bluuebunny/crossref_metadata_2025 huggingface dataset:
Cav3.1-driven bursting firing in ventromedial hypothalamic neurons exerts dual control of anxiety-like behavior and energy expenditure
Authors: Shao Jie , Gao Da-Shuang , Liu Yun-Hui , Chen Shan-Ping , Liu Nian , Zhang Lu , Zhou Xin-Yi , Xiao Qian , Wang Li-Ping , Hu Hai-Lan , Yang Fan
Published: March 2022

The central nervous system has evolved to coordinate the regulation of both the behavior response to the external environment and homeostasis of energy expenditure. Recent studies have indicated the dorsomedial ventromedial hypothalamus (dmVMH) as an important hub that regulates both innate behavior and energy homeostasis for coping stress. However, how dmVMH neurons control neuronal firing pattern to regulate chronic stress-induced anxiety and energy expenditure remains poorly understood. Here, we found enhanced neuronal activity in VMH after chronic stress, which is mainly induced by increased proportion of burst firing neurons. This enhancement of VMH burst firing is predominantly mediated by Cav3.1 expression. Optogenetically evoked burst firing of dmVMH neurons induced anxiety-like behavior, shifted the respiratory exchange ratio toward fat oxidation, and decreased food intake, while knockdown of Cav3.1 in the dmVMH had the opposite effects, suggested that Cav 3.1 as a crucial regulator. Interestingly, we found that fluoxetine (anxiolytics) could block the increase of Cav3.1 expression to inhibit the burst firing, and then rescued the anxiety-like behaviors and energy expenditure changes. Collectively, our study first revealed an important role of Cav3.1-driven bursting firing of dmVMH neurons in the control of anxiety-like behavior and energy expenditure, and provided potential therapeutic targets for treating the chronic stress-induced emotional malfunction and metabolism disorders.
UPF1 contributes to the maintenance of endometrial cancer stem cell phenotype by stabilizing LINC00963
Authors: Chen Hao , Ma Jian , Kong Fanfei , Song Ning , Wang Cuicui , Ma Xiaoxin
Published: March 2022

Endometrial cancer stem cells (ECSCs) play a vital role in endometrial cancer (EC) metastasis, relapse, and chemoresistance. However, the molecular mechanisms that sustain ECSCs remain elusive. Here, we showed that the expression of UPF1 was upregulated in EC tissues and ECSCs and correlated with poor clinicopathological characteristics. UPF1 silencing suppressed ECSC hallmarks, such as sphere formation ability, carboplatin resistance, migration and invasion, and cell cycle progression. UPF1 regulated the behavior and fate of ECSCs by stabilizing LINC00963. LINC00963 further shares the same miRNA response element with the core transcription factor SOX2 and relieved the suppression of SOX2 by miR-508-5p in self-renewing ECSCs. Notably, inhibition of UPF1 and LINC00963 in combination severely impaired the in vivo tumorigenic potential of ECSCs. We demonstrate that the UPF1/LINC00963/miR-508-5p/SOX2 axis has potential value in modulating ECSC maintenance, chemoresistance, and tumorigenesis in EC, which highlights a novel promising target for EC treatment.
Single-cell RNA-sequencing analysis reveals MYH9 promotes renal cell carcinoma development and sunitinib resistance via AKT signaling pathway
Authors: Xu Zhipeng , Liu Min , Wang Jin , Liu Kai , Xu Liuyu , Fan Demin , Zhang Hui , Hu Wenxin , Wei Dan , Wang Jianning
Published: March 2022

Clear cell renal cell carcinoma (ccRCC) is a serious threat to human health worldwide, while its heterogeneity limits therapeutic success and leads to poor survival outcomes. Single-cell RNA-sequencing (scRNA-seq) is an important technology, which provides deep insights into the genetic characteristics of carcinoma. In this study, we profiled the gene expression of single cells from human ccRCC tissues and adjacent normal tissues using the scRNA-seq. We found that MYH9 was commonly upregulated in the ccRCC cell subgroup. Additionally, MYH9 was of highly expression in ccRCC tissues and predicted poor prognosis of ccRCC patients. MYH9 knockdown in ccRCC cells dampened their proliferative and metastatic potentials, whereas MYH9 overexpression enhanced these properties. In vivo, MYH9 also promoted ccRCC growth. Mechanistic studies showed that MYH9 played these vital roles through AKT signaling pathway. Furthermore, MYH9/AKT axis determined the responses of ccRCC cells to sunitinib treatment and might serve as a biomarker for sunitinib benefits in ccRCC patients. Thus, MYH9 might be a novel therapeutic target and prognostic predictor for ccRCC.
GIT1 protects against breast cancer growth through negative regulation of Notch
Authors: Zhang Songbai , Miyakawa Ayako , Wickström Malin , Dyberg Cecilia , Louhivuori Lauri , Varas-Godoy Manuel , Kemppainen Kati , Kanatani Shigeaki , Kaczynska Dagmara , Ellström Ivar Dehnisch , Elfman Lotta , Kronqvist Pauliina , Repo Heli , Mikoshiba Katsuhiko , Sahlgren Cecilia , Johnsen John Inge , Uhlén Per
Published: March 2022

