bluuebunny/crossref_metadata_2025 huggingface dataset:
Low-Cost, Computer Vision-Based, Prebloom Cluster Count Prediction in Vineyards
Authors: Jaramillo Jonathan , Vanden Heuvel Justine , Petersen Kirstin H.
Published: April 2021

Traditional methods for estimating the number of grape clusters in a vineyard generally involve manually counting the number of clusters per vine in a subset of the vineyard and scaling by the total number of vines; a technique that can be laborious, costly, and with an accuracy that depends on the size of the sample. We demonstrate that traditional cluster counting has a high variance in yield estimate accuracy and is highly sensitive to the particular counter and choice of the subset of counted vines. We propose a simple computer vision-based method for improving the reliability of these yield estimates using cheap and easily accessible hardware for growers. This method detects, tracks, and counts clusters and shoots in videos collected using a smartphone camera that is driven or walked through the vineyard at night. With a random selection of calibration data, this method achieved an average cluster count error of 4.9% across two growing seasons and two cultivars by detecting and counting clusters. Traditional methods yielded an average cluster count error of 7.9% across the same dataset. Moreover, the proposed method yielded a maximum error of 12.6% while the traditional method yielded a maximum error of 23.5%. The proposed method can be deployed before flowering, while the canopy is sparse, which improves maximum visibility of clusters and shoots, generalizability across different cultivars and growing seasons, and earlier yield estimates compared to prior work in the area.
Molecularly Imprinted Electrochemical Sensor-Based Fe2O3@MWCNTs for Ivabradine Drug Determination in Pharmaceutical Formulation, Serum, and Urine Samples
Authors: Abdel-Haleem Fatehy M. , Gamal Eman , Rizk Mahmoud S. , Madbouly Adel , El Nashar Rasha M. , Anis Badawi , Elnabawy Hussam M. , Khalil Ahmed S. G. , Barhoum Ahmed
Published: April 2021

Ivabradine hydrochloride (IVR) is a medically important drug because of its ability to lower the heart rate. Techniques reported for IVR determination were expensive, laborious, besides being of poor selectivity. In this study, iron oxide @ carbon nanotube (Fe2O3@MWCNTs) nanocomposite and molecularly imprinted polymer (MIP) were synthesized and used in the fabrication of carbon paste electrodes (CPEs) for the potentiometric detection of IVR in biological and pharmaceutical samples. CPEs of the best sensor were formulated from graphite (41 wt%) as a carbon source, MIP (3 wt.%) as an ionophore, Fe2O3@MWCNTs (5 wt%) as a modifier, and nitrophenyl octyl ether (NPOE, 51 wt.%) as a conductive oil so-called plasticizer. The best sensor exhibits a Nernstian slope (response) of 56 mV decade–1 within the IVR concentration range from 1.0 × 10–3 M to 9.8 × 10–8 M with high selectivity against interfering species (ascorbic, maltose, glucose, lactose, dopamine, glycine) over those reported earlier. The use of Fe2O3@MWCNTs together with MIP in the electrode formulation was found to improve the limit of detection (LOD) from 630 to 98 nM along with high reversibility, a short response time of 30 s, and a good lifetime of more than 2 weeks. The sandwich membrane (SMM) method was used to quantify the H-bonding complexing strength of the MIP binding sites for IVR with Log βILn = 11.33. The constructed sensors were successfully applied for the IVR determination in blood serum, urine, and commercial formulations (Savapran®) with high sensitivity.
A Unique Junctional Interface at Contact Sites Between the Endoplasmic Reticulum and Lipid Droplets
Authors: Choudhary Vineet , Schneiter Roger
Published: April 2021

Lipid droplets (LDs) constitute compartments dedicated to the storage of metabolic energy in the form of neutral lipids. LDs originate from the endoplasmic reticulum (ER) with which they maintain close contact throughout their life cycle. These ER–LD junctions facilitate the exchange of both proteins and lipids between these two compartments. In recent years, proteins that are important for the proper formation of LDs and localize to ER–LD junctions have been identified. This junction is unique as it is generally believed to invoke a transition from the ER bilayer membrane to a lipid monolayer that delineates LDs. Proper formation of this junction requires the ordered assembly of proteins and lipids at specialized ER subdomains. Without such a well-ordered assembly of LD biogenesis factors, neutral lipids are synthesized throughout the ER membrane, resulting in the formation of aberrant LDs. Such ectopically formed LDs impact ER and lipid homeostasis, resulting in different types of lipid storage diseases. In response to starvation, the ER–LD junction recruits factors that tether the vacuole to these junctions to facilitate LD degradation. In addition, LDs maintain close contacts with peroxisomes and mitochondria for metabolic channeling of the released fatty acids toward beta-oxidation. In this review, we discuss the function of different components that ensure proper functioning of LD contact sites, their role in lipogenesis and lipolysis, and their relation to lipid storage diseases.
MicroRNA Signatures of the Developing Primate Fovea
Authors: Fishman Elizabeth S. , Louie Mikaela , Miltner Adam M. , Cheema Simranjeet K. , Wong Joanna , Schlaeger Nicholas M. , Moshiri Ala , Simó Sergi , Tarantal Alice F. , La Torre Anna
Published: April 2021

