bluuebunny/crossref_metadata_2025 huggingface dataset:
Thinking of Fish Population Discrimination: Population Average Phenotype vs. Population Phenotypes
Authors: Vasconcelos Joana , Jurado-Ruzafa Alba , Otero-Ferrer José Luis , Lombarte Antoni , Riera Rodrigo , Tuset Víctor M.
Published: October 2021

The genetic polymorphism and phenotypic variation are key in ecology and evolution. The morphological variability of the contour of fish otoliths has been extensively used for the delimitation of stocks. These studies are conventionally based on average phenotype using elliptic Fourier analysis and lineal discriminant analysis as classifier. Considering new analytical options, such as the wavelet transform and non-parametric algorithms, we here analyzed the otolith shape ofTrachurus picturatus(blue jack mackerel) from mainland Portugal, Madeira, and the Canaries. We explore the phenotypic variation throughout a latitudinal gradient, establish a hypothesis to explain this variability based on the reaction norms, and determine how the use of average phenotype and/or morphotypes influences in the delimitation of stocks. Four morphotypes were identified in all regions, with an increase of phenotypes in warmer waters. The findings demonstrated that stocks were clearly separated with classification rates over 90%. The use of morphotypes, revealed seasonal variations in their frequencies and per region. The presence of shared phenotypes in different proportions among fishing grounds may open new management approaches in migratory species. These results show the importance of the phenotypic diversity in fisheries management.
Underwater Sound Propagation Modeling in a Complex Shallow Water Environment
Authors: Oliveira Tiago C. A. , Lin Ying-Tsong , Porter Michael B.
Published: October 2021

Three-dimensional (3D) effects can profoundly influence underwater sound propagation in shallow-water environments, hence, affecting the underwater soundscape. Various geological features and coastal oceanographic processes can cause horizontal reflection, refraction, and diffraction of underwater sound. In this work, the ability of a parabolic equation (PE) model to simulate sound propagation in the extremely complicated shallow water environment of Long Island Sound (United States east coast) is investigated. First, the 2D and 3D versions of the PE model are compared with state-of-the-art normal mode and beam tracing models for two idealized cases representing the local environment in the Sound: (i) a 2D 50-m flat bottom and (ii) a 3D shallow water wedge. After that, the PE model is utilized to model sound propagation in three realistic local scenarios in the Sound. Frequencies of 500 and 1500 Hz are considered in all the simulations. In general, transmission loss (TL) results provided by the PE, normal mode and beam tracing models tend to agree with each other. Differences found emerge with (1) increasing the bathymetry complexity, (2) expanding the propagation range, and (3) approaching the limits of model applicability. The TL results from 3D PE simulations indicate that sound propagating along sand bars can experience significant 3D effects. Indeed, for the complex shallow bathymetry found in some areas of Long Island Sound, it is challenging for the models to track the interference effects in the sound pattern. Results emphasize that when choosing an underwater sound propagation model for practical applications in a complex shallow-water environment, a compromise will be made between the numerical model accuracy, computational time, and validity.
The Impact of Pollution on China Marine Fishery Culture: An Econometric Analysis of Heterogeneous Growth
Authors: Yuan Bin , Yue Fangzhou , Wang Xueye , Xu Hanxiao
Published: October 2021

The damage caused by pollution is not equal across individuals within a given population, due to the differences in pollution level and coping ability. Identifying the different impacts of environmental pollution on agricultural economic growth and the source of the pollution is of great reference significance for realizing the organic integration of ecological protection and relative poverty alleviation. This study takes marine fishery culture as an example, with the cultured products data of 53 coastal cities in China from 1994 to 2018 and empirically captures the heterogeneous effects of environmental pollution on mariculture growth by constructing a theoretical analysis framework of heterogeneity in pollution damage. Results show that the deepening of marine environmental pollution will reduce the growth rate of marine cultured output, emerging significant regional differences. Nevertheless, under the background of the complex environmental situation currently, further damages mainly derive from the difference in the ability to deal with environmental pollution rather than the difference in pollution degree. In terms of different wastewater sources, the impact of industrial wastewater discharge on marine aquaculture production is not very significant. In contrast, the adverse shocks of urban domestic sewage are more prominent. Notably, the environmental pollution has a significant cumulative effect, which is not reversed. Therefore, a pollution shock in one period may leave the region permanently further behind. Based on this, in the follow-up process of pollution control, we should fully consider the heterogeneity in coping ability of individuals. While promoting industrial wastewater emission reduction, we should emphasize strengthening of the urban domestic sewage treatment strategies and give overall consideration to the ecological environment treatment and regional coordinated development.
Delayed Re-epithelialization After Epithelium-Off Crosslinking: Predictors and Impact on Keratoconus Progression
Authors: Bonzano Chiara , Cutolo Carlo Alberto , Musetti Donatella , Di Mola Ilaria , Pizzorno Chiara , Scotto Riccardo , Traverso Carlo Enrico
Published: October 2021

Purpose: To investigate the demographic and corneal factors associated with the occurrence of delayed reepithelialization (DRE) after epithelium-off crosslinking (epi-off CXL).

Design:Retrospective case series.

Methods:A chart review was performed to identify patients treated with epi-off CXL. DRE was defined as a corneal epithelial defect detected by fluorescein staining that persisted for more than 10 days. Slit-lamp examination, anterior segment optical coherence tomography, corneal topography, and corneal in vivo confocal microscopy (IVCM) were always performed preoperatively and at each follow-up visit (1, 3, 6, 12 months). A generalized estimating equation was used to assess the baseline factors associated with DRE.

