b+/Ly-6G−/Ly-6Chigh inflammatory monocytes. LAD-ligated Cramp−/− mice lacking cathelicidin important in neutrophil-dependent monocyte chemotaxis as well as IFNγ−/− and TNFα−/− mice phenocopied Gr-1+ cell-depleted mice, supporting a regulatory role of IFN-γ impacting on both the sequence of inflammatory cell invasion and cardiac outcome early after MI. The use of conditional IFN-γ receptor deficient mice indicated a direct effect of IFN-γ on LysM+ cells in cardiac injury post-MI. Using IFN-γ reporter mice and flow cytometry, we identified cardiac lymphoid cells (CD4+ and CD8+ T cells and natural killer cells) as primary source of this cytokine in the cardiac inflammatory response post-MI.

Conclusion

IFN-γ directs a sequential chemotactic cellular immune response and determines survival and cardiac function post-MI.
Magnetic resonance hyperpolarization imaging detects early myocardial dysfunction in a porcine model of right ventricular heart failure
Authors: Agger Peter , Hyldebrandt Janus Adler , Hansen Esben Søvsø Szocska , Omann Camilla , Bøgh Nikolaj , Waziri Farhad , Nielsen Per Mose , Laustsen Christoffer
Published: April 2019

Aims

Early detection of heart failure is important for timely treatment. During the development of heart failure, adaptive intracellular metabolic processes that evolve prior to macro-anatomic remodelling, could provide an early signal of impending failure. We hypothesized that metabolic imaging with hyperpolarized magnetic resonance would detect the early development of heart failure before conventional echocardiography could reveal cardiac dysfunction.

Methods and results

Five 8.5 kg piglets were subjected to pulmonary banding and subsequently examined by [1-13C]pyruvate hyperpolarization, conventional magnetic resonance imaging, echocardiography, and blood testing, every 4 weeks for 16 weeks. They were compared with a weight matched, healthy control group. Conductance catheter examination at the end of the study showed impaired right ventricular systolic function along with compromised left ventricular diastolic function. After 16 weeks, we saw a significant decrease in the conversion ratio of pyruvate/bicarbonate in the left ventricle from 0.13 (0.04) in controls to 0.07 (0.02) in animals with pulmonary banding, along with a significant increase in the lactate/bicarbonate ratio to 3.47 (1.57) compared with 1.34 (0.81) in controls. N-terminal pro-hormone of brain natriuretic peptide was increased by more than 300%, while cardiac index was reduced to 2.8 (0.95) L/min/m2 compared with 3.9 (0.95) in controls. Echocardiography revealed no changes.

Conclusion

Hyperpolarization detected a shift towards anaerobic metabolism in early stages of right ventricular dysfunction, as evident by an increased lactate/bicarbonate ratio. Dysfunction was confirmed with conductance catheter assessment, but could not be detected by echocardiography. Hyperpolarization has a promising future in clinical assessment of heart failure in both acquired and congenital heart disease.
Evaluation of a simple technique aiming at optimizing point-by-point isolation of the left pulmonary veins: a randomized study
Authors: Kyriakopoulou Maria , Strisciuglio Teresa , El Haddad Milad , De Pooter Jan , Almorad Alexandre , Van Beeumen Katarina , Unger Philippe , Vandekerckhove Yves , Tavernier René , Duytschaever Mattias , Knecht Sébastien
Published: April 2019

Aims

We sought to evaluate the efficacy and the safety of a simple technique for stabilizing the ablation catheter during anterior pulmonary vein (PV) encirclement in patients ablated for paroxysmal atrial fibrillation. This consisted of bending the ablation catheter in the left atrium, creating a loop that was cautiously advanced together with the long sheath at the ostium and then within the left superior PV. The curve was then progressively released to reach a stable contact with the anterior part of the left PVs.

