bluuebunny/crossref_metadata_2025 huggingface dataset:
A Novel Image Analysis Approach Reveals a Role for Complement Receptors 1 and 2 in Follicular Dendritic Cell Organization in Germinal Centers
Authors: Anania Jessica C. , Westin Annika , Adler Jeremy , Heyman Birgitta
Published: April 2021

Follicular dendritic cells (FDCs) are rare and enigmatic cells that mainly reside in germinal centers (GCs). They are capable of capturing immune complexes,viatheir Fc (FcRs) and complement receptors (CRs) and storing them for long periods in non-degradative vesicles. Presentation of ICs on FDCs to B cells is believed to drive affinity maturation. CR1 and CR2 are expressed on B cells and FDCs. Cr2 knock out (KO) mice, lacking both receptors, have impaired antibody and GC responses. Utilizing a novel ImageJ macro to analyze confocal fluorescence microscopy images of spleen sections, we here investigate how FDCs in wild type (WT) and Cr2 KO mice behave during the first two weeks after immunization with sheep red blood cells (SRBC). Mice were immunized with SRBC i.v. and spleen and serum samples harvested at various time points. As expected, antibody and GC responses in Cr2 KO mice were impaired in comparison to WT mice. Fewer FDCs were identified in Cr2 KO mice, and these exhibited differential localization and organization in comparison to WT mice. WT FDCs were primarily located within GCs at the light zone/dark zone border. FDCs from WT but not Cr2 KO mice were actively dispersed in GCs, i.e. tended to move away from each other, presumably to increase their surface area for B cell interaction. FDCs from Cr2 KO mice were more often found on follicles outside of the GCs and those within the GCs were closer to the periphery in comparison to WT FDCs. Expression of CR1 and CR2, FcγRIIB, and FcµR increased in FDCs from WT mice during the course of immunization. The results suggest that decreased ability to capture ICs by FDCs lacking CR1 and CR2 may not be the only explanation for the impaired GC and antibody responses in Cr2 KO mice. Poor FDC organization in GCs and failure to increase receptor expression after immunization may further contribute to the inefficient immune responses observed.
Cutaneous Neuroimmune Interactions in Peripheral Neuropathic Pain States
Authors: Lowy Daniel B. , Makker Preet G. S. , Moalem-Taylor Gila
Published: April 2021

Bidirectional interplay between the peripheral immune and nervous systems plays a crucial role in maintaining homeostasis and responding to noxious stimuli. This crosstalk is facilitated by a variety of cytokines, inflammatory mediators and neuropeptides. Dysregulation of this delicate physiological balance is implicated in the pathological mechanisms of various skin disorders and peripheral neuropathies. The skin is a highly complex biological structure within which peripheral sensory nerve terminals and immune cells colocalise. Herein, we provide an overview of the sensory innervation of the skin and immune cells resident to the skin. We discuss modulation of cutaneous immune response by sensory neurons and their mediators (e.g., nociceptor-derived neuropeptides), and sensory neuron regulation by cutaneous immune cells (e.g., nociceptor sensitization by immune-derived mediators). In particular, we discuss recent findings concerning neuroimmune communication in skin infections, psoriasis, allergic contact dermatitis and atopic dermatitis. We then summarize evidence of neuroimmune mechanisms in the skin in the context of peripheral neuropathic pain states, including chemotherapy-induced peripheral neuropathy, diabetic polyneuropathy, post-herpetic neuralgia, HIV-induced neuropathy, as well as entrapment and traumatic neuropathies. Finally, we highlight the future promise of emerging therapies associated with skin neuroimmune crosstalk in neuropathic pain.
In Ovo and Oral Administration of Probiotic Lactobacilli Modulate Cell- and Antibody-Mediated Immune Responses in Newly Hatched Chicks
Authors: Alizadeh Mohammadali , Bavananthasivam Jegarubee , Shojadoost Bahram , Astill Jake , Taha-Abdelaziz Khaled , Alqazlan Nadiyah , Boodhoo Nitish , Shoja Doost Janan , Sharif Shayan
Published: April 2021

There is some evidence that lactobacilli can strengthen the immune system of chickens. This study evaluated the effects of in ovo and oral administration of a lactobacilli cocktail on cytokine gene expression, antibody-mediated immune responses, and spleen cellularity in chickens. Lactobacilli were administered either in ovo at embryonic day 18, orally at days 1, 7, 14, 21, and 28 post-hatches, or a combination of both in ovo and post-hatch inoculation. On day 5 and 10 post-hatch, spleen and bursa of Fabricius were collected for gene expression and cell composition analysis. On days 14 and 21 post-hatch, birds were immunized with sheep red blood cells (SRBC) and keyhole limpet hemocyanin (KLH), and sera were collected on days 7, 14, and 21 post-primary immunization. Birds that received lactobacilli (107 CFU) via in ovo followed by weekly oral administration showed a greater immune response by enhancing antibody responses, increasing the percentage of CD4+ and CD4+CD25+ T cells in the spleen and upregulating the expression of interferon (IFN)-α, IFN-β, interleukin (IL)-8, IL-13, and IL-18 in the spleen and expression of IFN-γ, IL-2, IL-6, IL-8, IL-12, and IL-18 in the bursa. These findings suggest that pre-and post-hatch administration of lactobacilli can modulate the immune response in newly hatched chickens.
The Ratio of IP10 to IL-8 in Plasma Reflects and Predicts the Response of Patients With Lung Cancer to Anti-PD-1 Immunotherapy Combined With Chemotherapy
Authors: Wu Liangliang , Xie Shengzhi , Wang Lingxiong , Li Jinfeng , Han Lu , Qin Boyu , Zhang Guoqing , Wu Qiyan , Gao Wenjuan , Zhang Lijun , Wei Huafeng , Liu Tianyi , Jiao Shunchang
Published: April 2021

