bluuebunny/crossref_metadata_2025 huggingface dataset:
Submersion of impacting spheres at low Bond and Weber numbers owing to a confined pool
Authors: Chen Han , Liu Hao-Ran , Gao Peng , Ding Hang
Published: December 2019

We numerically investigate the mechanism resulting in fate change of a hydrophobic sphere impacting onto a confined pool, that is, at the same impact speed, it does not submerge in a wide pool but does in a narrow pool. We find that the reflection of the impact-induced gravity-capillary waves from the pool boundary is responsible for this phenomenon. In particular, the return of the wave to the symmetry axis may coincide with the rising of the impacting sphere to the water surface, which corresponds to the critical conditions of the fate change. Moreover, for the spheres at the onset of submersion in a wide pool, our analysis suggests that this scenario also accounts for an interesting observation in the numerical simulations. That is, the effective pool size$S_{c}$, beyond which the submersion of impacting spheres is no longer affected by the pool size$S$, is mainly dependent on the sphere diameter, no matter whether the surface waves are the capillary or gravity waves. For$S<S_{c}$, two important pool sizes ($S_{w,1}$and$S_{w,2}$, and$S_{w,2}\geqslant S_{w,1}$) are identified at the same impact speed, and the sphere submersion takes place at$S_{w,1}\leqslant S\leqslant S_{w,2}$. Based on the flow features identified in simulations, a scaling law is proposed to correlate the Weber number and Bond number with$S_{w}$. The theoretical prediction is shown to agree well with the numerical results.
Public Committee Against Torture in Israel v. Government of Israel. Case No. HCJ 769/02
Authors: Bodansky Daniel , Ben-Naftali Orna , Michaeli Keren
Published: December 2019

Public Committee Against Torture in Israel v. Government of Israel. Case No. HCJ 769/02. At
.

Supreme Court of Israel, sitting as the High Court of Justice, December 13, 2006.

In Public Committee Against Torture in Israel v. Government of Israel1 Targeted Killings) the Supreme Court of Israel, sitting as the High Court of Justice, examined the legality of Israel's “preventative targeted killings” of members of militant Palestinian organizations. The Court's unanimous conclusion reads:

The result of the examination is not that such strikes are always permissible or that they are always forbidden. The approach of customary international law applying to armed conflicts of an international nature is that civilians are protected from attacks by the army. However, that protection does not exist regarding those civilians “for such time as they take a direct part in hostilities” (§51(3) of [Additional Protocol I]). Harming such civilians, even if the result is death, is permitted, on the condition that there is no less harmful means, and on the condition that innocent civilians are not harmed. Harm to the latter must be proportional. (Para. 60)
Four decades of socio-economic inequality and secular change in the physical growth of Guatemalans
Authors: Mansukoski Liina , Johnson William , Brooke-Wavell Katherine , Galvez-Sobral J Andres , Furlán Luis , Cole Tim J , Bogin Barry
Published: December 2019

Objective:

To investigate changes in socio-economic inequalities in growth in height, weight, BMI and grip strength in children born during 1955–1993 in Guatemala, a period of marked socio-economic-political change.

Design:

We modelled longitudinal data on height, weight, BMI and hand grip strength using Super-Imposition by Translation and Rotation (SITAR). Internal Z-scores summarising growth size, timing and intensity (peak growth velocity, e.g. cm/year) were created to investigate inequalities by socio-economic position (SEP; measured by school attended). Interactions of SEP with date of birth were investigated to capture secular changes in inequalities.

Setting:

Urban and peri-urban schools in the region of Guatemala City, Guatemala.

Participants:

Participants were 40 484 children and adolescents aged 3–19 years of Ladino and Maya ancestry (nobservations 157 067).

Results:

The difference in height (SITAR size) between lowest and highest SEP decreased from −2·0 (95 % CI −2·2, −1·9) sd to −1·4 (95 % CI −1·5, −1·3) sd in males, and from −2·0 (95 % CI −2·1, −1·9) sd to −1·2 (95 % CI −1·3, −1·2) sd in females over the study period. Inequalities also reduced for weight, BMI and grip strength, due to greater secular increases in lowest-SEP groups. The puberty period was earlier and shorter in higher-SEP individuals (earlier SITAR timing and higher SITAR intensity). All SEP groups showed increases in BMI intensity over time.

Conclusions:

Inequality narrowed between the 1960s and 1990s. The lowest-SEP groups were still >1 sd shorter than the highest. Risks remain for reduced human capital and poorer population health for urban Guatemalans.
Domestic Courts and the Paris Agreement's Climate Goals: The Need for a Comparative Approach
Authors: Saiger Anna-Julia
Published: December 2019

Domestic courts enjoy generous attention in international political and legal climate change literature. As a result of the reluctance of national governments to pursue climate protection measures, courts are called on to enforce international climate goals. This article assesses two domestic climate change cases (theThabametsi Caseand theVienna Airport Case) in the light of Anthea Roberts’ functional understanding of the role of domestic courts in international law. It argues that domestic courts play a pivotal role in linking international obligations of conduct with national obligations of result. This role depends on domestic contexts and, therefore, requires a comparative approach.
Legal regime sustainability in outer space: theory and practice
Authors: Martinez Larry F.
Published: December 2019

