bluuebunny/crossref_metadata_2025 huggingface dataset:
Distribution and Transport of Water Masses in the East Siberian Sea and Their Impacts on the Arctic Halocline
Authors: Wang Xiaoyu , Zhao Jinping , Lobanov Vyacheslav B. , Kaplunenko Dmitry , Rudykh Yan N. , He Yan , Chen Xianyao
Published: July 2021

We investigated the transport of Arctic shelf water and its impacts on the downstream hydrographic structures in the Amerasian Basin by combining data collected in the summer of 2016 from two international cruises in the Pacific sector. The East Siberian Sea (ESS), in which cold shelf water with salinity of 31.0–32.8 is produced, was identified to be a major source of the near‐freezing temperature water for the Makarov Basin. This relatively low‐salinity shelf water was transported into the Chukchi Abyssal Plain and occupied the subsurface layer (30–60 m), which led to the formation of a subsurface oceanic front stretching along the Chukchi Plateau and northern side of the Mendeleev Ridge. The offshore transport of waters from the ESS caused an intrusion of the Atlantic Water onto the shelf and promoted the formation of the diapycnally mixed Lower Halocline Water (D‐LHW) at the bottom of the outer shelf. Our findings indicate that the source of the D‐LHW in the Arctic Pacific sector might extend from the Chukchi Plateau to as far as the Makarov Basin. We hypothesize that advection of waters from the ESS into the Makarov Basin promotes development of the subsurface halocline in the Makarov Basin. The volume transport of surface waters (salinity less than 30) on the ESS shelf was estimated to be about 0.6 Sv (106 m3 s−1) eastward to the Canada Basin in 2016, consistent with the cyclonic Arctic circulation regime in 2016.
Crustal Motion and Strain Rates in the Southern Basin and Range Province
Authors: Sidder Aaron
Published: July 2021

New research teases out variations in strain rates and explores potential earthquake hazards across the southern Basin and Range and Colorado Plateau.
Comparison of GRACE and GNSS Seasonal Load Displacements Considering Regional Averages and Discrete Points
Authors: Zhang Lan , Tang He , Sun Wenke
Published: July 2021

The global navigation satellite system (GNSS) and gravity recovery and climate experiment (GRACE) are two independent geodetic technologies that can detect geometric and gravity deformations, respectively. The signals observed by the two technologies mainly include the internal tectonic movement and surface mass loading effects. The former generally exhibits a long‐term stable linear trend, whereas the latter exhibits strong seasonality. Many studies have compared seasonal deformations between GRACE and GNSS or combined them to study the water cycle or tectonic signals. However, whether GRACE and GNSS are comparable and what the magnitude of their differences still remain unclear. In this study, we present simulations and a case study of the Amazon basin to address this ambiguity. The loading deformations were simulated in response to load masses with varying resolutions and distributions. We found that the discrepancy is about 30% in the spatial average between the accurate loading displacement and the truncated‐result at degree‐60 after applying a G300 or DDK4 filter due to a single load mass. The simulated horizontal deformation may have larger discrepancies at a single point in response to the chessboard mass distributions. The case study in the Amazon basin basically verifies our simulation results, which indicate that there is an ∼40%–50% discrepancy between the GNSS‐observed and GRACE‐modeled displacements spatial average, and it may reach several times that at a single point. We demonstrate that the difference between the GRACE and GNSS is significant for both regional average and single‐point analyses.
Conserved immunomodulatory transcriptional networks underlie antipsychotic-induced weight gain
Authors: Zapata Rizaldy C. , Chaudry Besma S. , Valencia Mariela Lopez , Zhang Dinghong , Ochsner Scott A. , McKenna Neil J. , Osborn Olivia
Published: July 2021

Although antipsychotics, such as olanzapine, are effective in the management of psychiatric conditions, some patients experience excessive antipsychotic-induced weight gain (AIWG). To illuminate pathways underlying AIWG, we compared baseline blood gene expression profiles in two cohorts of mice that were either prone (AIWG-P) or resistant (AIWG-R) to weight gain in response to olanzapine treatment for two weeks. We found that transcripts elevated in AIWG-P mice relative to AIWG-R are enriched for high-confidence transcriptional targets of numerous inflammatory and immunomodulatory signaling nodes. Moreover, these nodes are themselves enriched for genes whose disruption in mice is associated with reduced body fat mass and slow postnatal weight gain. In addition, we identified gene expression profiles in common between our mouse AIWG-P gene set and an existing human AIWG-P gene set whose regulation by immunomodulatory transcription factors is highly conserved between species. Finally, we identified striking convergence between mouse AIWG-P transcriptional regulatory networks and those associated with body weight and body mass index in humans. We propose that immunomodulatory transcriptional networks drive AIWG, and that these networks have broader conserved roles in whole body-metabolism.
A minus-end directed kinesin motor directs gravitropism in Physcomitrella patens
Authors: Li Yufan , Deng Zhaoguo , Kamisugi Yasuko , Chen Zhiren , Wang Jiajun , Han Xue , Wei Yuxiao , He Hang , Terzaghi William , Cove David J. , Cuming Andrew C. , Chen Haodong
Published: July 2021

