bluuebunny/crossref_metadata_2025 huggingface dataset:
An artificial spiking quantum neuron
Authors: Kristensen Lasse Bjørn , Degroote Matthias , Wittek Peter , Aspuru-Guzik Alán , Zinner Nikolaj T.
Published: April 2021

Artificial spiking neural networks have found applications in areas where the temporal nature of activation offers an advantage, such as time series prediction and signal processing. To improve their efficiency, spiking architectures often run on custom-designed neuromorphic hardware, but, despite their attractive properties, these implementations have been limited to digital systems. We describe an artificial quantum spiking neuron that relies on the dynamical evolution of two easy to implement Hamiltonians and subsequent local measurements. The architecture allows exploiting complex amplitudes and back-action from measurements to influence the input. This approach to learning protocols is advantageous in the case where the input and output of the system are both quantum states. We demonstrate this through the classification of Bell pairs which can be seen as a certification protocol. Stacking the introduced elementary building blocks into larger networks combines the spatiotemporal features of a spiking neural network with the non-local quantum correlations across the graph.
Lattice-shifted nematic quantum critical point in FeSe1−xSx
Authors: Chibani S. , Farina D. , Massat P. , Cazayous M. , Sacuto A. , Urata T. , Tanabe Y. , Tanigaki K. , Böhmer A. E. , Canfield P. C. , Merz M. , Karlsson S. , Strobel P. , Toulemonde P. , Paul I. , Gallais Y.
Published: April 2021

We report the evolution of nematic fluctuations in FeSe1−xSx single crystals as a function of Sulfur content x across the nematic quantum critical point (QCP) xc ~ 0.17 via Raman scattering. The Raman spectra in the B1g nematic channel consist of two components, but only the low energy one displays clear fingerprints of critical behavior and is attributed to itinerant carriers. Curie–Weiss analysis of the associated nematic susceptibility indicates a substantial effect of nemato-elastic coupling, which shifts the location of the nematic QCP. We argue that this lattice-induced shift likely explains the absence of any enhancement of the superconducting transition temperature at the QCP. The presence of two components in the nematic fluctuations spectrum is attributed to the dual aspect of electronic degrees of freedom in Hund’s metals, with both itinerant carriers and local moments contributing to the nematic susceptibility.
Force of infection: a determinant of vaccine efficacy?
Authors: Kaslow David C.
Published: April 2021

Vaccine efficacy (VE) can vary in different settings. Of the many proposed setting-dependent determinants of VE, force of infection (FoI) stands out as one of the most direct, proximate, and actionable. As highlighted by the COVID-19 pandemic, modifying FoI through non-pharmaceutical interventions (NPIs) use can significantly contribute to controlling transmission and reducing disease incidence and severity absent highly effective pharmaceutical interventions, such as vaccines. Given that NPIs reduce the FoI, the question arises as to if and to what degree FoI, and by extension NPIs, can modify VE, and more practically, as vaccines become available for a pathogen, whether and which NPIs should continue to be used in conjunction with vaccines to optimize controlling transmission and reducing disease incidence and severity.
Structural basis of nucleosome transcription mediated by Chd1 and FACT
Authors: Farnung Lucas , Ochmann Moritz , Engeholm Maik , Cramer Patrick
Published: April 2021

Efficient transcription of RNA polymerase II (Pol II) through nucleosomes requires the help of various factors. Here we show biochemically that Pol II transcription through a nucleosome is facilitated by the chromatin remodeler Chd1 and the histone chaperone FACT when the elongation factors Spt4/5 and TFIIS are present. We report cryo-EM structures of transcribing Saccharomyces cerevisiae Pol II−Spt4/5−nucleosome complexes with bound Chd1 or FACT. In the first structure, Pol II transcription exposes the proximal histone H2A−H2B dimer that is bound by Spt5. Pol II has also released the inhibitory DNA-binding region of Chd1 that is poised to pump DNA toward Pol II. In the second structure, Pol II has generated a partially unraveled nucleosome that binds FACT, which excludes Chd1 and Spt5. These results suggest that Pol II progression through a nucleosome activates Chd1, enables FACT binding and eventually triggers transfer of FACT together with histones to upstream DNA.
Heidelberg colorectal data set for surgical data science in the sensor operating room
Authors: Maier-Hein Lena , Wagner Martin , Ross Tobias , Reinke Annika , Bodenstedt Sebastian , Full Peter M. , Hempe Hellena , Mindroc-Filimon Diana , Scholz Patrick , Tran Thuy Nuong , Bruno Pierangela , Kisilenko Anna , Müller Benjamin , Davitashvili Tornike , Capek Manuela , Tizabi Minu D. , Eisenmann Matthias , Adler Tim J. , Gröhl Janek , Schellenberg Melanie , Seidlitz Silvia , Lai T. Y. Emmy , Pekdemir Bünyamin , Roethlingshoefer Veith , Both Fabian , Bittel Sebastian , Mengler Marc , Mündermann Lars , Apitz Martin , Kopp-Schneider Annette , Speidel Stefanie , Nickel Felix , Probst Pascal , Kenngott Hannes G. , Müller-Stich Beat P.
Published: April 2021

