bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of Next-Generation H3 Influenza Vaccines in Ferrets Pre-Immune to Historical H3N2 Viruses
Authors: Allen James D. , Ross Ted M.
Published: August 2021

Each person has a unique immune history to past influenza virus infections. Exposure to influenza viruses early in life establishes memory B cell populations that influence future immune responses to influenza vaccination. Current influenza vaccines elicit antibodies that are typically strain specific and do not offer broad protection against antigenically drifted influenza strains in all age groups of people. This is particularly true for vaccine antigens of the A(H3N2) influenza virus subtype, where continual antigenic drift necessitates frequent vaccine reformulation. Broadly-reactive influenza virus vaccine antigens offer a solution to combat antigenic drift, but they also need to be equally effective in all populations, regardless of prior influenza virus exposure history. This study examined the role that pre-existing immunity plays on influenza virus vaccination. Ferrets were infected with historical A(H3N2) influenza viruses isolated from either the 1970’s, 1980’s, or 1990’s and then vaccinated with computationally optimized broadly reactive antigens (COBRA) or wild-type (WT) influenza virus like particles (VLPs) expressing hemagglutinin (HA) vaccine antigens to examine the expansion of immune breadth. Vaccines with the H3 COBRA HA antigens had more cross-reactive antibodies following a single vaccination in all three pre-immune regimens than vaccines with WT H3 HA antigens against historical, contemporary, and future drifted A(H3N2) influenza viruses. The H3 COBRA HA vaccines also induced antibodies capable of neutralizing live virus infections against modern drifted A(H3N2) strains at higher titers than the WT H3 HA vaccine comparators.
Mouse Models of Germinal Center Derived B-Cell Lymphomas
Authors: Meyer Stefanie N. , Koul Sanjay , Pasqualucci Laura
Published: August 2021

Over the last decades, the revolution in DNA sequencing has changed the way we understand the genetics and biology of B-cell lymphomas by uncovering a large number of recurrently mutated genes, whose aberrant function is likely to play an important role in the initiation and/or maintenance of these cancers. Dissecting how the involved genes contribute to the physiology and pathology of germinal center (GC) B cells –the origin of most B-cell lymphomas– will be key to advance our ability to diagnose and treat these patients. Genetically engineered mouse models (GEMM) that faithfully recapitulate lymphoma-associated genetic alterations offer a valuable platform to investigate the pathogenic roles of candidate oncogenes and tumor suppressors in vivo, and to pre-clinically develop new therapeutic principles in the context of an intact tumor immune microenvironment. In this review, we provide a summary of state-of-the art GEMMs obtained by accurately modelling the most common genetic alterations found in human GC B cell malignancies, with a focus on Burkitt lymphoma, follicular lymphoma, and diffuse large B-cell lymphoma, and we discuss how lessons learned from these models can help guide the design of novel therapeutic approaches for this disease.
Analysis of Iron and Iron-Interacting Protein Dynamics During T-Cell Activation
Authors: Teh Megan R. , Frost Joe N. , Armitage Andrew E. , Drakesmith Hal
Published: August 2021

Recent findings have shown that iron is a powerful regulator of immune responses, which is of broad importance because iron deficiency is highly prevalent worldwide. However, the underlying reasons of why iron is needed by lymphocytes remain unclear. Using a combination of mathematical modelling, bioinformatic analysis and experimental work, we studied how iron influences T-cells. We identified iron-interacting proteins in CD4+ and CD8+ T-cell proteomes that were differentially expressed during activation, suggesting that pathways enriched with such proteins, including histone demethylation, may be impaired by iron deficiency. Consistent with this, iron-starved Th17 cells showed elevated expression of the repressive histone mark H3K27me3 and displayed reduced RORγt and IL-17a, highlighting a previously unappreciated role for iron in T-cell differentiation. Quantitatively, we estimated T-cell iron content and calculated that T-cell iron demand rapidly and substantially increases after activation. We modelled that these increased requirements will not be met during clinically defined iron deficiency, indicating that normalizing serum iron may benefit adaptive immunity. Conversely, modelling predicted that excess serum iron would not enhance CD8+ T-cell responses, which we confirmed by immunising inducible hepcidin knock-out mice that have very high serum iron concentrations. Therefore, iron deficiency impairs multiple aspects of T-cell responses, while iron overload likely has milder effects.
DNA Damage Repair Profiles Alteration Characterize a Hepatocellular Carcinoma Subtype With Unique Molecular and Clinicopathologic Features
Authors: Lin Peng , Gao Rui-zhi , Wen Rong , He Yun , Yang Hong
Published: August 2021

Hepatocellular carcinoma (HCC) is one of the most common malignancies and displays high heterogeneity of molecular phenotypes. We investigated DNA damage repair (DDR) alterations in HCC by integrating multi-omics data. HCC patients were classified into two heterogeneous subtypes with distinct clinical and molecular features: the DDR-activated subtype and the DDR-suppressed subtype. The DDR-activated subgroup is characterized by inferior prognosis and clinicopathological features that result in aggressive clinical behavior. Tumors of the DDR-suppressed class, which have distinct clinical and molecular characteristics, tend to have superior survival. A DDR subtype signature was ultimately generated to enable HCC DDR classification, and the results were confirmed by using multi-layer date cohorts. Furthermore, immune profiles and immunotherapy responses are also different between the two DDR subtypes. Altogether, this study illustrates the DDR heterogeneity of HCCs and is helpful to the understanding of personalized clinicopathological and molecular mechanisms responsible for unique tumor DDR profiles.
Eosinophils and Neutrophils Eliminate Migrating Strongyloides ratti Larvae at the Site of Infection in the Context of Extracellular DNA Trap Formation
Authors: Ehrens Alexandra , Rüdiger Nikolas , Heepmann Lennart , Linnemann Lara , Hartmann Wiebke , Hübner Marc P. , Breloer Minka
Published: August 2021