Rod and cone photoreceptors differ in their shape, photopigment expression, synaptic connection patterns, light sensitivity, and distribution across the retina. Although rods greatly outnumber cones, human vision is mostly dependent on cone photoreceptors since cones are essential for our sharp visual acuity and color discrimination. In humans and other primates, the fovea centralis (fovea), a specialized region of the central retina, contains the highest density of cones. Despite the vast importance of the fovea for human vision, the molecular mechanisms guiding the development of this region are largely unknown. MicroRNAs (miRNAs) are small post-transcriptional regulators known to orchestrate developmental transitions and cell fate specification in the retina. Here, we have characterized the transcriptional landscape of the developing rhesus monkey retina. Our data indicates that non-human primate fovea development is significantly accelerated compared to the equivalent retinal region at the other side of the optic nerve head, as described previously. Notably, we also identify several miRNAs differentially expressed in the presumptive fovea, including miR-15b-5p, miR-342-5p, miR-30b-5p, miR-103-3p, miR-93-5p as well as the miRNA cluster miR-183/-96/-182. Interestingly, miR-342-5p is enriched in the nasal primate retina and in the peripheral developing mouse retina, while miR-15b is enriched in the temporal primate retina and increases over time in the mouse retina in a central-to-periphery gradient. Together our data constitutes the first characterization of the developing rhesus monkey retinal miRNome and provides novel datasets to attain a more comprehensive understanding of foveal development.
Phagocytosis by Peripheral Glia: Importance for Nervous System Functions and Implications in Injury and Disease
Authors: Nazareth Lynn , St John James , Murtaza Mariyam , Ekberg Jenny
Published: April 2021

The central nervous system (CNS) has very limited capacity to regenerate after traumatic injury or disease. In contrast, the peripheral nervous system (PNS) has far greater capacity for regeneration. This difference can be partly attributed to variances in glial-mediated functions, such as axon guidance, structural support, secretion of growth factors and phagocytic activity. Due to their growth-promoting characteristic, transplantation of PNS glia has been trialed for neural repair. After peripheral nerve injuries, Schwann cells (SCs, the main PNS glia) phagocytose myelin debris and attract macrophages to the injury site to aid in debris clearance. One peripheral nerve, the olfactory nerve, is unique in that it continuously regenerates throughout life. The olfactory nerve glia, olfactory ensheathing cells (OECs), are the primary phagocytes within this nerve, continuously clearing axonal debris arising from the normal regeneration of the nerve and after injury. In contrast to SCs, OECs do not appear to attract macrophages. SCs and OECs also respond to and phagocytose bacteria, a function likely critical for tackling microbial invasion of the CNS via peripheral nerves. However, phagocytosis is not always effective; inflammation, aging and/or genetic factors may contribute to compromised phagocytic activity. Here, we highlight the diverse roles of SCs and OECs with the focus on their phagocytic activity under physiological and pathological conditions. We also explore why understanding the contribution of peripheral glia phagocytosis may provide us with translational strategies for achieving axonal regeneration of the injured nervous system and potentially for the treatment of certain neurological diseases.
Tell the Difference Between Mitosis and Meiosis: Interplay Between Chromosomes, Cytoskeleton, and Cell Cycle Regulation
Authors: Sato Masamitsu , Kakui Yasutaka , Toya Mika
Published: April 2021

Meiosis is a specialized style of cell division conserved in eukaryotes, particularly designed for the production of gametes. A huge number of studies to date have demonstrated how chromosomes behave and how meiotic events are controlled. Yeast substantially contributed to the understanding of the molecular mechanisms of meiosis in the past decades. Recently, evidence began to accumulate to draw a perspective landscape showing that chromosomes and microtubules are mutually influenced: microtubules regulate chromosomes, whereas chromosomes also regulate microtubule behaviors. Here we focus on lessons from recent advancement in genetical and cytological studies of the fission yeastSchizosaccharomyces pombe, revealing how chromosomes, cytoskeleton, and cell cycle progression are organized and particularly how these are differentiated in mitosis and meiosis. These studies illuminate that meiosis is strategically designed to fulfill two missions: faithful segregation of genetic materials and production of genetic diversity in descendants through elaboration by meiosis-specific factors in collaboration with general factors.
Integrated Design of Working Fluid Mixtures and Absorption Refrigeration Cycles
Authors: Papadopoulos Athanasios I. , Kyriakides Alexios-Spyridon , Seferlis Panos , Hassan Ibrahim
Published: April 2021

This work presents a CAMD (computer-aided molecular design) approach for the design of working fluid mixtures used in ABR (absorption refrigeration) cycles. Compared to previous works, the proposed approach introduces two major improvements. It employs for the first time an ABR process model in the course of CAMD, hence enabling the evaluation of the generated mixtures considering process performance indicators. It enables for the first time the simultaneous generation and evaluation of molecular structures for both refrigerants and absorbents. The employed model and CAMD optimization problem formulation incorporates major ABR operational driving forces pertaining to efficient refrigeration, sufficient solubility of mixture components and ease of separation in the generator. The approach employs a multicriteria assessment methodology both during CAMD and for the evaluation of selected mixtures using a more rigorous ABR model at a second stage. The work identifies novel mixtures, with Acetaldehyde/2-Methoxyethyl acetate and Acetaldehyde/Methanediol exhibiting the highest performance. The latter exhibits 3% higher COP (coefficient of performance) and cooling output than the reference mixture NH3/H2O, whereas it operates at 87 and 89% lower high and low cycle pressures. The novel mixtures are also compared with novel mixtures previously identified through a heuristic approach by the authors. The latter mixtures indicate overall higher ABR performance but similar or worse performance in safety, health and environmental impact indices. Further performance improvements may be achieved by including into CAMD additional chemical groups to be able to simulate the complex absorbent structures available in published works.
CD Imaging at High Spatial Resolution at Diamond B23 Beamline: Evolution and Applications
Authors: Hussain Rohanah , Jávorfi Tamás , Siligardi Giuliano
Published: April 2021

