bluuebunny/crossref_metadata_2025 huggingface dataset:
Current approaches for the regeneration and reconstruction of ocular surface in dry eye
Authors: Singh Vimal Kishor , Sharma Pallavi , Vaksh Uttkarsh Kumar Sharma , Chandra Ramesh
Published: September 2022

Significant research revealed the preocular tear film composition and regulations that remain vital for maintaining Ocular surface functional integrity. Inflammation triggered by many factors is the hallmark of Ocular surface disorders or dry eyes syndrome (DES). The tear deficiencies may lead to ocular surface desiccation, corneal ulceration and/or perforation, higher rates of infectious disease, and the risk of severe visual impairment and blindness. Clinical management remains largely supportive, palliative, and frequent, lifelong use of different lubricating agents. However, few advancements such as punctal plugs, non-steroidal anti-inflammatory drugs, and salivary gland autografts are of limited use. Cell-based therapies, tissue engineering, and regenerative medicine, have recently evolved as long-term cures for many diseases, including ophthalmic diseases. The present article focuses on the different regenerative medicine and reconstruction/bioengineered lacrimal gland formation strategies reported so far, along with their limiting factors and feasibility as an effective cure in future.
Toxic epidermal necrolysis in hepatitis A infection with acute-on-chronic liver failure: Case report and literature review
Authors: Zang Xin , Chen Si , Zhang Lin , Zhai Yongzhen
Published: September 2022

Toxic epidermal necrolysis (TEN) and Stevens–Johnson syndrome (SJS) are acute inflammatory skin adverse reactions characterized by epidermal exfoliation and multi-site mucositis and are considered medical emergencies. The risk factors for SJS/TEN include immune disorders, malignancy, and genetic susceptibility. In most cases, medication is considered to be the leading cause of TEN. In addition, several studies suggest that infections, such as the herpes simplex virus, human immunodeficiency virus (HIV), Mycoplasma pneumoniae, streptococcus, and meningococcus infections, can trigger the occurrence of SJS/TEN. In this rare case, we share our experience managing TEN in a hepatitis A virus infection with an acute-on-chronic liver failure patient. A 38-year-old man was infected with hepatitis A virus on the basis of liver cirrhosis and progressed to acute-on-chronic liver failure. As the infection progressed, the target-like skin lesions accompanied by mucosal involvement worsened. The condition of the patient progressively worsened with a severe generalized rash, bullae, and epidermal detachment accompanied by severe erosive mucosal lesions. His skin detachment area gradually involved 30% of the body surface area (BSA), and the disease progressed to TEN. The intravenous infusion of corticosteroids alleviated the patient's hypersensitivity, and the patient obtained lasting remission without severe adverse reactions and complications.
Amphiphilic aminoglycosides: Modifications that revive old natural product antibiotics
Authors: Takemoto Jon Y. , Altenberg Guillermo A. , Poudyal Naveena , Subedi Yagya P. , Chang Cheng-Wei T.
Published: September 2022

Widely-used Streptomyces-derived antibacterial aminoglycosides have encountered challenges because of antibiotic resistance and toxicity. Today, they are largely relegated to medicinal topical applications. However, chemical modification to amphiphilic aminoglycosides can revive their efficacy against bacterial pathogens and expand their targets to other pathogenic microbes and disorders associated with hyperactive connexin hemichannels. For example, amphiphilic versions of neomycin and neamine are not subject to resistance and have expanded antibacterial spectra, and amphiphilic kanamycins are effective antifungals and have promising therapeutic uses as connexin hemichannel inhibitors. With further research and discoveries aimed at improved formulations and delivery, amphiphilic aminoglycosides may achieve new horizons in pharmacopeia and agriculture for Streptomyces aminoglycosides beyond just serving as topical antibacterials.
Comparative analysis reveals the modular functional structure of conjugative megaplasmid pTTS12 of Pseudomonas putida S12: A paradigm for transferable traits, plasmid stability, and inheritance?
Authors: Kusumawardhani Hadiastri , Hosseini Rohola , Verschoor Jo-Anne , de Winde Johannes H.
Published: September 2022

Originating from various environmental niches, large numbers of bacterial plasmids have been found carrying heavy metal and antibiotic resistance genes, degradation pathways and specific transporter genes for organic solvents or aromatic compounds. Such genes may constitute promising candidates for novel synthetic biology applications. Our systematic analysis of gene clusters encoded on megaplasmid pTTS12 from Pseudomonas putida S12 underscores that a large portion of its genes is involved in stress response to increase survival under harsh conditions like the presence of heavy metal and organic solvent. We investigated putative roles of genes encoded on pTTS12 and further elaborated on their roles in the establishment and maintenance under several stress conditions, specifically focusing on solvent tolerance in P. putida strains. The backbone of pTTS12 was found to be closely related to that of the carbapenem-resistance plasmid pOZ176, member of the IncP-2 incompatibility group, although the carbapenem resistance cassette is absent from pTTS12. Megaplasmid pTTS12 contains multiple transposon-flanked cassettes mediating resistance to various heavy metals such as tellurite, chromate (Tn7), and mercury (Tn5053 and Tn5563). Additionally, pTTS12 also contains a P-type, Type IV secretion system (T4SS) supporting self-transfer to other P. putida strains. This study increases our understanding in the modular structure of pTTS12 as a member of IncP-2 plasmid family and several promising exchangeable gene clusters to construct robust microbial hosts for biotechnology applications.
Identification of methylation signatures and rules for predicting the severity of SARS-CoV-2 infection with machine learning methods
Authors: Liu Zhiyang , Meng Mei , Ding ShiJian , Zhou XiaoChao , Feng KaiYan , Huang Tao , Cai Yu-Dong
Published: September 2022

