bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypoxia Generated by Avian Embryo Growth Induces the HIF-α Response and Critical Vascularization
Authors: Carroll Christopher , Engström Niklas , Nilsson Patrik F. , Haxen Emma R. , Mohlin Sofie , Berg Peter , Glud Ronnie N. , Hammarlund Emma U.
Published: June 2021

Cancer research has transformed our view on cellular mechanisms for oxygen sensing. It has been documented that these mechanisms are important for maintaining animal tissues and life in environments where oxygen (O2) concentrations fluctuate. In adult animals, oxygen sensing is governed by the Hypoxia Inducible Factors (HIFs) that are stabilized at low oxygen concentrations (hypoxia). However, the importance of hypoxia itself during development and for the onset of HIF-driven oxygen sensing remains poorly explored. Cellular responses to hypoxia associates with cell immaturity (stemness) and proper tissue and organ development. During mammalian development, the initial uterine environment is hypoxic. The oxygenation status during avian embryogenesis is more complex since O2 continuously equilibrates across the porous eggshell. Here, we investigate HIF dynamics and use microelectrodes to determine O2 concentrations within the egg and the embryo during the first four days of development. To determine the increased O2 consumption rates, we also obtain the O2 transport coefficient (DO2) of eggshell and associated inner and outer shell membranes, both directly (using microelectrodes in ovo for the first time) and indirectly (using water evaporation at 37.5°C for the first time). Our results demonstrate a distinct hypoxic phase (<5% O2) between day 1 and 2, concurring with the onset of HIF-α expression. This phase of hypoxia is demonstrably necessary for proper vascularization and survival. Our indirectly determined DO2 values are about 30% higher than those determined directly. A comparison with previously reported values indicates that this discrepancy may be real, reflecting that water vapor and O2 may be transported through the eggshell at different rates. Based on our obtained DO2 values, we demonstrate that increased O2 consumption of the growing embryo appears to generate the phase of hypoxia, which is also facilitated by the initially small gas cell and low membrane permeability. We infer that the phase of in ovo hypoxia facilitates correct avian development. These results support the view that hypoxic conditions, in which the animal clade evolved, remain functionally important during animal development. The study highlights that insights from the cancer field pertaining to the cellular capacities by which both somatic and cancer cells register and respond to fluctuations in O2 concentrations can broadly inform our exploration of animal development and success.
Rapid Evolution of Autosomal Binding Sites of the Dosage Compensation Complex in Drosophila melanogaster and Its Association With Transcription Divergence
Authors: Dai Aimei , Wang Yushuai , Greenberg Anthony , Liufu Zhongqi , Tang Tian
Published: June 2021

How pleiotropy influences evolution of protein sequence remains unclear. The male-specific lethal (MSL) complex in Drosophila mediates dosage compensation by 2-fold upregulation of the X chromosome in males. Nevertheless, several MSL proteins also bind autosomes and likely perform functions not related to dosage compensation. Here, we study the evolution of MOF, MSL1, and MSL2 biding sites in Drosophila melanogaster and its close relative Drosophila simulans. We found pervasive expansion of the MSL binding sites in D. melanogaster, particularly on autosomes. The majority of these newly-bound regions are unlikely to function in dosage compensation and associated with an increase in expression divergence between D. melanogaster and D. simulans. While dosage-compensation related sites show clear signatures of adaptive evolution, these signatures are even more marked among autosomal regions. Our study points to an intriguing avenue of investigation of pleiotropy as a mechanism promoting rapid protein sequence evolution.
Development of an Immune-Related LncRNA Prognostic Signature for Glioma
Authors: Cao Yudong , Zhu Hecheng , Tan Jun , Yin Wen , Zhou Quanwei , Xin Zhaoqi , Wu Zhaoping , Jiang Zhipeng , Guo Youwei , Kuang Yirui , Li Can , Zhao Ming , Jiang Xingjun , Peng Jiahui , Ren Caiping
Published: June 2021

Introduction

Glioma is the most common primary cancer of the central nervous system with dismal prognosis. Long noncoding RNAs (lncRNAs) have been discovered to play key roles in tumorigenesis in various cancers, including glioma. Because of the relevance between immune infiltrating and clinical outcome of glioma, identifying immune-related lncRNAs is urgent for better personalized management.

Materials and methods

Single-sample gene set enrichment analysis (ssGSEA) was applied to estimate immune infiltration, and glioma samples were divided into high immune cell infiltration group and low immune cell infiltration group. After screening differentially expressed lncRNAs in two immune groups, least absolute shrinkage and selection operator (LASSO) Cox regression analysis was performed to construct an immune-related prognostic signature. Additionally, we explored the correlation between immune infiltration and the prognostic signature.

Results

A total of 653 samples were appropriate for further analyses, and 10 lncRNAs were identified as immune-related lncRNAs in glioma. After univariate Cox regression and LASSO Cox regression analysis, six lncRNAs were identified to construct a prognostic signature for glioma, which could be taken as independent prognostic factors in both univariate and multivariate Cox regression analyses. Moreover, risk score was significantly correlated with all the 29 immune-related checkpoint expression (p < 0.05) in ssGSEA except neutrophils (p = 0.43).