Methods and results

Eighty consecutive patients (age 64 ± 11 years, left atrial diameter 43 ± 8 mm) undergoing ‘CLOSE’-guided PV isolation were prospectively randomized into two groups depending on whether the loop technique was used or not. When using the loop technique, the encirclement of the left PVs was shorter [20 min (interquartile range, IQR 17–24) vs. 26 min (IQR 18–33), P < 0.01] with a high rate of first pass isolation [(100%) vs. (97%), P = 0.9] and adenosine proof isolation [(93%) vs. (95%), P = 0.67]. Most specifically, at the anterior part of the left PVs, there were less dislocations [0 (IQR 0–0) vs. 1 (IQR 0–4), P < 0.001], radiofrequency duration was shorter (272 ± 85 s vs. 378 ± 122 s, P < 0.001), force-time integral was higher [524 gs (IQR 427–687) vs. 398 gs (IQR 354–451), P < 0.001], average contact force was higher [20 g (IQR 13–27) vs. 11g (IQR 9–16), P < 0.001], and impedance drop was higher [12 Ω (IQR 9–19) vs. 10 Ω (IQR 7–14), P < 0.001].

Conclusion

This study describes a simple technique to facilitate catheter stability at the anterior part of the left PVs, resulting in more efficient left PV encirclement without compromising safety.
Incidence of appropriate implantable cardioverter-defibrillator therapy and mortality after implantable cardioverter-defibrillator generator replacement: results from a real-world nationwide cohort
Authors: Ruwald Martin H , Ruwald Anne-Christine , Johansen Jens Brock , Gislason Gunnar , Nielsen Jens Cosedis , Philbert Berit , Riahi Sam , Vinther Michael , Lindhardt Tommi B
Published: April 2019

Aims

The safety of omitting implantable cardioverter-defibrillator (ICD) generator replacement in patients with no prior appropriate therapy, comorbid conditions, and advanced age is unclear. The aim was to investigate incidence of appropriate ICD therapy after generator replacement.

Methods and results

We identified patients implanted with a primary prevention ICD (n = 4630) from 2007 to 2016, who subsequently underwent an elective ICD generator replacement (n = 670) from the Danish Pacemaker and ICD Register. The data were linked to other databases and evaluated the outcomes of appropriate therapy and death. Predictors of ICD therapy were identified using multivariate Cox regression analyses. A total of 670 patients underwent elective ICD generator replacement. Of these, 197 (29.4%) patients had experienced appropriate therapy in their 1st generator period. During follow-up of 2.0 ± 1.6 years, 95 (14.2%) patients experienced appropriate therapy. Predictors of appropriate therapy in 2nd generator period was low initial left ventricular ejection fraction (≤25%) [hazard ratio (HR) 1.87, confidence interval (CI) 1.13–1.95] and appropriate therapy in 1st generator period (HR 3.95, CI 2.57–6.06). For patients with appropriate therapy in 1st generator period, 4-year incidence of appropriate therapy was 50.6% vs. 16.4% in those without (P < 0.001). Among patients >80 years with no prior appropriate therapy 8.8% of patients experienced appropriate therapy after replacement. Comorbidity burden and advanced age were associated with reduced device utilization after replacement and a high competing risk of death without preceding appropriate therapy.

Conclusion

A significant residual risk of appropriate therapy in the 2nd generator was present even among patients with advanced age and with a full prior generator period without any appropriate ICD events.
Patterns of alcohol consumption and alcohol-related harm among European university students
Authors: Cooke Richard , Beccaria Franca , Demant Jakob , Fernandes-Jesus Maria , Fleig Lena , Negreiros Jorge , Scholz Urte , de Visser Richard
Published: April 2019

Background

To compare patterns of alcohol consumption and alcohol-related harm from a survey of university students sampled from universities in Denmark, England, Germany, Italy, Portugal and Switzerland.

Methods

A total of 2191 university students (70% female, 90% white ethnic group, age range 18–25) completed the survey. Participants completed measures of demographic variables (age, age of onset, ethnic group and sex) and the Alcohol Use Disorders Identification Test (AUDIT), which was the primary outcome.