Circular Dichroism imaging in the 190–650 nm spectral region pionered at Diamond Light Source B23 beamline, has been made possible by the highly collimated microbeam generated at the beamline and has been used to study the homogeneity of the supramolecular structures of thin films of chiral materials deposited on fused quartz substrates. This facility has been expanded with the installation of a Mueller Matrix Polarimeter, MMP, coupled to the beamlight, of which a preliminary data will be discussed. In the solid state, the measurement of CD related to the supramolecular structure is hampered by the presence of circular birefringence, linear dichroism, and linear birefringence that can only be evaluated using the MMP technique. The ability to characterize the chiroptical property of thin chiral films prepared under a variety of conditions and protocols such as drop cast, spin coating, spray at different temperatures and concentrations will enable the determination of the critical parameters for reproducible, uniform and homogeneous specimen preparation, which is the sine qua non for any commercial application. This is of particular importance for optoelectronic materials, but it can also be extended to a broad variety of materials with applications from biosensors to biological tissues.
Vowel Quality and Direction of Stress Shift in a Predictive Model Explaining the Varying Impact of Misplaced Word Stress: Evidence From English
Authors: Ghosh Monica , Levis John M.
Published: April 2021

The use of suprasegmental cues to word stress occurs across many languages. Nevertheless, L1 English listeners' pay little attention to suprasegmental word stress cues and evidence shows that segmental cues are more important to L1 English listeners in how words are identified in speech. L1 English listeners assume strong syllables with full vowels mark the beginning of a new word, attempting alternative resegmentations only when this heuristic fails to identify a viable word string. English word stress errors have been shown to severely disrupt processing for both L1 and L2 listeners, but not all word stress errors are equally damaging. Vowel quality and direction of stress shift are thought to be predictors of the intelligibility of non-standard stress pronunciations—but most research so far on this topic has been limited to two-syllable words. The current study uses auditory lexical decision and delayed word identification tasks to test a hypothesized English Word Stress Error Gravity Hierarchy for words of two to five syllables. Results indicate that English word stress errors affect intelligibility most when they introduce concomitant vowel errors, an effect that is somewhat mediated by the direction of stress shift. As a consequence, the relative intelligibility impact of any particular lexical stress error can be predicted by the Hierarchy for both L1 and L2 English listeners. These findings have implications for L1 and L2 English pronunciation research and teaching. For research, our results demonstrate that varied findings about loss of intelligibility are connected to vowel quality changes of word stress errors and that these factors must be accounted for in intelligibility research. For teaching, the results indicate that not all word stress errors are equally important, and that only word stress errors that affect vowel quality should be prioritized.
An Update on Obstructive Sleep Apnea for Atherosclerosis: Mechanism, Diagnosis, and Treatment
Authors: Chen Jin , Lin Shu , Zeng Yiming
Published: April 2021

The occurrence and development of atherosclerosis could be influenced by intermittent hypoxia. Obstructive sleep apnea (OSA), characterized by intermittent hypoxia, is world-wide prevalence with increasing morbidity and mortality rates. Researches remain focused on the study of its mechanism and improvement of diagnosis and treatment. However, the underlying mechanism is complex, and the best practice for OSA diagnosis and treatment considering atherosclerosis and related cardiovascular diseases is still debatable. In this review, we provided an update on research in OSA in the last 5 years with regard to atherosclerosis. The processes of inflammation, oxidative stress, autonomic nervous system activation, vascular dysfunction, platelet activation, metabolite dysfunction, small molecule RNA regulation, and the cardioprotective occurrence was discussed. Additionally, improved diagnosis such as, the utilized of portable device, and treatment especially with inconsistent results in continuous positive airway pressure and mandibular advancement devices were illustrated in detail. Therefore, further fundamental and clinical research should be carried out for a better understanding the deep interaction between OSA and atherosclerosis, as well as the suggestion of newer diagnostic and treatment options.
Connection of Quasi-Resonant Amplification to the Delay in Atmospheric Residence Times Over India
Authors: Lakshmi Kumar T. V. , Durga G. Purna , Rao K. Koteswara , Barbosa Humberto , Kulkarni Ashwini , Patwardhan Savita , Mall R. K. , Rao V. Brahmananda
Published: April 2021

