bluuebunny/crossref_metadata_2025 huggingface dataset:
The Dynamic Response of Sea Ice to Warming in the Canadian Arctic Archipelago
Authors: Howell Stephen E. L. , Brady Mike
Published: November 2019

Ice arches in the Canadian Arctic Archipelago (CAA) block the inflow of Arctic Ocean ice for the majority of the year. A 22 year record (1997–2018) of Arctic Ocean‐CAA ice exchange was used to investigate the effect of warming on CAA sea ice dynamics. Larger ice area flux values were associated with longer flow duration and faster ice speed facilitated by increased open water leeway from the CAA's transition to a younger and thinner ice regime, which together have contributed to a significant ice area flux increase (103 km2/year) from Arctic Ocean into the northern CAA from 1997 to 2018. Remarkably, the 2016 Arctic Ocean ice area flux into the CAA (161 × 103 km2) was 7 times greater than the 1997–2018 average (23 × 103 km2) and almost double the 2007 ice area flux into Nares Strait (87 × 103 km2). Continued warming may result in the CAA becoming a larger outlet for Arctic Ocean ice area loss.
Structure of Electron‐Scale Plasma Mixing Along the Dayside Reconnection Separatrix
Authors: Holmes J. C. , Ergun R. E. , Nakamura R. , Roberts O. , Wilder F. D. , Newman D. L.
Published: November 2019

Interactions between magnetic reconnection inflows and outflows can result in a violent mixing process. In Magnetospheric MultiScale observations of asymmetric, low guide‐field reconnection, highly sheared electron flow paired with sharp density and temperature gradients have been found in association with bursts of strong (≥100 mV/m) electric fields parallel to the ambient magnetic field. It is likely that large spikes in E‖ are part of a dynamic, small‐scale structure which results from mixing between plasmas. In this study, a 1‐D Vlasov simulation with parameters directly comparable to the observed plasma environment and interaction timescale is used to demonstrate that mixing at a sharp boundary between magnetospheric and magnetosheath electrons is qualitatively consistent with measured particle distributions and signatures in E‖. Properties of mixing structures such as net electric potential are estimated and found capable of accelerating electron beams toward the electron diffusion region but are not necessarily sufficient to generate the strongest observed jets. Obliquely propagating lower hybrid drift waves are also present and likely provide most of the energy for acceleration. Drift waves may be responsible for cross‐field transport required to begin the mixing process. We conclude that parallel mixing primarily acts to mediate plasma boundaries, thermalizing electron beams contributing to the high anisotropy (Te‖>Te⊥) electron distributions found in the dayside reconnection magnetospheric inflow region.
Role of Iron in the Marquesas Island Mass Effect
Authors: Raapoto Hirohiti , Martinez Elodie , Petrenko Anne , Doglioli Andrea , Gorgues Thomas , Sauzède Raphaëlle , Maamaatuaiahutapu Keitapu , Maes Christophe , Menkes Christophe , Lefèvre Jérôme
Published: November 2019

A remarkable chlorophyll‐a concentration (Chl, a proxy of phytoplankton biomass) plume can be noticed on remotely sensed ocean color observations at the boundary separating the equatorial mesotrophic from the subtropical oligotrophic waters in the central South Pacific Ocean. This prominent biological feature is known as the island mass effect of the Marquesas archipelago. Waters surrounding these islands present high macronutrient concentrations but an iron depletion. In this study, the origin of Chl enhancement is investigated using a modeling approach. Four simulations based on identical physical and biogeochemical forcings but with different iron sources are conducted and analyzed. Only simulations considering an iron input from the island sediments present similar patterns (despite being too weak) of vertical and horizontal Chl distributions as compared to biogeochemical‐Argo profiling float and satellite observations. In addition, simulations with no other iron input than the boundary forcings reveal the relative importance of remote processes in modulating the seasonal pattern of Chl around the archipelago through horizontal advection of nutrient‐rich waters from the equator toward the archipelago and vertical mixing uplifting deep nutrient‐rich waters toward the upper lit layer.
Toward a Better Regional Ozone Forecast Over CONUS Using Rapid Data Assimilation of Clouds and Meteorology in WRF‐Chem
Authors: Ryu Young‐Hee , Hodzic Alma , Descombes Gael , Hu Ming , Barré Jérôme
Published: November 2019

Accuracy of cloud predictions in numerical weather models can considerably impact ozone (O3) forecast skill. This study assesses the benefits in surface O3 predictions of using the Rapid Refresh (RAP) forecasting system that assimilates clouds as well as conventional meteorological variables at hourly time scales. We evaluate and compare the WRF‐Chem simulations driven by RAP and the Global Forecast System (GFS) forecasts over the Contiguous United States (CONUS) for 2016 summer. The day 1 forecasts of surface O3 and temperature driven by RAP are in better agreements with observations. Reductions of 5 ppb in O3 mean bias error and 2.4 ppb in O3 root‐mean‐square‐error are obtained on average over CONUS with RAP compared to those with GFS. The WRF‐Chem simulation driven by GFS shows a higher probability of capturing O3 exceedances but exhibits more frequent false alarms, resulting from its tendency to overpredict O3. The O3 concentrations are found to respond mainly to the changes in boundary layer height that directly affects the mixing of O3 and its precursors. The RAP data assimilation shows improvements in the cloud forecast skill during the initial forecast hours, which reduces O3 forecast errors at the initial forecast hours especially under cloudy‐sky conditions. Sensitivity simulations utilizing satellite clouds show that the WRF‐Chem simulation with RAP produces too thick low‐level clouds, which leads to O3 underprediction in the boundary layer.
Low‐Latitude Calcareous Nannofossil Response in the Indo‐Pacific Warm Pool Across the Eocene‐Oligocene Transition of Java, Indonesia
Authors: Jones Amy P. , Dunkley Jones Tom , Coxall Helen , Pearson Paul N. , Nala Dominika , Hoggett Murray
Published: November 2019