Image-based tracking of medical instruments is an integral part of surgical data science applications. Previous research has addressed the tasks of detecting, segmenting and tracking medical instruments based on laparoscopic video data. However, the proposed methods still tend to fail when applied to challenging images and do not generalize well to data they have not been trained on. This paper introduces the Heidelberg Colorectal (HeiCo) data set - the first publicly available data set enabling comprehensive benchmarking of medical instrument detection and segmentation algorithms with a specific emphasis on method robustness and generalization capabilities. Our data set comprises 30 laparoscopic videos and corresponding sensor data from medical devices in the operating room for three different types of laparoscopic surgery. Annotations include surgical phase labels for all video frames as well as information on instrument presence and corresponding instance-wise segmentation masks for surgical instruments (if any) in more than 10,000 individual frames. The data has successfully been used to organize international competitions within the Endoscopic Vision Challenges 2017 and 2019.
Triple SILAC identified progestin-independent and dependent PRA and PRB interacting partners in breast cancer
Authors: Pateetin Prangwan , Hutvagner Gyorgy , Bajan Sarah , Padula Matthew P. , McGowan Eileen M. , Boonyaratanakornkit Viroj
Published: April 2021

Progesterone receptor (PR) isoforms, PRA and PRB, act in a progesterone-independent and dependent manner to differentially modulate the biology of breast cancer cells. Here we show that the differences in PRA and PRB structure facilitate the binding of common and distinct protein interacting partners affecting the downstream signaling events of each PR-isoform. Tet-inducible HA-tagged PRA or HA-tagged PRB constructs were expressed in T47DC42 (PR/ER negative) breast cancer cells. Affinity purification coupled with stable isotope labeling of amino acids in cell culture (SILAC) mass spectrometry technique was performed to comprehensively study PRA and PRB interacting partners in both unliganded and liganded conditions. To validate our findings, we applied both forward and reverse SILAC conditions to effectively minimize experimental errors. These datasets will be useful in investigating PRA- and PRB-specific molecular mechanisms and as a database for subsequent experiments to identify novel PRA and PRB interacting proteins that differentially mediated different biological functions in breast cancer.
Pro-inflammatory effects of DEHP in SGBS-derived adipocytes and THP-1 macrophages
Authors: Schaedlich Kristina , Beier Laura-Sophie , Kolbe Judith , Wabitsch Martin , Ernst Jana
Published: April 2021

In the member countries of the Organization for Economic Co-operation and Development (OECD), overweight and obesity affect the majority of the population. The use of environmental chemicals, such as the plasticizer DEHP, has largely increased simultaneously with this development. DEHP is an "obesogen" that interferes with normal adipocyte differentiation and energy homeostasis. Obesity in turn is accompanied by chronic low-grade adipose tissue inflammation, leading to metabolic disorders such as type II diabetes. The main actors in adipose tissue inflammation are adipocytes and macrophages. However, the impact of DEHP on adipose tissue inflammation and the crosstalk between adipocytes and macrophages are unknown and the subjects of the current study. The influence of DEHP on inflammation was investigated in human Simpson–Golabi–Behmel syndrome (SGBS)-derived adipocytes and human THP-1 macrophages. The proinflammatory markers IL8, MCP1, IL1β, TNFα and others were measured (qRT-PCR, ELISA) in SGBS-derived adipocytes treated with DEHP [day 0 (d0)–d4; 50 µg/ml] and THP-1 macrophages cultured with conditioned medium (CM) from DEHP-treated adipocytes (SGBS-CM) (from d4 and d8). DEHP exposure led to a proinflammatory state in SGBS-derived adipocytes (e.g., increased secretion of IL8 and MCP1). Surprisingly, exposure of THP-1 macrophages to SGBS-CM did not show DEHP-induced effects. However, we demonstrated that medium containing (pre)adipocyte-secreted factors had a significant impact on the expression and secretion of macrophage and inflammatory markers in THP-1 macrophages in general and led to the significantly increased accumulation of intracellular lipid droplets.
A flexible microfluidic system for single-cell transcriptome profiling elucidates phased transcriptional regulators of cell cycle
Authors: Davey Karen , Wong Daniel , Konopacki Filip , Kwa Eugene , Ly Tony , Fiegler Heike , Sibley Christopher R.
Published: April 2021

Single cell transcriptome profiling has emerged as a breakthrough technology for the high-resolution understanding of complex cellular systems. Here we report a flexible, cost-effective and user-friendly droplet-based microfluidics system, called the Nadia Instrument, that can allow 3′ mRNA capture of ~ 50,000 single cells or individual nuclei in a single run. The precise pressure-based system demonstrates highly reproducible droplet size, low doublet rates and high mRNA capture efficiencies that compare favorably in the field. Moreover, when combined with the Nadia Innovate, the system can be transformed into an adaptable setup that enables use of different buffers and barcoded bead configurations to facilitate diverse applications. Finally, by 3′ mRNA profiling asynchronous human and mouse cells at different phases of the cell cycle, we demonstrate the system's ability to readily distinguish distinct cell populations and infer underlying transcriptional regulatory networks. Notably this provided supportive evidence for multiple transcription factors that had little or no known link to the cell cycle (e.g. DRAP1, ZKSCAN1 and CEBPZ). In summary, the Nadia platform represents a promising and flexible technology for future transcriptomic studies, and other related applications, at cell resolution.
Low expression of the PPARγ-regulated gene thioredoxin-interacting protein accompanies human melanoma progression and promotes experimental lung metastases
Authors: Meylan Patrick , Pich Christine , Winkler Carine , Ginster Stefanie , Mury Lionel , Sgandurra Marie , Dreos René , Frederick Dennie Tompers , Hammond Marc , Boland Genevieve Marie , Michalik Liliane
Published: April 2021