Results:Data from 153 eyes were analyzed. The mean age of patients was 24.9 ± 8.5 years, and 47 (30.7%) were women. The average reepithelization time was 4.7 ± 1.8 days. Six eyes (3.9%) experienced DRE. In the multivariate model, both the age of the patient (OR = 1.30; p = 0.02) and the corneal steepest meridian (OR = 0.44, p = 0.047) were associated with DRE. Baseline nerve count was also associated with DRE (0.87, p = 0.03). Male gender was associated with a slower early nerve regrowth (1–6 months) (p = 0.048), but not with the occurrence of DRE (p = 0.27). Preoperative central corneal thickness was not related to DRE (p = 0.16). DRE was not associated with keratoconus progression after epi-off CXL (p = 0.520).

Conclusions:The association between DRE and age may reflect the age-related decrease in the corneal healing response. Also, low baseline corneal nerve count is associated with DRE. Gender seems to affect reinnervation measured by IVCM but not the reepithelization time. DRE does not seem to affect the efficacy of epi-off CXL.
Superiority of Supervised Machine Learning on Reading Chest X-Rays in Intensive Care Units
Authors: Tanaka Kumiko , Nakada Taka-aki , Takahashi Nozomi , Dozono Takahiro , Yoshimura Yuichiro , Yokota Hajime , Horikoshi Takuro , Nakaguchi Toshiya , Shinozaki Koichiro
Published: October 2021

Purpose: Portable chest radiographs are diagnostically indispensable in intensive care units (ICU). This study aimed to determine if the proposed machine learning technique increased in accuracy as the number of radiograph readings increased and if it was accurate in a clinical setting.

Methods: Two independent data sets of portable chest radiographs (n = 380, a single Japanese hospital; n = 1,720, The National Institution of Health [NIH] ChestX-ray8 dataset) were analyzed. Each data set was divided training data and study data. Images were classified as atelectasis, pleural effusion, pneumonia, or no emergency. DenseNet-121, as a pre-trained deep convolutional neural network was used and ensemble learning was performed on the best-performing algorithms. Diagnostic accuracy and processing time were compared to those of ICU physicians.

Results: In the single Japanese hospital data, the area under the curve (AUC) of diagnostic accuracy was 0.768. The area under the curve (AUC) of diagnostic accuracy significantly improved as the number of radiograph readings increased from 25 to 100% in the NIH data set. The AUC was higher than 0.9 for all categories toward the end of training with a large sample size. The time to complete 53 radiographs by machine learning was 70 times faster than the time taken by ICU physicians (9.66 s vs. 12 min). The diagnostic accuracy was higher by machine learning than by ICU physicians in most categories (atelectasis, AUC 0.744 vs. 0.555, P < 0.05; pleural effusion, 0.856 vs. 0.706, P < 0.01; pneumonia, 0.720 vs. 0.744, P = 0.88; no emergency, 0.751 vs. 0.698, P = 0.47).

Conclusions: We developed an automatic detection system for portable chest radiographs in ICU setting; its performance was superior and quite faster than ICU physicians.
Extracorporeal Membrane Oxygenation in Severe Acute Respiratory Distress Syndrome Caused by Chlamydia psittaci: A Case Report and Review of the Literature
Authors: Wang Lu , Shi Zhaokun , Chen Wei , Du Xianjin , Zhan Liying
Published: October 2021

Background: Infection of Chlamydia psittaci (C. psittaci) could lead to serious clinical manifestations in humans, including severe pneumonia with rapid progression, adult respiratory distress syndrome (ARDS), sepsis, multiple organ dysfunction syndromes (MODS), and probably death. Implementation of extracorporeal membrane oxygenation (ECMO) in the patient with severe ARDS gives a promising new method for recovery.

Case Presentation: We report our successful use of venovenous (VV) ECMO in a 48-year-old man who manifested with severe respiratory distress syndrome, acute kidney injury, and septic shock caused by a diagnosis of pneumonia. After the combination of therapy including anti-infection, mechanical ventilation, and continuous renal replacement therapy (CRRT), acute inflammatory syndrome developed. However, his respiratory status rapidly deteriorated. Then, venoarterial (VA)-ECMO support was placed on the patient as suddenly slowing of the heart rate. Harlequin (North-South) syndrome occurred after ECMO initiation. A series of the process could not relieve hypoxia in the upper body. At last, transition to VV-ECMO improved hypoxia. The duration of VV-ECMO was 7 days and the mechanical ventilation was weaned on the next day. On the day of ECMO weaning, nanopore targeted sequencing (NTS) of bronchoalveolar lavage fluid (BALF) reported the presence of C. psittaci. After 19 days of critical systemic rehabilitation and combination therapy, the patient fully recovered from C. psittaci.