Mean monthly Atmospheric Residence Times (ART), deduced from the global climate models of Coupled Model Intercomparison Project 5 (CMIP5) under RCP4.5 and RCP8.5 emission scenarios over Indian landmass, show a perceptible increase by the end of the 21st century. India, being a tropical country, faces prolonged ART, particularly during the June month of Southwest monsoon season (June to September) which will be an indicative measure of the increased frequency of extreme weather events. Here we show a possible connection of quasi-resonant amplification (QRA) to the recent (August 2018) Kerala heavy rains that resulted in severe floods and claimed more than 400 mortalities. Remarkable delay in residence times over India during June is shown to have an association with QRA evidenced by the higher magnitudes of amplitudes at the wavenumbers six and seven from the 19 global climate models of CMIP5 under the RCP4.5 and RCP8.5 scenarios.
Impact of Biomass Burning on Ozone, Carbon Monoxide, and Nitrogen Dioxide in Northern Thailand
Authors: Khodmanee Suratsawadee , Amnuaylojaroen Teerachai
Published: April 2021

The problem of smoke haze pollution in Northern Thailand affects both the environment and residents. The main sources of smoke are wildfires and open burning during the dry season, which release many pollutants, especially surface O3, impacting health and causing an air pollution crisis. The aim of this research was to study the impact of biomass burning on the surface O3, CO, and NO2 levels in Northern Thailand using the Weather Research and Forecasting Model with Chemistry (WRF-Chem). The simulation domain was configured with two domains with a grid spacing of 50 and 10 km in March 2014. To elucidate the effect of biomass burning, the model simulation was conducted for two cases: 1) a simulation with anthropogenic, biogenic, and biomass burning emissions; and 2) a simulation excluding biomass burning emissions. Owing to the model performance, the diurnal temperature and precipitation were consistent with observations, as indicated by the index of agreement (IOA) ranges of 0.74–0.76, while those of O3, CO, and NO2 were in the ranges of 0.12–0.71. The results show that biomass burning increased O3, CO, and NO2 levels by 9, 51, and 96%, respectively.
Modulatory Effects of Probiotics During Pathogenic Infections With Emphasis on Immune Regulation
Authors: Raheem Abdul , Liang Lin , Zhang Guangzhi , Cui Shangjin
Published: April 2021

In order to inhibit pathogenic complications and to enhance animal and poultry growth, antibiotics have been extensively used for many years. Antibiotics applications not only affect target pathogens but also intestinal beneficially microbes, inducing long-lasting changes in intestinal microbiota associated with diseases. The application of antibiotics also has many other side effects like, intestinal barrier dysfunction, antibiotics residues in foodstuffs, nephropathy, allergy, bone marrow toxicity, mutagenicity, reproductive disorders, hepatotoxicity carcinogenicity, and antibiotic-resistant bacteria, which greatly compromise the efficacy of antibiotics. Thus, the development of new antibiotics is necessary, while the search for antibiotic alternatives continues. Probiotics are considered the ideal antibiotic substitute; in recent years, probiotic research concerning their application during pathogenic infections in humans, aquaculture, poultry, and livestock industry, with emphasis on modulating the immune system of the host, has been attracting considerable interest. Hence, the adverse effects of antibiotics and remedial effects of probiotics during infectious diseases have become central points of focus among researchers. Probiotics are live microorganisms, and when given in adequate quantities, confer good health effects to the host through different mechanisms. Among them, the regulation of host immune response during pathogenic infections is one of the most important mechanisms. A number of studies have investigated different aspects of probiotics. In this review, we mainly summarize recent discoveries and discuss two important aspects: (1) the application of probiotics during pathogenic infections; and (2) their modulatory effects on the immune response of the host during infectious and non-infectious diseases.
Digestive Tract and the Muscular Pharynx/Esophagus in Wild Leptocephalus Larvae of European Eel (Anguilla anguilla)
Authors: Knutsen Helene Rønquist , Sørensen Sune Riis , Munk Peter , Bardal Tora , Kjørsvik Elin
Published: April 2021

Several aspects of the biology of European eel (Anguilla anguilla) larvae are still unknown; particularly, information about their functional development and feeding is sparse. In the present study, we histologically characterize the digestive system of wild caught specimens of European eel leptocephalus larvae. The aim was to provide more understanding about how food may be ingested and mechanically processed in the leptocephalus larvae, and to discuss this in the context of its hypothesized feeding strategy. Larvae were caught in the Sargasso Sea during the “Danish Eel Expedition 2014” with the Danish research vessel Dana. The larval sizes ranged from 7.0 to 23.3 mm standard length (SL) at catch. We found that the mouth/pharynx, especially the anterior esophagus, was surrounded by a multi-layered striated muscle tissue and that the epithelium in the mouth/pharynx had a rough filamentous surface, followed by epithelial columnar cells with multiple cilia in the anterior esophagus. This suggests an expandable pharynx/esophagus, well-suited for the transportation of ingested food and likely with a food-crushing or grinding function. The digestive tract of the larvae consisted of a straight esophagus and intestine ventrally aligned within the larval body, and its length was linearly correlated to the larval length (SL). The length of the intestinal part constituted up to 63% of the total length of the digestive tract. The intestinal epithelium had a typical absorptive epithelium structure, with a brush border and a well-developed villi structure. Some cilia were observed in the intestine, but any surrounding muscularis was not observed. The liver was observed along the posterior part of the esophagus, and pancreatic tissue was located anterior to the intestine. Our findings support the hypothesis that the eel leptocephalus may ingest easily digestible gelatinous plankton and/or marine snow aggregates. The muscular esophagus and the ciliated epithelium appear sufficient to ensure nutrient transport and absorption of the ingested food through the digestive tract.
Reduced Graphene Oxide-Poly (Ionic Liquid) Composite Films of High Mechanical Performance
Authors: Chang Jian , Zhou Xianjing , Zhao Qiang , Cao Wei , Zhang Miao , Yuan Jiayin
Published: April 2021