Patients infected with SARS-CoV-2 at various severities have different clinical manifestations and treatments. Mild or moderate patients usually recover with conventional medical treatment, but severe patients require prompt professional treatment. Thus, stratifying infected patients for targeted treatment is meaningful. A computational workflow was designed in this study to identify key blood methylation features and rules that can distinguish the severity of SARS-CoV-2 infection. First, the methylation features in the expression profile were deeply analyzed by a Monte Carlo feature selection method. A feature list was generated. Next, this ranked feature list was fed into the incremental feature selection method to determine the optimal features for different classification algorithms, thereby further building optimal classifiers. These selected key features were analyzed by functional enrichment to detect their biofunctional information. Furthermore, a set of rules were set up by a white-box algorithm, decision tree, to uncover different methylation patterns on various severity of SARS-CoV-2 infection. Some genes (PARP9, MX1, IRF7), corresponding to essential methylation sites, and rules were validated by published academic literature. Overall, this study contributes to revealing potential expression features and provides a reference for patient stratification. The physicians can prioritize and allocate health and medical resources for COVID-19 patients based on their predicted severe clinical outcomes.
Knowing the unknown: The underestimation of monkeypox cases. Insights and implications from an integrative review of the literature
Authors: Bragazzi Nicola Luigi , Woldegerima Woldegebriel Assefa , Iyaniwura Sarafa Adewale , Han Qing , Wang Xiaoying , Shausan Aminath , Badu Kingsley , Okwen Patrick , Prescod Cheryl , Westin Michelle , Omame Andrew , Converti Manlio , Mellado Bruce , Wu Jianhong , Kong Jude Dzevela
Published: September 2022

Monkeypox is an emerging zoonotic disease caused by the monkeypox virus, which is an infectious agent belonging to thegenus Orthopoxvirus. Currently, commencing from the end of April 2022, an outbreak of monkeypox is ongoing, with more than 43,000 cases reported as of 23 August 2022, involving 99 countries and territories across all the six World Health Organization (WHO) regions. On 23 July 2022, the Director-General of the WHO declared monkeypox a global public health emergency of international concern (PHEIC), since the outbreak represents an extraordinary, unusual, and unexpected event that poses a significant risk for international spread, requiring an immediate, coordinated international response. However, the real magnitude of the burden of disease could be masked by failures in ascertainment and under-detection. As such, underestimation affects the efficiency and reliability of surveillance and notification systems and compromises the possibility of making informed and evidence-based policy decisions in terms of the adoption and implementation ofad hocadequate preventive measures. In this review, synthesizing 53 papers, we summarize the determinants of the underestimation of sexually transmitted diseases, in general, and, in particular, monkeypox, in terms of all their various components and dimensions (under-ascertainment, underreporting, under-detection, under-diagnosis, misdiagnosis/misclassification, and under-notification).
Identification of Leuconostoc species based on novel marker genes identified using real-time PCR via computational pangenome analysis
Authors: Kim Eiseul , Yang Seung-Min , Kim Ik-Seon , Lee So-Yun , Kim Hae-Yeong
Published: September 2022

Leuconostoc species are important microorganisms in food fermentation but also cause food spoilage. Although these species are commercially important, their taxonomy is still based on inaccurate identification methods. Here, we used computational pangenome analysis to develop a real-time PCR-based method for identifying and differentiating the 12 major Leuconostoc species found in food. Analysis of pan and core-genome phylogenies showed clustering of strains into 12 distinct groups according to the species. Pangenome analysis of 130 Leuconostoc genomes from these 12 species enabled the identification of each species-specific gene. In silico testing of the species-specific genes against 143 publicly available Leuconostoc and 100 other lactic acid bacterial genomes showed that all the assays had 100% inclusivity/exclusivity. We also verified the specificity for each primer pair targeting each specific gene using 23 target and 124 non-target strains and found high specificity (100%). The sensitivity of the real-time PCR method was 102 colony forming units (CFUs)/ml in pure culture and spiked food samples. All standard curves showed good linear correlations, with an R2 value of ≥0.996, suggesting that screened targets have good specificity and strong anti-interference ability from food sample matrices and non-target strains. The real-time PCR method can be potentially used to determine the taxonomic status and identify the Leuconostoc species in foods.
Of its five acyl carrier proteins, only AcpP1 functions in Ralstonia solanacearum fatty acid synthesis
Authors: Yin Yu , Li Rui , Liang Wei-Ting , Zhang Wen-Bin , Hu Zhe , Ma Jin-Cheng , Wang Hai-Hong
Published: September 2022