We reconstruct the calcareous nannofossil response to the Eocene‐Oligocene Transition (EOT)—the most significant climate transition of the Cenozoic—in the Indo‐Pacific Warm Pool. Data from south central Java consist of species relative abundance counts of well‐preserved nannofossil assemblages. From the late middle Eocene to early Oligocene species biodiversity declined, with the most rapid species loss occurring across the latest Eocene rosette‐shaped discoaster extinction event (DEE; ~34.44–34.77 Ma). A decline in abundance of oligotrophic indicator taxa across the DEE indicates increased nutrient supply to the tropical surface ocean in the early stages of the EOT. The mean lith size of reticulofenestrids also increases across the DEE driven by a marked reduction in the abundance of smallReticulofenestramorphotypes (<3.5 μm). There is no preferential loss of largerReticulofenestracell sizes (coccoliths > 8 μm) across the EOT, indicating that coccolith size was apparently not limited by atmospheric CO2concentrations at this time. Overall, the main phase of tropical phytoplankton ecosystem change preceded the interval of rapid Antarctic ice sheet growth and is closely associated with the biotic perturbations that define the start of the EOT. This suggests that enhancement of Southern Ocean controls on tropical ocean biogeochemistry and nutrient pathways may have played a role in triggering the transition to an icehouse climate state.
Groundwater cable bacteria conserve energy by sulfur disproportionation
Authors: Müller Hubert , Marozava Sviatlana , Probst Alexander J , Meckenstock Rainer U
Published: November 2019

Cable bacteria of the family Desulfobulbaceae couple spatially separated sulfur oxidation and oxygen or nitrate reduction by long-distance electron transfer, which can constitute the dominant sulfur oxidation process in shallow sediments. However, it remains unknown how cells in the anoxic part of the centimeter-long filaments conserve energy. We found 16S rRNA gene sequences similar to groundwater cable bacteria in a 1-methylnaphthalene-degrading culture (1MN). Cultivation with elemental sulfur and thiosulfate with ferrihydrite or nitrate as electron acceptors resulted in a first cable bacteria enrichment culture dominated >90% by 16S rRNA sequences belonging to the Desulfobulbaceae. Desulfobulbaceae-specific fluorescence in situ hybridization (FISH) unveiled single cells and filaments of up to several hundred micrometers length to belong to the same species. The Desulfobulbaceae filaments also showed the distinctive cable bacteria morphology with their continuous ridge pattern as revealed by atomic force microscopy. The cable bacteria grew with nitrate as electron acceptor and elemental sulfur and thiosulfate as electron donor, but also by sulfur disproportionation when Fe(Cl)2 or Fe(OH)3 were present as sulfide scavengers. Metabolic reconstruction based on the first nearly complete genome of groundwater cable bacteria revealed the potential for sulfur disproportionation and a chemo-litho-autotrophic metabolism. The presence of different types of hydrogenases in the genome suggests that they can utilize hydrogen as alternative electron donor. Our results imply that cable bacteria not only use sulfide oxidation coupled to oxygen or nitrate reduction by LDET for energy conservation, but sulfur disproportionation might constitute the energy metabolism for cells in large parts of the cable bacterial filaments.
Schizophrenia polygenic risk score and 20-year course of illness in psychotic disorders
Authors: Jonas Katherine G. , Lencz Todd , Li Kaiqiao , Malhotra Anil K. , Perlman Greg , Fochtmann Laura J. , Bromet Evelyn J. , Kotov Roman
Published: November 2019

Understanding whether and how the schizophrenia polygenic risk score (SZ PRS) predicts course of illness could improve diagnosis and prognostication in psychotic disorders. We tested whether the SZ PRS predicts symptoms, cognition, illness severity, and diagnostic changes over the 20 years following first admission. The Suffolk County Mental Health Project is an inception cohort study of first-admission patients with psychosis. Patients were assessed six times over 20 years, and 249 provided DNA. Geographically- and demographically-matched never psychotic adults were recruited at year 20, and 205 provided DNA. Symptoms were rated using the Schedule for the Assessment of Positive Symptoms and Schedule for the Assessment of Negative Symptoms. Cognition was evaluated with a comprehensive neuropsychological battery. Illness severity and diagnosis were determined by consensus of study psychiatrists. SZ PRS was significantly higher in first-admission than never psychotic groups. Within the psychosis cohort, the SZ PRS predicted more severe negative symptoms (β = 0.21), greater illness severity (β = 0.28), and worse cognition (β = −0.35), across the follow-up. The SZ PRS was the strongest predictor of diagnostic shifts from affective to non-affective psychosis over the 20 years (AUC = 0.62). The SZ PRS predicts persistent differences in cognition and negative symptoms. The SZ PRS also predicts who among those who appear to have a mood disorder with psychosis at first admission will ultimately be diagnosed with a schizophrenia spectrum disorder. These findings show potential for the SZ PRS to become a tool for diagnosis and treatment planning.
Cisplatin exposure causes c-Myc-dependent resistance to CDK4/6 inhibition in HPV-negative head and neck squamous cell carcinoma
Authors: Robinson Anthony M. , Rathore Richa , Redlich Nathan J. , Adkins Douglas R. , VanArsdale Todd , Van Tine Brian A. , Michel Loren S.
Published: November 2019