Antibodies against checkpoint inhibitors such as anti-programmed cell death protein 1 (PD-1) and its ligand anti-programmed death ligand 1 (PD-L1) have shown clinical efficacy in the treatment of multiple cancers. However, there are only a few studies on biomarkers for these targeted immunotherapies, especially in peripheral blood. We first studied the role of interferon-induced protein-10 (IP10) combined with interleukin-8 (IL-8) in peripheral blood as a biomarker of immune-combined chemotherapy for lung cancer and multiple cancers. We used the high-throughput cytokine detection platform and performed bioinformatics analysis of blood samples from 67 patients with lung cancer and 24 with multiple cancers. We selected the ratio of IP-10 to IL-8 (S2/S0, ratio of changes at 10–12 weeks after treatment to baseline) to predict the response to immunotherapy combined with chemotherapy and evaluate the survival of lung cancer patients and mixed cancer patients. In patients treated with the combination therapy, the specificity and sensitivity of IL-8 and IP10 together as predictors were improved compared with those of IL-8 and IP10 alone. Our conclusion was verified in not only lung cancer but also multiple cancer research cohorts. We then further validated the predictive effect of biomarkers in different histologic types of NSCLC and chemotherapy combined with different PD-1 drug groups. Subsequent validation should be conducted with a larger number of patients. The proposed marker IP10 (S2/S0)/IL-8 (S2/S0), as a predictive immunotherapy biomarker, has broad prospects for future clinical applications in treating patients with multiple intractable neoplasms.
COVID-19 Vaccines: Current Understanding on Immunogenicity, Safety, and Further Considerations
Authors: He Qian , Mao Qunying , Zhang Jialu , Bian Lianlian , Gao Fan , Wang Junzhi , Xu Miao , Liang Zhenglun
Published: April 2021

The world has entered the second wave of the COVID-19 pandemic, and its intensity is significantly higher than that of the first wave of early 2020. Many countries or regions have been forced to start the second round of lockdowns. To respond rapidly to this global pandemic, dozens of COVID-19 vaccine candidates have been developed and many are undergoing clinical testing. Evaluating and defining effective vaccine candidates for human use is crucial for prioritizing vaccination programs against COVID-19. In this review, we have summarized and analyzed the efficacy, immunogenicity and safety data from clinical reports on different COVID-19 vaccines. We discuss the various guidelines laid out for the development of vaccines and the importance of biological standards for comparing the performance of vaccines. Lastly, we highlight the key remaining challenges, possible strategies for addressing them and the expected improvements in the next generation of COVID-19 vaccines.
Seagrass Structural Traits Drive Fish Assemblages in Small-Scale Fisheries
Authors: Jones Benjamin L. , Nordlund Lina M. , Unsworth Richard K. F. , Jiddawi Narriman S. , Eklöf Johan S.
Published: April 2021

Seagrasses – a group of foundation species in coastal ecosystems – provide key habitat for diverse and abundant faunal assemblages and support numerous ecosystem functions and services. However, whether the habitat role of seagrasses is influenced by seagrass diversity, by dominant species or both, remains unclear. To that end, we sought to investigate the specific seagrass characteristics (e.g., species diversity, seagrass traits) that influence tropical fish assemblages, and place this in the context of small-scale fishery use. We surveyed seagrass variables at 55 plots, nested within 12 sites around Zanzibar (Tanzania) in the Western Indian Ocean, and used Baited Remote Underwater Video (BRUV) systems to assess fish assemblages across plots. Using linear mixed models, we reveal that seagrass structural complexity and depth were the best predictors of fish abundance, with higher abundance occurring in deeper meadows or meadows with high canopy, leaf length and number of leaves per shoot. Moreover, an interaction between seagrass cover and land-use was the best predictor of fish species richness, where sites closer to human impacts were less affected by cover than sites with lower human impact. Overall, models with seagrass species richness or functional diversity as predictors poorly explained fish assemblages. Fish taxa that were important for small-scale fishery sectors (e.g., emperors, snappers, rabbitfish, and parrotfish) were primarily driven by seagrass structural complexity. Our results provide a unique analysis of the relationship between seagrass habitat and its associated fish assemblages in that we show that seagrass species diversity had little effect on seagrass fish assemblages, which instead appear driven by specific seagrass traits and seagrass cover. If conserving high value species that support adjacent fisheries is the priority for protecting seagrass meadows, then seagrass areas should be chosen with high cover and structural complexity that are in deeper waters. Any conservation measures also need to balance the needs of fishers that use the resources supported by seagrasses.
The Unique Amphipoda and Tanaidacea (Crustacea: Peracarida) Associated With the Brown Algae Dictyota sp. From the Oceanic Trindade Island, Southwestern Atlantic, With Biogeographic and Phylogenetic Insights
Authors: Iwasa-Arai Tammy , Siqueira Silvana G. L. , Segadilha Juliana L. , Leite Fosca P. P.
Published: April 2021