Results

Sixty-three percent of the sample scored negative for harmful drinking on the AUDIT (<8), with 30% categorized as hazardous drinkers, 4% harmful drinkers and 3% with probable dependence. Analysis of variance, including demographic factors as covariates, identified a main effect of country on AUDIT scores F(5, 2086) = 70.97, P < 0.001, partial eta square = 0.15. AUDIT scores were highest in England (M = 9.99; SD = 6.17) and Denmark (M = 9.52; SD = 4.86) and lowest in Portugal (M = 4.90; ° = 4.60). Post hoc tests indicated large effect size differences between scores in Denmark and England and scores in all other countries (0.79 < d < 0.94; all P’s < 0.001).

Conclusions

European university students in our sample mainly reported low risk patterns of alcohol consumption and alcohol-related harm. However, students from Northern European countries had significantly higher AUDIT scores compared with students from Central and Southern European countries. Research is needed to replicate the present study using nationally representative samples to estimate the prevalence of alcohol use disorders among university students in different European countries.
Discovered by genomics: putative reductive dehalogenases with N-terminus transmembrane helixes
Authors: Atashgahi Siavash
Published: April 2019

Attempts for bioremediation of toxic organohalogens resulted in the identification of organohalide-respiring bacteria harbouring reductive dehalogenases (RDases) enzymes. RDases consist of the catalytic subunit (RdhA, encoded by rdhA) that does not have membrane-integral domains, and a small putative membrane anchor (RdhB, encoded by rdhB) that (presumably) locates the A subunit to the outside of the cytoplasmic membrane. Recent genomic studies identified a putative rdh gene in an uncultured deltaproteobacterial genome that was not accompanied by an rdhB gene, but contained transmembrane helixes in N-terminus. Therefore, rather than having a separate membrane anchor protein, this putative RDase is likely a hybrid of RdhA and RdhB, and directly connected to the membrane with transmembrane helixes. However, functionality of the hybrid putative RDase remains unknown. Further analysis showed that the hybrid putative rdh genes are present in the genomes of pure cultures and uncultured members of Bacteriodetes and Deltaproteobacteria, but also in the genomes of the candidate divisions. The encoded hybrid putative RDases have cytoplasmic or exoplasmic C-terminus localization, and cluster phylogenetically separately from the existing RDase groups. With increasing availability of (meta)genomes, more diverse and likely novel rdh genes are expected, but questions regarding their functionality and ecological roles remain open.
A de novo substitution in BCL11B leads to loss of interaction with transcriptional complexes and craniosynostosis
Authors: Goos Jacqueline A C , Vogel Walter K , Mlcochova Hana , Millard Christopher J , Esfandiari Elahe , Selman Wisam H , Calpena Eduardo , Koelling Nils , Carpenter Evan L , Swagemakers Sigrid M A , van der Spek Peter J , Filtz Theresa M , Schwabe John W R , Iwaniec Urszula T , Mathijssen Irene M J , Leid Mark , Twigg Stephen R F
Published: April 2019

Craniosynostosis, the premature ossification of cranial sutures, is a developmental disorder of the skull vault, occurring in approximately 1 in 2250 births. The causes are heterogeneous, with a monogenic basis identified in ~25% of patients. Using whole-genome sequencing, we identified a novel, de novo variant in BCL11B, c.7C>A, encoding an R3S substitution (p.R3S), in a male patient with coronal suture synostosis. BCL11B is a transcription factor that interacts directly with the nucleosome remodelling and deacetylation complex (NuRD) and polycomb-related complex 2 (PRC2) through the invariant proteins RBBP4 and RBBP7. The p.R3S substitution occurs within a conserved amino-terminal motif (RRKQxxP) of BCL11B and reduces interaction with both transcriptional complexes. Equilibrium binding studies and molecular dynamics simulations show that the p.R3S substitution disrupts ionic coordination between BCL11B and the RBBP4–MTA1 complex, a subassembly of the NuRD complex, and increases the conformational flexibility of Arg-4, Lys-5 and Gln-6 of BCL11B. These alterations collectively reduce the affinity of BCL11B p.R3S for the RBBP4–MTA1 complex by nearly an order of magnitude. We generated a mouse model of the BCL11B p.R3S substitution using a CRISPR-Cas9-based approach, and we report herein that these mice exhibit craniosynostosis of the coronal suture, as well as other cranial sutures. This finding provides strong evidence that the BCL11B p.R3S substitution is causally associated with craniosynostosis and confirms an important role for BCL11B in the maintenance of cranial suture patency.
Sexually Antagonistic Mitonuclear Coevolution in Duplicate Oxidative Phosphorylation Genes
Authors: Havird Justin C , McConie Hunter J
Published: April 2019

