bluuebunny/crossref_metadata_2025 huggingface dataset:
Exome Analysis Reveals Novel Missense and Deletion Variants in the CC2D2A Gene as Causative of Joubert Syndrome
Authors: Cabrita Pinto Rute Luísa , Viaggi Silvia , Canale Edoardo , Martinez Popple Marina , Capra Valeria , Conteduca Giuseppina , Testa Barbara , Coviello Domenico , Covone Angela Elvira
Published: March 2023

The CC2D2A gene is essential for primary cilia formation, and its disruption has been associated with Joubert Syndrome-9 (JBTS9), a ciliopathy with typical neurodevelopmental features. Here, we describe an Italian pediatric patient with typical features of Joubert Syndrome (JBTS): “Molar Tooth Sign”, global developmental delay, nystagmus, mild hypotonia, and oculomotor apraxia. Whole exome sequencing and segregation analysis identified in our infant patient a novel heterozygous germline missense variant c.3626C > T; p.(Pro1209Leu) inherited from the father and a novel 7.16 kb deletion inherited from the mother. To the best of our knowledge, this is the first report showing a novel missense and deletion variant involving exon 30 of the CC2D2A gene.
Metagenomics Provides a Deeper Assessment of the Diversity of Bacterial Communities in Polar Soils Than Metabarcoding
Authors: Becker Burkhard , Pushkareva Ekaterina
Published: March 2023

The diversity of soil bacteria was analyzed via metabarcoding and metagenomic approaches using DNA samples isolated from the biocrusts of 12 different Arctic and Antarctic sites. For the metabarcoding approach, the V3-4 region of the 16S rRNA was targeted. Our results showed that nearly all operational taxonomic units (OTUs = taxa) found in metabarcoding analyses were recovered in metagenomic analyses. In contrast, metagenomics identified a large number of additional OTUs absent in metabarcoding analyses. In addition, we found huge differences in the abundance of OTUs between the two methods. The reasons for these differences seem to be (1) the higher sequencing depth in metagenomics studies, which allows the detection of low-abundance community members in metagenomics, and (2) bias of primer pairs used to amplify the targeted sequence in metabarcoding, which can change the community composition dramatically even at the lower taxonomic levels. We strongly recommend using only metagenomic approaches when establishing the taxonomic profiles of whole biological communities.
Topic Modeling-Based Analysis of News Keywords Related to Patients with Diabetes during the COVID-19 Pandemic
Authors: Han Jeong-Won , Kim Jung Min , Lee Hanna
Published: March 2023

This study analyzed major issues related to diabetes during the coronavirus disease (COVID-19) pandemic by using topic modeling analysis of online news articles provided by BIGKind dating from 20 January 2020, the onset of the COVID-19 outbreak in Korea, to 17 April 2022, the lifting of the social distancing restrictions. We selected 226 articles and conducted topic modeling analysis to identify the main agenda of news related to patients with diabetes in the context of the COVID-19 pandemic; both latent Dirichlet allocation and visualization were conducted by generating keywords extracted from news text as a matrix using Python 3.0. Four main topics were extracted from the news articles related to “COVID-19” and “diabetes” during the COVID-19 pandemic, including “COVID-19 high-risk group,” “health management through digital healthcare,” “risk of metabolic disease related to quarantine policy,” and “child and adolescent obesity and diabetes.” This study is significant because it uses big data related to diabetes that was reported in the mass media during the new epidemic to identify problems in the health management of patients with diabetes during a new epidemic and discuss areas that should be considered for future interventions.
Distinct Predictors of Clinical Response after Repetitive Transcranial Magnetic Stimulation between Bipolar and Unipolar Disorders
Authors: Lacroix Aurélie , Paquet Aude , Okassa Mireille , Vinais Théodore , Lannaud Marilyne , Plansont Brigitte , Buisson Alexandre , Guignandon Sandrine , Malauzat Dominique , Girard Murielle , Calvet Benjamin
Published: March 2023

Background: Repetitive transcranial magnetic stimulation (rTMS) has been shown to be therapeutically effective for patients suffering from drug-resistant depression. The distinction between bipolar and unipolar disorders would be of great interests to better adapt their respective treatments. Methods: We aimed to identify the factors predicting clinical improvement at one month (M1) after the start of rTMS treatment for each diagnosis, which was preceded by a comparison of the patients’ clinical conditions. We used the data collected and the method employed in a previous publication on 291 patients. Results: Although the bipolar group had fewer responders, these patients seemed to better maintain their post-rTMS improvement on anxiety and perception of the severity of their illness than those in the unipolar group. For the bipolar group, young age coupled with low number of medications and high fatigue was shown to be the best combination for predicting improvement at M1. The duration of current depressive episode, which was previously demonstrated for whole group, combined with being attached was shown to favor clinical improvement among the patients in unipolar group. Conclusion: We were able to define a combination of specific factors related to each diagnosis for predicting the patients’ clinical response. This could be extremely useful to predict the efficacy of rTMS during routine clinical practice in neuromodulation services.
The Contribution of Environmental Science to Mental Health Research: A Scoping Review
Authors: Roberts Michaela , Colley Kathryn , Currie Margaret , Eastwood Antonia , Li Kuang-Heng , Avery Lisa M. , Beevers Lindsay C. , Braithwaite Isobel , Dallimer Martin , Davies Zoe G. , Fisher Helen L. , Gidlow Christopher J. , Memon Anjum , Mudway Ian S. , Naylor Larissa A. , Reis Stefan , Smith Pete , Stansfeld Stephen A. , Wilkie Stephanie , Irvine Katherine N.
Published: March 2023