Graphene and its derivatives are a classical group of two-dimensional (2D) building blocks possessing excellent mechanical and/or electrical properties in favor of preparing flexible electronic devices. Natural materials, such as nacre, provide inspiration and an exciting guideline for assembling 2D nanosheets into functional nanocomposites. In this context, despite recent advance, methods to assemble graphene-derived nanosheets into nanocomposites with the integrated enhancement of mechanical properties and electrical conductivity are eagerly pursued. Here, a rational design has been proposed and demonstrated, which utilizes synergistic supramolecular interactions between a polymeric additive and reduced graphene-oxide nanosheets to fabricate exceptional, integrated, strong, and tough nanocomposite films with high electrical conductivity. Such materials can be applied in areas such as, aerospace, artificial muscle, tissue engineering, and flexible electronics.
Research Progress of Bionic Adaptive Camouflage Materials
Authors: Qiao Yu , Meng Zihui , Wang Piaopiao , Yan Dan
Published: April 2021

Bionic adaptive camouflage material is a new artificial functional material, whose surface color can change adaptively according to the optical environments. Therefore, how to reduce the visual detectability of this material becomes a research hotspot of digital camouflage stealth technology. In order to clarify the limitations and opportunities of the bionic adaptive camouflage materials in the field of visual stealth, we summarize the applications of current adaptive camouflage materials and carry out a prospect of next-generation photonic crystal infrared camouflage material in this review. It is expected to provide a solution for the demand of digital camouflage adaptive materials in the modern battle field.
Engineering Tissue-Informed Biomaterials to Advance Pulmonary Regenerative Medicine
Authors: Campbell Donald R. , Senger Christiana N. , Ryan Amy L. , Magin Chelsea M.
Published: April 2021

Biomaterials intentionally designed to support the expansion, differentiation, and three-dimensional (3D) culture of induced-pluripotent stem cells (iPSCs) may pave the way to cell-based therapies for chronic respiratory diseases. These conditions are endured by millions of people worldwide and represent a significant cause of morbidity and mortality. Currently, there are no effective treatments for the majority of advanced lung diseases and lung transplantation remains the only hope for many chronically ill patients. Key opinion leaders speculate that the novel coronavirus, COVID-19, may lead to long-term lung damage, further exacerbating the need for regenerative therapies. New strategies for regenerative cell-based therapies harness the differentiation capability of human iPSCs for studying pulmonary disease pathogenesis and treatment. Excitingly, biomaterials are a cell culture platform that can be precisely designed to direct stem cell differentiation. Here, we present a closer look at the state-of-the-art of iPSC differentiation for pulmonary engineering, offer evidence supporting the power of biomaterials to improve stem cell differentiation, and discuss our perspective on the potential for tissue-informed biomaterials to transform pulmonary regenerative medicine.
Efficacy of Antiviral Treatment in Liver Biopsy-Proven Immune-Tolerant Chronic Hepatitis B Patients: A Retrospective Cohort Study
Authors: Liu Na , Yang Nan , Ma Wenqi , Yang Shujuan , Hu Chunhua , Li Juan , Zhao Yingren , Xu Guanghua , He Yingli
Published: April 2021

The optimal timing of initiating antiviral treatment for immune-tolerant (IT) patients remains unknown. We conducted this study in liver biopsy-proven IT patients to compare the long-term outcomes of untreated and treated patients suffering non-cirrhotic chronic hepatitis B (CHB). This retrospective cohort study recruited 171 consecutive treatment-naïve CHB patients who completed liver biopsy test. Patients were stratified into IT (n = 60), mildly-active (MA; n = 31), immune-active (IA; n = 80), according to alanine aminotransferase (ALT) and liver biopsy data. One hundred and nine patients receiving antiviral treatment constituted the treated set, and 62 patients under close follow-up comprised the untreated set. Primary outcomes were virological response, HBeAg seroconversion, HBsAg loss, ALT normalization, and liver stiffness measurement normalization (NCT03740789). The study population was predominantly male (62.6%) with a mean age of 31 years. The proportion of virological response in treated patients in the MA phase was 57.1%, and the proportion of HBeAg seroconversion was 28.6%, which showed no difference with the 43.8% virological response and 31.5% HBeAg seroconversion in IA patients. The proportions of virological response and seroconversion were 18.2 and 9.1%, respectively, in the IT phase, which were lower than the rates in the MA and IA phases. However, 95.5% of IT patients persisted normal ALT, and 100% of IT patients persisted normal liver stiffness measurement in the treated group. Therefore, antiviral treatment should be considered for CHB patients with high viral load regardless of phase to minimize further damage to hepatocytes.
Genomic Insight of Alicyclobacillus mali FL18 Isolated From an Arsenic-Rich Hot Spring
Authors: Aulitto Martina , Gallo Giovanni , Puopolo Rosanna , Mormone Angela , Limauro Danila , Contursi Patrizia , Piochi Monica , Bartolucci Simonetta , Fiorentino Gabriella
Published: April 2021

