bluuebunny/crossref_metadata_2025 huggingface dataset:
Opportunities, Challenges and Countermeasures of China's Rural Internet Finance Development under the New Situation
Authors: Li Jiafeng , Wang Binghua , Qi Yongkang , Zhang Xinyu
Published: November 2022

Rural internet finance is a new business mode combining traditional rural finance with internet technology, which has the functions of accelerating the innovation of rural financial products and inclusive finance, and has important practical significance for promoting agricultural modernization and solving the problems of agriculture, rural areas and farmers. On the basis of expounding the present situation of China's rural Internet finance development, this paper analyzes the opportunities and challenges faced by China's rural Internet finance development, and puts forward some countermeasures to promote the healthy development of rural Internet finance from five aspects: strengthening the supervision of rural Internet finance, perfecting the rural credit system, establishing and perfecting the risk control system of rural Internet finance, increasing the publicity of rural Internet finance, and cultivating rural Internet finance talents.
Design and sizing of solar PV system for the laboratory building at the Technical College of Engineering/Mosul and simulation with the PV*SOL program
Authors: Hamoodi Ali Nadhim , Abdulla Fawaz Sultan , Sulaiman Sarmad Mezher
Published: November 2022

Solar energy is the most important source of renewable energies that turn light or radiation into electrical power. In Iraq, solar stations are now being installed in homes, farms and small markets. In this paper, the design and sizing of the solar PV system for laboratories building in Technical college of Engineering/Mosul to cover its electrical power requirements then simulations this work with the PV*SOL program (3D) selection was used. All solar PV system componetes were determined and similar appeared to the mathmatical calculations.
Risk factors for central venous catheter-related bloodstream infection in oncology patients: an integrative review
Authors: Bastos Elaine Cristina Bezerra , Carvalho Francisco Samuel , Chaves Filipe Nobre , Costa Fábio Wildson Gurgel , Costa Antonio Neudimar Bastos , Mesquita Camila Melo , Carvalho Maria Raquel Raquel R
Published: November 2022

The aim of this integrative review was to identify scientific studies on risk factors for bloodstream infections associated with central venous catheters (CVC) in cancer patients. The research question was formulated according to the PICO framework. An electronic search was conducted on the SciELO digital library, the Virtual Health Library, and the MEDLINE/PubMed databases using the descriptors “cancer”, “infection”, “central venous catheters”, and “risk factors”. A total of 356 publications were identified (356 in PubMed, 00 in the VHL, and 00 in SciELO). Based on the PRISMA guidelines, 32 articles were included in this review. Recent study dates from 2021. The handling of the central catheters by professionals and the administration of parenteral nutrition were the main risk factors for CVC infections. The implementation of basic healthcare and hygiene measures is essential for the prevention and reduction of bloodstream infections associated with central catheters.
Reducing Heat Conduction Enhances the Photothermal Efficiency of Upcycled Adsorbents
Authors: Li Meng , Liu Bowen , Liu Zhijian , Xiao Yumeng , Guo Hongmin , An Zehao , Wang Lidong , James Tony D.
Published: November 2022

Solar steam generation is an efficient way to address global freshwater shortages. However, water evaporation suffers from either inefficient heat conduction or relies on expensive materials and complex equipment. Herein, a porous hydrogel (AC‐H) with molecular meshes, micron channels, and internal gaps is fabricated and used for metal ion adsorption. AC‐H exhibits excellent uptake ability and can attain the levels required by industrial water safety standards. Subsequently, the exhausted AC‐H hydrogel is vulcanized in situ (AC‐MS) and upcycled for solar steam generation resulting in ≈1.41 kg m−2 h−1 evaporation rate under one sun irradition, which reduces costs and converts the waste into a resource. Furthermore, a heat management strategy is developed where a cold surface of specific area is introduced between the AC‐MSx and bulk water to adsorb the heat loss. When the cold area is increased, the energy in the bulk water can be extracted by the coldsurface. which enhances the water evaporation rate. Significantly, the theoretical simulations are in good agreement with the experimental results. Therefore, this research provides a novel strategy to upcycle exhausted materials for photothermal technologies and reduces the heat conduction during solar‐to‐thermal evaporation.
Retina‐Inspired Organic Photonic Synapses for Selective Detection of SWIR Light
Authors: Wang Song , Chen Hao , Liu Tianhua , Wei Yanan , Yao Guo , Lin Qijie , Han Xiao , Zhang Chunfeng , Huang Hui
Published: November 2022

Photonic synapses with the dual function of optical signal detection and information processing can simulate human visual system. However, photonic synapses with selective detection of short‐wavelength infrared (SWIR) light have never been reported, which can not only broaden the human vision region but also integrate neuromorphic computation and infrared optical communication. Here, organic photonic synapses based on a new donor‐acceptor copolymer P1 are fabricated, which exhibit excellent synaptic characteristics with selective detection for SWIR and extremely low energy consumption (2.85 fJ). The working mechanism is rooted in energy level barriers and unbalanced charge transportation. Moreover, these photonic synapses demonstrate excellent performance in multi‐signal logic editing, letter imaging and memory with noise reduction function. This contribution provides ideas of constructing selective‐response synapses for artificial visual system and neuromorphic computing.
Transformable Plasmonic Helix with Swinging Gold Nanoparticles
Authors: Peil Andreas , Zhan Pengfei , Duan Xiaoyang , Krahne Roman , Garoli Denis , M. Liz‐Marzán Luis , Liu Na
Published: November 2022