Conclusion

The study constructed an immune-related prognostic signature for glioma, which contributed to improve clinical outcome prediction and guide immunotherapy.
Structural Comparison Between MHC Classes I and II; in Evolution, a Class-II-Like Molecule Probably Came First
Authors: Wu Yanan , Zhang Nianzhi , Hashimoto Keiichiro , Xia Chun , Dijkstra Johannes M.
Published: June 2021

Structures of peptide-loaded major histocompatibility complex class I (pMHC-I) and class II (pMHC-II) complexes are similar. However, whereas pMHC-II complexes include similar-sized IIα and IIβ chains, pMHC-I complexes include a heavy chain (HC) and a single domain molecule β2-microglobulin (β2-m). Recently, we elucidated several pMHC-I and pMHC-II structures of primitive vertebrate species. In the present study, a comprehensive comparison of pMHC-I and pMHC-II structures helps to understand pMHC structural evolution and supports the earlier proposed—though debated—direction of MHC evolution from class II-type to class I. Extant pMHC-II structures share major functional characteristics with a deduced MHC-II-type homodimer ancestor. Evolutionary establishment of pMHC-I presumably involved important new functions such as (i) increased peptide selectivity by binding the peptides in a closed groove (ii), structural amplification of peptide ligand sequence differences by binding in a non-relaxed fashion, and (iii) increased peptide selectivity by syngeneic heterotrimer complex formation between peptide, HC, and β2-m. These new functions were associated with structures that since their establishment in early pMHC-I have been very well conserved, including a shifted and reorganized P1 pocket (aka A pocket), and insertion of a β2-m hydrophobic knob into the peptide binding domain β-sheet floor. A comparison between divergent species indicates better sequence conservation of peptide binding domains among MHC-I than among MHC-II, agreeing with more demanding interactions within pMHC-I complexes. In lungfishes, genes encoding fusions of all MHC-IIα and MHC-IIβ extracellular domains were identified, and although these lungfish genes presumably derived from classical MHC-II, they provide an alternative mechanistic hypothesis for how evolution from class II-type to class I may have occurred.
Expression of ACE2, Soluble ACE2, Angiotensin I, Angiotensin II and Angiotensin-(1-7) Is Modulated in COVID-19 Patients
Authors: Osman Ikram Omar , Melenotte Cléa , Brouqui Philippe , Million Matthieu , Lagier Jean-Christophe , Parola Philippe , Stein Andréas , La Scola Bernard , Meddeb Line , Mege Jean-Louis , Raoult Didier , Devaux Christian A.
Published: June 2021

The etiological agent of COVID-19 SARS-CoV-2, is primarily a pulmonary-tropic coronavirus. Infection of alveolar pneumocytes by SARS-CoV-2 requires virus binding to the angiotensin I converting enzyme 2 (ACE2) monocarboxypeptidase. ACE2, present on the surface of many cell types, is known to be a regulator of blood pressure homeostasis through its ability to catalyze the proteolysis of Angiotensin II (Ang II) into Angiotensin-(1-7) [Ang-(1-7)]. We therefore hypothesized that SARS-CoV-2 could trigger variations of ACE2 expression and Ang II plasma concentration in SARS-CoV-2-infected patients. We report here, that circulating blood cells from COVID-19 patients express less ACE2 mRNA than cells from healthy volunteers. At the level of circulating cells, this ACE2 gene dysregulation mainly affects the monocytes, which also show a lower expression of membrane ACE2 protein. Moreover, soluble ACE2 (sACE2) plasma concentrations are lower in prolonged viral shedders than in healthy controls, while the concentration of sACE2 returns to normal levels in short viral shedders. In the plasma of prolonged viral shedders, we also found higher concentrations of Ang II and angiotensin I (Ang I). On the other hand, the plasma levels of Ang-(1-7) remains almost stable in prolonged viral shedders but seems insufficient to prevent the adverse effects of Ang II accumulation. Altogether, these data evidence that the SARS-CoV-2 may affect the expression of blood pressure regulators with possible harmful consequences on COVID-19 outcome.
Characterization of Human Genes Modulated by Porphyromonas gingivalis Highlights the Ribosome, Hypothalamus, and Cholinergic Neurons
Authors: Patel Sejal , Howard Derek , Chowdhury Nityananda , Derieux Casey , Wellslager Bridgette , Yilmaz Özlem , French Leon
Published: June 2021

Porphyromonas gingivalis, a bacterium associated with periodontal disease, is a suspected cause of Alzheimer’s disease. This bacterium is reliant on gingipain proteases, which cleave host proteins after arginine and lysine residues. To characterize gingipain susceptibility, we performed enrichment analyses of arginine and lysine proportion proteome-wide. Genes differentially expressed in brain samples with detected P. gingivalis reads were also examined. Genes from these analyses were tested for functional enrichment and specific neuroanatomical expression patterns. Proteins in the SRP-dependent cotranslational protein targeting to membrane pathway were enriched for these residues and previously associated with periodontal and Alzheimer’s disease. These ribosomal genes are up-regulated in prefrontal cortex samples with detected P. gingivalis sequences. Other differentially expressed genes have been previously associated with dementia (ITM2B, MAPT, ZNF267, and DHX37). For an anatomical perspective, we characterized the expression of the P. gingivalis associated genes in the mouse and human brain. This analysis highlighted the hypothalamus, cholinergic neurons, and the basal forebrain. Our results suggest markers of neural P. gingivalis infection and link the cholinergic and gingipain hypotheses of Alzheimer’s disease.
Monocytic Ontogeny of Regenerated Macrophages Characterizes the Mesotheliomagenic Responses to Carbon Nanotubes
Authors: Orsi Micaela , Palmai-Pallag Mihaly , Yakoub Yousof , Ibouraadaten Saloua , De Beukelaer Michèle , Bouzin Caroline , Bearzatto Bertrand , Ambroise Jérôme , Gala Jean-Luc , Brusa Davide , Lison Dominique , Huaux François
Published: June 2021