Hyperactive Notch signalling is frequently observed in breast cancer and correlates with poor prognosis. However, relatively few mutations in the core Notch signalling pathway have been identified in breast cancer, suggesting that as yet unknown mechanisms increase Notch activity. Here we show that increased expression levels of GIT1 correlate with high relapse-free survival in oestrogen receptor-negative (ER(-)) breast cancer patients and that GIT1 mediates negative regulation of Notch. GIT1 knockdown in ER(-) breast tumour cells increased signalling downstream of Notch and activity of aldehyde dehydrogenase, a predictor of poor clinical outcome. GIT1 interacts with the Notch intracellular domain (ICD) and influences signalling by inhibiting the cytoplasm-to-nucleus transport of the Notch ICD. In xenograft experiments, overexpression of GIT1 in ER(-) cells prevented or reduced Notch-driven tumour formation. These results identify GIT1 as a modulator of Notch signalling and a guardian against breast cancer growth.
Combinatorial optimization of mRNA structure, stability, and translation for RNA-based therapeutics
Authors: Leppek Kathrin , Byeon Gun Woo , Kladwang Wipapat , Wayment-Steele Hannah K. , Kerr Craig H. , Xu Adele F. , Kim Do Soon , Topkar Ved V. , Choe Christian , Rothschild Daphna , Tiu Gerald C. , Wellington-Oguri Roger , Fujii Kotaro , Sharma Eesha , Watkins Andrew M. , Nicol John J. , Romano Jonathan , Tunguz Bojan , Diaz Fernando , Cai Hui , Guo Pengbo , Wu Jiewei , Meng Fanyu , Shi Shuai , Participants Eterna , Dormitzer Philip R. , Solórzano Alicia , Barna Maria , Das Rhiju
Published: March 2022

Therapeutic mRNAs and vaccines are being developed for a broad range of human diseases, including COVID-19. However, their optimization is hindered by mRNA instability and inefficient protein expression. Here, we describe design principles that overcome these barriers. We develop an RNA sequencing-based platform called PERSIST-seq to systematically delineate in-cell mRNA stability, ribosome load, as well as in-solution stability of a library of diverse mRNAs. We find that, surprisingly, in-cell stability is a greater driver of protein output than high ribosome load. We further introduce a method called In-line-seq, applied to thousands of diverse RNAs, that reveals sequence and structure-based rules for mitigating hydrolytic degradation. Our findings show that highly structured “superfolder” mRNAs can be designed to improve both stability and expression with further enhancement through pseudouridine nucleoside modification. Together, our study demonstrates simultaneous improvement of mRNA stability and protein expression and provides a computational-experimental platform for the enhancement of mRNA medicines.
Amontons-Coulomb-like slip dynamics in acousto-microfluidics
Authors: Quelennec Aurore , Gorman Jason J. , Reyes Darwin R.
Published: March 2022

Acousto-microfluidics uses acoustic waves to manipulate and sense particles and fluids, and its integration into biomedical technologies has grown substantially in recent years. Fluid manipulation and measurement with surface acoustic waves rely on the efficient transmission of acoustic energy from the device to the fluid. Acoustic transmission into the fluid can be reduced significantly by slip at the fluid-solid interface, but, up until now, this phenomenon has been widely neglected during the design of acousto-microfluidic devices. Here our interpretation supports that the slip dynamics at the liquid-solid interface in acousto-microfluidics are highly analogous to the Amontons-Coulomb laws for dry friction between solids. In particular, there is a relationship between the local fluid pressure and shear stress, where we show that pressure-shear stress conditions can be divided into slip and no-slip regions, similar to the cone of friction found in dry friction. This improved understanding of slip will enable more reliable and predictable acousto-microfluidic technologies, thus expanding their use in new applications in biology and medicine.
Transcription factors modulate RNA polymerase conformational equilibrium
Authors: Zhu Chengjin , Guo Xieyang , Dumas Philippe , Takacs Maria , Abdelkareem Mo’men , Vanden Broeck Arnaud , Saint-André Charlotte , Papai Gabor , Crucifix Corinne , Ortiz Julio , Weixlbaumer Albert
Published: March 2022

RNA polymerase (RNAP) frequently pauses during the transcription of DNA to RNA to regulate gene expression. Transcription factors NusA and NusG modulate pausing, have opposing roles, but can bind RNAP simultaneously. Here we report cryo-EM reconstructions of Escherichia coli RNAP bound to NusG, or NusA, or both. RNAP conformational changes, referred to as swivelling, correlate with transcriptional pausing. NusA facilitates RNAP swivelling to further increase pausing, while NusG counteracts this role. Their structural effects are consistent with biochemical results on two categories of transcriptional pauses. In addition, the structures suggest a cooperative mechanism of NusA and NusG during Rho-mediated transcription termination. Our results provide a structural rationale for the stochastic nature of pausing and termination and how NusA and NusG can modulate it.
Midbrain projection to the basolateral amygdala encodes anxiety-like but not depression-like behaviors
Authors: Morel Carole , Montgomery Sarah E. , Li Long , Durand-de Cuttoli Romain , Teichman Emily M. , Juarez Barbara , Tzavaras Nikos , Ku Stacy M. , Flanigan Meghan E. , Cai Min , Walsh Jessica J. , Russo Scott J. , Nestler Eric J. , Calipari Erin S. , Friedman Allyson K. , Han Ming-Hu
Published: March 2022

