bluuebunny/crossref_metadata_2025 huggingface dataset:
Shoreline Evolutionary Trends Along Calabrian Coasts: Causes and Classification
Authors: Foti Giandomenico , Barbaro Giuseppe , Barillà Giuseppina Chiara , Mancuso Pierluigi , Puntorieri Pierfabrizio
Published: March 2022

The issue of coastal erosion currently affects most of the world’s coastal territories. This erosion is generally caused by an alteration of coastal and river dynamics both due to the action of natural factors and to the increase in anthropogenic pressure, mainly observed in the second half of the last century after the end of the Second World War. In the future, this issue may be more affected by climate change. This paper describes the shoreline evolutionary trends at different time scale along the Calabrian coasts, a region in southern Italy, in over 50 sample areas. Calabria represents an interesting case study due to its geomorphological peculiarities and due to its considerable anthropogenic pressures, which have caused extensive erosive processes. In addition, this paper analyzes the main causes of these evolutionary trends and classifies them using a quick methodology based on a shoreline variation rate of a fixed area. This is an index-based methodology and is a part of a new generally index-based coastal risk assessment methodology, developed by the Mediterranea University of Reggio Calabria and the Calabria Region and which is currently in progress. The main result is that the sample areas in the erosion classes prevail over those in the advancement class for very long-term, long-term and middle-term time interval while for short-term and most recent time interval the sample areas in the advancement class prevail over those in the erosion classes.
The Effects of Selective Harvest on Exploited Population and Economic Benefits
Authors: Sun Peng , Yu Jie , Sun Runlong , Liu Guankui , Xi Xiaoyu , Tian Yongjun
Published: March 2022

The composition of catch is affected by exploited fishing gear and its selectivity, and long-term selective harvest induces the change in biological characters and economic value of exploited population. Stow net is the main fishing gear to capture commercially important fish species small yellow croaker (Larimichthys polyactis) in Haizhou Bay, China. Long-term stow net selective harvest affects both the biological characters and economic benefits of small yellow croaker. Therefore, an appropriate harvest scenario that can achieve the high economic benefits and the sustainable use of resource needs to be explored. In this study, we develop a bio-economic model for small yellow croaker and focus on different harvest scenarios for obtaining maximum economic benefit and sustainable utilization of resource. Our results indicate that the increase in mesh size has positive effects on the protection of small yellow croaker population, and optimal harvest scenario achieves the short- or long-term economic benefits to different stakeholders. Fishing with small mesh size gets high economic value in short-term, while fishing with large mesh size achieves better economic value and effectively protect small yellow croaker resource under long-term fishing pressure. This study provides evidence to balance the long-term economic benefits and sustainable utilization of fishery resource, and it also offers a basis for the scientific formulation of fishery policy.
Dynamic Desalination of Intruding Seawater After Construction of Cut-Off Walls in a Coastal Unconfined Aquifer
Authors: Zheng Tianyuan , Gao Mingpeng , Chang Qinpeng , Zheng Xilai , Walther Marc
Published: March 2022

Fresh groundwater resources in coastal regions are valuable but deteriorated by seawater intrusion. To prevent deterioration of the fresh groundwater resources, a common approach is to build cut-off walls. However, the construction of cut-off walls may trap a large amount of residual saltwater in the landward aquifer. This study explored the dynamic behavior and the desalination process of the intruding seawater after the construction of a cut-off wall, using a numerical model validated against a laboratory experiment. Field-scale simulations reveal that a fast saltwater repulsion process proceeds within a short period (100-150 days), while the retreat of the residual saltwater wedge is rather slow at the beginning. This is because the desalination process always starts first in the vertical direction. Meanwhile, the saltwater area significantly increases in the downstream of the cut-off wall. The amount of residual saltwater mainly depends on the depth and the hydraulic conductivity of the cut-off wall, while the retreat time is affected by the location of the wall. Although a deeper cut-off wall can enhance the removal of residual saltwater, the desalination effectiveness may notably decrease when the depth exceeds a certain value (25 m in the simulated scenarios). The desalination performance degrades dramatically when the hydraulic conductivity of the wall is greater than a certain threshold (8×10-7 m/s in the simulated cases). A near-complete removal of residual saltwater can be achieved within three years with optimal designs of the depth, location, and hydraulic conductivity of the cut-off wall.
A Substituted Diphenyl Amide Based Novel Scaffold Inhibits Staphylococcus aureus Virulence in a Galleria mellonella Infection Model
Authors: Mishra Biswajit , Khader Rajamohammed , Felix Lewis Oscar , Frate Marissa , Mylonakis Eleftherios , Meschwitz Susan , Fuchs Beth Burgwyn
Published: March 2022

