Nutrigenomics-guided lifestyle intervention programmes: A critical scoping review with directions for future research.

Genetic testing is increasingly used in clinical practice to provide personalized information and recommendations about health risks and lifestyle habits at a relatively low cost. Research on the effectiveness of nutrigenomics-guided lifestyle interventions is growing. A scoping review approach was adopted to identify pertinent published studies on nutrigenomics-guided intervention programmes from 2007 to 2023.

Objectives and achievements of the HUMN project on its 26th anniversary.

Micronuclei (MN) are a nuclear abnormality that occurs when chromosome fragments or whole chromosomes are not properly segregated during mitosis and consequently are excluded from the main nuclei and wrapped within nuclear membrane to form small nuclei. This maldistribution of genetic material leads to abnormal cellular genomes which may increase risk of developmental defects, cancers, and accelerated aging. Despite the potential importance of MN as biomarkers of genotoxicity, very little was known about the optimal way to measure MN in humans, the normal ranges of values of MN in healthy humans and the prospective association of MN with developmental and degenerative diseases prior to the 1980's.

MD-1 downregulation is associated with reduced cell surface CD180 expression in CLL.

CD180 is a toll-like receptor that is highly expressed in complex with the MD-1 satellite molecule on the surface of B cells. In chronic lymphocytic leukaemia (CLL) however, the expression of CD180 is highly variable and overall, significantly reduced when compared to normal B cells. We have recently shown that reduced CD180 expression in CLL lymph nodes is associated with inferior overall survival.

The role of CD180 in hematological malignancies and inflammatory disorders.

Toll-like receptors play a significant role in the innate immune system and are also involved in the pathophysiology of many different diseases. Over the past 35 years, there have been a growing number of publications exploring the role of the orphan toll-like receptor, CD180. We therefore set out to provide a narrative review of the current evidence surrounding CD180 in both health and disease.

A correlational analysis of COVID-19 incidence and mortality and urban determinants of vitamin D status across the London boroughs.

One of the biggest challenges of the COVID-19 pandemic is the heterogeneity in disease severity exhibited amongst patients. Among multiple factors, latest studies suggest vitamin D deficiency and pre-existing health conditions to be major contributors to death from COVID-19. It is known that certain urban form attributes can impact sun exposure and vitamin D synthesis.

Obesity, oxidative DNA damage and vitamin D as predictors of genomic instability in children and adolescents.

Background/objectives: Epidemiological evidence indicates obesity in childhood and adolescence to be an independent risk factor for cancer and premature mortality in adulthood. Pathological implications from excess adiposity may begin early in life. Obesity is concurrent with a state of chronic inflammation, a well-known aetiological factor for DNA damage.

Patient-specific Alzheimer-like pathology in trisomy 21 cerebral organoids reveals BACE2 as a gene dose-sensitive AD suppressor in human brain.

A population of more than six million people worldwide at high risk of Alzheimer's disease (AD) are those with Down Syndrome (DS, caused by trisomy 21 (T21)), 70% of whom develop dementia during lifetime, caused by an extra copy of β-amyloid-(Aβ)-precursor-protein gene. We report AD-like pathology in cerebral organoids grown in vitro from non-invasively sampled strands of hair from 71% of DS donors. The pathology consisted of extracellular diffuse and fibrillar Aβ deposits, hyperphosphorylated/pathologically conformed Tau, and premature neuronal loss.

DNA damage in obesity: Initiator, promoter and predictor of cancer.

Epidemiological evidence linking obesity with increased risk of cancer is steadily growing, although the causative aspects underpinning this association are only partially understood. Obesity leads to a physiological imbalance in the regulation of adipose tissue and its normal functioning, resulting in hyperglycaemia, dyslipidaemia and inflammation. These states promote the generation of oxidative stress, which is exacerbated in obesity by a decline in anti-oxidant defence systems.

In vivo modeling of human neuron dynamics and Down syndrome.

Harnessing the potential of human stem cells for modeling the physiology and diseases of cortical circuitry requires monitoring cellular dynamics in vivo. We show that human induced pluripotent stem cell (iPSC)-derived cortical neurons transplanted into the adult mouse cortex consistently organized into large (up to ~100 mm) vascularized neuron-glia territories with complex cytoarchitecture. Longitudinal imaging of >4000 grafted developing human neurons revealed that neuronal arbors refined via branch-specific retraction; human synaptic networks substantially restructured over 4 months, with balanced rates of synapse formation and elimination; and oscillatory population activity mirrored the patterns of fetal neural networks.

Corrigendum: Whole genome analysis of a schistosomiasis-transmitting freshwater snail.

This corrects the article DOI: 10.1038/ncomms15451.

Whole genome analysis of a schistosomiasis-transmitting freshwater snail.