The loss of p16 is a signature event in Human Papilloma Virus (HPV)-negative head and neck squamous cell carcinoma (HNSCC) that leads to increased Cyclin Dependent Kinase 4/6 (CDK) signaling. Palbociclib, a CDK4/6 inhibitor, is active for the treatment of a subset of HNSCC. In this study, we analyzed patient response data from a phase I clinical trial of palbociclib in HNSCC and observed an association between prior cisplatin exposure and CDK inhibitor resistance. We studied the effects of palbociclib on cisplatin-sensitive and -resistant HNSCC cell lines. We found that while palbociclib is highly effective against chemo-naive HNSCC cell lines and tumor xenografts, prior cisplatin exposure induces intrinsic resistance to palbociclib in vivo, a relationship that was not observed in vitro. Mechanistically, in the course of provoking a DNA damage-resistance phenotype, cisplatin exposure upregulates both c-Myc and cyclin E, and combination treatment with palbociclib and the c-Myc bromodomain inhibitor JQ1 exerts a synergistic anti-growth effect in cisplatin-resistant cells. These data show the benefit of exploiting the inherent resistance mechanisms of HNSCC to overcome cisplatin- and palbociclib resistance through the use of c-Myc inhibition.
Targeting melanoma’s MCL1 bias unleashes the apoptotic potential of BRAF and ERK1/2 pathway inhibitors
Authors: Sale Matthew J. , Minihane Emma , Monks Noel R. , Gilley Rebecca , Richards Frances M. , Schifferli Kevin P. , Andersen Courtney L. , Davies Emma J. , Vicente Mario Aladren , Ozono Eiko , Markovets Aleksandra , Dry Jonathan R. , Drew Lisa , Flemington Vikki , Proia Theresa , Jodrell Duncan I. , Smith Paul D. , Cook Simon J.
Published: November 2019

BRAF and MEK1/2 inhibitors are effective in melanoma but resistance inevitably develops. Despite increasing the abundance of pro-apoptotic BIM and BMF, ERK1/2 pathway inhibition is predominantly cytostatic, reflecting residual pro-survival BCL2 family activity. Here, we show that uniquely low BCL-XL expression in melanoma biases the pro-survival pool towards MCL1. Consequently, BRAF or MEK1/2 inhibitors are synthetic lethal with the MCL1 inhibitor AZD5991, driving profound tumour cell death that requires BAK/BAX, BIM and BMF, and inhibiting tumour growth in vivo. Combination of ERK1/2 pathway inhibitors with BCL2/BCL-w/BCL-XL inhibitors is stronger in CRC, correlating with a low MCL1:BCL-XL ratio; indeed the MCL1:BCL-XL ratio is predictive of ERK1/2 pathway inhibitor synergy with MCL1 or BCL2/BCL-w/BCL-XL inhibitors. Finally, AZD5991 delays acquired BRAFi/MEKi resistance and enhances the efficacy of an ERK1/2 inhibitor in a model of acquired BRAFi + MEKi resistance. Thus combining ERK1/2 pathway inhibitors with MCL1 antagonists in melanoma could improve therapeutic index and patient outcomes.
Destabilization of NOXA mRNA as a common resistance mechanism to targeted therapies
Authors: Montero Joan , Gstalder Cécile , Kim Daniel J. , Sadowicz Dorota , Miles Wayne , Manos Michael , Cidado Justin R. , Paul Secrist J. , Tron Adriana E. , Flaherty Keith , Stephen Hodi F. , Yoon Charles H. , Letai Anthony , Fisher David E. , Haq Rizwan
Published: November 2019

Most targeted cancer therapies fail to achieve complete tumor regressions or attain durable remissions. To understand why these treatments fail to induce robust cytotoxic responses despite appropriately targeting oncogenic drivers, here we systematically interrogated the dependence of cancer cells on the BCL-2 family of apoptotic proteins after drug treatment. We observe that multiple targeted therapies, including BRAF or EGFR inhibitors, rapidly deplete the pro-apoptotic factor NOXA, thus creating a dependence on the anti-apoptotic protein MCL-1. This adaptation requires a pathway leading to destabilization of the NOXA mRNA transcript. We find that interruption of this mechanism of anti-apoptotic adaptive resistance dramatically increases cytotoxic responses in cell lines and a murine melanoma model. These results identify NOXA mRNA destabilization/MCL-1 adaptation as a non-genomic mechanism that limits apoptotic responses, suggesting that sequencing of MCL-1 inhibitors with targeted therapies could overcome such widespread and clinically important resistance.
Hyperpolarized relaxometry based nuclear T1 noise spectroscopy in diamond
Authors: Ajoy A. , Safvati B. , Nazaryan R. , Oon J. T. , Han B. , Raghavan P. , Nirodi R. , Aguilar A. , Liu K. , Cai X. , Lv X. , Druga E. , Ramanathan C. , Reimer J. A. , Meriles C. A. , Suter D. , Pines A.
Published: November 2019

The origins of spin lifetimes in quantum systems is a matter of importance in several areas of quantum information. Spectrally mapping spin relaxation processes provides insight into their origin and motivates methods to mitigate them. In this paper, we map nuclear relaxation in a prototypical system of $${}^{13}{\rm{C}}$$

13

C
nuclei in diamond coupled to Nitrogen Vacancy (NV) centers over a wide field range (1 mT-7 T). Nuclear hyperpolarization through optically pumped NV electrons allows signal measurement savings exceeding million-fold over conventional methods. Through a systematic study with varying substitutional electron (P1 center) and $${}^{13}{\rm{C}}$$

13

C
concentrations, we identify the operational relaxation channels for the nuclei at different fields as well as the dominant role played by $${}^{13}{\rm{C}}$$