Oceanic islands are known by their unique evolutionary histories and high endemicity caused by isolation. This is the first survey on the biodiversity of Peracarida from Trindade Island, a volcanic island located about 1,160 km off the Brazilian coast, with the first reports of Tanaidacea from the island and the description ofSynapseudes isissp. nov. and three new species of Amphipoda (Ampithoe thaixsp. nov.,Elasmopus gabrielisp. nov., andEusiroides lucaisp. nov.). The results of the phylogenetic analysis ofSynapseudesbased on morphological characters and its biogeography through the Bayesian Binary MCMC analysis (BBM) suggested an Indo-Pacific origin for the genus. Finally, the biodiversity of Trindade Island is compared to that of the Abrolhos Archipelago, the closest islands from the coast on the continental shelf, suggesting a high endemicity of Peracarida, corresponding to 44% of Amphipoda and 50% of Tanaidacea species in the island of Trindade.
The Contributions of Shellfish Aquaculture to Global Food Security: Assessing Its Characteristics From a Future Food Perspective
Authors: Azra Mohamad Nor , Okomoda Victor Tosin , Tabatabaei Meisam , Hassan Marina , Ikhwanuddin Mhd
Published: April 2021

The United Nation’s 2030 development agenda adopted in 2015 outlines 17 Sustainable Development Goals (SDGs), and the organization has continued to put food security in the center of its vocalization. Aquaculture is currently the fastest-growing food production sector globally and a sustainable option for attaining food security. Food as a basic necessity for man’s survival is always a timely issue. Hence, owing to aquaculture’s unique role, it is expected that the demand for aquatic products (especially seafood) will continue to increase due to geometric population growth. Many seafood products are among the critical protein sources in the world. This is partly because they have micronutrients and essential fatty acids that are not present in land-based protein sources. According to the Food and Agriculture Organization, shellfish is one of the main cultured aquaculture groups in the world. Hence, the development of shellfish aquaculture has an important role in sustainable food supply and food security. In this article, an overview of the current and projected contributions of shellfish aquaculture to global food security is presented. Apparently, shellfish aquaculture in the next few decades will have to be intensified to bridge the gap between demand and supply in a cost-effective manner. Also, food waste would have to be reduced and natural resources should be used more efficiently to minimize the negative impacts on aquaculture on the environment.
The Effects of Nisin-Producing Lactococcus lactis Strain Used as Probiotic on Gilthead Sea Bream (Sparus aurata) Growth, Gut Microbiota, and Transcriptional Response
Authors: Moroni Federico , Naya-Català Fernando , Piazzon M. Carla , Rimoldi Simona , Calduch-Giner Josep , Giardini Alberto , Martínez Inés , Brambilla Fabio , Pérez-Sánchez Jaume , Terova Genciana
Published: April 2021

The present research tested the effects of dietary nisin-producingLactococcus lactison growth performance, feed utilization, intestinal morphology, transcriptional response, and microbiota in gilthead sea bream (Sparus aurata). A feeding trial was conducted with fish weighting 70–90 g. Fish were tagged with passive, integrated transponders and distributed in nine 500 L tanks with 40 fish each. Fish were fed for 12 weeks with either a control (diet A) or experimental diets (diets B and C) in triplicate (3 tanks/diet). Extruded pellets of diets B and C were supplemented with a low (2 × 109CFU/kg) and a high (5 × 109CFU/kg) dose of probiotic, respectively. No significant differences were found between groups for the feed conversion ratio or specific growth rates. However, the final body weight of fish fed diet C was significantly higher than the control group with intermediate values for fish fed diet B. Histological analysis conducted using a semi-quantitative scoring system showed that probiotic did not alter the morphology of the intestine and did not trigger inflammation. With regard to the transcriptomic response, a customized PCR array layout was designed to simultaneously profile a panel of 44 selected genes. Significant differences in the expression of key genes involved in innate and acquired immunity were detected between fish fed probiotic and control diets. To analyze the microbiota associated to the feeds and the gut autochthonous microbial communities, we used the Illumina MiSeq platform for sequencing the 16S rRNA gene and a metagenomics pipeline based on VSEARCH and RDP databases. The analysis of gut microbiota revealed a lack of colonization of the probiotic in the host’s intestinal mucosa. However, probiotic did modulate the fish gut microbiota, confirming that colonization is not always necessary to induce host modification. In fact, diets B and C were enriched with Actinomycetales, as compared to diet A, which instead showed a higher percentage ofPseudomonas,Sphyngomonas, andLactobacillusgenera. These results were confirmed by the clear separation of gut bacterial community of fish fed with the probiotic from the bacterial community of control fish group in the beta-diversity and PLS-DA (supervised partial least-squares discriminant analysis) analyses.
Composite MWCNT/ MIL-101 (Cr)/CaCl2 as High-Capacity Water Adsorbent for Long-Term Thermal Energy Storage
Authors: Lou Lanting , Xu Min , Huai Xiulan , Huang Caifeng , Liu Zhangli
Published: April 2021