Parasitic nematodes such as hookworms actively penetrate the skin of their hosts, encountering skin-resident innate immune cells that represent the host´s first line of defense. Here we useStrongyloides rattias a model for an intestinal helminth parasite with tissue migrating stages. We show that interception and killing of migrating larvae in mice during a 1stinfection occurred predominantly in skin and muscle tissue before larvae migratedvialung and head tissue to the intestine. Inhibition of larval migration was even more efficient in immune mice during a 2ndinfection where larvae barely left the site of entry i.e. the foot. Using cell-deficient mice we show that interception in the tissue was predominantly mediated by neutrophils and eosinophils while basophils and mast cells were dispensablein vivo. Likewise, neutrophils and eosinophils inhibitedS. rattiL3 motilityin vitroin the context of ETosis. Thereby eosinophils were strictly dependent on the presence of anti-S. rattiantibodies while neutrophils inhibited L3 motility as such. Also, MPO and MMP-9 were released by neutrophils in response to L3 alone, but immune plasma further stimulated MPO release in an antibody-dependent manner. In summary, our findings highlight the central role of the skin as first line of defense against helminth parasites in both, innate and adaptive immunity.
Kynurenic Acid and Its Synthetic Derivatives Protect Against Sepsis-Associated Neutrophil Activation and Brain Mitochondrial Dysfunction in Rats
Authors: Poles Marietta Z. , Nászai Anna , Gulácsi Levente , Czakó Bálint L. , Gál Krisztián G. , Glenz Romy J. , Dookhun Dishana , Rutai Attila , Tallósy Szabolcs P. , Szabó Andrea , Lőrinczi Bálint , Szatmári István , Fülöp Ferenc , Vécsei László , Boros Mihály , Juhász László , Kaszaki József
Published: August 2021

Background and Aims

The systemic host response in sepsis is frequently accompanied by central nervous system (CNS) dysfunction. Evidence suggests that excessive formation of neutrophil extracellular traps (NETs) can increase the permeability of the blood–brain barrier (BBB) and that the evolving mitochondrial damage may contribute to the pathogenesis of sepsis-associated encephalopathy. Kynurenic acid (KYNA), a metabolite of tryptophan catabolism, exerts pleiotropic cell-protective effects under pro-inflammatory conditions. Our aim was to investigate whether exogenous KYNA or its synthetic analogues SZR-72 and SZR-104 affect BBB permeability secondary to NET formation and influence cerebral mitochondrial disturbances in a clinically relevant rodent model of intraabdominal sepsis.

Methods

Sprague–Dawley rats were subjected to fecal peritonitis (0.6 g kg-1 ip) or a sham operation. Septic animals were treated with saline or KYNA, SZR-72 or SZR-104 (160 µmol kg-1 each ip) 16h and 22h after induction. Invasive monitoring was performed on anesthetized animals to evaluate respiratory, cardiovascular, renal, hepatic and metabolic parameters to calculate rat organ failure assessment (ROFA) scores. NET components (citrullinated histone H3 (CitH3); myeloperoxidase (MPO)) and the NET inducer IL-1β, as well as IL-6 and a brain injury marker (S100B) were detected from plasma samples. After 24h, leukocyte infiltration (tissue MPO) and mitochondrial complex I- and II-linked (CI–CII) oxidative phosphorylation (OXPHOS) were evaluated. In a separate series, Evans Blue extravasation and the edema index were used to assess BBB permeability in the same regions.

Results

Sepsis was characterized by significantly elevated ROFA scores, while the increased BBB permeability and plasma S100B levels demonstrated brain damage. Plasma levels of CitH3, MPO and IL-1β were elevated in sepsis but were ameliorated by KYNA and its synthetic analogues. The sepsis-induced deterioration in tissue CI–CII-linked OXPHOS and BBB parameters as well as the increase in tissue MPO content were positively affected by KYNA/KYNA analogues.

Conclusion

This study is the first to report that KYNA and KYNA analogues are potential neuroprotective agents in experimental sepsis. The proposed mechanistic steps involve reduced peripheral NET formation, lowered BBB permeability changes and alleviation of mitochondrial dysfunction in the CNS.
Water Quality Improvement Shifts the Dominant Phytoplankton Group From Cryptophytes to Diatoms in a Coastal Ecosystem
Authors: Kang Yoonja , Moon Chang-Ho , Kim Hyun-Jung , Yoon Yang Ho , Kang Chang-Keun
Published: August 2021