The fatty acid synthesis (FAS) pathway is essential for bacterial survival. Acyl carrier proteins (ACPs), donors of acyl moieties, play a central role in FAS and are considered potential targets for the development of antibacterial agents. Ralstonia solanacearum, a primary phytopathogenic bacterium, causes bacterial wilt in more than 200 plant species. The genome of R. solanacearum contains five annotated acp genes, acpP1, acpP2, acpP3, acpP4, and acpP5. In this study, we characterized the five putative ACPs and confirmed that only AcpP1 is involved in FAS and is necessary for the growth of R. solanacearum. We also found that AcpP2 and AcpP4 participate in the polyketide synthesis pathway. Unexpectedly, the disruption of four acp genes (acpP2, acpP3, acpP4, and acpP5) allowed the mutant strain to grow as well as the wild-type strain, but attenuated the bacterium’s pathogenicity in the host plant tomato, suggesting that these four ACPs contribute to the virulence of R. solanacearum through mechanisms other than the FAS pathway.
Construction of chicken infectious anemia virus infectious clone and study on its pathogenicity
Authors: Wang Jinjin , Li Yan , Zhang Yawen , Chen Longfei , Fang Lichun , Chang Shuang , Wang Yixin , Zhao Peng
Published: September 2022

Chicken infectious anemia virus (CIAV) can be transmitted through contaminated live poultry vaccine. However, the pathogenicity of contaminated CIAV strains is rarely reported. Previously, the chickens showed the typical symptoms of anemia after using the attenuated live fowl pox virus (FPV) vaccine. Therefore, exogenous CIAV contamination was suspected. We detected anti-CIAV antibodies in SPF chicks vaccinated with the FPV vaccine. CIAV contamination was confirmed in the FPV vaccine, and the CIAV strain was named JS2020-FPV. This study aims to rescue JS2020-FPV by reverse genetic assays and investigate its pathogenicity. Firstly, double-copies infectious clone of JS2020-FPV was constructed. For the pathogenicity study, infectious clone of JS2020-FPV was used to inoculate 1-day-old SPF chicks. The typical symptoms of anemia were observed in the JS2020-PFV group 14  days post inoculation. The hematocrit and body weight of chicks in the JS2020-PFV group were significantly lower than those in the mock group. Notably, the thymus development index and antibody levels of NDV were lower in chicks in the JS2020-PFV group than those in the mock group. Different degrees of apoptosis of MSB1 and DF-1 were observed after inoculated with the JS2020-FPV VP3 recombinant fusion protein expressed by E. coli system, indicating that VP3 induced apoptosis in the transformed cells. Overall, the pathogenicity of the CIAV detected in the contaminated vaccine was confirmed by inoculating SPF chicks with the double-copies infectious DNA clone in this study. Our findings indicate that the dangers of vaccine contamination cannot be ignored.
Small Intestine Microbiome and Metabolome of High and Low Residual Feed Intake Angus Heifers
Authors: Liu Yue , Liu Chang , Wu Hao , Meng Qingxiang , Zhou Zhenming
Published: September 2022

The gastrointestinal tract (GIT) contains complex microbial communities and plays an essential role in the overall health of the host. Previous studies of beef cattle feed efficiency have primarily concentrated on the ruminal microbiota because it plays a key role in energy production and nutrient supply in the host. Although the small intestine is the important site of post-ruminal digestion and absorption of nutrients, only a few studies have explored the relationship between the microbial populations in the small intestine and feed efficiency. Moreover, variations in GIT metabolites contribute to differences in feed efficiency. The objective of this study was to investigate relationships among bacterial populations of duodenum, jejunum, ileum; microbial metabolites; and RFI phenotype of beef cattle. We carried out by using Illumina MiSeq sequencing of the 16S rRNA V3-V4 region and liquid chromatography-mass spectrometry (LC–MS). In the duodenum, the relative abundances of Firmicutes ( p < 0.01), Lachnospiraceae, Ruminococcaceae, Family_XIII, Christensenellaceae, Christensenellaceae_R-7_group ( p < 0.05), and Lachnospiraceae_NK3A20_group ( p < 0.05) were higher in the low residual feed intake (LRFI) group compared with the high residual feed intake (HRFI) group, whereas the HRFI group had higher abundances of Proteobacteria and Acinetobacter ( p < 0.01). In the jejunum, the relative abundances of Lachnospiraceae and Lachnospiraceae_NK3A20_group were higher in the LRFI group ( p < 0.05). In the ileum, the relative abundances of Ruminococcaceae ( p < 0.01), Christensenellaceae, Christensenellaceae_R-7_group, and Ruminococcus_2 were also higher in the LRFI group ( p < 0.05). Moreover, the genera Lachnospiraceae_NK3A20_group, Christensenellaceae_R-7_group, and Ruminococcus_2 were negatively associated with RFI, while the genus Acinetobacter was positively associated with RFI. The metabolomics analysis revealed that the LRFI group significantly improved protein digestion and absorption, as well as glycerophospholipid metabolism in the duodenum, jejunum, ileum. The correlation between intestinal microorganisms and metabolites revealed that some microorganisms play an important role in amino acid metabolism, glycerophospholipid metabolism, nutrient digestion and absorption, and antioxidant enhancement. The present study provides a better understanding of the small intestinal microbiota and metabolites of beef cattle with different RFI phenotypes and the relationships among them, which are potentially important for the improvement of beef cattle feed efficiency.
Batch Experiments Demonstrating a Two-Stage Bacterial Process Coupling Methanotrophic and Heterotrophic Bacteria for 1-Alkene Production From Methane
Authors: Khanongnuch Ramita , Mangayil Rahul , Santala Ville , Hestnes Anne Grethe , Svenning Mette Marianne , Rissanen Antti J.
Published: September 2022