13

C
coupling to the interacting P1 electronic spin bath. These results motivate quantum control techniques for dissipation engineering to boost spin lifetimes in diamond, with applications including engineered quantum memories and hyperpolarized $${}^{13}{\rm{C}}$$

13

C
imaging.
Chemokine receptor trafficking coordinates neutrophil clustering and dispersal at wounds in zebrafish
Authors: Coombs Caroline , Georgantzoglou Antonios , Walker Hazel A. , Patt Julian , Merten Nicole , Poplimont Hugo , Busch-Nentwich Elisabeth M. , Williams Sarah , Kotsi Christina , Kostenis Evi , Sarris Milka
Published: November 2019

Immune cells congregate at specific loci to fight infections during inflammatory responses, a process that must be transient and self-resolving. Cell dispersal promotes resolution, but it remains unclear how transition from clustering to dispersal is regulated. Here we show, using quantitative live imaging in zebrafish, that differential ligand-induced trafficking of chemokine receptors such as Cxcr1 and Cxcr2 orchestrates the state of neutrophil congregation at sites of tissue damage. Through receptor mutagenesis and biosensors, we show that Cxcr1 promotes clustering at wound sites, but is promptly desensitized and internalized, which prevents excess congregation. By contrast, Cxcr2 promotes bidirectional motility and is sustained at the plasma membrane. Persistent plasma membrane residence of Cxcr2 prolongs downstream signaling and is required for sustained exploratory motion conducive to dispersal. Thus, differential trafficking of two chemokine receptors allows coordination of antagonistic cell behaviors, promoting a self-resolving migratory response.
A thalamocortical pathway for fast rerouting of tactile information to occipital cortex in congenital blindness
Authors: Müller Franziska , Niso Guiomar , Samiee Soheila , Ptito Maurice , Baillet Sylvain , Kupers Ron
Published: November 2019

In congenitally blind individuals, the occipital cortex responds to various nonvisual inputs. Some animal studies raise the possibility that a subcortical pathway allows fast re-routing of tactile information to the occipital cortex, but this has not been shown in humans. Here we show using magnetoencephalography (MEG) that tactile stimulation produces occipital cortex activations, starting as early as 35 ms in congenitally blind individuals, but not in blindfolded sighted controls. Given our measured thalamic response latencies of 20 ms and a mean estimated lateral geniculate nucleus to primary visual cortex transfer time of 15 ms, we claim that this early occipital response is mediated by a direct thalamo-cortical pathway. We also observed stronger directed connectivity in the alpha band range from posterior thalamus to occipital cortex in congenitally blind participants. Our results strongly suggest the contribution of a fast thalamo-cortical pathway in the cross-modal activation of the occipital cortex in congenitally blind humans.
The wax gourd genomes offer insights into the genetic diversity and ancestral cucurbit karyotype
Authors: Xie Dasen , Xu Yuanchao , Wang Jinpeng , Liu Wenrui , Zhou Qian , Luo Shaobo , Huang Wu , He Xiaoming , Li Qing , Peng Qingwu , Yang Xueyong , Yuan Jiaqing , Yu Jigao , Wang Xiyin , Lucas William J. , Huang Sanwen , Jiang Biao , Zhang Zhonghua
Published: November 2019

The botanical family Cucurbitaceae includes a variety of fruit crops with global or local economic importance. How their genomes evolve and the genetic basis of diversity remain largely unexplored. In this study, we sequence the genome of the wax gourd (Benincasa hispida), which bears giant fruit up to 80 cm in length and weighing over 20 kg. Comparative analyses of six cucurbit genomes reveal that the wax gourd genome represents the most ancestral karyotype, with the predicted ancestral genome having 15 proto-chromosomes. We also resequence 146 lines of diverse germplasm and build a variation map consisting of 16 million variations. Combining population genetics and linkage mapping, we identify a number of regions/genes potentially selected during domestication and improvement, some of which likely contribute to the large fruit size in wax gourds. Our analyses of these data help to understand genome evolution and function in cucurbits.
Pathways to defense metabolites and evading fruit bitterness in genus Solanum evolved through 2-oxoglutarate-dependent dioxygenases
Authors: Cárdenas Pablo D. , Sonawane Prashant D. , Heinig Uwe , Jozwiak Adam , Panda Sayantan , Abebie Bekele , Kazachkova Yana , Pliner Margarita , Unger Tamar , Wolf Dalia , Ofner Itai , Vilaprinyo Ester , Meir Sagit , Davydov Olga , Gal-on Amit , Burdman Saul , Giri Ashok , Zamir Dani , Scherf Tali , Szymanski Jedrzej , Rogachev Ilana , Aharoni Asaph
Published: November 2019

The genus Solanum comprises three food crops (potato, tomato, and eggplant), which are consumed on daily basis worldwide and also producers of notorious anti-nutritional steroidal glycoalkaloids (SGAs). Hydroxylated SGAs (i.e. leptinines) serve as precursors for leptines that act as defenses against Colorado Potato Beetle (Leptinotarsa decemlineata Say), an important pest of potato worldwide. However, SGA hydroxylating enzymes remain unknown. Here, we discover that 2-OXOGLUTARATE-DEPENDENT-DIOXYGENASE (2-ODD) enzymes catalyze SGA-hydroxylation across various Solanum species. In contrast to cultivated potato, Solanum chacoense, a widespread wild potato species, has evolved a 2-ODD enzyme leading to the formation of leptinines. Furthermore, we find a related 2-ODD in tomato that catalyzes the hydroxylation of the bitter α-tomatine to hydroxytomatine, the first committed step in the chemical shift towards downstream ripening-associated non-bitter SGAs (e.g. esculeoside A). This 2-ODD enzyme prevents bitterness in ripe tomato fruit consumed today which otherwise would remain unpleasant in taste and more toxic.
Rice life cycle-based global mercury biotransport and human methylmercury exposure
Authors: Liu Maodian , Zhang Qianru , Cheng Menghan , He Yipeng , Chen Long , Zhang Haoran , Cao Hanlin , Shen Huizhong , Zhang Wei , Tao Shu , Wang Xuejun
Published: November 2019