Mental health is influenced by multiple complex and interacting genetic, psychological, social, and environmental factors. As such, developing state-of-the-art mental health knowledge requires collaboration across academic disciplines, including environmental science. To assess the current contribution of environmental science to this field, a scoping review of the literature on environmental influences on mental health (including conditions of cognitive development and decline) was conducted. The review protocol was developed in consultation with experts working across mental health and environmental science. The scoping review included 202 English-language papers, published between 2010 and 2020 (prior to the COVID-19 pandemic), on environmental themes that had not already been the subject of recent systematic reviews; 26 reviews on climate change, flooding, air pollution, and urban green space were additionally considered. Studies largely focused on populations in the USA, China, or Europe and involved limited environmental science input. Environmental science research methods are primarily focused on quantitative approaches utilising secondary datasets or field data. Mental health measurement was dominated by the use of self-report psychometric scales. Measures of environmental states or exposures were often lacking in specificity (e.g., limited to the presence or absence of an environmental state). Based on the scoping review findings and our synthesis of the recent reviews, a research agenda for environmental science’s future contribution to mental health scholarship is set out. This includes recommendations to expand the geographical scope and broaden the representation of different environmental science areas, improve measurement of environmental exposure, prioritise experimental and longitudinal research designs, and giving greater consideration to variation between and within communities and the mediating pathways by which environment influences mental health. There is also considerable opportunity to increase interdisciplinarity within the field via the integration of conceptual models, the inclusion of mixed methods and qualitative approaches, as well as further consideration of the socio-political context and the environmental states that can help support good mental health. The findings were used to propose a conceptual model to parse contributions and connections between environmental science and mental health to inform future studies.
Social Networks, New Technologies, and Wellbeing—An Interview Study on Factors Influencing Older Adults’ Successful Ageing
Authors: Betlej Alina
Published: March 2023

Many factors are considered vital in supporting successful ageing and older adults’ wellbeing. Whilst evidence exists around facilitating and hindering factors in the general use of various forms of institutional and family support and personal development-oriented education and/or new technologies, evidence is limited with regards to older people’s motivations, expectations, and experiences surrounding ageing. Hence, in this study, the author used a qualitative explanatory method to interpret the factors influencing seniors’ successful ageing. The author’s focus was on how seniors experience ageing. The second issue was how they have been organizing life in old age. The third point concerned their expectations towards ageing now and in the future. Thirteen older adults (60+) were interviewed nationwide using a semi-structured scenario tool. Their objective was to give rich descriptions of their experiences of ageing. The interviews revealed the older adults’ own experiences and enabled an understanding of their motivations, perceptions, moderators, and expectations around successful ageing. Based on the analysis of the qualitative data, the author developed three main themes, each with its own sub-themes: 1. Life satisfaction (transitioning to retirement, using coping strategies in adaptation to negative changes, reaching personal goals, leading a meaningful life); 2. Supportive environments (being independent but using temporary assistance from relatives and/or people close to oneself, living with family members (e.g., husband or wife, children, grandchildren), having access to health care system); 3. Social integration (social relations, social engagement, independence in using technological advancements). The main categories that emerged from the three themes were social networks, new technologies, and wellbeing. To analyze these issues, the author used a sociological approach. The theoretic explorations were embedded mainly in two methods: criticism of writing and the analytical and comparative one.
Liver Function in Patients with Long-Term Coronavirus Disease 2019 of up to 20 Months: A Cross-Sectional Study
Authors: de Lima Igor , de Menezes Daniel , Uesugi Juliana , Bichara Cléa , da Costa Vasconcelos Pedro , Quaresma Juarez , Falcão Luiz
Published: March 2023

The long-term laboratory aspects of the effects of coronavirus disease 2019 (COVID-19) on liver function are still not well understood. Therefore, this study aimed to evaluate the hepatic clinical laboratory profile of patients with up to 20 months of long-term COVID-19. A total of 243 patients of both sexes aged 18 years or older admitted during the acute phase of COVID-19 were included in this study. Liver function analysis was performed. Changes were identified in the mean levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), gamma-glutamyl transferase (GGT), and ferritin. A ferritin level of >300 U/L was observed in the group that presented more changes in liver function markers (ALT, AST, and GGT). Age ≥ 60 years, male sex, AST level > 25 U/L, and GGT level ≥ 50 or 32 U/L were associated with an ALT level > 29 U/L. A correlation was found between ALT and AST, LDH, GGT, and ferritin. Our findings suggest that ALT and AST levels may be elevated in patients with long-term COVID-19, especially in those hospitalised during the acute phase. In addition, an ALT level > 29 U/L was associated with changes in the levels of other markers of liver injury, such as LDH, GGT, and ferritin.
Pyrethroid and Chlorpyrifos Pesticide Exposure, General Intellectual Abilities, and Executive Functions of School Children from Montevideo, Uruguay
Authors: Rodríguez Danelly , Barg Gabriel , Queirolo Elena I. , Olson James R. , Mañay Nelly , Kordas Katarzyna
Published: March 2023