Gravity is a critical environmental factor regulating directional growth and morphogenesis in plants, and gravitropism is the process by which plants perceive and respond to the gravity vector. The cytoskeleton is proposed to play important roles in gravitropism, but the underlying mechanisms are obscure. Here we use genetic screening in Physcomitrella patens, to identify a locus GTRC, that when mutated, reverses the direction of protonemal gravitropism. GTRC encodes a processive minus-end-directed KCHb kinesin, and its N-terminal, C-terminal and motor domains are all essential for transducing the gravity signal. Chimeric analysis between GTRC/KCHb and KCHa reveal a unique role for the N-terminus of GTRC in gravitropism. Further study shows that gravity-triggered normal asymmetric distribution of actin filaments in the tip of protonema is dependent on GTRC. Thus, our work identifies a microtubule-based cellular motor that determines the direction of plant gravitropism via mediating the asymmetric distribution of actin filaments.
Ternary aromatic and anti-aromatic clusters derived from the hypho species [Sn2Sb5]3−
Authors: Xu Yu-He , Tkachenko Nikolay V. , Popov Ivan A. , Qiao Lei , Muñoz-Castro Alvaro , Boldyrev Alexander I. , Sun Zhong-Ming
Published: July 2021

Heterometallic clusters have attracted broad interests in the synthetic chemistry due to their various coordination modes and potential applications in heterogeneous catalysis. Here we report the synthesis, experimental, and theoretical characterizations of four ternary clusters ([M2(CO)6Sn2Sb5]3− (M = Cr, Mo), and [(MSn2Sb5)2]4−, (M = Cu, Ag)) in the process of capturing the hypho- [Sn2Sb5]3− in ethylenediamine (en) solution. We show that the coordination of the binary anion to transition-metal ions or fragments provides additional stabilization due to the formation of locally σ-aromatic units, producing a spherical aromatic shielding region in the cages. While in the case of [Mo2(CO)6Sn2Sb5]3− stabilization arises from locally σ-aromatic three-centre and five-centre two-electron bonds, aromatic islands in [(AgSn2Sb5)2]4− and [(CuSn2Sb5)2]4− render them globally antiaromatic. This work describes the coordination chemistry of the versatile building block [Sn2Sb5]3−, thus providing conceptual advances in the field of metal-metal bonding in clusters.
Efficient experimental quantum fingerprinting with channel multiplexing and simultaneous detection
Authors: Zhong Xiaoqing , Xu Feihu , Lo Hoi-Kwong , Qian Li
Published: July 2021

Quantum communication complexity explores the minimum amount of communication required to achieve certain tasks using quantum states. One representative example is quantum fingerprinting, in which the minimum amount of communication could be exponentially smaller than the classical fingerprinting. Here, we propose a quantum fingerprinting protocol where coherent states and channel multiplexing are used, with simultaneous detection of signals carried by multiple channels. Compared with an existing coherent quantum fingerprinting protocol, our protocol could consistently reduce communication time and the amount of communication by orders of magnitude by increasing the number of channels. Our proposed protocol can even beat the classical limit without using superconducting-nanowire single photon detectors. We also report a proof-of-concept experimental demonstration with six wavelength channels to validate the advantage of our protocol in the amount of communication. The experimental results clearly prove that our protocol not only surpasses the best-known classical protocol, but also remarkably outperforms the existing coherent quantum fingerprinting protocol.
An on-demand, drop-on-drop method for studying enzyme catalysis by serial crystallography
Authors: Butryn Agata , Simon Philipp S. , Aller Pierre , Hinchliffe Philip , Massad Ramzi N. , Leen Gabriel , Tooke Catherine L. , Bogacz Isabel , Kim In-Sik , Bhowmick Asmit , Brewster Aaron S. , Devenish Nicholas E. , Brem Jürgen , Kamps Jos J. A. G. , Lang Pauline A. , Rabe Patrick , Axford Danny , Beale John H. , Davy Bradley , Ebrahim Ali , Orlans Julien , Storm Selina L. S. , Zhou Tiankun , Owada Shigeki , Tanaka Rie , Tono Kensuke , Evans Gwyndaf , Owen Robin L. , Houle Frances A. , Sauter Nicholas K. , Schofield Christopher J. , Spencer James , Yachandra Vittal K. , Yano Junko , Kern Jan F. , Orville Allen M.
Published: July 2021

Serial femtosecond crystallography has opened up many new opportunities in structural biology. In recent years, several approaches employing light-inducible systems have emerged to enable time-resolved experiments that reveal protein dynamics at high atomic and temporal resolutions. However, very few enzymes are light-dependent, whereas macromolecules requiring ligand diffusion into an active site are ubiquitous. In this work we present a drop-on-drop sample delivery system that enables the study of enzyme-catalyzed reactions in microcrystal slurries. The system delivers ligand solutions in bursts of multiple picoliter-sized drops on top of a larger crystal-containing drop inducing turbulent mixing and transports the mixture to the X-ray interaction region with temporal resolution. We demonstrate mixing using fluorescent dyes, numerical simulations and time-resolved serial femtosecond crystallography, which show rapid ligand diffusion through microdroplets. The drop-on-drop method has the potential to be widely applicable to serial crystallography studies, particularly of enzyme reactions with small molecule substrates.
All-inorganic perovskite quantum dot light-emitting memories
Authors: Yen Meng-Cheng , Lee Chia-Jung , Liu Kang-Hsiang , Peng Yi , Leng Junfu , Chang Tzu-Hsuan , Chang Chun-Chieh , Tamada Kaoru , Lee Ya-Ju
Published: July 2021