The thioredoxin system plays key roles in regulating cancer cell malignancy. Here we identify the Thioredoxin-interacting protein (TXNIP) as a gene, which expression is regulated by PPARγ in melanoma cells. We show that high TXNIP expression levels associate with benign melanocytic lesions, with tumor regression in patients on MAP kinase targeted therapy, with decreased proliferation in patients’ melanoma biopsies, and with cell cycle arrest in human melanoma cell lines. In contrast, reduced TXNIP expression associates with advanced melanoma and with disease progression in patients. TXNIP depletion in human melanoma cells altered the expression of integrin beta-3 and the localization of the integrin alpha-v/beta-3 dimer at their surface. Moreover, TXNIP depletion affected human melanoma cell motility and improved their capacity to colonize mouse lungs in an in vivo assay. This study establishes TXNIP as a PPARγ-regulated gene in melanoma cells, thereby suggesting a link between these two proteins both involved in the regulation of cancer and of energy metabolism. It also reveals that the decrease in TXNIP expression, which is observed in advanced patient tumors, likely favors lung metastatic seeding of malignant cells.
Root NRT, NiR, AMT, GS, GOGAT and GDH expression levels reveal NO and ABA mediated drought tolerance in Brassica juncea L.
Authors: Sahay Seema , Robledo-Arratia Luis , Glowacka Katarzyna , Gupta Meetu
Published: April 2021

Little is known about the interactive effects of exogenous nitric oxide (NO) and abscisic acid (ABA) on nitrogen (N) metabolism and related changes at molecular and biochemical levels under drought stress. The present study highlights the independent and combined effect of NO and ABA (grouped as “nitrate agonists”) on expression profiles of representative key genes known to be involved in N-uptake and assimilation, together with proline metabolism, N–NO metabolism enzyme’s activity and nutrient content in polyethylene glycol (PEG) treated roots of Indian mustard (B. juncea cv.Varuna). Here we report that PEG mediated drought stress negatively inhibited growth performance, as manifested by reduced biomass (fresh and dry weight) production. Total N content and other nitrogenous compounds (NO3−, NO2−) were decreased; however, NH4+, NH4+/ NO3−ratio and total free amino acids content were increased. These results were positively correlated with the PEG induced changes in expression of genes and enzymes involved in N-uptake and assimilation. Also, PEG supply lowered the content of macro- and micro-nutrients but proline level and the activity of ∆1-pyrroline-5-carboxylate synthetase increased indicating increased oxidative stress. However, all these responses were reversed upon the exogenous application of nitrate agonists (PEG + NO, PEG + NO + ABA, and PEG + ABA) where NO containing nitrate agonist treatment i.e. PEG + NO was significantly more effective than PEG + ABA in alleviating drought stress. Further, increases in activities of L-arginine dependent NOS-like enzyme and S-nitrosoglutathione reductase were observed under nitrate agonist treatments. This indicates that the balanced endogenous change in NO and ABA levels together during synthesis and degradation of NO mitigated the oxidative stress in Indian mustard seedlings. Overall, our results reveal that NO independently or together with ABA may contribute to improved crop growth and productivity under drought stress.
Association of preoperative seizures with tumor metabolites quantified by magnetic resonance spectroscopy in gliomas
Authors: Nakae Shunsuke , Kumon Masanobu , Murayama Kazuhiro , Ohba Shigeo , Sasaki Hikaru , Inamasu Joji , Kuwahara Kiyonori , Yamada Seiji , Abe Masato , Hirose Yuichi
Published: April 2021

Seizures are common in patients with gliomas; however, the mechanisms of epileptogenesis in gliomas have not been fully understood. This study hypothesized that analyzing quantified metabolites using magnetic resonance spectroscopy (MRS) might provide novel insights to better understand the epileptogenesis in gliomas, and specific metabolites might be indicators of preoperative seizures in gliomas. We retrospectively investigated patient information (gender, age at diagnosis of tumor, their survival time) and tumor information (location, histology, genetic features, and metabolites according to MRS) in patients with gliomas. The data were correlated with the incidence of seizure and analyzed statistically. Of 146 adult supratentorial gliomas, isocitrate dehydrogenase (IDH) mutant tumors significantly indicated higher incidence of preoperative seizures than IDH wild-type gliomas. However, MRS study indicated that glutamate concentration in IDH wild-type gliomas was higher than that in IDH mutant gliomas. Glutamate was not associated with high frequency of preoperative seizures in patients with gliomas. Instead, increased total N-acetyl-l-aspartate (tNAA) was significantly associated with them. Moreover, multivariable analysis indicated that increased level of tNAA was an independent predictor of preoperative seizures. According to MRS analysis, tNAA, rather than glutamate, might be a useful to detect preoperative seizures in patient with supratentorial gliomas.
Novel Prosopis juliflora leaf ethanolic extract as natural antimicrobial agent against food spoiling microorganisms
Authors: Saleh Iman , Abu-Dieyeh Mohammed H.
Published: April 2021