Antimicrobial compounds can combat microbes through modulating host immune defense, inhibiting bacteria survival and growth, or through impeding or inhibiting virulence factors. In the present study, a panel of substituted diphenyl amide compounds previously found to disrupt bacterial quorum sensing were investigated and several were found to promote survival in the Galleria mellonella model when provided therapeutically to treat a Gram-positive bacterial infection from methicillin-resistant Staphylococcus aureus strain MW2. Out of 21 tested compounds, N-4-Methoxyphenyl-3-(4-methoxyphenyl)-propanamide (AMI 82B) was the most potent at disrupting S. aureus virulence and promoted 50% larvae survival at 120 and 96 h when delivered at 0.5 and 5 mg/Kg, respectively, compared to untreated controls (p < 0.0001). AMI 82B did not exhibit G. mellonella toxicity (LC50 > 144 h) at a delivery concentration up to 5 mg/Kg. Further assessment with mammalian cells suggest AMI 82B hemolytic effects against erythrocytes has an HL50 greater than the highest tested concentration of 64 μg/mL. Against HepG2 hepatic cells, AMI 82B demonstrated an LD50 greater than 64 μg/mL. AMI 82B lacked direct bacteria inhibition with a minimal inhibitory concentration that exceeds 64 μg/mL and no significant reduction in S. aureus growth curve at the same concentration. Assessment via qPCR revealed that AMI 82B significantly depressed quorum sensing genes agr, spa, and icaA (p < 0.05). Thus, AMI 82B therapeutic effect against S. aureus in the G. mellonella infection model is likely an influence on bacterial quorum sensing driven virulence factors and provides an interesting hit compound for this medically important pathogen.
Role of Efflux in Antibiotic Resistance of Achromobacter xylosoxidans and Achromobacter insuavis Isolates From Patients With Cystic Fibrosis
Authors: Chalhoub Hussein , Kampmeier Stefanie , Kahl Barbara C. , Van Bambeke Françoise
Published: March 2022

Achromobacter genus (including Achromobacter xylosoxidans, the most prevalent Achromobacter species in patients with cystic fibrosis) is poorly susceptible to most conventional antibiotics. Contribution of efflux by AxyABM, AxyXY-OprZ, and AxyEF-OprN and of target mutations were studied in clinical isolates of A. xylosoxidans and Achromobacter insuavis. Forty-one isolates longitudinally collected from 21 patients with CF were studied by whole-genome sequencing (WGS)-typing, determination of minimum inhibitory concentrations (MICs) of β-lactams, aminoglycosides, colistin, azithromycin, ciprofloxacin, chloramphenicol, and doxycycline, and expression (quantitative RT-PCR) and function (measure of the uptake of a fluorescent substrate) of efflux pumps. WGS-based typing resulted in 10 clusters comprising 2 or 3 isolates and 20 singletons. The efflux activity was high in strains with elevated MICs for amikacin or azithromycin. This work sheds a new light on the impact of efflux and target mutations in resistance of Achromobacter to several drugs.
Oligotrophic Growth of Nitrate-Dependent Fe2+-Oxidising Microorganisms Under Simulated Early Martian Conditions
Authors: Price Alex , Macey Michael C. , Pearson Victoria K. , Schwenzer Susanne P. , Ramkissoon Nisha K. , Olsson-Francis Karen
Published: March 2022

Nitrate-dependent Fe2+ oxidation (NDFO) is a microbially mediated process observed in many anaerobic, low-nutrient (oligotrophic) neutral–alkaline environments on Earth, which describes oxidation of Fe2+ to Fe3+ in tandem with microbial nitrate reduction. Evidence suggests that similar environments existed on Mars during the Noachian epoch (4.1–3.7 Ga) and in periodic, localised environments more recently, indicating that NDFO metabolism could have played a role in a potential early martian biosphere. In this paper, three NDFO microorganisms, Acidovorax sp. strain BoFeN1, Pseudogulbenkiania sp. strain 2002 and Paracoccus sp. strain KS1, were assessed for their ability to grow oligotrophically in simulated martian brines and in a minimal medium with olivine as a solid Fe2+ source. These simulant-derived media were developed from modelled fluids based on the geochemistry of Mars sample locations at Rocknest (contemporary Mars soil), Paso Robles (sulphur-rich soil), Haematite Slope (haematite-rich soil) and a Shergottite meteorite (common basalt). The Shergottite medium was able to support growth of all three organisms, while the contemporary Mars medium supported growth of Acidovorax sp. strain BoFeN1 and Pseudogulbenkiania sp. strain 2002; however, growth was not accompanied by significant Fe2+ oxidation. Each of the strains was also able to grow in oligotrophic minimal media with olivine as the sole Fe2+ source. Biomineralised cells of Pseudogulbenkiania sp. strain 2002 were identified on the surface of the olivine, representing a potential biosignature for NDFO microorganisms in martian samples. The results suggest that NDFO microorganisms could have thrived in early martian groundwaters under oligotrophic conditions, depending on the local lithology. This can guide missions in identifying palaeoenvironments of interest for biosignature detection. Indeed, biomineralised cells identified on the olivine surface provide a previously unexplored mechanism for the preservation of morphological biosignatures in the martian geological record.
The Current Landscape of Antibiotic Resistance of Salmonella Infantis in Italy: The Expansion of Extended-Spectrum Beta-Lactamase Producers on a Local Scale
Authors: Di Marcantonio Lisa , Romantini Romina , Marotta Francesca , Chiaverini Alexandra , Zilli Katiuscia , Abass Anna , Di Giannatale Elisabetta , Garofolo Giuliano , Janowicz Anna
Published: March 2022