Non-technical abstract

Sustainable access to outer space is increasingly threatened by growing orbital clouds of satellites and debris. A boom in competitively priced commercial rocket launches has lowered prices, prompting satellite operators to begin deploying thousands of satellites. Six decades ago, ‘hard law’ international treaties established governance for outer space designed for the few governmental space programmes. Today, non-governmental commercial entities are operating under voluntary ‘soft law’ rules of the road that expose the deficiencies of the original treaties to empower regulatory supervision of the expanding commercial orbital presence. This paper suggests how a ‘sustainable’ system of governance, required for sustainable space access and exploration, may be promoted by increasing the costs of non-compliance.
Representing Grasslands Using Dynamic Prognostic Phenology Based on Biological Growth Stages: Part 2. Carbon Cycling
Authors: Haynes Katherine D. , Baker Ian T. , Denning A. Scott , Wolf Sebastian , Wohlfahrt Georg , Kiely Gerard , Minaya Renee C. , Haynes John M.
Published: December 2019

Grasslands are one of the most widely distributed and abundant vegetation types globally, and land surface models struggle to accurately simulate grassland carbon dioxide, energy, and water fluxes. Here we hypothesize that this is due to land surface models having difficulties in reproducing grassland phenology, in particular in response to the seasonal and interannual variability of precipitation. Using leaf area index (LAI), net primary productivity, and flux data at 55 sites spanning climate zones, the aim of this study is to evaluate a novel prognostic phenology model (Simple Biosphere Model, SiB4) while simultaneously illustrating grassland relationships across precipitation gradients. Evaluating from 2000 to 2014, SiB4 predicts daily LAI, carbon, and energy fluxes with root‐mean‐square errors < 15% and individual biases <10%; however, not including management likely reduces its performance. Grassland mean annual LAI increases linearly with mean annual precipitation, with both SiB4 and the Moderate Resolution Imaging Spectroradiometer (MODIS) showing a 0.13 increase in LAI per 100‐mm increase in precipitation. Both gross primary production and ecosystem respiration increase with growing season length by ∼8.5 g C m−2per day, with SiB4 and Fluxnet estimates within 18%. Despite differences in mean annual precipitation and growing season length, all grassland sites shift to seasonal carbon sinks one month prior to peak uptake. During a U.S. drought, MODIS and SiB4 had nearly identical LAI responses, and the LAI change due to drought was less than the LAI change across the precipitation gradient, indicating that grassland drought response is not as strong as the overlying climate response.
Sea Ice Targeted Geoengineering Can Delay Arctic Sea Ice Decline but not Global Warming
Authors: Zampieri Lorenzo , Goessling Helge F.
Published: December 2019

To counteract global warming, a geoengineering approach that aims at intervening in the Arctic ice‐albedo feedback has been proposed. A large number of wind‐driven pumps shall spread seawater on the surface in winter to enhance ice growth, allowing more ice to survive the summer melt. We test this idea with a coupled climate model by modifying the surface exchange processes such that the physical effect of the pumps is simulated. Based on experiments with RCP 8.5 scenario forcing, we find that it is possible to keep the late‐summer sea ice cover at the current extent for the next ∼60 years. The increased ice extent is accompanied by significant Arctic late‐summer cooling by ∼1.3 K on average north of the polar circle (2021–2060). However, this cooling is not conveyed to lower latitudes. Moreover, the Arctic experiences substantial winter warming in regions with active pumps. The global annual‐mean near‐surface air temperature is reduced by only 0.02 K (2021–2060). Our results cast doubt on the potential of sea ice targeted geoengineering to mitigate climate change.
Reduced CaCO3Flux to the Seafloor and Weaker Bottom Current Speeds Curtail Benthic CaCO3Dissolution Over the 21st Century
Authors: Sulpis Olivier , Dufour Carolina O. , Trossman David S. , Fassbender Andrea J. , Arbic Brian K. , Boudreau Bernard P. , Dunne John P. , Mucci Alfonso
Published: December 2019

Results from a range of Earth System and climate models of various resolution run under high‐CO2emission scenarios challenge the paradigm that seafloor CaCO3dissolution will grow in extent and intensify as ocean acidification develops over the next century. Under the “business as usual,” RCP8.5 scenario, CaCO3dissolution increases in some areas of the deep ocean, such as the eastern central Pacific Ocean, but is projected to decrease in the Northern Pacific and abyssal Atlantic Ocean by the year 2100. The flux of CaCO3to the seafloor and bottom‐current speeds, both of which are expected to decrease globally through the 21st century, govern changes in benthic CaCO3dissolution rates over 53% and 31% of the dissolving seafloor, respectively. Below the calcite compensation depth, a reduced CaCO3flux to the CaCO3‐free seabed modulates the amount of CaCO3material dissolved at the sediment‐water interface. Slower bottom‐water circulation leads to thicker diffusive boundary layers above the sediment bed and a consequent stronger transport barrier to CaCO3dissolution. While all investigated models predict a weakening of bottom current speeds over most of the seafloor by the end of the 21st century, strong discrepancies exist in the magnitude of the predicted speeds. Overall, the poor performance of most models in reproducing modern bottom‐water velocities and CaCO3rain rates coupled with the existence of large disparities in predicted bottom‐water chemistry across models hampers our ability to robustly estimate the magnitude and temporal evolution of anthropogenic CaCO3dissolution rates and the associated anthropogenic CO2neutralization.
Seismic Structure of the Upper Crust From 0–75 Ma in the Equatorial Atlantic Ocean on the African Plate Using Ultralong Offset Seismic Data
Authors: Audhkhasi P. , Singh S. C.
Published: December 2019