Protecting the environment and enhancing food security are among the world’s greatest challenges. Fish consumption is widely considered to be the single significant dietary source of methylmercury. Nevertheless, by synthesizing data from the past six decades and using a variety of models, we find that rice could be a significant global dietary source of human methylmercury exposure, especially in South and Southeast Asia. In 2013, globalization caused 9.9% of human methylmercury exposure via the international rice trade and significantly aggravated rice-derived exposure in Africa (62%), Central Asia (98%) and Europe (42%). In 2016, 180 metric tons of mercury were generated in rice plants, 14-fold greater than that exported from oceans via global fisheries. We suggest that future research should consider both the joint ingestion of rice with fish and the food trade in methylmercury exposure assessments, and anthropogenic biovectors such as crops should be considered in the global mercury cycle.
Reliable and explainable machine-learning methods for accelerated material discovery
Authors: Kailkhura Bhavya , Gallagher Brian , Kim Sookyung , Hiszpanski Anna , Han T. Yong-Jin
Published: November 2019

Despite ML’s impressive performance in commercial applications, several unique challenges exist when applying ML in materials science applications. In such a context, the contributions of this work are twofold. First, we identify common pitfalls of existing ML techniques when learning from underrepresented/imbalanced material data. Specifically, we show that with imbalanced data, standard methods for assessing quality of ML models break down and lead to misleading conclusions. Furthermore, we find that the model’s own confidence score cannot be trusted and model introspection methods (using simpler models) do not help as they result in loss of predictive performance (reliability-explainability trade-off). Second, to overcome these challenges, we propose a general-purpose explainable and reliable machine-learning framework. Specifically, we propose a generic pipeline that employs an ensemble of simpler models to reliably predict material properties. We also propose a transfer learning technique and show that the performance loss due to models’ simplicity can be overcome by exploiting correlations among different material properties. A new evaluation metric and a trust score to better quantify the confidence in the predictions are also proposed. To improve the interpretability, we add a rationale generator component to our framework which provides both model-level and decision-level explanations. Finally, we demonstrate the versatility of our technique on two applications: (1) predicting properties of crystalline compounds and (2) identifying potentially stable solar cell materials. We also point to some outstanding issues yet to be resolved for a successful application of ML in material science.
Identification and targeted management of a neurodegenerative disorder caused by biallelic mutations in SLC5A6
Authors: Byrne Alicia B. , Arts Peer , Polyak Steven W. , Feng Jinghua , Schreiber Andreas W. , Kassahn Karin S. , Hahn Christopher N. , Mordaunt Dylan A. , Fletcher Janice M. , Lipsett Jillian , Bratkovic Drago , Booker Grant W. , Smith Nicholas J. , Scott Hamish S.
Published: November 2019

We describe a sibling pair displaying an early infantile-onset, progressive neurodegenerative phenotype, with symptoms of developmental delay and epileptic encephalopathy developing from 12 to 14 months of age. Using whole exome sequencing, compound heterozygous variants were identified in SLC5A6, which encodes the sodium-dependent multivitamin transporter (SMVT) protein. SMVT is an important transporter of the B-group vitamins biotin, pantothenate, and lipoate. The protein is ubiquitously expressed and has major roles in vitamin uptake in the digestive system, as well as transport of these vitamins across the blood–brain barrier. Pathogenicity of the identified variants was demonstrated by impaired biotin uptake of mutant SMVT. Identification of this vitamin transporter as the genetic basis of this disorder guided targeted therapeutic intervention, resulting clinically in improvement of the patient’s neurocognitive and neuromotor function. This is the second report of biallelic mutations in SLC5A6 leading to a neurodegenerative disorder due to impaired biotin, pantothenate and lipoate uptake. The genetic and phenotypic overlap of these cases confirms mutations in SLC5A6 as the genetic cause of this disease phenotype. Recognition of the genetic disorder caused by SLC5A6 mutations is essential for early diagnosis and to facilitate timely intervention by triple vitamin (biotin, pantothenate, and lipoate) replacement therapy.
Tropical forest soils serve as substantial and persistent methane sinks
Authors: Zhao Jun-Fu , Peng Shu-Shi , Chen Meng-Ping , Wang Guan-Ze , Cui Yi-Bin , Liao Li-Guo , Feng Ji-Guang , Zhu Biao , Liu Wen-Jie , Yang Lian-Yan , Tan Zheng-Hong
Published: November 2019