Mitochondrial function is critical in eukaryotes. To maintain an adequate supply of energy, precise interactions must be maintained between nuclear- and mitochondrial-encoded gene products. Such interactions are paramount in chimeric enzymes such as the oxidative phosphorylation (OXPHOS) complexes. Mutualistic coevolution between the two genomes has therefore been suggested to be a critical, ubiquitous feature of eukaryotes that acts to maintain cellular function. However, mitochondrial genomes can also act selfishly and increase their own transmission at the expense of organismal function. For example, male-harming mutations are predisposed to accumulate in mitochondrial genomes due to their maternal inheritance (“mother’s curse”). Here, we investigate sexually antagonistic mitonuclear coevolution in nuclear-encoded OXPHOS paralogs from mammals and Drosophila. These duplicate genes are highly divergent but must interact with the same set of mitochondrial-encoded genes. Many such paralogs show testis-specific expression, prompting previous hypotheses suggesting they may have evolved under selection to counteract male-harming mitochondrial mutations. We found increased rates of evolution in OXPHOS paralogs with testis-specific expression in mammals and Drosophila, supporting this hypothesis. However, further analyses suggested such patterns may be due to relaxed, not positive selection, especially in Drosophila. Structural data also suggest that mitonuclear interactions do not play a major role in the evolution of many OXPHOS paralogs in a consistent way. In conclusion, no single OXPHOS paralog met all our criteria for being under selection to counteract male-harming mitochondrial mutations. We discuss alternative explanations for the drastic patterns of evolution in these genes, including mutualistic mitonuclear coevolution, adaptive subfunctionalization after gene duplication, and relaxed selection on OXPHOS in male tissues.
Developing spatio-temporal models using multiple data types for evaluating population trends and habitat usage
Authors: Grüss Arnaud , Thorson James T
Published: April 2019

Spatio-temporal models have become key tools for evaluating population trends and habitat usage. We developed a spatio-temporal modelling framework employing a combination of encounter/non-encounter, count, and biomass data collected by different monitoring programs (“combined data”). The three data types are predicted using a computationally efficient approximation to a compound Poisson-gamma process. We fitted spatio-temporal models to combined data for Gulf of Mexico (GOM) red snapper (Lutjanus campechanus) for 2006–2014. These spatio-temporal models provided insights into GOM red snapper spatial distribution patterns, which we corroborated by comparing to past predictions generated using only encounter/non-encounter data. However, relying on biomass and count data in addition to encounter/non-encounter data also allowed us to reconstruct biomass trends for GOM red snapper and to examine patterns of distribution shifts and range expansion/contraction for this population for the first time. Moreover, combining multiple data types improved the precision of reconstructed population trends and some variables quantifying habitat usage. Finally, scenarios and simulation experiments conditioned upon red snapper data showed that the improvement in fitting to combined data is greater when biomass data for the study population are lacking for an entire subregion and, to a lesser extent, for an entire time period (e.g. in early years).
Excluding Women
Authors: Dauvergne Catherine , Lindy Hannah
Published: April 2019