Salmonella enterica serovar Infantis is one of the five main causes of human salmonellosis in the European Union (EU) and in recent years, has been increasingly reported to carry multiple antimicrobial resistance determinants, including extended-spectrum beta-lactamase (ESBL) genes. In our study, we used WGS-based tools to characterize S. Infantis strains circulating in the Abruzzo and Molise regions of Italy between 2017 and 2020 and compared this local dataset to the S. Infantis population present in Italy over the last two decades. Phylogenetic analyses demonstrated that the majority of strains isolated from poultry and turkeys from Abruzzo and Molise were closely related and belonged to one of the two main genetic clusters present in Italy, which were grouped predominantly as ESBL-producing strains that harbored pESI-like plasmid. We showed that 60% of the local strains carried multiple antibiotic resistance genes, including ESBL gene blaCTX–M–1 as well as aadA1, dfrA1, dfrA14, sul1, and tet(A) genes present on the pESI-like megaplasmid. The analysis of strains from Abruzzo and Molise and the publicly available Italian S. Infantis sequences revealed a dramatic increase in the number of identified AMR genes in the strains isolated after 2011. Moreover, the number of strains resistant to five or more antibiotic classes increased from 20–80% in the last decade likely due to the acquisition of the megaplasmid. The persistence of the ESBL-producing and the multidrug-resistant (MDR) clone of S. Infantis in poultry populations in Italy and in Europe requires rapid and efficient intervention strategies to prevent further expansion of the clone.
Global Grassland Diazotrophic Communities Are Structured by Combined Abiotic, Biotic, and Spatial Distance Factors but Resilient to Fertilization
Authors: Nepel Maximilian , Angel Roey , Borer Elizabeth T. , Frey Beat , MacDougall Andrew S. , McCulley Rebecca L. , Risch Anita C. , Schütz Martin , Seabloom Eric W. , Woebken Dagmar
Published: March 2022

Grassland ecosystems cover around 37% of the ice-free land surface on Earth and have critical socioeconomic importance globally. As in many terrestrial ecosystems, biological dinitrogen (N2) fixation represents an essential natural source of nitrogen (N). The ability to fix atmospheric N2 is limited to diazotrophs, a diverse guild of bacteria and archaea. To elucidate the abiotic (climatic, edaphic), biotic (vegetation), and spatial factors that govern diazotrophic community composition in global grassland soils, amplicon sequencing of the dinitrogenase reductase gene—nifH—was performed on samples from a replicated standardized nutrient [N, phosphorus (P)] addition experiment in 23 grassland sites spanning four continents. Sites harbored distinct and diverse diazotrophic communities, with most of reads assigned to diazotrophic taxa within the Alphaproteobacteria (e.g., Rhizobiales), Cyanobacteria (e.g., Nostocales), and Deltaproteobacteria (e.g., Desulforomonadales) groups. Likely because of the wide range of climatic and edaphic conditions and spatial distance among sampling sites, only a few of the taxa were present at all sites. The best model describing the variation among soil diazotrophic communities at the OTU level combined climate seasonality (temperature in the wettest quarter and precipitation in the warmest quarter) with edaphic (C:N ratio, soil texture) and vegetation factors (various perennial plant covers). Additionally, spatial variables (geographic distance) correlated with diazotrophic community variation, suggesting an interplay of environmental variables and spatial distance. The diazotrophic communities appeared to be resilient to elevated nutrient levels, as 2–4 years of chronic N and P additions had little effect on the community composition. However, it remains to be seen, whether changes in the community composition occur after exposure to long-term, chronic fertilization regimes.
Orf Virus Detection in the Saliva and Milk of Dairy Goats
Authors: Ma Wentao , Pang Ming , Lei Xinyu , Wang Zishuo , Feng Hao , Li Shaofei , Chen Dekun
Published: March 2022

Orf is a zoonotic and highly contagious disease caused by Orf virus (ORFV) infection. Orf outbreaks in sheep and goats usually lead to high culling rate and mortality in newborn kids and lambs, posing a great threat to the development of goat and sheep industry. Human Orf occurs via direct contact with infected animals or fomites. While this disease is traditionally thought to spread through direct contact, whether other transmission routes exist remains unclear. Herein, we report the detection of ORFV in the saliva and milk of dairy goats without clinical Orf symptoms. Further analyses showed that these ORFV are infectious, as they can induce characteristic cytopathic changes in primary mammary and lip cells. Importantly, these ORFV can induce typical Orf lesions after inoculation in ORFV-free dairy goats. This is the first study showing that live, infectious ORFV can be isolated from the saliva and milk of asymptomatic goats, highlighting novel potential transmission routes of ORFV. These findings provide a novel idea for the prevention and control of Orf spread.
Glutathione Synthesis Regulated by CtrA Protects Ehrlichia chaffeensis From Host Cell Oxidative Stress
Authors: Yan Jiaqi , Liang Qi’an , Chai Zhouyi , Duan Nan , Li Xiaoxiao , Liu Yajing , Yang Nan , Li Meifang , Jin Yongxin , Bai Fang , Wu Weihui , Cheng Zhihui
Published: March 2022

Ehrlichia chaffeensis, a small Gram-negative obligatory intracellular bacterium, infects human monocytes or macrophages, and causes human monocytic ehrlichiosis, one of the most prevalent, life-threatening emerging zoonoses. Reactive oxygen species are produced by the host immune cells in response to bacterial infections. The mechanisms exploited by E. chaffeensis to resist oxidative stress have not been comprehensively demonstrated. Here, we found that E. chaffeensis encodes two functional enzymes, GshA and GshB, to synthesize glutathione that confers E. chaffeensis the oxidative stress resistance, and that the expression of gshA and gshB is upregulated by CtrA, a global transcriptional regulator, upon oxidative stress. We found that in E. chaffeensis, the expression of gshA and gshB was upregulated upon oxidative stress using quantitative RT-PCR. Ehrlichia chaffeensis GshA or GshB restored the ability of Pseudomonas aeruginosa GshA or GshB mutant to cope with oxidative stress, respectively. Recombinant E. chaffeensis CtrA directly bound to the promoters of gshA and gshB, determined with electrophoretic mobility shift assay, and activated the expression of gshA and gshB determined with reporter assay. Peptide nucleic acid transfection of E. chaffeensis, which reduced the CtrA protein level, inhibited the oxidative stress-induced upregulation of gshA and gshB. Our findings provide insights into the function and regulation of the two enzymes critical for E. chaffeensis resistance to oxidative stress and may deepen our understanding of E. chaffeensis pathogenesis and adaptation in hosts.
Role of Ectomycorrhizal Symbiosis Behind the Host Plants Ameliorated Tolerance Against Heavy Metal Stress
Authors: Chot Eetika , Reddy Mondem Sudhakara
Published: March 2022