Control over multiple optical elements that can be dynamically rearranged to yield substantial three‐dimensional structural transformations is of great importance to realize reconfigurable plasmonic nanoarchitectures with sensitive and distinct optical feedback. In this work, we demonstrate a transformable plasmonic helix system, in which multiple gold nanoparticles (AuNPs) can be directly transported by DNA swingarms to target positions without undergoing consecutive stepwise movements. The swingarms allow for programmable AuNP translocations in large leaps within plasmonic nanoarchitectures, giving rise to tailored circular dichroism spectra. Our work provides an instructive bottom‐up solution to building complex dynamic plasmonic systems, which can exhibit prominent optical responses through cooperative rearrangements of the constituent optical elements with high fidelity and programmability.
Late‐Stage Modification of Drugs via Alkene Formal Insertion into Benzylic C−F Bond
Authors: Wang Jing , Wang Yahui , Liang Yan , Zhou Liejin , Liu Lijuan , Zhang Zuxiao
Published: November 2022

C−F insertion of carbon‐atom units is underdeveloped although it poses significant potential applications in both drug discovery and development. Herein, we report a photocatalytic protocol for late‐stage modification of trifluoromethyl aromatic drugs involving formal insertion of abundant alkene feedstocks into a benzylic C−F bond selectively. This redox‐neutral transformation features mild conditions and extraordinary functional group tolerance. Preliminary studies are consistent with this transformation involving a radical‐polar crossover pathway. Additionally, it offers an alternative strategy for difunctionalization of alkenes via quenching of the carbocation intermediate with nucleophiles other than external fluoride.
Dual‐Color Photoconvertible Fluorescent Probes Based on Directed Photooxidation Induced Conversion for Bioimaging
Authors: Saladin Lazare , Breton Victor , Dal Pra Ophélie , Klymchenko Andrey S. , Danglot Lydia , Didier Pascal , Collot Mayeul
Published: November 2022

We herein present a new concept to produce dual‐color photoconvertible probes based on a mechanism called Directed Photooxidation Induced Conversion (DPIC). As a support of this mechanism, styryl‐coumarins (SCs) bearing Aromatic Singlet Oxygen Reactive Moieties (ASORMs) like furan and pyrrole have been synthesized. SCs are bright fluorophores, which undergo a hypsochromic conversion upon visible light irradiation due to directed photooxidation of the ASORM that leads to the disruption of conjugation. SC‐P, a yellow emitting probe bearing a pyrrole moiety, converts to a stable blue emitting coumarin with a 68 nm shift allowing the photoconversion and tracking of lipid droplet in live cells. This new approach might pave the way to a new generation of photoconvertible dyes for advanced bioimaging applications.
Combining genetic engineering and bioprocess concepts for improved phenylpropanoid production
Authors: Virklund Alexander , Jensen Sheila I. , Nielsen Alex T. , Woodley John M.
Published: November 2022

The group of natural aromatic compounds known as phenylpropanoids has diverse applications, but current methods of production which are largely based on synthesis from petrochemicals or extraction from agricultural biomass are unsustainable. Bioprocessing is a promising alternative, but improvements in production titers and rates are required to make this method profitable. Here the recent advances in genetic engineering and bioprocess concepts for the production of phenylpropanoids are presented for the purpose of identifying successful strategies, including adaptive laboratory evolution, enzyme engineering, in‐situ product removal, and biocatalysis. The pros and cons of bacterial and yeast hosts for phenylpropanoid production are discussed, also in the context of different phenylpropanoid targets and bioprocess concepts. Finally, some broad recommendations are made regarding targets for continued improvement and areas requiring specific attention from researchers to further improve production titers and rates.
Systematic review: External carbon source for biological denitrification for wastewater
Authors: Ahmed Sanjrani Manzoor , Rind Saeeda , Rani Keenjhar
Published: November 2022

Nitrogen mitigation is serious environmental issue around the globe. Several methods for wastewater treatment have been introduced, but biological denitrification has been recommended, particularly with addition of the best external carbon source. The key sites of denitrification are wetlands; it can be carried out with different methods. To highlight the aforementioned technology, this paper deals to review the literature to evaluate biological denitrification and to demonstrate cost effective external carbon sources. The results of systematic review disclose the denitrification process and addition of different external carbon sources. The online literature exploration was accomplished using the most well‐known databases, that is, science direct and the web of science database, resulting 625 review articles and 3084 research articles, published in peer‐reviewed journals between 2015 and 2021 were identified in first process. After doing an in‐depth literature survey and exclusion criteria, we started to shape the review from selected review and research articles. A number of studies confirmed that both nitrification and denitrification are significant for biological treatment of wastewater. The studies proved that the carbon source is the main contributor and is a booster for the denitrification. Based on the literature reviewed it is concluded that biological denitrification with addition of external carbon source is cost effective and best option in nitrogen mitigation in a changing world. Our study recommends textile waste for recovery of carbon source.
KIAA1429 mediates epithelial mesenchymal transition in sorafenib‐resistant hepatocellular carcinoma through m6A methylation modification
Authors: Kuang Ye , Cheng Yun , Wang Jia , Li Hongyan , Cao Xianghong , Wang Yang
Published: November 2022

Background

Hepatocellular carcinoma (HCC) is a primary liver cancer with high mortality. The long‐term use of sorafenib, a targeted drug for hepatocellular carcinoma, will lead to drug resistance, and patients are prone to cancer metastasis, the molecular mechanism of which is still unclear.