This article reviews 16 years of Canadian case law applying the Refugee Convention’s exclusion provisions to women. Despite a quarter of a century of strong scholarly and policy-making work asserting the need for attention to gender in refugee law, this dataset shows that, in questions of exclusion, gendered analysis is almost entirely absent. By contrast, in seeking explanations for the factual basis of exclusion in these cases, gender is almost always an explanatory factor. This stark observation leads us to conclude that significant additional work – both scholarly and policy-focused – is required. The article also considers whether a more robust application of existing Supreme Court jurisprudence can address the problems we have identified and reaches a mixed conclusion. Overall, the article points out an important gap in current understandings of gender in refugee law, and maps a way forward for future work in the area.
Stabilization of high order cut finite element methods on surfaces
Authors: Larson Mats G , Zahedi Sara
Published: April 2019

We develop and analyse a stabilization term for cut finite element approximations of an elliptic second-order partial differential equation on a surface embedded in ${\mathbb{R}}^d$. The new stabilization term combines properly scaled normal derivatives at the surface together with control of the jump in the normal derivatives across faces, and provides control of the variation of the finite element solution on the active three-dimensional elements that intersect the surface. We show that the condition number of the stiffness matrix is $O(h^{-2})$, where $h$ is the mesh parameter. The stabilization term works for linear as well as for higher-order elements and the derivation of its stabilizing properties is quite straightforward, which we illustrate by discussing the extension of the analysis to general $n$-dimensional smooth manifolds embedded in ${\mathbb{R}}^d$, with codimension $d-n$. We also state the properties of a general stabilization term that are sufficient to prove optimal scaling of the condition number and optimal error estimates in energy- and $L^2$-norm. We finally present numerical studies confirming our theoretical results.
Effect of TIPE1 on Immune Function of Dendritic Cells and Its Signaling Pathway in Septic Mice
Authors: Luan Ying-yi , Zhang Lei , Zhu Fu-jun , Dong Ning , Lu Jiang-yang , Yao Yong-ming
Published: April 2019

Dendritic cell (DC) dysfunction plays a pivotal role in sepsis-induced immunosuppression. Tumor necrosis factor α (TNF-α)–induced protein 8 like-1 (TIPE1), a new member of the tumor necrosis factor α–induced protein 8 family, may be related to cell death. The aim of the present study was to elucidate the effect of TIPE1 on the immune function of DCs and its regulatory mechanism via PD-L1/PD-1 signaling in mice. Sepsis was induced in adult C57BL/6 male mice via cecal ligation and puncture. In vitro, we found that expression of CD80, CD86, and major histocompatibility complex class II in DCs and levels of cytokines, including tumor necrosis factor α and interleukin 12p40, were elevated; similarly, T-cell proliferation and differentiation were promoted when the gene expressing TIPE1 was silenced. Next, we examined the in vivo role of TIPE1 in a cecal ligation and puncture animal model system. Flow cytometry of the immune functional status in DCs revealed negative regulation of TIPE1 on DC maturation, as well as activation. Moreover, changes in PD-L1/PD-1 levels confirmed the negative effect of TIPE1 in DCs. Collectively, we report that TIPE1 might exert negative regulation in sepsis, at least in part by inhibiting DC maturation and subsequent T-cell–mediated immunity via PD-L1/PD-1 signaling.
Species Diversity and Seasonal Distribution of Hard Ticks (Acari: Ixodidae) Infesting Mammalian Hosts in Various Districts of Riyadh Province, Saudi Arabia
Authors: Alanazi Abdullah D , Al-Mohammed Hamdan I , Alyousif Mohamed S , Said Ashraf E , Salim Bashir , Abdel-Shafy Sobhy , Shaapan Raafat M
Published: April 2019