Although tropical forest soils contributed substantially global soil methane uptake, observations on soil methane fluxes in tropical forests are still sparse, especially in Southeast Asia, leading to large uncertainty in the estimation of global soil methane uptake. Here, we conducted two-year (from Sep, 2016 to Sep, 2018) measurements of soil methane fluxes in a lowland tropical forest site in Hainan island, China. At this tropical forest site, soils were substantial methane sink, and average annual soil methane uptake was estimated at 2.00 kg CH4-C ha−1 yr−1. The seasonality of soil methane uptake showed strong methane uptake in the dry season (−1.00 nmol m−2 s−1) and almost neutral or weak soil methane uptake in the wet season (−0.24 nmol m−2 s−1). The peak soil methane uptake rate was observed as −1.43 nmol m−2 s−1 in February, 2018, the driest and coolest month during the past 24 months. Soil moisture was the dominant controller of methane fluxes, and could explain 94% seasonal variation of soil methane fluxes. Soil temperature could not enhance the explanation of seasonal variation of soil methane fluxes on the top of soil moisture. A positive relationship between soil methane uptake and soil respiration was also detected, which might indicate co-variation in activities of methanotroph and roots and/or microbes for soil heterotrophic respiration. Our study highlights that tropical forests in this region acted as a methane sink.
High Temperature and Power Dependent Photoluminescence Analysis on Commercial Lighting and Display LED Materials for Future Power Electronic Modules
Authors: Sabbar Abbas , Madhusoodhanan Syam , Al-Kabi Sattar , Dong Binzhong , Wang Jiangbo , Atcitty Stanley , Kaplar Robert , Ding Ding , Mantooth Alan , Yu Shui-Qing , Chen Zhong
Published: November 2019

Commercial light emitting diode (LED) materials - blue (i.e., InGaN/GaN multiple quantum wells (MQWs) for display and lighting), green (i.e., InGaN/GaN MQWs for display), and red (i.e., Al0.05Ga0.45In0.5P/Al0.4Ga0.1In0.5P for display) are evaluated in range of temperature (77–800) K for future applications in high density power electronic modules. The spontaneous emission quantum efficiency (QE) of blue, green, and red LED materials with different wavelengths was calculated using photoluminescence (PL) spectroscopy. The spontaneous emission QE was obtained based on a known model so-called the ABC model. This model has been recently used extensively to calculate the internal quantum efficiency and its droop in the III-nitride LED. At 800 K, the spontaneous emission quantum efficiencies are around 40% for blue for lighting and blue for display LED materials, and it is about 44.5% for green for display LED materials. The spontaneous emission QE is approximately 30% for red for display LED material at 800 K. The advance reported in this paper evidences the possibility of improving high temperature optocouplers with an operating temperature of 500 K and above.
Relative sorption coefficient: Key to tracing petroleum migration and other subsurface fluids
Authors: Zhang L. , Wang Y. , Li M.-W. , Yin Q.-Z. , Zhang W.
Published: November 2019

The accumulation and spatial distribution of economically important petroleum in sedimentary basins are primarily controlled by its migration from source rocks through permeable carrier beds to reservoirs. Tracing petroleum migration entails the use of molecular indices established according to sorption capacities of polar molecules in migrating petroleum. However, little is known about molecular sorption capacities in natural migration systems, rendering these indices unreliable. Here, we present a new approach based on a novel concept of relative sorption coefficient for quantitatively assessing sorption capacities of polar molecules during natural petroleum migration. Using this approach, we discovered previously unrecognized “stripping” and “impeding” effects that significantly reduce the sorption capacities of polar compounds. These discoveries provide new insights into the behaviors of polar compounds and can easily explain why traditional molecular indices yield incorrect information about petroleum migration. In light of these new findings, we established new molecular indices for tracing petroleum migration. We demonstrate via case studies that the newly established indices, unlike traditional molecular indices, are reliable and effective in tracing petroleum migration. Our approach can be applied to diverse basins around the world to reveal distribution patterns of petroleum, which would decrease environmental risks of exploration by reducing unsuccessful wells.
Complex life histories discovered in a critically endangered fish
Authors: Hobbs James A. , Lewis Levi S. , Willmes Malte , Denney Christian , Bush Eva
Published: November 2019

Effective conservation of endangered species requires knowledge of the full range of life-history strategies used to maximize population resilience within a stochastic and ever-changing environment. California’s endemic Delta Smelt (Hypomesus transpacificus) is rapidly approaching extinction in the San Francisco Estuary, placing it in the crossfire between human and environmental uses of limited freshwater resources. Though managed as a semi-anadromous species, recent studies have challenged this lifecycle model for Delta Smelt, suggesting the species is an estuarine resident with several localized “hot-spots” of abundance. Using laser-ablation otolith strontium isotope microchemistry, we discovered three distinct life-history phenotypes including freshwater resident (FWR), brackish-water resident (BWR), and semi-anadromous (SA) fish. We further refined life-history phenotypes using an unsupervised algorithm and hierarchical clustering and found that in the last resilient year-class, the FWR (12%) and BWR (7%) comprised a small portion of the population, while the majority of fish were SA (81%). Furthermore, the semi-anadromous fish could be clustered into at least four additional life-history phenotypes that varied by natal origin, dispersal age and adult salinity history. These diverse life-history strategies should be incorporated into future conservation and management efforts aimed at preventing the extinction of Delta Smelt in the wild.
Effect of Water Compressibility, Sea-floor Elasticity, and Field Gravitational Potential on Tsunami Phase Speed
Authors: Abdolali Ali , Kadri Usama , Kirby James T.
Published: November 2019

Tsunamis can propagate thousands of kilometres across the ocean. Precise calculations of arrival times are essential for reliable early warning systems, determination of source and earth properties using the inverse problem, and time series modulation due to frequency dependency of phase speed. Far field observatories show a systematic discrepancy between observed and calculated arrival times. Models in present use and based on incompressible hydrodynamics and interaction with a rigid ocean floor overestimate the phase speed of tsunamis, leading to arrival time differences exceeding tens of minutes. These models neglect the simultaneous effects of the slight compressibility of water, sea-bed elasticity, and static compression of the ocean under gravity, hereinafter gravity. Here, we show that taking these effects into account results in more accurate phase speeds and travel times that agree with observations. Moreover, the semi-analytical model that we propose can be employed near real-time, which is essential for early warning inverse models and mitigation systems that rely on accurate phase speed calculations.
Dopamine D2 receptor modulates Wnt expression and control of cell proliferation
Authors: Han Fei , Konkalmatt Prasad , Mokashi Chaitanya , Kumar Megha , Zhang Yanrong , Ko Allen , Farino Zachary J. , Asico Laureano D. , Xu Gaosi , Gildea John , Zheng Xiaoxu , Felder Robin A. , Lee Robin E. C. , Jose Pedro A. , Freyberg Zachary , Armando Ines
Published: November 2019