Mil-101 (Cr) material is considered to be one of the most potential thermochemical energy storage materials in recent years. It has the advantages of a typical S-type water adsorption isotherm. Has low working temperature and large water adsorption amount. However, the adsorption properties of the material need to be improved under low water pressure. To improve the performance, the acidified MWCNTs were added before the hydrothermal reaction of mil-101 (Cr) materials to optimize the micropore structure. After the preparation, the new composite thermochemical energy storage materials were prepared by impregnation with a certain concentration of calcium chloride aqueous solution. The effects of multi-walled carbon nanotubes and calcium chloride on the physical and chemical properties of the materials were discussed. Through X-ray diffraction experiment, scanning electron microscope, microstructure analysis, nitrogen adsorption capacity test, water adsorption capacity test, and other means, the micro characteristics, pore structure, crystal morphology, and chemical composition of the materials were characterized, and the water adsorption performance of the materials was synthesized. The experimental results show that the addition of carbon nanotubes can improve the pore properties of the materials so that the porous organic skeleton can accommodate more calcium chloride particles. The composite materials with calcium chloride can provide excellent hydrophilicity and high water adsorption capacity. Also, the water absorption rate and adsorption-desorption cycle capacity of the material have been significantly improved. The experimental results show that when the mass fraction of calcium chloride reaches 30% when 90 mg acidified MWCNTs are added into every four chromium nitrate crystals, the hydrophilicity and adsorption capacity of the composite can reach a high equilibrium state. At the same time, the experimental yield of the material is high, the product is easy to obtain, the environmental friendliness is also reflected, so it is expected to become the adsorption heat pump thermochemical energy storage material with research potential.
Iron Metabolism: An Under Investigated Driver of Renal Pathology in Lupus Nephritis
Authors: Wlazlo Ewa , Mehrad Borna , Morel Laurence , Scindia Yogesh
Published: April 2021

Nephritis is a common manifestation of systemic lupus erythematosus, a condition associated with inflammation and iron imbalance. Renal tubules are the work horse of the nephron. They contain a large number of mitochondria that require iron for oxidative phosphorylation, and a tight control of intracellular iron prevents excessive generation of reactive oxygen species. Iron supply to the kidney is dependent on systemic iron availability, which is regulated by the hepcidin-ferroportin axis. Most of the filtered plasma iron is reabsorbed in proximal tubules, a process that is controlled in part by iron regulatory proteins. This review summarizes tubulointerstitial injury in lupus nephritis and current understanding of how renal tubular cells regulate intracellular iron levels, highlighting the role of iron imbalance in the proximal tubules as a driver of tubulointerstitial injury in lupus nephritis. We propose a model based on the dynamic ability of iron to catalyze reactive oxygen species, which can lead to an accumulation of lipid hydroperoxides in proximal tubular epithelial cells. These iron-catalyzed oxidative species can also accentuate protein and autoantibody-induced inflammatory transcription factors leading to matrix, cytokine/chemokine production and immune cell infiltration. This could potentially explain the interplay between increased glomerular permeability and the ensuing tubular injury, tubulointerstitial inflammation and progression to renal failure in LN, and open new avenues of research to develop novel therapies targeting iron metabolism.
Reprogramming Intestinal Epithelial Cell Polarity by Interleukin-22
Authors: Delbue Deborah , Lebenheim Lydia , Cardoso-Silva Danielle , Dony Violaine , Krug Susanne M. , Richter Jan F. , Manna Subhakankha , Muñoz Melba , Wolk Kerstin , Heldt Claudia , Heimesaat Markus M. , Sabat Robert , Siegmund Britta , Schumann Michael
Published: April 2021

Background: Interleukin-22 (IL-22) impacts the integrity of intestinal epithelia and has been associated with the development of colitis-associated cancer and inflammatory bowel diseases (IBD). Previous data suggest that IL-22 protects the mucosal barrier and promotes wound healing and barrier defect. We hypothesized, that IL-22 modulates cell polarity of intestinal epithelial cells (IECs) acting on tight junction assembly. The aim of the study was to investigate IL-22-dependent mechanisms in the reprogramming of intestinal epithelia.

Methods: IECs were exposed to IL-22 at various concentrations. IECs in Matrigel® were grown to 3-dimensional cysts in the presence or absence of IL-22 and morphology and expression of polarity proteins were analyzed by confocal microscopy. Epithelial cell barrier (TER and sandwich assay) and TJ assembly analysis (calcium-switch assay) were performed. TJ and cell polarity protein expression were assessed by western blotting and confocal microscopy. Cell migration and invasion assays were performed. Induction of epithelial-mesenchymal transition (EMT) was assessed by RT-qPCR analysis and western blotting. Signaling pathway analyses were performed by phosphoblotting and functional assays after blocking STAT3 and ERK signaling pathways. Using the toxoplasma-model of terminal ileitis, IL-22-knock-out mice were compared to wild-type littermates, analyzed for barrier function using one-path-impedance-analysis and macromolecular flux (H3-mannitol, Ussing-chambers).

Results: IECs exhibited a barrier defect after IL-22 exposure. TJ protein distribution and expression were severely impaired. Delayed recovery in the calcium-switch assay was observed suggesting a defect in TJ assembly. Analyzing the 3D-cyst model, IL-22 induced multi-lumen and aberrant cysts, and altered the localization of cell polarity proteins. Cell migration and invasion was caused by IL-22 as well as induction of EMT. Interestingly, only inhibition of the MAPK pathway, rescued the TJal barrier defect, while blocking STAT3 was relevant for cell survival. In addition, ileal mucosa of IL-22 deficient mice was protected from the barrier defect seen in Toxoplasma gondii-induced ileitis in wild type mice shown by significantly higher Re values and correspondingly lower macromolecule fluxes.

Conclusion: IL-22 impairs intestinal epithelial cell barrier by inducing EMT, causing defects in epithelial cell polarity and increasing cell motility and cell invasion. IL-22 modulates TJ protein expression and mediates tight junctional (TJal) barrier defects via ERK pathway.
Relationship of Soluble Interleukin-6 Receptors With Asthma: A Mendelian Randomization Study
Authors: Raita Yoshihiko , Zhu Zhaozhong , Camargo Carlos A. , Freishtat Robert J. , Ngo Debby , Liang Liming , Hasegawa Kohei
Published: April 2021

Purpose: Emerging evidence suggests a potential role of interleukin-6 pathways—trans-signaling with soluble interleukin-6 receptors—in the asthma pathobiology. Despite the evidence for their associations with asthma, the causal role of soluble interleukin-6 receptors remains uncertain. We investigated the relations of soluble interleukin-6 receptors with asthma and its major phenotypes.