Macrophages are not only derived from circulating blood monocytes or embryonic precursors but also expand by proliferation. The origin determines macrophage fate and functions in steady state and pathological conditions. Macrophages predominantly infiltrate fibre-induced mesothelioma tumors and contribute to cancer development. Here, we revealed their ontogeny by comparing the response to needle-like mesotheliomagenic carbon nanotubes (CNT-7) with tangled-like non-mesotheliomagenic CNT-T. In a rat peritoneal cavity model of mesothelioma, both CNT induced a rapid macrophage disappearance reaction (MDR) of MHCIIlow resident macrophages generating an empty niche available for macrophage repopulation. Macrophage depletion after mesotheliomagenic CNT-7 was followed by a substantial inflammatory reaction, and macrophage replenishment completed after 7 days. Thirty days after non-mesotheliomagenic CNT-T, macrophage repopulation was still incomplete and accompanied by a limited inflammatory reaction. Cell depletion experiments, flow cytometry and RNA-seq analysis demonstrated that, after mesotheliomagenic CNT-7 exposure, resident macrophages were mainly replaced by an influx of monocytes, which differentiated locally into MHCIIhigh inflammatory macrophages. In contrast, the low inflammatory response induced by CNT-T was associated by the accumulation of self-renewing MHCIIlow macrophages that initially derive from monocytes. In conclusion, the mesotheliomagenic response to CNT specifically relies on macrophage niche recolonization by monocyte-derived inflammatory macrophages. In contrast, the apparent homeostasis after non-mesotheliomagenic CNT treatment involves a macrophage regeneration by proliferation. Macrophage depletion and repopulation are thus decisive events characterizing the carcinogenic activity of particles and fibres.
Activation of the Anti-Oxidative Stress Response Reactivates Latent HIV-1 Through the Mitochondrial Antiviral Signaling Protein Isoform MiniMAVS
Authors: Sarabia Indra , Novis Camille L. , Macedo Amanda B. , Takata Hiroshi , Nell Racheal , Kakazu Juyeon C. , Furler Robert L. , Shakya Binita , Schubert Heidi L. , Hill Christopher P. , DePaula-Silva Ana Beatriz , Spivak Adam M. , Trautmann Lydie , Planelles Vicente , Bosque Alberto
Published: June 2021

The mitochondrial antiviral signaling protein (MAVS) is part of the cell’s innate immune mechanism of defense. MAVS mRNA is bicistronic and can give rise to a full length-MAVS and a shorter isoform termed miniMAVS. In response to viral infections, viral RNA can be sensed by the cytosolic RNA sensors retinoic acid-inducible gene I (RIG-I) and/or melanoma differentiation-associated protein 5 (MDA5) and activate NF-κB through interaction with MAVS. MAVS can also sense cellular stress and activate an anti-oxidative stress (AOS) response through the activation of NF-κB. Because NF-κB is a main cellular transcription factor for HIV-1, we wanted to address what role MAVS plays in HIV-1 reactivation from latency in CD4 T cells. Our results indicate that RIG-I agonists required full length-MAVS whereas the AOS response induced by Dynasore through its catechol group can reactivate latent HIV-1 in a MAVS dependent manner through miniMAVS isoform. Furthermore, we uncover that PKC agonists, a class of latency-reversing agents, induce an AOS response in CD4 T cells and require miniMAVS to fully reactivate latent HIV-1. Our results indicate that the AOS response, through miniMAVS, can induce HIV-1 transcription in response to cellular stress and targeting this pathway adds to the repertoire of approaches to reactivate latent HIV-1 in ‘shock-and-kill’ strategies.
Impaired Meningeal Lymphatic Flow in NMOSD Patients With Acute Attack
Authors: Wang Xinxin , Tian Haiyan , Liu Han , Liang Dongxiao , Qin Chi , Zhu Qingyong , Meng Lin , Fu Yu , Xu Shuqin , Zhai Yanping , Ding Xuebing , Wang Xuejing
Published: June 2021

The meningeal lymphatic vessels (mLVs) in central nervous system (CNS) have been validated by rodent and human studies. The mLVs play a vital role in draining soluble molecules and trafficking lymphocytes, antigens and antibodies from CNS into cervical lymph nodes (CLNs). This indicates that mLVs may serve as a link between the CNS and peripheral immune system, perhaps involving in the neuroinflammatory disease. However, the morphology and drainage function of mLVs in patients with neuroinflammatory disease, such as neuromyelitis optica spectrum disorders (NMOSD), remains unexplored. Using the dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), we found that slower flow through mLVs along superior sagittal sinus in NMOSD patients with acute attack instead of NMOSD patients in chronic phase. The reduced flow in mLVs correlated with the disease severity evaluated by expanded disability status scale (EDSS). The receiver operating characteristic curve (ROC) indicated DCE-MRI might provide objective evidence to predict the acute relapse of NMOSD through evaluating the function of mLVs. Promoting or restoring the function of mLVs might be a new target for the treatment of NMOSD relapse.
Impact of Anti-Citrullinated Protein Antibodies on Progressive Systemic Bone Mineral Density Loss in Patients With Early Rheumatoid Arthritis After Two Years of Treat-to-Target
Authors: Bugatti Serena , Bogliolo Laura , Manzo Antonio , De Stefano Ludovico , Delvino Paolo , Motta Francesca , Montecucco Carlomaurizio
Published: June 2021

Objectives

To investigate the association of anti-citrullinated protein antibodies (ACPA) with changes in systemic bone mineral density (BMD) in patients with early rheumatoid arthritis (RA) after two years of treat-to-target.