The uppermost oceanic crust composes of Layers 2A and 2B, and the boundary between them is debated to be a lava/dike transition or a hydrothermal alteration boundary within the lava unit. Here, we present the analyses of ultralong multichannel seismic data along a 1,500 km long profile covering 0–75 Ma of the oceanic lithosphere on the African plate in the equatorial Atlantic Ocean. We find that the Layer 2A is observed along the whole profile, with its
velocity increasing from 2.5 km/s near the ridge axis to
4 km/s at
4 Ma with slight variations thereafter. We also find that the sediment thickness increases rapidly from 0 m at the ridge axis to 170 m at 4 Ma, suggesting that there is a link between the high sedimentation rate and the increase in Layer 2A velocity. These observations indicate that crust younger than 4 Myr may be influenced by active hydrothermal circulation. The observed thickness of Layer 2A decreases from
850 m near the ridge axis to
600 m at 15 Ma with no significant changes beyond. We also find an increase in Layer 2B velocity from 5.1 km/s at 4 Myr to 5.5 km/s at 46 Myr, suggesting that passive hydrothermal circulation may extend deeper than Layer 2A/2B boundary. We propose Layer 2A/2B boundary to be a lava/dike transition at the ridge axis and a hydrothermal alteration boundary within the extrusive section away from the ridge axis.
Ordinary and Slow Earthquakes Reproduced in a Simple Continuum System With Stochastic Temporal Stress Fluctuations
Authors: Aso Naofumi , Ando Ryosuke , Ide Satoshi
Published: December 2019

Earthquakes are complex and diverse, ranging from energetic and destructive megathrust earthquakes to slow earthquakes. Complex earthquake rupture processes are generally modeled by prescribing a deterministic system and solving deterministic differential equations. However, such approaches cannot adequately capture the temporal evolution of a complex fault system because of the inherent unpredictability that results from various unprescribed processes. Such unpredictability may be better represented by time‐dependent stochastic fluctuations in addition to the deterministic estimates. Here, we demonstrate that the consideration of time‐dependent stochastic stress fluctuations in ordinary crack simulations can reproduce a variety of ruptures, including both crack‐like and pulse‐like ordinary (fast) earthquakes and slow earthquakes, by simply changing the strength drop and the initial stress level. The results indicate that stochasticity is effective for reproducing and better understanding the diversity of earthquakes, including slow earthquakes.
The Western Tibetan Vortex as an Emergent Feature of Near‐Surface Temperature Variations
Authors: de Kok Remco J. , Immerzeel Walter W.
Published: December 2019

Glaciers around the world are shrinking, yet in a region in northwestern High Mountain Asia (HMA), glaciers show growth. A proposed explanation for this anomalous behavior is related to the variability of the “Western Tibetan Vortex” (WTV), which correlates well with near‐surface temperatures in northwestern HMA. Using analytical formulations and ERA5 reanalysis data, we show that the WTV is the change of wind field resulting from changes in near‐surface temperature gradients in geostrophic flow and that it is not unique to northwestern HMA. Instead, we argue that net radiation is likely the main driver of near‐surface temperatures in Western HMA in summer and autumn. The decreasing strength of the WTV during summer in the twentieth century is thus likely the result of decreasing net radiation. We do argue that the WTV is a useful concept that could yield insights in other regions as well.
Pten haploinsufficiency disrupts scaling across brain areas during development in mice
Authors: Clipperton-Allen Amy E. , Cohen Ori S. , Aceti Massimiliano , Zucca Aya , Levy Jenna , Ellegood Jacob , Lerch Jason P. , Page Damon T.
Published: December 2019

Haploinsufficiency for PTEN is a cause of autism spectrum disorder and brain overgrowth; however, it is not known if PTEN mutations disrupt scaling across brain areas during development. To address this question, we used magnetic resonance imaging to analyze brains of male Pten haploinsufficient (Pten+/−) mice and wild-type littermates during early postnatal development and adulthood. Adult Pten+/− mice display a consistent pattern of abnormal scaling across brain areas, with white matter (WM) areas being particularly affected. This regional and WM enlargement recapitulates structural abnormalities found in individuals with PTEN haploinsufficiency and autism. Early postnatal Pten+/− mice do not display the same pattern, instead exhibiting greater variability across mice and brain regions than controls. This suggests that Pten haploinsufficiency may desynchronize growth across brain regions during early development before stabilizing by maturity. Pten+/− cortical cultures display increased proliferation of glial cell populations, indicating a potential substrate of WM enlargement, and provide a platform for testing candidate therapeutics. Pten haploinsufficiency dysregulates coordinated growth across brain regions during development. This results in abnormally scaled brain areas and associated behavioral deficits, potentially explaining the relationship between PTEN mutations and neurodevelopmental disorders.
IGF2BP2 regulates DANCR by serving as an N6-methyladenosine reader
Authors: Hu Xiaoge , Peng Wan-Xin , Zhou Huaixiang , Jiang Jiahong , Zhou Xinchun , Huang Dongsheng , Mo Yin-Yuan , Yang Liu
Published: December 2019