We investigated long-term variations in the dominant phytoplankton groups with improvements in water quality over 11 years in the Yeongil Bay on the southeastern coast of Korea. River discharge declined during the study period but TN from river discharge remained stable, indicating the input of enriched nutrients to the bay was fairly consistent. NH4+ levels decreased with a decrease in TN from the POSCO industrial complex. While the study region was characterized by the P-limited and deficient environment, cryptophytes dominated with the intensified P-limitations. The relative abundance of cryptophytes declined from 70% in 2010 to 10% in 2016, but that of diatoms increased from 70% in 2009 to 90% in 2016. Correlation analysis showed a positive correlation of cryptophytes with NH4+ and a negative correlation with photic depth. Generalized additive models also exhibited an increase in diatom dominance and a decrease in cryptophyte dominance with an increase in water quality, indicating that a decrease in NH4+ and increase in light favored the diatom growth but suppressed the cryptophyte growth. Thus, water quality improvements shift the dominant group in the coastal ecological niche from cryptophytes to diatoms.
Reproduction and Sexual Maturity of European Sardine (Sardina pilchardus) in the Central Mediterranean Sea
Authors: Basilone Gualtiero , Ferreri Rosalia , Aronica Salvatore , Mazzola Salvatore , Bonanno Angelo , Gargano Antonella , Pulizzi Maurizio , Fontana Ignazio , Giacalone Giovanni , Calandrino Pietro , Genovese Simona , Barra Marco
Published: August 2021

Understanding drivers of fish maturity is essential to predict the productivity, stability, and resiliency of exploited populations. Size at maturity for European sardine (Sardina pilchardus) in the Central Mediterranean Sea has never been published within rigorous peer review process. In the past, stock assessment working groups in the Mediterranean requested such information; however, the size at which 50% of the fish population reaches the sexual maturity (L50) often received weak estimates based on a single or few years of observation, which do not necessarily reflect the whole stock. To address this data gap for the Central Mediterranean Sea, the present research estimated size at maturity of European sardine in the Strait of Sicily. In the study period (2009–2017), sampled individuals exhibited significant differences in size range as well as in body condition and reproductive effort. Data also permitted a clear identification of the spawning season, starting in September–October and ending in March–April the following year. Along the analyzed period, the size at first maturity ranged from 108 to 124 mm (total length) for females and from 102 to 122 mm for males. Significant differences were recorded among genders and years. Moreover, a goodness-of-fit measure was proposed to assess the robustness and reliability of L50 estimates, and thus selecting those that minimize the fitting-associated errors. Finally, results suggested that the low proportion of immature individuals in the samples represents the main source of bias in L50 estimation and possible solution was also proposed.
Printed and Laser-Scribed Stretchable Conductors on Thin Elastomers for Soft and Wearable Electronics
Authors: Keller Kirill , Grafinger David , Greco Francesco
Published: August 2021

As printed electronics is evolving toward applications in biosensing and wearables, the need for novel routes to fabricate flat, lightweight, stretchable conductors is increasing in importance but still represents a challenge, limiting the actual adoption of ultrathin wearable devices in real scenarios. A suitable strategy for creating soft yet robust and stretchable interconnections in the aforementioned technological applications is to use print-related techniques to pattern conductors on top of elastomer substrates. In this study, some thin elastomeric sheets—two forms of medical grade thermoplastic polyurethanes and a medical grade silicone—are considered as suitable substrates. Their mechanical, surface, and moisture barrier properties—relevant for their application in soft and wearable electronics—are first investigated. Various approaches are tested to pattern conductors, based on screen printing of 1) conducting polymer [poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS)] or 2) stretchable Ag ink and 3) laser scribing of laser-induced graphene (LIG). The electromechanical properties of these materials are investigated by means of tensile testing and concurrent electrical measurements up to a maximum strain of 100%. Performance of the different stretchable conductors is compared and rationalized, evidencing the differences in onset and propagation of failure. LIG conductors embedded into MPU have shown the best compromise in terms of electromechanical performance for the envisioned application. LIG/MPU showed full recovery of initial resistance after multiple stretching up to 30% strain and recovery of functionality even after 100% stretch. These have been then used in a proof-of-concept application as connectors for a wearable tattoo biosensor, providing a stable and lightweight connection for external wiring.
Strain Rate Effect on Mechanical Properties of the 3D-Printed Metamaterial Foams With Tunable Negative Poisson’s Ratio
Authors: Gao Di , Wang Bin , Gao Haoqiang , Ren Fuguang , Guo Chunxia , Ma Shuai , Cao Tiewa , Xia Yu , Wu Yansen
Published: August 2021

As a kind of metamaterial, the negative Poisson’s ratio foams, which expand (shrink) in the transverse direction when stretched (compressed) in the longitudinal direction, have many potential applications in fields such as aerospace and mechanical and biomedical engineering. In this paper, the out-of-plane crushing behaviors of four types of the orthogonal isotropic NPR convex-concave foams (CCF) were extensively studied using an electronic universal testing machine and Instron machine at different strain rates where each test was conducted at a constant compressive velocity under uniaxial compression. Strain rate effect on mechanical properties of these foams is experimentally studied. When the strain rate increases, the compressive force enhancement of the foams is obvious and varies with different specimens. The difference in energy absorption and deformation patterns for these foams between quasi-static and dynamic loading conditions is also analyzed. We find that the deformation patterns for the specimens are not only related to the compressive velocities but also the topologies of the specimens. The research in this paper is expected to be meaningful for the optimization design of the foam structures/materials widely used in the fields of aerospace and mechanical and biomedical engineering.
Case Report: Drug-Induced Immune Haemolytic Anaemia Caused by Cefoperazone-Tazobactam/ Sulbactam Combination Therapy
Authors: Wu Yuanjun , Wu Yong , Ji Yanli , Liang Jiajie , He Ziyi , Liu Yanhui , Tang Li , Guo Ganping
Published: August 2021