Methane (CH4) is a sustainable carbon feedstock for value-added chemical production in aerobic CH4-oxidizing bacteria (methanotrophs). Under substrate-limited (e.g., oxygen and nitrogen) conditions, CH4 oxidation results in the production of various short-chain organic acids and platform chemicals. These CH4-derived products could be broadened by utilizing them as feedstocks for heterotrophic bacteria. As a proof of concept, a two-stage system for CH4 abatement and 1-alkene production was developed in this study. Type I and Type II methanotrophs, Methylobacter tundripaludum SV96 and Methylocystis rosea SV97, respectively, were investigated in batch tests under different CH4 and air supplementation schemes. CH4 oxidation under either microaerobic or aerobic conditions induced the production of formate, acetate, succinate, and malate in M. tundripaludum SV96, accounting for 4.8–7.0% of consumed carbon from CH4 (C-CH4), while M. rosea SV97 produced the same compounds except for malate, and with lower efficiency than M. tundripaludum SV96, accounting for 0.7–1.8% of consumed C-CH4. For the first time, this study demonstrated the use of organic acid-rich spent media of methanotrophs cultivating engineered Acinetobacter baylyi ADP1 ‘tesA-undA cells for 1-alkene production. The highest yield of 1-undecene was obtained from the spent medium of M. tundripaludum SV96 at 68.9 ± 11.6 μmol mol Csubstrate–1. However, further large-scale studies on fermenters and their optimization are required to increase the production yields of organic acids in methanotrophs.
Effects of fecal microbiota transplantation from yaks on weaning diarrhea, fecal microbiota composition, microbial network structure and functional pathways in Chinese Holstein calves
Authors: Li Yuanyuan , Li Xin , Wu Yanyan , Zhang Wenju
Published: September 2022

This study was conducted to investigate the effect of fecal microbiota transplantation (FMT) from yaks on weaning diarrhea, fecal microbiota composition, microbial network structure and functional pathways in Chinese Holstein Calves. In this study, 50 calves were randomly divided into five groups of 10 each: NC group (no supplementation), Control group (normal saline), low concentration FMT group (LFMT, 1 × 108 CFU/ml), high concentration FMT group (HMFT, 1 × 109 CFU/ml), and sterilized FMT group (SMFT, sterilized bacterial solution). The test lasted for 30 days. We found that FMT reduced the incidence of diarrhea in weaned calves, and the anti-diarrhea effect of LFMT was stronger than those of HFMT and SFMT. Calf feces were collected by rectal palpation on days 5, 10, 15, and 20 post-weaning, and high-throughput sequencing of bacterial 16S rRNA and fungal internal transcribed spacer region of fecal microbiota was performed. We observed that the richness and diversity of bacterial microbiota in the LFMT, HFMT, and SFMT groups were higher than those in the NC and Control groups at day 20 after weaning. The treatment had a significant effect on bacterial richness (p < 0.05), but not on fungal diversity or richness. The analysis of gut microbiome showed that Firmicutes and Bacteroides were the main bacterial phyla in the feces of weaned calves, and norank_ f Muribaculaceae, UCG-005, Rikenellaceae_RC9_gut_group, Bacteroides, and Blautia were the main genera. Ascomycota and Basidiomycota were the main fungal phyla. Compared to abundance parameters in the Control and NC groups, relative abundances of Firmicutes in the FMT groups increased at different time points after weaning. The relative abundance of Blautia and Lactobacillus in the LFMT group increased significantly after weaning. In addition, abundances of Ruminococcus and Romboutsia, which produce short-chain fatty acids, were also increased in different FMT groups. FMT significantly increased the relative abundance of beneficial bacteria, enhanced the complexity of the fecal microbial network, and promoted important metabolic and cellular processes in weaned calves. In conclusion, our study provides a reference and theoretical basis for FMT to prevent calf weaning diarrhea and other intestinal diseases in ruminants.
Use of Quantitative Metagenomics Next-Generation Sequencing to Confirm Fever of Unknown Origin and Infectious Disease
Authors: Dong Yuxin , Gao Yulei , Chai Yanfen , Shou Songtao
Published: September 2022

A body temperature >38.3°C that lasts ≥3 weeks and lacks a clear diagnosis after 1 week of standard hospital examination and treatment is called “fever of unknown origin” (FUO). The main causes of FUO are infections, hematological diseases, autoimmune diseases, and other non-infectious inflammatory diseases. In recent years, quantitative metagenomics next-generation sequencing (Q-mNGS) has been used widely to detect pathogenic microorganisms, especially in the contribution of rare or new (e.g., severe acute respiratory syndrome-coronavirus-2) pathogens. This review addresses the undetermined cause of fever and its evaluation by Q-mNGS.
The influence of gastric atrophy on Helicobacter pylori antibiotics resistance in therapy-naïve patients
Authors: Goni Elisabetta , Tammer Ina , Schütte Kerstin , Thon Cosima , Jechorek Dörthe , Mahajan Ujjwal Mukund , Vasapolli Riccardo , Macke Lukas , Aulinger Benedikt , Selgrad Michael , Link Alexander , Malfertheiner Peter , Schulz Christian
Published: September 2022

Background

Antibiotic susceptibility of Helicobacter pylori to antibiotics may vary among different niches of the stomach. The progression of chronic H. pylori gastritis to atrophy changes intragastric physiology that may influence selection of resistant strains.