Children’s developing brains are susceptible to pesticides. Less is known about the effect of exposure to chlorpyrifos and pyrethroids on executive functions (EF). We measured urinary 3,5,6-trichloro-2-pyridinol (TCPy), a metabolite of chlorpyrifos, and urinary 3-phenoxybenzoic acid (3-PBA), a general, nonspecific metabolite of pyrethroids in first-grade children from Montevideo, Uruguay (n = 241, age 80.6 ± 6.4 months, 58.1% boys). EFs were assessed with the Intra-dimensional/Extra-dimensional shift (IED), Spatial Span (SSP), and Stockings of Cambridge (SOC) tests from the Cambridge Neuropsychological Test Automated (CANTAB) Battery. General intellectual ability (GIA) was assessed using the Woodcock–Muñoz Cognitive battery. Median (range) urinary TCPy and 3-PBA levels were 16.7 (1.9, 356.9) ng/mg of creatinine and 3.3 (0.3, 110.6) ng/mg of creatinine, respectively. In multivariable generalized linear models, urinary TCPy was inversely associated with postdimensional errors on the IED task β [95% CI]: −0.11 [−0.17, −0.06]. Urinary 3-PBA was inversely associated with the total number of trials −0.07 [−0.10, −0.04], and the total number of errors −0.12 [−0.18, −0.07] on the IED task. When TCPy and 3-PBA were modeled together, the associations did not differ from single-metabolite models. We found no evidence of effect modification by blood lead level (BLL). Pesticide exposure may affect EF performance in urban children.
Analysis and Forecast of Traffic Flow between Urban Functional Areas Based on Ride-Hailing Trajectories
Authors: Liao Zhuhua , Huang Haokai , Zhao Yijiang , Liu Yizhi , Zhang Guoqiang
Published: March 2023

Urban planning and function layout have important implications for the journeys of a large percentage of commuters, which often make up the majority of daily traffic in many cities. Therefore, the analysis and forecast of traffic flow among urban functional areas are of great significance for detecting urban traffic flow directions and traffic congestion causes, as well as helping commuters plan routes in advance. Existing methods based on ride-hailing trajectories are relatively effective solution schemes, but they often lack in-depth analyses on time and space. In the paper, to explore the rules and trends of traffic flow among functional areas, a new spatiotemporal characteristics analysis and forecast method of traffic flow among functional areas based on urban ride-hailing trajectories is proposed. Firstly, a city is divided into areas based on the actual urban road topology, and all functional areas are generated by using areas of interest (AOI); then, according to the proximity and periodicity of inter-area traffic flow data, the periodic sequence and the adjacent sequence are established, and the topological structure is learned through graph convolutional neural (GCN) networks to extract the spatial correlation of traffic flow among functional areas. Furthermore, we propose an attention-based gated graph convolutional network (AG-GCN) forecast method, which is used to extract the temporal features of traffic flow among functional areas and make predictions. In the experiment, the proposed method is verified by using real urban traffic flow data. The results show that the method can not only mine the traffic flow characteristics among functional areas under different time periods, directions, and distances, but also forecast the spatiotemporal change trend of traffic flow among functional areas in a multi-step manner, and the accuracy of the forecasting results is higher than that of common benchmark methods, reaching 96.82%.
Diacylglycerol Activates the Drosophila Light Sensitive Channel TRPL Expressed in HEK Cells
Authors: Rhodes-Mordov Elisheva , Brandwine-Shemmer Tal , Zaguri Rachel , Gutorov Rita , Peters Maximilian , Minke Baruch
Published: March 2023

Physiological activation by light of the Drosophila TRP and TRP-like (TRPL) channels requires the activation of phospholipase Cβ (PLC). The hydrolysis of phosphatidylinositol 4,5, bisphosphate (PIP2) by PLC is a crucial step in the still-unclear light activation, while the generation of Diacylglycerol (DAG) by PLC seems to be involved. In this study, we re-examined the ability of a DAG analogue 1-oleoyl-2-acetyl-sn-glycerol (OAG) to activate the TRPL channels expressed in HEK cells. Unlike previous studies, we added OAG into the cytosol via a patch-clamp pipette and observed robust activation of the expressed TRPL channels. However, TRPL channel activation was much slower than the physiologically activated TRPL by light. Therefore, we used a picosecond-fast optically activated DAG analogue, OptoDArG. Inactive OptoDArG was added into the intracellular solution with the patch-clamp pipette, and it slowly accumulated on the surface membrane of the recorded HEK cell in the dark. A fast application of intense UV light to the recorded cell resulted in a robust and relatively fast TRPL-dependent current that was greatly accelerated by the constitutively active TRPLF557I pore-region mutation. However, this current of the mutant channel was still considerably slower than the native light-induced TRPL current, suggesting that DAG alone is not sufficient for TRPL channel activation under physiological conditions.
Long Non-Coding RNAs (lncRNAs) as Regulators of the PI3K/AKT/mTOR Pathway in Gastric Carcinoma
Authors: Riquelme Ismael , Pérez-Moreno Pablo , Mora-Lagos Bárbara , Ili Carmen , Brebi Priscilla , Roa Juan Carlos
Published: March 2023

Gastric cancer (GC) represents ~10% of the global cancer-related deaths, increasingly affecting the younger population in active stages of life. The high mortality of GC is due to late diagnosis, the presence of metastasis and drug resistance development. Additionally, current clinical markers do not guide the patient management adequately, thereby new and more reliable biomarkers and therapeutic targets are still needed for this disease. RNA-seq technology has allowed the discovery of new types of RNA transcripts including long non-coding RNAs (lncRNAs), which are able to regulate the gene/protein expression of many signaling pathways (e.g., the PI3K/AKT/mTOR pathway) in cancer cells by diverse molecular mechanisms. In addition, these lncRNAs might also be proposed as promising diagnostic or prognostic biomarkers or as potential therapeutic targets in GC. This review describes important topics about some lncRNAs that have been described as regulators of the PI3K/AKT/mTOR signaling pathway, and hence, their potential oncogenic role in the development of this malignancy.
Notch-RBPJ Pathway for the Differentiation of Bone Marrow Mesenchymal Stem Cells in Femoral Head Necrosis
Authors: Liu Kangping , Ge Hongfan , Liu Chengyin , Jiang Yixin , Yu Yaling , Zhou Zhenlei
Published: March 2023