The Wnt/β-catenin pathway is one of the most conserved signaling pathways across species with essential roles in development, cell proliferation, and disease. Wnt signaling occurs at the protein level and via β-catenin-mediated transcription of target genes. However, little is known about the underlying mechanisms regulating the expression of the key Wnt ligand Wnt3a or the modulation of its activity. Here, we provide evidence that there is significant cross-talk between the dopamine D2 receptor (D2R) and Wnt/β-catenin signaling pathways. Our data suggest that D2R-dependent cross-talk modulates Wnt3a expression via an evolutionarily-conserved TCF/LEF site within the WNT3A promoter. Moreover, D2R signaling also modulates cell proliferation and modifies the pathology in a renal ischemia/reperfusion-injury disease model, via its effects on Wnt/β-catenin signaling. Together, our results suggest that D2R is a transcriptional modulator of Wnt/β-catenin signal transduction with broad implications for health and development of new therapeutics.
A Frailty Index based on clinical data to quantify mortality risk in dogs
Authors: Banzato Tommaso , Franzo Giovanni , Di Maggio Roberta , Nicoletto Elisa , Burti Silvia , Cesari Matteo , Canevelli Marco
Published: November 2019

Frailty is defined as a decline in an organism’s physiological reserves resulting in increased vulnerability to stressors. In humans, a single continuous variable, the so-called Frailty Index (FI), can be obtained by multidimensionally assessing the biological complexity of an ageing organism. Here, we evaluate this variability in dogs and compare it to the data available for humans. In dogs, there was a moderate correlation between age and the FI, and the distribution of the FI increased with age. Deficit accumulation was strongly related to mortality. The effect of age, when combined with the FI, was negligible. No sex-related differences were evident. The FI could be considered in epidemiological studies and/or experimental trials to account for the potential confounding effects of the health status of individual dogs. The age-related deficit accumulation reported in dogs is similar to that demonstrated in humans. Therefore, dogs might represent an excellent model for human aging studies.
Emotional learning promotes perceptual predictions by remodeling stimulus representation in visual cortex
Authors: Meaux E. , Sterpenich V. , Vuilleumier P.
Published: November 2019

Emotions exert powerful effects on perception and memory, notably by modulating activity in sensory cortices so as to capture attention. Here, we examine whether emotional significance acquired by a visual stimulus can also change its cortical representation by linking neuronal populations coding for different memorized versions of the same stimulus, a mechanism that would facilitate recognition across different appearances. Using fMRI, we show that after pairing a given face with threat through conditioning, viewing this face activates the representation of another viewpoint of the same person, which itself was never conditioned, leading to robust repetition-priming across viewpoints in the ventral visual stream (including medial fusiform, lateral occipital, and anterior temporal cortex). We also observed a functional-anatomical segregation for coding view-invariant and view-specific identity information. These results indicate emotional signals may induce plasticity of stimulus representations in visual cortex, serving to generate new sensory predictions about different appearances of threat-associated stimuli.
Characterization of GUCA1A-associated dominant cone/cone-rod dystrophy: low prevalence among Japanese patients with inherited retinal dystrophies
Authors: Mizobuchi Kei , Hayashi Takaaki , Katagiri Satoshi , Yoshitake Kazutoshi , Fujinami Kaoru , Yang Lizhu , Kuniyoshi Kazuki , Shinoda Kei , Machida Shigeki , Kondo Mineo , Ueno Shinji , Terasaki Hiroko , Matsuura Tomokazu , Tsunoda Kazushige , Iwata Takeshi , Nakano Tadashi
Published: November 2019

GUCA1A gene variants are associated with autosomal dominant (AD) cone dystrophy (COD) and cone-rod dystrophy (CORD). GUCA1A-associated AD-COD/CORD has never been reported in the Japanese population. The purpose of this study was to investigate clinical and genetic features of GUCA1A-associated AD-COD/CORD from a large Japanese cohort. We identified 8 variants [c.C50_80del (p.E17VfsX22), c.T124A (p.F42I), c.C204G (p.D68E), c.C238A (p.L80I), c.T295A (p.Y99N), c.A296C (p.Y99S), c.C451T (p.L151F), and c.A551G (p.Q184R)] in 14 families from our whole exome sequencing database composed of 1385 patients with inherited retinal diseases (IRDs) from 1192 families. Three variants (p.Y99N, p.Y99S, and p.L151F), which are located on/around EF-hand domains 3 and 4, were confirmed as “pathogenic”, whereas the other five variants, which did not co-segregate with IRDs, were considered “non-pathogenic”. Ophthalmic findings of 9 patients from 3 families with the pathogenic variants showed central visual impairment from early to middle-age onset and progressive macular atrophy. Electroretinography revealed severely decreased or non-recordable cone responses, whereas rod responses were highly variable, ranging from nearly normal to non-recordable. Our results indicate that the three pathogenic variants, two of which were novel, underlie AD-COD/CORD with progressive retinal atrophy, and the prevalence (0.25%, 3/1192 families) of GUCA1A-associated IRDs may be low among Japanese patients.
Spatial-temporal risk assessment of urbanization impacts on ecosystem services based on pressure-status - response framework
Authors: Kang Peng , Chen Weiping , Hou Ying , Li Yuanzheng
Published: November 2019