Aim

To study the antibiotic resistance of H. pylori taking the severity of atrophic gastritis in antrum and corpus into account.

Methods

Helicobacter pylori-positive patients (n = 110, m = 32, mean age 52.6 ± 13.9 years) without prior H. pylori eradication undergoing upper gastrointestinal (GI) endoscopy for dyspeptic symptoms were included in a prospective study. Patients were stratified into three groups depending on the grade of atrophy: no atrophy (OLGA Stage 0), mild atrophy (OLGA Stage I–II) and moderate/severe atrophy (OLGA Stage III–IV). Two biopsies each from the antrum and the corpus and one from the angulus were taken and assessed according to the updated Sydney system. H. pylori strains were isolated from antrum and corpus biopsies and tested for antibiotic susceptibility (AST) for amoxicillin, clarithromycin, metronidazole, levofloxacin, tetracycline, and rifampicin by the agar dilution methods. A Chi-square test of independence with a 95% confidence interval was used to detect differences in the proportion of patients with susceptible and resistant H. pylori strains.

Results

Among 110 patients, primary clarithromycin resistance (R) was 30.0%, both in the antrum and corpus; metronidazole resistance accounted for 36.4 and 34.5% in the antrum and corpus; and levofloxacin was 19.1 and 22.7% in the antrum and corpus, respectively. Resistance rates to amoxicillin, tetracycline, and rifampicin were below 5%. Dual antibiotic resistance rate was 21.8%, and triple resistance rate was 9.1%. There was a significant difference in the resistance rate distribution in antrum (p < 0.0001) and corpus (p < 0.0001). With increasing severity of atrophy according to OLGA stages, there was a significant increase in clarithromycin-R and metronidazole-R.

Conclusion

In treatment-naïve patients, antibiotic resistance and heteroresistance were related to the severity of atrophy. The high clarithromycin resistance in atrophic gastritis suggests that H. pylori antibiotic susceptibility testing should always be performed in this condition before selecting the eradication regimen.
Candida guilliermondii as an agent of postpartum subacute mastitis in Rio de Janeiro, Brazil: Case report
Authors: Pinto Tatiane Nobre , Kohn Alana , da Costa Gisela Lara , Oliveira Laura M. A. , Pinto Tatiana C. A. , Oliveira Manoel M. E.
Published: September 2022

Candida spp. can cause mild-to-severe human infections. Certain species have been described as the etiologic agent of human mastitis, inflammation of the breast tissue. Mastitis affects millions of lactating women and can be a source of disease transmission to the infant. In this work, we report the detection of the unusual etiologic agent of human mastitis, Candida guilliermondii, isolated from the milk of a puerperal woman with subacute mastitis in Rio de Janeiro, Brazil. Species identification was performed by MALDI-TOF MS and genetic sequencing. The patient had a full recovery after antifungal therapy.
Whole-genome sequence analysis for evaluating the safety and probiotic potential of Lactiplantibacillus pentosus 9D3, a gamma-aminobutyric acid (GABA)-producing strain isolated from Thai pickled weed
Authors: Raethong Nachon , Santivarangkna Chalat , Visessanguan Wonnop , Santiyanont Pannita , Mhuantong Wuttichai , Chokesajjawatee Nipa
Published: September 2022

Lactiplantibacillus pentosus 9D3, a prominent gamma-aminobutyric acid (GABA)-producing bacteria isolated from Thai pickled weed was characterized for its safety and probiotic properties via whole-genome analysis and in vitro testing. The whole-genome sequence of L. pentosus 9D3 was determined using a hybrid-sequencing approach, combining PacBio and Illumina technologies. A 3.81-Mbp genome of L. pentosus 9D3 consisting of one 3.65-Mbp chromosome and six plasmids (1.9–71.9 Kbp) was identified with an estimated GC content of 46.09% and 3,456 predicted genes. The strain was confirmed to be Lactiplantibacillus pentosus according to the high average nucleotide identity value of >95% and digital DNA–DNA hybridization scores of >70% to the L. pentosus type strain. Comparative genome analysis with other L. pentosus strains showed that the GABA-producing capability was specific to the strain 9D3. Genes related to GABA biosynthesis and transport were identified on a plasmid, pLPE-70K, indicating the acquired nature of this property. The safety of L. pentosus 9D3 was demonstrated through the lack of genes related to the production of toxins, biogenic amines, and antimicrobial drugs. Although the strain exhibited resistance to ampicillin and chloramphenicol, none of the antimicrobial resistance (AMR) genes were associated with mobile elements, i.e., plasmids and prophages. Therefore, the strain is considered to have low risk of transferring the AMR genes to other, potentially pathogenic bacteria. In addition, L. pentosus 9D3 showed good survivability in the gastrointestinal tract environment and was able to adhere to the intestinal cell in vitro. Therefore, L. pentosus 9D3 is concluded to be safe, with the potential to be used as a probiotic, exerting its health benefit through GABA production in the food system. The GABA-producing capability of the strain in vivo is the subject of further investigation.
Heterologous vaccine immunogenicity, efficacy, and immune correlates of protection of a modified-live virus porcine reproductive and respiratory syndrome virus vaccine
Authors: Proctor Jessica , Wolf Iman , Brodsky David , Cortes Lizette M. , Frias-De-Diego Alba , Almond Glen W. , Crisci Elisa , Negrão Watanabe Tatiane Terumi , Hammer James M. , Käser Tobias
Published: September 2022

