Enhanced detection and genotyping of disease-associated tandem repeats using HMMSTR and targeted long-read sequencing.

Tandem repeat sequences comprise approximately 8% of the human genome and are linked to more than 50 neurodegenerative disorders. Accurate characterization of disease-associated repeat loci remains resource intensive and often lacks high resolution genotype calls. We introduce a multiplexed, targeted nanopore sequencing panel and HMMSTR, a sequence-based tandem repeat copy number caller which outperforms current signal- and sequence-based callers relative to two assemblies and we show it performs with high accuracy in heterozygous regions and at low read coverage.

A longitudinal single-cell atlas of anti-tumour necrosis factor treatment in inflammatory bowel disease.

Precision medicine in immune-mediated inflammatory diseases (IMIDs) requires a cellular understanding of treatment response. We describe a therapeutic atlas for Crohn's disease (CD) and ulcerative colitis (UC) following adalimumab, an anti-tumour necrosis factor (anti-TNF) treatment. We generated ~1 million single-cell transcriptomes, organised into 109 cell states, from 216 gut biopsies (41 subjects), revealing disease-specific differences.

Shared fate was associated with sustained cooperation during the COVID-19 pandemic.

Did the COVID-19 pandemic bring people together or push them apart? While infectious diseases tend to push people apart, crises can also bring people together through positive interdependence. We studied this question by asking an international sample (N = 1,006) about their inclinations to cooperate, perceptions of interdependence (i.e.

Singapore's urbanised coral reefs: Changes in heavy metal pollution between 1994 and 2021.

The heavy metal load in coral reefs of Singapore has not been comprehensively assessed since 1994. Here, we repeated the surveys conducted 27 years ago to quantify the levels of Cd, Cu, Cr, Fe, Pb, Ti, Zn in sediment and the sea urchin Diadema setosum from seven reefs. Cu and Cd showed significant reductions, Pb and Cr remained stable, while Fe, Ti and Zn had increased significantly.

AAGGG repeat expansions trigger -independent synaptic dysregulation in human CANVAS neurons.

Cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) is a recessively inherited neurodegenerative disorder caused by intronic biallelic, nonreference CCCTT/AAGGG repeat expansions within . To investigate how these repeats cause disease, we generated patient induced pluripotent stem cell-derived neurons (iNeurons). CCCTT/AAGGG repeat expansions do not alter neuronal splicing, expression, or DNA repair pathway function.

Stress granule formation helps to mitigate neurodegeneration.

Cellular stress pathways that inhibit translation initiation lead to transient formation of cytoplasmic RNA/protein complexes known as stress granules. Many of the proteins found within stress granules and the dynamics of stress granule formation and dissolution are implicated in neurodegenerative disease. Whether stress granule formation is protective or harmful in neurodegenerative conditions is not known.

Where should I search next? Messages embedded in storybooks influence children's strategic exploration in Turkey and the United States.

Despite the vital role of curiosity-driven exploration in learning, our understanding of how to enhance children's curiosity remains limited. Here, we tested whether hearing a strategic curiosity story with curiosity-promoting themes (e.g.

TDP43 autoregulation gives rise to shortened isoforms that are tightly controlled by both transcriptional and post-translational mechanisms.

The nuclear RNA-binding protein TDP43 is integrally involved in the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Previous studies uncovered N-terminal TDP43 isoforms that are predominantly cytosolic in localization, highly prone to aggregation, and enriched in susceptible spinal motor neurons. In healthy cells, however, these shortened (s)TDP43 isoforms are difficult to detect in comparison to full-length (fl)TDP43, raising questions regarding their origin and selective regulation.

Enhanced Detection and Genotyping of Disease-Associated Tandem Repeats Using HMMSTR and Targeted Long-Read Sequencing.

Tandem repeat sequences comprise approximately 8% of the human genome and are linked to more than 50 neurodegenerative disorders. Accurate characterization of disease-associated repeat loci remains resource intensive and often lacks high resolution genotype calls. We introduce a multiplexed, targeted nanopore sequencing panel and HMMSTR, a sequence-based tandem repeat copy number caller.

Relative predation intensity of an intertidal gastropod on artificial coastal defense structures.

Despite seawalls becoming ubiquitous coastal features, and having some physical similarities to natural rocky shores, it remains unclear how these urban habitats influence predator-prey interactions. Predators can affect intertidal mobile prey densities through two pathways: (1) successful predation directly influences prey mortality rates, and (2) direct and indirect effects of predation can scare and induce motile prey to seek safer areas. In this study, we investigated whether intertidal predators affect the density of the marine gastropod, , at four seawall sites in Singapore.

Genome-wide analysis to uncover how Pocillopora acuta survives the challenging intertidal environment.

Characterisation of genomic variation among corals can help uncover variants underlying trait differences and contribute towards genotype prioritisation in coastal restoration projects. For example, there is growing interest in identifying resilient genotypes for transplantation, and to better understand the genetic processes that allow some individuals to survive in specific conditions better than others. The coral species Pocillopora acuta is known to survive in a wide range of habitats, from reefs artificial coastal defences, suggesting its potential use as a starter species for ecological engineering efforts involving coral transplantation onto intertidal seawalls.

Trapping of microplastics and other anthropogenic particles in seagrass beds: Ubiquity across a vertical and horizontal sampling gradient.

Seagrass beds can trap large amounts of marine debris leading to areas of accumulation, known as 'sinks', of anthropogenic particles. While the presence of vegetation can enhance accumulation, less is known about how the trapping effect changes from vegetated to less vegetated patches. To test this, vegetation and sediment were sampled along a vegetation percent cover gradient from the centre of seagrass beds to nearby less vegetated patches.