Methods

BMD was measured at the lumbar spine (LS) and femoral neck (FN) in 100 patients with recent onset RA at baseline and after 24 months of treatment aimed at low disease activity (LDA) according to the 28-joints disease activity score (DAS28 <3.2). Multivariable regression analyses were performed to determine independent associations between autoantibodies and other disease and treatment-related parameters with BMD loss.

Results

After 24 months, the majority of the patients were at least in LDA (78%), with slightly more ACPA-positive subjects achieving the target. The BMD had significantly decreased at both the LS (mean [SD] percent loss -1.8 [6.2], p=0.03) and the FN (-2.4 [7.3], p=0.03) in ACPA-positive but not in ACPA-negative patients. Consequently, the proportion of patients with reduced BMD (Z score ≤-1) after 24 months was significantly higher among ACPA-positive patients at both the spine (39.5% vs 19.3%, p=0.05) and the hip (37.2% vs 12.2%, p=0.007). The association between ACPA and BMD loss was independent of other variables including age, gender, disease activity, cumulative dose of glucocorticoids and duration of therapy with bisphosphonates at the LS but not the FN.

Conclusions

ACPA are associated with ongoing BMD loss at the spine despite suppression of inflammation and adoption of prophylactic measures. ACPA-positive RA patients should be therefore strictly monitored for the development of osteoporosis.
Thrombin Generation and Platelet Function in ICU Patients Undergoing CVVHD Using Regional Citrate Anticoagulation
Authors: Wiegele Marion , Infanger Lukas , Lacom Conrad , Koch Stefan , Baierl Andreas , Schaden Eva
Published: June 2021

Background: To investigate pro- and anticoagulant alterations in uremic critically ill patients prior to and during continuous renal replacement therapy. In addition to the conventional thrombin generation assay (TGA), we performed a thrombomodulin-modified variant to better elucidate procoagulant imbalances. Platelet function was determined via multiple electrode aggregometry (MEA) to round off hemostatic analysis.

Methods: We prospectively enrolled patients at surgical intensive care units (ICU) with acute kidney injury undergoing continuous veno-venous hemodialysis using regional citrate anticoagulation. TGA and platelet function testing were performed at baseline (≤ 12 h prior to continuous renal replacement therapy) and on 3 consecutive days (day A–C) of extracorporeal therapy.

Results: We did not observe significant changes in thrombin generation after start or during renal replacement therapy. Ratios of endogenous thrombin potential in patients were significantly increased (p < 0.001) compared to standardized plasma of healthy donors confirming the assumed procoagulant alterations in ICU patients. Test results of the conventional TGA differed significantly (p < 0.05) from those of the thrombomodulin-modified assay. The area under the curve remained below MEA reference values during the entire observation period, indicating a persistent reduction in platelet function.

Conclusion: In summary, in-depth analysis using standard and modified TGA, as well as calculation of endogenous thrombin potential (ETP) ratios, revealed no further aggravation of the procoagulatory shift in the critically ill patient during CVVHD using regional citrate anticoagulation. MEA ruled out the potential impact of platelets.

Clinical Trial Registration: German Clinical Trials Register (DRKS00004336), 29 August 2012; www.drks.de.
Abnormal Fibrinogen Level as a Prognostic Indicator in Coronavirus Disease Patients: A Retrospective Cohort Study
Authors: Long Wei , Yang Jie , Li Zhengwei , Li Jinpeng , Chen Sichao , Chen Danyang , Wang Shipei , Li Qianqian , Hu Di , Huang Jianglong , Zeng Wen , Guo Liang , Wu Xiaohui
Published: June 2021

Purpose: The coronavirus disease (COVID-19) pandemic poses a global threat, and identification of its prognostic biomarkers could prove invaluable. Fibrinogen (FIB) could be one such indicator as coagulation and fibrinolysis abnormalities are common among COVID-19 patients. We examined the role of FIB levels in the prognosis of COVID-19.

Methods: This retrospective cohort study enrolled 1,643 COVID-19 patients from the Leishenshan Hospital in Wuhan, China. The follow-up was conducted from February 8, 2020 to April 15, 2020. The cohort was divided into three groups according to the FIB level on admission, and associations with mortality and disease severity were determined using Cox and logistic regression analyses, respectively. Further, Kaplan–Meier (K–M) analyses by log-rank tests were used to assess the survival of patients with varying FIB levels.

Results: Patients with FIB < 2.2 g/L [hazard ratio (HR): 9.02, 95% confidence interval (CI): 1.91–42.59, P = 0.006] and >4.2 g/L (HR: 4.79, 95% CI: 1.14–20.20, P = 0.033) showed higher mortality risks compared to those with FIB between 2.2 and 4.2 g/L. The survival curves showed similar results in K–M analyses (P < 0.001). Additionally, an elevated FIB level was associated with a greater risk of developing critical disease (odds ratio: 2.16, 95% CI: 1.04–4.46, P = 0.038) than a FIB level within the normal range.