Methods

In our study, we constructed a sorafenib‐resistant hepatocellular carcinoma cell line (HepG2/Sora) and validated the resistance in vivo and in vitro. Transwell assays confirmed the invasion and migration abilities of cells. Colorimetric assays confirmed that the level of m6A methylation modification in cells. RT‐qPCR and Western blot assays confirmed that the expression levels of KIAA1429 in HepG2/Sora cells and tissues. The EMT related proteins were detected by Western blot assay.

Results

Transwell and Western blot assays confirmed that HepG2/Sora cells had higher invasion and migration abilities and showed EMT phenomena. Colorimetric assays confirmed that the level of m6A methylation modification was upregulated in HepG2/Sora cells. Transwell and Western blot assays confirmed that inhibiting m6A methylation in HepG2/Sora cells inhibited their invasion, migration ability and EMT phenomenon. RT‐qPCR and Western blot assays confirmed that the expression levels of KIAA1429 in HepG2/Sora cells and tissues was increased. Silencing KIAA1429 in HepG2/Sora cells inhibited their invasion, migration ability and EMT phenomenon. Finally, we found that the medium supernatant of sorafenib‐resistant HepG2/Sora cells induced vascular production of EA.hy926 cells, and silencing KIAA1429 inhibited this induction effect.

Conclusion

We suggest that KIAA1429 promotes sorafenib‐resistant hepatocellular carcinoma invasion, migration and EMT by mediating m6A methylation. KIAA1429 with its mediated m6A methylation may be a key factor for sorafenib‐resistant patients prone to cancer cell metastasis.
Highly sensitive temperature sensing probe based on two cascaded Fabry–Perot interferometers and Vernier effect
Authors: Zhu Xiping , Jiang Chao , Chen Hailin , Huang Huiling , Sun Simei
Published: November 2022

In this paper, a temperature sensing probe is designed using two cascaded Fabry‐Perot interferometers (FPIs). FPI1 is made by splicing single‐mode optical fiber (SMF)‐no‐core optical fiber‐capillary‐SMF in turn, and then drilling a micro‐hole on the capillary wall of FPI1 with femtosecond laser, and injecting dimethyl silicone oil (DSO) into the capillary through the micro‐hole with immersion method. FPI2 is made by splicing SMF‐capillary‐SMF sequentially. Due to the thermal sensitivity of DSO, the temperature sensitivity of a single FPI1 reaches −0.3674 nm/°C. When the free spectral ranges of FPI1 and FPI2 are close, their cascaded sensor will produce a Vernier effect for improving the sensitivity. The experimental results show that the sensitivity of the sensing probe is as high as 1.8456 nm/°C. In addition, the sensor has a compact structure and can be used flexibly in confined space temperature measurement.
Synergy‐Compensation Effect of Ferroelectric Polarization and Cationic Vacancy Collaboratively Promoting CO2 Photoreduction
Authors: Li Shuguan , Chen Fang , Chu Shengqi , Zhang Zeyu , Huang Jindi , Wang Shengyao , Feng Yibo , Wang Cong , Huang Hongwei
Published: November 2022

Photocatalytic CO2 reduction is severely limited by the rapid recombination of photo‐generated charges and insufficient reactive sites. Creating electric field and defects are effective strategies to inhibit charge recombination and enrich catalytic sites, respectively. Herein, a coupled strategy of ferroelectric poling and cationic vacancy is developed to achieve high‐performance CO2 photoreduction on ferroelectric Bi2MoO6, and their interesting synergy‐compensation relationship is first disclosed. Corona poling increases the remnant polarization of Bi2MoO6 to enhance the intrinsic electric field for promoting charge separation, while it decreases the CO2 adsorption. The introduced Mo vacancy (VMo) facilitates the adsorption and activation of CO2, and surface charge separation by creating local electric field. Unfortunately, VMo largely reduces the remnant polarization intensity. Coupling poling and VMo not only integrate their advantages, resulting in an approximately sevenfold increased surface charge transfer efficiency, but also compensate for their shortcomings, for example, VMo largely alleviates the negative effects of ferroelectric poling on CO2 adsorption. In the absence of co‐catalyst or sacrificial agent, the poled Bi2MoO6 with VMo exhibits a superior CO2‐to‐CO evolution rate of 19.75 µmol g−1 h−1, ≈8.4 times higher than the Bi2MoO6 nanosheets. This work provides new ideas for exploring the role of polarization and defects in photocatalysis.
Anemone bleaching impacts the larval recruitment success of an anemone-associated fish
Authors: Besson Marc , Feeney William E. , Gache Camille , O’Brien Duncan A. , Berthe Cécile , Cowan Zara-Louise , Brooker Rohan M. , Laudet Vincent , Lecchini David
Published: November 2022

