The dynamics of the piglet gut microbiome during the weaning transition in association with health and nutrition

Background: Understanding the composition of the microbial community and its functional capacity during weaning is important for pig production as bacteria play important roles in the pig’s health and growth performance. However,limited information is available regarding the composition and function of the gut microbiome of piglets in early-life.Therefore, we performed 16 S rRNA gene and whole metagenome shotgun sequencing of DNA from fecal samples from healthy piglets during weaning to measure microbiome shifts, and to identify the potential contribution of the early-life microbiota in shaping piglet health with a focus on microbial stress responses, carbohydrate and amino acid metabolism.Results: The analysis of 16 S rR NA genes and whole metagenome shotgun sequencing revealed significant compositional and functional differences between the fecal microbiome in nursing and weaned piglets. The fecal microbiome of the nursing piglets showed higher relative abundance of bacteria in the genus Bacteroides with abundant gene families related to the utilization of lactose and galactose. Prevotel a and Lactobacil us were enriched in weaned piglets with an enrichment for the gene families associated with carbohydrate and amino acid metabolism. In addition, an analysis of the functional capacity of the fecal microbiome showed higher abundances of genes associated with heat shock and oxidative stress in the metagenome of weaned piglets compared to nursing piglets.Conclusions: Overal, our data show that microbial shifts and changes in functional capacities of the piglet fecal microbiome resulted in potential reductions in the effects of stress, including dietary changes that occur during weaning.These results provide us with new insights into the piglet gut microbiome that contributes to the growth of the animal.

Genomic characterization of velogenic avian orthoavulavirus 1 isolates from poultry workers: Implications to emergence and its zoonotic potential towards public health

Objective:To carry out the genetic characterization and evolutionary analysis of three avian orthoavulavirus 1(AOAV-1)isolates from poultry workers with respiratory symptoms.Methods:Using Illumina Mi Seq,whole-genome sequencing was carried out to assess the evolutionary dynamics of three AOAV-1 isolates.A phylogenetic and comparative analysis of all coding genes was done using bioinformatics tools.Results:Phylogenetic analysis and genetic distance estimation suggested a close relationship among human-and avian-originated velogenic strains of genotypeⅩⅢ,sub-genotypeⅩⅢ.2.1.Several substitutions in the significant structural and biological motifs were exclusively identified in the human-originated strains.Conclusions:To our knowledge,this is the first report of a velogenic AOAV-1 isolate from natural infection of the human upper respiratory tract.Our findings highlight the evolution and zoonotic potential of velogenic AOAV-1 in a disease endemic setting.

Development of H5 subtype-specific monoclonal antibodies (MAb) and MAb-based assays for rapid detection of H5 avian influenza

Avian influenza (AI) virology surveillance is the most important method to monitor AI virus (AIV) in poultry so as to effectively prevent and control AI outbreaks. Monoclonal antibodies (MAb)-based assays are highly sensitive and specific for AIV detection, and much practical and economic for test-in-field or onsite. Many such assays have been developed and are still in developing since the H5N1 highly pathogenic AI (HPAI) outbreaks occurred in South East Asia in 2003. A MAb-based dot-enzyme-linked immunosorbent assay (ELISA) has been developed in our lab during late 1990s and early 2000s. Meanwhile, AIV H7 and H5 subtype specific-MAbs have been successfully developed in our laboratory to enhance the Dot-ELISA and other MAb-based assays for AIV detection. Production and purification of the H7 and H5 MAbs were made to provide essential reagents for Dot-ELISA and other immunoassays, and the current development of a novel Biosensor technique for rapid detection of AIV from clinical and field specimens.

A Survey of <i>Escherichia coli</i>O157:H7 Virulence Factors: The First 25 Years and 13 Genomes

Escherichia coli O157:H7 is a human pathogen that was first identified from a foodborne outbreak in 1982, and in the 25 years that followed, many new strains were identified and emerged in numerous outbreaks of human disease. Extensive research has been conducted to identify virulence factor genes involved in the pathogenesis of E. coli O157:H7 and many genome sequences of E. coli O157:H7 strains have become available to the scientific community. Here, we provide a comprehensive overview of the research that has been conducted over the first 25 years to identify 394 known or putative virulence factor genes present in the genomes of E. coli O157:H7 strains. Finally, an examination of the conservation of these 394 virulence factor genes across additional genomes of E. coli O157:H7 is provided which summarizes the first 25 years and 13 genomes of this human pathogen.