The major function of Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) is to regulate cell metabolism. However, emerging evidence indicates that IGF2BP2 plays a role in cancer, but the underlying mechanism is largely unknown. Here we showed that upregulation of IGF2BP2 is associated with poor outcomes of pancreatic cancer patients and suppression of IGF2BP2 inhibits cell proliferation. We further showed that IGF2BP2 regulates lncRNA DANCR. Ectopic expression IGF2BP2 enhances, whereas knockdown (KD) or knockout (KO) of IGF2BP2 suppresses DANCR expression. Moreover, in vivo RNA precipitation and reciprocal RNA immunoprecipitation revealed that IGF2BP2 interacts with DANCR. DANCR promotes cell proliferation and stemness-like properties. Experiments with xenograft models revealed that while ectopic expression of DANCR promotes, DANCR KO suppresses tumor growth. Mechanistically, DANCR is modified at N6-methyladenosine (m6A) and mutagenesis assay identified that adenosine at 664 of DANCR is critical to the interaction between IGF2BP2 and DANCR where IGF2BP2 serves a reader for m6A modified DANCR and stabilizes DANCR RNA. Together, these results suggest that DANCR is a novel target for IGF2BP2 through m6A modification, and IGF2BP2 and DANCR work together to promote cancer stemness-like properties and pancreatic cancer pathogenesis.
LRRC8/VRAC channels exhibit a noncanonical permeability to glutathione, which modulates epithelial-to-mesenchymal transition (EMT)
Authors: Friard Jonas , Corinus Alain , Cougnon Marc , Tauc Michel , Pisani Didier F. , Duranton Christophe , Rubera Isabelle
Published: December 2019

Volume-regulated anion channels (VRAC) are chloride channels activated in response to osmotic stress to regulate cellular volume and also participate in other cellular processes, including cell division and cell death. Recently, members of the LRRC8 family have been identified as the main contributors of VRAC conductance. LRRC8/VRAC is permeable to chloride ions but also exhibits significant permeability to various substrates that vary strongly in charge and size. In this study, we explored the intriguing ability of LRRC8/VRAC to transport glutathione (GSH), the major cellular reactive oxygen species (ROS) scavenger, and its involvement in epithelial-to-mesenchymal transition (EMT), a cellular process in which cellular oxidative status is a crucial step. First, in HEK293-WT cells, we showed that a hypotonic condition induced LRRC8/VRAC-dependent GSH conductance (PGSH/PCl of ~0.1) and a marked decrease in intracellular GSH content. GSH currents and GSH intracellular decrease were both inhibited by DCPIB, an inhibitor of LRRC8/VRAC, and were not observed in HEK293-LRRC8A KO cells. Then, we induced EMT by exposing renal proximal tubule epithelial cells to the pleiotropic growth factor TGFβ1, and we measured the contribution of LRRC8/VRAC in this process by measuring (i) EMT marker expression (assessed both at the gene and protein levels), (ii) cell morphology and (iii) the increase in migration ability. Interestingly, pharmacologic targeting of LRRC8/VRAC (DCPIB) or RNA interference-mediated inhibition (LRRC8A siRNA) attenuated the TGFβ1-induced EMT response by controlling GSH and ROS levels. Interestingly, TGFβ1 exposure triggered DCPIB-sensitive chloride conductance. These results suggest that LRRC8/VRAC, due to its native permeability to GSH and thus its ability to modulate ROS levels, plays a critical role in EMT and might contribute to other physiological and pathophysiological processes associated with oxidative stress.
Accumulation and fractionation of rare earth elements are conserved traits in the Phytolacca genus
Authors: Grosjean Nicolas , Le Jean Marie , Berthelot Charlotte , Chalot Michel , Gross Elisabeth Maria , Blaudez Damien
Published: December 2019

Rare earth elements (REEs) are now considered emerging pollutants in the environment. Phytolacca americana, an REE hyperaccumulating plant, has been proposed for the remediation of REE-contaminated soils. However, there is no REE-related information for other Phytolacca species. Here, we examined five species (P. americana, P. acinosa, P. clavigera, P. bogotensis, and P. icosandra) for their response to REEs. REE accumulation and fractionation traits both occurred on the same order of magnitude among the five species. Heavy REEs were preferentially transferred to leaves relative to light REEs. Regardless of the species, lateral root length and chlorophyll content decreased under REE exposure, and lateral roots and foliar anthocyanins increased. However, plants did not experience or only slightly experienced oxidative stress. Finally, REE exposure strongly modulated the ionome of roots and, to a lesser extent, that of leaves, with a negative correlation between REE and Mn contents. In conclusion, our study provides new data on the response of several Phytolacca species to REEs. Moreover, we highlighted that the REE accumulation trait was conserved among Phytolacca species. Thus, we provide valuable information for the phytoremediation of REE-contaminated sites since the most appropriate Phytolacca species could be selected depending on the climatic/pedological area to be remediated.
Unpacking the aggregation-oligomerization-fibrillization process of naturally-occurring hIAPP amyloid oligomers isolated directly from sera of children with obesity or diabetes mellitus
Authors: Altamirano-Bustamante Myriam M. , Altamirano-Bustamante Nelly F. , Larralde-Laborde Mateo , Lara-Martínez Reyna , Leyva-García Edgar , Garrido-Magaña Eulalia , Rojas Gerardo , Jiménez-García Luis Felipe , Revilla-Monsalve Cristina , Altamirano Perla , Calzada-León Raúl
Published: December 2019