In marine environments, mutualisms such as those between corals or sea anemones and their algal symbionts (Symbiodiniaceae) play a key role for supporting surrounding biodiversity. However, as the breakdown of the mutualism between corals and/or anemones and Symbiodiniaceae (i.e. bleaching) become increasingly frequent and severe, the risk of losing the additional species that rely on them may also increase. While the effects of anemone bleaching on the biology and ecology of anemone-associated fishes have been the subject of recent research, relatively little is known about the impacts that anemone bleaching might have on the recruitment of larval fish. Here, we report that climate change-induced anemone bleaching impairs a secondary mutualism between anemones and an anemone-associated fish species, the threespot dascyllus (Dascyllus trimaculatus). Field-based monitoring over a 1-year period showed anemones that bleached experienced decreased recruitment of larval D. trimaculatus compared to those that did not bleach, with abundances of newly settled D. trimaculatus three times lower in bleached versus unbleached anemones. A visual choice experiment showed that this pattern is associated with fish being less attracted to bleached anemones, and a predation experiment demonstrated that fish associated with bleached anemones experienced higher mortality compared to those associated with unbleached anemones. These results suggests that the decreased recruitment of D. trimaculatus observed in bleached anemones may be driven by hampered pre-settlement (habitat selection) and post-settlement (survival to predation) processes for larval D. trimaculatus in bleached hosts. This study highlights the risk of cascading mutualism breakdowns in coral reefs as conditions deteriorate and stresses the importance of protecting these mutualisms for the maintenance of coral reef biodiversity.
Experimental separation of the onset of slip and sharkskin melt instabilities during the extrusion of silica-filled, styrene–butadiene rubber compounds
Authors: Gansen Alex , Řehoř Martin , Sill Clemens , Polińska Patrycja , Westermann Stephan , Dheur Jean , Hale Jack S. , Baller Jörg
Published: November 2022

The flow curves of polymers often reveal the onset of melt instabilities such as sharkskin, stick–slip, or gross melt fracture, in order of increasing shear rates. The focus of this work lies in the application of the Göttfert sharkskin option to the investigation of flow curves of styrene-butadiene rubber (SBR) compounds. The sharkskin option consists of highly sensitive pressure transducers located inside a slit die of a capillary rheometer. This tool allows the detection of in-situ pressure fluctuation characteristics of different melt instabilities. It is shown that the change of slope of the transition region in the flow curves is only linked to slip. Dynamic Mechanical Analysis (DMA) measurements furthermore show that the shear rate at which the change of slope can be observed shows the same temperature dependency as the viscous and elastic properties of the compounds.
Promoting Peace Across Cultures
Authors: Marks Amy K. , Roberg Regina , Luehrs Rose E. , Coll Cynthia García
Published: November 2022

Children’s healthy development is shaped by the myriad person-context interactions that promote—or harm—growth and well-being. Many children and their families who have migrated or immigrated across cultures have experienced war, poverty, natural disasters, or suffered extreme hardship. Forced migration experiences too frequently include exposure to interpersonal violence, trauma, and other severe hardships that can have lasting, deleterious effects on children’s development. Exposure to premigration (e.g., war, gang violence), migration (e.g., parental separations, child trafficking), and postmigration (e.g., racism, discrimination) violence, its mental health effects, and consequent life disruptions are discussed throughout this chapter. The chapter also emphasizes the latest research and thinking about how to support posttraumatic growth and personal/interpersonal healing among immigrant youth. Using evidence-based knowledge from these areas, the chapter suggests next steps for delivering clinical care, as well as designing programs and policies that support migrant-origin child and youth well-being.
Dignity in Care
Authors: Chochinov Harvey Max
Published: November 2022

Dignity in Care: The Human Side of Medicine brings together decades of clinical experience and rigorous research from one of the world’s leading authorities on palliative care and dignity in the healthcare setting. Dr. Harvey Max Chochinov, a seasoned psychiatrist, healthcare leader, and prolific researcher, has distilled his insights about caring for patients and achieving dignity in care for anyone facing the need for healthcare. This book has been written for everyone who deals with patients as part of their work, be they doctors, nurses, social workers, hospital chaplains, occupational therapists, physiotherapists, physician’s assistants, healthcare aides, x-ray technologists, radiation therapists, respiratory therapists, pharmacists, medical receptionists, or healthcare trainees of any kind. Dignity in Care: The Human Side of Medicine explains why patients respond as they do and how the disposition and attitude of healthcare providers indelibly shapes patient experience. The text details the various components of optimal therapeutic communication and offers ways of understanding and delivering dignity in care. This book, already hailed as “a must read for all healthcare providers,” is chock full of wonderful stories and impeccable evidence designed to move healthcare providers—and those they care for—toward the human side of medicine.
PlantServation: time-series phenotyping using machine learning revealed seasonal pigment fluctuation in diploid and polyploidArabidopsis
Authors: Akiyama Reiko , Goto Takao , Tameshige Toshiaki , Sugisaka Jiro , Kuroki Ken , Sun Jianqiang , Akita Junichi , Hatakeyama Masaomi , Kudoh Hiroshi , Kenta Tanaka , Tonouchi Aya , Shimahara Yuki , Sese Jun , Kutsuna Natsumaro , Shimizu-Inatsugi Rie , Shimizu Kentaro K.
Published: November 2022

Long-term field monitoring of leaf pigment content is informative for understanding plant responses to environments distinct from regulated chambers, but is impractical by conventional destructive measurements. We developed PlantServation, a method incorporating robust image-acquisition hardware and deep learning-based software to analyze field images, where the plant shape, color, and background vary over months. We estimated the anthocyanin contents of small individuals of fourArabidopsisspecies using color information and verified the results experimentally. We obtained >4 million plant images over three field seasons to study anthocyanin fluctuations. We found significant effects of past radiation, coldness, and precipitation on the anthocyanin content in the field. The synthetic allopolyploidA. kamchaticarecapitulated the fluctuations of natural polyploids by integrating diploid responses. The data support a long-standing hypothesis stating that allopolyploids can inherit and combine the traits of progenitors. PlantServation pipeline facilitates the study of plant responses to complex environments termed “in natura.”
Fragment-Based Hit Discovery via Unsupervised Learning of Fragment-Protein Complexes
Authors: McCorkindale William , Ahel Ivan , Barr Haim , Correy Galen J. , Fraser James S. , London Nir , Schuller Marion , Shurrush Khriesto , Lee Alpha A.
Published: November 2022