Femoral head necrosis (FHN) is a common leg disease in broilers, resulting in economic losses in the poultry industry. The occurrence of FHN is closely related to the decrease in the number of bone marrow mesenchymal stem cells (BMSCs) and the change in differentiation direction. This study aimed to investigate the function of differentiation of BMSCs in the development of FHN. We isolated and cultured BMSCs from spontaneous FHN-affected broilers and normal broilers, assessed the ability of BMSCs into three lineages by multiple staining methods, and found that BMSCs isolated from FHN-affected broilers demonstrated enhanced lipogenic differentiation, activated Notch-RBPJ signaling pathway, and diminished osteogenic and chondrogenic differentiation. The treatment of BMSCs with methylprednisolone (MP) revealed a significant decrease in the expressions of Runx2, BMP2, Col2a1 and Aggrecan, while the expressions of p-Notch1/Notch1, Notch2 and RBPJ were increased significantly. Jagged-1 (JAG-1, Notch activator)/DAPT (γ-secretase inhibitor) could promote/inhibit the osteogenic or chondrogenic ability of MP-treated BMSCs, respectively, whereas the differentiation ability of BMSCs was restored after transfection with si-RBPJ. The above results suggest that the Notch-RBPJ pathway plays important role in FHN progression by modulating the osteogenic and chondrogenic differentiation of BMSCs.
Cytomegalovirus Glycoprotein B Genotype in Patients with Anterior Segment Infection
Authors: Huang Chu-Yen , Cheng Yu-Chun , Hwang Yih-Shiou , Kang Eugene Yu-Chuan , Hsiao Ching-Hsi
Published: March 2023

(1) The glycoprotein B (gB) on the viral envelope, encoded by the most widely characterised polymorphic gene, gpUL55, is responsible for cytomegalovirus (CMV) entry into the host and could serve as a potential marker of pathogenicity. The aim of the present study is to investigate the distribution of the CMV gB genotype in anterior segment infection in Taiwan and its correlation with clinical manifestations and outcomes. (2) Fifty-seven patients with CMV anterior segment infection were identified according to clinical features and positivity for CMV DNA in aqueous humour samples. CMV gB genotyping was performed through polymerase chain reaction assays. Patients’ medical records were retrospectively reviewed. (3) Among the 57 aqueous humour samples tested for gB, 40 (70.28%) had multiple gB genotypes, and only 17 (29.82%) had a single gB genotype. Compared with single-genotype infection, multiple-genotype infection was correlated with higher CMV loads (p < 0.001) but not correlated with outcome. A higher proportion of patients with the gB3 genotype had received filtering surgery before antiviral treatment than those without the gB3 genotype (p = 0.046). (4) Multiple-genotype infection was highly prevalent in CMV anterior segment infection in Taiwan, and gB1 and gB3 were predominant. Multiple-genotype infection was correlated with higher CMV loads but not with specific clinical manifestations or prognostic outcomes. The gB3 genotype may be correlated with poor intraocular pressure control.
On the Use of Pseudo-Protic Ionic Liquids to Extract Gold(III) from HCl Solutions
Authors: Alguacil Francisco Jose , Robla Jose Ignacio
Published: March 2023

Solvent extraction of gold(III) from HCl media using pseudo-protic ionic liquids (PPILs) dissolved in toluene as the extractant phase is investigated. Three PPILs are generated from the reaction of commercially available amines and 1 M HCl solution and named as pri-NH2H+Cl− (derived from the primary amine Primene 81R), sec-NHH+Cl− (derived from the secondary amine Amberlite LA2) and ter-NH+Cl− (derived from the tertiary amine Hostarex A327). In the above structures, -NH2H+Cl−, -NHH+Cl− and -NH+Cl− represented the active groups (anion exchangers) of the respective PPIL. In the case of gold(III) extraction, the experimental variables investigated included the equilibration time (2.5–30 min), temperature (20–60 °C), HCl concentrations (1–10 M) in the aqueous phase, gold(III) concentration (0.005–0.05 g/L) in this same phase, and PPILs concentrations in the organic phase. From the experimental data, and using the Specific Interaction Theory, the interaction coefficients (ε) for the pair AuCl4−, H+ are estimated for the systems involving the three PPILs. Gold(III) is recovered from the metal-loaded organic phases using sodium thiocyanate solutions, and from these, gold is finally recovered by the precipitation of zero-valent gold (ZVG) nanoparticles.
Deciphering the Mechanism of Tolerance to Apple Replant Disease Using a Genetic Mapping Approach in a Malling 9 × M. × robusta 5 Population Identifies SNP Markers Linked to Candidate Genes
Authors: Reim Stefanie , Emeriewen Ofere Francis , Peil Andreas , Flachowsky Henryk
Published: March 2023