Anxiety disorders are complex diseases, and often co-occur with depression. It is as yet unclear if a common neural circuit controls anxiety-related behaviors in both anxiety-alone and comorbid conditions. Here, utilizing the chronic social defeat stress (CSDS) paradigm that induces singular or combined anxiety- and depressive-like phenotypes in mice, we show that a ventral tegmental area (VTA) dopamine circuit projecting to the basolateral amygdala (BLA) selectively controls anxiety- but not depression-like behaviors. Using circuit-dissecting ex vivo electrophysiology and in vivo fiber photometry approaches, we establish that expression of anxiety-like, but not depressive-like, phenotypes are negatively correlated with VTA → BLA dopamine neuron activity. Further, our optogenetic studies demonstrate a causal link between such neuronal activity and anxiety-like behaviors. Overall, these data establish a functional role for VTA → BLA dopamine neurons in bi-directionally controlling anxiety-related behaviors not only in anxiety-alone, but also in anxiety-depressive comorbid conditions in mice.
Longitudinal piezoelectric resonant photoelastic modulator for efficient intensity modulation at megahertz frequencies
Authors: Atalar Okan , Van Laer Raphaël , Safavi-Naeini Amir H. , Arbabian Amin
Published: March 2022

Intensity modulators are an essential component in optics for controlling free-space beams. Many applications require the intensity of a free-space beam to be modulated at a single frequency, including wide-field lock-in detection for sensitive measurements, mode-locking in lasers, and phase-shift time-of-flight imaging (LiDAR). Here, we report a new type of single frequency intensity modulator that we refer to as a longitudinal piezoelectric resonant photoelastic modulator. The modulator consists of a thin lithium niobate wafer coated with transparent surface electrodes. One of the fundamental acoustic modes of the modulator is excited through the surface electrodes, confining an acoustic standing wave to the electrode region. The modulator is placed between optical polarizers; light propagating through the modulator and polarizers is intensity modulated with a wide acceptance angle and record breaking modulation efficiency in the megahertz frequency regime. As an illustration of the potential of our approach, we show that the proposed modulator can be integrated with a standard image sensor to effectively convert it into a time-of-flight imaging system.
Deep-learning two-photon fiberscopy for video-rate brain imaging in freely-behaving mice
Authors: Guan Honghua , Li Dawei , Park Hyeon-cheol , Li Ang , Yue Yuanlei , Gau Yung-Tian A. , Li Ming-Jun , Bergles Dwight E. , Lu Hui , Li Xingde
Published: March 2022

Scanning two-photon (2P) fiberscopes (also termed endomicroscopes) have the potential to transform our understanding of how discrete neural activity patterns result in distinct behaviors, as they are capable of high resolution, sub cellular imaging yet small and light enough to allow free movement of mice. However, their acquisition speed is currently suboptimal, due to opto-mechanical size and weight constraints. Here we demonstrate significant advances in 2P fiberscopy that allow high resolution imaging at high speeds (26 fps) in freely-behaving mice. A high-speed scanner and a down-sampling scheme are developed to boost imaging speed, and a deep learning (DL) algorithm is introduced to recover image quality. For the DL algorithm, a two-stage learning transfer strategy is established to generate proper training datasets for enhancing the quality of in vivo images. Implementation enables video-rate imaging at ~26 fps, representing 10-fold improvement in imaging speed over the previous 2P fiberscopy technology while maintaining a high signal-to-noise ratio and imaging resolution. This DL-assisted 2P fiberscope is capable of imaging the arousal-induced activity changes in populations of layer2/3 pyramidal neurons in the primary motor cortex of freely-behaving mice, providing opportunities to define the neural basis of behavior.
Structures of pseudorabies virus capsids
Authors: Wang Guosong , Zha Zhenghui , Huang Pengfei , Sun Hui , Huang Yang , He Maozhou , Chen Tian , Lin Lina , Chen Zhenqin , Kong Zhibo , Que Yuqiong , Li Tingting , Gu Ying , Yu Hai , Zhang Jun , Zheng Qingbing , Chen Yixin , Li Shaowei , Xia Ningshao
Published: March 2022

Pseudorabies virus (PRV) is a major etiological agent of swine infectious diseases and is responsible for significant economic losses in the swine industry. Recent data points to human viral encephalitis caused by PRV infection, suggesting that PRV may be able to overcome the species barrier to infect humans. To date, there is no available therapeutic for PRV infection. Here, we report the near-atomic structures of the PRV A-capsid and C-capsid, and illustrate the interaction that occurs between these subunits. We show that the C-capsid portal complex is decorated with capsid-associated tegument complexes. The PRV capsid structure is highly reminiscent of other α-herpesviruses, with some additional structural features of β- and γ-herpesviruses. These results illustrate the structure of the PRV capsid and elucidate the underlying assembly mechanism at the molecular level. This knowledge may be useful for the development of oncolytic agents or specific therapeutics against this arm of the herpesvirus family.
SkewDB, a comprehensive database of GC and 10 other skews for over 30,000 chromosomes and plasmids
Authors: Hubert Bert
Published: March 2022

GC skew denotes the relative excess of G nucleotides over C nucleotides on the leading versus the lagging replication strand of eubacteria. While the effect is small, typically around 2.5%, it is robust and pervasive. GC skew and the analogous TA skew are a localized deviation from Chargaff’s second parity rule, which states that G and C, and T and A occur with (mostly) equal frequency even within a strand. Different bacterial phyla show different kinds of skew, and differing relations between TA and GC skew. This article introduces an open access database (https://skewdb.org) of GC and 10 other skews for over 30,000 chromosomes and plasmids. Further details like codon bias, strand bias, strand lengths and taxonomic data are also included. The SkewDB can be used to generate or verify hypotheses. Since the origins of both the second parity rule and GC skew itself are not yet satisfactorily explained, such a database may enhance our understanding of prokaryotic DNA.
A point-like thermal light source as a probe for sensing light-matter interaction
Authors: Korn S. , Popp M. A. , Weber H. B.
Published: March 2022