The process of finding molecules that bind to a target protein is a challenging first step in drug discovery. Crystallographic fragment screening is a strategy based on elucidating binding modes of small polar compounds and then building potency by expanding or merging them. Recent advances in high-throughput crystallography enable screening of large fragment libraries, reading out dense ensembles of fragments spanning the binding site. However, fragments typically have low affinity thus the road to potency is often long and fraught with false starts. Here, we take advantage of high-throughput crystallography to reframe fragment-based hit discovery as a denoising problem – identifying significant pharmacophore distributions from a fragment ensemble amid noise due to weak binders – and employ an unsupervised machine learning method to tackle this problem. Our method screens potential molecules by evaluating whether they recapitulate those fragment-derived pharmacophore distributions. We retrospectively validated our approach on an open science campaign against SARS-CoV-2 main protease (Mpro), showing that our method can distinguish active compounds from inactive ones using only structural data of fragment-protein complexes, without any activity data. Further, we prospectively found novel hits for Mpro and the Mac1 domain of SARS-CoV-2 non-structural protein 3. More broadly, our results demonstrate how unsupervised machine learning helps interpret high throughput crystallography data to rapidly discover of potent chemical modulators of protein function.
Anti-integrin αvβ6 autoantibodies are a novel predictive biomarker in ulcerative colitis
Authors: Livanos Alexandra E , Dunn Alexandra , Fischer Jeremy , Ungaro Ryan C , Turpin Williams , Lee Sun-Ho , Rui Shumin , Del Valle Diane Marie , Jougon Julia J , Martinez-Delgado Gustavo , Riddle Mark S , Murray Joseph A , Laird Renee M , Torres Joana , Agrawal Manasi , Magee Jared S , Dervieux Thierry , Gnjatic Sacha , Sheppard Dean , Sands Bruce E , Porter Chad K , Croitoru Kenneth , Petralia Francesca ,   CCC-GEM Project Research Consortium,   OSCCAR Consortium, Colombel Jean-Frederic , Mehandru Saurabh
Published: November 2022

Background and Aims

Better biomarkers for prediction of ulcerative colitis (UC) development and prognostication are needed. Anti-integrin αvβ6 autoantibodies (anti-αvβ6) have been described in UC patients. Here, we tested for the presence of anti-αvβ6 antibodies in the pre-clinical phase of UC and studied their association with disease-related outcomes after diagnosis.

Methods

Anti-αvβ6 were measured in 4 longitudinal serum samples collected from 82 subjects who later developed UC and 82 matched controls from a Department of Defense pre-clinical cohort (PREDICTS). In a distinct, external validation cohort (GEM), we tested 12 pre-UC subjects and 49 matched controls. Further, anti-αvβ6 were measured in 2 incident UC cohorts (COMPASS n=55 and OSCCAR n=104) and associations between anti-αvβ6 and UC-related outcomes were defined using Cox proportional-hazards model.

Results

Anti-αvβ6 were significantly higher among individuals who developed UC compared to controls up to 10 years before diagnosis in PREDICTS. The anti-αvβ6 seropositivity was 12.2% 10 years before diagnosis and increased to 52.4% at the time of diagnosis in subjects who developed UC compared with 2.7% in controls across the 4 timepoints. Anti-αvβ6 predicted UC development with an AUC of at least 0.8 up to 10 years before diagnosis. The presence of anti-αvβ6 in pre-clinical UC samples was validated in the GEM cohort. Finally, high anti-αvβ6 was associated with a composite of adverse UC-outcomes including hospitalization, disease extension, colectomy, systemic steroid use and/or escalation to biologic therapy in recently diagnosed UC.

Conclusion

Anti-integrin αvβ6 auto-antibodies precede the clinical diagnosis of UC by up to 10 years and are associated with adverse UC-related outcomes.
Taste adaptations associated with host-specialization in the specialistDrosophila sechellia
Authors: Reisenman Carolina E. , Wong Joshua , Vedagarbha Namrata , Livelo Catherine , Scott Kristin
Published: November 2022

Chemosensory-driven hostplant specialization is a major force mediating insect ecological adaptation and speciation.Drosophila sechellia, a species endemic to the Seychelles islands, feeds and oviposits onMorinda citrifoliaalmost exclusively. This fruit is harmless toD. sechelliabut toxic to otherDrosophilidae, including the closely related generalistsD. simulansandD. melanogaster, due to its high content of fatty acids. While several olfactory adaptations mediatingD. sechellia’spreference for its host have been uncovered, the role of taste has been much less examined. We found thatD. sechelliahas reduced taste and feeding aversion to bitter compounds and host fatty acids that are aversive toD. melanogasterandD. simulans. The loss of aversion to canavanine, coumarin, and fatty acids arose in theD. sechellialineage, as its sister speciesD. simulansshowed responses akin to those ofD. melanogaster. D. sechelliahas increased taste and feeding responses towardsM. citrifolia. These results are in line withD. sechellia’sloss of genes encoding bitter gustatory receptors (GRs) inD. melanogaster. We found that twoGRgenes which are lost inD. sechellia,GR39a.aandGR28b.a, influence the reduction of aversive responses to some bitter compounds. Also,D. sechelliahas increased appetite for a prominent host fatty acid compound that is toxic to its relatives. Our results support the hypothesis that changes in the taste system, specifically a reduction of sensitivity to bitter compounds that deter generalist ancestors, contribute to the specialization ofD. sechelliafor its host.