Conclusion: This is the first reported case of the patient receiving ECMO for C. psittaci pneumonia. ECMO puts the lungs on temporary rest, promotes the recovery of pulmonary function, and also wins time for finding the pathogens, which is crucial in the treatment of rare pathogens.
Optimization of Growth Conditions to Produce Sustainable Polyhydroxyalkanoate Bioplastic by Pseudomonas aeruginosa EO1
Authors: Mahato Richa Prasad , Kumar Saurabh , Singh Padma
Published: October 2021

Polyhydroxyalkanoates (PHAs) are intracellularly synthesized by bacteria as carbonosomes that exhibit biodegradable thermoplastics and elastomeric properties. The use of cheaper edible oils as a source of carbon assists in the reduction of the production cost of such biopolyesters. In this work, different edible oils, such as groundnut oil (GNO), mustard oil, sesame oil, and soybean oil (SBO) were used to check their effect on PHA production from Pseudomonas aeruginosa EO1 (MK049902). Pseudomonas aeruginosa EO1 was used in a two-stage production system. In the first stage, bacterial growth was favored and, in the second, PHA was synthesized. GNO was found as the best carbon source for PHA production. The use of 2% (v/v) GNO, rich in saturated fatty acids, allowed PHA content of 58.41% and dry cell weight (DCW) of 10.5g/L at pH7 and temperature 35°C for 72h. Groundnut has a high potential for oil production and for the diversification of co-products with some potential of value aggregation. Such a perennial and sustainable species will almost certainly meet the criteria for becoming a significant commercial oilseed crop. Fourier transform infrared spectroscopy (FTIR) spectra showed strong characteristic bands at 1,282, 1,725, 2,935, 2,999, and 3,137cm−1 for the PHA polymer. Gas chromatography-mass spectrometry (GC-MS) detects the presence of PHA copolymers.
The Hypoxia-Associated Localization of Chemotaxis Protein CheZ in Azorhizorbium caulinodans
Authors: Liu Xiaolin , Liu Yanan , Wang Yixuan , Wang Dandan , Johnson Kevin Scot , Xie Zhihong
Published: October 2021

Spatial organization of chemotactic proteins is important for cooperative response to external stimuli. However, factors affecting the localization dynamics of chemotaxis proteins are less studied. According to some reports, the polar localization of chemotaxis system I is induced by hypoxia and starvation in Vibrio cholerae. However, in V. cholerae, the chemotaxis system I is not involved in flagellum-mediated chemotaxis, and it may play other alternative cellular functions. In this study, we found that the polar localization of CheZ, a phosphatase regulating chemotactic movement in Azorhizobium caulinodans ORS571, can also be affected by hypoxia and cellular energy-status. The conserved phosphatase active site D165 and the C-terminus of CheZ are essential for the energy-related localization, indicating a cross link between hypoxia-related localization changes and phosphatase activity of CheZ. Furthermore, three of five Aer-like chemoreceptors containing PAS domains participate in the cellular localization of CheZ. In contrast to carbon starvation, free-living nitrogen fixation can alleviate the role of nitrogen limitation and hypoxia on polar localization of CheZ. These results showed that the localization changes induced by hypoxia might be a strategy for bacteria to adapt to complex environment.
Tomato Endophytic Bacteria Composition and Mechanism of Suppressiveness of Wilt Disease (Fusarium oxysporum)
Authors: Zhang Zeyu , Li Ji , Zhang Zengqiang , Liu Youzhou , Wei Yuquan
Published: October 2021

Tomato wilt disease, caused by theFusarium oxysporumis an ever-increasing threat for agricultural production, and unreasonable fertilization and pesticide abuse caused environmental challenge. Increasing evidence suggested that microbiomes or those associated with crops, played key roles on plant health. Plant disease dynamics were affected by multiple biotic and abiotic factors including phytopathogen population density, the genetic type of the pathogen and the host, in particular, the composition and assembly of the host-associated microbiome. However, it was unclear how pathogen invasion interaction and correlate with endophytic bacterial communities in natural field conditions. To study this, we sampled temporally the tomato plants that were exposed toF. oxysporuminvasions over one crop season. High-throughput sequencing were performed to explore the correlation between agricultural practice, pathogen invasion, and endophytic microbiota communities. Results showed that pathogen invasion had clear effect on the endophytic and a strong link between increased pathogen densities and reduced abundance ofBacillussp., which are crucial taxonomy for suppressiveness toF. oxysporum in vitroand in greenhouse condition. In summary, monitoring the dynamics of endophytic bacteria communities and densities of pathogen could thus open new avenue for more accurate disease diagnostics and high-efficiency screening antagonisms methods in the future, and our results will broaden the agricultural view of beneficial microbiota as biological control agents against plant pathogen.
Study on the Characteristic Codon Usage Pattern in Porcine Epidemic Diarrhea Virus Genomes and Its Host Adaptation Phenotype
Authors: Si Fusheng , Jiang Li , Yu Ruisong , Wei Wenqiang , Li Zhen
Published: October 2021

Porcine epidemic diarrhea virus (PEDV), which classified in the genus Alphacoronavirus, family Coronaviridae, is one of the most important pathogens that cause heavy economic losses in pig industry. Although intensive mutation and recombination analysis of PEDV strains were provided, systematic genome analysis were needed to elucidate the evolution mechanism and codon usage adaptation profiles of the pathogen. Here, a comprehensive investigation was carried out to reveal the systematic evolutionary processes of synonymous codon usage and host-adapted evolution phenotype of PEDV genome. We found a low codon usage bias (CUB) in PEDV genome and that nucleotide compositions, natural selection, mutation pressure and geographical diversity shapes the codon usage patterns of PEDV, with natural selection dominated the overall codon usage bias in PEDV than the others. By using the relative codon deoptimization index (RCDI) and similarity index (SiD) analysis, we observed that genotype II PEDV strains showed the highest level of adaptation phenotype to Sus scrofa than another divergent clade. To the best of our knowledge, this is the first comprehensive report elaborating the codon usage and host adaptation of PEDV. The findings offer an insight into our understanding of factors involved in PEDV evolution, adaptation and fitness toward their hosts.
Large-Scale Characterization of the Soil Microbiome in Ancient Tea Plantations Using High-Throughput 16S rRNA and Internal Transcribed Spacer Amplicon Sequencing
Authors: Kui Ling , Xiang Guisheng , Wang Ya , Wang Zijun , Li Guorong , Li Dawei , Yan Jing , Ye Shuang , Wang Chunping , Yang Ling , Zhang Shiyu , Zhang Shuangyan , Zhou Ling , Gui Heng , Xu Jianchu , Chen Wei , Zhang Jun , Huang Tingyuan , Majeed Aasim , Sheng Jun , Dong Yang
Published: October 2021