Historically, thermal radiation is related to 3D cavities. In practice, however, it is known that almost any hot surface radiates according to Planck’s law. This approximate universality roots in the smooth electromagnetic mode structure of free space, into which the radiation is emitted. Here, we study the effect for a strongly patterned mode structure and use quasi-transparent point-like thermal light emitters as a probe. As such, we choose current-driven graphene nanojunctions for which the emission into free space obeys Planck’s law. Placed in front of a mirror, however, this process is highly sensitive to a node/antinode pattern of light modes. By varying the distance, we can sample the latter with atomic precision, and observe a deep imprint on the observed spectrum. The experiment allows an unprecedented view on thermal radiation in a spatially/spectrally patterned electromagnetic environment.
A new versatile x–y–z electrospinning equipment for nanofiber synthesis in both far and near field
Authors: Calzado-Delgado Mar , Guerrero-Pérez M. Olga , Yeung King Lun
Published: March 2022

This work describes a versatile electrospinning equipment with rapid, independent, and precise x–y–z movements for large-area depositions of electrospun fibers, direct writing or assembly of fibers into sub-millimeter and micron-sized patterns, and printing of 3D micro- and nanostructures. Its versatility is demonstrated thought the preparation of multilayered functional nanofibers for wound healing, nanofiber mesh for particle filtration, high-aspect ratio printed lines, and freestanding aligned nanofibers.
Decay of homologous chromosome pairs and discovery of males in the thelytokous fungus-growing ant Mycocepurus smithii
Authors: Barros Luísa Antônia Campos , Rabeling Christian , Teixeira Gisele Amaro , dos Santos Ferreira Mariano Cléa , Delabie Jacques Hubert Charles , de Aguiar Hilton Jeferson Alves Cardoso
Published: March 2022

The prevalent mode of reproduction among ants is arrhenotokous parthenogenesis where unfertilized eggs give rise to haploid males and fertilized eggs develop into diploid females. Some ant species are capable of thelytokous parthenogenesis, a type of asexual reproduction where females develop from unfertilized diploid eggs. Thelytoky is well-documented in more than 20 ant species. Cytogenetic data are available for six species demonstrating that some thelytokous ant species are capable of producing males occasionally as well as maintaining their chromosome numbers and proper chromosome pairings. Mycocepurus smithii is a thelytokous fungus-growing ant species that inhabits large parts of Central and South America. Cytogenetic data are unavailable for M. smithii and male individuals were never documented for this species, although the presence of males is expected because genetic recombination was observed in a few sexually reproducing populations in Brazil and haploid sperm was documented from the spermathecae of M. smithii queens. This study aims at comparatively studying asexual and sexual populations of M. smithii using classical and molecular cytogenetic methods to test whether karyotype configuration is modified according to the mode of reproduction in M. smithii. Moreover, we report the discovery of M. smithii males from a sexually reproducing population in the Brazilian state Pará, diagnose the male of M. smithii, and morphologically characterize their spermatozoa. Karyotypic variation was observed within the asexual population (2n = 9, 10, or 11), whereas the chromosome number was fixed in the sexual population (2n = 14, n = 7). Identical karyotypes were maintained within individual M. smithii colonies and karyotype variation was only observed between colonies. In asexual individuals, the karyomorphs showed a decay of homologous chromosome pairs, especially in individuals with the karyomorph 2n = 11, which is potentially caused by relaxed natural selection on proper chromosome pairing. In contrast, females in the sexual population showed proper homologous chromosome pairings. In individuals of both asexual and sexual populations, we find that heterochromatin was localized in centromeric regions and on the short arms of the chromosomes, GC-rich regions were associated with heterochromatic regions, and 18S rDNA genes were located on the largest chromosome pair. This comparative cytogenetic analysis contributes to our understanding about the cytological mechanisms associated with thelytokous parthenogenesis in ants and suggests the decay of chromosome structure in the absence of meiosis and genetic recombination.
Removal of yttrium from rare-earth wastewater by Serratia marcescens: biosorption optimization and mechanisms studies
Authors: Liang Chang-li , Shen Ji-li
Published: March 2022

The discharge of yttrium containing wastewater is a potential risk to human health. Although biosorption is a promising method to remove yttrium from wastewater, whereas the application of it is limited due to the lack of efficient biosorbents. In this study, the removal of yttrium from wastewater using Serratia marcescens as a biosorbent was conducted. The effects of six parameters including pH (2–5.5), initial yttrium concentration (10–110 mg/L), biosorbent dosage (0.1–0.5 g/L), biosorption time (10–700 min), stirring speed (50–300 rpm) and temperature (20–60 °C) were evaluated. The main parameters were optimized using response surface methodology. The results showed that the adsorption capacity reached 123.65 mg/g at the optimized conditions. The biosorption mechanism was revealed based on a combined analysis using field emission transmission electron microscope-energy dispersion spectrum, Fourier transform infrared spectrophotometer, and X-ray photoelectron spectroscopy. These results revealed that the hydroxyl, carboxyl, and amino groups were the adsorption functional groups for yttrium ions. Biosorption of yttrium by S. marcescens is under the combination of ion exchange, electrostatic attraction and complexation. These findings indicated that S. marcescens can be used as an efficient biosorbent to remove yttrium from wastewater. In addition, its adsorption capacity can be further improved by the enhancement of adsorption functional groups on the surface through chemical modification.
A study on Ti-doped Fe3O4 anode for Li ion battery using machine learning, electrochemical and distribution function of relaxation times (DFRTs) analyses
Authors: Chi Po-Wei , Paul Tanmoy , Su Yu-Hsuan , Su Kai-Han , Su Cherng-Yuh , Wu Phillip M. , Wang Sea-Fue , Wu Maw-Kuen
Published: March 2022