Soil heavy metal (HM) pollution, which arises from natural and anthropogenic sources, is a prime threat to the environment due to its accumulative property and non-biodegradability. Ectomycorrhizal (ECM) symbiosis is highly efficient in conferring enhanced metal tolerance to their host plants, enabling their regeneration on metal-contaminated lands for bioremediation programs. Numerous reports are available regarding ECM fungal potential to colonize metal-contaminated lands and various defense mechanisms of ECM fungi and plants against HM stress separately. To utilize ECM–plant symbiosis successfully for bioremediation of metal-contaminated lands, understanding the fundamental regulatory mechanisms through which ECM symbiosis develops an enhanced metal tolerance in their host plants has prime importance. As this field is highly understudied, the present review emphasizes how plant’s various defense systems and their nutrient dynamics with soil are affected by ECM fungal symbiosis under metal stress, ultimately leading to their host plants ameliorated tolerance and growth. Overall, we conclude that ECM symbiosis improves the plant growth and tolerance against metal stress by (i) preventing their roots direct exposure to toxic soil HMs, (ii) improving plant antioxidant activity and intracellular metal sequestration potential, and (iii) altering plant nutrient uptake from the soil in such a way to enhance their tolerance against metal stress. In some cases, ECM symbiosis promotes HM accumulation in metal stressed plants simultaneous to improved growth under the HM dilution effect.
Rapid and Routine Molecular Typing Using Multiplex Polymerase Chain Reaction and MinION Sequencer
Authors: Liao Yu-Chieh , Wu Han-Chieh , Liou Ci-Hong , Lauderdale Tsai-Ling Yang , Huang I-Wen , Lai Jui-Fen , Chen Feng-Jui
Published: March 2022

Molecular typing is an essential tool that has been extensively applied in laboratories as well as in clinical settings. Next-generation sequencing technologies promise high-throughput and cost-effective molecular applications; however, the accessibility of these technologies is limited due to the high capital cost. Oxford Nanopore Technologies (ONT) offers a MinION device with the advantages of real-time data analysis, rapid library preparation, and low cost per test. However, the advantages of the MinION device are often overshadowed by its lower raw accuracy. Herein, we present a concise multilocus sequence typing protocol of Staphylococcus aureus using multiplex polymerase chain reaction and Rapid Barcoding Kit for barcoding and MinION device for sequencing. Moreover, to clarify the effects of carryover DNA on tasks that require high sequence accuracy, we used the MinION flow cell in successive runs of washing and reusing. Our results revealed that the MinION flow cell could achieve accurate typing of a total of 467 samples with 3,269 kilobase-long genes within a total of 5 runs. This thus demonstrates the effectiveness of a portable nanopore MinION sequencer in providing accurate, rapid, and routine molecular typing.
Decoding Genetic Markers of Multiple Phenotypic Layers Through Biologically Constrained Genome-To-Phenome Bayesian Sparse Regression
Authors: Deprez Marie , Moreira Julien , Sermesant Maxime , Lorenzi Marco
Published: March 2022

The applicability of multivariate approaches for the joint analysis of genomics and phenomics information is currently limited by the lack of scalability, and by the difficulty of interpreting the related findings from a biological perspective. To tackle these limitations, we present Bayesian Genome-to-Phenome Sparse Regression (G2PSR), a novel multivariate regression method based on sparse SNP-gene constraints. The statistical framework of G2PSR is based on a Bayesian neural network, were constraints on SNPs-genes associations are integrated by incorporating a priori knowledge linking variants to their respective genes, to then reconstruct the phenotypic data in the output layer. Interpretability is promoted by inducing sparsity on the genes through variational dropout, allowing to estimate the uncertainty associated with each gene, and related SNPs, in the reconstruction task. Ultimately, G2PSR is conceived to prevent multiple testing correction and to assess the combined effect of SNPs, thus increasing the statistical power in detecting genome-to-phenome associations. The effectiveness of G2PSR was demonstrated on synthetic and real data, with respect to state-of-the-art methods based on group-wise sparsity constraints. The application on real data consisted in an imaging-genetics analysis on the Alzheimer’s Disease Neuroimaging Initiative data, relating SNPs from more than 3,500 genes to clinical and multi-variate brain volumetric information. The experimental results show that our method can provide accurate selection of relevant genes in dataset with large SNPs-to-samples ratio, thus overcoming the main limitations of current genome-to-phenome association methods.
Proteomic Analysis of Serum Lysine Acetylation in Uyghur Patients With T2DM
Authors: Yin Liang , Feng Gang , Huang Chun , Cai Weijuan
Published: March 2022

