Acute Myeloid Leukaemia and Acute Lymphoblastic Leukaemia Classification and Metabolic Characteristics for Informing and Advancing Treatment.

Acute myeloid leukaemia (AML) and acute lymphoblastic leukaemia (ALL) remain significant challenges in haematological oncology. This review examines the pathophysiology, classification, and risk stratification of these aggressive malignancies, emphasising their impact on treatment strategies and prognosis. We discuss current standard-of-care treatments, including chemotherapy regimens and targeted therapies, while addressing the associated adverse effects and hypersensitivity reactions.

Draft genome sequence of a non-human primate-derived isolate of .

is a common human commensal and opportunistic fungal pathogen that is also found in non-human primates (NHPs). Here, we report the first draft sequence of NCYC 4418, a fecal isolate from an adult cynomolgus macaque.

An multi-organ microphysiological system (MPS) to investigate the gut-to-brain translocation of neurotoxins.

The death of dopamine-producing neurons in the substantia nigra in the base of the brain is a defining pathological feature in the development of Parkinson's disease (PD). PD is, however, a multi-systemic disease, also affecting the peripheral nervous system and gastrointestinal tract (GIT) that interact via the gut-brain axis (GBA). Our dual-flow GIT-brain microphysiological system (MPS) was modified to investigate the gut-to-brain translocation of the neurotoxin trigger of PD, 1-methyl-4-phenylpyridinium (MPP), and its impact on key GIT and brain cells that contribute to the GBA.

Assessing In Vivo Bacterial Extracellular Vesicle (BEV) Biodistribution Using Fluorescent Lipophilic Membrane Stains.

Bacterial extracellular vesicles (BEVs) are nano-size vesicles containing a cargo of bioactive molecules that can play key roles in microbe-microbe and microbe-host interactions. In tracking their biodistribution in vivo, BEVs can cross several physical host barriers including the intestinal epithelium, vascular endothelium, and blood-brain-barrier (BBB) to ultimately accumulate in tissues such as the liver, lungs, spleen, and the brain. This tissue-specific dissemination has been exploited for the delivery of biomolecules such as vaccines for mucosal delivery.

The use of a multicellular model to investigate uptake and migration of bacterial extracellular vesicles derived from the human gut commensal .

Bacterial extracellular vesicles (BEVs) are increasingly seen as key signalling mediators between the gut microbiota and the host. Recent studies have provided evidence of BEVs ability to transmigrate across cellular barriers to elicit responses in other tissues, such as the central nervous system (CNS). Here we use a combination of single-, two- and three-cell culture systems to demonstrate the transmigration of derived BEVs (Bt-BEVs) across gut epithelium and blood brain barrier (BBB) endothelium, and their subsequent acquisition and downstream effects in neuronal cells.

Assessing Functional Capacity in Myalgic Encephalopathy/Chronic Fatigue Syndrome: A Patient-Informed Questionnaire.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is an acquired disease with significant morbidity that affects both children and adults. Post-exertional malaise is a cardinal symptom of ME/CFS and impacts a patient's functional capacity (FC). The absence of effective tools to assess FC has significant consequences for timely diagnosis, clinical follow-up, assessments for patient disability benefits, and research studies.

Nanopore and Illumina sequencing reveal different viral populations from human gut samples.

The advent of viral metagenomics, or viromics, has improved our knowledge and understanding of global viral diversity. High-throughput sequencing technologies enable explorations of the ecological roles, contributions to host metabolism, and the influence of viruses in various environments, including the human intestinal microbiome. However, bacterial metagenomic studies frequently have the advantage.

Differential temporal release and lipoprotein loading in B. thetaiotaomicron bacterial extracellular vesicles.

Bacterial extracellular vesicles (BEVs) contribute to stress responses, quorum sensing, biofilm formation and interspecies and interkingdom communication. However, the factors that regulate their release and heterogeneity are not well understood. We set out to investigate these factors in the common gut commensal Bacteroides thetaiotaomicron by studying BEV release throughout their growth cycle.

Corrigendum: Extracellular vesicles produced by the human gut commensal bacterium elicit anti-inflammatory responses from innate immune cells.

[This corrects the article DOI: 10.3389/fmicb.2022.