Among many transition-metal oxides, Fe3O4 anode based lithium ion batteries (LIBs) have been well-investigated because of their high energy and high capacity. Iron is known for elemental abundance and is relatively environmentally friendly as well contains with low toxicity. However, LIBs based on Fe3O4 suffer from particle aggregation during charge–discharge processes that affects the cycling performance. This study conjectures that iron agglomeration and material performance could be affected by dopant choice, and improvements are sought with Fe3O4 nanoparticles doped with 0.2% Ti. The electrochemical measurements show a stable specific capacity of 450 mAh g−1 at 0.1 C rate for at least 100 cycles in Ti doped Fe3O4. The stability in discharge capacity for Ti doped Fe3O4 is achieved, arising from good electronic conductivity and stability in microstructure and crystal structure, which has been further confirmed by density functional theory (DFT) calculation. Detailed distribution function of relaxation times (DFRTs) analyses based on the impedance spectra reveal two different types of Li ion transport phenomena, which are closely related with the electron density difference near the two Fe-sites. Detailed analyses on EIS measurements using DFRTs for Ti doped Fe3O4 indicate that improvement in interfacial charge transfer processes between electrode and Li metal along with an intermediate lithiated phase helps to enhance the electrochemical performance.
Ultrafast neuromorphic photonic image processing with a VCSEL neuron
Authors: Robertson Joshua , Kirkland Paul , Alanis Juan Arturo , Hejda Matěj , Bueno Julián , Di Caterina Gaetano , Hurtado Antonio
Published: March 2022

The ever-increasing demand for artificial intelligence (AI) systems is underlining a significant requirement for new, AI-optimised hardware. Neuromorphic (brain-like) processors are one highly-promising solution, with photonic-enabled realizations receiving increasing attention. Among these, approaches based upon vertical cavity surface emitting lasers (VCSELs) are attracting interest given their favourable attributes and mature technology. Here, we demonstrate a hardware-friendly neuromorphic photonic spike processor, using a single VCSEL, for all-optical image edge-feature detection. This exploits the ability of a VCSEL-based photonic neuron to integrate temporally-encoded pixel data at high speed; and fire fast (100 ps-long) optical spikes upon detecting desired image features. Furthermore, the photonic system is combined with a software-implemented spiking neural network yielding a full platform for complex image classification tasks. This work therefore highlights the potential of VCSEL-based platforms for novel, ultrafast, all-optical neuromorphic processors interfacing with current computation and communication systems for use in future light-enabled AI and computer vision functionalities.
Calibration and validation of the Angstrom–Prescott model in solar radiation estimation using optimization algorithms
Authors: Banihashemi Dehkordi Seyedeh Nafiseh , Bakhtiari Bahram , Qaderi Kourosh , Ahmadi Mohammad Mehdi
Published: March 2022

The Angstrom–Prescott (A–P) model is widely suggested for estimating solar radiation (Rs) in areas without measured or deficiency of data. The aim of this research was calibration and validation of the coefficients of the A–P model at six meteorological stations across arid and semi-arid regions of Iran. This model has improved by adding the air temperature and relative humidity terms. Besides, the coefficients of the A–P model and improved models have calibrated using some optimization algorithms including Harmony Search (HS) and Shuffled Complex Evolution (SCE). Performance indices, i.e., Root Mean Square Error (RMSE), Mean Bias Error, and coefficient of determination (R2) have used to analyze the models ability in estimating Rs. The results indicated that the performance of the A–P model had more precision and less error than improved models in all the stations. In addition, the best results have obtained for the A–P model with the SCE algorithm. The RMSE varies between 0.82 and 2.67 MJ m−2 day−1for the A–P model with the SCE algorithm in the calibration phase. In the SCE algorithm, the values of RMSE had decreased about 4% and 7% for Mashhad and Kerman stations in the calibration phase compared to the HS algorithm, respectively.
A green protocol for the electrochemical synthesis of a fluorescent dye with antibacterial activity from imipramine oxidation
Authors: Souri Zahra , Masoudi Khoram Mahmood , Nematollahi Davood , Mazloum-Ardakani Mohammad , Alizadeh Hojjat
Published: March 2022

Electrochemical oxidation of imipramine (IMP) has been studied in aqueous solutions by cyclic voltammetry and controlled-potential coulometry techniques. Our voltammetric results show a complex behavior for oxidation of IMP at different pH values. In this study, we focused our attention on the electrochemical oxidation of IMP at a pH of about 5. Under these conditions, our results show that the oxidation of IMP leads to the formation of a unique dimer of IMP (DIMP). The structure of synthesized dimer is fully characterized by UV–visible, FTIR,1H NMR,13C NMR and mass spectrometry techniques. It seems that the first step in the oxidation of IMP is the cleavage of the alkyl group (formation of IMPH). After this, a domino oxidation-hydroxylation-dimerization-oxidation reaction, converts IMPH to (E)-10,10′,11,11′-tetrahydro-[2,2′-bidibenzo[b,f]azepinylidene]-1,1′(5H,5′H)-dione (DIMP). The synthesis of DIMP is performed in an aqueous solution under mild conditions, without the need for any catalyst or oxidant. Based on our electrochemical findings as well as the identification of the final product, a possible reaction mechanism for IMP oxidation has been proposed. Conjugated double bonds in the DIMP structure cause the compound to become colored with sufficient fluorescence activity (excitation wave-length 535 nm and emission wave-length 625 nm). Moreover, DIMP has been evaluated for in vitro antibacterial. The antibacterial tests indicated that DIMP showed good antibacterial performance against all examined gram-positive and gram-negative bacteria (Staphylococcus aureus, Bacillus cereus, Escherichia coliandShigella sonnei).
Weakly supervised end-to-end artificial intelligence in gastrointestinal endoscopy
Authors: Buendgens Lukas , Cifci Didem , Ghaffari Laleh Narmin , van Treeck Marko , Koenen Maria T. , Zimmermann Henning W. , Herbold Till , Lux Thomas Joachim , Hann Alexander , Trautwein Christian , Kather Jakob Nikolas
Published: March 2022