Field-induced ionic motions in all-inorganic CsPbBr3 perovskite quantum dots (QDs) strongly dictate not only their electro-optical characteristics but also the ultimate optoelectronic device performance. Here, we show that the functionality of a single Ag/CsPbBr3/ITO device can be actively switched on a sub-millisecond scale from a resistive random-access memory (RRAM) to a light-emitting electrochemical cell (LEC), or vice versa, by simply modulating its bias polarity. We then realize for the first time a fast, all-perovskite light-emitting memory (LEM) operating at 5 kHz by pairing such two identical devices in series, in which one functions as an RRAM to electrically read the encoded data while the other simultaneously as an LEC for a parallel, non-contact optical reading. We further show that the digital status of the LEM can be perceived in real time from its emission color. Our work opens up a completely new horizon for more advanced all-inorganic perovskite optoelectronic technologies.
Rotational and nuclear-spin level dependent photodissociation dynamics of H2S
Authors: Zhao Yarui , Luo Zijie , Chang Yao , Wu Yucheng , Zhang Su-e , Li Zhenxing , Ding Hongbin , Wu Guorong , Campbell Jyoti S. , Hansen Christopher S. , Crane Stuart W. , Western Colin M. , Ashfold Michael N. R. , Yuan Kaijun , Yang Xueming
Published: July 2021

The detailed features of molecular photochemistry are key to understanding chemical processes enabled by non-adiabatic transitions between potential energy surfaces. But even in a small molecule like hydrogen sulphide (H2S), the influence of non-adiabatic transitions is not yet well understood. Here we report high resolution translational spectroscopy measurements of the H and S(1D) photoproducts formed following excitation of H2S to selected quantum levels of a Rydberg state with 1B1 electronic symmetry at wavelengths λ ~ 139.1 nm, revealing rich photofragmentation dynamics. Analysis reveals formation of SH(X), SH(A), S(3P) and H2 co-fragments, and in the diatomic products, inverted internal state population distributions. These nuclear dynamics are rationalised in terms of vibronic and rotational dependent predissociations, with relative probabilities depending on the parent quantum level. The study suggests likely formation routes for the S atoms attributed to solar photolysis of H2S in the coma of comets like C/1995 O1 and C/2014 Q2.
National parochialism is ubiquitous across 42 nations around the world
Authors: Romano Angelo , Sutter Matthias , Liu James H. , Yamagishi Toshio , Balliet Daniel
Published: July 2021

Cooperation within and across borders is of paramount importance for the provision of public goods. Parochialism – the tendency to cooperate more with ingroup than outgroup members – limits contributions to global public goods. National parochialism (i.e., greater cooperation among members of the same nation) could vary across nations and has been hypothesized to be associated with rule of law, exposure to world religions, relational mobility and pathogen stress. We conduct an experiment in participants from 42 nations (N = 18,411), and observe cooperation in a prisoner’s dilemma with ingroup, outgroup, and unidentified partners. We observe that national parochialism is a ubiquitous phenomenon: it is present to a similar degree across the nations studied here, is independent of cultural distance, and occurs both when decisions are private or public. These findings inform existing theories of parochialism and suggest it may be an obstacle to the provision of global public goods.
Bidirectional interconversion of microwave and light with thin-film lithium niobate
Authors: Xu Yuntao , Sayem Ayed Al , Fan Linran , Zou Chang-Ling , Wang Sihao , Cheng Risheng , Fu Wei , Yang Likai , Xu Mingrui , Tang Hong X.
Published: July 2021

Superconducting cavity electro-optics presents a promising route to coherently convert microwave and optical photons and distribute quantum entanglement between superconducting circuits over long-distance. Strong Pockels nonlinearity and high-performance optical cavity are the prerequisites for high conversion efficiency. Thin-film lithium niobate (TFLN) offers these desired characteristics. Despite significant recent progresses, only unidirectional conversion with efficiencies on the order of 10−5 has been realized. In this article, we demonstrate the bidirectional electro-optic conversion in TFLN-superconductor hybrid system, with conversion efficiency improved by more than three orders of magnitude. Our air-clad device architecture boosts the sustainable intracavity pump power at cryogenic temperatures by suppressing the prominent photorefractive effect that limits cryogenic performance of TFLN, and reaches an efficiency of 1.02% (internal efficiency of 15.2%). This work firmly establishes the TFLN-superconductor hybrid EO system as a highly competitive transduction platform for future quantum network applications.
Poor response to neoadjuvant chemotherapy in metaplastic breast carcinoma
Authors: Wong Willard , Brogi Edi , Reis-Filho Jorge S. , Plitas George , Robson Mark , Norton Larry , Morrow Monica , Wen Hannah Y.
Published: July 2021

Metaplastic breast carcinoma (MpBC) is a rare special histologic subtype of breast carcinoma characterized by the presence of squamous and/or mesenchymal differentiation. Most MpBCs are of triple-negative phenotype and neoadjuvant chemotherapy (NAC) is frequently utilized in patients with MpBC. The aim of this study was to evaluate response to NAC in a retrospective cohort of MpBCs. We identified 44 patients with MpBC treated with NAC at our center between 2002 and 2018. Median age was 48 years, 86% were clinical stage II–III, and 36% were clinically node-positive. Most (80%) MpBCs were triple-negative or low (1–10%) hormonal receptor positive and HER2 negative on pre-NAC biopsy. While on NAC, 49% showed no clinical response or clinico-radiological progression. Matrix-producing subtype was associated with clinico-radiological response (p = 0.0036). Post NAC, two patients initially ineligible for breast-conserving surgery (BCS) were downstaged to be eligible for BCS, whereas three patients potentially eligible for BCS before treatment became ineligible due to disease progression. Only one (2%) patient had a pathologic complete response (pCR). Among the 16 patients presenting with biopsy-proven clinical node-positive disease, 3 (19%) had nodal pCR. Axillary lymph node dissection was avoided in 3 (19%) patients who had successful axillary downstaging. Residual cancer burden (RCB) was assessed in 22 patients and was significantly associated with disease-free survival and overall survival. We observed a poor response or even disease progression on NAC among patients with MpBC, suggesting that NAC should be reserved for patients with inoperable MpBC.
Alterations in the activity and sleep of Drosophila melanogaster under simulated microgravity
Authors: Zhang Hongying , Wang Yahong , Zhang Ziyan , Zhang Lu , Tang Chao , Sun Boqun , Jiang Zhihao , Ding Bo , Cai Peng
Published: July 2021