There is a special interaction between the environment, soil microorganisms, and tea plants, which constitute the ecosystem of tea plantations. Influenced by environmental factors and human management, the changes in soil microbial community affected the growth, quality, and yield of tea plants. However, little is known about the composition and structure of soil bacterial and fungal communities in 100-year-old tea plantations and the mechanisms by which they are affected. In this regard, we characterized the microbiome of tea plantation soils by considering the bacterial and fungal communities in 448 soil samples from 101 ancient tea plantations in eight counties of Lincang city, which is one of the tea domestication centers in the world. 16S and Internal Transcribed Spacer (ITS) rRNA high-throughput amplicon sequencing techniques were applied in this study. The results showed that the abundance, diversity, and composition of the bacterial and fungal communities have different sensitivity with varying pH, altitude, and latitude. pH and altitude affect soil microbial communities, and bacterial communities are more sensitive than fungi in terms of abundance and diversity to pH. The highest α-diversity of bacterial communities is shown in the pH 4.50–5.00 and 2,200-m group, and fungi peaked in the pH 5.00–5.50 and 900-m group. Because of environmental and geographical factors, all microbes are similarly changing, and further correlations showed that the composition and structure of bacterial communities are more sensitive than fungal communities, which were affected by latitude and altitude. In conclusion, the interference of anthropogenic activities plays a more important role in governing fungal community selection than environmental or geographical factors, whereas for the bacterial community, it is more selective to environment adaptation than to adaptation to human activities.
Francisella tularensis Outer Membrane Vesicles Participate in the Early Phase of Interaction With Macrophages
Authors: Pavkova Ivona , Klimentova Jana , Bavlovic Jan , Horcickova Lenka , Kubelkova Klara , Vlcak Erik , Raabova Helena , Filimonenko Vlada , Ballek Ondrej , Stulik Jiri
Published: October 2021

Francisella tularensis is known to release unusually shaped tubular outer membrane vesicles (OMV) containing a number of previously identified virulence factors and immunomodulatory proteins. In this study, we present that OMV isolated from the F. tularensis subsp. holarctica strain FSC200 enter readily into primary bone marrow-derived macrophages (BMDM) and seem to reside in structures resembling late endosomes in the later intervals. The isolated OMV enter BMDM generally via macropinocytosis and clathrin-dependent endocytosis, with a minor role played by lipid raft-dependent endocytosis. OMVs proved to be non-toxic and had no negative impact on the viability of BMDM. Unlike the parent bacterium itself, isolated OMV induced massive and dose-dependent proinflammatory responses in BMDM. Using transmission electron microscopy, we also evaluated OMV release from the bacterial surface during several stages of the interaction of Francisella with BMDM. During adherence and the early phase of the uptake of bacteria, we observed numerous tubular OMV-like protrusions bulging from the bacteria in close proximity to the macrophage plasma membrane. This suggests a possible role of OMV in the entry of bacteria into host cells. On the contrary, the OMV release from the bacterial surface during its cytosolic phase was negligible. We propose that OMV play some role in the extracellular phase of the interaction of Francisella with the host and that they are involved in the entry mechanism of the bacteria into macrophages.
Characterization of HIV-1 Epidemic in Kyrgyzstan
Authors: Sivay Mariya V. , Totmenin Alexei V. , Zyryanova Daria P. , Osipova Irina P. , Nalimova Tatyana M. , Gashnikova Mariya P. , Ivlev Vladimir V. , Meshkov Ivan O. , Chokmorova Umut Z. , Narmatova Elmira , Motorov Ulukbek , Akmatova Zhyldyz , Asybalieva Nazgul , Bekbolotov Aybek A. , Kadyrbekov Ulan K. , Maksutov Rinat A. , Gashnikova Natalya M.
Published: October 2021

Kyrgyzstan has one of the highest rates of HIV-1 spread in Central Asia. In this study, we used molecular–epidemiological approaches to examine the HIV-1 epidemic in Kyrgyzstan. Samples were obtained from HIV-positive individuals who visited HIV/AIDS clinics. Partial pol gene sequences were used to identify HIV-1 subtypes and drug resistance mutations (DRMs) and to perform phylogenetic analysis. Genetic diversity and history reconstruction of the major HIV-1 subtypes were explored using BEAST. This study includes an analysis of 555 HIV-positive individuals. The study population was equally represented by men and women aged 1–72 years. Heterosexual transmission was the most frequent, followed by nosocomial infection. Men were more likely to acquire HIV-1 during injection drug use and while getting clinical services, while women were more likely to be infected through sexual contacts (p < 0.01). Heterosexual transmission was the more prevalent among individuals 25–49 years old; individuals over 49 years old were more likely to be persons who inject drugs (PWID). The major HIV-1 variants were CRF02_AG, CRF63_02A, and sub-subtype A6. Major DRMs were detected in 26.9% of the study individuals; 62.2% of those had DRMs to at least two antiretroviral (ARV) drug classes. Phylogenetic analysis revealed a well-defined structure of CRF02_AG, indicating locally evolving sub-epidemics. The lack of well-defined phylogenetic structure was observed for sub-subtype A6. The estimated origin date of CRF02_AG was January 1997; CRF63_02A, April 2004; and A6, June 1995. A rapid evolutionary dynamic of CRF02_AG and A6 among Kyrgyz population since the mid-1990s was observed. We observed the high levels of HIV-1 genetic diversity and drug resistance in the study population. Complex patterns of HIV-1 phylogenetics in Kyrgyzstan were found. This study highlights the importance of molecular–epidemiological analysis for HIV-1 surveillance and treatment implementation to reduce new HIV-1 infections.
Association of Elevated Plasma Total Homocysteine With Dementia With Lewy Bodies: A Case-Control Study
Authors: Zhang Guili , Liu Shuai , Chen Zhichao , Shi Zhihong , Hu Wenzheng , Ma Lingyun , Wang Xiaodan , Li Xudong , Ji Yong
Published: October 2021