Fresh produces spoilage is a worldwide concern that accompany the global increase in food demand. Adverse human health and environmental effects of commercial spoilage control agents are major public concern. In this study,Prosopis julifloraleaves and fruit extracts had their antimicrobial activities evaluated against the growth of selected bacteria and yeast, and against mycelial growth and conidial germination of selected mycotoxins-producing fungi.P. juliflorawater-soluble leaf ethanolic (PJ-WS-LE) extract with its novel extraction method showed the strongest antibacterial activity. Antimicrobial tests showed total inhibition ofBotrytis cinerea,Alternaria alternata,Bacillus subtilis,Staphylococcus aureusandCandida albicanswith MICs ranging between 0.125 and 1 mg/ml. Percent inhibition of mycelial growth (PIMG) of the extract was also determined against seven other fungal strains with highest value againstGeotrichum candidum(66.2%). Even the least affected fungal strain showed alterations in their hyphae and spores exposed to PJ-WS-LE extract when observed using scanning electron microscope (SEM), alterations include exfoliated flakes, pores, vacuolation and applanation. Small-scale fruit bioassays controlled experiment showed high efficacy of the extract in protecting inoculated cherry tomato samples fromB. cinereaandA. alternatainfections. In conclusion, PJ-WS-LE extract is a feasible, natural antifungal agent that can replace common anti-spoiling chemicals.
The ratio and difference of urine protein-to-creatinine ratio and albumin-to-creatinine ratio facilitate risk prediction of all-cause mortality
Authors: Chang David Ray , Yeh Hung-Chieh , Ting I-Wen , Lin Chen-Yuan , Huang Han-Chun , Chiang Hsiu-Yin , Chang Shih-Ni , Tsai Hsiu-Chen , Lo Yen-Chun , Hsiao Chiung-Tzu , Chu Pei-Lun , Kuo Chin-Chi
Published: April 2021

The role of the difference and ratio of albuminuria (urine albumin-to-creatinine ratio, uACR) and proteinuria (urine protein-to-creatinine ratio, uPCR) has not been systematically evaluated with all-cause mortality. We retrospectively analyzed 2904 patients with concurrently measured uACR and uPCR from the same urine specimen in a tertiary hospital in Taiwan. The urinary albumin-to-protein ratio (uAPR) was derived by dividing uACR by uPCR, whereas urinary non-albumin protein (uNAP) was calculated by subtracting uACR from uPCR. Conventional severity categories of uACR and uPCR were also used to establish a concordance matrix and develop a corresponding risk matrix. The median age at enrollment was 58.6 years (interquartile range 45.4–70.8). During the 12,391 person-years of follow-up, 657 deaths occurred. For each doubling increase in uPCR, uACR, and uNAP, the adjusted hazard ratios (aHRs) of all-cause mortality were 1.29 (95% confidence interval [CI] 1.24–1.35), 1.12 (1.09–1.16), and 1.41 (1.34–1.49), respectively. For each 10% increase in uAPR, it was 1.02 (95% CI 0.98–1.06). The linear dose–response association with all-cause mortality was only observed with uPCR and uNAP. The 3 × 3 risk matrices revealed that patients with severe proteinuria and normal albuminuria had the highest risk of all-cause mortality (aHR 5.25, 95% CI 1.88, 14.63). uNAP significantly improved the discriminative performance compared to that of uPCR (c statistics: 0.834 vs. 0.828, p-value = 0.032). Our study findings advocate for simultaneous measurements of uPCR and uACR in daily practice to derive uAPR and uNAP, which can provide a better mortality prognostic assessment.
Anticipating the impact of COVID19 and comorbidities on the South African healthcare system by agent-based simulations
Authors: Schlüter Jan Christian , Sörensen Leif , Bossert Andreas , Kersting Moritz , Staab Wieland , Wacker Benjamin
Published: April 2021

Tuberculosis (TB) is the 10th leading cause of death worldwide, and since 2007 it has been the main cause of death from a single infectious agent, ranking above HIV/AIDS. The current COVID-19 is a pandemic which caused many deaths around the world. The danger is not only a coinfection as observed for TB and HIV for a long time, but that both TB and SARS-CoV-2 affect the respiratory organs and thus potentiate their effect or accelerate the critical course. A key public health priority during the emergence of a novel pathogen is the estimation of the clinical need to assure adequate medical treatment. This requires a correct adjustment to the critical case detection rate and the prediction of possible scenarios based on known patterns. The African continent faces constraining preconditions in regard to healthcare capacities and social welfare which may hinder required countermeasures. However, given the high TB prevalence rates, COVID-19 may show a particular severe course in respective African countries, e.g. South Africa. Using WHO’s TB and public infrastructure data, we conservatively estimate that the symptomatic critical case rate, which affects the healthcare system, is between 8 and 12% due to the interaction of COVID-19 and TB, for a TB population of 0.52% in South Africa. This TB prevalence leads to a significant increase in the peak load of critical cases of COVID-19 patients and potentially exceeds current healthcare capacities.
Optimized imaging methods for species-level identification of food-contaminating beetles
Authors: Bera Tanmay , Wu Leihong , Ding Hongjian , Semey Howard , Barnes Amy , Liu Zhichao , Vyas Himansu , Tong Weida , Xu Joshua
Published: April 2021

Identifying the exact species of pantry beetle responsible for food contamination, is imperative in assessing the risks associated with contamination scenarios. Each beetle species is known to have unique patterns on their hardened forewings (known as elytra) through which they can be identified. Currently, this is done through manual microanalysis of the insect or their fragments in contaminated food samples. We envision that the use of automated pattern analysis would expedite and scale up the identification process. However, such automation would require images to be captured in a consistent manner, thereby enabling the creation of large repositories of high-quality images. Presently, there is no standard imaging technique for capturing images of beetle elytra, which consequently means, there is no standard method of beetle species identification through elytral pattern analysis. This deficiency inspired us to optimize and standardize imaging methods, especially for food-contaminating beetles. For this endeavor, we chose multiple species of beetles belonging to different families or genera that have near-identical elytral patterns, and thus are difficult to identify correctly at the species level. Our optimized imaging method provides enhanced images such that the elytral patterns between individual species could easily be distinguished from each other, through visual observation. We believe such standardization is critical in developing automated species identification of pantry beetles and/or other insects. This eventually may lead to improved taxonomical classification, allowing for better management of food contamination and ecological conservation.
Cardiometabolic risks of SARS-CoV-2 hospitalization using Mendelian Randomization
Authors: Lorincz-Comi Noah , Zhu Xiaofeng
Published: April 2021