Methods: We conducted a two-sample Mendelian randomization study. As genetic instruments, we selected 33 independent cis-acting variants strongly associated with the level of plasma soluble interleukin-6 receptor in the INTERVAL study. To investigate the association of variants with asthma and its phenotypes, we used genome-wide association study data from the UK Biobank. We combined variant-specific causal estimates by the inverse-variance weighted method for each outcome.

Results: Genetically-instrumented soluble interleukin-6 receptor level was associated with a significantly higher risk of overall asthma (OR per one standard deviation increment in inverse-rank normalized soluble interleukin-6 receptor level, 1.02; 95%CI, 1.01–1.03; P = 0.004). Sensitivity analyses demonstrated consistent results and indicated no directional pleiotropy—e.g., MR-Egger (OR, 1.03; 95%CI, 1.01–1.05; P = 0.002; Pintercept =0.37). In the stratified analysis, the significant association persisted across asthma phenotypes—e.g., childhood asthma (OR, 1.05; 95%CI, 1.02–1.08; P < 0.001) and obese asthma (OR, 1.02; 95%CI 1.01–1.03; P = 0.007). Sensitivity analysis using 16 variants selected with different thresholds also demonstrated significant associations with overall asthma and its phenotypes.

Conclusion: Genetically-instrumented soluble interleukin-6 receptor level was causally associated with modestly but significantly higher risks of asthma and its phenotypes. Our observations support further investigations into identifying specific endotypes in which interleukin-6 pathways may play major roles.
Clonal CTX-M-15-Producing Escherichia coli ST-949 Are Present in German Surface Water
Authors: Falgenhauer Linda , zur Nieden Anja , Harpel Susanne , Falgenhauer Jane , Domann Eugen
Published: April 2021

Extended-spectrum beta-lactamase (ESBL)-producing bacterial isolates are emerging within the last years. To understand this emergence, a thorough genome-based analysis of ESBL isolates from different sources (One Health approach) is needed. Among these, analysis of surface water is underrepresented. Therefore, we performed a genome-based analysis of ESBL-producing Escherichia coli isolates from surface water samples. Water samples were collected from eleven different surface water sites (lakes, river). ESBL-producing E. coli were recovered from these samples using filters and chromogenic media. Whole-genome sequencing of ESBL-producing E. coli was performed followed by determination of the multilocus sequence type (ST), ESBL-type, and virulence genes. Phylogenetic analysis was done using single nucleotide analysis. From all water samples taken, nineteen ESBL-producing E. coli were recovered. All of them harbored an ESBL gene. Nine different multilocus STs were determined, among which ST-949 was the ST detected most frequently. Phylogenetic analysis of ST-949 isolates revealed that all those isolates were closely related. In addition, they harbored an identical chromosomal insertion of blaCTX–M–15, indicating a clonal relationship among these isolates. Genetic comparison with isolates from all over the world revealed that these isolates were closely related to human clinical isolates derived from New Zealand and Sweden. An ESBL-producing E. coli ST-949 clone was detected in German surface waters. Its close relationship to human clinical isolates suggests its ability to colonize or even infect humans. Our findings reveal that water sources indeed may play a hitherto underreported role in spread of ESBL-producing isolates.
CAZymes in Maribacter dokdonensis 62–1 From the Patagonian Shelf: Genomics and Physiology Compared to Related Flavobacteria and a Co-occurring Alteromonas Strain
Authors: Wolter Laura A. , Mitulla Maximilian , Kalem Jovan , Daniel Rolf , Simon Meinhard , Wietz Matthias
Published: April 2021

Carbohydrate-active enzymes (CAZymes) are an important feature of bacteria in productive marine systems such as continental shelves, where phytoplankton and macroalgae produce diverse polysaccharides. We herein describe Maribacter dokdonensis 62–1, a novel strain of this flavobacterial species, isolated from alginate-supplemented seawater collected at the Patagonian continental shelf. M. dokdonensis 62–1 harbors a diverse array of CAZymes in multiple polysaccharide utilization loci (PUL). Two PUL encoding polysaccharide lyases from families 6, 7, 12, and 17 allow substantial growth with alginate as sole carbon source, with simultaneous utilization of mannuronate and guluronate as demonstrated by HPLC. Furthermore, strain 62-1 harbors a mixed-feature PUL encoding both ulvan- and fucoidan-targeting CAZymes. Core-genome phylogeny and pangenome analysis revealed variable occurrence of these PUL in related Maribacter and Zobellia strains, indicating specialization to certain “polysaccharide niches.” Furthermore, lineage- and strain-specific genomic signatures for exopolysaccharide synthesis possibly mediate distinct strategies for surface attachment and host interaction. The wide detection of CAZyme homologs in algae-derived metagenomes suggests global occurrence in algal holobionts, supported by sharing multiple adaptive features with the hydrolytic model flavobacterium Zobellia galactanivorans. Comparison with Alteromonas sp. 76-1 isolated from the same seawater sample revealed that these co-occurring strains target similar polysaccharides but with different genomic repertoires, coincident with differing growth behavior on alginate that might mediate ecological specialization. Altogether, our study contributes to the perception of Maribacter as versatile flavobacterial polysaccharide degrader, with implications for biogeochemical cycles, niche specialization and bacteria-algae interactions in the oceans.
Metagenomic Analysis of Microbial Composition Revealed Cross-Contamination Pathway of Bacteria at a Foodservice Facility
Authors: Lim Eun Seob , Kim Jin Ju , Sul Woo Jun , Kim Joo-Sung , Kim Bomin , Kim Hun , Koo Ok Kyung
Published: April 2021