Background: Elevated plasma total homocysteine (tHcy) level, a known risk factor for vascular disease, is reported to be an independent risk factor for cognitive impairment and Alzheimer’s disease (AD) in most studies. tHcy may also be associated with dementia with Lewy bodies (DLB).

Objective: To investigate the association between plasma tHcy levels and DLB or AD.

Methods: This is a case-control study including 132 DLB patients, 264 AD patients, and 295 age-matched healthy controls. We used multivariate logistic regression model to analyze the data with adjustments for confounding variables.

Results: The highest tHcy tertile (>13.9 μmol/L) was significantly independently associated with DLB [adjusted odds ratio (OR): 4.65, 95% confidence interval (CI): 1.95–11.10, P = 0.001] and AD (adjusted OR: 1.82, 95% CI: 1.02–3.23, P = 0.041) compared to the lowest tertile (<10.7 μmol/L). The cumulative frequency plots showed a shift in the distribution of the tHcy concentrations to higher values in patients with DLB compared to AD. The mean tHcy levels were stable and not altered by the duration of cognitive impairment prior to the collection of blood samples from DLB patients.

Conclusion: Elevated plasma tHcy levels were independently associated with DLB, and the association was stronger for DLB than for AD. The lack of a relationship between tHcy levels and symptom duration may refute these observed associations being a consequence of DLB, and future longitudinal studies will be required to confirm whether tHcy plays a causative role in DLB.
Galectins and Their Ligand Glycoconjugates in the Central Nervous System Under Physiological and Pathological Conditions
Authors: Nio-Kobayashi Junko , Itabashi Tetsuya
Published: October 2021

Galectins are β-galactoside-binding lectins consisting of 15 members in mammals. Galectin-1,-3,-4,-8, and -9 are predominantly expressed in the central nervous system (CNS) and regulate various physiological and pathological events. This review summarizes the current knowledge of the cellular expression and role of galectins in the CNS, and discusses their functions in neurite outgrowth, myelination, and neural stem/progenitor cell niches, as well as in ischemic/hypoxic/traumatic injuries and neurodegenerative diseases such as multiple sclerosis. Galectins are expressed in both neurons and glial cells. Galectin-1 is mainly expressed in motoneurons, whereas galectin-3-positive neurons are broadly distributed throughout the brain, especially in the hypothalamus, indicating its function in the regulation of homeostasis, stress response, and the endocrine/autonomic system. Astrocytes predominantly contain galectin-1, and galectin-3 and−9 are upregulated along with its activation. Activated, but not resting, microglia contain galectin-3, supporting its phagocytic activity. Galectin-1,−3, and -4 are characteristically expressed during oligodendrocyte differentiation. Galectin-3 from microglia promotes oligodendrocyte differentiation and myelination, while galectin-1 and axonal galectin-4 suppress its differentiation and myelination. Galectin-1- and- 3-positive cells are involved in neural stem cell niche formation in the subventricular zone and hippocampal dentate gyrus, and the migration of newly generated neurons and glial cells to the olfactory bulb or damaged lesions. In neurodegenerative diseases, galectin-1,-8, and -9 have neuroprotective and anti-inflammatory activities. Galectin-3 facilitates pro-inflammatory action; however, it also plays an important role during the recovery period. Several ligand glycoconjugates have been identified so far such as laminin, integrins, neural cell adhesion molecule L1, sulfatide, neuropilin-1/plexinA4 receptor complex, triggering receptor on myeloid cells 2, and T cell immunoglobulin and mucin domain. N-glycan branching on lymphocytes and oligodendroglial progenitors mediated by β1,6-N-acetylglucosaminyltransferase V (Mgat5/GnTV) influences galectin-binding, modulating inflammatory responses and remyelination in neurodegenerative diseases. De-sulfated galactosaminoglycans such as keratan sulfate are potential ligands for galectins, especially galectin-3, regulating neural regeneration. Galectins have multitudinous functions depending on cell type and context as well as post-translational modifications, including oxidization, phosphorylation, S-nitrosylation, and cleavage, but there should be certain rules in the expression patterns of galectins and their ligand glycoconjugates, possibly related to glucose metabolism in cells.
Extensive Anti-CoA Immunostaining in Alzheimer’s Disease and Covalent Modification of Tau by a Key Cellular Metabolite Coenzyme A
Authors: Lashley Tammaryn , Tossounian Maria-Armineh , Costello Heaven Neve , Wallworth Samantha , Peak-Chew Sew , Bradshaw Aaron , Cooper J. Mark , de Silva Rohan , Srai Surjit Kaila , Malanchuk Oksana , Filonenko Valeriy , Koopman Margreet B. , Rüdiger Stefan G. D. , Skehel Mark , Gout Ivan
Published: October 2021