Lysine acetylation is a reversible modification process after protein translation, which plays a key regulatory role in various metabolic diseases such as diabetes. The prevalence of type 2 diabetes mellitus (T2DM) in the Uyghur population is high, but the acetylation status of proteomics in Uyghur with T2DM is still unclear. Herein, we performed a quantitative proteomic study of lysine acetylation in T2DM patients using Tandem Mass Tags (TMTs) labeling, acetylation enrichment techniques, and high-resolution liquid chromatography-tandem mass spectrometry. We quantified 422 acetylation sites on 120 proteins, of which 347 sites of 103 proteins contained quantitative information. Compared with the control, we found that a total of eight acetylated sites within proteins were significantly differentially expressed with three upregulated and five downregulated, including histones H4 and H3.3C. Meanwhile, we completed bioinformatics analysis, including protein annotation, functional classification, functional enrichment, and cluster analysis, based on functional enrichment. In addition, the mRNA (ApoB-100, histones H4 and H3.3C) and protein (histones H4 and H3.3C) levels were verified through 60 samples. Besides, we also performed histone H4 chromatin immunoprecipitation analysis at the level of INS-1 cells. These could be potentially useful markers for the prediction of prediabetes and also provided a basis for the pathogenesis of T2DM.
The Tudor Domain-Containing Protein, Kotsubu (CG9925), Localizes to the Nuage and Functions in piRNA Biogenesis in D. melanogaster
Authors: Lim Lin-Xenia , Isshiki Wakana , Iki Taichiro , Kawaguchi Shinichi , Kai Toshie
Published: March 2022

Silencing of transposable elements (TEs) by Piwi-interacting RNAs (piRNAs) is crucial for maintaining germline genome integrity and fertility in animals. To repress TEs, PIWI clade Argonaute proteins cooperate with several Tudor domain-containing (Tdrd) proteins at membraneless perinuclear organelles, called nuage, to produce piRNAs to repress transposons. Here, we identify and characterize Kotsubu (Kots), one of the Drosophila Tudor domain-containing protein-1 (Tdrd1) orthologs, encoded by the CG9925 gene, that localizes to the nuage in gonads. We further show the dynamic localization of Kots in the male germline, where it shows perinuclear signals in spermatogonia but forms large cytoplasmic condensates in the spermatocytes that overlap with components of piNG-body, a nuage-associated organelle. The loss of kots results in a notable upregulation of stellate and a corresponding reduction in the suppressor of stellate piRNAs in the mutants. Furthermore, a moderate yet significant reduction of other piRNAs was observed in kots mutant testes. Taken together, we propose that Kots functions in the piRNA pathway, predominantly in the male germline by forming discrete cytoplasmic granules.
Facial Stimulation Induces Long-Term Potentiation of Mossy Fiber-Granule Cell Synaptic Transmission via GluN2A-Containing N-Methyl-D-Aspartate Receptor/Nitric Oxide Cascade in the Mouse Cerebellum
Authors: Lu Di , Wan Peng , Liu Yang , Jin Xian-Hua , Chu Chun-Ping , Bing Yan-Hua , Qiu De-Lai
Published: March 2022

Long-term synaptic plasticity in the cerebellar cortex is a possible mechanism for motor learning. Previous studies have demonstrated the induction of mossy fiber-granule cell (MF-GrC) synaptic plasticity under in vitro and in vivo conditions, but the mechanisms underlying sensory stimulation-evoked long-term synaptic plasticity of MF-GrC in living animals are unclear. In this study, we investigated the mechanism of long-term potentiation (LTP) of MF-GrC synaptic transmission in the cerebellum induced by train of facial stimulation at 20 Hz in urethane-anesthetized mice using electrophysiological recording, immunohistochemistry techniques, and pharmacological methods. Blockade of GABAA receptor activity and repetitive facial stimulation at 20 Hz (240 pulses) induced an LTP of MF-GrC synapses in the mouse cerebellar cortical folium Crus II, accompanied with a decrease in paired-pulse ratio (N2/N1). The facial stimulation-induced MF-GrC LTP was abolished by either an N-methyl-D-aspartate (NMDA) receptor blocker, i.e., D-APV, or a specific GluNR2A subunit-containing NMDA receptor antagonist, PEAQX, but was not prevented by selective GluNR2B or GluNR2C/D subunit-containing NMDA receptor blockers. Application of GNE-0723, a selective and brain-penetrant-positive allosteric modulator of GluN2A subunit-containing NMDA receptors, produced an LTP of N1, accompanied with a decrease in N2/N1 ratio, and occluded the 20-Hz facial stimulation-induced MF-GrC LTP. Inhibition of nitric oxide synthesis (NOS) prevented the facial stimulation-induced MF-GrC LTP, while activation of NOS produced an LTP of N1, with a decrease in N2/N1 ratio, and occluded the 20-Hz facial stimulation-induced MF-GrC LTP. In addition, GluN2A-containing NMDA receptor immunoreactivity was observed in the mouse cerebellar granular layer. These results indicate that facial stimulation at 20 Hz induced LTP of MF-GrC synaptic transmission via the GluN2A-containing NMDA receptor/nitric oxide cascade in mice. The results suggest that the sensory stimulation-evoked LTP of MF-GrC synaptic transmission in the granular layer may play a critical role in cerebellar adaptation to native mossy fiber excitatory inputs and motor learning behavior in living animals.
Facilitators and Barriers to Dementia Assessment and Diagnosis: Perspectives From Dementia Experts Within a Global Health Context
Authors: Bernstein Sideman Alissa , Al-Rousan Tala , Tsoy Elena , Piña Escudero Stefanie D. , Pintado-Caipa Maritza , Kanjanapong Suchanan , Mbakile-Mahlanza Lingani , Okada de Oliveira Maira , De la Cruz-Puebla Myriam , Zygouris Stelios , Ashour Mohamed Aya , Ibrahim Hany , Goode Collette A. , Miller Bruce L. , Valcour Victor , Possin Katherine L.
Published: March 2022

Objectives

Dementia poses one of the greatest global health challenges, affecting 50 million people worldwide. With 10 million new cases each year, dementia is a growing burden, particularly in low- and middle-income countries (LMIC). This study aimed to identify the facilitators and barriers to providing quality dementia assessment and care in LMICs from a global health perspective.