Conclusion: Abnormal FIB levels may be associated with mortality risk among COVID-19 patients and could predict critical disease development. Thus, assessment of FIB levels may assist in determining the prognosis of COVID-19 patients.
Soft Devices for High-Resolution Neuro-Stimulation: The Interplay Between Low-Rigidity and Resolution
Authors: Vėbraitė Ieva , Hanein Yael
Published: June 2021

The field of neurostimulation has evolved over the last few decades from a crude, low-resolution approach to a highly sophisticated methodology entailing the use of state-of-the-art technologies. Neurostimulation has been tested for a growing number of neurological applications, demonstrating great promise and attracting growing attention in both academia and industry. Despite tremendous progress, long-term stability of the implants, their large dimensions, their rigidity and the methods of their introduction and anchoring to sensitive neural tissue remain challenging. The purpose of this review is to provide a concise introduction to the field of high-resolution neurostimulation from a technological perspective and to focus on opportunities stemming from developments in materials sciences and engineering to reduce device rigidity while optimizing electrode small dimensions. We discuss how these factors may contribute to smaller, lighter, softer and higher electrode density devices.
The Evaluation and Validation of Blood-Derived Novel Biomarkers for Precise and Rapid Diagnosis of Tuberculosis in Areas With High-TB Burden
Authors: Gong Zhen , Gu Yinzhong , Xiong Kunlong , Niu Jinxia , Zheng Ruijuan , Su Bo , Fan Lin , Xie Jianping
Published: June 2021

Tuberculosis (TB) remains a highly contagious public health threat. Precise and prompt diagnosis and monitoring of treatment responses are urgently needed for clinics. To pursue novel and satisfied host blood-derived biomarkers, we streamlined a bioinformatic pipeline by integrating differentially expressed genes, a gene co-expression network, and short time-series analysis to mine the published transcriptomes derived from whole blood of TB patients in the GEO database, followed by validating the diagnostic performance of biomarkers in both independent datasets and blood samples of Chinese patients using quantitative real-time PCR (qRT-PCR). We found that four genes, namely UBE2L6 (Ubiquitin/ISG15-conjugating enzyme E2 L6), BATF2 (Basic leucine zipper transcriptional factor ATF-like), SERPING1 (Plasma protease C1 inhibitor), and VAMP5 (Vesicle-associated membrane protein 5), had high diagnostic value for active TB. The transcription levels of these four gene combinations can reach up to 88% sensitivity and 78% specificity (average) for the diagnosis of active TB; the highest sensitivity can achieve 100% by parallel of BATF2 and VAMP5, and the highest specificity can reach 89.5% through a combination of SERPIG1, UBE2L6, and VAMP5, which were significantly higher than 75.3% sensitivity and 69.1% specificity by T-SPOT.TB in the same patients. Quite unexpectedly, the gene set can assess the efficacy of anti-TB response and differentiate active TB from Latent TB infection. The data demonstrated these four biomarkers might have great potency and advantage over IGRAs in the diagnosis of TB.
Synergistic Application of Molecular Markers and Community-Based Microbial Source Tracking Methods for Identification of Fecal Pollution in River Water During Dry and Wet Seasons
Authors: Liang Hongxia , Yu Zhisheng , Wang Bobo , Ndayisenga Fabrice , Liu Ruyin , Zhang Hongxun , Wu Gang
Published: June 2021

It is important to track fecal sources from humans and animals that negatively influence the water quality of rural rivers and human health. In this study, microbial source tracking (MST) methods using molecular markers and the community-based FEAST (fast expectation–maximization microbial source tracking) program were synergistically applied to distinguish the fecal contributions of multiple sources in a rural river located in Beijing, China. The performance of eight markers were evaluated using 133 fecal samples based on real-time quantitative (qPCR) technique. Among them, six markers, including universal (BacUni), human-associated (HF183-1 and BacH), swine-associated (Pig-2-Bac), ruminant-associated (Rum-2-Bac), and avian-associated (AV4143) markers, performed well in the study. A total of 96 water samples from the river and outfalls showed a coordinated composition of fecal pollution, which revealed that outfall water might be a potential input of the Fsq River. In the FEAST program, bacterial 16S rRNA genes of 58 fecal and 12 water samples were sequenced to build the “source” library and “sink,” respectively. The relative contribution (<4.01% of sequence reads) of each source (i.e., human, swine, bovine, or sheep) was calculated based on simultaneous screening of the operational taxonomic units (OTUs) of sources and sinks, which indicated that community-based MST methods could be promising tools for identifying fecal sources from a more comprehensive perspective. Results of the qPCR assays indicated that fecal contamination from human was dominant during dry weather and that fecal sources from swine and ruminant were more prevalent in samples during the wet season than in those during the dry season, which were consistent with the findings predicted by the FEAST program using a very small sample size. Information from the study could be valuable for the development of improved regulation policies to reduce the levels of fecal contamination in rural rivers.
A Simple Culture Method Enhances the Recovery of Culturable Actinobacteria From Coastal Sediments
Authors: Huang Zhaobin , Mo Shiqing , Yan Lifei , Wei Xiaomei , Huang Yuanyuan , Zhang Lizhen , Zhang Shuhui , Liu Jianzong , Xiao Qingqing , Lin Hong , Guo Yu
Published: June 2021