Bacterial contamination of food-contact surfaces can be a potential risk factor for food quality and safety. To evaluate the spatial and temporal variations of the potential cross-contamination routes, we conducted a biogeographical assessment of bacteria in a foodservice facility based on the diversity of microflora on each surface. To this end, we performed high-throughput amplicon sequencing of 13 food-contact and non-food contact surfaces in a foodservice facility throughout a year. The results showed that Bacillus, Acinetobacter, Streptophyta, Enterobacter, Pseudomonas, Serratia, Enhydrobacter, Staphylococcus, Paracoccus, and Lysinibacillus were the dominant genera found on the kitchen surfaces of the foodservice facility. Depending on the season, changes in Firmicute/Proteobacteria ratios were observed, and the fan becomes the main source of outdoor air contamination. The microbial flow associated with spoilage was also observed throughout food preparation. Taken together, our results would be a powerful reference to hygiene managers for improvement of food processes.
Cross-Talk Between Butyric Acid and Gut Microbiota in Ulcerative Colitis Following Fecal Microbiota Transplantation
Authors: Xu Hao-Ming , Huang Hong-Li , Xu Jing , He Jie , Zhao Chong , Peng Yao , Zhao Hai-Lan , Huang Wen-Qi , Cao Chuang-Yu , Zhou Yong-Jian , Zhou You-Lian , Nie Yu-Qiang
Published: April 2021

Fecal microbiota transplantation (FMT) can inhibit the progression of ulcerative colitis (UC). However, how FMT modulates the gut microbiota and which biomarker is valuable for evaluating the efficacy of FMT have not been clarified. This study aimed to determine the changes in the gut microbiota and their relationship with butyric acid following FMT for UC. Fecal microbiota (FM) was isolated from healthy individuals or mice and transplanted into 12 UC patients or colitis mice induced by dextran sulfate sodium (DSS). Their clinical colitis severities were monitored. Their gut microbiota were analyzed by 16S sequencing and bioinformatics. The levels of fecal short-chain fatty acids (SCFAs) from five UC patients with recurrent symptoms after FMT and individual mice were quantified by liquid chromatography–mass spectrometry (LC–MS). The impact of butyric acid on the abundance and diversity of the gut microbiota was tested in vitro. The effect of the combination of butyric acid-producing bacterium and FMT on the clinical responses of 45 UC patients was retrospectively analyzed. Compared with that in the controls, the FMT significantly increased the abundance of butyric acid-producing bacteria and fecal butyric acid levels in UC patients. The FMT significantly increased the α-diversity, changed gut microbial structure, and elevated fecal butyric acid levels in colitis mice. Anaerobic culture with butyrate significantly increased the α-diversity of the gut microbiota from colitis mice and changed their structure. FMT combination with Clostridium butyricum-containing probiotics significantly prolonged the UC remission in the clinic. Therefore, fecal butyric acid level may be a biomarker for evaluating the efficacy of FMT for UC, and addition of butyrate-producing bacteria may prolong the therapeutic effect of FMT on UC by changing the gut microbiota.
LncRNA ST7-AS1 is a Potential Novel Biomarker and Correlated With Immune Infiltrates for Breast Cancer
Authors: Zhang Ziwen , Zhang Han , Li Dongbo , Zhou Xiaoping , Wang Jinlu , Zhang Qingyuan
Published: April 2021

Background: Long noncoding RNA (lncRNA) ST7-AS1 can be observed in various cancers, but its role in breast cancer (BRC) remains unclear. Our aim is to, on the basis of The Cancer Genome Atlas (TCGA) database, prove the correlation between lncRNA ST7-AS1 and BRC.

Methods: The lncRNA ST7-AS1 expression and its roles in the prognosis of BRC were explored using data from the TCGA database. The expression level of lncRNA ST7-AS1 in BRC samples was detected using RT-PCR. The 1-, 3-, or 5-year survival rate was predicted using a nomogram established through Cox proportional hazard regression. At last, the biological function was explored through gene ontology (GO) analysis and gene set enrichment analysis (GSEA). The hallmark pathways significantly involved in hub genes were described through functional enrichment analysis. The correlation between lncRNA ST7-AS1 expression and immune infiltration was analyzed through single-sample GSEA (ssGSEA).

Results: LncRNA ST7-AS1 expression was downregulated in BRC. Decreased lncRNA ST7-AS1 expression in BRC was correlated with advanced clinical pathologic characteristics (high grade, histological type, age, menopause status, and HER2 status), survival time, and poor prognosis. The nomogram was established for using lncRNA ST7-AS1 to predict 1-, 3-, or 5-year survival in patients with BRC. In addition, GO and pathway analyses suggested the involvement of lncRNA ST7-AS1 in cell cycle, DNA repair, and immune cell infiltration in the BRC immune microenvironment. We found the correlation of lncRNA ST7-AS1 with T helper cells and DC cells.