Many cardiometabolic conditions have demonstrated associative evidence with COVID-19 hospitalization risk. However, the observational designs of the studies in which these associations are observed preclude causal inferences of hospitalization risk. Mendelian Randomization (MR) is an alternative risk estimation method more robust to these limitations that allows for causal inferences. We applied four MR methods (MRMix, IMRP, IVW, MREgger) to publicly available GWAS summary statistics from European (COVID-19 GWAS n = 2956) and multi-ethnic populations (COVID-19 GWAS n = 10,908) to better understand extant causal associations between Type II Diabetes (GWAS n = 659,316), BMI (n = 681,275), diastolic and systolic blood pressure, and pulse pressure (n = 757,601 for each) and COVID-19 hospitalization risk across populations. Although no significant causal effect evidence was observed, our data suggested a trend of increasing hospitalization risk for Type II diabetes (IMRP OR, 95% CI 1.67, 0.96–2.92) and pulse pressure (OR, 95% CI 1.27, 0.97–1.66) in the multi-ethnic sample. Type II diabetes and Pulse pressure demonstrates a potential causal association with COVID-19 hospitalization risk, the proper treatment of which may work to reduce the risk of a severe COVID-19 illness requiring hospitalization. However, GWAS of COVID-19 with large sample size is warranted to confirm the causality.
Novel resistance strategies to soybean cyst nematode (SCN) in wild soybean
Authors: Kofsky Janice , Zhang Hengyou , Song Bao-Hua
Published: April 2021

Soybean cyst nematode (SCN, Heterodera glycineIchinohe) is the most damaging soybean pest worldwide and management of SCN remains challenging. The current SCN resistant soybean cultivars, mainly developed from the cultivated soybean gene pool, are losing resistance due to SCN race shifts. The domestication process and modern breeding practices of soybean cultivars often involve strong selection for desired agronomic traits, and thus, decreased genetic variation in modern cultivars, which consequently resulted in limited sources of SCN resistance. Wild soybean (Glycine soja) is the wild ancestor of cultivated soybean (Glycine max) and it’s gene pool is indisputably more diverse thanG. max. Our aim is to identify novel resistant genetic resources from wild soybean for the development of new SCN resistant cultivars. In this study, resistance response to HG type 2.5.7 (race 5) of SCN was investigated in a newly identified SCN resistant ecotype, NRS100. To understand the resistance mechanism in this ecotype, we compared RNA seq-based transcriptomes of NRS100 with two SCN-susceptible accessions ofG. sojaandG. max, as well as an extensively studied SCN resistant cultivar, Peking, under both control and nematode J2-treated conditions. The proposed mechanisms of resistance in NRS100 includes the suppression of the jasmonic acid (JA) signaling pathway in order to allow for salicylic acid (SA) signaling-activated resistance response and polyamine synthesis to promote structural integrity of root cell walls. Our study identifies a set of novel candidate genes and associated pathways involved in SCN resistance and the finding provides insight into the mechanism of SCN resistance in wild soybean, advancing the understanding of resistance and the use of wild soybean-sourced resistance for soybean improvement.
Topological clustering of regulatory genes confers pathogenic tolerance to cassava brown streak virus (CBSV) in cassava
Authors: Jaemthaworn Thanakorn , Kalapanulak Saowalak , Saithong Treenut
Published: April 2021

Robustness, a naïve property of biological systems, enables organisms to maintain functions during perturbation and is crucial for improving the resilience of crops to prevailing stress conditions and diseases, guaranteeing food security. Most studies of robustness in crops have focused on genetic superiority based upon individual genes, overlooking the collaborative actions of multiple responsive genes and the regulatory network topology. This research aims to uncover patterns of gene cooperation leading to organismal robustness by studying the topology of gene co-expression networks (GCNs) of both CBSV virus resistant and susceptible cassava cultivars. The resulting GCNs show higher topological clustering of cooperative genes in the resistant cultivar, suggesting that the network architecture is central to attaining robustness. Despite a reduction in the number of hub genes in the resistant cultivar following the perturbation, essential biological functions contained in the network were maintained through neighboring genes that withstood the shock. The susceptible cultivar seemingly coped by inducing more gene actions in the network but could not maintain the functions required for plant growth. These findings underscore the importance of regulatory network architecture in ensuring phenotypic robustness and deepen our understanding of transcriptional regulation.
An updated analysis of the epidemiologic trends of neuroendocrine tumors in Taiwan
Authors: Chang Jeffrey S. , Chen Li-Tzong , Shan Yan-Shen , Chu Pei-Yi , Tsai Chia-Rong , Tsai Hui-Jen
Published: April 2021

The incidence of neuroendocrine tumors (NETs) has been increasing in recent decades. Previously, we reported the incidence and survival of NETs in Taiwan by analyzing the 1996–2008 data from the Taiwan Cancer Registry. Here we performed an updated analysis on the incidence and survival of NETs in Taiwan from 1996 to 2015. The incidence of NETs was 0.244 per 100,000 in 1996 and increased to 3.162 per 100,000 in 2015. The most common site of NETs was rectum (29.65%), followed by lung/bronchus (17.22%), and pancreas (10.71%). The 5- and 10-year overall survival rates of all NETs were 54.6% and 45.3%, respectively. Female and younger NETs patients had a better survival. The survival of all NETs diagnosed between 2010 and 2015 was better than those diagnosed between 2004 and 2009. Among the common sites of NETs, an improved survival of pancreatic NETs diagnosed between 2010 and 2015 compared to those diagnosed between 2004 and 2009 was observed. Overall, the incidence of NETs in Taiwan has continued to increase. The survival of pancreatic NET has shown a recent improvement. The development of novel therapeutic agents has the potential to improve the prognosis of NETs of other sites in the near future.
Multisubstituted pyrimidines effectively inhibit bacterial growth and biofilm formation of Staphylococcus aureus
Authors: Provenzani Riccardo , San-Martin-Galindo Paola , Hassan Ghada , Legehar Ashenafi , Kallio Aleksi , Xhaard Henri , Fallarero Adyary , Yli-Kauhaluoma Jari
Published: April 2021