Investigating the Human Intestinal DNA Virome and Predicting Disease-Associated Virus-Host Interactions in Severe Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

Understanding how the human virome, and which of its constituents, contributes to health or disease states is reliant on obtaining comprehensive virome profiles. By combining DNA viromes from isolated virus-like particles (VLPs) and whole metagenomes from the same faecal sample of a small cohort of healthy individuals and patients with severe myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), we have obtained a more inclusive profile of the human intestinal DNA virome. Key features are the identification of a core virome comprising tailed phages of the class , and a greater diversity of DNA viruses including extracellular phages and integrated prophages.

Investigating Antibody Reactivity to the Intestinal Microbiome in Severe Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A Feasibility Study.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multisystemic disease of unknown aetiology that is characterised by disabling chronic fatigue and involves both the immune and gastrointestinal (GI) systems. Patients display alterations in GI microbiome with a significant proportion experiencing GI discomfort and pain and elevated blood biomarkers for altered intestinal permeability compared with healthy individuals. To investigate a possible GI origin of ME/CFS we designed a feasibility study to test the hypothesis that ME/CFS pathogenesis is a consequence of increased intestinal permeability that results in microbial translocation and a breakdown in immune tolerance leading to generation of antibodies reactive to indigenous intestinal microbes.

Development of a dual-flow tissue perfusion device for modeling the gastrointestinal tract-brain axis.

Despite the large number of microfluidic devices that have been described over the past decade for the study of tissues and organs, few have become widely adopted. There are many reasons for this lack of adoption, primarily that devices are constructed for a single purpose or because they are highly complex and require relatively expensive investment in facilities and training. Here, we describe a microphysiological system (MPS) that is simple to use and provides fluid channels above and below cells, or tissue biopsies, maintained on a disposable, poly(methyl methacrylate), carrier held between polycarbonate outer plates.

Draft Genome Sequence of a Primate Isolate of Kazachstania pintolopesii.

Kazachstania pintolopesii is an opportunistic mammalian pathobiont from the K. telluris species complex. No draft genomes of this species are currently available.

A Possible Aquatic Origin of the Thiaminase TenA of the Human Gut Symbiont Bacteroides thetaiotaomicron.

TenA thiamin-degrading enzymes are commonly found in prokaryotes, plants, fungi and algae and are involved in the thiamin salvage pathway. The gut symbiont Bacteroides thetaiotaomicron (Bt) produces a TenA protein (BtTenA) which is packaged into its extracellular vesicles. An alignment of BtTenA protein sequence with proteins from different databases using the basic local alignment search tool (BLAST) and the generation of a phylogenetic tree revealed that BtTenA is related to TenA-like proteins not only found in a small number of intestinal bacterial species but also in some aquatic bacteria, aquatic invertebrates, and freshwater fish.

Draft Genome Sequence of a Preterm Infant-Derived Isolate of Candida parapsilosis.

Candida parapsilosis is a human fungal pathogen of increasing incidence and causes invasive candidiasis, notably in preterm or low-birthweight neonates. Here, we present the genome sequence of C. parapsilosis NCYC 4289, a fecal isolate from a preterm male infant.

Extracellular vesicles produced by the human gut commensal bacterium elicit anti-inflammatory responses from innate immune cells.

Bacterial extracellular vesicles (BEVs) produced by gut commensal bacteria have been proposed to play an important role in maintaining host homeostasis interactions with the immune system. Details of the mediators and pathways of BEV-immune cell interactions are however incomplete. In this study, we provide evidence for the anti-inflammatory and immunomodulatory properties of extracellular vesicles produced by the prominent human gut commensal bacterium (Bt BEVs) and identify the molecular mechanisms underlying their interaction with innate immune cells.

A protocol paper for the MOTION Study-A longitudinal study in a cohort aged 60 years and older to obtain mechanistic knowledge of the role of the gut microbiome during normal healthy ageing in order to develop strategies that will improve lifelong health and wellbeing.

Background: Advances in medicine and public health mean that people are living longer; however, a significant proportion of that increased lifespan is spent in a prolonged state of declining health and wellbeing which places increasing pressure on medical, health and social services. There is a social and economic need to develop strategies to prevent or delay age-related disease and maintain lifelong health. Several studies have suggested links between the gut microbiome and age-related disease, which if confirmed would present a modifiable target for intervention development.

The Cynomolgus Macaque Intestinal Mycobiome Is Dominated by the Genus and Species.