Apple replant disease (ARD) is a worldwide economic risk in apple production. Although several studies have shown that the wild apple accession Malus × robusta 5 (Mr5) is ARD-tolerant, the genetics of this tolerance have not yet been elucidated. A genetic mapping approach with a biparental population derived from contrasting parents involving molecular markers provides a means for marker-assisted selection of genetically complex traits and for determining candidate genes. In this study, we crossed the ARD-tolerant wild apple accession Mr5 and the ARD-susceptible rootstock ‘M9’ and analyzed the resultant progeny for ARD tolerance. Hence, a high-density genetic map using a tunable genotyping-by-sequencing (tGBS) approach was established. A total of 4804 SNPs together with 77 SSR markers were included in the parental maps comprising 17 linkage groups. The phenotypic responses to ARD were evaluated for 106 offspring and classified by an ARD-susceptibility index (ASI). A Kruskal–Wallis test identified SNP markers and one SSR marker on linkage groups (LG) 6 and 2 that correlated with ARD tolerance. We found nine candidate genes linked with these markers, which may be associated with plant response to ARD. These candidate genes provide some insight into the defense mechanisms against ARD and should be studied in more detail.
Hyperglycemia Aggravates Periodontitis via Autophagy Impairment and ROS-Inflammasome-Mediated Macrophage Pyroptosis
Authors: Zhao Zhenxing , Ming Ye , Li Xiang , Tan Hao , He Xinyi , Yang Lan , Song Jinlin , Zheng Leilei
Published: March 2023

Macrophage pyroptosis drives the secretion of IL-1β, which has been recently reported to be a featured salivary biomarker for discriminating periodontitis in the presence of diabetes. This study aimed to explore whether macrophage pyroptosis plays a role in the development of diabetes mellitus–periodontitis, as well as potential therapeutic strategies. By establishing a model of experimental diabetes mellitus–periodontitis in rats, we found that IL-1β and gasdermin D were highly expressed, leading to aggravated destruction of periodontal tissue. MCC950, a potent and selective molecule inhibitor of the NLRP3 inflammasome, effectively inhibited macrophage pyroptosis and attenuated alveolar bone losses in diabetes mellitus–periodontitis. Consistently, in vitro, high glucose could induce macrophage pyroptosis and thus promoted IL-1β production in macrophages stimulated by lipopolysaccharide. In addition, autophagy blockade by high glucose via the mTOR-ULK1 pathway led to severe oxidative stress response in macrophages stimulated by lipopolysaccharide. Activation of autophagy by rapamycin, clearance of mitochondrial ROS by mitoTEMPO, and inhibition of inflammasome by MCC950 could significantly reduce macrophage pyroptosis and IL-1β secretion. Our study demonstrates that hyperglycemia promotes IL-1β production and pyroptosis in macrophages suffered by periodontal microbial stimuli. Modulation of autophagy activity and specific targeting of the ROS-inflammasome pathway may offer promising therapeutic strategies to alleviate diabetes mellitus–periodontitis.
Effect of Electric Field on α-Synuclein Fibrils: Revealed by Molecular Dynamics Simulations
Authors: Razzokov Jamoliddin , Fazliev Sunnatullo , Makhkamov Mukhriddin , Marimuthu Parthiban , Baev Artyom , Kurganov Erkin
Published: March 2023

The self-association of amylogenic proteins to the fibril form is considered a pivotal factor in the pathogenesis of neurodegenerative diseases, including Parkinson’s disease (PD). PD causes unintended or uncontrollable movements in its common symptoms. α-synuclein is the major cause of PD development and thus has been the main target of numerous studies to suppress and sequester its expression or effectively degrade it. Nonetheless, to date, there are no efficient and proven ways to prevent pathological protein aggregation. Recent investigations proposed applying an external electric field to interrupt the fibrils. This method is a non-invasive approach that has a certain benefit over others. We performed molecular dynamics (MD) simulations by applying an electric field on highly toxic fibrils of α-synuclein to gain a molecular-level insight into fibril disruption mechanisms. The results revealed that the applied external electric field induces substantial changes in the conformation of the α-synuclein fibrils. Furthermore, we show the threshold value for electric field strength required to completely disrupt the α-synuclein fibrils by opening the hydrophobic core of the fibril. Thus, our findings might serve as a valuable foundation to better understand molecular-level mechanisms of the α-synuclein fibrils disaggregation process under an applied external electric field.
DNA Damage-Mediated Neurotoxicity in Parkinson’s Disease
Authors: Wang Zhong-Xuan , Li Yao-Lin , Pu Jia-Li , Zhang Bao-Rong
Published: March 2023

Parkinson’s disease (PD) is the second most common neurodegenerative disease around the world; however, its pathogenesis remains unclear so far. Recent advances have shown that DNA damage and repair deficiency play an important role in the pathophysiology of PD. There is growing evidence suggesting that DNA damage is involved in the propagation of cellular damage in PD, leading to neuropathology under different conditions. Here, we reviewed the current work on DNA damage repair in PD. First, we outlined the evidence and causes of DNA damage in PD. Second, we described the potential pathways by which DNA damage mediates neurotoxicity in PD and discussed the precise mechanisms that drive these processes by DNA damage. In addition, we looked ahead to the potential interventions targeting DNA damage and repair. Finally, based on the current status of research, key problems that need to be addressed in future research were proposed.
The Regulatory Axis of PD-L1 Isoform 2/TNF/T Cell Proliferation Is Required for the Canonical Immune-Suppressive Effects of PD-L1 Isoform 1 in Liver Cancer
Authors: Zheng Xixi , Chen Xingdong , Wu Weicheng
Published: March 2023