The formation of amyloid oligomers and fibrils of the human islet amyloid polypeptide (hIAPP) has been linked with β- cell failure and death which causes the onset, progression, and comorbidities of diabetes. We begin to unpack the aggregation-oligomerization-fibrillization process of these oligomers taken from sera of pediatric patients. The naturally occurring or real hIAPP (not synthetic) amyloid oligomers (RIAO) were successfully isolated, we demonstrated the presence of homo (dodecamers, hexamers, and trimers) and hetero-RIAO, as well as several biophysical characterizations which allow us to learn from the real phenomenon taking place. We found that the aggregation/oligomerization process is active in the sera and showed that it happens very fast. The RIAO can form fibers and react with anti-hIAPP and anti-amyloid oligomers antibodies. Our results opens the epistemic horizon and reveal real differences between the four groups (Controls vs obesity, T1DM or T2DM) accelerating the process of understanding and discovering novel and more efficient prevention, diagnostic, transmission and therapeutic pathways.
Modeling of neotame and fructose thermochemistry: Comparison with mono and divalent metal ions by Computational and experimental approach
Authors: Sharma Deepali , Kanchi Suvardhan , Bathinapatla Ayyappa , Inamuddin  , Asiri Abdullah M.
Published: December 2019

The metal complexes can demonstrate various interesting biological activities in the human body. However, the role of certain metal ions for specific cell activities is still subject to debate. This study is aimed at comparing the thermochemical properties of neotame (artificial sweetener) and α, β-fructose in gas phase and water medium. The interaction of α and β-fructose, neotame with monovalent and divalent metal ions was studied and comprehended by density functional theory (DFT) using B3LYP functional, 6–311 + G (d, p) and D3 basis set. Metal ion affinities (MIA) values depicted that ionic radius of metal ions played an important role in the interaction of α, β-fructose and neotame. The ∆G parameter was calculated to predict and understand the interaction of metal ions with α and β-fructose, neotame. The results suggested that the presence of hydroxyl groups and oxygen atoms in sugar molecules acted as preferred sites for the binding and interaction of mono and divalent ions. For the first time computational study has been introduced in the present study to review the progress in the application of metal binding with sugar molecules especially with neotame. Moreover, voltammetric behaviour of neotame-Zn2+ was studied using cyclic and differential pulse voltammetry. The obtained results suggest that the peak at −1.13 V is due to the reduction of Zn2+ in 0.1 M phosphate buffer medium at pH 5.5. Whereas, addition of 6-fold higher concentration of neotame to the ZnCl2.2H2O resulted in a new irreversible cathodic peak at −0.83, due to the reduction of neotame-Zn2+ complex. The Fourier transform infrared spectroscopy (FTIR) results indicates that the β-amino group (-NH) and carboxyl carbonyl (-C = O) groups of neotame is participating in the chelation process, which is further supported by DFT studies. The findings of this study identify the efficient chelation factors as major contributors into metal ion affinities, with promising possibilities to determine important biological processes in cell wall and glucose transmembrane transport.
New insights in oocyte dynamics shed light on the complexities associated with fish reproductive strategies
Authors: Serrat Alba , Saborido-Rey Fran , Garcia-Fernandez Cristina , Muñoz Marta , Lloret Josep , Thorsen Anders , Kjesbu Olav Sigurd
Published: December 2019

Information on temporal variations in stock reproductive potential (SRP) is essential in fisheries management. Despite this relevance, fundamental understanding of egg production variability remains largely unclear due to difficulties in tracking the underlying complex fluctuations in early oocyte recruitment that determines fecundity. We applied advanced oocyte packing density theory to get in-depth, quantitative insights across oocyte stages and seasons, selecting the commercially valuable European hake (Merluccius merluccius) as a case study. Our work evidenced sophisticated seasonal oocyte recruitment dynamics and patterns, mostly driven by a low-cost predefinition of fecundity as a function of fish body size, likely influenced also by environmental cues. Fecundity seems to be defined at a much earlier stage of oocyte development than previously thought, implying a quasi-determinate – rather than indeterminate – fecundity type in hake. These results imply a major change in the conceptual approach to reproductive strategies in teleosts. These findings not only question the current binary classification of fecundity as either determinate or indeterminate, but also suggest that current practices regarding potential fecundity estimation in fishes should be complemented with studies on primary oocyte dynamics. Accordingly, the methodology and approach adopted in this study may be profitably applied for unravelling some of the complexities associated with oocyte recruitment and thereby SRP variability.
Statistical characteristics of amino acid covariance as possible descriptors of viral genomic complexity
Authors: Sruthi C. K. , Prakash Meher K.
Published: December 2019

At the sequence level it is hard to describe the complexity of viruses which allows them to challenge host immune system, some for a few weeks and others up to a complete compromise. Paradoxically, viral genomes are both complex and simple. Complex because amino acid mutation rates are very high, and yet viruses remain functional. Simple because they have barely around 10 types of proteins, so viral protein-protein interaction networks are not insightful. In this work we use fine-grained amino acid level information and their evolutionary characteristics obtained from large-scale genomic data to develop a statistical panel, towards the goal of developing quantitative descriptors for the biological complexity of viruses. Networks were constructed from pairwise covariation of amino acids and were statistically analyzed. Three differentiating factors arise: predominantly intra- vs inter-protein covariance relations, the nature of the node degree distribution and network density. Interestingly, the covariance relations were primarily intra-protein in avian influenza and inter-protein in HIV. The degree distributions showed two universality classes: a power-law with exponent −1 in HIV and avian-influenza, random behavior in human flu and dengue. The calculated covariance network density correlates well with the mortality strengths of viruses on the viral-Richter scale. These observations suggest the potential utility of the statistical metrics for describing the covariance patterns in viruses. Our host-virus interaction analysis point to the possibility that host proteins which can interact with multiple viral proteins may be responsible for shaping the inter-protein covariance relations. With the available data, it appears that network density might be a surrogate for the virus Richter scale, however the hypothesis needs a re-examination when large scale complete genome data for more viruses becomes available.
Tsunami records of the last 8000 years in the Andaman Island, India, from mega and large earthquakes: Insights on recurrence interval
Authors: Malik Javed N. , Johnson Frango C. , Khan Afzal , Sahoo Santiswarup , Irshad Roohi , Paul Debajyoti , Arora Shreya , Baghel Pankaj Kumar , Chopra Sundeep
Published: December 2019