Biofilms are multicellular communities of microorganisms that generally attach to surfaces in a self-produced matrix. Unlike planktonic cells, biofilms can withstand conventional antibiotics, causing significant challenges in the healthcare system. Currently, new chemical entities are urgently needed to develop novel anti-biofilm agents. In this study, we designed and synthesized a set of 2,4,5,6-tetrasubstituted pyrimidines and assessed their antibacterial activity against planktonic cells and biofilms formed by Staphylococcus aureus. Compounds 9e, 10d, and 10e displayed potent activity for inhibiting the onset of biofilm formation as well as for killing pre-formed biofilms of S. aureus ATCC 25923 and Newman strains, with half-maximal inhibitory concentration (IC50) values ranging from 11.6 to 62.0 µM. These pyrimidines, at 100 µM, not only decreased the number of viable bacteria within the pre-formed biofilm by 2–3 log10 but also reduced the amount of total biomass by 30–50%. Furthermore, these compounds were effective against planktonic cells with minimum inhibitory concentration (MIC) values lower than 60 µM for both staphylococcal strains. Compound 10d inhibited the growth of S. aureus ATCC 25923 in a concentration-dependent manner and displayed a bactericidal anti-staphylococcal activity. Taken together, our study highlights the value of multisubstituted pyrimidines to develop novel anti-biofilm agents.
Coeval primary and diagenetic carbonates in lacustrine sediments challenge palaeoclimate interpretations
Authors: McCormack Jeremy , Kwiecien Ola
Published: April 2021

Lakes are sensitive to climate change and their sediments play a pivotal role as environmental recorders. The oxygen and carbon isotope composition (δ18O and δ13C) of carbonates from alkaline lakes is featured in numerous studies attempting a quantitative reconstruction of rainfall, temperature and precipitation-evaporation changes. An often-overlooked challenge consists in the mineralogically mixed nature of carbonates themselves. We document a large variability of carbonate components and their respective distinct δ18O and δ13C values from sediments of Lake Van (Turkey) covering the last 150 kyr. The carbonate inventory consists of primary (1) inorganic calcite and aragonite precipitating in the surface-water, (2) biogenic calcite ostracod valves; and post-depositional phases: (3) dolomite forming in the sediment, and previously overlooked, (4) aragonite encrustations formed rapidly around decaying organic matter. We find a systematic relation between the lithology and the dominant deep-water carbonate phase formed recurrently under specific hydrological conditions. The presence of the different carbonates is never mutually exclusive, and the isotopic composition of each phase forms a distinctive cluster characteristic for the depth and timing of their formation. Our findings stretch the envelope of mechanisms forming lacustrine carbonates and highlight the urge to identify and separate carbonate components prior to geochemical analyses.
Constitutive depletion of Slc34a2/NaPi-IIb in rats causes perinatal mortality
Authors: Pastor-Arroyo Eva Maria , Rodriguez Josep M. Monné , Pellegrini Giovanni , Bettoni Carla , Levi Moshe , Hernando Nati , Wagner Carsten A.
Published: April 2021

Absorption of dietary phosphate (Pi) across intestinal epithelia is a regulated process mediated by transcellular and paracellular pathways. Although hyperphosphatemia is a risk factor for the development of cardiovascular disease, the amount of ingested Pi in a typical Western diet is above physiological needs. While blocking intestinal absorption has been suggested as a therapeutic approach to prevent hyperphosphatemia, a complete picture regarding the identity and regulation of the mechanism(s) responsible for intestinal absorption of Pi is missing. The Na+/Pi cotransporter NaPi-IIb is a secondary active transporter encoded by the Slc34a2 gene. This transporter has a wide tissue distribution and within the intestinal tract is located at the apical membrane of epithelial cells. Based on mouse models deficient in NaPi-IIb, this cotransporter is assumed to mediate the bulk of active intestinal absorption of Pi. However, whether or not this is also applicable to humans is unknown, since human patients with inactivating mutations in SLC34A2 have not been reported to suffer from Pi depletion. Thus, mice may not be the most appropriate experimental model for the translation of intestinal Pi handling to humans. Here, we describe the generation of a rat model with Crispr/Cas-driven constitutive depletion of Slc34a2. Slc34a2 heterozygous rats were indistinguishable from wild type animals under standard dietary conditions as well as upon 3 days feeding on low Pi. However, unlike in humans, homozygosity resulted in perinatal lethality.
Fusion and fission events regulate endosome maturation and viral escape
Authors: Castro Mario , Lythe Grant , Smit Jolanda , Molina-París Carmen
Published: April 2021