Methods/Design

A qualitative semi-structured interview study with 20 dementia expert healthcare providers from 19 countries. To be included, providers had to: practice dementia assessment or care in LMICs where the population over age 60 is projected to more than double by 2050 and be recognized as a leading dementia expert in the region based on position, research publications, and/or policy leadership. Interviews were analyzed by a multidisciplinary team of researchers using thematic analysis.

Results

Barriers to dementia assessment and care included stigma about dementia, poor patient engagement in and access to healthcare, inadequate linguistic and cultural validation, limited dementia capable workforce, competing healthcare system priorities, and insufficient health financing. Facilitators included the rise in dementia awareness campaigns, dementia training for general practitioners, availability of family support and family caregivers, and national and international collaborations including coordinated policy efforts and involvement in international research initiatives.

Conclusions

Findings from this study provide insights for prioritizing dementia assessment and care capacity-building in LMICs as a global health priority and for tailored public health approaches to strengthen dementia assessment and care at the individual, community, national, and multi-national levels.
Virtuous and Vicious Cycles of Arm Use and Function Post-stroke
Authors: Ballester Belen R. , Winstein Carolee , Schweighofer Nicolas
Published: March 2022

Large doses of movement practice have been shown to restore upper extremities' motor function in a significant subset of individuals post-stroke. However, such large doses are both difficult to implement in the clinic and highly inefficient. In addition, an important reduction in upper extremity function and use is commonly seen following rehabilitation-induced gains, resulting in “rehabilitation in vain”. For those with mild to moderate sensorimotor impairment, the limited spontaneous use of the more affected limb during activities of daily living has been previously proposed to cause a decline of motor function, initiating a vicious cycle of recovery, in which non-use and poor performance reinforce each other. Here, we review computational, experimental, and clinical studies that support the view that if arm use is raised above an effective threshold, one enters a virtuous cycle in which arm use and function can reinforce each other via self-practice in the wild. If not, one enters a vicious cycle of declining arm use and function. In turn, and in line with best practice therapy recommendations, this virtuous/vicious cycle model advocates for a paradigm shift in neurorehabilitation whereby rehabilitation be embedded in activities of daily living such that self-practice with the aid of wearable technology that reminds and motivates can enhance paretic limb use of those who possess adequate residual sensorimotor capacity. Altogether, this model points to a user-centered approach to recovery post-stroke that is tailored to the participant's level of arm use and designed to motivate and engage in self-practice through progressive success in accomplishing meaningful activities in the wild.
Breathing Abnormalities During Sleep and Wakefulness in Rett Syndrome: Clinical Relevance and Paradoxical Relationship With Circulating Pro-oxidant Markers
Authors: Leoncini Silvia , Signorini Cinzia , Boasiako Lidia , Scandurra Valeria , Hayek Joussef , Ciccoli Lucia , Rossi Marcello , Canitano Roberto , De Felice Claudio
Published: March 2022

Background

Breathing abnormalities are common in Rett syndrome (RTT), a pervasive neurodevelopmental disorder almost exclusively affecting females. RTT is linked to mutations in the methyl-CpG-binding protein 2 (MeCP2) gene. Our aim was to assess the clinical relevance of apneas during sleep-wakefulness cycle in a population with RTT and the possible impact of apneas on circulating oxidative stress markers.

Methods

Female patients with a clinical diagnosis of typical RTT (n = 66), MECP2 gene mutation, and apneas were enrolled (mean age: 12.5 years). Baseline clinical severity, arterial blood gas analysis, and red blood cell count were assessed. Breathing was monitored during the wakefulness and sleep states (average recording time: 13 ± 0.5 h) with a portable polygraphic screening device. According to prevalence of breath holdings, the population was categorized into the wakefulness apnea (WA) and sleep apnea (SA) groups, and apnea-hypopnea index (AHI) was calculated. The impact of respiratory events on oxidative stress was assessed by plasma and intra-erythrocyte non-protein-bound iron (P-NPBI and IE-NPBI, respectively), and plasma F2-isoprostane (F2-IsoP) assays.

Results

Significant prevalence of obstructive apneas with values of AHI > 15 was present in 69.7% of the population with RTT. The group with SA showed significantly increased AHI values > 15 (p = 0.0032), total breath holding episodes (p = 0.007), and average SpO2 (p = 0.0001) as well as lower nadir SpO2 (p = 0.0004) compared with the patients with WAs. The subgroups of patients with WA and SA showed no significant differences in arterial blood gas analysis variables (p > 0.089). Decreased mean cell hemoglobin (MCH) (p = 0.038) was observed in the group with WAs. P-NPBI levels were significantly higher in the group with WA than in that with SAs (p = 0.0001). Stepwise multiple linear regression models showed WA being related to nadir SpO2, average SpO2, and P-NPBI (adjusted R2 = 0.613, multiple correlation coefficient = 0.795 p < 0.0001), and P-NPBI being related to average SpO2, blood PaCO2, red blood cell mean corpuscular volume (MCV), age, and topiramate treatment (adjusted R2 = 0.551, multiple correlation coefficient = 0.765, p < 0.0001).

Conclusion

Our findings indicate that the impact of apneas in RTT is uneven according to the sleep-wakefulness cycle, and that plasma redox active iron represents a potential novel therapeutic target.
Eye Position Shifts Body Sway Under Foot Dominance Bias in the Absence of Visual Feedback
Authors: Tamaru Yoshiki , Matsugi Akiyoshi
Published: March 2022

Purpose

The purpose of this study was to investigate whether information on extraocular muscle proprioception without visual information affects postural control.