As many as seven tsunamis from the past 8000 years are evidenced by sand sheets that rest on buried wetland soils at Badabalu, southern Andaman Island, along northern part of the fault rupture of the giant 2004 Aceh-Andaman earthquake. The uppermost of these deposits represents the 2004 tsunami. Underlying deposits likely correspond to historical tsunamis of 1881, 1762, and 1679 CE, and provide evidence for prehistoric tsunamis in 1300–1400 CE, in 2000–3000 and 3020–1780 BCE, and before 5600–5300 BCE. The sequence includes an unexplained hiatus of two or three millennia ending around 1400 CE, which could be attributed to accelerated erosion due to Relative Sea-Level (RSL) fall at ~3500 BP. A tsunami in 1300–1400, comparable to the one in 2004, was previously identified geologically on other Indian Ocean shores. The tsunamis assigned to 1679, 1762, and 1881, by contrast, were more nearly confined to the northeast Indian Ocean. Sources have not been determined for the three earliest of the inferred tsunamis. We suggest a recurrence of 420–750 years for mega-earthquakes having different source, and a shorter interval of 80–120 years for large magnitude earthquakes.
Novel Bead-Based Epitope Assay is a sensitive and reliable tool for profiling epitope-specific antibody repertoire in food allergy
Authors: Suprun Maria , Getts Robert , Raghunathan Rohit , Grishina Galina , Witmer Marc , Gimenez Gustavo , Sampson Hugh A. , Suárez-Fariñas Mayte
Published: December 2019

Identification of allergenic IgE epitopes is instrumental for the development of novel diagnostic and prognostic methods in food allergy. In this work, we present the quantification and validation of a Bead-Based Epitope Assay (BBEA) that through multiplexing of epitopes and multiple sample processing enables completion of large experiments in a short period of time, using minimal quantities of patients’ blood. Peptides that are uniquely coupled to beads are incubated with serum or plasma samples, and after a secondary fluorophore-labeled antibody is added, the level of fluorescence is quantified with a Luminex reader. The signal is then normalized and converted to epitope-specific antibody binding values. We show that the effect of technical artifacts, i.e. well position or reading order, is minimal; and batch effects - different individual microplate runs - can be easily estimated and eliminated from the data. Epitope-specific antibody binding quantified with BBEA is highly reliable, reproducible and has greater sensitivity of epitope detection compared to peptide microarrays. IgE directed at allergenic epitopes is a sensitive biomarker of food allergy and can be used to predict allergy severity and phenotypes; and quantification of the relationship between epitope-specific IgE and IgG4 can further improve our understanding of the immune mechanisms behind allergic sensitization.
Inter-relationships between Gender, Frailty and 10-Year Survival in Older Italian Adults: an observational longitudinal study
Authors: Corbi Graziamaria , Cacciatore Francesco , Komici Klara , Rengo Giuseppe , Vitale Dino Franco , Furgi Giuseppe , Pagano Gennaro , Bencivenga Leonardo , Davinelli Sergio , Ferrara Nicola
Published: December 2019

Aim of the present study was to assess the impact of gender on the relationship between long-term mortality and clinical frailty. In an observational, longitudinal study on 10-year mortality, we examined 1284 subjects. The Frailty Staging System was used to assess frailty. The Cox model was employed to assess variables independently associated with survival using a backward stepwise algorithm. To investigate the possible interactions between gender and the selected variables, an extension of the multivariable fractional polynomial algorithm was adopted. Women were more likely to be older, have a higher disability, present with more comorbidities, consume more drugs, be frail and have a higher rate of survival at the follow-up than were men. At the Cox multivariate analysis only age (HR 2.26), female gender (HR 0.43), and number of drugs (HR 1.57) were significant and independent factors associated with all-cause mortality. In the survival analyses, only frailty (vs no frailty) showed significant interaction with gender (p < 0.001, HR = 1.92). While the presence of frailty reduced the survival rate in women, no effect was observed in men. Importantly, frail women showed higher survival rates than did both frail and no frail men. The main finding of the present study is that gender shapes up the association between frailty and long-term survival rates.
Postsynaptic CaV1.1-driven calcium signaling coordinates presynaptic differentiation at the developing neuromuscular junction
Authors: Kaplan Mehmet Mahsum , Flucher Bernhard E.
Published: December 2019