Artificial intelligence (AI) is widely used to analyze gastrointestinal (GI) endoscopy image data. AI has led to several clinically approved algorithms for polyp detection, but application of AI beyond this specific task is limited by the high cost of manual annotations. Here, we show that a weakly supervised AI can be trained on data from a clinical routine database to learn visual patterns of GI diseases without any manual labeling or annotation. We trained a deep neural network on a dataset of N = 29,506 gastroscopy and N = 18,942 colonoscopy examinations from a large endoscopy unit serving patients in Germany, the Netherlands and Belgium, using only routine diagnosis data for the 42 most common diseases. Despite a high data heterogeneity, the AI system reached a high performance for diagnosis of multiple diseases, including inflammatory, degenerative, infectious and neoplastic diseases. Specifically, a cross-validated area under the receiver operating curve (AUROC) of above 0.70 was reached for 13 diseases, and an AUROC of above 0.80 was reached for two diseases in the primary data set. In an external validation set including six disease categories, the AI system was able to significantly predict the presence of diverticulosis, candidiasis, colon and rectal cancer with AUROCs above 0.76. Reverse engineering the predictions demonstrated that plausible patterns were learned on the level of images and within images and potential confounders were identified. In summary, our study demonstrates the potential of weakly supervised AI to generate high-performing classifiers and identify clinically relevant visual patterns based on non-annotated routine image data in GI endoscopy and potentially other clinical imaging modalities.
The design of an inkjet drive waveform using machine learning
Authors: Kim Seongju , Cho Minsu , Jung Sungjune
Published: March 2022

A drive waveform, which needs to be optimized with ink’s fluid properties, is critical to reliable inkjet printing. A generally adopted rule of thumb for its design is mostly dependent on time-consuming and repetitive manual manipulation of its parameters. This work presents a closed-loop machine learning approach to designing an optimal drive waveform for satellite-free inkjet printing at a target velocity. Each of the representative 11 model inks with different fluid properties was ink-jetted with 1100 distinct waveform designs. The high-speed images of their jetting behaviors were acquired and the big datasets of the resulting drop formation and velocity were extracted from the jetting images. Five machine learning models were examined and compared to predict the characteristics of jetting behavior. Among a variety of machine learning models, Multi-layer Perceptron affords the highest prediction accuracy. A closed-loop prediction algorithm that determined the optimal set of waveform parameters for satellite-free drop formation at a target velocity and employed the most superior learning model was established. The proposed method was confirmed through the printing of an unknown model ink with a recommended waveform.
Gabrb3 endothelial cell-specific knockout mice display abnormal blood flow, hypertension, and behavioral dysfunction
Authors: Agrud Anass , Subburaju Sivan , Goel Pranay , Ren Jun , Kumar Ashwin Srinivasan , Caldarone Barbara J. , Dai Wangde , Chavez Jesus , Fukumura Dai , Jain Rakesh K. , Kloner Robert A. , Vasudevan Anju
Published: March 2022

Our recent studies uncovered a novel GABA signaling pathway in embryonic forebrain endothelial cells that works independently from neuronal GABA signaling and revealed that disruptions in endothelial GABAA receptor-GABA signaling from early embryonic stages can directly contribute to the origin of psychiatric disorders. In the GABAA receptor β3 subunit endothelial cell conditional knockout (Gabrb3ECKO) mice, the β3 subunit is deleted selectively from endothelial cells, therefore endothelial GABAA receptors become inactivated and dysfunctional. There is a reduction in vessel densities and increased vessel morphology in the Gabrb3ECKO telencephalon that persists in the adult neocortex. Gabrb3ECKO mice show behavioral deficits such as impaired reciprocal social interactions, communication deficits, heightened anxiety, and depression. Here, we characterize the functional changes in Gabrb3ECKO mice by evaluating cortical blood flow, examine the consequences of loss of endothelial Gabrb3 on cardiac tissue, and define more in-depth altered behaviors. Red blood cell velocity and blood flow were increased in the cortical microcirculation of the Gabrb3ECKO mice. The Gabrb3ECKO mice had a reduction in vessel densities in the heart, similar to the brain; exhibited wavy, myocardial fibers, with elongated ‘worm-like’ nuclei in their cardiac histology, and developed hypertension. Additional alterations in behavioral function were observed in the Gabrb3ECKO mice such as increased spontaneous exploratory activity and rearing in an open field, reduced short term memory, decreased ambulatory activity in CLAMS testing, and altered prepulse inhibition to startle, an important biomarker of psychiatric diseases such as schizophrenia. Our results imply that vascular Gabrb3 is a key player in the brain as well as the heart, and its loss in both organs can lead to concurrent development of psychiatric and cardiac dysfunction.
Effect of prepartum dietary energy density on beef cow energy metabolites, and birth weight and antioxidative capabilities of neonatal calves
Authors: Chen Hao , Wang Chunjie , Huasai Simujide , Chen Aorigele
Published: March 2022