There has previously been a report of a patient developing haemolytic anaemia following exposure to cefoperazone. Another case has been reported involving the detection of cefoperazone-dependent antibodies in the absence of immune haemolytic anaemia. To date, no serological evidence has been reported to suggest that cefoperazone can lead to drug-induced immune haemolytic anaemia (DIIHA). This report aims to fill these gaps in knowledge by describing a case of DIIHA caused by cefoperazone-dependent antibodies. A 59-year-old man developed fatal haemolytic anaemia while receiving cefoperazone-tazobactam or cefoperazone-sulbactam for the treatment of a lung infection that occurred after craniocerebral surgery. This eventually led to renal function impairment. Prior to the discontinuation of cefoperazone treatment, the patient showed strong positive (4+) results for both anti-IgG and anti-C3d direct antiglobulin test (DAT), while cefoperazone-dependent IgM and IgG antibodies were detected. The patient's plasma and O-type RBCs were incubated with tazobactam or sulbactam solution at 37°C for 3 h, the results of DAT for anti-IgG and anti-C3d were both positive. Forty-three days after the discontinuation of cefoperazone, the results of DAT for anti-IgG and anti-C3d were negative. Meanwhile incubation of the patient's fresh serum and his own RBCs with cefoperazone at 37°C, gave rise to mild haemolysis, and the results of DAT for both anti-IgG and anti-C3d were positive. It is suggested that cefoperazone-dependent antibodies can activate complement, and the non-immunologic protein adsorption effect of tazobactam or sulbactam can enhance IgG and complement binding to RBCs. This may promote the formation of immunocomplexes and complement activation, thereby aggravating haemolysis.
Candidatus Methylumidiphilus Drives Peaks in Methanotrophic Relative Abundance in Stratified Lakes and Ponds Across Northern Landscapes
Authors: Martin Gaëtan , Rissanen Antti J. , Garcia Sarahi L. , Mehrshad Maliheh , Buck Moritz , Peura Sari
Published: August 2021

Boreal lakes and ponds produce two-thirds of the total natural methane emissions above the latitude of 50° North. These lake emissions are regulated by methanotrophs which can oxidize up to 99% of the methane produced in the sediments and the water column. Despite their importance, the diversity and distribution of the methanotrophs in lakes are still poorly understood. Here, we used shotgun metagenomic data to explore the diversity and distribution of methanotrophs in 40 oxygen-stratified water bodies in boreal and subarctic areas in Europe and North America. In our data, gammaproteobacterial methanotrophs (order Methylococcales) generally dominated the methanotrophic communities throughout the water columns. A recently discovered lineage of Methylococcales, Candidatus Methylumidiphilus, was present in all the studied water bodies and dominated the methanotrophic community in lakes with a high relative abundance of methanotrophs. Alphaproteobacterial methanotrophs were the second most abundant group of methanotrophs. In the top layer of the lakes, characterized by low CH4 concentration, their abundance could surpass that of the gammaproteobacterial methanotrophs. These results support the theory that the alphaproteobacterial methanotrophs have a high affinity for CH4 and can be considered stress-tolerant strategists. In contrast, the gammaproteobacterial methanotrophs are competitive strategists. In addition, relative abundances of anaerobic methanotrophs, Candidatus Methanoperedenaceae and Candidatus Methylomirabilis, were strongly correlated, suggesting possible co-metabolism. Our data also suggest that these anaerobic methanotrophs could be active even in the oxic layers. In non-metric multidimensional scaling, alpha- and gammaproteobacterial methanotrophs formed separate clusters based on their abundances in the samples, except for the gammaproteobacterial Candidatus Methylumidiphilus, which was separated from these two clusters. This may reflect similarities in the niche and environmental requirements of the different genera within alpha- and gammaproteobacterial methanotrophs. Our study confirms the importance of O2 and CH4 in shaping the methanotrophic communities and suggests that one variable cannot explain the diversity and distribution of the methanotrophs across lakes. Instead, we suggest that the diversity and distribution of freshwater methanotrophs are regulated by lake-specific factors.
A Multi-Sensor Mini-Bioreactor to Preselect Silage Inoculants by Tracking Metabolic Activity in situ During Fermentation
Authors: Shan Guilin , Rosner Victoria , Milimonka Andreas , Buescher Wolfgang , Lipski André , Maack Christian , Berchtold Wilfried , Wang Ye , Grantz David A. , Sun Yurui
Published: August 2021