Proper formation of neuromuscular synapses requires the reciprocal communication between motor neurons and muscle cells. Several anterograde and retrograde signals involved in neuromuscular junction formation are known. However the postsynaptic mechanisms regulating presynaptic differentiation are still incompletely understood. Here we report that the skeletal muscle calcium channel (CaV1.1) is required for motor nerve differentiation and that the mechanism by which CaV1.1 controls presynaptic differentiation utilizes activity-dependent calcium signaling in muscle. In mice lacking CaV1.1 or CaV1.1-driven calcium signaling motor nerves are ectopically located and aberrantly defasciculated. Axons fail to recognize their postsynaptic target structures and synaptic vesicles and active zones fail to correctly accumulate at the nerve terminals opposite AChR clusters. These presynaptic defects are independent of aberrant AChR patterning and more sensitive to deficient calcium signals. Thus, our results identify CaV1.1-driven calcium signaling in muscle as a major regulator coordinating multiple aspects of presynaptic differentiation at the neuromuscular synapse.
Running Stride Length And Rate Are Changed And Mechanical Efficiency Is Preserved After Cycling In Middle-Level Triathletes
Authors: da Rosa Rodrigo Gomes , Oliveira Henrique Bianchi de , Ardigò Luca Paolo , Gomeñuka Natalia Andrea , Fischer Gabriela , Peyré-Tartaruga Leonardo Alexandre
Published: December 2019

Although cycling impairs the subsequent metabolic cost and performance of running in some triathletes, the consequences on mechanical efficiency (Eff) and kinetic and potential energy fluctuations of the body center of mass are still unknown. The aim of this study was to investigate the effects of previous cycling on the cost-of-transport, Eff, mechanical energy fluctuations (Wtot), spring stiffness (Kleg and Kvert) and spatiotemporal parameters. Fourteen middle-level triathletes (mean ± SD: maximal oxygen uptake, $$\dot{{\rm{V}}}$$

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O2max = 65.3 ± 2.7 ml.kg−1.min−1, age = 30 ± 5 years, practice time = 6.8 ± 3.0 years) performed four tests. Two maximal oxygen uptake tests on a cycle ergometer and treadmill, and two submaximal 20-minute running tests (14 km.h−1) with (prior-cycling) and without (control) a previous submaximal 30-minute cycling test. No differences were observed between the control and post-cycling groups in Eff or Wtot. The Eff remains unchanged between conditions. On the other hand, the Kvert (20.2 vs 24.4 kN.m−1) and Kleg (7.1 vs 8.2 kN.m−1, p < 0.05) were lower and the cost-of-transport was higher (p = 0.018, 3.71 vs 3.31 J.kg−1.m−1) when running was preceded by cycling. Significantly higher stride frequency (p < 0.05, 1.46 vs 1.43 Hz) and lower stride length (p < 0.05, 2.60 vs 2.65 m) were observed in the running after cycling condition in comparison with control condition. Mechanical adjustments were needed to maintain the Eff, even resulting in an impaired metabolic cost after cycling performed at moderate intensity. These findings are compatible with the concept that specific adjustments in spatiotemporal parameters preserve the Eff when running is preceded by cycling in middle-level triathletes, though the cost-of-transport increased.
Publisher Correction: Biological surface properties in extracellular vesicles and their effect on cargo proteins
Authors: Santucci Laura , Bruschi Maurizio , Del Zotto Genny , Antonini Francesca , Ghiggeri Gian Marco , Panfoli Isabella , Candiano Giovanni
Published: December 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Vocal individuality of Holstein-Friesian cattle is maintained across putatively positive and negative farming contexts
Authors: Green Alexandra , Clark Cameron , Favaro Livio , Lomax Sabrina , Reby David
Published: December 2019

Cattle mother-offspring contact calls encode individual-identity information; however, it is unknown whether cattle are able to maintain individuality when vocalising to familiar conspecifics over other positively and negatively valenced farming contexts. Accordingly, we recorded 333 high-frequency vocalisations from 13 Holstein-Friesian heifers during oestrus and anticipation of feed (putatively positive), as well as denied feed access and upon both physical and physical & visual isolation from conspecifics (putatively negative). We measured 21 source-related and nonlinear vocal parameters and stepwise discriminant function analyses (DFA) were performed. Calls were divided into positive (n = 170) and negative valence (n = 163) with each valence acting as a ‘training set’ to classify calls in the oppositely valenced ‘test set’. Furthermore, MANOVAs were conducted to determine which vocal parameters were implicated in individual distinctiveness. Within the putatively positive ‘training set’, the cross-validated DFA correctly classified 68.2% of the putatively positive calls and 52.1% of the putatively negative calls to the correct individual, respectively. Within the putatively negative ‘training set’, the cross-validated DFA correctly assigned 60.1% of putatively negative calls and 49.4% of putatively positive calls to the correct individual, respectively. All DFAs exceeded chance expectations indicating that vocal individuality of high-frequency calls is maintained across putatively positive and negative valence, with all vocal parameters except subharmonics responsible for this individual distinctiveness. This study shows that cattle vocal individuality of high-frequency calls is stable across different emotionally loaded farming contexts. Individual distinctiveness is likely to attract social support from conspecifics, and knowledge of these individuality cues could assist farmers in detecting individual cattle for welfare or production purposes.
The incidence and etiology of sixth cranial nerve palsy in Koreans: A 10-year nationwide cohort study
Authors: Jung Eun Hye , Kim Seong-Joon , Lee Joo Yeon , Cho Bum-Joo
Published: December 2019