Molecular methods revealed that the majority of microbes in natural environments remains uncultivated. To fully understand the physiological and metabolic characteristics of microbes, however, culturing is still critical for microbial studies. Here, we used bacterial community analysis and four culture media, namely, traditional marine broth 2216 (MB), water extracted matter (WEM), methanol extracted matter (MEM), and starch casein agar (SCA), to investigate the diversity of cultivated bacteria in coastal sediments. A total of 1,036 isolates were obtained in pure culture, and they were classified into five groups, namely, Alphaproteobacteria (52.51%), Gammaproteobacteria (23.26%), Actinobacteria (13.32%), Firmicutes, and Bacteroidetes. Compared to other three media, WEM recovered a high diversity of actinobacteria (42 of 63 genotypes), with Micromonospora and Streptomyces as the most cultivated genera. Amplicon sequencing of the bacterial 16S ribosomal RNA (rRNA) gene V3–V4 fragment revealed eight dominant groups, Alphaproteobacteria (12.81%), Gammaproteobacteria (20.07%), Deltaproteobacteria (12.95%), Chloroflexi (13.09%), Bacteroidetes (8.28%), Actinobacteria (7.34%), Cyanobacteria (6.20%), and Acidobacteria (5.71%). The dominant members affiliated to Actinobacteria belonged to “Candidatus Actinomarinales,” “Candidatus Microtrichales,” and Nitriliruptorales. The cultivated actinobacteria accounted for a small proportion (<5%) compared to the actinobacterial community, which supported that the majority of actinobacteria are still waiting for cultivation. Our study concluded that WEM could be a useful and simple culture medium that enhanced the recovery of culturable actinobacteria from coastal sediments.
Attributes of Drying Define the Structure and Functioning of Microbial Communities in Temperate Riverbed Sediment
Authors: Schreckinger José , Mutz Michael , Mendoza-Lera Clara , Frossard Aline
Published: June 2021

Combined effects of climate change and increasing anthropogenic water demand have increased and extended dry period occurrences in rivers worldwide. Riverbed drying can significantly affect sediment microorganisms, crucial drivers of biogeochemical processes in lotic systems. In this study, we evaluated how sediment bacterial and fungal community structure and composition (based on 16S rRNA gene and ITS metabarcoding) and microbial functions (community respiration and extracellular enzymatic activities) respond to different riverbed drying intensities over 90 days. Riverbed sediment collected in a flowing reach of the Spree river in northeastern Germany was dried under different rates in outdoor mesocosms during the summer months of 2018. Our results demonstrate that drying attributes (duration and intensity) and sediment organic matter (OM) content play a crucial role in sediment microbial community assembly and functioning throughout drying. Milder drying surprisingly triggered a more rapid and drastic change in the microbial community composition and diversity. After 90 days of drying, Bacilli (Firmicutes) became the dominant bacterial class in most treatments, except in sediments with low OM content under the most severe drying treatment. Fungal amplicon sequence variants (ASVs) from Dothideomycetes (Ascomycota) had by far the highest relative abundance in all our treatments at the end of the drying experiment, making up 65.1% to 94.0% of the fungal reads. CO2 fluxes, a proxy for sediment community respiration, were rapidly and strongly affected by drying in all treatments. Our results imply that even short riverbed drying periods are likely to have significant consequences for the biogeochemical dynamics in recently formed non-perennial temperate rivers.
Therapeutic Peptides Targeting PPI in Clinical Development: Overview, Mechanism of Action and Perspectives
Authors: Cabri Walter , Cantelmi Paolo , Corbisiero Dario , Fantoni Tommaso , Ferrazzano Lucia , Martelli Giulia , Mattellone Alexia , Tolomelli Alessandra
Published: June 2021

Targeting protein-protein interactions (PPIs) has been recently recognized as an emerging therapeutic approach for several diseases. Up today, more than half a million PPI dysregulations have been found to be involved in pathological events. The dynamic nature of these processes and the involvement of large protein surfaces discouraged anyway the scientific community in considering them promising therapeutic targets. More recently peptide drugs received renewed attention since drug discovery has offered a broad range of structural diverse sequences, moving from traditionally endogenous peptides to sequences possessing improved pharmaceutical profiles. About 70 peptides are currently on the marked but several others are in clinical development. In this review we want to report the update on these novel APIs, focusing our attention on the molecules in clinical development, representing the direct consequence of the drug discovery process of the last 10 years. The comprehensive collection will be classified in function of the structural characteristics (native, analogous, heterologous) and on the basis of the therapeutic targets. The mechanism of interference on PPI will also be reported to offer useful information for novel peptide design.
Mild Cognitive Impairment and Neurofeedback: A Randomized Controlled Trial
Authors: Lavy Yotam , Dwolatzky Tzvi , Kaplan Zeev , Guez Jonathan , Todder Doron
Published: June 2021

Background and Objectives: Mild cognitive impairment (MCI) is often a precursor of dementia, and in particular of Alzheimer's Disease (AD) which is the most common cause of dementia. Individuals with amnestic MCI are several-fold more likely to develop AD than the general population. Therefore, MCI comprises a well-detectable, early stage time-point for therapeutic intervention and strategic prevention. Based on common electroencephalographical (EEG) pattern changes seen in individuals with MCI, we postulated that EEG-based neurofeedback could help improve the memory performance of patients with MCI. Memory performance is of particular importance in these patients, since memory decline is the most prominent symptom in most patients with MCI, and is the most predictive symptom for cognitive deterioration and the development of AD.

Methods: In order to improve the memory performance of patients with MCI we used a system of EEG-based neurofeedback in an attempt to reverse alterations of the EEG that are known to be common in patients with MCI. Our protocol comprised the provision of positive feedback in order to enhance the activity level of the upper alpha band. Participants were divided to two groups receiving either neurofeedback training to enhance the upper alpha frequency (Experimental group) or random feedbacks (Sham group)

Results: We witnessed a significant improvement in memory performance in subjects in the experimental group compared to those in the sham group. This improvement was maintained for at least 1 month.