Piglet gut microbial shifts early in life:causes and effects

The gut microbiome has long been known to play fundamentally important roles in the animal health and the well-being of its host. As such, the establishment and maintenance of a beneficial gut microbiota early in life is crucial in pigs, since early gut colonizers are pivotal in the establishment of permanent microbial community structures affecting the health and growth performance of pigs later in life. Emphasizing this importance of early gut colonizers, it is critical to understand the factors impacting the establishment of the piglet gut microbiome at weaning. Factors include, among others, diet, in-feed antibiotics, probiotics and prebiotic administration. The impact of these factors on establishment of the gut microbiome of piglets at weaning includes effects on piglet gut microbial diversity, structure, and succession. In this review, we thoroughly reviewed the most recent findings on the piglet gut microbiome shifts as influenced by weaning, and how these microbiome changes brought about by various factors that have been shown to affect the development of microbiota in piglets. This review will provide a general overview of recent studies that can help to facilitate the design of new strategies to modulate the gut microbiome in order to enhance gastrointestinal health, growth performance and well-being of piglets.

Autoantibodies in Alzheimer's disease:potential biomarkers,pathogenic roles,and therapeutic implications

Alzheimer＇s disease （AD） is a prevalent and debilitating neurodegenerative disorder in the elderly. The etiology of AD has not been fully defined and currently there is no cure for this devastating disease. Compelling evidence sug- gests that the immune system plays a critical role in the pathophysiology ofAD. Autoantibodies against a variety of molecules have been associated with AD. The roles of these autoantibodies in AD, however, are not well understood. This review attempts to summarize recent findings on these autoantibodies and explore their potential as diagnostic/ prognostic biomarkers for AD, their roles in the pathogenesis of AD, and their implications in the development of effective immunotherapies for AD.

Detection of viral protein–protein interaction by microplate-format luminescence-based mammalian interactome mapping(LUMIER)

Dear Editor,Viruses are intracellular parasites that depend on cellular components to replicate.Viruses communicate withthe cellular machinery through protein–protein interactions(PPIs),for which each individual virus encodes aunique array of proteins.Each viral protein is capable ofindependently interacting with multiple cellular

Convergence of the turkey gut microbiota following cohabitation under commercial settings

Background:Microbiota development is a critical aspect of turkey poult maturation,and the succession of microbes in the turkey gut has been shown to correlate with poult performance.The purpose of this study was to determine the fate of the microbiota in turkey poults after movement of birds first raised in an isolated hatch brood system into a more traditional commercial brood facility with pre-existing birds.Turkey poults were first divided into groups raised in conventional brood pens from day-of-hatch and those raised in an experimental hatch brood system.After 11 days of growth,hatch brood birds were moved into pens within the conventional brood barn and monitored for an additional 18 days.Sampling of both hatch brood and conventional pen birds was performed at multiple timepoints throughout the study,and cecal content was used to analyze the bacterial microbiota using 16S rRNA gene amplicon sequencing.Results:Alpha diversity tended to be higher in samples from conventional pen birds compared to those from hatch brood birds prior to the day 11 move,but the difference between systems was not observed post-move.Using beta diversity metrics,bacterial community succession appeared delayed in the hatch brood system birds pre-move,but post-move community composition quickly converged with that of the conventional pen birds.This was validated through assessment of significantly different genera between hatch brood system and conventional pen birds,where numbers of significantly different taxa quickly decreased following the move.Some key taxa previously associated with poult performance were delayed in their appearance and relative abundance in hatch brood birds.Conclusions:Overall,this study demonstrates that the use of isolated hatch brood systems has an impact on the poult gut microbiota,but its impact is resolved quickly once the birds are introduced into a conventional brood environment.Therefore,the benefits of pathogen reduction with hatch brood systems may outweigh negative microbiota impacts due to isolation.

Studies of non-metallic organic disinfectants on inactivation of avian influenza viruses

Six different kinds of non-metallic or organic disinfectants were obtained in this research study including “Neutral Electrolyzed Water”, “M22” organic disinfectant solution, Superoxy Food Wash disinfectant, Hydrogen Peroxide, Clorox Germicidal Bleach and Clidox-S. The effectiveness of these disinfectants was studied against various subtypes of avian influenza virus (AIV). The virus-disinfectant mixtures were prepared in serial dilutions of each disinfectant with a constant virus titer and incubated at ambient temperature in different time intervals for virus inactivation. The virus inactivation results were determined by virus recovery in embryonating chicken eggs. Among the six different kinds of nonmetallic disinfectants obtained for this research project, Neutral Electrolyzed Water, “M22” solution, Clorox Germicidal Bleach and Clidox-S were effectively inactivated AIV with appropriate working dilutions and reaction times. Superoxy Food Wash disinfectant and Hydrogen Peroxide were found having limited effect on virus inactivation with extended exposure times of more than 2 hours. These research findings provide scientific data to poultry industry with guidelines to select and use non-metallic organic disinfectants for poultry flock sanitation and disinfection to effectively prevent and control of avian influenza outbreaks.