We aimed to investigate the incidence, prevalence, and etiology of sixth cranial nerve (CN6) palsy in the general Korean population. The nationally representative dataset of the Korea National Health Insurance Service–National Sample Cohort from 2006 through 2015 was analyzed. The incidence and prevalence of CN6 palsy were estimated in the cohort population, confirming that incident cases of CN6 palsy involved a preceding disease-free period of ≥4 years. The etiologies of CN6 palsy were presumed using comorbidity conditions. Among the 1,108,256 cohort subjects, CN6 palsy developed in 486 patients during the 10-year follow-up. The overall incidence of CN6 palsy was estimated to be 4.66 per 100,000 person-years (95% confidence interval [CI], 4.26–5.08) in the general population. This incidence increased with age, accelerating after 60 years of age and peaking at 70–74 years of age. The mean male-to-female incidence ratio was estimated as 1.41 in the whole population, and the incidence and prevalence of CN6 palsy showed an increasing trend over time in the study period. Surgical incidence for CN6 palsy was only 0.19 per 100,000 person-years (95% CI, 0.12–0.29). The etiologies were presumed to be vascular (56.6%), idiopathic (27.2%), neoplastic (5.6%), and traumatic (4.9%). In conclusion, the incidence of CN6 palsy increases with age, peaking at around 70 years, and shows a mild male predominance in Koreans.
Expression of apoptotic and proliferation factors in gastric mucosa of patients with systemic sclerosis correlates with form of the disease
Authors: Boric Katarina , Mardesic Snjezana , Martinovic Kaliterna Dusanka , Radic Mislav , Tadin Hadjina Ivana , Vukojevic Katarina , Kosovic Ivona , Solic Ivana , Zekic Tomas Sandra , Saraga-Babic Mirna
Published: December 2019

Despite high prevalence of patients with gastric disease in systemic sclerosis (SSc), its pathogenesis is still poorly understood. We immunohistochemically analysed biopsies of gastric mucosa (GM) in 5 controls and 15 patients with different forms of SSc: limited cutaneous (lc), diffuse cutaneous moderate (sys1) and severe (sys2). The number of positive cells was analysed by a Kruskall-Wallis test,P < 0.05 was considered statistically significant. Percentage of proliferating (Ki-67 positive) cells was highest in sys1 (3% in superficial and 4,6% in deeper parts of GM), which dropped to 1% in sys2. Percentage of α-smooth muscle actin (α-SMA) positive cells was 5% in controls, 9% in superficial GM, while in deeper GM rose from 7% to 19% in sys1 and sys2, thus indicating increased myofibroblast population. Caspase-3 positive apoptotic cells characterized 1,5–2% of controls, 8% of superficial and 6% of deeper GM cells in sys1. In sys2, apoptosis affected 50% of surface epithelial and gland cells and 30% of deeper glands, and correlated with increased fibrosis and decreased syndecan-1 expression. Our data demonstrate that sys1 is the most „active” proliferating form of SSc. Sys2 characterize collagen deposition, surface epithelium defects, extensive apoptosis and low proliferation, GM atrophy and loss of function.
The long term impact of Daylight Saving Time regulations in daily life at several circles of latitude
Authors: Martín-Olalla José María
Published: December 2019

We analyze large scale (N ~ 10000) time use surveys in United States, Spain, Italy, France and Great Britain to ascertain seasonal variations in the sleep/wake cycle and the labor cycle after daylight saving time regulations have stood up for at least forty years. That is, not the usual search for the impact of the biannual transitions, but a search for how industrialized societies have answered to DST regulations at different circles of latitude. Results show that the labor cycle is equally distributed through seasons if measured in local time. It is an everyday experience which is a major outcome of DST. The sleep/wake cycle displays disturbances punctuated by solar events: sunrise, sunset and noon. In week-ends, under free preferences, sleep onset delays in summer, opposing to the regulation and following the delay in sunset time, while sleep offset advances, despite clock time already advanced in the spring transition. This advance still follows the advance in sunrise times. The best explanation for these findings is that human cycles are not misaligned by the size and direction of DST regulations, which explains the success of that practice. The sleep/wake cycle in Great Britain and France exhibit fewer statistically significant excursions than the sleep/wake cycle in Spain, Italy and United States, despite light and dark seasonal deviations are larger. That could be indicating that the preference for a seasonal regulation of time decreases with increasing latitude above 47°. The preferences for a seasonal regulation of clocks and for the choice of permanent summer time or permanent winter time are sketched from a previous report on human activity.
Ventral Tegmental Area Projection Regulates Glutamatergic Transmission in Nucleus Accumbens
Authors: Yu Jun , Ishikawa Masago , Wang Junshi , Schlüter Oliver M. , Sesack Susan R. , Dong Yan
Published: December 2019

The ventral tegmental area (VTA) projection to the nucleus accumbens shell (NAcSh) regulates NAcSh-mediated motivated behaviors in part by modulating the glutamatergic inputs. This modulation is likely to be mediated by multiple substances released from VTA axons, whose phenotypic diversity is illustrated here by ultrastructural examination. Furthermore, we show in mouse brain slices that a brief optogenetic stimulation of VTA-to-NAc projection induced a transient inhibition of excitatory postsynaptic currents (EPSCs) in NAcSh principal medium spiny neurons (MSNs). This inhibition was not accompanied by detectable alterations in presynaptic release properties of electrically-evoked EPSCs, suggesting a postsynaptic mechanism. The VTA projection to the NAcSh releases dopamine, GABA and glutamate, and induces the release of other neuronal substrates that are capable of regulating synaptic transmission. However, pharmacological inhibition of dopamine D1 or D2 receptors, GABAA or GABAB receptors, NMDA receptors, P2Y1 ATP receptors, metabotropic glutamate receptor 5, and TRP channels did not prevent this short-term inhibition. These results suggest that an unknown mechanism mediates this form of short-term plasticity induced by the VTA-to-NAc projection.