Rapid urbanization is a global phenomenon that has altered many ecosystems, generating ecological risks such as causing a decline in many ecosystem services. In this study, ecosystem service oriented risk assessment combined with PSR were quantifying how urbanization influences the ecosystem services about Beijing-Tianjin-Hebei urban agglomeration of China between 2000 year and 2010 year. The mean value of ecosystem services in three gradient (rural areas, suburban, and urban area) declined from 4.12 Yuan/m2 to 1.75 Yuan/m2 in 2000 year, while the mean value in 2010 year showed significant decrease and also represented urban-rural gradient. The average of pressure in PSR framework increased from 0.145 to 0.162 between two periods, while the average of status decrease from 0.378 to 0.311, and the status value decrease from 0.096 to 0.087. The higher risk degree V increased 6.95% between two periods, while the lower risk degree I decrease 6.89%. Two main types including high value gathering field and low value gathering field existed between two periods, the higher gathering field owned the ratio of 9.85%, mainly distributed around the urban area of Beijing and Tianjin, while the lower gathering field possess the ratio of 10.69%, mainly distributed in the northern and western in region. Overall, the analytical framework proposed in this study can provide comprehensive information to evaluate the impacts of complex practice in land-use planning and region ecosystem management.
Using bear rub data and spatial capture-recapture models to estimate trend in a brown bear population
Authors: Kendall Katherine C. , Graves Tabitha A. , Royle J. Andrew , Macleod Amy C. , McKelvey Kevin S. , Boulanger John , Waller John S.
Published: November 2019

Trends in population abundance can be challenging to quantify during range expansion and contraction, when there is spatial variation in trend, or the conservation area is large. We used genetic detection data from natural bear rubbing sites and spatial capture-recapture (SCR) modeling to estimate local density and population growth rates in a grizzly bear population in northwestern Montana, USA. We visited bear rubs to collect hair in 2004, 2009—2012 (3,579—4,802 rubs) and detected 249—355 individual bears each year. We estimated the finite annual population rate of change 2004—2012 was 1.043 (95% CI = 1.017—1.069). Population density shifted from being concentrated in the north in 2004 to a more even distribution across the ecosystem by 2012. Our genetic detection sampling approach coupled with SCR modeling allowed us to estimate spatially variable growth rates of an expanding grizzly bear population and provided insight into how those patterns developed. The ability of SCR to utilize unstructured data and produce spatially explicit maps that indicate where population change is occurring promises to facilitate the monitoring of difficult-to-study species across large spatial areas.
An evaluation of the SureID 23comp Human Identification Kit for kinship testing
Authors: Alsafiah Hussain M. , Aljanabi Ali A. , Hadi Sibte , Alturayeif Saleh S. , Goodwin William
Published: November 2019

Short tandem repeat (STR) profiling has been routinely used in kinship testing since the introduction of commercial kits in the mid-1990s. While 15 to 23 STR loci normally give definitive results in simple kinship testing, additional loci are sometimes required to resolve complex cases. The SureID 23comp Human Identification Kit, recently released by Health Gene Technologies (China), multiplexes amelogenin and 22 autosomal STRs, 17 of which are non-CODIS STRs. This enables the profiling of 38–40 loci when used in conjunction with widely used commercial kits. In this study, the kit was evaluated for kinship applications as a supplementary STR kit following the minimum criteria for validation recommended by the European Network of Forensic Science Institutes (ENFSI) and the Scientific Working Group on DNA Analysis Methods (SWGDAM) using 500 samples. Performance was comparable with other commercial kits demonstrating: repeatability and reproducibility; precision (maximum s.d. 0.1048 nt); accuracy, all alleles were within ±0.41 nt compared to the actual sizes; heterozygous peak balances at all loci >68%; stutter ratios ranged from 3.8% to 16.15%; full profiles were generated with 125 pg DNA (95.12% of alleles at 62 pg),; and we found 100% concordance over 5 common STRs with the GlobalFiler kit.
DAMIAN: an open source bioinformatics tool for fast, systematic and cohort based analysis of microorganisms in diagnostic samples
Authors: Alawi Malik , Burkhardt Lia , Indenbirken Daniela , Reumann Kerstin , Christopeit Maximilian , Kröger Nicolaus , Lütgehetmann Marc , Aepfelbacher Martin , Fischer Nicole , Grundhoff Adam
Published: November 2019

We describe DAMIAN, an open source bioinformatics tool designed for the identification of pathogenic microorganisms in diagnostic samples. By using authentic clinical samples and comparing our results to those from established analysis pipelines as well as conventional diagnostics, we demonstrate that DAMIAN rapidly identifies pathogens in different diagnostic entities, and accurately classifies viral agents down to the strain level. We furthermore show that DAMIAN is able to assemble full-length viral genomes even in samples co-infected with multiple virus strains, an ability which is of considerable advantage for the investigation of outbreak scenarios. While DAMIAN, similar to other pipelines, analyzes single samples to perform classification of sequences according to their likely taxonomic origin, it also includes a tool for cohort-based analysis. This tool uses cross-sample comparisons to identify sequence signatures that are frequently present in a sample group of interest (e.g., a disease-associated cohort), but occur less frequently in control cohorts. As this approach does not require homology searches in databases, it principally allows the identification of not only known, but also completely novel pathogens. Using samples from a meningitis outbreak, we demonstrate the feasibility of this approach in identifying enterovirus as the causative agent.