CCR10 and its ligands in regulation of epithelial immunity and diseases

Epithelial tissues covering the external and internal surface of a body are constantly under physical,chemical or biological assaults.To protect the epithelial tissues and maintain their homeostasis,multiple layers of immune defense mechanisms are required.Besides the epithelial tissue-resident immune cells that provide the first line of defense,circulating immune cells are also recruited into the local tissues in response to challenges.Chemokines and chemokine receptors regulate tissue-specific migration,maintenance and functions of immune cells.Among them,chemokine receptor CCR10 and its ligands chemokines CCL27 and CCL28 are uniquely involved in the epithelial immunity.CCL27 is expressed predominantly in the skin by keratinocytes while CCL28 is expressed by epithelial cells of various mucosal tissues.CCR10 is expressed by various subsets of innate-like T cells that are programmed to localize to the skin during their developmental processes in the thymus.Circulating T cells might be imprinted by skin-associated antigen-presenting cells to express CCR10 for their recruitment to the skin during the local immune response.On the other hand,IgA antibody-producing B cells generated in mucosa-associated lymphoid tissues express CCR10 for their migration and maintenance at mucosal sites.Increasing evidence also found that CCR10/ligands are involved in regulation of other immune cells in epithelial immunity and are frequently exploited by epithelium-localizing or-originated cancer cells for their survival,proliferation and evasion from immune surveillance.Herein,we review current knowledge on roles of CCR10/ligands in regulation of epithelial immunity and diseases and speculate on related important questions worth further investigation.

Telomere dynamics in induced pluripotent stem cells:Potentials for Human disease modeling

Recent advances in reprograming somatic cells from normal and diseased tissues into induced pluripotent stem cells (iPSCs) provide exciting possibilities for generating renewed tissues for disease modeling and therapy. However, questions remain on whether iPSCs still retain certain markers (e.g. aging) of the original somatic cells that could limit their replicative potential and utility. A reliable biological marker for measuring cellular aging is telomere length, which is maintained by a specialized form of cellular polymerase known as telomerase. Telomerase is composed of the cellular reverse transcriptase protein, the integral RNA component, and other cellular proteins (e.g. dyskerin). Mutations in any of these components of telomerase can lead to a severe form of marrow def iciency known as dyskeratosis congenita (DC). This review summarizes recent f indings on the effect of cellular reprograming via iPS of normal or DC patient-derived tissues on telomerase function and consequently on telomere length maintenance. The potentials and challenges of using iPSCs in a clinical setting will also be discussed.

Establishment and function of tissue-residenl nnate lymphoid cells in the skin

Innate lymphoid cells （ILCs） are a newly classified family of immune cells of the lymphoid lineage. While they could be found in both lymphoid organs and non-lym-phoid tissues, ILCs are preferentially enriched in barrier tissues such as the skin, intestine, and lung where they could play important roles in maintenance of tissue integrity and function and protection against assaults of foreign agents. On the other hand, dysregulated activation of ILCs could contribute to tissue inflammatory diseases. In spite of recent progress towards understanding roles of ILCs in the health and disease, mech-anisms regulating specific establishment, activation, and function of ILCs in barrier tissues are still poorly understood. We herein review the up-to-date understanding of tissue-specific relevance of ILCs. Particularly we will focus on resident ILCs of the skin, the outmost barrier tissue critical in protection against various foreign hazardous agents and maintenance of thermal and water balance. In addition, we will discuss remaining outstanding questions yet to be addressed.