Summary statement

Taste specializations in the specialistDrosophila sechelliainclude a lineage-specific reduced sensitivity to bitter compounds associated with losses of gustatory receptors, and increased appetite for Noni and host fatty acids.
Adaptive nanopore sequencing for single cell characterization of cancer mutations and gene rearrangements
Authors: Grimes Susan M. , Kim Heon Seok , Roy Sharmili , Sathe Anuja , Ayala Carlos I. , Almeda-Notestine Alison F. , Haebe Sarah , Shree Tanaya , Levy Ronald , Lau Billy T. , Ji Hanlee P.
Published: November 2022

In this proof-of-concept study, we developed a single cell method that identifies somatic alterations found in coding regions of mRNAs and integrates these mutation genotypes with their matching cell transcriptomes. We used nanopore adaptive sampling on single cell cDNA libraries, generated long read sequences from target gene transcripts and identified coding variants among individual cells. Short-read single cell transcriptomes characterized the cell types with mutations. We delineated CRISPR edits from a cancer cell line. From primary cancer samples, we targeted hundreds of cancer genes, identified somatic coding mutations and a gene rearrangement among individual tumor cells.
Neighbourhood species richness and drought-tolerance traits modulate tree growth and δ13C responses to drought
Authors: Schnabel Florian , Barry Kathryn E. , Eckhardt Susanne , Guillemot Joannès , Geilmann Heike , Kahl Anja , Moossen Heiko , Bauhus Jürgen , Wirth Christian
Published: November 2022

Mixed-species forests are promoted as a forest management strategy for climate change adaptation, but whether they are more resistant to drought than monospecific forests remains contested. Particularly, the trait-based mechanisms driving the role of tree diversity under drought remain elusive.

Using tree cores from a large-scale biodiversity experiment, we investigated tree growth and physiological stress responses (i.e. increase in wood carbon isotopic ratio; δ13C) to changes in climate-induced water availability (wet to dry years) along gradients in neighbourhood tree species richness and drought-tolerance traits. We hypothesized that neighbourhood species richness increases growth and decreases δ13C and that these relationships are modulated by the abiotic (i.e. climatic conditions) and the biotic context. We characterized the biotic context using drought-tolerance traits of focal trees and their neighbours. These traits are related to cavitation resistance vs resource acquisition and stomatal control.

Tree growth increased with neighbourhood species richness. However, we did not observe a universal relief of water stress in species-rich neighbourhoods. Neighbourhood species richness effects on growth and δ13C did not strengthen from wet to dry years. Instead, richness-growth and richness-δ13C relationships were modulated by climatic conditions and the traits of trees and their neighbours. At either end of each drought-tolerance gradient, species responded in opposing directions during drought and non-drought years.

We show that species’ drought-tolerance traits can explain the strength and nature of biodiversity-ecosystem functioning relationships in experimental tree communities experiencing drought. Mixing tree species can increase growth but may not universally relieve drought stress.

One-sentence summary

The drought-tolerance traits of trees and their neighbours determine biodiversity-ecosystem functioning relationships in experimental tree communities.
Lidocaine Induces Apoptosis in Head and Neck Squamous Cell Carcinoma Through Activation of Bitter Taste Receptor T2R14
Authors: Miller Zoey A. , Mueller Arielle , Holivert Jennifer F , Ma Ray Z. , Muthuswami Sahil , Park April , McMahon Derek B. , Carey Ryan M. , Lee Robert J.
Published: November 2022

Head and neck squamous cell carcinomas (HNSCCs) have high mortality and significant treatment-related morbidity. It is vital to discover effective, minimally invasive therapies that improve survival and quality of life. Bitter taste receptors (T2Rs) are expressed in HNSCCs and their activation can induce apoptosis. Lidocaine is a local anesthetic used in various clinical applications which can also activate bitter taste receptor 14 (T2R14). Lidocaine may have some anti-tumor effects in other cancers, but the mechanism has been mysterious. Here, we found that lidocaine causes intracellular Ca2+mobilization through activation of T2R14 in HSNCC cells. T2R14 activation with lidocaine depolarizes the mitochondrial membrane, inhibits cell proliferation, and induces apoptosis. Concomitant mitochondrial Ca2+influx, ROS production causes T2R14-dependent accumulation of poly-ubiquinated proteins, suggesting inhibition of the proteasome as a novel component of T2R14-induced apoptosis. Lidocaine may have therapeutic potential in HNSCC as a topical gel or intratumor injection, warranting future clinical studies.