Despite the well-studied effects of the full-length membrane-locating isoform Iso1 of Programmed Cell Death Protein-Ligand 1 (PD-L1) on immunosuppression, little is known about another membrane-locating isoform, Iso2. While expressional and survival analysis of liver cancer patients indicated that Iso2 plays a tumor-suppressive role, our results also indicated that the tumor-promoting and immune-suppressive effects of Iso1 depended on the positive expression of Iso2. Through mediation analysis, we discovered several downstream genes or pathways of Iso2 and investigated their effects on the Iso1-regulating survival. Among all potential downstream immune factors, Iso2 was inclined to activate the proliferation of T cells by regulating chemokine activity and increasing CD3 levels by promoting TNF expression. Similar results were confirmed in the Mongolian liver cancer cohort, and the Iso2/TNF/T-cell axis was verified in several other cancers in the TCGA cohort. Finally, we demonstrated the promoting effects of Iso2 in terms of producing TNF and increasing T cells both in vitro and in vivo. Our findings illustrate that PD-L1 Iso2 can increase the number of T cells in the tumor microenvironment by elevating TNF levels, which is a necessary part of the tumor-suppressive effects of Iso1 in liver cancer.
Searching for Osmosensing Determinants in Poplar Histidine-Aspartate Kinases
Authors: Makhokh Hanae , Lafite Pierre , Larcher Mélanie , Lamblin Frédéric , Chefdor Françoise , Depierreux Christiane , Tanigawa Mirai , Maeda Tatsuya , Carpin Sabine , Héricourt François
Published: March 2023

Previous works have shown the existence of protein partnership, belonging to a MultiStep Phosphorelay (MSP), potentially involved in osmosensing in Populus. The first actor of this signalling pathway belongs to the histidine-aspartate kinase (HK) family, which also includes the yeast osmosensor Sln1, as well as the Arabidopsis putative osmosensor AHK1. In poplar, the homologous AHK1 protein corresponds to a pair of paralogous proteins, HK1a and HK1b, exhibiting an extracellular domain (ECD), as in Sln1 and AHK1. An ECD alignment of AHK1-like proteins, from different plant species, showed a particularly well conserved ECD and revealed the presence of a cache domain. This level of conservation suggested a functional role of this domain in osmosensing. Thus, we tested this possibility by modelling assisted mutational analysis of the cache domain of the Populus HK1 proteins. The mutants were assessed for their ability to respond to different osmotic stress and the results point to an involvement of this domain in HK1 functionality. Furthermore, since HK1b was shown to respond better to stress than HK1a, these two receptors constituted a good system to search for osmosensing determinants responsible for this difference in efficiency. With domain swapping experiments, we finally demonstrated that the cache domain, as well as the second transmembrane domain, are involved in the osmosensing efficiency of these receptors.
miR-125b-5p, miR-155-3p, and miR-214-5p and Target E2F2 Gene in Oral Squamous Cell Carcinoma
Authors: Gołąbek Karolina , Hudy Dorota , Świętek Agata , Gaździcka Jadwiga , Dąbrowska Natalia , Miśkiewicz-Orczyk Katarzyna , Zięba Natalia , Misiołek Maciej , Strzelczyk Joanna Katarzyna
Published: March 2023

It is known that E2F2 (E2F transcription factor 2) plays an important role as controller in the cell cycle. This study aimed to analyse the expression of the E2F2 gene and E2F2 protein and demonstrate E2F2 target microRNAs (miRNAs) candidates (miR-125b-5p, miR-155-3p, and miR-214-5p) in oral squamous cell carcinoma tumour and margin samples. The study group consisted 50 patients. The E2F2 gene and miRNAs expression levels were assessed by qPCR, while the E2F2 protein was assessed by ELISA. When analysing the effect of miRNAs expression on E2F2 gene expression and E2F2 protein level, we observed no statistically significant correlations. miR-125b-5p was downregulated, while miR-155-3p, and miR-214-5p were upregulated in tumour samples compared to margin. We observed a difference between the miR-125b-5p expression level in smokers and non-smokers in margin samples. Furthermore, HPV-positive individuals had a significantly higher miR-125b-5p and miR-214-5p expression level compared to HPV-negative patients in tumour samples. The study result showed that the E2F2 gene is not the target for analysed miRNAs in OSCC. Moreover, miR-155-3p and miR-125b-5p could play roles in the pathogenesis of OSCC. A differential expression of the analysed miRNAs was observed in response to tobacco smoke and HPV status.
Toughening Thermoelectric Materials: From Mechanisms to Applications
Authors: Wu Luoqi , Feng Xiaobin , Cao Ke , Li Guodong
Published: March 2023

With the tendency of thermoelectric semiconductor devices towards miniaturization, integration, and flexibility, there is an urgent need to develop high-performance thermoelectric materials. Compared with the continuously enhanced thermoelectric properties of thermoelectric materials, the understanding of toughening mechanisms lags behind. Recent advances in thermoelectric materials with novel crystal structures show intrinsic ductility. In addition, some promising toughening strategies provide new opportunities for further improving the mechanical strength and ductility of thermoelectric materials. The synergistic mechanisms between microstructure-mechanical performances are expected to show a large set of potential applications in flexible thermoelectric devices. This review explores enlightening research into recent intrinsically ductile thermoelectric materials and promising toughening strategies of thermoelectric materials to elucidate their applications in the field of flexible thermoelectric devices.
The Novel Compound SUL-138 Counteracts Endothelial Cell and Kidney Dysfunction in Sepsis by Preserving Mitochondrial Function
Authors: Star Bastiaan S. , van der Slikke Elisabeth C. , van Buiten Azuwerus , Henning Robert H. , Bouma Hjalmar R.
Published: March 2023