Hard ticks are among the most important blood sucking arthropods that transmit pathogens to humans and animals. This study was designed to determine prevalence, mapping, geographical distribution, and seasonal activity of hard tick species infesting the most common domestic and wild mammals in various districts of Riyadh Province, Saudi Arabia, during the period January to December 2017. In total, 10,832 adult hard ticks were collected from the bodies of 8,435 animals belonging to 18 different mammalian species. The ticks were preserved in 70% alcohol and microscopy was used to identify species. Two genera, Hyalomma and Rhipicephalus, were identified, comprising 10 species of hard ticks, with Hyalomma comprising 68.3% and Rhipicephalus comprising 31.7% of species. The most common species on domestic mammalian hosts was Hyalomma dromedarii (Koch 1844) (39.9%) followed by Rhipicephalus turanicus (Pomerantsev, Matikashvili & Lotosky 1936) (34.9%), whereas on wild mammalian hosts Rhipicephalus sanguineus (Latreille 1806) was by far the most prevalent species (83.0%). However, ticks were most abundant during May through July (36.0%) in the studied areas, and tick intensity and abundance differed among seasons. Our results provide information for human and animal health service managers, as well as governmental authorities, to gain a better understanding of hard ticks infesting mammalian hosts in Riyadh Province, Saudi Arabia, which can help improve prevention and control of tick-borne diseases, especially during outbreaks.
Influence of Clothing on Decomposition and Presence of Insects on Rabbit Carcasses
Authors: Mashaly Ashraf M , Mahmoud Ahmed , Ebaid Hossam
Published: April 2019

The decomposition rate and insects attraction to carcasses are affected by a number of factors such as temperature, body mass, the presence of poisons, humidity, and insect activity. The present study was planned to investigate the influence of clothing on both the decomposition process and the presence of insects on rabbit carcasses. The study was performed in May 2016 and involved the use of 18 live mature rabbits (Oryctolagus cuniculus L.), which were euthanized by chloroform. Rabbit carcasses were divided into three replicates with six rabbits in each replicate. Rabbits in each replicate were further subdivided, so that three rabbits were wrapped with cloth, whereas the remaining three were left unclothed. Both clothed and unclothed carcasses reached the dry stage within 6 d. The results of this study showed that clothes neither affect the decomposition process nor the presence of insects (flies and beetles). The pattern of flies and beetles, however, did vary significantly in the different decomposition stages. In total, 2,849 insects, including 2,459 flies and 390 beetles, were collected and sorted during the decomposition process. Among the dominant species, flies were assigned to the families Calliphoridae and Muscidae, whereas beetles were assigned to the families Dermestidae and Histeridae. Lucilia sericata Meigen, Musca domestica L., Dermestes maculatus DeGeer, and Saprinus moyses Marseul were the most abundant species occurring on both the clothed and unclothed carcasses. In conclusion, this study emphasized that, the clothes have no effect when dealing with decay process and insect attraction to the carrions.
Stability of West Nile Virus (Flaviviridae: Flavivirus) RNA in Mosquito Excreta
Authors: Ramírez Ana L , Hall-Mendelin Sonja , Hewitson Glen R , McMahon Jamie L , Staunton Kyran M , Ritchie Scott A , van den Hurk Andrew F
Published: April 2019

Arbovirus surveillance is crucial for the implementation of vector-borne disease control measures. Recently, it has been demonstrated that mosquitoes with a disseminated arbovirus infection excrete viral RNA, which can be detected by molecular methods. Thereby, mosquito excreta has been proposed as a sample type that could be utilized for arbovirus surveillance. In this study, we evaluated if West Nile virus (Kunjin strain, WNVKUN) RNA in Culex annulirostris Skuse (Diptera: Culicidae) excreta deposited on different substrates could be detected after storage for up to 2 wk at tropical conditions of high heat and humidity. No significant drop in relative quantity of WNVKUN RNA (determined by comparison of Ct values) in excreta deposited on Flinders Associate Technologies (FTA) cards was observed over 14 d, suggesting that RNA was stable for that time. There was no significant difference in relative quantity of WNVKUN RNA in excreta deposited on FTA cards or polycarbonate substrates after 24 h. However, after 7 and 14 d, there was a significant decline in the relative quantity of viral RNA in the excreta stored on polycarbonate substrates. For incorporation in arbovirus surveillance programs, we recommend the use of polycarbonate substrates for excreta collection in mosquito traps deployed overnight, and the integration of FTA cards in traps serviced weekly or fortnightly. Polycarbonate substrates facilitate the collection of the majority of excreta from a trap, and while FTA cards offer limited area coverage, they enable preservation of viral RNA in tropical conditions for extended periods of time.
Metachronous Contralateral Male Breast Cancer: Case Report and Literature Review
Authors: O’Leary Thomas R , Shriver Craig D , Wind Gary
Published: April 2019