This study aimed to investigate alterations in the activity and sleep of Drosophila melanogaster under simulated microgravity, which was implemented through the random positioning machine, while different light conditions (normal photoperiod and constant dark) were set. Fruit flies of different strains and sexes were treated for 3 days, and activity and sleep were monitored using the Drosophila Activity Monitoring System. After 3 days of treatment, fruit flies were sampled to detect the relative expression levels of the major clock genes and some neurotransmitter-related genes. The results showed that for the normal photoperiod (LD) condition, the activity increased and sleep decreased under simulated microgravity, while for the constant dark (DD) condition, the activity and sleep rhythms appeared disordered and the activity increased, thus decreasing the likelihood of waking up during the day. Light conditions, strains, and sexes, individually or in combination, had impacts on the simulated microgravity effects on behaviors. The clock genes and neurotransmitter-related genes had different degrees of response among sexes and strains, although the overall changes were slight. The results indicated that the normal photoperiod could ease the effects of simulated microgravity on fruit flies’ activity and sleep and possible unidentified pathways involved in the regulatory mechanism need further exploration. This study is expected to provide ideas and references for studying the effects of microgravity on space life science.
Microstructured capacitive sensor with broad detection range and long-term stability for human activity detection
Authors: He Xin , Liu Zhihao , Shen Gengzhe , He Xiang , Liang Jionghong , Zhong Yu , Liang Tianlong , He Jie , Xin Yue , Zhang Chi , Ye Dongdong , Cai Guofa
Published: July 2021

In recent years, flexible stress sensors capable of monitoring diverse body movements and physiological signals have been attracting great attention in the fields of healthcare systems, human–machine interfaces, and wearable electronics. Inspired by the structure of natural eggshell inner membrane (ESIM), we developed a pressure sensor based on MXene (Ti3C2Tx)/Ag NWs (silver nanowires) composite electrodes and the micro-structured dielectric layer to meet the application requirements of wide detection range and long-term stability for the sensors. In the light of the nanoscale-microarray of the dielectric layer and the rough surface of electrode materials, this pressure sensor is expected to allow great and persistent deformation during the loading process. As a result, the device is characterized by an improved sensitivity, fast response (in the millisecond range), wide detection range (0–600 kPa), and long-term stability. The outstanding performance of the proposed sensor makes it possible to detect various human activities, such as speaking, air blowing, clenching, walking, finger/knee/elbow bending, and striking, demonstrating its good application prospects in wearable and flexible electronic devices.
resistancebank.org, an open-access repository for surveys of antimicrobial resistance in animals
Authors: Criscuolo Nicola G. , Pires João , Zhao Cheng , Van Boeckel Thomas P.
Published: July 2021

Antimicrobial resistance (AMR) is a growing threat to the health of humans and animals that requires global actions. In high-income countries, surveillance systems helped inform policies to curb AMR in animals. In low- and middle-income countries (LMICs), demand for meat is rising, and developing policies against AMR is urgent. However, surveillance of AMR is at best nascent, and the current evidence base to inform policymakers is geographically heterogeneous. We present resistancebank.org, an online platform that centralizes information on AMR in animals from 1,285 surveys from LMICs. Surveys were conducted between 2000 and 2019 and include 22,403 resistance rates for pathogens isolated from chickens, cattle, sheep, and pigs. The platform is built as a shiny application that provides access to individual surveys, country-level reports, and maps of AMR at 10 × 10 kilometers resolution. The platform is accessed via any internet browser and enables users to upload surveys to strengthen a global database. resistancebank.org aims to be a focal point for sharing AMR data in LMICs and to help international funders prioritize their actions.
Powered flight in hatchling pterosaurs: evidence from wing form and bone strength
Authors: Naish Darren , Witton Mark P. , Martin-Silverstone Elizabeth
Published: July 2021

Competing views exist on the behaviour and lifestyle of pterosaurs during the earliest phases of life. A ‘flap-early’ model proposes that hatchlings were capable of independent life and flapping flight, a ‘fly-late’ model posits that juveniles were not flight capable until 50% of adult size, and a ‘glide-early’ model requires that young juveniles were flight-capable but only able to glide. We test these models by quantifying the flight abilities of very young juvenile pterosaurs via analysis of wing bone strength, wing loading, wingspan and wing aspect ratios, primarily using data from embryonic and hatchling specimens of Pterodaustro guinazui and Sinopterus dongi. We argue that a young Sinopterus specimen has been mischaracterised as a distinct taxon. The humeri of pterosaur juveniles are similar in bending strength to those of adults and able to withstand launch and flight; wing size and wing aspect ratios of young juveniles are also in keeping with powered flight. We therefore reject the ‘fly-late’ and ‘glide-early’ models. We further show that young juveniles were excellent gliders, albeit not reliant on specialist gliding. The wing forms of very young juveniles differ significantly from larger individuals, meaning that variation in speed, manoeuvrability, take-off angle and so on was present across a species as it matured. Juveniles appear to have been adapted for flight in cluttered environments, in contrast to larger, older individuals. We propose on the basis of these conclusions that pterosaur species occupied distinct niches across ontogeny.
The first draft genome of Picrorhiza kurrooa, an endangered medicinal herb from Himalayas
Authors: Sharma Tanvi , Sharma Nitesh Kumar , Kumar Prakash , Panzade Ganesh , Rana Tanuja , Swarnkar Mohit Kumar , Singh Anil Kumar , Singh Dharam , Shankar Ravi , Kumar Sanjay
Published: July 2021