Extreme environments are excellent places to find microorganisms capable of tolerating extreme temperature, pH, salinity pressure, and elevated concentration of heavy metals and other toxic compounds. In the last decades, extremophilic microorganisms have been extensively studied since they can be applied in several fields of biotechnology along with their enzymes. In this context, the characterization of heavy metal resistance determinants in thermophilic microorganisms is the starting point for the development of new biosystems and bioprocesses for environmental monitoring and remediation. This work focuses on the isolation and the genomic exploration of a new arsenic-tolerant microorganism, classified as Alicyclobacillus mali FL18. The bacterium was isolated from a hot mud pool of the solfataric terrains in Pisciarelli, a well-known hydrothermally active zone of the Campi Flegrei volcano near Naples in Italy. A. mali FL18 showed a good tolerance to arsenite (MIC value of 41 mM), as well as to other metals such as nickel (MIC 30 mM), cobalt, and mercury (MIC 3 mM and 17 μM, respectively). Signatures of arsenic resistance genes (one arsenate reductase, one arsenite methyltransferase, and several arsenite exporters) were found interspersed in the genome as well as several multidrug resistance efflux transporters that could be involved in the export of drugs and heavy metal ions. Moreover, the strain showed a high resistance to bacitracin and ciprofloxacin, suggesting that the extreme environment has positively selected multiple resistances to different toxic compounds. This work provides, for the first time, insights into the heavy metal tolerance and antibiotic susceptibility of an Alicyclobacillus strain and highlights its putative molecular determinants.
Thiocyanate and Organic Carbon Inputs Drive Convergent Selection for Specific Autotrophic Afipia and Thiobacillus Strains Within Complex Microbiomes
Authors: Huddy Robert J. , Sachdeva Rohan , Kadzinga Fadzai , Kantor Rose S. , Harrison Susan T. L. , Banfield Jillian F.
Published: April 2021

Thiocyanate (SCN–) contamination threatens aquatic ecosystems and pollutes vital freshwater supplies. SCN–-degrading microbial consortia are commercially adapted for remediation, but the impact of organic amendments on selection within SCN–-degrading microbial communities has not been investigated. Here, we tested whether specific strains capable of degrading SCN– could be reproducibly selected for based on SCN– loading and the presence or absence of added organic carbon. Complex microbial communities derived from those used to treat SCN–-contaminated water were exposed to systematically increased input SCN concentrations in molasses-amended and -unamended reactors and in reactors switched to unamended conditions after establishing the active SCN–-degrading consortium. Five experiments were conducted over 790 days, and genome-resolved metagenomics was used to resolve community composition at the strain level. A single Thiobacillus strain proliferated in all reactors at high loadings. Despite the presence of many Rhizobiales strains, a single Afipia variant dominated the molasses-free reactor at moderately high loadings. This strain is predicted to break down SCN– using a novel thiocyanate desulfurase, oxidize resulting reduced sulfur, degrade product cyanate to ammonia and CO2 via cyanate hydratase, and fix CO2 via the Calvin–Benson–Bassham cycle. Removal of molasses from input feed solutions reproducibly led to dominance of this strain. Although sustained by autotrophy, reactors without molasses did not stably degrade SCN– at high loading rates, perhaps due to loss of biofilm-associated niche diversity. Overall, convergence in environmental conditions led to convergence in the strain composition, although reactor history also impacted the trajectory of community compositional change.
Vascular Aging in the Invertebrate Chordate, Botryllus schlosseri
Authors: Rodriguez Delany , Taketa Daryl A. , Madhu Roopa , Kassmer Susannah , Loerke Dinah , Valentine Megan T. , Tomaso Anthony W. De
Published: April 2021

Vascular diseases affect over 1 billion people worldwide and are highly prevalent among the elderly, due to a progressive deterioration of the structure of vascular cells. Most of our understanding of these age-related cellular changes comes from in vitro studies on human cell lines. Further studies of the mechanisms underlying vascular aging in vivo are needed to provide insight into the pathobiology of age-associated vascular diseases, but are difficult to carry out on vertebrate model organisms. We are studying the effects of aging on the vasculature of the invertebrate chordate, Botryllus schlosseri. This extracorporeal vascular network of Botryllus is transparent and particularly amenable to imaging and manipulation. Here we use a combination of transcriptomics, immunostaining and live-imaging, as well as in vivo pharmacological treatments and regeneration assays to show that morphological, transcriptional, and functional age-associated changes within vascular cells are key hallmarks of aging in B. schlosseri, and occur independent of genotype. We show that age-associated changes in the cytoskeleton and the extracellular matrix reshape vascular cells into a flattened and elongated form and there are major changes in the structure of the basement membrane over time. The vessels narrow, reducing blood flow, and become less responsive to stimuli inducing vascular regression. The extracorporeal vasculature is highly regenerative following injury, and while age does not affect the regeneration potential, newly regenerated vascular cells maintain the same aged phenotype, suggesting that aging of the vasculature is a result of heritable epigenetic changes.
Selective 1H-14N Distance Measurements by 14N Overtone Solid-State NMR Spectroscopy at Fast MAS
Authors: Duong Nghia Tuan , Gan Zhehong , Nishiyama Yusuke
Published: April 2021