The objective of this study was to investigate the effect of prepartum diets that differ in energy density on beef cow energy metabolites and birth weight, immunity and antioxidative capabilities of neonatal calves. On d 0 (approximately 45 d before calving), 90 multiparous Angus cows (BW = 510 ± 16 kg) were randomly allocated into 1 of 9 drylot pens (10 cows/pen). Each pen was randomly assigned to a treatment condition (three pens/treatment), the cows in each treatment were assigned randomly to receive a high-energy (HE) density diet (NEm = 1.67 Mcal/kg of DM), medium-energy (ME) density diet (NEm = 1.53 Mcal/kg of DM), or low-energy (LE) density diet (NEm = 1.36 Mcal/kg of DM). Blood samples were collected − 45, − 21, − 14, and − 7 d from calving, and plasma concentrations of cortisol, glucose, total protein, β-hydroxybutyrate (BHBA), and nonesterified fatty acids (NEFAs) were measured. After calving, the birth weights, body height, body length, thoracic girth and umbilical girth of the calves in each group were recorded, and blood samples were collected for analysis of IgG, IL-2, IL-4, IL-6, total antioxidant capacity, superoxide dismutase, glutathione peroxidase, and maleic dialdehyde levels. The amounts of feed offered and orts were recorded for individual cows 4 d/wk. The results indicated that although dry matter intake (DMI) levels did not differ among the LE, ME, and or HE groups before parturition, the group that received the HE diet had higher plasma glucose concentrations and lower prepartum blood NEFA concentrations than the other groups. Birth weight, body height, thoracic girth, and levels of IL-2, cortisol, total antioxidant capacity, and superoxide dismutase were increased in calves of the HE group compared with those of the LE group. The plasma IL-4 and serum IgG concentrations tended to be decreased in the ME group compared with the HE group, and the ME group had lower maleic dialdehyde concentrations; maleic dialdehyde levels were significantly increased in the LE group compared with the HE group. Overall, these results indicate that feeding of a low-energy diet during the last 45 d before parturition has negative effects on the growth, immunity, and antioxidative capabilities of neonatal calves. Increasing maternal energy density during late gestation may be useful to improve the energy status of cows.
Unraveling structural and conformational dynamics of DGAT1 missense nsSNPs in dairy cattle
Authors: Pathak Rajesh Kumar , Lim Byeonghwi , Park Yejee , Kim Jun-Mo
Published: March 2022

Cattle are domestic animals that have been nourishing humans for thousands of years. Milk from cattle represents a key source of high-quality protein, fat, and other nutrients. The nutritional value of milk and dairy products is closely associated with the fat content, providing up to 30% of the total fat consumed in the human diet. The fat content in cattle milk represents a major concern for the scientific community due to its association with human health. The relationship between milk fat content and diacylglycerol o-acyltransferase 1 gene (DGAT1) is well described in literature. Several studies demonstrated the difference in fat contents and other milk production traits in a wide range of cattle breeds, to be associated with missense non-synonymous single nucleotide polymorphisms (nsSNPs) of the DGAT1 gene. As a result, an nsSNPs analysis is crucial for unraveling the DGAT1 structural and conformational dynamics linked to milk fat content. DGAT1-nsSNPs are yet to be studied in terms of their structural and functional impact. Therefore, state-of-the-art computational and structural genomic methods were used to analyze five selected variants (W128R, W214R, C215G, P245R, and W459G), along with the wild type DGAT1. Significant structural and conformational changes in the variants were observed. We illustrate how single amino acid substitutions affect DGAT1 function, how this contributes to our understanding of the molecular basis of variations in DGAT1, and ultimately its impact in improving fat quality in milk.
Compatibility and synergistic interactions of fungi, Metarhizium anisopliae, and insecticide combinations against the cotton aphid, Aphis gossypii Glover (Hemiptera: Aphididae)
Authors: Nawaz Ahmad , Razzaq Fatima , Razzaq Amna , Gogi Muhammad Dildar , Fernández-Grandon G. Mandela , Tayib Muhammad , Ayub Muhammad Ahsin , Sufyan Muhammad , Shahid Muhammad Rafiq , Qayyum Mirza Abdul , Naveed Muhammad , Ijaz Anam , Arif Muhammad Jalal
Published: March 2022

Aphids are major pests affecting cereals, vegetables, fruit, forestry and horticultural produce. A multimodal approach may be an effective route to controlling this prolific pest. We assessed the individual and combined effect of eight insecticides and the entomopathogenic fungi,Metarhizium anisopliae(Metschin.) against the cotton aphid,Aphis gossypiiGlover (Hemiptera: Aphididae), under laboratory conditions. Six of the insecticides tested were found to be highly compatible (flonicamid, imidacloprid, nitenpyram, dinotefuran, pyriproxyfen and spirotetramat), showing positive integration with the fungus and were selected for bioassays. The combination mixtures (1:1 ratio ofM. anisopliae: insecticide) were significantly more toxic toA. gossypiithan individual treatments. Maximum mortality (91.68%) ofA. gossypiiwas recorded with combination of flonicamid andM. anisopliae(2.4 × 106 cfu/ml) 72 h after application. While minimum mortality (17.08%) was observed with the individual treatment ofM. anisopliae(2.4 × 106 cfu/ml). The insecticides revealed toxicity consistent with their compatibility withM. anisopliae,ranking for efficacy exactly as they did for compatibility. In addition, the synergy factor (SF) and co-toxicity coefficient (CTC) values indicated synergistic interactions at different time intervals. The synergistic efficacy revealed the potential of fungus-insecticide integration against sucking insect pests.
A metagenomic analysis of the bacterial microbiome of limestone, and the role of associated biofilms in the biodeterioration of heritage stone surfaces
Authors: Skipper Philip J. A. , Skipper Lynda K. , Dixon Ronald A.
Published: March 2022