Although porcine reproductive and respiratory syndrome virus (PRRSV) vaccines have been available in North America for almost 30 years, many vaccines face a significant hurdle: they must provide cross-protection against the highly diverse PRRSV strains. This cross-protection, or heterologous vaccine efficacy, relies greatly on the vaccine’s ability to induce a strong immune response against various strains—heterologous immunogenicity. Thus, this study investigated vaccine efficacy and immunogenicity of a modified live virus (MLV) against four heterologous type 2 PRRSV (PRRSV-2) strains. In this study, 60 pigs were divided into 10 groups. Half were MOCK-vaccinated, and the other half vaccinated with the Prevacent® PRRS MLV vaccine. Four weeks after vaccination, groups were challenged with either MOCK, or four PRRSV-2 strains from three different lineages—NC174 or NADC30 (both lineage 1), VR2332 (lineage 5), or NADC20 (lineage 8). Pre-and post-challenge, lung pathology, viral loads in both nasal swabs and sera, anti-PRRSV IgA/G, neutralizing antibodies, and the PRRSV-2 strain-specific T-cell response were evaluated. At necropsy, the lung samples were collected to assess viral loads, macroscopical and histopathological findings, and IgA levels in bronchoalveolar lavage. Lung lesions were only induced by NC174, NADC20, and NADC30; within these, vaccination resulted in lower gross and microscopic lung lesion scores of the NADC20 and NADC30 strains. All pigs became viremic and vaccinated pigs had decreased viremia upon challenge with NADC20, NADC30, and VR2332. Regarding vaccine immunogenicity, vaccination induced a strong systemic IgG response and boosted the post-challenge serum IgG levels for all strains. Furthermore, vaccination increased the number of animals with neutralizing antibodies against three of the four challenge strains—NADC20, NADC30, and VR2332. The heterologous T-cell response was also improved by vaccination: Not only did vaccination increase the induction of heterologous effector/memory CD4 T cells, but it also improved the heterologous CD4 and CD8 proliferative and/or IFN-γ response against all strains. Importantly, correlation analyses revealed that the (non-PRRSV strain-specific) serum IgG levels and the PRRSV strain-specific CD4 T-cell response were the best immune correlates of protection. Overall, the Prevacent elicited various degrees of efficacy and immunogenicity against four heterologous and phylogenetically distant strains of PRRSV-2.
Metabolomic and metagenomic analyses of the Chinese mitten crab Eriocheir sinensis after challenge with Metschnikowia bicuspidata
Authors: Jiang Hongbo , Bao Jie , Xing Yuenan , Cao Gangnan , Li Xiaodong , Chen Qijun
Published: September 2022

Milky disease caused by Metschnikowia bicuspidata fungus has significantly harmed the Chinese mitten crab Eriocheir sinensis aquaculture industry. However, the effect of M. bicuspidata infection on the metabolism and intestinal flora of the crab remains unclear. In this study, we aimed to explore the changes in the metabolism and intestinal flora E. sinensis after 48 h of infection with M. bicuspidata, using metabolomic and metagenomic analyses. Metabolomic analysis results revealed 420 significantly different metabolites between the infected and control groups, and these metabolites were enriched in 58 metabolic pathways. M. bicuspidata infection decreased the levels of metabolites related to amino acid biosynthesis, the tricarboxylic acid cycle, as well as lysine, histidine, linolenic, arachidonic, and linoleic acid metabolism. These results indicated that M. bicuspidata infection significantly affected the energy metabolism, growth, and immunity of E. sinensis. The results of metagenomic analysis showed that the anaerobes and ascomycetes populations significantly increased and decreased, respectively, after M. bicuspidata infection. These changes in intestinal flora significantly upregulated metabolic and synthetic pathways while downregulating immunity-related pathways. The results of integrated metabolomic and metagenomic analyses showed that 55 differentially expressed genes and 28 operational taxonomic units were correlated with 420 differential metabolites. Thus, the intestinal flora changes caused by M. bicuspidata infection also affected the metabolites. This study provides novel insights into the metabolic-and intestinal microflora-based effects of M. bicuspidata infection in E. sinensis, as well as a theoretical basis for the interaction between fungi and crustaceans.
The metabolic plasticity of B cells
Authors: Vivas-García Yurena , Efeyan Alejo
Published: September 2022

The humoral response requires rapid growth, biosynthetic capacity, proliferation and differentiation of B cells. These processes involve profound B-cell phenotypic transitions that are coupled to drastic changes in metabolism so as to meet the extremely different energetic requirements as B cells switch from resting to an activated, highly proliferative state and to plasma or memory cell fates. Thus, B cells execute a multi-step, energetically dynamic process of profound metabolic rewiring from low ATP production to transient and large increments of energy expenditure that depend on high uptake and consumption of glucose and fatty acids. Such metabolic plasticity is under tight transcriptional and post-transcriptional regulation. Alterations in B-cell metabolism driven by genetic mutations or by extrinsic insults impair B-cell functions and differentiation and may underlie the anomalous behavior of pathological B cells. Herein, we review molecular switches that control B-cell metabolism and fuel utilization, as well as the emerging awareness of the impact of dynamic metabolic adaptations of B cells throughout the different phases of the humoral response.
Plasma glycocholic acid and linoleic acid identified as potential mediators of mitochondrial bioenergetics in Alzheimer’s dementia
Authors: Amick K. Allison , Mahapatra Gargi , Gao Zhengrong , Dewitt Amber , Craft Suzanne , Jain Mohit , Molina Anthony J. A.
Published: September 2022