Endosomes are intracellular vesicles that mediate the communication of the cell with its extracellular environment. They are an essential part of the cell’s machinery regulating intracellular trafficking via the endocytic pathway. Many viruses, which in order to replicate require a host cell, attach themselves to the cellular membrane; an event which usually initiates uptake of a viral particle through the endocytic pathway. In this way viruses hijack endosomes for their journey towards intracellular sites of replication and avoid degradation without host detection by escaping the endosomal compartment. Recent experimental techniques have defined the role of endosomal maturation in the ability of enveloped viruses to release their genetic material into the cytoplasm. Endosome maturation depends on a family of small hydrolase enzymes (or GTPases) called Rab proteins, arranged on the cytoplasmic surface of its membrane. Here, we model endosomes as intracellular compartments described by two variables (its levels of active Rab5 and Rab7 proteins) and which can undergo coagulation (or fusion) and fragmentation (or fission). The key element in our approach is the “per-cell endosomal distribution” and its dynamical (Boltzmann) equation. The Boltzmann equation allows us to derive the dynamics of the total number of endosomes in a cell, as well as the mean and the standard deviation of its active Rab5 and Rab7 levels. We compare our mathematical results with experiments of Dengue viral escape from endosomes. The relationship between endosomal active Rab levels and pH suggests a mechanism that can account for the observed variability in viral escape times, which in turn regulate the viability of a viral intracellular infection.
The association of enteric neuropathy with gut phenotypes in acute and progressive models of Parkinson’s disease
Authors: McQuade Rachel M. , Singleton Lewis M. , Wu Hongyi , Lee Sophie , Constable Remy , Di Natale Madeleine , Ringuet Mitchell T. , Berger Joel P. , Kauhausen Jessica , Parish Clare L. , Finkelstein David I. , Furness John B. , Diwakarla Shanti
Published: April 2021

Parkinson’s disease (PD) is associated with neuronal damage in the brain and gut. This work compares changes in the enteric nervous system (ENS) of commonly used mouse models of PD that exhibit central neuropathy and a gut phenotype. Enteric neuropathy was assessed in five mouse models: peripheral injection of MPTP; intracerebral injection of 6-OHDA; oral rotenone; and mice transgenic for A53T variant human α-synuclein with and without rotenone. Changes in the ENS of the colon were quantified using pan-neuronal marker, Hu, and neuronal nitric oxide synthase (nNOS) and were correlated with GI function. MPTP had no effect on the number of Hu+ neurons but was associated with an increase in Hu+ nuclear translocation (P < 0.04). 6-OHDA lesioned mice had significantly fewer Hu+ neurons/ganglion (P < 0.02) and a reduced proportion of nNOS+ neurons in colon (P < 0.001). A53T mice had significantly fewer Hu+ neurons/area (P < 0.001) and exhibited larger soma size (P < 0.03). Treatment with rotenone reduced the number of Hu+ cells/mm2in WT mice (P < 0.006) and increased the proportion of Hu+ translocated cells in both WT (P < 0.02) and A53T mice (P < 0.04). All PD models exhibited a degree of enteric neuropathy, the extent and type of damage to the ENS, however, was dependent on the model.
Accessible chromatin reveals regulatory mechanisms underlying cell fate decisions during early embryogenesis
Authors: Fan Tongqiang , Huang Youjun
Published: April 2021

This study was conducted to investigate epigenetic landscape across multiple species and identify transcription factors (TFs) and their roles in controlling cell fate decision events during early embryogenesis. We made a comprehensively joint-research of chromatin accessibility of five species during embryogenesis by integration of ATAC-seq and RNA-seq datasets. Regulatory roles of candidate early embryonic TFs were investigated. Widespread accessible chromatin in early embryos overlapped with putative cis-regulatory sequences. Sets of cell-fate-determining TFs were identified. YOX1, a key cell cycle regulator, were found to homologous to clusters of TFs that are involved in neuron and epidermal cell-fate determination. Our research provides an intriguing insight into evolution of cell-fate decision during early embryogenesis among organisms.
Higher order mode supercontinuum generation in tantalum pentoxide (Ta2O5) channel waveguide
Authors: Fan Ranran , Lin Yuan-Yao , Chang Lin , Boes Andreas , Bowers John , Liu Jia-Wei , Lin Chao-Hong , Wang Te-Keng , Qiao Junpeng , Kuo Hao-Chung , Lin Gong-Ru , Shih Min-Hsiung , Hung Yung-Jr , Chiu Yi-Jen , Lee Chao-Kuei
Published: April 2021

We fabricated tantalum pentoxide (Ta2O5) channel waveguides and used them to experimentally demonstrate higher-order mode supercontinuum (SC) generation. The Ta2O5 waveguide has a high nonlinear refractive index which was in an order magnitude of 10–14 cm2/W and was designed to be anomalously dispersive at the pumping wavelength. To the best of our knowledge, this is the first time a higher-order mode femtosecond pump based broadband SC has been measured from a nonlinear waveguide using the phase-matching method. This enabled us to demonstrate a SC spectrum spanning from 842 to 1462 nm (at − 30 dB), which corresponds to 0.83 octaves, when using the TM10 waveguide mode. When using the TE10 mode, the SC bandwidth is slightly reduced for the same excitation peak power. In addition, we theoretically estimated and discussed the possibility of using the broadband higher-order modes emitted from the Ta2O5 waveguide for trapping nanoparticles. Hence, we believe that demonstrated Ta2O5 waveguide are a promising broadband light source for optical applications such as frequency metrology, Raman spectroscopy, molecular spectroscopy and optical coherence tomography.
Efficacy of broflanilide (VECTRON T500), a new meta-diamide insecticide, for indoor residual spraying against pyrethroid-resistant malaria vectors
Authors: Ngufor Corine , Govoetchan Renaud , Fongnikin Augustin , Vigninou Estelle , Syme Thomas , Akogbeto Martin , Rowland Mark
Published: April 2021