HIGHLIGHTS

Lidocaine activates bitter taste receptor 14 (T2R14) to increase intracellular Ca2+and decrease cAMP in head and neck squamous cell carcinoma (HSNCC) cells

Lidocaine decreases cell viability and cell proliferation, depolarizes the mitochondrial membrane, and causes production of reactive oxygen species (ROS)

T2R14 activation with lidocaine induces apoptosis and inhibits the ubiquitin proteasome system (UPS)

Lung squamous cell carcinoma (SCC) cells and HNSCC tumor spheroids undergo apoptosis or structural disbandment, respectively, with lidocaine
Binding and sequestration of poison frog alkaloids by a plasma globulin
Authors: Alvarez-Buylla Aurora , Moya-Garzon Maria Dolores , Rangel Alexandra E. , Tapia Elicio E. , Tanzo Julia , Soh H. Tom , Coloma Luis A. , Long Jonathan Z. , O’Connell Lauren A.
Published: November 2022

Alkaloids are important bioactive molecules throughout the natural world, and in many animals they serve as a source of chemical defense against predation. Dendrobatid poison frogs bioaccumulate alkaloids from their diet to make themselves toxic or unpalatable to predators. Despite the proposed roles of plasma proteins as mediators of alkaloid trafficking and bioavailability, the responsible proteins have not been identified. We use chemical approaches to show that a ~50 kDa plasma protein is the principal alkaloid binding molecule in blood from poison frogs. Proteomic and biochemical studies establish this plasma protein to be liver-derived alkaloid-binding globulin (ABG) that is a member of the serine-protease inhibitor (serpin) family. In addition to alkaloid binding activity, ABG sequesters and regulates the bioavailability of “free” plasma alkaloidsin vitro. Unexpectedly, ABG is not related to saxiphilin, albumin, or other known vitamin carriers, but instead exhibits sequence and structural homology to mammalian hormone carriers and amphibian biliverdin binding proteins. Alkaloid-binding globulin (ABG) represents a new small molecule binding functionality in serpin proteins, a novel mechanism of plasma alkaloid transport in poison frogs, and more broadly points towards serpins acting as tunable scaffolds for small molecule binding and transport across different organisms.
Optimization-Based Decoding of Imaging Spatial Transcriptomics Data
Authors: Bryan John P. , Binan Loïc , McCann Cai , Eldar Yonina C. , Farhi Samouil L. , Cleary Brian
Published: November 2022

Motivation

Imaging Spatial Transcriptomics (iST) techniques characterize gene expression in cells in their native context by imaging barcoded probes for mRNA with single molecule resolution. However, the need to acquire many rounds of high-magnification imaging data limits the throughput and impact of existing methods.

Results

We describe the Joint Sparse method for Imaging Transcriptomics (JSIT), an algorithm for decoding lower magnification IT data than that used in standard experimental workflows. JSIT incorporates codebook knowledge and sparsity assumptions into an optimization problem which is less reliant on well separated optical signals than current pipelines. Using experimental data obtained by performing Multiplexed Error-Robust Fluorescence in situ Hybridization (MERFISH) on tissue from mouse motor cortex, we demonstrate that JSIT enables improved throughput and recovery performance over standard decoding methods.

Contact

yonina.eldar@weizmann.ac.il,sfarhi@broadinstitute.org,bcleary@bu.edu

Availability and Implementation

Software implementation of JSIT, together with example files, are available athttps://github.com/jpbryan13/JSIT.

Supplementary Information

Supplementary data are available atBioinformaticsonline.
A Sexual Bias in mitochondrial protein-coding gene expression across different tissues and the prognostic value in multiple cancers
Authors: Tardin da Silva Alan , dos Santos Ferreira Cristina , Medina-Acosta Enrique
Published: November 2022

Mitochondria in mammalian cells provide ATP through oxidative phosphorylation. The overproduction of reactive oxygen species (ROS) in mitochondrial cells promotes cancer by modifying gene expression or function. Mating introduces competing mitochondrial (mtDNA) and nuclear DNA (nDNA) gene products, leading to biological differences between males and females for diseases and disorders such as cancer. There is a significant sex bias in aging-related conditions. We aimed to investigate whether sex and age affect mitochondrial protein-coding gene expression in cancer and, if so, to determine the prognosis value in survival outcomes, stemness, and immune cell infiltrates. We compared normal versus primary tumor transcriptomes (bulk RNA-Seq) from The Cancer Genome Atlas (TCGA), and the Genotype-Tissue Expression (GTEx) projects to test these hypotheses. Correlations between gene expression, survival, protective or risk factor, stemness, and immune cell infiltrate were performed in RStudio using UCSC Xena Shiny. Eleven mitochondrial protein-coding genes were altered in brain cancer (MT-ND2,MT-ND1,MT-ATP8,MT-ATP6,MT-CO2,MT-CYB,MT-CO3,MT-ND4L,MT-ND4,MT-ND3,MT-CO1). MT-ND5 and MT-ND6 are disproportionately expressed in female brain tissues. Mitochondrial global polymorphic expression sites of variation were more significant in the 50-59 and 60-79-year-old age groups than in the 20-49-year-old age groups. Pan-cancer survival analysis revealed a 4-component gene signature (MT-CO1,MT-CO2,MT-ND5,and MT-ND6) downregulated in low-grade glioma (LGG). This gene signature increased LGG overall survival, disease-specific survival, and progression-free interval without sex-specific association. However, the correlation with disease-free interval survival was female-specific. The 4-component gene signature was protective in LGG but risky in thymoma cancer and uterine corpus endometrial carcinoma. In LGG, the 4-component gene signature positively correlated with immune monocyte, NK, and B cell infiltrates and negatively correlated with T cell CD4+ Th2, macrophage M1 and M2, myeloid dendritic cell, and neutrophil. We identified a 13-component mitochondrial protein-coding gene signature associated with stemness in kidney chromophobe. A sex-biased effect was observed in mitochondrial protein-coding for brain tissues, with a female bias. However, an aging effect with higher polymorphic site expression was observed in male tissues. We conclude that the differentially expressed mitochondrial protein-coding genes provide new insights into carcinogenesis, helping to identify new prognostic markers. The overexpression of the 4-component gene signature is associated with a better prognosis in LGG, with positive and negative correlations with immune cell infiltrates.
Rapid Real-time Squiggle Classification for Read Until Using RawMap
Authors: Sadasivan Harisankar , Wadden Jack , Goliya Kush , Ranjan Piyush , Dickson Robert P. , Blaauw David , Das Reetuparna , Narayanasamy Satish
Published: November 2022