Mitochondrial bioenergetic alterations occur in the brain and peripheral cells of patients with Alzheimer’s disease (AD). This study focuses on plasma circulating factors, namely lipids, as mediators of systemic bioenergetic differences in participants with normal cognition (NC), mild cognitive impairment (MCI), and dementia due to probable AD (DEM). We examined bioenergetic differences across cognitive groups by measuring the mitochondrial respiration of peripheral blood mononuclear cells (PBMCs) from 37 participants (12 NC, 12 MCI, 13 DEM). PBMC bioenergetics were lower in the DEM group compared to the NC group. To determine whether circulating factors can mediate bioenergetic differences according to cognitive status, we exposed naïve neuronal Neuro-2a (N2a) cells to plasma from each participant in vitro. N2a bioenergetics were lower following plasma exposure from DEM compared to NC group participants. Notably, PBMC Max and N2a Max positively correlated, suggesting that circulating factors modulate the bioenergetics of naïve N2a cells according to the bioenergetic capacity of donor primary PBMCs. To identify lipid metabolites that may contribute to bioenergetic differences between cognitive groups, we performed liquid chromatography-mass spectrometry to assess the abundance of individual lipid species and correlated PBMC and N2a bioenergetics. Glycocholic acid (GCA) positively correlated with PBMC and N2a bioenergetics, while linoleic acid (LA) was negatively correlated. These data suggest that GCA and LA may contribute to the stimulatory and inhibitory bioenergetics effects related to cognitive status. Post hoc analyses revealed that GCA abundance was lower by 52.9% in the DEM group compared to the NC group and that LA abundance was higher by 55.7% in the DEM group compared to the NC group. To validate these findings, we examined the abundance of GCA and LA in the larger, more diverse, parent cohort (n = 378) and found similar results; GCA abundance was lower by 29.7% in the DEM group compared to the NC group and LA abundance was higher by 17.8% in the DEM group compared to the NC group. These data demonstrate that circulating factors have a direct effect on mitochondrial bioenergetics and that individual circulating factors identified to be associated with mitochondrial function are differentially expressed in patients with dementia.
Relationship among number of close friends, subclinical geriatric depression, and subjective cognitive decline based on regional homogeneity of functional magnetic resonance imaging data
Authors: Zhang Zhao , Li Guangfei , Song Zeyu , Han Ying , Tang Xiaoying
Published: September 2022

The relationship between geriatric depression and dementia has been widely debated, and the neurological mechanisms underlying subjective cognitive decline (SCD) associated with social relationships remain elusive. Subclinical geriatric depression (SGD) is common in patients with SCD, and close friends (CFs) have a great influence on a person’s social life. Studies have proven that communication or leisure activities with CFs can improve the cognitive performance of elderly. However, it remains unclear whether the engagement of specific brain regions mediates having CFs, SGD, and SCD. In this study, we aimed to assess the association between social relationships (that is, CFs), SGD, and SCD from the perspective of brain function. We examined the data of 66 patients with SCD and 63 normal controls (NC). Compared with NC, SGD was significantly inversely correlated with the number of CFs in the SCD group. We calculated regional homogeneity (ReHo) of functional magnetic resonance imaging (MRI) data of each subject. At a corrected threshold, the right occipital gyrus (SOG.R) and right fusiform gyrus (FFG.R) exhibited positive correlation with SGD in patients with SCD. Mediation analyses to query the inter-relationships between the neural markers and clinical variables exhibited a best fit of the model with CFs → FFG.R → SGD → SOG.R → SCD. These findings suggested a pathway whereby social relationships alter the function of specific brain regions, and SGD may be an early symptom of SCD. We observed that the FFG.R mediate social relationships and SGD, and the abnormality of the SOG.R may be a key factor in the SCD caused by depression. Moreover, a greater number of CFs may reduce the risk of developing SGD.
Physical activities and risk of neurodegenerative diseases: A two-sample Mendelian randomization study
Authors: Liao Qiao , He Jian , Huang Kun
Published: September 2022

Objectives

Physical activity (PA) is considered beneficial in slowing the progression and improving the neurodegenerative disease prognosis. However, the association between PA and neurodegenerative diseases remains unknown. In this study, we conducted a two-sample Mendelian randomization (MR) analysis to estimate the causal association between PA phenotypes and neurodegenerative diseases.

Materials and methods

Genetic variants robustly associated with PA phenotypes, used as instrumental variables, were extracted from public genome-wide association study (GWAS) summary statistics. Neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD), and Alzheimer’s disease (AD), were considered outcomes. GWAS information was also obtained from the most recent large population study of individuals with European ancestry. Multiple MR methods, pleiotropy tests and sensitivity analyses were performed to obtain a robust and valid estimation.