Conclusion: Low expression of lncRNA ST7-AS1 indicates poor prognosis and has an impact on cell cycle, DNA repair, and proportion of infiltrating immune cells in the BRC microenvironment. Therefore, lncRNA ST7-AS1 can be used as a protective prognostic marker and a potential treatment target for BRC.
Automated in vivo Tracking of Cortical Oligodendrocytes
Authors: Xu Yu Kang T. , Call Cody L. , Sulam Jeremias , Bergles Dwight E.
Published: April 2021

Oligodendrocytes exert a profound influence on neural circuits by accelerating action potential conduction, altering excitability, and providing metabolic support. As oligodendrogenesis continues in the adult brain and is essential for myelin repair, uncovering the factors that control their dynamics is necessary to understand the consequences of adaptive myelination and develop new strategies to enhance remyelination in diseases such as multiple sclerosis. Unfortunately, few methods exist for analysis of oligodendrocyte dynamics, and even fewer are suitable for in vivo investigation. Here, we describe the development of a fully automated cell tracking pipeline using convolutional neural networks (Oligo-Track) that provides rapid volumetric segmentation and tracking of thousands of cells over weeks in vivo. This system reliably replicated human analysis, outperformed traditional analytic approaches, and extracted injury and repair dynamics at multiple cortical depths, establishing that oligodendrogenesis after cuprizone-mediated demyelination is suppressed in deeper cortical layers. Volumetric data provided by this analysis revealed that oligodendrocyte soma size progressively decreases after their generation, and declines further prior to death, providing a means to predict cell age and eventual cell death from individual time points. This new CNN-based analysis pipeline offers a rapid, robust method to quantitatively analyze oligodendrocyte dynamics in vivo, which will aid in understanding how changes in these myelinating cells influence circuit function and recovery from injury and disease.
Evaluation of the Direct Effect of Bilateral Deep Brain Stimulation of the Subthalamic Nucleus on Levodopa-Induced On-Dyskinesia in Parkinson's Disease
Authors: Li Jiping , Mei Shanshan , Jia Xiaofei , Zhang Yuqing
Published: April 2021

Objective: This study aimed to evaluate the direct anti-dyskinesia effect of deep brain stimulation (DBS) of subthalamic nucleus (STN) on levodopa-induced on-dyskinesia in Parkinson's disease (PD) patients during the early period after surgery without reducing the levodopa dosage.

Methods: We retrospectively reviewed PD patients who underwent STN-DBS from January 2017 to October 2019 and enrolled patients with levodopa-induced on-dyskinesia before surgery and without a history of thalamotomy or pallidotomy. The Unified Dyskinesia Rating Scale (UDysRS) parts I+III+IV and the Unified Parkinson's Disease Rating Scale part III (UPDRS-III) were monitored prior to surgery, and at the 3-month follow-up, the location of active contacts was calculated by postoperative CT–MRI image fusion to identify stimulation sites with good anti-dyskinesia effect.

Results: There were 41 patients enrolled. The postoperative levodopa equivalent daily dose (LEDD) (823.1 ± 201.5 mg/day) was not significantly changed from baseline (844.6 ± 266.1 mg/day, P = 0.348), while the UDysRS on-dyskinesia subscores significantly decreased from 24 (10–58) to 0 (0–18) [median (range)] after STN stimulation (P < 0.0001). The levodopa-induced on-dyskinesia recurred in stimulation-off/medication-on state in all the 41 patients and disappeared in 39 patients when DBS stimulation was switched on at 3 months of follow-up. The active contacts which correspond to good effect for dyskinesia were located above the STN, and the mean coordinate was 13.05 ± 1.24 mm lateral, −0.13 ± 1.16 mm posterior, and 0.72 ± 0.78 mm superior to the midcommissural point.

Conclusions: High-frequency electrical stimulation of the area above the STN can directly suppress levodopa-induced on-dyskinesia.
Cognitive and Emotional Mapping With SEEG
Authors: Drane Daniel L. , Pedersen Nigel P. , Sabsevitz David S. , Block Cady , Dickey Adam S. , Alwaki Abdulrahman , Kheder Ammar
Published: April 2021

Mapping of cortical functions is critical for the best clinical care of patients undergoing epilepsy and tumor surgery, but also to better understand human brain function and connectivity. The purpose of this review is to explore existing and potential means of mapping higher cortical functions, including stimulation mapping, passive mapping, and connectivity analyses. We examine the history of mapping, differences between subdural and stereoelectroencephalographic approaches, and some risks and safety aspects, before examining different types of functional mapping. Much of this review explores the prospects for new mapping approaches to better understand other components of language, memory, spatial skills, executive, and socio-emotional functions. We also touch on brain-machine interfaces, philosophical aspects of aligning tasks to brain circuits, and the study of consciousness. We end by discussing multi-modal testing and virtual reality approaches to mapping higher cortical functions.
Case Report: Autoimmune Encephalitis Associated With Anti-glutamic Acid Decarboxylase Antibodies: A Pediatric Case Series
Authors: Ren Changhong , Ren Haitao , Ren Xiaotun , Zhang Weihua , Li Jiuwei , Dai Lifang , Guan Hongzhi , Fang Fang
Published: April 2021

Background: Antibodies against glutamic acid decarboxylase (GAD) are associated with various neurologic conditions described in patients, including stiff person syndrome, cerebellar ataxia, refractory epilepsy, and limbic and extralimbic encephalitis. There have been some case reports and investigations regarding anti-GAD65 antibody-associated encephalitis in adult populations, but pediatric cases are rare. We retrospectively analyzed the clinical data of three anti-GAD65 antibody-positive patients to explore the diversity and clinical features of anti-GAD65 antibody-associated pediatric autoimmune encephalitis.