Alzheimer’s disease (AD) is a neurodegenerative disorder, accounting for at least two-thirds of dementia cases. A combination of genetic, epigenetic and environmental triggers is widely accepted to be responsible for the onset and development of AD. Accumulating evidence shows that oxidative stress and dysregulation of energy metabolism play an important role in AD pathogenesis, leading to neuronal dysfunction and death. Redox-induced protein modifications have been reported in the brain of AD patients, indicating excessive oxidative damage. Coenzyme A (CoA) is essential for diverse metabolic pathways, regulation of gene expression and biosynthesis of neurotransmitters. Dysregulation of CoA biosynthesis in animal models and inborn mutations in human genes involved in the CoA biosynthetic pathway have been associated with neurodegeneration. Recent studies have uncovered the antioxidant function of CoA, involving covalent protein modification by this cofactor (CoAlation) in cellular response to oxidative or metabolic stress. Protein CoAlation has been shown to both modulate the activity of modified proteins and protect cysteine residues from irreversible overoxidation. In this study, immunohistochemistry analysis with highly specific anti-CoA monoclonal antibody was used to reveal protein CoAlation across numerous neurodegenerative diseases, which appeared particularly frequent in AD. Furthermore, protein CoAlation consistently co-localized with tau-positive neurofibrillary tangles, underpinning one of the key pathological hallmarks of AD. Double immunihistochemical staining with tau and CoA antibodies in AD brain tissue revealed co-localization of the two immunoreactive signals. Further, recombinant 2N3R and 2N4R tau isoforms were found to be CoAlated in vitro and the site of CoAlation mapped by mass spectrometry to conserved cysteine 322, located in the microtubule binding region. We also report the reversible H2O2-induced dimerization of recombinant 2N3R, which is inhibited by CoAlation. Moreover, CoAlation of transiently expressed 2N4R tau was observed in diamide-treated HEK293/Pank1β cells. Taken together, this study demonstrates for the first time extensive anti-CoA immunoreactivity in AD brain samples, which occurs in structures resembling neurofibrillary tangles and neuropil threads. Covalent modification of recombinant tau at cysteine 322 suggests that CoAlation may play an important role in protecting redox-sensitive tau cysteine from irreversible overoxidation and may modulate its acetyltransferase activity and functional interactions.
Involvement of the Choroid Plexus in the Pathogenesis of Niemann-Pick Disease Type C
Authors: Van Hoecke Lien , Van Cauwenberghe Caroline , Dominko Kristina , Van Imschoot Griet , Van Wonterghem Elien , Castelein Jonas , Xie Junhua , Claeys Wouter , Vandendriessche Charysse , Kremer Anna , Borghgraef Peter , De Rycke Riet , Hecimovic Silva , Vandenbroucke Roosmarijn E.
Published: October 2021

Niemann-Pick type C (NPC) disease, sometimes called childhood Alzheimer’s, is a rare neurovisceral lipid storage disease with progressive neurodegeneration leading to premature death. The disease is caused by loss-of-function mutations in the Npc1 or Npc2 gene which both result into lipid accumulation in the late endosomes and lysosomes. Since the disease presents with a broad heterogenous clinical spectrum, the involved disease mechanisms are still incompletely understood and this hampers finding an effective treatment. As NPC patients, who carry NPC1 mutations, have shown to share several pathological features with Alzheimer’s disease (AD) and we and others have previously shown that AD is associated with a dysfunctionality of the blood-cerebrospinal fluid (CSF) barrier located at choroid plexus, we investigated the functionality of this latter barrier in NPC1 pathology. Using NPC1–/– mice, we show that despite an increase in inflammatory gene expression in choroid plexus epithelial (CPE) cells, the blood-CSF barrier integrity is not dramatically affected. Interestingly, we did observe a massive increase in autophagosomes in CPE cells and enlarged extracellular vesicles (EVs) in CSF upon NPC1 pathology. Additionally, we revealed that these EVs exert toxic effects on brain tissue, in vitro as well as in vivo. Moreover, we observed that EVs derived from the supernatant of NPC1–/– choroid plexus explants are able to induce typical brain pathology characteristics of NPC1–/–, more specifically microgliosis and astrogliosis. Taken together, our data reveal for the first time that the choroid plexus and CSF EVs might play a role in the brain-related pathogenesis of NPC1.
Effects of 60 Min Electrostimulation With the EXOPULSE Mollii Suit on Objective Signs of Spasticity
Authors: Pennati Gaia Valentina , Bergling Hanna , Carment Loïc , Borg Jörgen , Lindberg Påvel G. , Palmcrantz Susanne
Published: October 2021

Background:The EXOPULSE Mollii method is an innovative full-body suit approach for non-invasive electrical stimulation, primarily designed to reduce disabling spasticity and improve motor function through the mechanism of reciprocal inhibition. This study aimed to evaluate the effectiveness of one session of stimulation with the EXOPULSE Mollii suit at different stimulation frequencies on objective signs of spasticity and clinical measures, and the subjective perceptions of the intervention.

Methods:Twenty patients in the chronic phase after stroke were enrolled in a cross-over, double-blind controlled study. Electrical stimulation delivered through EXOPULSE Mollii was applied for 60 min at two active frequencies (20 and 30 Hz) and in OFF-settings (placebo) in a randomized order, every second day. Spasticity was assessed with controlled-velocity passive muscle stretches using the NeuroFlexor hand and foot modules. Surface electromyography (EMG) for characterizing flexor carpi radialis, medial gastrocnemius, and soleus muscles activation, Modified Ashworth Scale and range of motion were used as complementary tests. Finally, a questionnaire was used to assess the participants' perceptions of using the EXOPULSE Mollii suit.