The microbiome in silage may vary substantially from the onset to the completion of fermentation. Improved additives and inoculants are being developed to accelerate the ensiling process, to enhance fermentation quality, and to delay spoilage during feed-out. However, current methods for preselecting and characterizing these amendments are time-consuming and costly. Here, we have developed a multi-sensor mini-bioreactor (MSMB) to track microbial fermentation in situ and additionally presented a mathematical model for the optimal assessment among candidate inoculants based on the Bolza equation, a fundamental formula in optimal control theory. Three sensors [pH, CO2, and ethanol (EtOH)] provided data for assessment, with four additional sensors (O2, gas pressure, temperature, and atmospheric pressure) to monitor/control the fermentation environment. This advanced MSMB is demonstrated with an experimental method for evaluating three typical species of lactic acid bacteria (LAB), Lentilactobacillus buchneri (LB) alone, and LB mixed with Lactiplantibacillus plantarum (LBLP) or with Enterococcus faecium (LBEF), all cultured in De Man, Rogosa, and Sharpe (MRS) broth. The fermentation process was monitored in situ over 48 h with these candidate microbial strains using the MSMB. The experimental results combine acidification characteristics with production of CO2 and EtOH, optimal assessment of the microbes, analysis of the metabolic sensitivity to pH, and partitioning of the contribution of each species to fermentation. These new data demonstrate that the MSMB associated with the novel rapid data-processing method may expedite development of microbial amendments for silage additives.
Duo: A Signature Based Method to Batch-Analyze Functional Similarities of Proteins
Authors: Fei Xiao , Li Qiuchun , Olsen John Elmerdahl , Jiao Xinan
Published: August 2021

With the rapid advancement of sequencing technology, handling of large sequencing data to analyze for protein coding capacity and functionality of predicted proteins has become an urgent demand. There is a lack of simple and effective tools to functionally annotate large number of unknown proteins in a personalized and customized workflow. To address this, we developed Duo, which batch-analyze functional similarities of predicted proteins. Duo can screen query proteins with specific characteristics based on highly flexible and customizable reference inputs from the user. In the current study, Duo was applied to screen for virulence associated proteins in the genome-sequence of Salmonella Typhimurium. Based on the analysis, recommendation for choice of Seed_database in order to get a reasonable number of predicted proteins for further analysis, and recommendation for preparing a Reference_proteins set for Duo was given. Delta-bitscore analysis was shown to be useful tool to focus the follow-up on predicted proteins. A successful screen for virulence proteins in the bacterial genome-sequence was further performed in a selection of 32 pathogenic bacteria, documenting the ability of Duo to work on a broad collection of bacteria. We anticipate that Duo will be a useful auxiliary tool for personalized and customized protein function research in the future.
Metabolomic Predictors of Non-alcoholic Steatohepatitis and Advanced Fibrosis in Children
Authors: Kordy Kattayoun , Li Fan , Lee David J. , Kinchen Jason M. , Jew Michael H. , La Rocque Maria Eduarda , Zabih Sara , Saavedra Monica , Woodward Cora , Cunningham Nicole J. , Tobin Nicole H. , Aldrovandi Grace M.
Published: August 2021

Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in western countries both in children and adults. Metabolic dysregulation associated with gut microbial dysbiosis may influence disease progression from hepatic steatosis to inflammation and subsequent fibrosis. Using a multi-omics approach, we profiled the oral and fecal microbiome and plasma metabolites from 241 predominantly Latino children with non-alcoholic steatohepatitis (NASH), non-alcoholic fatty liver (NAFL), and controls. Children with more severe liver pathology were dysbiotic and had increased gene content associated with lipopolysaccharide biosynthesis and lipid, amino acid and carbohydrate metabolism. These changes were driven by increases in Bacteroides and concomitant decreases of Akkermansia, Anaerococcus, Corynebacterium, and Finegoldia. Non-targeted mass spectrometry revealed perturbations in one-carbon metabolism, mitochondrial dysfunction, and increased oxidative stress in children with steatohepatitis and fibrosis. Random forests modeling of plasma metabolites was highly predictive of non-alcoholic steatohepatitis (NASH) (97% accuracy) and hepatic fibrosis, steatosis and lobular inflammation (93.8% accuracy), and can differentiate steatohepatitis from simple steatosis (90.0% accuracy). Multi-omics predictive models for disease and histology findings revealed perturbations in one-carbon metabolism, mitochondrial dysfunction, and increased oxidative stress in children with steatohepatitis and fibrosis. These results highlight the promise of non-invasive biomarkers for the growing epidemic of fatty liver disease.
Investigation of Volatile Compounds, Microbial Succession, and Their Relation During Spontaneous Fermentation of Petit Manseng
Authors: Ma Yanqin , Li Tian , Xu Xiaoyu , Ji Yanyu , Jiang Xia , Shi Xuewei , Wang Bin
Published: August 2021

Petit Manseng is widely used for fermenting sweet wine and is popular among younger consumers because of its sweet taste and attractive flavor. To understand the mechanisms underlying spontaneous fermentation of Petit Manseng sweet wine in Xinjiang, the dynamic changes in the microbial population and volatile compounds were investigated through high-throughput sequencing (HTS) and headspace solid-phase microextraction (HS-SPME) coupled to gas chromatography-mass spectrometry (GC-MS) technology, respectively. Moreover, the relationship between the microbial population and volatile compounds was deduced via multivariate data analysis. Candida and Mortierella were dominant genera in Petit Manseng wine during spontaneous fermentation. Many fermentative aroma compounds, including ethyl octanoate, isoamyl acetate, ethyl butyrate, ethyl decanoate, isoamyl alcohol, ethyl laurate, isopropyl acetate, hexanoic acid, and octanoic acid, were noted and found to be responsible for the strong fruity and fatty aroma of Petit Manseng sweet wine. Multivariate data analysis indicated that the predominant microorganisms contributed to the formation of these fermentative aroma compounds. Hannaella and Neomicrosphaeropsis displayed a significantly positive correlation with the 6-methylhept-5-en-2-one produced. The current results provide a reference for producing Petit Manseng sweet wine with desirable characteristics.
LZerD Protein-Protein Docking Webserver Enhanced With de novo Structure Prediction
Authors: Christoffer Charles , Bharadwaj Vijay , Luu Ryan , Kihara Daisuke
Published: August 2021