Ribosomal quality control factors inhibit repeat-associated non-AUG translation from GC-rich repeats.

A GGGGCC (G4C2) hexanucleotide repeat expansion in C9ORF72 causes amyotrophic lateral sclerosis and frontotemporal dementia (C9ALS/FTD), while a CGG trinucleotide repeat expansion in FMR1 leads to the neurodegenerative disorder Fragile X-associated tremor/ataxia syndrome (FXTAS). These GC-rich repeats form RNA secondary structures that support repeat-associated non-AUG (RAN) translation of toxic proteins that contribute to disease pathogenesis. Here we assessed whether these same repeats might trigger stalling and interfere with translational elongation.

The effect of coral colony morphology, coral surface condition, particle size, and seeding point on the trapping and deposition of microplastics.

Coral reefs are increasingly identified as microplastic sinks. Understanding the trapping and deposition effects on microplastics among coral colonies of different morphologies can help identify which corals and coral reefs are at higher risk of microplastic exposure. Here, we used a current-generating saltwater flume to explore microplastic trapping and deposition among branching coral, Pocillopora acuta, colonies with contrasting morphologies (open and compact), together with varying coral surface conditions (live, dead, and waxed), microplastic sizes (400 to 500 μm and 900 to 1000 μm), and seeding points (above-colony and mid-colony).

AAGGG repeat expansions trigger RFC1-independent synaptic dysregulation in human CANVAS Neurons.

Cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) is a late onset, recessively inherited neurodegenerative disorder caused by biallelic, non-reference pentameric AAGGG(CCCTT) repeat expansions within the second intron of replication factor complex subunit 1 (). To investigate how these repeats cause disease, we generated CANVAS patient induced pluripotent stem cell (iPSC) derived neurons (iNeurons) and utilized calcium imaging and transcriptomic analysis to define repeat-elicited gain-of-function and loss-of-function contributions to neuronal toxicity. AAGGG repeat expansions do not alter neuronal RFC1 splicing, expression, or DNA repair pathway functions.

Stress granule formation helps to mitigate neurodegeneration.

Cellular stress pathways that inhibit translation initiation lead to transient formation of cytoplasmic RNA/protein complexes known as stress granules. Many of the proteins found within stress granules and the dynamics of stress granule formation and dissolution are implicated in neurodegenerative disease. Whether stress granule formation is protective or harmful in neurodegenerative conditions is not known.

Biocatalytic reductive amination as a route to isotopically labelled amino acids suitable for analysis of large proteins by NMR.

We demonstrate an atom-efficient and easy to use H-driven biocatalytic platform for the enantioselective incorporation of H-atoms into amino acids. By combining the biocatalytic deuteration catalyst with amino acid dehydrogenase enzymes capable of reductive amination, we synthesised a library of multiply isotopically labelled amino acids from low-cost isotopic precursors, such as HO and NH. The chosen approach avoids the use of pre-labeled H-reducing agents, and therefore vastly simplifies product cleanup.

Neural evidence of switch processes during semantic and phonetic foraging in human memory.

Humans may retrieve words from memory by exploring and exploiting in "semantic space" similar to how nonhuman animals forage for resources in physical space. This has been studied using the verbal fluency test (VFT), in which participants generate words belonging to a semantic or phonetic category in a limited time. People produce bursts of related items during VFT, referred to as "clustering" and "switching.

Chemically Mediated Interactions with Macroalgae Negatively Affect Coral Health but Induce Limited Changes in Coral Microbiomes.

Allelopathic chemicals facilitated by the direct contact of macroalgae with corals are potentially an important mechanism mediating coral-macroalgal interactions, but only a few studies have explored their impacts on coral health and microbiomes and the coral's ability to recover. We conducted a field experiment on an equatorial urbanized reef to assess the allelopathic effects of four macroalgal species ( sp., , and ) on the health and microbiomes of three coral species (, and ).

Insight and Recommendations for Fragile X-Premutation-Associated Conditions from the Fifth International Conference on Premutation.

The premutation of the fragile X messenger ribonucleoprotein 1 () gene is characterized by an expansion of the CGG trinucleotide repeats (55 to 200 CGGs) in the 5' untranslated region and increased levels of mRNA. Molecular mechanisms leading to fragile X-premutation-associated conditions (FXPAC) include cotranscriptional R-loop formations, mRNA toxicity through both RNA gelation into nuclear foci and sequestration of various CGG-repeat-binding proteins, and the repeat-associated non-AUG (RAN)-initiated translation of potentially toxic proteins. Such molecular mechanisms contribute to subsequent consequences, including mitochondrial dysfunction and neuronal death.

The comparative effects of chronic microplastic and sediment deposition on the scleractinian coral Merulina ampliata.

Despite increasing research into the effects of microplastics on corals, no study to date has compared this relatively novel pollutant with a well-established stressor such as downwelling sediments. Here, Merulina ampliata coral fragments were exposed to polyethylene terephthalate (PET) and calcium carbonate particles (200-300 μm) at two deposition levels, high (115.20 ± 5.

Descriptive norms caused increases in mask wearing during the COVID-19 pandemic.

Human sociality is governed by two types of social norms: injunctive norms, which prescribe what people ought to do, and descriptive norms, which reflect what people actually do. The process by which these norms emerge and their causal influences on cooperative behavior over time are not well understood. Here, we study these questions through social norms influencing mask wearing during the COVID-19 pandemic.