Results:At group level, analyses showed no significant effect of stimulation at any frequency on NeuroFlexor neural component (NC) and EMG amplitude in the upper or lower extremities (p> 0.35). Nevertheless, the effect was highly variable at the individual level, with eight patients exhibiting reduced NC (>1 N) in the upper extremity after stimulation at 30 Hz, 5 at 20 Hz and 3 in OFF settings. All these patients presented severe spasticity at baseline, i.e., NC > 8 N. Modified Ashworth ratings of spasticity and range of motion did not change significantly after stimulation at any frequency. Finally, 75% of participants reported an overall feeling of well-being during stimulation, with 25% patients describing a muscle-relaxing effect on the affected hand and/or foot at both 20 and 30 Hz.

Conclusions:The 60 min of electrical stimulation with EXOPULSE Mollii suit did not reduce spasticity consistently in the upper and lower extremities in the chronic phase after stroke. Findings suggest a need for further studies in patients with severe spasticity after stroke including repeated stimulation sessions.

Clinical Trial Registration:https://clinicaltrials.gov/ct2/show/NCT04076878, identifier: NCT04076878.
Voxel-Wise Quantitative Mapping of the Brain Association Ability
Authors: Chen Kai , Wang Lijie , Zeng Jianguang , Chen Ai , Gao Zhao , Wang Jiaojian
Published: October 2021

The association cortices of the brain are essential for integrating multimodal information that subserves complex and high-order cognitive functions. To delineate the changing pattern of associative cortices can provide critical insight into brain development, aging, plasticity, and disease-triggered functional abnormalities. However, how to quantitatively characterize the association capability of the brain is elusive. Here, we developed a new method of association index (Asso) at the voxel level to quantitatively characterize the brain association ability. Using the Asso method, we found high Asso values in association cortical networks, and low values in visual and limbic networks, suggesting a pattern of significant gradient distribution in neural functions. The spatial distribution patterns of Asso show high similarities across different thresholds suggesting that Asso mapping is a threshold-free method. In addition, compared with functional connectivity strength, i.e., degree centrality method, Asso mapping showed different patterns for association cortices and primary cortices. Finally, the Asso method was applied to investigate aging effects and identified similar findings with previous studies. All these results indicated that Asso can characterize the brain association patterns effectively and open a new avenue to reveal a neural basis for development, aging, and brain disorders.
Predicting Space Radiation Single Ion Exposure in Rodents: A Machine Learning Approach
Authors: Prelich Matthew T. , Matar Mona , Gokoglu Suleyman A. , Gallo Christopher A. , Schepelmann Alexander , Iqbal Asad K. , Lewandowski Beth E. , Britten Richard A. , Prabhu R. K. , Myers Jerry G.
Published: October 2021

This study presents a data-driven machine learning approach to predict individual Galactic Cosmic Radiation (GCR) ion exposure for 4He, 16O, 28Si, 48Ti, or 56Fe up to 150 mGy, based on Attentional Set-shifting (ATSET) experimental tests. The ATSET assay consists of a series of cognitive performance tasks on irradiated male Wistar rats. The GCR ion doses represent the expected cumulative radiation astronauts may receive during a Mars mission on an individual ion basis. The primary objective is to synthesize and assess predictive models on a per-subject level through Machine Learning (ML) classifiers. The raw cognitive performance data from individual rodent subjects are used as features to train the models and to explore the capabilities of three different ML techniques for elucidating a range of correlations between received radiation on rodents and their performance outcomes. The analysis employs scores of selected input features and different normalization approaches which yield varying degrees of model performance. The current study shows that support vector machine, Gaussian naive Bayes, and random forest models are capable of predicting individual ion exposure using ATSET scores where corresponding Matthews correlation coefficients and F1 scores reflect model performance exceeding random chance. The study suggests a decremental effect on cognitive performance in rodents due to ≤150 mGy of single ion exposure, inasmuch as the models can discriminate between 0 mGy and any exposure level in the performance score feature space. A number of observations about the utility and limitations in specific normalization routines and evaluation scores are examined as well as best practices for ML with imbalanced datasets observed.
Using 77Se-Labelled Foliar Fertilisers to Determine How Se Transfers Within Wheat Over Time
Authors: Ramkissoon Chandnee , Degryse Fien , Young Scott , Bailey Elizabeth H. , McLaughlin Michael J.
Published: October 2021

Foliar selenium (Se) fertilisation has been shown to be more efficient than soil-applied fertilisation, but the dynamics of absorption and translocation have not yet been explored. An experiment was undertaken to investigate time-dependent changes in the absorption, transformation, and distribution of Se in wheat when 77Se-enriched sodium selenate (Sefert) was applied to the leaves at a rate of 3.33 μg Se per kg soil (equivalent to 10 g ha−1) and two growth stages, namely stem elongation, Zadoks stage 31/32 (GS1), and heading stage, Zadoks stage 57 (GS2). The effect of urea inclusion in foliar Se fertilisers on the penetration rates of Se was also investigated. Wheat was harvested at 3, 10, and 17 days and 3, 10, and 34 days after Se applications at GS1 and GS2, respectively. Applying foliar Se, irrespective of the formulation, brought grain Se concentration to a level high enough to be considered adequate for biofortification. Inclusion of N in the foliar Se solution applied at an early growth stage increased recoveries in the plants, likely due to improved absorption of applied Se through the young leaves. At a later growth stage, the inclusion of N in foliar Se solutions was also beneficial as it improved the assimilation of applied inorganic Se into bioavailable selenomethionine, which was then rapidly translocated to the grain. The practical knowledge gained about the optimisation of Se fertiliser formulation, method, and timing of application will be of importance in refining biofortification programs across different climatic regimes.
Altered Gut Microbiota Associated With Hemorrhage in Chronic Radiation Proctitis
Authors: Liu Liangzhe , Chen Chaoyun , Liu Xia , Chen Bingcheng , Ding Chen , Liang Jinjun
Published: October 2021