There is growing concern surrounding the aesthetic and physical effects of microbial biofilms on heritage buildings and monuments. Carboniferous stones, such as limestone and marble, are soluble in weak acid solutions and therefore particularly vulnerable to biocorrosion. This paper aims to determine the differences and commonalities between the microbiome of physically damaged and undamaged Lincolnshire limestone, an area of research which has not been previously studied. A lack of information about the core microbiome has resulted in conflicting claims in the literature regarding the biodeteriorative potential of many microorganisms. To address this, we used metagenomics alongside traditional microbiological techniques to produce an in-depth analysis of differences between the bacterial microbiomes found on deteriorated and undamaged external limestone surfaces. We demonstrate there is a core microbiome on Lincolnshire limestone present on both damaged and undamaged surfaces. In addition to the core microbiome, significant differences were found between species isolated from undamaged compared to damaged surfaces. Isolated species were characterised for biofilm formation and biodeteriorative processes, resulting in the association of species with biodeterioration that had not been previously described. Additionally, we have identified a previously undescribed method of biofilm-associated biomechanical damage. This research adds significant new understanding to the field, aiding decision making in conservation of stone surfaces.
Transboundary aerosol transport process and its impact on aerosol-radiation-cloud feedbacks in springtime over Northeast Asia
Authors: Lee Hyo-Jung , Jo Yu-Jin , Kim Seungwoo , Kim Daecheol , Kim Jong-Min , Choi Daniel , Jo Hyun-Young , Bak Juseon , Park Shin-Young , Jeon Wonbae , Kim Cheol-Hee
Published: March 2022

Northeast Asia has been suffering from dramatic increases of particulate matter (PM) since the late 1990s, and it still continues to undergo haze despite various abating regulations. In this study, we investigated aerosol-cloud-precipitation (ACP) interactions with the varied PM, and the impact of long-range transport (LRT) process on ACP in springtime was assessed in Northeast Asia. Our long-term (1995–2019) analysis of PM10exhibited the correlation with decreases of both sunshine duration and drizzle occurrences that can be interpreted as direct and indirect aerosol effects, while cloud cover induced by the varied PM10was found only in more than 90% cloud cover (9/10–10/10 category). The online WRF-Chem with wind-blown dust simulation indicated that cloud water was affected by secondary inorganic aerosol (SIA) formation near the surface in upwind areas dominantly, whereas, along the LRT pathway, cloud water perturbation altitudes were increased quasi-linearly toward downward between 1 and 3 km. The gas-to-particle conversion ratios of sulfur ([SO42−]/[SO2 + SO42−]) and nitrogen ([NO3−]/[NO2 + NO3−]) both remain aloft long at the same vertical levels of most perturbed cloud altitude enough to be transported over long distance in springtime. Formations of sulfate and nitrate showed different ACP interaction timing; distinctive shifts in the ratios observed at the exit (Shanghai-Yellow Sea) by nitrate, and entrance areas (Seoul-Tokyo) by sulfate along the LRT pathway, respectively, with higher ratios of 0.8 or more in springtime. Our results indicate that ACP processes have been enhanced at a LRT-related altitude with different SIA production timings that can be considered in species-specific springtime PM abatements over Northeast Asia.
Development and identification of four new synthetic hexaploid wheat lines with solid stems
Authors: Liang Dongyu , Zhang Minghu , Liu Xin , Li Hui , Jia Zhenjiao , Wang Dinghao , Peng Ting , Hao Ming , Liu Dengcai , Jiang Bo , Huang Lin , Ning Shunzong , Yuan Zhongwei , Chen Xuejiao , Zhang Lianquan
Published: March 2022

Stem solidness is an important agronomic trait for increasing the ability of wheat to resist lodging. In this study, four new synthetic hexaploid wheat with solid stems were developed from natural chromosome doubling of F1 hybrids between a solid-stemmed durum wheat (Triticum turgidum ssp. durum, 2n = 4x = 28, AABB) and four Aegilops tauschii (2n = 2x = 14, DD) accessions. The solid expression of the second internode at the base of the stem was stable for two synthetic hexalpoid wheat Syn-SAU-117 and Syn-SAU-119 grown in both the greenhouse and field. The lodging resistance of four synthetic solid-stem wheats is stronger than that of CS, and Syn-SAU-116 has the strongest lodging resistance, followed by Syn-SAU-119. The paraffin sections of the second internode showed that four synthetic wheat lines had large outer diameters, well-developed mechanical tissues, large number of vascular bundles, and similar anatomical characteristics with solid-stemmed durum wheat. The chromosomal composition of four synthetic hexaploid wheat was identified by FISH (fluorescence in situ hybridization) using Oligo-pSc119.2-1 and Oligo-pTa535-1. At adult stage, all four synthetic hexaploid wheat showed high resistance to mixed physiological races of stripe rust pathogen (CYR31, CYR32, CYR33, CYR34). These synthetic hexaploid wheat lines provide new materials for the improvement of common wheat.