Biomphalaria snails are instrumental in transmission of the human blood fluke Schistosoma mansoni. With the World Health Organization's goal to eliminate schistosomiasis as a global health problem by 2025, there is now renewed emphasis on snail control. Here, we characterize the genome of Biomphalaria glabrata, a lophotrochozoan protostome, and provide timely and important information on snail biology.

Language impairment in a case of a complex chromosomal rearrangement with a breakpoint downstream of FOXP2.

Background: We report on a young female, who presents with a severe speech and language disorder and a balanced de novo complex chromosomal rearrangement, likely to have resulted from a chromosome 7 pericentromeric inversion, followed by a chromosome 7 and 11 translocation.

Results: Using molecular cytogenetics, we mapped the four breakpoints to 7p21.1-15.

De novo and rare inherited mutations implicate the transcriptional coregulator TCF20/SPBP in autism spectrum disorder.

Background: Autism spectrum disorders (ASDs) are common and have a strong genetic basis, yet the cause of ∼70-80% ASDs remains unknown. By clinical cytogenetic testing, we identified a family in which two brothers had ASD, mild intellectual disability and a chromosome 22 pericentric inversion, not detected in either parent, indicating de novo mutation with parental germinal mosaicism. We hypothesised that the rearrangement was causative of their ASD and localised the chromosome 22 breakpoints.

Detailed phenotypic and genotypic characterization of bietti crystalline dystrophy.

Objective: To provide a detailed phenotype/genotype characterization of Bietti crystalline dystrophy (BCD).

Design: Observational case series.

Participants: Twenty patients from 17 families recruited from a multiethnic British population.

Integrated view of genome structure and sequence of a single DNA molecule in a nanofluidic device.

We show how a bird's-eye view of genomic structure can be obtained at ∼1-kb resolution from long (∼2 Mb) DNA molecules extracted from whole chromosomes in a nanofluidic laboratory-on-a-chip. We use an improved single-molecule denaturation mapping approach to detect repetitive elements and known as well as unique structural variation. Following its mapping, a molecule of interest was rescued from the chip; amplified and localized to a chromosome by FISH; and interrogated down to 1-bp resolution with a commercial sequencer, thereby reconciling haplotype-phased chromosome substructure with sequence.

Comprehensive cytogenomic profile of the in vitro neuronal model SH-SY5Y.

The widely studied SH-SY5Y human neuroblastoma cell line provides a classic example of how a cancer cell line can be instrumental for discoveries of broad biological and clinical significance. An important feature of the SH-SY5Y cells is their ability to differentiate into a functionally mature neuronal phenotype. This property has conferred them the potential to be used as an in vitro model for studies of neurodegenerative and neurodevelopmental disorders.

Structures of lysenin reveal a shared evolutionary origin for pore-forming proteins and its mode of sphingomyelin recognition.

Pore-forming proteins insert from solution into membranes to create lesions, undergoing a structural rearrangement often accompanied by oligomerization. Lysenin, a pore-forming toxin from the earthworm Eisenia fetida, specifically interacts with sphingomyelin (SM) and may confer innate immunity against parasites by attacking their membranes to form pores. SM has important roles in cell membranes and lysenin is a popular SM-labeling reagent.

Perforin activity at membranes leads to invaginations and vesicle formation.

The cytotoxic cell granule secretory pathway is essential for immune defence. How the pore-forming protein perforin (PFN) facilitates the cytosolic delivery of granule-associated proteases (granzymes) remains enigmatic. Here we show that PFN is able to induce invaginations and formation of complete internal vesicles in giant unilamellar vesicles.

Combining M-FISH and Quantum Dot technology for fast chromosomal assignment of transgenic insertions.

Background: Physical mapping of transgenic insertions by Fluorescence in situ Hybridization (FISH) is a reliable and cost-effective technique. Chromosomal assignment is commonly achieved either by concurrent G-banding or by a multi-color FISH approach consisting of iteratively co-hybridizing the transgenic sequence of interest with one or more chromosome-specific probes at a time, until the location of the transgenic insertion is identified.

Results: Here we report a technical development for fast chromosomal assignment of transgenic insertions at the single cell level in mouse and rat models.

Characterization of a dominant cone degeneration in a green fluorescent protein-reporter mouse with disruption of Loci associated with human dominant retinal dystrophy.

PURPOSE. To characterize anatomically and functionally the retinal degeneration observed in a transgenic mouse line (OPN1LW-EGFP) expressing enhanced green fluorescent protein (EGFP) in a subpopulation of cone photoreceptors, and to map the location of the transgenic insertion. METHODS.

Functional human artificial chromosomes are generated and stably maintained in human embryonic stem cells.

We present a novel and efficient non-integrating gene expression system in human embryonic stem cells (hESc) utilizing human artificial chromosomes (HAC), which behave as autonomous endogenous host chromosomes and segregate correctly during cell division. HAC are important vectors for investigating the organization and structure of the kinetochore, and gene complementation. HAC have so far been obtained in immortalized or tumour-derived cell lines, but never in stem cells, thus limiting their potential therapeutic application.