Methods

Thirty-five healthy young volunteers participated in the study. Postural control outcomes included the center of pressure (CoP) for static standing, the total length of the sway of the CoP (LNG), and the sway area (SA), as well as the mean CoP in the mediolateral and anteroposterior directions. The following five eye-fixing positions were used: eye-up (E-Up), eye-down (E-Down), eye-right (E-Right), eye-left (E-Left), and eye-center (Center eye position). One-way ANOVA and Bonferroni correction was performed for statistical processing. Electrooculograms were recorded to detect eye orientation errors, measured with the eyes closed.

Results

The results of this study showed no significant difference between the LNG and SA results when comparing respective eye positions (E-up, E-down, E-right, E-left) relative to E-Center (control). However, the average CoP was shifted to the right at E-Up, E-Down, and E-Left.

Conclusion

These findings indicate that postural control may be affected by eye-body coordination depending on the position of the eyes, even without visual information.
The Jrecan Device: Preclinical Data of a Novel Thrombectomy Device in Acute Thromboembolism Model of Beagle Dogs
Authors: Li Chen , Zhou Ji , Zhang Yi-Qun , Lv Jin , Zhang Ying-Ying , Qiu Han-Cheng , Liu Ao-Fei , Jiang Wei-Jian
Published: March 2022

Objective

The aim of this study is to investigate the safety and efficiency of a Jrecan® flow restoration system, a novel thrombectomy device, in an arterial thromboembolic occlusion model of Beagle dogs.

Methods

A total of 12 Beagle dogs with acute thromboembolism were randomized to receive mechanical thrombectomy with either Jrecan® flow restoration device or TrevoTM PROVUE Device (2:1). The efficacy and safety of the two devices, including recanalization rate, the presence of distal embolism, vasospasm, vessel perforation, and vessel injuries were evaluated through DSA and microscopic examination.

Result

A 100% recanalization rate (mTICI 2b/3) was achieved in both groups. Endothelial and subendothelial injuries occurred in all target vessels. Focal disruption of internal elastic lamina was observed in 4 cases. The mean vessel injury score of the Jrecan® group was 1.16 ± 0.48, significantly lower than that of the TrevoTM group (1.54 ± 0.8) (P < 0.001).

Conclusion

The Jrecan® and TrevoTM devices demonstrated an equally high recanalization rate in Beagle dogs with acute thromboembolism. However, histological findings revealed that the Jrecan® stent seemed to be safer than the TrevoTM device during clot retrieval, which might be related to a more appropriate radial force provided by the Jrecan® stent that resulted from its wider cell design.
Docosahexaenoic and Eicosapentaenoic Intervention Modifies Plasma and Erythrocyte Omega-3 Fatty Acid Profiles But Not the Clinical Course of Children With Autism Spectrum Disorder: A Randomized Control Trial
Authors: de la Torre-Aguilar Maria Jose , Gomez-Fernandez Antonio , Flores-Rojas Katherine , Martin-Borreguero Pilar , Mesa María Dolores , Perez-Navero Juan Luis , Olivares Mónica , Gil Angel , Gil-Campos Mercedes
Published: March 2022

Background

The pathogenesis of autism spectrum disorder (ASD) is under investigation and one of the main alterations relates to the metabolic and inflammatory system dysfunctions. Indeed, based on a possible deficit of omega-3 fatty acids (FAs) of patients with ASD and looking for an anti-inflammatory effect, dietary supplements with omega-3 fatty acids have been proposed. We aimed to evaluate differences in plasma and erythrocyte FA profiles and plasma cytokines in patients with infantile ASD after supplementation with docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids or placebo and both compared at baseline with a reference healthy group.

Methods

A double-blind, randomized placebo-controlled intervention with DHA/EPA for 6 months was carried out in 54 children between 2 and 6 years diagnosed with ASD. They were selected and randomly assigned into two groups: 19 children received 800 mg/day of DHA and 25 mg/day of EPA, or placebo. In addition, another reference group of 59 healthy children of the same age was included. Plasma lipids and cytokines, and FA profiles in plasma and erythrocytes were measured at baseline and after 6 months of treatment in ASD children, and at baseline in the reference group.

Results

There were no differences in demographic, anthropometric characteristics, and omega-3 intake between the healthy reference group and the ASD children at baseline. Children with ASD showed the higher plasma percentages of palmitic acid and total saturated FA and lower total omega-6 polyunsaturated FA (PUFA) compared with healthy children. An increased level of DHA and reduced EPA level in erythrocytes were detected in the ASD group vs. the reference group. After 6 months of treatment, the ASD group that received DHA enriched product significantly increased the plasma and erythrocyte percentages of DHA, but no differences were observed in the clinical test scores and other parameters as plasma cytokines between the two groups of ASD related to the intervention.

Conclusion

Spanish children with ASD exhibit an appropriate omega-3 FA status in plasma and erythrocytes. Neither a clinical improvement of ASD children nor a better anti-inflammatory or fatty acid state has been found after an intervention with DHA/EPA for 6 months. So, the prescription of n-3 LC-PUFA and other dietary supplements in ASD should be only indicated after a confirmed alteration of FA metabolism or omega-3 LC-PUFA deficiency evaluated by specific erythrocyte FA.