Picrorhiza kurrooa is an endangered medicinal herb which is distributed across the Himalayan region at an altitude between 3000–5000 m above mean sea level. The medicinal properties of P. kurrooa are attributed to monoterpenoid picrosides present in leaf, rhizome and root of the plant. However, no genomic information is currently available for P. kurrooa, which limits our understanding about its molecular systems and associated responses. The present study brings the first assembled draft genome of P. kurrooa by using 227 Gb of raw data generated by Illumina and PacBio RS II sequencing platforms. The assembled genome has a size of n = ~ 1.7 Gb with 12,924 scaffolds. Four pronged assembly quality validations studies, including experimentally reported ESTs mapping and directed sequencing of the assembled contigs, confirmed high reliability of the assembly. About 76% of the genome is covered by complex repeats alone. Annotation revealed 24,798 protein coding and 9789 non-coding genes. Using the assembled genome, a total of 710 miRNAs were discovered, many of which were found responsible for molecular response against temperature changes. The miRNAs and targets were validated experimentally. The availability of draft genome sequence will aid in genetic improvement and conservation of P. kurrooa. Also, this study provided an efficient approach for assembling complex genomes while dealing with repeats when regular assemblers failed to progress due to repeats.
Nutrient provision capacity of alternative livestock farming systems per area of arable farmland required
Authors: Lee M. R. F. , Domingues J. P. , McAuliffe G. A. , Tichit M. , Accatino F. , Takahashi T.
Published: July 2021

Although climate impacts of ruminant agriculture are a major concern worldwide, using policy instruments to force grazing farms out of the livestock industry may diminish opportunities to produce nutritious food without exacerbating the food-feed competition for fertile and accessible land resources. Here, we present a new set of quantitative evidence to demonstrate that, per unit of overall nutrient value supplied by a given commodity, the demand for land suitable for human-edible crop production is considerably smaller under ruminant systems than monogastric systems, and consistently so at both farm and regional scales. We also demonstrate that imposition of a naïvely designed “red meat tax” has the potential to invite socioeconomic losses far greater than its environmental benefits, due largely to the induced misallocation of resources at the national scale. Our results reiterate the risk inherent in an excessively climate-focused debate on the role of livestock in human society and call for more multidimensional approaches of sustainability assessment to draw better-balanced policy packages.
Gut microbiota-generated metabolite, trimethylamine-N-oxide, and subclinical myocardial damage: a multicenter study from Thailand
Authors: Senthong Vichai , Kiatchoosakun Songsak , Wongvipaporn Chaiyasith , Phetcharaburanin Jutarop , Tatsanavivat Pyatat , Sritara Piyamitr , Phrommintikul Arintaya
Published: July 2021

Plasma Trimethylamine-N-oxide (TMAO), a gut microbiota metabolite from dietary phosphatidylcholine, is mechanistically linked to cardiovascular disease (CVD) and adverse cardiovascular events. We aimed to examine the relationship between plasma TMAO levels and subclinical myocardial damage using high-sensitivity cardiac troponin-T (hs-cTnT). We studied 134 patients for whom TMAO data were available from the Cohort Of patients at a high Risk of Cardiovascular Events—Thailand (CORE-Thailand) registry, including 123 (92%) patients with established atherosclerotic disease and 11 (8%) with multiple risk factors. Plasma TMAO was measured by NMR spectroscopy. In our study cohort (mean age 64 ± 8.9 years; 61% men), median TMAO was 3.81 μM (interquartile range [IQR] 2.89–5.50 μM), and median hs-cTnT was 15.65 ng/L (IQR 10.17–26.67). Older patients and those with diabetic or hypertension were more likely to have higher TMAO levels. Plasma TMAO levels correlated with those of hs-cTnT (r = 0.54; p < 0.0001) and were significantly higher in patients with subclinical myocardial damage (hs-cTnT ≥ 14 ng/L; 4.48 μM vs 2.98 μM p < 0.0001). After adjusting for traditional risk factors, elevated TMAO levels remained independently associated with subclinical myocardial damage (adjusted odds ratio [OR]: 1.58; 95% CI 1.24–2.08; p = 0.0007). This study demonstrated that plasma TMAO was an independent predictor for subclinical myocardial damage in this study population.
Topoisomerase II deficiency leads to a postreplicative structural shift in all Saccharomyces cerevisiae chromosomes
Authors: Ayra-Plasencia Jessel , Ramos-Pérez Cristina , Santana-Sosa Silvia , Quevedo Oliver , Medina-Suárez Sara , Matos-Perdomo Emiliano , Zamora-Dorta Marcos , Brown Grant W. , Lisby Michael , Machín Félix
Published: July 2021