Protein-protein docking is a useful tool for modeling the structures of protein complexes that have yet to be experimentally determined. Understanding the structures of protein complexes is a key component for formulating hypotheses in biophysics regarding the functional mechanisms of complexes. Protein-protein docking is an established technique for cases where the structures of the subunits have been determined. While the number of known structures deposited in the Protein Data Bank is increasing, there are still many cases where the structures of individual proteins that users want to dock are not determined yet. Here, we have integrated the AttentiveDist method for protein structure prediction into our LZerD webserver for protein-protein docking, which enables users to simply submit protein sequences and obtain full-complex atomic models, without having to supply any structure themselves. We have further extended the LZerD docking interface with a symmetrical homodimer mode. The LZerD server is available at https://lzerd.kiharalab.org/.
Cerebral Cortex Apoptosis in Early Aged Hypertension: Effects of Epigallocatechin-3-Gallate
Authors: Hsieh Min-Huang , Cui Zhen-Yang , Yang Ai-Lun , Nhu Nguyen Thanh , Ting Shih-Ying , Yu Shao-Hong , Cheng Yu-Jung , Lin Yi-Yuan , Wu Xu-Bo , Lee Shin-Da
Published: August 2021

This study aimed to investigate cerebral cortex apoptosis on the early aged hypertension and the effects of green tea flavonoid epigallocatechin-3-gallate (EGCG). Twenty-four rats were divided into three groups: a control Wistar-Kyoto group (WKY, n = 8), a spontaneously early aged hypertensive group (SHR, n = 8), and an early aged hypertension with EGCG treatment group (SHR-EGCG, n = 8; daily oral EGCG 200 mg/kg—94%, 12 weeks). At 48 weeks old, blood pressures (BPs) were evaluated and cerebral cortexes were isolated for TUNEL assay and Western blotting. Systolic, diastolic, and mean blood pressure levels in the SHR-EGCG were reduced compared to the SHR. The percentage of neural cell deaths, the levels of cytosolic Endonuclease G, cytosolic AIF (Caspase-independent apoptotic pathway), Fas, Fas Ligand, FADD, Caspase-8 (Fas-mediated apoptotic pathway), t-Bid, Bax/Bcl-2, Bak/Bcl-xL, cytosolic Cytochrome C, Apaf-1, Caspase-9 (Mitochondrial-mediated apoptotic pathway), and Caspase-3 (Fas-mediated and Mitochondria-mediated apoptotic pathways) were increased in the SHR relative to WKY and reduced in SHR-EGCG relative to SHR. In contrast, the levels of Bcl-2, Bcl-xL, p-Bad, 14-3-3, Bcl-2/Bax, Bcl-xL/Bak, and p-Bad/Bad (Bcl-2 family-related pro-survival pathway), as well as Sirt1, p-PI3K/PI3K and p-AKT/AKT (Sirt1/PI3K/AKT-related pro-survival pathway), were reduced in SHR relative WKY and enhanced in SHR-EGCG relative to SHR. In conclusion, green tea flavonoid epigallocatechin-3-gallate (EGCG) might prevent neural apoptotic pathways and activate neural survival pathways, providing therapeutic effects on early aged hypertension-induced neural apoptosis.
Decreased Alpha Peak Frequency Is Linked to Episodic Memory Impairment in Pathological Aging
Authors: Puttaert Delphine , Wens Vincent , Fery Patrick , Rovai Antonin , Trotta Nicola , Coquelet Nicolas , De Breucker Sandra , Sadeghi Niloufar , Coolen Tim , Goldman Serge , Peigneux Philippe , Bier Jean-Christophe , De Tiège Xavier
Published: August 2021

The Free and Cued Selective Reminding Test (FCSRT) is a largely validated neuropsychological test for the identification of amnestic syndrome from the early stage of Alzheimer’s disease (AD). Previous electrophysiological data suggested a slowing down of the alpha rhythm in the AD-continuum as well as a key role of this rhythmic brain activity for episodic memory processes. This study therefore investigates the link between alpha brain activity and alterations in episodic memory as assessed by the FCSRT. For that purpose, 37 patients with altered FCSRT performance underwent a comprehensive neuropsychological assessment, supplemented by 18F-fluorodeoxyglucose positron emission tomography/structural magnetic resonance imaging (18FDG-PET/MR), and 10 min of resting-state magnetoencephalography (MEG). The individual alpha peak frequency (APF) in MEG resting-state data was positively correlated with patients’ encoding efficiency as well as with the efficacy of semantic cues in facilitating patients’ retrieval of previous stored word. The APF also correlated positively with patients’ hippocampal volume and their regional glucose consumption in the posterior cingulate cortex. Overall, this study demonstrates that alterations in the ability to learn and store new information for a relatively short-term period are related to a slowing down of alpha rhythmic activity, possibly due to altered interactions in the extended mnemonic system. As such, a decreased APF may be considered as an electrophysiological correlate of short-term episodic memory dysfunction accompanying pathological aging.
Evolution of Globus Pallidus Targeting for Parkinson's and Dystonia Deep Brain Stimulation: A 15-Year Experience
Authors: Holanda Vanessa M. , Eisinger Robert Stephen , Almeida Leonardo , Tsuboi Takashi , Wang Huimin , Okun Michael S. , Deeb Wissam , Patterson Addie , Wagle Shukla Aparna , Lobo Lopes Janine , Foote Kelly Douglas
Published: August 2021

Objective: The aim of this study is to evaluate the evolution of GPi DBS targeting.