Clinical Trial Registration

[www.ClinicalTrials.gov], identifier [NCT03620097].
Associations of Ready-to-Eat Cereal Consumption and Income With Dietary Outcomes: Results From the National Health and Nutrition Examination Survey 2015–2018
Authors: Smith Jessica , Jain Neha , Normington James , Holschuh Norton , Zhu Yong
Published: March 2022

Background

Ready-to-eat (RTE) cereal has been associated with higher diet quality but it is not known if this association differs by income.

Objective

To investigate the association of RTE cereal with dietary outcomes in a US population stratified by income [measured using the poverty-to-income ratio (PIR)].

Methods

Data from children 2–18 years (n = 5,028) and adults 19 years and older (n = 9,813) with 24-h dietary recalls from the cross-sectional, US nationally-representative 2015–2016 and 2017–2018 National Health and Nutrition Examination Surveys (NHANES) were used in a multivariable linear model that included cereal eating status (based on day 1 24 h dietary recall), PIR category (Low-PIR <1.85; Mid-PIR 1.85–3.50; High-PIR >3.50) and their interaction. PIR is based on the ratio of the family household income to the poverty level set by the US Department of Health and Human Services and higher PIR values indicate higher household income.

Results

For children, there were positive associations between RTE cereal consumption and nutrient (e.g., iron, calcium, fiber, potassium and vitamin D, p < 0.001) and food group (e.g., whole grain and dairy, p < 0.001) intake and 2015-HEI (p < 0.0001) but no association with PIR or RTE cereal-PIR interaction. For adults, PIR category was positively associated with the intake of nutrients (e.g., fiber, magnesium, potassium, and vitamin C, p < 0.001) as was RTE cereal consumption (e.g., fiber, calcium, vitamin D, potassium, vitamin B12, among others, p < 0.001). Both PIR and RTE cereal were positively associated with whole grain, dairy, and fruit (p < 0.001) and 2015-HEI (p < 0.0001) for adults. We also found a significant interaction between PIR and RTE cereal for adults for iron, phosphorus, B vitamins, and dairy (p < 0.001). RTE cereal contributed to one quarter or more of daily intake, across all age and PIR groups, for several B vitamins, iron, zinc, and whole grains. Added sugar intake was not associated with RTE cereal consumption in either children or adults.

Conclusion

RTE cereal was associated with improved dietary outcomes, including increased intake of under-consumed nutrients, increased intake of recommended food groups, and higher diet quality, at all income levels. This work can help inform future dietary recommendations.
Nuts as a Part of Dietary Strategy to Improve Metabolic Biomarkers: A Narrative Review
Authors: Khalili Leila , A-Elgadir Thoraya Mohamed Elhassan , Mallick Ayaz Khurram , El Enshasy Hesham Ali , Sayyed R. Z.
Published: March 2022

Background

Nuts are in the spotlight because of their association with improved health outcomes. We aimed to summarize the findings of previous studies to evaluate the impact of nuts consumption on glycaemic and lipid profile, inflammation, and oxidative stress.

Methods

Electronic searches for observational and intervention studies were undertaken in PubMed, Embase, Web of Science, and Science Direct until 2022 for searching the studies aiming the application of different types of nuts and the beneficial effects of nuts in improving glycemia, dyslipidemia, inflammation, and oxidative stress.

Results

Results from 56 interventional, 9 narrative and 3 systematic reviews, and 12 meta-analysis studies, aiming at the evaluating beneficial effects of different types of nuts on metabolic markers, showed that nut consumption could improve metabolic markers, including glycaemic factors, lipid profile, and inflammatory and oxidative stress parameters in both healthy and individuals with metabolic disorders in a type-, dose- and duration-dependent manner. According to their unique nutrient components, nuts can be known as a part of a healthy diet, resulting in improved metabolic biomarkers.

Conclusion

Considering the efficacy of nuts in improving metabolic markers, incorporation of, incorporating nuts the effectiveness of nuts in improving metabolic markers, incorporating nuts in the diet may prevent the incidence or aggravation of chronic metabolic diseases. Considering the health benefits of the nuts' components, including essential micronutrients, if consumed in the appropriate dose and duration to provide the necessary amount of effective micronutrients to improve health, we will see an improvement in metabolic factors. At the same time, more research is required to determine the optimal type, dose, and duration of nut intervention with regards to metabolic control and reducing the risk of developing metabolic disorders.
Integrated Multi-Omics Analysis Identified PTPRG and CHL1 as Key Regulators of Immunophenotypes in Clear Cell Renal Cell Carcinoma(ccRCC)
Authors: Zeng Xing , Li Le , Hu Zhiquan , Peng Dan
Published: March 2022

Despite the increasing importance and status of immune checkpoint blockade (ICB), little is known about the underlying molecular mechanisms determining the target clear cell renal cell carcinoma (ccRCC) population. In this study, we screened out 6 immune cells strongly correlated with expression levels of PD-L1 and IFN-γ based on the ccRCC samples extracted from GSE and TCGA data sets. By performing unsupervised clustering and lasso regression analysis, we grouped the ccRCC into 4 clusters and selected the two most distinct sub-clusters for further investigation—cluster A1 and B1. Next, we compared the two clusters in terms of mRNA, somatic mutations, copy number variations, DNA methylation, miRNA, lncRNA and constructed the differentially expressed genes (DEGs) hub by combing together the previous results at levels of DNA methylation, miRNA, and lncRNA. PTPRG and CHL1 were identified as key nodes in the regulation hub of immunophenotypes in ccRCC patients. Finally, we established the prognosis model by using Lasso-Cox regression and Kaplan–Meier analysis, recognizing WNT2, C17orf66, and PAEP as independent significant risk factors while IRF4 as an independent protective factor.