Conclusions: Neurofeedback may be a promising and affordable novel approach for treating the decline in memory witnessed in patients with MCI.
Exercise Improves Movement by Regulating the Plasticity of Cortical Function in Hemiparkinsonian Rats
Authors: Shi Kaixuan , Liu Xiaoli , Hou Lijuan , Qiao Decai , Peng Yuan
Published: June 2021

Aberrant cortical spike-local field potential (LFP) coupling leads to abnormal basal ganglia activity, disruption of cortical function, and impaired movement in Parkinson's disease (PD). Here, the primary motor cortex mediated plasticity mechanism underlying behavioral improvement by exercise intervention was investigated. Exercise alleviates motor dysfunction and induces neuroplasticity in PD. In this study, Sprague-Dawley (SD) rats were injected with 6-hydroxydopamine (6-OHDA) to induce unilateral nigrostriatal dopamine depletion. Two weeks later, a 4-week exercise intervention was initiated in the PD + exercise (Ex) group. Multichannel recording technology recorded spikes and LFPs in rat motor cortices, and balanced ability tests evaluated behavioral performance. The balanced ability test showed that the total crossing time/front leg error/input latency time was significantly lower in PD + Ex rats than in PD rats (P < 0.05). Scalograms and LFP power spectra indicated increased beta-range LFP power in lesioned hemispheres, with exercise reducing LFP power spectral density. Spike-triggered LFP waveform averages showed strong phase-locking in PD motor cortex cells, and exercise reduced spike-LFP synchronization. Our results suggest that exercise can suppress overexcitability of LFPs and minimize spike-LFP synchronization in the motor cortex, leading to motor-improving effects in PD.
Advances in Theoretical Calculation of Halide Perovskites for Photocatalysis
Authors: Liu Xiaolin , Fan Jichao , Huang Changzhu
Published: June 2021

Photocatalysis, which includes water splitting for hydrogen fuel generation, degradation of organic pollutants, and CO2 reduction using renewable solar energy, is one of the most promising solutions for environmental protection and energy conversion. Halide perovskite has recently emerged as a new promising material for photocatalytic applications. The exploration of new efficient halide perovskite-based photocatalysts and understanding of photocatalytic reaction mechanisms can be revealed using theoretical calculations. The progress and applications of first-principles atomistic modeling and simulation of halide perovskite photocatalysts, including metal halide perovskites, halide perovskite heterojunctions, and other promising perovskite derivatives, are presented in this review. Critical insights into the challenges and future research directions of photocatalysis using halide perovskites are also discussed.
TDP-43 and Phosphorylated TDP-43 Levels in Paired Plasma and CSF Samples in Amyotrophic Lateral Sclerosis
Authors: Ren Yuting , Li Siyuan , Chen Siyu , Sun Xiaosun , Yang Fei , Wang Hongfen , Li Mao , Cui Fang , Huang Xusheng
Published: June 2021

Objective: The aim of this study was to measure both plasma and cerebrospinal fluid (CSF) TAR DNA-binding protein 43 (TDP-43) and phosphorylated TDP-43 (pTDP-43) levels in sporadic amyotrophic lateral sclerosis (sALS) patients, and to compare them with that of healthy controls. The correlation between plasma or CSF TDP-43/pTDP-43 and clinical indicators of ALS patients was assessed.

Methods: Paired plasma and CSF TDP-43/pTDP-43 levels in 69 ALS patients and 59 healthy controls were measured by sandwich ELISA. Time to generalization (TTG), an indicator suggested that the time of symptoms spreading from spinal or bulbar localization to both, was evaluated in all patients screened for mutations in genes associated with ALS.

Results: Both of the plasma TDP-43 and pTDP-43 levels were significantly higher in ALS patients than HCs (P < 0.001). The pTDP-43/TDP-43 ratios in plasma were significantly higher in HCs than ALS patients (P < 0.001). The area under the curve (AUC) value was 0.924 for plasma TDP-43 level, with a 91.3% sensitivity and 91.5% specificity. Moreover, the correlation between plasma and CSF TDP-43 was observed in each ALS patient (r = 0.195, P = 0.027). A correlation between CSF pTDP-43 levels and the ALSFRS-R (r = −0.245; P = 0.042) was established. A correlation was observed between plasma TDP-43 levels and TTG in ALS patients, which indicated that high levels of plasma TDP-43 correlated with prolonged TTG (r = 0.415; P = 0.004).

Conclusion: The plasma TDP-43 and pTDP-43 levels might play an important role in diagnosis in the future study of ALS. The plasma TDP-43 might differentiate ALS and HC groups based on high sensitivity and specificity, and as an indicator of progression of disease.
REM Sleep Behaviour Disorder in Multiple System Atrophy: From Prodromal to Progression of Disease
Authors: Giannini Giulia , Provini Federica , Cortelli Pietro , Calandra-Buonaura Giovanna
Published: June 2021