The cynomolgus macaque, , is a non-human primate (NHP) widely used in biomedical research as its genetics, immunology and physiology are similar to those of humans. They may also be a useful model of the intestinal microbiome as their prokaryome resembles that of humans. However, beyond the prokaryome relatively little is known about other constituents of the macaque intestinal microbiome including the mycobiome.

Nutrient smuggling: Commensal gut bacteria-derived extracellular vesicles scavenge vitamin B12 and related cobamides for microbe and host acquisition.

The processes by which bacteria proactively scavenge essential nutrients in crowded environments such as the gastrointestinal tract are not fully understood. In this context, we observed that bacterial extracellular vesicles (BEVs) produced by the human commensal gut microbe contain multiple high-affinity vitamin B binding proteins suggesting that the vesicles play a role in micronutrient scavenging. Vitamin B belongs to the cobamide family of cofactors that regulate microbial communities through their limited bioavailability.

Outer Membrane Vesicles: Biogenesis, Functions, and Issues.

This review focuses on nonlytic outer membrane vesicles (OMVs), a subtype of bacterial extracellular vesicles (BEVs) produced by Gram-negative organisms focusing on the mechanisms of their biogenesis, cargo, and function. Throughout, we highlight issues concerning the characterization of OMVs and distinguishing them from other types of BEVs. We also highlight the shortcomings of commonly used methodologies for the study of BEVs that impact the interpretation of their functionality and suggest solutions to standardize protocols for OMV studies.

The early-life gut microbiome and vaccine efficacy.

Vaccines are one of the greatest successes of public health, preventing millions of cases of disease and death in children each year. However, the efficacy of many vaccines can vary greatly between infants from geographically and socioeconomically distinct locations. Differences in the composition of the intestinal microbiome have emerged as one of the main factors that can account for variations in immunisation outcomes.

Absence of Bacteria Permits Fungal Gut-To-Brain Translocation and Invasion in Germfree Mice but Ageing Alone Does Not Drive Pathobiont Expansion in Conventionally Raised Mice.

Age-associated changes in the structure of the intestinal microbiome and in its interaction with the brain via the gut-brain axis are increasingly being implicated in neurological and neurodegenerative diseases. Intestinal microbial dysbiosis and translocation of microbes and microbial products including fungal species into the brain have been implicated in the development of dementias such as Alzheimer's disease. Using germ-free mice, we investigated if the fungal gut commensal, , an opportunistic pathogen in humans, can traverse the gastrointestinal barrier and disseminate to brain tissue and whether ageing impacts on the gut mycobiome as a pre-disposing factor in fungal brain infection.

The Proteome of Extracellular Vesicles Produced by the Human Gut Bacteria Bacteroides thetaiotaomicron Is Influenced by Environmental and Host-Derived Factors.

Bacterial extracellular vesicles (BEVs) released from both Gram-negative and Gram-positive bacteria provide an effective means of communication and trafficking of cell signaling molecules. In the gastrointestinal tract (GIT) BEVs produced by members of the intestinal microbiota can impact host health by mediating microbe-host cell interactions. A major unresolved question, however, is what factors influence the composition of BEV proteins and whether the host influences protein packaging into BEVs and secretion into the GIT.

Fecal microbiota transfer between young and aged mice reverses hallmarks of the aging gut, eye, and brain.

Background: Altered intestinal microbiota composition in later life is associated with inflammaging, declining tissue function, and increased susceptibility to age-associated chronic diseases, including neurodegenerative dementias. Here, we tested the hypothesis that manipulating the intestinal microbiota influences the development of major comorbidities associated with aging and, in particular, inflammation affecting the brain and retina.

Methods: Using fecal microbiota transplantation, we exchanged the intestinal microbiota of young (3 months), old (18 months), and aged (24 months) mice.

A systems genomics approach to uncover patient-specific pathogenic pathways and proteins in ulcerative colitis.

We describe a precision medicine workflow, the integrated single nucleotide polymorphism network platform (iSNP), designed to determine the mechanisms by which SNPs affect cellular regulatory networks, and how SNP co-occurrences contribute to disease pathogenesis in ulcerative colitis (UC). Using SNP profiles of 378 UC patients we map the regulatory effects of the SNPs to a human signalling network containing protein-protein, miRNA-mRNA and transcription factor binding interactions. With unsupervised clustering algorithms we group these patient-specific networks into four distinct clusters driven by PRKCB, HLA, SNAI1/CEBPB/PTPN1 and VEGFA/XPO5/POLH hubs.