Methods: This retrospective, single-center study included patients implanted with GPi DBS leads for dystonia or PD during the years 2004 to 2018 at the University of Florida Fixel Institute for Neurological Diseases. Each patient underwent a high-resolution targeting study on the day prior to the surgery, which was fused with a high resolution CT scan that was acquired on the day of the procedure. Intraoperative target location was selected using a digitized 3D Schaltenbrand-Bailey atlas. All patients underwent a high-resolution head CT scan without contrast approximately one month after lead implantation and accurate measurement of neuroanatomical lead position was acquired after fusion of pre-operative and post-operative image studies.

Results: We analyzed 253 PD patients with 352 leads and 80 dystonia patients with 141 leads. During 15 years of follow-up, lead locations in the PD group migrated more laterally (β = 0.09, p < 0.0001), posteriorly [slope (β) = 0.04, p < 0.05], and dorsally (β = 0.07, p < 0.001), whereas leads in the dystonia group did not significantly change position aside from a trend in the dorsal direction (β = 0.06, p = 0.053).

Conclusion: The evolving target likely results from multiple factors including improvements in targeting techniques and clinical feedback intraoperatively and post-operatively. Our demonstrates the potential importance of a systematic post-operative DBS lead measurement protocol to ensure quality control and to inform and optimize DBS programming.
Migraine in Multiple Sclerosis Patients Affects Functional Connectivity of the Brain Circuitry Involved in Pain Processing
Authors: Pravatà Emanuele , Riccitelli Gianna C. , Sestieri Carlo , Sacco Rosaria , Cianfoni Alessandro , Gobbi Claudio , Zecca Chiara
Published: August 2021

Migraine is particularly common in patients with multiple sclerosis (MS) and has been linked to the dysfunction of the brain circuitry modulating the peripheral nociceptive stimuli. Using MRI, we explored whether changes in the resting state-functional connectivity (RS-FC) may characterize the occurrence of migraine in patients with MS. The RS-FC characteristics in concerned brain regions were explored in 20 MS patients with migraine (MS+M) during the interictal phase, and compared with 19 MS patients without migraine (MS-M), which served as a control group. Functional differences were correlated to the frequency and severity of previous migraine attacks, and with the resulting impact on daily activities. In MS+M, the loss of periaqueductal gray matter (PAG) positive connectivity with the default mode network and the left posterior cranial pons was associated with an increase of migraine attacks frequency. In contrast, the loss of PAG negative connectivity with sensorimotor and visual network was linked to migraine symptom severity and related daily activities impact. Finally, a PAG negative connection was established with the prefrontal executive control network. Migraine in MS+M patients and its impact on daily activities, underlies RS-FC rearrangements between brain regions involved in pain perception and modulation.
Patient Outcomes in Disorders of Consciousness Following Transcranial Magnetic Stimulation: A Systematic Review and Meta-Analysis of Individual Patient Data
Authors: O'Neal Christen M. , Schroeder Lindsey N. , Wells Allison A. , Chen Sixia , Stephens Tressie M. , Glenn Chad A. , Conner Andrew K.
Published: August 2021

Background: There are few treatments with limited efficacy for patients with disorders of consciousness (DoC), such as minimally conscious and persistent vegetative state (MCS and PVS).

Objective: In this meta-analysis of individual patient data (IPD), we examine studies utilizing transcranial magnetic stimulation (TMS) as a treatment in DoC to determine patient and protocol-specific factors associated with improved outcomes.

Methods: We conducted a systematic review of PubMed, Ovid Medline, and Clinicaltrials.gov through April 2020 using the following terms: “minimally conscious state,” or “persistent vegetative state,” or “unresponsive wakefulness syndrome,” or “disorders of consciousness” and “transcranial magnetic stimulation.” Studies utilizing TMS as an intervention and reporting individual pre- and post-TMS Coma Recovery Scale-Revised (CRS-R) scores and subscores were included. Studies utilizing diagnostic TMS were excluded. We performed a meta-analysis at two time points to generate a pooled estimate for absolute change in CRS-R Index, and performed a second meta-analysis to determine the treatment effect of TMS using data from sham-controlled crossover studies. A linear regression model was also created using significant predictors of absolute CRS-R index change.

Results: The search yielded 118 papers, of which 10 papers with 90 patients were included. Patients demonstrated a mean pooled absolute change in CRS-R Index of 2.74 (95% CI, 0.62–4.85) after one session of TMS and 5.88 (95% CI, 3.68–8.07) at last post-TMS CRS-R assessment. The standardized mean difference between real rTMS and sham was 2.82 (95% CI, −1.50 to 7.14), favoring rTMS. The linear regression model showed that patients had significantly greater CRS-R index changes if they were in MCS, had an etiology of stroke or intracranial hemorrhage, received 10 or more sessions of TMS, or if TMS was initiated within 3 months from injury.