A higher frequency of motor and breathing sleep-related disorders in multiple system atrophy (MSA) populations is reported. REM sleep behaviour disorder (RBD) is one of the most robust markers of an underlying alpha-synucleinopathy. Although a large corpus of literature documented the higher prevalence of RBD in MSA, few studies have systematically investigated the prevalence of RBD as mode of disease onset and its role in disease progression. Moreover, there has been increasing interest in phenoconversion into synucleinopathies of cohorts of patients with isolated RBD (iRBD). Finally, some studies investigated RBD as predictive factor of conversion in isolated autonomic failure, a synucleinopathy presenting with autonomic failure as the sole clinical manifestation that could convert to a manifest central nervous system synucleinopathy. As the field of neurodegenerative disorders moves increasingly towards developing disease-modifying therapies, detecting individuals in the prodromal stage of these synucleinopathies becomes crucial. The aims of this review are to summarise (1) the prevalence of RBD during the course of MSA and as presenting feature of MSA (iRBD), (2) the RBD features in MSA, (3) MSA progression and prognosis in the subgroup of patients with RBD predating disease onset, and (4) the prevalence of MSA conversion in iRBD cohorts. Moreover, we summarise previous results on the role of RBD in the context of isolated autonomic failure as marker of phenoconversion to other synucleinopathies and, in particular, to MSA.
Two Aspects of Feedforward Control During a Fencing Lunge: Early and Anticipatory Postural Adjustments
Authors: Akbaş Anna , Marszałek Wojciech , Bacik Bogdan , Juras Grzegorz
Published: June 2021

The present study investigated whether expertise in fencing influences the onset of postural preparation during the fencing lunge and how it changes under different performance conditions. We also questioned if the onset of feedforward control can be categorized into one of the postural phases: anticipatory or early postural adjustment. Eight elite fencers and nine physical education students performed an attack with a lunge in self-paced and reaction time conditions from three different initial stance widths. The onset of the center of pressure (COP) displacement and EMG activities for the tibialis anterior (TA) of both limbs were recorded. The results show that expertise in fencing delays the onset of the activity of TA of the front leg and the onset of COP displacement during fencing lunge performance in comparison to controls. Additionally, in contrast to the control group, fencers produce typical APA patterns in the activation of TA under different performance conditions, delayed reaction time in comparison to self-initiated lunging, and constant time of APA onset under different widths of stance. According to different times and functions of TA activity and COP displacement in lunging, we propose to address them as anticipatory postural adjustment and early postural adjustment, respectively.
Radiofrequency Lesioning for Movement and Psychiatric Disorders-Experience of 107 Cases
Authors: Doshi Paresh K.
Published: June 2021

Background

Radiofrequency lesioning (RFL) though used since the 1950s, had been replaced by DBS in the 1990s. The availability of magnetic resonance-guided focused ultrasound for lesioning has renewed the interest in RFL.

Objective

This paper analysis RFL in contemporary Functional Neurosurgery for various indications and its outcome. Complication rates of RFL are compared with the same author’s experience of DBS.

Methods

One hundred and seven patients underwent RFL between 1998 and 2019. Indications included Parkinson’s Disease (PD), tremors, dystonia, and obsessive-compulsive disorders (OCD). The surgeries performed include thalamotomy (29), pallidotomy (49), subthalamotomy (23), and anterior capsulotomy/nucleus accumbens lesioning (6). Appropriate rating scales were used for preoperative and postoperative evaluations.

Results

There was a 25% recurrence rate of tremors for PD after thalamotomy. Writer’s cramp rating scale improved from a mean of 10.54–1.6 in task specific dystonia (TSD) patients, after thalamotomy. In PD patients, after pallidotomy, contralateral motor Unified Parkinson’s Disease Rating Scale (UPDRS) and dyskinesia scores, improved by 41 and 57%, respectively, at 1-year. Burke-Fahn-Marsden Dystonia Rating Scale in hemidystonia patients improved from 18.04 to 6.91, at 1-year. There was 32 and 31% improvement in total and motor UPDRS, respectively, in the subthalamotomy patients, at 2-year. All patients of OCD were in remission. There were three deaths in the pallidotomy group. Postoperative, dysarthria, confusion, hemiparesis, dyskinesia, and paraesthesia occurred in 12 patients, of which, 7 were transient.

Conclusion

RFL is a useful option in a select group of patients with tremors and dystonia. It is our preferred treatment option for TSD and OCD.
MRIES: A Matlab Toolbox for Mapping the Responses to Intracranial Electrical Stimulation
Authors: Sun Kaijia , Wang Haixiang , Bai Yunxian , Zhou Wenjing , Wang Liang
Published: June 2021

Propose

Directed cortical responses to intracranial electrical stimulation are a good standard for mapping inter-regional direct connectivity. Cortico-cortical evoked potential (CCEP), elicited by single pulse electrical stimulation (SPES), has been widely used to map the normal and abnormal brain effective network. However, automated processing of CCEP datasets and visualization of connectivity results remain challenging for researchers and clinicians. In this study, we develop a Matlab toolbox named MRIES (Mapping the Responses to Intracranial Electrical Stimulation) to automatically process CCEP data and visualize the connectivity results.

Method

The MRIES integrates the processing pipeline of the CCEP datasets and various methods for connectivity calculation based on low- and high-frequency signals with stimulation artifacts removed. The connectivity matrices are saved in different folders for visualization. Different visualization patterns (connectivity matrix, circle map, surface map, and volume map) are also integrated to the graphical user interface (GUI), which makes it easy to intuitively display and compare different connectivity measurements. Furthermore, one sample CCEP data set collected from eight epilepsy patients is used to validate the MRIES toolbox.

Result

We show the GUI and visualization functions of MRIES using one example CCEP data that has been described in a complete tutorial. We applied this toolbox to the sample CCEP data set to investigate the direct connectivity between the medial temporal lobe and the insular cortex. We find bidirectional connectivity between MTL and insular that are consistent with the findings of previous studies.

Conclusion

MRIES has a friendly GUI and integrates the full processing pipeline of CCEP data and various visualization methods. The MRIES toolbox, tutorial, and example data can be freely downloaded. As an open-source package, MRIES is expected to improve the reproducibility of CCEP findings and facilitate clinical translation.