Helicobacter pylori in ancient human remains

The bacterium Helicobacter pylori(H.pylori)infects the stomachs of approximately 50%of all humans.With its universal occurrence,high infectivity and virulence properties it is considered as one of the most severe global burdens of modern humankind.It has accompanied humans for many thousands of years,and due to its high genetic variability and vertical transmission,its population genetics reflects the history of human migrations.However,especially complex demographic events such as the colonisation of Europe cannot be resolved with population genetic analysis of modern H.pylori strains alone.This is best exemplified with the reconstruction of the 5300-year-old H.pylori genome of the Iceman,a European Copper Age mummy.Our analysis provided precious insights into the ancestry and evolution of the pathogen and underlined the high complexity of ancient European population history.In this review we will provide an overview on the molecular analysis of H.pylori in mummified human remains that were done so far and we will outline methodological advancements in the field of ancient DNA research that support the reconstruction and authentication of ancient H.pylori genome sequences.

The gut microbiome: an orchestrator of xenobiotic metabolism

Microbes inhabiting the intestinal tract of humans represent a site for xenobiotic metabolism.The gut microbiome,the collection of microorganisms in the gastrointestinal tract,can alter the metabolic outcome of pharmaceuticals,environmental toxicants,and heavy metals,thereby changing their pharmacokinetics.Direct chemical modification of xenobiotics by the gut microbiome,either through the intestinal tract or re-entering the gut via enterohepatic circulation,can lead to increased metabolism or bioactivation,depending on the enzymatic activity within the microbial niche.Unique enzymes encoded within the microbiome include those that reverse the modifications imparted by host detoxification pathways.Additionally,the microbiome can limit xenobiotic absorption in the small intestine by increasing the expression of cell-cell adhesion proteins,supporting the protective mucosal layer,and/or directly sequestering chemicals.Lastly,host gene expression is regulated by the microbiome,including CYP450s,multi-drug resistance proteins,and the transcription factors that regulate them.While the microbiome affects the host and pharmacokinetics of the xenobiotic,xenobiotics can also influence the viability and metabolism of the microbiome.Our understanding of the complex interconnectedness between host,microbiome,and metabolism will advance with new modeling systems,technology development and refinement,and mechanistic studies focused on the contribution of human and microbial metabolism.

Vaccine booster efficiently inhibits entry of SARS-CoV-2 omicron variant

The newly emerged omicron strain of SARS-CoV-2 is spreading fast globally,replacing the previously dominant delta strain in many parts of the world[1].Compared to the early prototypic strains,the delta strain evades the human immune system more easily,causing many breakthrough infections in vaccinated people[2].It is imperative to understand in a timely fashion whether the omicron strain escapes immune surveillances.The information will be critical for public health measures.

Early CD8 T-cell memory precursors and terminal effectors exhibit equipotent in vivo degranulation

Early after priming, effector CD8 T cells are distinguished into memory precursor and short-lived effector cell subsets （MPECs and SLECs）. Here, we delineated a distinct in vivo heterogeneity in killer cell lectin-like receptor G1 （KLRG-1） expression, which was strongly associated with diverse MPEC and SLEC fates. These in vivo MPECs and SLECs expressed equivalent levels of cytotoxic molecules and effector cytokines. Using a unique in vivodegranulation assay, we found that the MPECs and SLECs similarly encountered infected target cells and elaborated equivalent levels of cytotoxicity in vivo. These data provide direct in vivoevidence that memory-fated ceils pass through a robust effector phase. Additionally, the preferential localization of the MPECs in the lymph nodes, where a lesser degree of cytotoxicity was elaborated, suggests that the MPECs may be protected from excessive stimulation and terminal differentiation by virtue of their differential tissue localization. These data provide novel mechanistic insights into the linear decreasing potential model of memory differentiation.

Pharmacological intervention of HIV-1 maturation

Despite significant advances in antiretroviral therapy,increasing drug resistance and toxicities observed among many of the current approved human immunodeficiency virus(HIV) drugs indicate a need for discovery and development of potent and safe antivirals with a novel mechanism of action.Maturation inhibitors(MIs) represent one such new class of HIV therapies.MIs inhibit a late step in the HIV-1 Gag processing cascade,causing defective core condensation and the release of non-infectious virus particles from infected cells,thus blocking the spread of the infection to new cells.Clinical proof-ofconcept for the MIs was established with betulinic acid derived bevirimat,the prototype HIV-1 MI.Despite the discontinuation of its further clinical development in 2010 due to a lack of uniform patient response caused by naturally occurring drug resistance Gag polymorphisms,several second-generation MIs with improved activity against viruses exhibiting Gag polymorphism mediated resistance have been recently discovered and are under clinical evaluation in HIV/AID patients.In this review,current understanding of HIV-1 MIs is described and recent progress made toward elucidating the mechanism of action,target identification and development of second-generation MIs is reviewed.