Male breast cancer (MBC) is rare and consequently understudied. Here we present the case of contralateral breast cancer in a male patient nearly a quarter century following his initial breast cancer diagnosis and treatment. The epidemiology, risk factors, diagnosis, characterization, treatment, and prognosis of male breast cancer are reviewed. MBC accounts for <1% of all breast cancer with an estimated incidence nearly 1.25 per 100,000 person years. Our patient tested positive for ATM mutation of undetermined significance. More commonly in males, a BRCA2 mutation confers a >1 in 15 lifetime risk of breast cancer and is present in >11% of MBC patients, while BRCA1 is present in an estimated <1.5% of MBC patients. The risk of contralateral breast cancer developing in a male with a unilateral lesion is much higher than for a primary male breast cancer in the general population. Men tend to be diagnosed at a later age and stage than females. Prognosis for male and female breast cancer is similar considering both age of patient and stage of the tumor at diagnosis, and similar treatment paradigms have resulted in similar outcomes. Although lumpectomy with radiation therapy may have the same prognosis as mastectomy, the standard of care for male breast cancer continues to be simple mastectomy with sentinel lymph node biopsy.
Simulated Casualty Evacuation Performance Is Augmented by Deadlift Peak Force
Authors: Poser Whitney M , Trautman Kara A , Dicks Nathan D , Christensen Bryan K , Lyman Katie J , Hackney Kyle J
Published: April 2019

Introduction

The purpose of the current study was to examine if isometric peak force and rate of force development (RFD) were related to the ability to successfully perform a simulated casualty evacuation task in both unweighted and weighted conditions.

Methods

Eighteen male participants from Army Reserve Officers’ Training Corps (ROTC) completed a maximum isometric deadlift on a force plate (IRB#HE16227). Isometric peak force and RFD were calculated from ground reaction force. Two simulated casualty evacuation performance trials were then completed. The unweighted trial consisted of lifting and carrying a 75 kg dummy as quickly as possible for 50 m. The weighted trial was similar except 9 kg vests were added to both the simulation dummy and the participant to represent 18 kg of duty gear. Independent sample t-tests and Pearson correlations were performed to compare the characteristics of those who passed and failed the weighted trial.

Results

All of the participants (n = 18) completed the unweighted casualty evacuation trial, while 72% (n = 13) were able to complete the weighted casualty evacuation trial. The participants that successfully completed the weighted evacuation trial had significantly (p < 0.05) greater isometric peak force (1420 ± 165 vs. 1076 ± 256 N) and lean mass (74.18 ± 3.89 vs. 65.34 ± 3.89 kg) when compared to participants (n = 5) that could not complete the weighted evacuating task trial. Additionally, greater Army Physical Fitness Test scores (288 ± 13 vs. 269 ± 16 arbitrary units) and significantly faster (30.34 ± 4.41 vs. 44.92 ± 10.62 seconds) unweighted evacuation trial times were observed in participants that could complete the weighted evacuation task. Peak force was also significantly correlated with lean mass (r = 0.51, p < 0.05). There was no relationship between RFD and performance of the unweighted or weight trial.

Conclusion

Isometric deadlift peak force represents an important determinant for the success of a simulated casualty evacuation task and may be a useful marker to include in periodic fitness evaluations of military personnel.