Pelvic cancer radiotherapy may cause chronic radiation proctitis (CRP) that adversely affects patient’s quality of life, especially in patients with prolonged hematochezia. However, previous studies of radiation enteropathy mainly focused on acute irradiation hazards, and the detailed pathogenesis process and mechanism of prolonged hematochezia associated with radiation-induced toxicity remain unclear. In this study, we characterized the gut microbiota of 32 female CRP patients with or without hematochezia. Differential patterns of dysbiosis were observed. The abundance of Peptostreptococcaceae, Eubacterium, and Allisonella was significantly higher in CRP patients with hematochezia, while the compositions of the Lachnospiraceae, Megasphera, Megamonas, and Ruminococcaceae were lower in the microbiota of non-hematochezia patients. Functional prediction suggested significant difference in the expression of mineral absorption and the arachidonic acid metabolism proteins between hematochezia and non-hematochezia patients, possibly interdependent on radiation-induced inflammation. This study provides new insight into the altered composition and function of gut microbiota in patients with hematochezia, implying the potential use of probiotics and prebiotics for assessment and treatment of CRP.
Tumor Suppressor miRNA in Cancer Cells and the Tumor Microenvironment: Mechanism of Deregulation and Clinical Implications
Authors: Otmani Khalid , Lewalle Philippe
Published: October 2021

MicroRNAs (miRNAs) are noncoding RNAs that have been identified as important posttranscriptional regulators of gene expression. miRNAs production is controlled at multiple levels, including transcriptional and posttranscriptional regulation. Extensive profiling studies have shown that the regulation of mature miRNAs expression plays a causal role in cancer development and progression. miRNAs have been identified to act as tumor suppressors (TS) or as oncogenes based on their modulating effect on the expression of their target genes. Upregulation of oncogenic miRNAs blocks TS genes and leads to tumor formation. In contrast, downregulation of miRNAs with TS function increases the translation of oncogenes. Several miRNAs exhibiting TS properties have been studied. In this review we focus on recent studies on the role of TS miRNAs in cancer cells and the tumor microenvironment (TME). Furthermore, we discuss how TS miRNA impacts the aggressiveness of cancer cells, with focus of the mechanism that regulate its expression. The study of the mechanisms of miRNA regulation in cancer cells and the TME may paved the way to understand its critical role in the development and progression of cancer and is likely to have important clinical implications in a near future. Finally, the potential roles of miRNAs as specific biomarkers for the diagnosis and the prognosis of cancer and the replacement of tumor suppressive miRNAs using miRNA mimics could be promising approaches for cancer therapy.
MicroRNA-483-5p Predicts Poor Prognosis and Promotes Cancer Metastasis by Targeting EGR3 in Nasopharyngeal Carcinoma
Authors: Li Xi-Zhao , Tu Yi-Jun , Zhou Ting , Zhang Jiang-Bo , Xiao Ruo-Wen , Yang Da-Wei , Zhang Pei-Fen , You Peng-Tao , Zheng Xiao-Hui
Published: October 2021

Background

MicroRNAs, as small non-coding RNAs, play an important role in tumorigenesis. MiR-483-5p was found to have a significant increase as a diagnostic biomarker of nasopharyngeal carcinoma (NPC), not only in plasma from NPC patients but also in tumor cell lines and biopsy tissues in our previous study. However, its function and mechanism in NPC are still unclear.

Methods

Tissue microarray including 178 primary NPC and 35 adjacent non-cancerous nasopharyngeal mucosal tissues was used to further validate the overexpression of miR-483-5p. Wound healing and invasion assays were conducted to verify its biological function. RNA sequencing (RNA-seq) and dual-luciferase reporter assay was performed to explore its target, and it was verified in fresh biopsy tissues from 23 NPC patients and 9 patients with chronic nasopharyngitis.

Results

MiR-483-5p was highly expressed in NPC tissues than in adjacent non-cancerous tissues. It was found to have a significant correlation with poor overall survival (OS) [hazard ratio (HR) = 2.89, 95% confidence interval (CI) = 1.00–8.35, p = 0.041] and progression-free survival (PFS) (HR = 1.95, 95%CI = 1.06–3.60, p = 0.029) of NPC patients. Silencing of its expression inhibited the migratory and invasive capacities of NPC cells in vitro. EGR3 (early growth response 3) was identified as a direct target, and inhibiting miR-483-5p expression markedly enhanced the expression of EGR3 at both the mRNA and protein levels. Besides, a significant decrease of EGR3 expression was found in fresh biopsy tissues from NPC patients, in contrast to miR-483-5p expression. Furthermore, directly decreasing the expression of EGR3 could enhance the migration and invasion of NPC cells.

Conclusion

The newly identified miR-483-5p/EGR3 pathway provides further insights into the development and metastasis of NPC and may provide a potential therapeutic target for NPC treatment in order to improve survival of NPC patients.