ReadUntil enables Oxford Nanopore Technology’s (ONT) sequencers to selectively sequence reads of target species in real-time. This enables efficient microbial enrichment for applications such as microbial abundance estimation and is particularly beneficial for metagenomic samples with a very high fraction of non-target reads (>99% can be human reads). However, read-until requires a fast and accurate software filter that analyzes a short prefix of a read and determines if it belongs to a microbe of interest (target) or not. The baseline Read Until pipeline uses a deep neural network-based basecaller called Guppy and is slow and inaccurate for this task (∼60% of bases sequenced are unclassified).

We present RawMap, an efficient CPU-only microbial species-agnostic Read Until classifier for filtering non-target human reads in the squiggle space. RawMap uses a Support Vector Machine (SVM), which is trained to distinguish human from microbe using non-linear and non-stationary characteristics of ONT’s squiggle output (continuous electrical signals). Compared to the baseline Read Until pipeline, RawMap is a 1327X faster classifier and significantly improves the sequencing time and cost, and compute time savings. We show that RawMap augmented pipelines reduce sequencing time and cost by ∼24% and computing cost by ∼22%. Additionally, since RawMap is agnostic to microbial species, it can also classify microbial species it is not trained on.

We also discuss how RawMap may be used as an alternative to the RT-PCR test for viral load quantification of SARS-CoV-2.

Availability and implementation

Software is released with MIT License and available on GitHub:https://github.com/harisankarsadasivan/RawMap
Region- and variance-based DNA methylation analyses reveal novel disease genes and pathways for systemic lupus erythematosus
Authors: Guo Mengbiao , Wang Ting-You , Shen Jiangshan Jane , Wang Yong-Fei , Lau Yu-Lung , Yang Wanling
Published: November 2022

Background

Systemic lupus erythematosus (SLE) is a prototype autoimmune disease with unclear pathogenesis. DNA methylation is an important regulatory mechanism on gene expression, providing a key angle to understand disease mechanisms. To understand the pathways involved in SLE, and to develop biomarkers for its diagnosis and treatment, we analyzed DNA methylation profiles on blood cells from SLE patients and healthy controls.

Results

We identified most differentially methylated regions (DMRs) in T cells, while majority of differentially variable sites (DVSs) were found in B cells, featuring hypervariability in enhancers. We observed a prominent T cell receptor (TCR) signaling cluster with consistent hypermethylation and a B cell receptor (BCR) cluster with highly increased variability in SLE. Genes involved in innate immunity were often found hypomethylated, while adaptive immunity genes were featured with hypermethylation. Using a machine learning approach, we identified 60 genes that accurately distinguished SLE patients from healthy individuals, which also showed correlation with disease activities.

Conclusions

This study highlights the role of lymphocyte receptor aberrations in the disease and identified a list of genes showing great potential as biomarkers and shedding new light on disease mechanisms, through novel analyses of methylation data.
1000 years of population, warfare, and climate change in pre-Columbian societies of the Central Andes
Authors: Lima Mauricio , Gayó Eugenia M. , Gurruchaga Andone , Estay Sergio A. , Santoro Calogero M.
Published: November 2022

Different Andean societies underwent processes of expansion and collapse during propitious or adverse climate conditions, resource boost or depletion along with population variations. Previous studies have emphasized that demographic collapses of polities in the Central Andes Area were triggered by warfare and the negative impacts of fluctuating climate (droughts) on crop productivity. Nevertheless, the interactions between climatic variability, demography and warfare have been less thoroughly evaluated. We develop population dynamic models to test feedback relationships between population growth, climate change and warfare in the Central Andes, where considerable regional hydroclimate variations have occurred over a millennium. Through population models, we found out that the rise and demise of social polities in the northern coast of the Central Andes appear to be a consequence of climate change. In contrast, for the highlands of Peru and the Titicaca basin, population models suggest that warfare intensity has a negative effect on population growth rates.
Fake IDs? Widespread misannotation of DNA Transposons as a General Transcription Factor
Authors: Hassan Nozhat T. , Adelson David L.
Published: November 2022

The annotation of transposable elements (TEs) is a critical part of our understanding of genomes, however, the accuracy of annotation pipelines remains an issue as TEs are frequently underestimated or misannotated. We report the General Transcription Factor II-I Repeat Domain-Containing Protein 2 (GTF2IRD2) was used to erroneously annotate DNA transposons in a variety of non-mammalian species as GTF2IRD2 contains a 3’ fused hAT transposase domain. This study emphasises that the misannotation of TEs astrans-regulatory elements, such as transcription factors, can lead to errors in phylogenetic trees based on orthologs and to significant wasted time for investigators interested in gene regulation and characterising non-mammalian genomes.