Sepsis is defined as a dysregulated host response leading to organ dysfunction, which may ultimately result in the patient’s death. Mitochondrial dysfunction plays a key role in developing organ dysfunction in sepsis. In this study, we explored the efficacy of the novel mitochondrial protective compound, SUL-138, in sepsis models in HUVECs and mice. In LPS-challenged HUVECs, SUL-138 preserved mitochondrial membrane potential and oxygen consumption and limited mitochondrial oxidative stress, resulting in increased survival at 48 h. Further, SUL-138 dampened the LPS-induced expression of IL-1β, but not of NLRP3, and IL-18 in HUVECs. Sepsis in mice induced by cecal ligation and puncture (CLP) led to a lower mitochondrial membrane potential and increased levels of mitochondrial oxidative stress in the kidney, which SUL-138 limited. In addition, SUL-138 mitigated the CLP-induced increase in kidney dysfunction markers NGAL and urea. It dampened the rise in kidney expression of IL-6, IL-1β, and ICAM-1, but not TNF-α and E-selectin. Yet, SUL-138 limited the increase in plasma levels of IL-6 and TNF-α of CLP mice. These results demonstrate that SUL-138 supports mitochondrial function, resulting in a limitation of systemic inflammation and preservation of kidney function.
Linking Benzene, in Utero Carcinogenicity and Fetal Hematopoietic Stem Cell Niches: A Mechanistic Review
Authors: Yusoff Nur Afizah , Abd Hamid Zariyantey , Budin Siti Balkis , Taib Izatus Shima
Published: March 2023

Previous research reported that prolonged benzene exposure during in utero fetal development causes greater fetal abnormalities than in adult-stage exposure. This phenomenon increases the risk for disease development at the fetal stage, particularly carcinogenesis, which is mainly associated with hematological malignancies. Benzene has been reported to potentially act via multiple modes of action that target the hematopoietic stem cell (HSCs) niche, a complex microenvironment in which HSCs and multilineage hematopoietic stem and progenitor cells (HSPCs) reside. Oxidative stress, chromosomal aberration and epigenetic modification are among the known mechanisms mediating benzene-induced genetic and epigenetic modification in fetal stem cells leading to in utero carcinogenesis. Hence, it is crucial to monitor exposure to carcinogenic benzene via environmental, occupational or lifestyle factors among pregnant women. Benzene is a well-known cause of adult leukemia. However, proof of benzene involvement with childhood leukemia remains scarce despite previously reported research linking incidences of hematological disorders and maternal benzene exposure. Furthermore, accumulating evidence has shown that maternal benzene exposure is able to alter the developmental and functional properties of HSPCs, leading to hematological disorders in fetus and children. Since HSPCs are parental blood cells that regulate hematopoiesis during the fetal and adult stages, benzene exposure that targets HSPCs may induce damage to the population and trigger the development of hematological diseases. Therefore, the mechanism of in utero carcinogenicity by benzene in targeting fetal HSPCs is the primary focus of this review.
Transcriptomic Analysis from Normal Glucose Tolerance to T2D of Obese Individuals Using Bioinformatic Tools
Authors: Errafii Khaoula , Boujraf Said , Chikri Mohamed
Published: March 2023

Understanding the role of white adipose tissue (WAT) in the occurrence and progression of metabolic syndrome is of considerable interest; among the metabolic syndromes are obesity and type 2 diabetes (T2D). Insulin resistance is a key factor in the development of T2D. When the target cells become resistant to insulin, the pancreas responds by producing more insulin to try to lower blood glucose. Over time, this can lead to a state of hyperinsulinemia (high levels of insulin in the blood), which can further exacerbate insulin resistance and contribute to the development of T2D. In order to understand the difference between healthy and unhealthy obese individuals, we have used published transcriptomic profiling to compare differences between the WAT obtained from obese diabetics and subjects who are obese with normal glucose tolerance and insulin resistance. The identification of aberrantly expressed messenger RNA (mRNA) and the resulting molecular interactions and signaling networks is essential for a better understanding of the progression from normal glucose-tolerant obese individuals to obese diabetics. Computational analyses using Ingenuity Pathway Analysis (IPA) identified multiple activated signaling networks in obesity progression from insulin-resistant and normal glucose-tolerant (IR-NGT) individuals to those with T2D. The pathways affected are: Tumor Necrosis Factor (TNF), Extracellular signal-Regulated protein Kinase 1/2 ERK1/2, Interleukin 1 A (IL1A), Protein kinase C (Pkcs), Convertase C5, Vascular endothelial growth factor (Vegf), REL-associated protein (RELA), Interleukin1/1 B (IL1/1B), Triggering receptor expressed on myeloid cells (TREM1) and Nuclear factor KB1 (NFKB1) networks, while functional annotation highlighted Liver X Receptor (LXR) activation, phagosome formation, tumor microenvironment pathway, LPS/IL-1 mediated inhibition of RXR function, TREM1 signaling and IL-6 signaling. Together, by conducting a thorough bioinformatics study of protein-coding RNAs, prospective targets could be exploited to clarify the molecular pathways underlying the development of obesity-related type 2 diabetes.
Mir-302a/TWF1 Axis Impairs the Myogenic Differentiation of Progenitor Cells through F-Actin-Mediated YAP1 Activation
Authors: Nguyen Mai Thi , Lee Wan
Published: March 2023