Conclusions: TMS may improve outcomes in MCS and PVS. Further evaluation with randomized, clinical trials is necessary to determine its efficacy in this patient population.
ERP Effects of Malicious Envy on Schadenfreude in Gain and Loss Frames
Authors: Lin Huiyan , Liang Jiafeng
Published: August 2021

Previous behavioral and neural studies have shown the effects of malicious envy on schadenfreude. However, it is unclear whether these effects are modulated by contextual frames (e.g., gain and loss frames). Thus, the present study aimed to investigate whether behavioral and event-related potential (ERP) effects of malicious envy on schadenfreude were different in gain and loss frames. To address this issue, the participants in the present study believed they were playing a monetary game with several other players. In the malicious envy condition, the participants won less money than the player in the gain frame and lost more money in the loss frame; in the control condition, both participants and the player gained little money in the gain frame and lost much in the loss frame. Subsequently, the participants were informed that the player encountered a misfortune, i.e., gained little in the gain frame and lost much in the loss frame. Results showed that malicious envy increased feelings of schadenfreude and ERP responses when the player encountered a misfortune. Moreover, increased ERP responses by malicious envy occurred at the feedback-related negativity (FRN), and early late positive potential (LPP) time ranges in the gain frame but at the late LPP time range in the loss frame. The findings might suggest that malicious envy affects schadenfreude and corresponding neural activity, whereas the neural effects occur at comparatively early time ranges in the gain frame but at a later time range in the loss frame.
The Relation Between Complexity and Resilient Motor Performance and the Effects of Differential Learning
Authors: Den Hartigh Ruud J. R. , Otten Sem , Gruszczynska Zuzanna M. , Hill Yannick
Published: August 2021

Complex systems typically demonstrate a mixture of regularity and flexibility in their behavior, which would make them adaptive. At the same time, adapting to perturbations is a core characteristic of resilience. The first aim of the current research was therefore to test the possible relation between complexity and resilient motor performance (i.e., performance while being perturbed). The second aim was to test whether complexity and resilient performance improve through differential learning. To address our aims, we designed two parallel experiments involving a motor task, in which participants moved a stick with their non-dominant hand along a slider. Participants could score points by moving a cursor as fast and accurately as possible between two boxes, positioned on the right- and left side of the screen in front of them. In a first session, we determined the complexity by analyzing the temporal structure of variation in the box-to-box movement intervals with a Detrended Fluctuation Analysis. Then, we introduced perturbations to the task: We altered the tracking speed of the cursor relative to the stick-movements briefly (i.e., 4 s) at intervals of 1 min (Experiment 1), or we induced a prolonged change of the tracking speed each minute (Experiment 2). Subsequently, participants had three sessions of either classical learning or differential learning. Participants in the classical learning condition were trained to perform the ideal movement pattern, whereas those in the differential learning condition had to perform additional and irrelevant movements. Finally, we conducted a posttest that was the same as the first session. In both experiments, results showed moderate positive correlations between complexity and points scored (i.e., box touches) in the perturbation-period of the first session. Across the two experiments, only differential learning led to a higher complexity index (i.e., more prominent patterns of pink noise) from baseline to post-test. Unexpectedly, the classical learning group improved more in their resilient performance than the differential learning group. Together, this research provides empirical support for the relation between complexity and resilience, and between complexity and differential learning in human motor performance, which should be examined further.
Similarities and Differences Between Vestibular and Cochlear Systems – A Review of Clinical and Physiological Evidence
Authors: Curthoys Ian S. , Grant John Wally , Pastras Christopher J. , Fröhlich Laura , Brown Daniel J.
Published: August 2021

The evoked response to repeated brief stimuli, such as clicks or short tone bursts, is used for clinical evaluation of the function of both the auditory and vestibular systems. One auditory response is a neural potential — the Auditory Brainstem Response (ABR) — recorded by surface electrodes on the head. The clinical analogue for testing the otolithic response to abrupt sounds and vibration is the myogenic potential recorded from tensed muscles — the vestibular evoked myogenic potential (VEMP). VEMPs have provided clinicians with a long sought-after tool — a simple, clinically realistic indicator of the function of each of the 4 otolithic sensory regions. We review the basic neural evidence for VEMPs and discuss the similarities and differences between otolithic and cochlear receptors and afferents. VEMPs are probably initiated by sound or vibration selectively activating afferent neurons with irregular resting discharge originating from the unique type I receptors at a specialized region of the otolithic maculae (the striola). We review how changes in VEMP responses indicate the functional state of peripheral vestibular function and the likely transduction mechanisms allowing otolithic receptors and afferents to trigger such very short latency responses. In section “ELECTROPHYSIOLOGY” we show how cochlear and vestibular receptors and afferents have many similar electrophysiological characteristics [e.g., both generate microphonics, summating potentials, and compound action potentials (the vestibular evoked potential, VsEP)]. Recent electrophysiological evidence shows that the hydrodynamic changes in the labyrinth caused by increased fluid volume (endolymphatic hydrops), change the responses of utricular receptors and afferents in a way which mimics the changes in vestibular function attributed to endolymphatic hydrops in human patients. In section “MECHANICS OF OTOLITHS IN VEMPS TESTING” we show how the major VEMP results (latency and frequency response) follow from modeling the physical characteristics of the macula (dimensions, stiffness etc.). In particular, the structure and mechanical operation of the utricular macula explains the very fast response of the type I receptors and irregular afferents which is the very basis of VEMPs and these structural changes of the macula in Menière’s Disease (MD) predict the upward shift of VEMP tuning in these patients.