The key role of Topoisomerase II (Top2) is the removal of topological intertwines between sister chromatids. In yeast, inactivation of Top2 brings about distinct cell cycle responses. In the case of the conditional top2-5 allele, interphase and mitosis progress on schedule but cells suffer from a chromosome segregation catastrophe. We here show that top2-5 chromosomes fail to enter a Pulsed-Field Gel Electrophoresis (PFGE) in the first cell cycle, a behavior traditionally linked to the presence of replication and recombination intermediates. We distinguished two classes of affected chromosomes: the rDNA-bearing chromosome XII, which fails to enter a PFGE at the beginning of S-phase, and all the other chromosomes, which fail at a postreplicative stage. In synchronously cycling cells, this late PFGE retention is observed in anaphase; however, we demonstrate that this behavior is independent of cytokinesis, stabilization of anaphase bridges, spindle pulling forces and, probably, anaphase onset. Strikingly, once the PFGE retention has occurred it becomes refractory to Top2 re-activation. DNA combing, two-dimensional electrophoresis, genetic analyses, and GFP-tagged DNA damage markers suggest that neither recombination intermediates nor unfinished replication account for the postreplicative PFGE shift, which is further supported by the fact that the shift does not trigger the G2/M checkpoint. We propose that the absence of Top2 activity leads to a general chromosome structural/topological change in mitosis.
Agro-economic and socio-environmental assessments of food and virtual water trades of Iran
Authors: Karandish Fatemeh , Nouri Hamideh , Brugnach Marcela
Published: July 2021

Ending hunger and ensuring food security are among targets of 2030’s SDGs. While food trade and the embedded (virtual) water (VW) may improve food availability and accessibility for more people all year round, the sustainability and efficiency of food and VW trade needs to be revisited. In this research, we assess the sustainability and efficiency of food and VW trades under two food security scenarios for Iran, a country suffering from an escalating water crisis. These scenarios are (1) Individual Crop Food Security (ICFS), which restricts calorie fulfillment from individual crops and (2) Crop Category Food Security (CCFS), which promotes “eating local” by suggesting food substitution within the crop category. To this end, we simulate the water footprint and VW trades of 27 major crops, within 8 crop categories, in 30 provinces of Iran (2005–2015). We investigate the impacts of these two scenarios on (a) provincial food security (FSp) and exports; (b) sustainable and efficient blue water consumption, and (c) blue VW export. We then test the correlation between agro-economic and socio-environmental indicators and provincial food security. Our results show that most provinces were threatened by unsustainable and inefficient blue water consumption for crop production, particularly in the summertime. This water mismanagement results in 14.41 and 8.45 billion m3 y−1 unsustainable and inefficient blue VW exports under ICFS. “Eating local” improves the FSp value by up to 210% which lessens the unsustainable and inefficient blue VW export from hotspots. As illustrated in the graphical abstract, the FSp value strongly correlates with different agro-economic and socio-environmental indicators, but in different ways. Our findings promote “eating local” besides improving agro-economic and socio-environmental conditions to take transformative steps toward eradicating food insecurity not only in Iran but also in other countries facing water limitations.
Diagnostic accuracy of dual-phase 18F-FP-CIT PET imaging for detection and differential diagnosis of Parkinsonism
Authors: Oh Minyoung , Lee Narae , Kim Chanwoo , Son Hye Joo , Sung Changhwan , Oh Seung Jun , Lee Sang Ju , Chung Sun Ju , Lee Chong Sik , Kim Jae Seung
Published: July 2021

Delayed phase 18F-FP-CIT PET (dCIT) can assess the striatal dopamine transporter binding to detect degenerative parkinsonism (DP). Early phase 18F-FP-CIT (eCIT) can assess the regional brain activity for differential diagnosis among parkinsonism similar with 18F-FDG PET. We evaluated the diagnostic performance of dual phase 18F-FP-CIT PET (dual CIT) and 18F-FDG PET compared with clinical diagnosis in 141 subjects [36 with idiopathic Parkinson’s disease (IPD), 77 with multiple system atrophy (MSA), 18 with progressive supranuclear palsy (PSP), and 10 with non-DP)]. Visual assessment of eCIT, dCIT, dual CIT, 18F-FDG and 18F-FDG PET with dCIT was in agreement with the clinical diagnosis in 61.7%, 69.5%, 95.7%, 81.6%, and 97.2% of cases, respectively. ECIT showed about 90% concordance with non-DP and MSA, and 8.3% and 27.8% with IPD and PSP, respectively. DCIT showed ≥ 88% concordance with non-DP, IPD, and PSP, and 49.4% concordance with MSA. Dual CIT showed ≥ 90% concordance in all groups. 18F-FDG PET showed ≥ 90% concordance with non-DP, MSA, and PSP, but only 33.3% concordance with IPD. The combination of 18F-FDG and dCIT yielded ≥ 90% concordance in all groups. Dual CIT may represent a powerful alternative to the combination of 18F-FDG PET and dCIT for differential diagnosis of parkinsonian disorders.
Circular noncoding RNA hsa_circ_0005986 as a prognostic biomarker for hepatocellular carcinoma
Authors: Kim Gyeonghwa , Han Ja Ryung , Park Soo Young , Tak Won Young , Kweon Young-Oh , Lee Yu Rim , Han Young Seok , Park Jung Gil , Kang Min Kyu , Lee Hye Won , Lee Won Kee , Kim Deokhoon , Jang Se Young , Hur Keun
Published: July 2021