Methods: The clinical data of a series of three patients positive for anti-GAD65 antibody were retrospectively analyzed. GAD65 antibodies were determined in serum and CSF using a cell-based assay.

Results: All three patients were female, and the onset ages were 4 years and 9 months, 6 years, and 16 years old. Their clinical phenotypes included autoimmune limbic encephalitis, extralimbic encephalitis, and encephalitis combining limbic and extralimbic encephalitis. The clinical symptoms included seizures, memory deficits, drowsiness, dysautonomia, and headache. All patients had abnormal carinal MRI and EEG. All patients received immunotherapy and had transiently good responsiveness, but one patient then experienced relapse. In follow-up, one patient with extralimbic encephalitis recovered completely, while two patients with limbic involvement had poor outcomes with refractory focal epilepsy.

Conclusion: In addition to limbic encephalitis, extralimbic encephalitis is also an important phenotype in patients who are positive for anti-GAD65 antibodies. Early diagnosis and immunotherapy can improve the symptoms. However, patients with limbic encephalitis often have refractory epilepsy in the chronic phase and have a poor long-term outcome.
Optimization of Early Mobilization Program for Patients With Acute Ischemic Stroke: An Orthogonal Design
Authors: Zhang Min , Wang Qing , Jiang Yuanyuan , Shi Huiling , Peng Tiantian , Wang Mengyue
Published: April 2021

Background and purpose: Early mobilization is considered to have favorable outcomes for stroke patients, but there is currently a lack of specific data to guide this early mobilization, including the initiation time, intensity, frequency, and duration of each activity. Therefore, the optimal strategy for early mobilization is unclear. In this study, we investigated the best combination of different factors to achieve early mobilization, to develop the optimal program.

Methods: We conducted an L9 (33) orthogonal experiment with a blinded follow-up assessment. Patients with ischemic stroke, admitted to a stroke unit within 24–72 h of its onset, were recruited. Eligible subjects were randomly assigned to one of nine different programs of early mobilization. The outcomes were assessed at baseline, discharge, and 1 and 3 months after discharge to observe the changes in various efficacy indicators and determine the main factors affecting outcome.

Results: We analyzed 57 of 63 patients, after six were excluded for poor compliance, failure to cooperate with the study, or worsening of the disease. The initiation time, intensity, and frequency of mobilization were the main factors affecting outcome (all P < 0.05), and the duration of each activity was a secondary factor (P > 0.05). A comprehensive analysis of the various parameters showed that the optimal level of the early mobilization program was an initiation time: 24–48 h after stroke; intensity: bed and chair transfer, sitting out of bed, standing and walking or climbing stairs when mobility permitted; frequency: 2–3 times/day; duration of each mobilization: determined according to the actual situation of the patient.

Conclusions: Early rehabilitation with high-intensity physical exercise at 24–48 h after the onset of stroke, 2–3 times/day, may benefit stroke patients. Applying the optimized program of early mobilization to stroke patients effectively alleviated their symptoms of neurological deficit, improved their capacity for self-care, restored their self-efficacy, improved their quality of life and social participation, and reduced post-stroke fatigue at 3 months.
Repetitive Transcranial Magnetic Stimulation for Tinnitus Treatment in Vestibular Schwannoma: A Pilot Study
Authors: Leao Maria Teresa , Machetanz Kathrin , Sandritter Joey , Liebsch Marina , Stengel Andreas , Tatagiba Marcos , Naros Georgios
Published: April 2021

Background: Vestibular schwannomas (VS) are brain tumors affecting the vestibulocochlear nerve. Thus, VS patients suffer from tinnitus (TN). While the pathophysiology is mainly unclear, there is an increasing interest in repetitive transcranial magnetic stimulation (rTMS) for TN treatment. However, the results have been divergent. In addition to the methodological aspects, the heterogeneity of the patients might affect the outcome. Yet, there is no study evaluating rTMS exclusively in VS-associated tinnitus. Thus, the present pilot study evaluates low-frequency rTMS to the right dorsolateral pre-frontal cortex (DLPFC) in a VS-associated tinnitus.

Methods: This prospective pilot study enrolled nine patients with a monoaural VS-associated tinnitus ipsilateral to the tumor. Patients were treated with a 10-day rTMS regime (1 Hz, 100% RMT, 1,200 pulses, right DLPFC). The primary endpoint of the study was the reduction of TN distress (according to the Tinnitus Handicap Inventory, THI). The secondary endpoint was a reduction of TN intensity (according to the Tinnitus Matching Test, TMT) and the evaluation of factors predicting tinnitus outcome (i.e., hearing impairment, TN duration, type of tinnitus).

Results: No complications or side effects occurred. There was one drop-out due to a non-responsiveness of the complaint. There was a significant acute effect of rTMS on the THI and TMT. However, there was no significant long-term effect after 4 weeks. While the THI failed to detect any clinically relevant acute effect of rTMS in 56% of the patients, TMT revealed a reduction of TN intensity for more than 20 in 89% and for more than 50 in 56% of the patients. Notably, the acute effect of rTMS was influenced by the TN type and duration. In general, patients with a tonal TN and shorter TN duration showed a better response to the rTMS therapy.

Conclusion: The present pilot study is the first one to exclusively evaluate the effect of low-frequency rTMS to the right DLPFC in a VS-associated tinnitus. Our results prove the feasibility and the efficacy of rTMS in this patient cohort. There is a significant acute but a limited long-term effect. In addition, there is evidence that patients with a tonal tinnitus and shorter tinnitus duration might have the strongest benefit. A larger, randomized controlled study is necessary to prove these initial findings.