Accurate distance measurements between proton and nitrogen can provide detailed information on the structures and dynamics of various molecules. The combination of broadband phase-modulated (PM) pulse and rotational-echo saturation-pulse double-resonance (RESPDOR) sequence at fast magic-angle spinning (MAS) has enabled the measurement of multiple 1H-14N distances with high accuracy. However, complications may arise when applying this sequence to systems with multiple inequivalent 14N nuclei, especially a single 1H sitting close to multiple 14N atoms. Due to its broadband characteristics, the PM pulse saturates all 14N atoms; hence, the single 1H simultaneously experiences the RESPDOR effect from multiple 1H-14N couplings. Consequently, no reliable H-N distances are obtained. To overcome the problem, selective 14N saturation is desired, but it is difficult because 14N is an integer quadrupolar nucleus. Alternatively, 14N overtone (OT) NMR spectroscopy can be employed owing to its narrow bandwidth for selectivity. Moreover, owing to the sole presence of two energy levels (m = ± 1), the 14N OT spin dynamics behaves similarly to that of spin-1/2. This allows the interchangeability between RESPDOR and rotational-echo double-resonance (REDOR) since their principles are the same except the degree of 14N OT population transfer; saturation for the former whereas inversion for the latter. As the ideal saturation/inversion is impractical due to the slow and orientation-dependent effective nutation of 14N OT, the working condition is usually an intermediate between REDOR and RESPDOR. The degree of 14N OT population transfer can be determined from the results of protons with short distances to 14N and then can be used to obtain long-distance determination of other protons to the same 14N site. Herein, we combine the 14N OT and REDOR/RESPDOR to explore the feasibility of selective 1H-14N distance measurements. Experimental demonstrations on simple biological compounds of L-tyrosine.HCl, N-acetyl-L-alanine, and L-alanyl-L-alanine were performed at 14.1 T and MAS frequency of 62.5 kHz. The former two consist of a single 14N site, whereas the latter consists of two 14N sites. The experimental optimizations and reliable fittings by the universal curves are described. The extracted 1H-14N distances by OT-REDOR are in good agreement with those determined by PM-RESPDOR and diffraction techniques.
An Emerging Role for Post-translational Modifications in Regulating RNP Condensates in the Germ Line
Authors: Schisa Jennifer A. , Elaswad Mohamed T.
Published: April 2021

RNA-binding proteins undergo regulated phase transitions in an array of cell types. The phase separation of RNA-binding proteins, and subsequent formation of RNP condensates or granules, occurs during physiological conditions and can also be induced by stress. Some RNP granules have roles in post-transcriptionally regulating mRNAs, and mutations that prevent the condensation of RNA-binding proteins can reduce an organism’s fitness. The reversible and multivalent interactions among RNP granule components can result in RNP complexes that transition among diffuse and condensed states, the latter of which can be pathological; for example, in neurons solid RNP aggregates contribute to disease states such as amyotrophic lateral sclerosis (ALS), and the dysregulation of RNP granules in human germ cells may be involved in Fragile X-associated primary ovarian insufficiency. Thus, regulating the assembly of mRNAs and RNA-binding proteins into discrete granules appears to provide important functions at both cellular and physiological levels. Here we review our current understanding of the role of post-translational modifications (PTMs) in regulating the condensation of RNA-binding proteins in the germ line. We compare and contrast thein vitroevidence that methylation inhibits phase separation of RNA binding proteins, with the extent to which these results apply to thein vivogerm line environment of several model systems. We also focus on the role of phosphorylation in modulating the dynamics of RNP granules in the germ line. Finally, we consider the gaps that exist in our understanding of the role of PTMs in regulating germ line RNP granules.
Interplay Between Microglia and Alzheimer’s Disease—Focus on the Most Relevant Risks: APOE Genotype, Sex and Age
Authors: Chen Yanting , Hong Tingting , Chen Feng , Sun Yuanhong , Wang Yan , Cui Lili
Published: April 2021

As the main immune cells of the central nervous system (CNS), microglia regulates normal development, homeostasis and general brain physiology. These functions put microglia at the forefront of CNS repair and recovery. Uncontrolled activation of microglia is related to the course of neurodegenerative diseases such as Alzheimer’s disease. It is clear that the classic pathologies of amyloid β (Aβ) and Tau are usually accompanied by the activation of microglia, and the activation of microglia also serves as an early event in the pathogenesis of AD. Therefore, during the occurrence and development of AD, the key susceptibility factors for AD—apolipoprotein E (APOE) genotype, sex and age—may further interact with microglia to exacerbate neurodegeneration. In this review, we discuss the role of microglia in the progression of AD related to the three risk factors for AD: APOE genotype, sex and aging. APOE-expressing microglia accumulates around Aβ plaques, and the presence of APOE4 may disrupt the phagocytosis of Aβ aggregates and aggravate neurodegeneration in Tau disease models. In addition, females have a high incidence of AD, and normal female microglia and estrogen have protective effects under normal conditions. However, under the influence of AD, female microglia seem to lose their protective effect and instead accelerate the course of AD. Aging, another major risk factor, may increase the sensitivity of microglia, leading to the exacerbation of microglial dysfunction in elderly AD. Obviously, in the role of microglia in AD, the three main risk factors of APOE, sex, and aging are not independent and have synergistic effects that contribute to the risk of AD. Moreover, new microglia can replace dysfunctional microglia after microglial depletion, which is a new promising strategy for AD treatment.
Central Thalamic-Medial Prefrontal Control of Adaptive Responding in the Rat: Many Players in the Chamber
Authors: Mair Robert G. , Francoeur Miranda J. , Gibson Brett M.
Published: April 2021