Circular RNAs (circRNAs) represent potential biomarkers because of their highly stable structure and robust expression pattern in clinical samples. The aim of this study was to evaluate the expression of a recently identified circRNA, hsa_circ_0005986; determine its clinical significance; and evaluate its potential as a biomarker of hepatocellular carcinoma (HCC). We evaluated hsa_circ_0005986 expression in 123 HCC tissue samples, its clinical significance, and its association with patients’ clinicopathological characteristics and survival. Hsa_circ_0005986 expression was downregulated in HCC tissues. Low hsa_circ_0005986 expression was more common in tumors larger than 5 cm [odds ratio (OR), 3.19; 95% confidence interval (CI), 1.51–6.76; p = 0.002], advanced TNM stage (III/IV; OR, 2.39; 95% CI, 1.16–4.95; p = 0.018), and higher BCLC stage (B/C; OR, 2.71; 95% CI, 1.30–5.65; p = 0.007). High hsa_circ_0005986 expression was associated with improved survival and was an independent prognostic factor for overall [hazard ratio (HR), 0.572; 95% CI, 0.339–0.966; p = 0.037] and progression-free (HR, 0.573; 95% CI, 0.362–0.906; p = 0.017) survival. Moreover, the circRNA–miRNA–mRNA network was constructed using RNA-seq/miRNA-seq data and clinical information from TCGA-LIHC dataset. Our findings indicate a promising role for hsa_circ_0005986 as a prognostic biomarker in patients with HCC.
International﻿ fisheries threaten globally endangered sharks in the Eastern Tropical Pacific Ocean: the case of the Fu Yuan Yu Leng 999 reefer vessel seized within the Galápagos Marine Reserve
Authors: Bonaccorso Elisa , Ordóñez-Garza Nicté , Pazmiño Diana A. , Hearn Alex , Páez-Rosas Diego , Cruz Sebastián , Muñoz-Pérez Juan Pablo , Espinoza Eduardo , Suárez Jenifer , Muñoz-Rosado Lauren D. , Vizuete Andrea , Chaves Jaime A. , Torres Maria de Lourde , Bustos Walter , Rueda Danny , Hirschfeld Maximilian , Guayasamin Juan M.
Published: July 2021

Shark fishing, driven by the fin trade, is the primary cause of global shark population declines. Here, we present a case study that exemplifies how industrial fisheries are likely depleting shark populations in the Eastern Tropical Pacific Ocean. In August 2017, the vessel Fu Yuan Yu Leng 999, of Chinese flag, was detained while crossing through the Galápagos Marine Reserve without authorization. This vessel contained 7639 sharks, representing one of the largest seizures recorded to date. Based on a sample of 929 individuals (12%), we found 12 shark species: 9 considered as Vulnerable or higher risk by the IUCN and 8 listed in CITES. Four species showed a higher proportion of immature than mature individuals, whereas size-distribution hints that at least some of the fishing ships associated with the operation may have been using purse-seine gear fishing equipment, which, for some species, goes against international conventions. Our data expose the magnitude of the threat that fishing industries and illegal trade represent to sharks in the Eastern Tropical Pacific Ocean.
Diffusion tensor imaging in cubital tunnel syndrome
Authors: Griffiths Timothy T. , Flather Robert , Teh Irvin , Haroon Hamied A. , Shelley David , Plein Sven , Bourke Grainne , Wade Ryckie G.
Published: July 2021

Cubital tunnel syndrome (CuTS) is the 2nd most common compressive neuropathy. To improve both diagnosis and the selection of patients for surgery, there is a pressing need to develop a reliable and objective test of ulnar nerve ‘health’. Diffusion tensor imaging (DTI) characterises tissue microstructure and may identify differences in the normal ulnar from those affected by CuTS. The aim of this study was to compare the DTI metrics from the ulnar nerves of healthy (asymptomatic) adults and patients with CuTS awaiting surgery. DTI was acquired at 3.0 T using single-shot echo-planar imaging (55 axial slices, 3 mm thick, 1.5 mm2 in-plane) with 30 diffusion sensitising gradient directions, a b-value of 800 s/mm2 and 4 signal averages. The sequence was repeated with the phase-encoding direction reversed. Data were combined and corrected using the FMRIB Software Library (FSL) and reconstructed using generalized q-sampling imaging in DSI Studio. Throughout the length of the ulnar nerve, the fractional anisotropy (FA), quantitative anisotropy (QA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) were extracted, then compared using mixed-effects linear regression. Thirteen healthy controls (8 males, 5 females) and 8 patients with CuTS (6 males, 2 females) completed the study. Throughout the length of the ulnar nerve, diffusion was more isotropic in patients with CuTS. Overall, patients with CuTS had a 6% lower FA than controls, with the largest difference observed proximal to the cubital tunnel (mean difference 0.087 [95% CI 0.035, 0.141]). Patients with CuTS also had a higher RD than controls, with the largest disparity observed within the forearm (mean difference 0.252 × 10–4 mm2/s [95% CI 0.085 × 10–4, 0.419 × 10–4]). There were no significant differences between patients and controls in QA, MD or AD. Throughout the length of the ulnar nerve, the fractional anisotropy and radial diffusivity in patients with CuTS are different to healthy controls. These findings suggest that DTI may provide an objective assessment of the ulnar nerve and potentially, improve the management of CuTS.
Cannabis constituents interact at the drug efflux pump BCRP to markedly increase plasma cannabidiolic acid concentrations
Authors: Anderson Lyndsey L. , Etchart Maia G. , Bahceci Dilara , Golembiewski Taliesin A. , Arnold Jonathon C.
Published: July 2021

Cannabis is a complex mixture of hundreds of bioactive molecules. This provides the potential for pharmacological interactions between cannabis constituents, a phenomenon referred to as “the entourage effect” by the medicinal cannabis community. We hypothesize that pharmacokinetic interactions between cannabis constituents could substantially alter systemic cannabinoid concentrations. To address this hypothesis we compared pharmacokinetic parameters of cannabinoids administered orally in a cannabis extract to those administered as individual cannabinoids at equivalent doses in mice. Astonishingly, plasma cannabidiolic acid (CBDA) concentrations were 14-times higher following administration in the cannabis extract than when administered as a single molecule. In vitro transwell assays identified CBDA as a substrate of the drug efflux transporter breast cancer resistance protein (BCRP), and that cannabigerol and Δ9-tetrahydrocannabinol inhibited the BCRP-mediated transport of CBDA. Such a cannabinoid-cannabinoid interaction at BCRP transporters located in the intestine would inhibit efflux of CBDA, thus resulting in increased plasma concentrations. Our results suggest that cannabis extracts provide a natural vehicle to substantially enhance plasma CBDA concentrations. Moreover, CBDA might have a more significant contribution to the pharmacological effects of orally administered cannabis extracts than previously thought.
Photocontrolled apoptosis induction using precursor miR-664a and an RNA carrier-conjugated with photosensitizer
Authors: Watanabe Kazunori , Nawachi Tomoko , Okutani Ruriko , Ohtsuki Takashi
Published: July 2021