Actin cytoskeleton dynamics have been found to regulate myogenesis in various progenitor cells, and twinfilin-1 (TWF1), an actin-depolymerizing factor, plays a vital role in actin dynamics and myoblast differentiation. Nevertheless, the molecular mechanisms underlying the epigenetic regulation and biological significance of TWF1 in obesity and muscle wasting have not been explored. Here, we investigated the roles of miR-302a in TWF1 expression, actin filament modulation, proliferation, and myogenic differentiation in C2C12 progenitor cells. Palmitic acid, the most prevalent saturated fatty acid (SFA) in the diet, decreased the expression of TWF1 and impeded myogenic differentiation while increasing the miR-302a levels in C2C12 myoblasts. Interestingly, miR-302a inhibited TWF1 expression directly by targeting its 3′UTR. Furthermore, ectopic expression of miR-302a promoted cell cycle progression and proliferation by increasing the filamentous actin (F-actin) accumulation, which facilitated the nuclear translocation of Yes-associated protein 1 (YAP1). Consequently, by suppressing the expressions of myogenic factors, i.e., MyoD, MyoG, and MyHC, miR-302a impaired myoblast differentiation. Hence, this study demonstrated that SFA-inducible miR-302a suppresses TWF1 expression epigenetically and impairs myogenic differentiation by facilitating myoblast proliferation via F-actin-mediated YAP1 activation.
The Succession of the Cellulolytic Microbial Community from the Soil during Oat Straw Decomposition
Authors: Kimeklis Anastasiia K. , Gladkov Grigory V. , Orlova Olga V. , Afonin Alexey M. , Gribchenko Emma S. , Aksenova Tatiana S. , Kichko Arina A. , Pinaev Alexander G. , Andronov Evgeny E.
Published: March 2023

The process of straw decomposition is dynamic and is accompanied by the succession of the microbial decomposing community, which is driven by poorly understood interactions between microorganisms. Soil is a complex ecological niche, and the soil microbiome can serve as a source of potentially active cellulolytic microorganisms. Here, we performed an experiment on the de novo colonization of oat straw by the soil microbial community by placing nylon bags with sterilized oat straw in the pots filled with chernozem soil and incubating them for 6 months. The aim was to investigate the changes in decomposer microbiota during this process using conventional sequencing techniques. The bacterial succession during straw decomposition occurred in three phases: the early phase (first month) was characterized by high microbial activity and low diversity, the middle phase (second to third month) was characterized by low activity and low diversity, and the late phase (fourth to sixth months) was characterized by low activity and high diversity. Analysis of amplicon sequencing data revealed three groups of co-changing phylotypes corresponding to these phases. The early active phase was abundant in the cellulolytic members from Pseudomonadota, Bacteroidota, Bacillota, and Actinobacteriota for bacteria and Ascomycota for fungi, and most of the primary phylotypes were gone by the end of the phase. The second intermediate phase was marked by the set of phylotypes from the same phyla persisting in the community. In the mature community of the late phase, apart from the core phylotypes, non-cellulolytic members from Bdellovibrionota, Myxococcota, Chloroflexota, and Thermoproteota appeared. Full metagenome sequencing of the microbial community from the end of the middle phase confirmed that major bacterial and fungal members of this consortium had genes of glycoside hydrolases (GH) connected to cellulose and chitin degradation. The real-time analysis of the selection of these genes showed that their representation varied between phases, and this occurred under the influence of the host, and not the GH family factor. Our findings demonstrate that soil microbial community may act as an efficient source of cellulolytic microorganisms and that colonization of the cellulolytic substrate occurs in several phases, each characterized by its own taxonomic and functional profile.
The Zinc-BED Transcription Factor Bedwarfed Promotes Proportional Dendritic Growth and Branching through Transcriptional and Translational Regulation in Drosophila
Authors: Bhattacharjee Shatabdi , Iyer Eswar Prasad R. , Iyer Srividya Chandramouli , Nanda Sumit , Rubaharan Myurajan , Ascoli Giorgio A. , Cox Daniel N.
Published: March 2023

Dendrites are the primary points of sensory or synaptic input to a neuron and play an essential role in synaptic integration and neural function. Despite the functional importance of dendrites, relatively less is known about the underlying mechanisms regulating cell type-specific dendritic patterning. Herein, we have dissected the functional roles of a previously uncharacterized gene, CG3995, in cell type-specific dendritic development in Drosophila melanogaster. CG3995, which we have named bedwarfed (bdwf), encodes a zinc-finger BED-type protein that is required for proportional growth and branching of dendritic arbors. It also exhibits nucleocytoplasmic expression and functions in both transcriptional and translational cellular pathways. At the transcriptional level, we demonstrate a reciprocal regulatory relationship between Bdwf and the homeodomain transcription factor (TF) Cut. We show that Cut positively regulates Bdwf expression and that Bdwf acts as a downstream effector of Cut-mediated dendritic development, whereas overexpression of Bdwf negatively regulates Cut expression in multidendritic sensory neurons. Proteomic analyses revealed that Bdwf interacts with ribosomal proteins and disruption of these proteins resulted in phenotypically similar dendritic hypotrophy defects as observed in bdwf mutant neurons. We further demonstrate that Bdwf and its ribosomal protein interactors are required for normal microtubule and F-actin cytoskeletal architecture. Finally, our findings reveal that Bdwf is required to promote protein translation and ribosome trafficking along the dendritic arbor. These findings shed light on the complex, combinatorial, and multi-functional roles of transcription factors (TFs) in directing the diversification of cell type-specific dendritic development.