The rotational use of insecticides with different modes of action for indoor residual spraying (IRS) is recommended for improving malaria vector control and managing insecticide resistance. Insecticides with new chemistries are urgently needed. Broflanilide is a newly discovered insecticide under consideration. We investigated the efficacy of a wettable powder (WP) formulation of broflanilide (VECTRON T500) for IRS on mud and cement wall substrates in laboratory and experimental hut studies against pyrethroid-resistant malaria vectors in Benin, in comparison with pirimiphos-methyl CS (Actellic 300CS). There was no evidence of cross-resistance to pyrethroids and broflanilide in CDC bottle bioassays. In laboratory cone bioassays, broflanilide WP-treated substrates killed > 80% of susceptible and pyrethroid-resistant An. gambiae sl for 6–14 months. At application rates of 100 mg/m2 and 150 mg/m2, mortality of wild pyrethroid-resistant An. gambiae sl entering experimental huts in Covè, Benin treated with VECTRON T500 was similar to pirimiphos-methyl CS (57–66% vs. 56%, P > 0.05). Throughout the 6-month hut trial, monthly wall cone bioassay mortality on VECTRON T500 treated hut walls remained > 80%. IRS with broflanilide shows potential to significantly improve the control of malaria transmitted by pyrethroid-resistant mosquito vectors and could thus be a crucial addition to the current portfolio of IRS insecticides.
Trees outside forests are an underestimated resource in a country with low forest cover
Authors: Thomas Nathan , Baltezar Priscilla , Lagomasino David , Stovall Atticus , Iqbal Zaheer , Fatoyinbo Lola
Published: April 2021

Trees outside forests (TOF) are an underrepresented resource in forest poor nations. As a result of their frequent omission from national forest resource assessments and a lack of readily available very-high-resolution remotely sensed imagery, TOF status and characterization has until now, been unknown. Here, we assess the capacity of openly available 10 m ESA Sentinel constellation satellite imagery for mapping TOF extent at the national level in Bangladesh. In addition, we estimate canopy height for TOF using a TanDEM-X DEM. We map 2,233,578 ha of TOF in Bangladesh with a mean canopy height of 7.3 m. We map 31 and 53% more TOF than existing estimates of TOF and forest, respectively. We find TOF in Bangladesh is nationally fragmented as a consequence of agricultural activity, yet is capable of maintaining connectedness between remaining stands. Now, TOF accounting is feasible at the national scale using readily available datasets, enabling the mainstream inclusion of TOF in national forest resource assessments for other countries.
Serum sodium variation is a major determinant of peridialytic blood pressure trends in haemodialysis outpatients
Authors: Jaques David A. , Davenport Andrew
Published: April 2021

Intradialytic hypotension (IDH) and peridialytic blood pressure (BP) trends are associated with morbidity and mortality in haemodialysis (HD) patients. We aimed to characterise the respective influence of volume status and small solutes variation on peridialytic systolic BP (SBP) trends during HD. We retrospectively analysed the relative peridialytic SBP decrease in 647 prevalent outpatients attending for their mid-week session with corresponding pre- and post-HD bioelectrical impedance analysis. Mean SBP decreased by 10.5 ± 23.6 mmHg. Factors positively associated with the relative decrease in SBP were: serum sodium (Na) decrease, body mass index, serum albumin, dialysis vintage, ultrafiltration rate and urea Kt/V (p < 0.05 for all). Antihypertensive medications and higher dialysate calcium were negatively associated with the relative decrease in SBP (p < 0.05 for both). Age had a quadratic relationship with SBP trends (p < 0.05). Pre-HD volume status measured by extracellular to total body water ratio was not associated with SBP variation (p = 0.216). Peridialytic SBP trends represent a continuum with serum Na variation being a major determinant while volume status has negligible influence. Middle-aged and overweight patients are particularly prone to SBP decline. Tailoring Na and calcium dialysate concentrations could influence haemodynamic stability during HD and improve patient experience and outcomes.
Coexistence of inhibitory and activating killer-cell immunoglobulin-like receptors to the same cognate HLA-C2 and Bw4 ligands confer breast cancer risk
Authors: Ashouri Elham , Rajalingam Karan , Barani Shaghik , Farjadian Shirin , Ghaderi Abbas , Rajalingam Raja
Published: April 2021

Human leukocyte antigen (HLA) class I-specific killer-cell immunoglobulin-like receptors (KIR) regulate natural killer (NK) cell function in eliminating malignancy. Breast cancer (BC) patients exhibit reduced NK-cytotoxicity in peripheral blood. To test the hypothesis that certain KIR-HLA combinations impairing NK-cytotoxicity predispose to BC risk, we analyzed KIR and HLA polymorphisms in 162 women with BC and 278 controls. KIR-Bx genotypes increased significantly in BC than controls (83.3% vs. 71.9%, OR 1.95), and the increase was more pronounced in advanced-cancer (OR 5.3). No difference was observed with inhibitory KIR (iKIR) and HLA-ligand combinations. The activating KIR (aKIR) and HLA-ligand combinations, 2DS1 + C2 (OR 2.98) and 3DS1 + Bw4 (OR 2.6), were significantly increased in advanced-BC. All patients with advanced-cancer carrying 2DS1 + C2 or 3DS1 + Bw4 also have their iKIR counterparts 2DL1 and 3DL1, respectively. Contrarily, the 2DL1 + C2 and 3DL1 + Bw4 pairs without their aKIR counterparts are significantly higher in controls. These data suggest that NK cells expressing iKIR to the cognate HLA-ligands in the absence of putative aKIR counterpart are instrumental in antitumor response. These data provide a new framework for improving the utility of genetic risk scores for individualized surveillance.