The medial prefrontal cortex (mPFC) has robust afferent and efferent connections with multiple nuclei clustered in the central thalamus. These nuclei are elements in large-scale networks linking mPFC with the hippocampus, basal ganglia, amygdala, other cortical areas, and visceral and arousal systems in the brainstem that give rise to adaptive goal-directed behavior. Lesions of the mediodorsal nucleus (MD), the main source of thalamic input to middle layers of PFC, have limited effects on delayed conditional discriminations, like DMTP and DNMTP, that depend on mPFC. Recent evidence suggests that MD sustains and amplifies neuronal responses in mPFC that represent salient task-related information and is important for detecting and encoding contingencies between actions and their consequences. Lesions of rostral intralaminar (rIL) and ventromedial (VM) nuclei produce delay-independent impairments of egocentric DMTP and DNMTP that resemble effects of mPFC lesions on response speed and accuracy: results consistent with projections of rIL to striatum and VM to motor cortices. The ventral midline and anterior thalamic nuclei affect allocentric spatial cognition and memory consistent with their connections to mPFC and hippocampus. The dorsal midline nuclei spare DMTP and DNMTP. They have been implicated in behavioral-state control and response to salient stimuli in associative learning. mPFC functions are served during DNMTP by discrete populations of neurons with responses related to motor preparation, movements, lever press responses, reinforcement anticipation, reinforcement delivery, and memory delay. Population analyses show that different responses are timed so that they effectively tile the temporal interval from when DNMTP trials are initiated until the end. Event-related responses of MD neurons during DNMTP are predominantly related to movement and reinforcement, information important for DNMTP choice. These responses closely mirror the activity of mPFC neurons with similar responses. Pharmacological inactivation of MD and adjacent rIL affects the expression of diverse action- and outcome-related responses of mPFC neurons. Lesions of MD before training are associated with a shift away from movement-related responses in mPFC important for DNMTP choice. These results suggest that MD has short-term effects on the expression of event-related activity in mPFC and long-term effects that tune mPFC neurons to respond to task-specific information.
A Reciprocal Excitatory Reflex Between Extensors Reproduces the Prolongation of Stance Phase in Walking Cats: Analysis on a Robotic Platform
Authors: Tanikawa Toyoaki , Masuda Yoichi , Ishikawa Masato
Published: April 2021

Spinal reflex is essential to the robust locomotion of quadruped animals. To investigate the reflex mechanisms, we developed a quadruped robot platform that emulates the neuromuscular dynamics of animals. The leg is designed to be highly back-drivable, and four Hill-type muscles and neuronal pathways are simulated on each leg using software. By searching for the reflex circuit that contributes to the generation of steady gait in cats through robotic experiments, we found a simple reflex circuit that could produce leg trajectories and a steady gait. In addition, this circuit can reproduce the experimental behavior observed in cats. As a major contribution of this study, we show that the underlying structure of the reflex circuit is the reciprocal coupling between extensor muscles via excitatory neural pathways. In the walking experiments on the robot, a steady gait and experimental behaviors of walking cats emerged from the reflex circuit without any central pattern generators. Furthermore, to take advantage of walking experiments using a neurophysiological robotic platform, we conducted experiments in which a part of the proposed reflex circuit was disconnected for a certain period of time during walking. The results showed that the prolongation of the stance phase caused by the reciprocal excitatory reflex contributed greatly to the generation of a steady gait.
A Cable-Driven Three-DOF Wrist Rehabilitation Exoskeleton With Improved Performance
Authors: Shi Ke , Song Aiguo , Li Ye , Li Huijun , Chen Dapeng , Zhu Lifeng
Published: April 2021

This paper developed a cable-driven three-degree-of-freedom (DOF) wrist rehabilitation exoskeleton actuated by the distributed active semi-active (DASA) system. Compared with the conventional cable-driven robots, the workspace of this robot is increased greatly by adding the rotating compensation mechanism and by optimizing the distribution of the cable attachment points. In the meanwhile, the efficiency of the cable tension is improved, and the parasitic force (the force acting on the joint along the limb) is reduced. Besides, in order to reduce the effects of compliant elements (e.g., cables or Bowden cables) between the actuators and output, and to improve the force bandwidth, we designed the DASA system composed of one geared DC motor and four magnetorheological (MR) clutches, which has low output inertia. A fast unbinding strategy is presented to ensure safety in abnormal conditions. A passive training algorithm and an assist-as-needed (AAN) algorithm were implemented to control the exoskeleton. Several experiments were conducted on both healthy and impaired subjects to test the performance and effectiveness of the proposed system for rehabilitation. The results show that the system can meet the needs of rehabilitation training for workspace and force-feedback, and provide efficient active and passive training.