Results

We found a positive association between moderate-to-vigorous physical activities and ALS based on the inverse variance weighted MR analysis method (OR: 2.507, 95% CI: 1.218–5.160, p = 0.013). The pleiotropy test and sensitivity analysis confirmed the robustness and validity of these MR results. No causal effects of PA phenotypes were found on PD and AD.

Conclusion

Our study indicates a causal effect of PA on the risk of neurodegenerative diseases. Genetically predicted increases in self-reported moderate-to-vigorous PA participation could increase the risk of ALS in individuals of European ancestry. Precise and individualized prescriptions of physical activity should be provided to the elderly population.
The effects of acute high-intensity aerobic exercise on cognitive performance: A structured narrative review
Authors: Sudo Mizuki , Costello Joseph T. , McMorris Terry , Ando Soichi
Published: September 2022

It is well established that acute moderate-intensity exercise improves cognitive performance. However, the effects of acute high-intensity aerobic exercise on cognitive performance have not been well characterized. In this review, we summarize the literature investigating the exercise-cognition interaction, especially focusing on high-intensity aerobic exercise. We discuss methodological and physiological factors that potentially mediate cognitive performance in response to high-intensity exercise. We propose that the effects of high-intensity exercise on cognitive performance are primarily affected by the timing of cognitive task (during vs. after exercise, and the time delay after exercise). In particular, cognitive performance is more likely to be impaired during high-intensity exercise when both cognitive and physiological demands are high and completed simultaneously (i.e., the dual-task paradigm). The effects may also be affected by the type of cognitive task, physical fitness, exercise mode/duration, and age. Second, we suggest that interactions between changes in regional cerebral blood flow (CBF), cerebral oxygenation, cerebral metabolism, neuromodulation by neurotransmitters/neurotrophic factors, and a variety of psychological factors are promising candidates that determine cognitive performance in response to acute high-intensity exercise. The present review has implications for recreational, sporting, and occupational activities where high cognitive and physiological demands are required to be completed concurrently.
Synchronous firing of dorsal horn neurons at the origin of dorsal root reflexes in naïve and paw-inflamed mice
Authors: Lucas-Romero Javier , Rivera-Arconada Ivan , Lopez-Garcia Jose A.
Published: September 2022

Spinal interneurons located in the dorsal horn induce primary afferent depolarization (PAD) controlling the excitability of the afferent’s terminals. Following inflammation, PAD may reach firing threshold contributing to maintain inflammation and pain. Our aim was to study the collective behavior of dorsal horn neurons, its relation to backfiring of primary afferents and the effects of a peripheral inflammation in this system. Experiments were performed on slices of spinal cord obtained from naïve adult mice or mice that had suffered an inflammatory pretreatment. Simultaneous recordings from groups of dorsal horn neurons and primary afferents were obtained and machine-learning methodology was used to analyze effective connectivity between them. Dorsal horn recordings showed grouping of spontaneous action potentials from different neurons in “population bursts.” These occurred at irregular intervals and were formed by action potentials from all classes of neurons recorded. Compared to naïve, population bursts from treated animals concentrated more action potentials, had a faster onset and a slower decay. Population bursts were disrupted by perfusion of picrotoxin and held a strong temporal correlation with backfiring of afferents. Effective connectivity analysis allowed pinpointing specific neurons holding pre- or post-synaptic relation to the afferents. Many of these neurons had an irregular fast bursting pattern of spontaneous firing. We conclude that population bursts contain action potentials from neurons presynaptic to the afferents which are likely to control their excitability. Peripheral inflammation may enhance synchrony in these neurons, increasing the chance of triggering action potentials in primary afferents and contributing toward central sensitization.
Neuronal activity-dependent ATP enhances the pro-growth effect of repair Schwann cell extracellular vesicles by increasing their miRNA-21 loading
Authors: Saquel Cristian , Catalan Romina J. , Lopez-Leal Rodrigo , Ramirez Ramon A. , Necuñir David , Wyneken Ursula , Lamaze Christophe , Court Felipe A.
Published: September 2022

Functional recovery after peripheral nerve injuries is critically dependent on axonal regeneration. Several autonomous and non-cell autonomous processes regulate axonal regeneration, including the activation of a growth-associated transcriptional program in neurons and the reprogramming of differentiated Schwann cells (dSCs) into repair SCs (rSCs), triggering the secretion of neurotrophic factors and the activation of an inflammatory response. Repair Schwann cells also release pro-regenerative extracellular vesicles (EVs), but is still unknown whether EV secretion is regulated non-cell autonomously by the regenerating neuron. Interestingly, it has been described that nerve activity enhances axonal regeneration by increasing the secretion of neurotrophic factors by rSC, but whether this activity modulates pro-regenerative EV secretion by rSC has not yet been explored. Here, we demonstrate that neuronal activity enhances the release of rSC-derived EVs and their transfer to neurons. This effect is mediated by activation of P2Y receptors in SCs after activity-dependent ATP release from sensory neurons. Importantly, activation of P2Y in rSCs also increases the amount of miRNA-21 present in rSC-EVs. Taken together, our results demonstrate that neuron to glia communication by ATP-P2Y signaling regulates the content of SC-derived EVs and their transfer to axons, modulating axonal elongation in a non-cell autonomous manner.