Methods to spatially induce apoptosis are useful for cancer therapy. To control the induction of apoptosis, methods using light, such as photochemical internalization (PCI), have been developed. We hypothesized that photoinduced delivery of microRNAs (miRNAs) that regulate apoptosis could spatially induce apoptosis. In this study, we identified pre-miR-664a as a novel apoptosis-inducing miRNA via mitochondrial apoptotic pathway. Further, we demonstrated the utility of photoinduced cytosolic dispersion of RNA (PCDR), which is an intracellular RNA delivery method based on PCI. Indeed, apoptosis is spatially regulated by pre-miR-664a and PCDR. In addition, we found that apoptosis induced by pre-miR-664a delivered by PCDR was more rapid than that by lipofection. These results suggest that pre-miR-664a is a nucleic acid drug candidate for cancer therapy and PCDR and pre-miR-664a-based strategies have potential therapeutic uses for diseases affecting various cell types.
Context-dependent effects of whole-genome duplication during mammary tumor recurrence
Authors: Newcomb Rachel , Dean Emily , McKinney Brock J. , Alvarez James V.
Published: July 2021

Whole-genome duplication (WGD) generates polyploid cells possessing more than two copies of the genome and is among the most common genetic abnormalities in cancer. The frequency of WGD increases in advanced and metastatic tumors, and WGD is associated with poor prognosis in diverse tumor types, suggesting a functional role for polyploidy in tumor progression. Experimental evidence suggests that polyploidy has both tumor-promoting and suppressing effects, but how polyploidy regulates tumor progression remains unclear. Using a genetically engineered mouse model of Her2-driven breast cancer, we explored the prevalence and consequences of whole-genome duplication during tumor growth and recurrence. While primary tumors in this model are invariably diploid, nearly 40% of recurrent tumors undergo WGD. WGD in recurrent tumors was associated with increased chromosomal instability, decreased proliferation and increased survival in stress conditions. The effects of WGD on tumor growth were dependent on tumor stage. Surprisingly, in recurrent tumor cells WGD slowed tumor formation, growth rate and opposed the process of recurrence, while WGD promoted the growth of primary tumors. These findings highlight the importance of identifying conditions that promote the growth of polyploid tumors, including the cooperating genetic mutations that allow cells to overcome the barriers to WGD tumor cell growth and proliferation.
Linoleic and oleic acids enhance cell migration by altering the dynamics of microtubules and the remodeling of the actin cytoskeleton at the leading edge
Authors: Masner M. , Lujea N. , Bisbal M. , Acosta C. , Kunda Patricia
Published: July 2021

Fatty acids (FA) have a multitude of biological actions on living cells. A target of their action is cell motility, a process of critical importance during cancer cell dissemination. Here, we studied the effect of unsaturated FA on ovarian cancer cell migration in vitro and its role in regulating cytoskeleton structures that are essential for cell motility. Scratch wound assays on human ovary cancer SKOV-3 cell monolayers revealed that low doses (16 μM) of linoleic acid (LA, 18:2 ω6) and oleic acid (OA; 18:1 ω9) promoted migration, while α-linolenic acid (ALA, 18:3 ω3), showed a migration rate similar to that of the control group. Single cell tracking demonstrated that LA and OA-treated cells migrated faster and were more orientated towards the wound closure than control. In vitro addition of those FA resulted in an increased number, length and protrusion speed of filopodia and also in a prominent and dynamic lamellipodia at the cell leading edge. Using time-lapse video-microscopy and FRAP we observed an increase in both the speed and frequency of actin waves associated with more mobile actin and augmented Rac1 activity. We also observed that FA induced microtubule-organizing center (MTOC)-orientation towards the cell front and affected the dynamics of microtubules (MT) in the direction of cell migration. We propose that environmental cues such as OA and LA present in ascitic fluid, should be taken into account as key factors for the regulation of cell migration.
A novel framework for designing a multi-DoF prosthetic wrist control using machine learning
Authors: Swami Chinmay P. , Lenhard Nicholas , Kang Jiyeon
Published: July 2021

Prosthetic arms can significantly increase the upper limb function of individuals with upper limb loss, however despite the development of various multi-DoF prosthetic arms the rate of prosthesis abandonment is still high. One of the major challenges is to design a multi-DoF controller that has high precision, robustness, and intuitiveness for daily use. The present study demonstrates a novel framework for developing a controller leveraging machine learning algorithms and movement synergies to implement natural control of a 2-DoF prosthetic wrist for activities of daily living (ADL). The data was collected during ADL tasks of ten individuals with a wrist brace emulating the absence of wrist function. Using this data, the neural network classifies the movement and then random forest regression computes the desired velocity of the prosthetic wrist. The models were trained/tested with ADLs where their robustness was tested using cross-validation and holdout data sets. The proposed framework demonstrated high accuracy (F-1 score of 99% for the classifier and Pearson’s correlation of 0.98 for the regression). Additionally, the interpretable nature of random forest regression was used to verify the targeted movement synergies. The present work provides a novel and effective framework to develop an intuitive control for multi-DoF prosthetic devices.