Single-character insertion-deletion model preserves long indels in ancestral sequence reconstruction.

Insertions and deletions (indels) play a significant role in genome evolution across species. Realistic modelling of indel evolution is challenging and is still an open research question. Several attempts have been made to explicitly model multi-character (long) indels, such as TKF92, by relaxing the site independence assumption and introducing fragments.

Insertions and Deletions: Computational Methods, Evolutionary Dynamics, and Biological Applications.

Insertions and deletions constitute the second most important source of natural genomic variation. Insertions and deletions make up to 25% of genomic variants in humans and are involved in complex evolutionary processes including genomic rearrangements, adaptation, and speciation. Recent advances in long-read sequencing technologies allow detailed inference of insertions and deletion variation in species and populations.

d-Serine Inhibits Non-ionotropic NMDA Receptor Signaling.

NMDA-type glutamate receptors (NMDARs) are widely recognized as master regulators of synaptic plasticity, most notably for driving long-term changes in synapse size and strength that support learning. NMDARs are unique among neurotransmitter receptors in that they require binding of both neurotransmitter (glutamate) and co-agonist (e.g.

APP fragment controls both ionotropic and non-ionotropic signaling of NMDA receptors.

NMDA receptors (NMDARs) are ionotropic receptors crucial for brain information processing. Yet, evidence also supports an ion-flux-independent signaling mode mediating synaptic long-term depression (LTD) and spine shrinkage. Here, we identify AETA (Aη), an amyloid-β precursor protein (APP) cleavage product, as an NMDAR modulator with the unique dual regulatory capacity to impact both signaling modes.

D-Serine inhibits non-ionotropic NMDA receptor signaling.

Unlabelled: NMDA-type glutamate receptors (NMDARs) are widely recognized as master regulators of synaptic plasticity, most notably for driving long-term changes in synapse size and strength that support learning. NMDARs are unique among neurotransmitter receptors in that they require binding of both neurotransmitter (glutamate) and co-agonist (e.g.

Please Mind the Gap: Indel-Aware Parsimony for Fast and Accurate Ancestral Sequence Reconstruction and Multiple Sequence Alignment Including Long Indels.

Despite having important biological implications, insertion, and deletion (indel) events are often disregarded or mishandled during phylogenetic inference. In multiple sequence alignment, indels are represented as gaps and are estimated without considering the distinct evolutionary history of insertions and deletions. Consequently, indels are usually excluded from subsequent inference steps, such as ancestral sequence reconstruction and phylogenetic tree search.

Short tandem repeat mutations regulate gene expression in colorectal cancer.

Short tandem repeat (STR) mutations are prevalent in colorectal cancer (CRC), especially in tumours with the microsatellite instability (MSI) phenotype. While STR length variations are known to regulate gene expression under physiological conditions, the functional impact of STR mutations in CRC remains unclear. Here, we integrate STR mutation data with clinical information and gene expression data to study the gene regulatory effects of STR mutations in CRC.

Activity-Dependent Stabilization of Nascent Dendritic Spines Requires Nonenzymatic CaMKIIα Function.

The outgrowth and stabilization of nascent dendritic spines are crucial processes underlying learning and memory. Most new spines retract shortly after growth; only a small subset is stabilized and integrated into the new circuit connections that support learning. New spine stabilization has been shown to rely upon activity-dependent molecular mechanisms that also contribute to long-term potentiation (LTP) of synaptic strength.

WebSTR: A Population-wide Database of Short Tandem Repeat Variation in Humans.

Short tandem repeats (STRs) are consecutive repetitions of one to six nucleotide motifs. They are hypervariable due to the high prevalence of repeat unit insertions or deletions primarily caused by polymerase slippage during replication. Genetic variation at STRs has been shown to influence a range of traits in humans, including gene expression, cancer risk, and autism.

Body composition as an indicator of metabolic changes in mice obtained by in vitro fertilization.

To identify body systems subject to epigenetic transformation during in vitro fertilization (IVF), comparative morphological and functional studies were performed on sexually mature offspring of outbred CD1 mice, specific-pathogen-free (SPF), obtained by IVF (experiment) and natural conception (control). The studies included assessment of age-related changes in body weight and composition, energy intake and expenditure, and glucose homeostasis. To level the effects caused by the different number of newborns in the control and in the experiment, the size of the fed litters was halved in the control females.

A novel hypervariable variable number tandem repeat in the dopamine transporter gene ().

The dopamine transporter gene, , has received substantial attention in genetic association studies of various phenotypes. Although some variable number tandem repeats (VNTRs) present in have been tested in genetic association studies, results have not been consistent. VNTRs in that have not been examined genetically were characterized.

Computational Literature-based Discovery for Natural Products Research: Current State and Future Prospects.

Literature-based discovery (LBD) mines existing literature in order to generate new hypotheses by finding links between previously disconnected pieces of knowledge. Although automated LBD systems are becoming widespread and indispensable in a wide variety of knowledge domains, little has been done to introduce LBD to the field of natural products research. Despite growing knowledge in the natural product domain, most of the accumulated information is found in detached data pools.

Mother-Fetus Immune Cross-Talk Coordinates "Extrinsic"/"Intrinsic" Embryo Gene Expression Noise and Growth Stability.

Developmental instability (DI) is thought to be inversely related to a capacity of an organism to buffer its development against random genetic and environmental perturbations. DI is represented by a trait's inter- and intra-individual variabilities. The inter-individual variability (inversely referred to as canalization) indicates the capability of organisms to reproduce a trait from individual to individual.

Mutation and selection processes regulating short tandem repeats give rise to genetic and phenotypic diversity across species.

Short tandem repeats (STRs) are units of 1-6 bp that repeat in a tandem fashion in DNA. Along with single nucleotide polymorphisms and large structural variations, they are among the major genomic variants underlying genetic, and likely phenotypic, divergence. STRs experience mutation rates that are orders of magnitude higher than other well-studied genotypic variants.

Bio-SODA UX: enabling natural language question answering over knowledge graphs with user disambiguation.

The problem of natural language processing over structured data has become a growing research field, both within the relational database and the Semantic Web community, with significant efforts involved in question answering over knowledge graphs (KGQA). However, many of these approaches are either specifically targeted at question answering using DBpedia, or require to translate a natural language question to SPARQL in order to query the knowledge graph. Hence, these approaches often cannot be applied directly to complex where no prior training data is available.

ARPIP: Ancestral Sequence Reconstruction with Insertions and Deletions under the Poisson Indel Process.

Modern phylogenetic methods allow inference of ancestral molecular sequences given an alignment and phylogeny relating present-day sequences. This provides insight into the evolutionary history of molecules, helping to understand gene function and to study biological processes such as adaptation and convergent evolution across a variety of applications. Here, we propose a dynamic programming algorithm for fast joint likelihood-based reconstruction of ancestral sequences under the Poisson Indel Process (PIP).

Cross-reactive immunity potentially drives global oscillation and opposed alternation patterns of seasonal influenza A viruses.

Several human pathogens exhibit distinct patterns of seasonality and circulate as pairs. For instance, influenza A virus subtypes oscillate and peak during winter seasons of the world's temperate climate zones. Alternation of dominant strains in successive influenza seasons makes epidemic forecasting a major challenge.

Reduced d-serine levels drive enhanced non-ionotropic NMDA receptor signaling and destabilization of dendritic spines in a mouse model for studying schizophrenia.

Schizophrenia is a psychiatric disorder that affects over 20 million people globally. Notably, schizophrenia is associated with decreased density of dendritic spines and decreased levels of d-serine, a co-agonist required for opening of the N-methyl-d-aspartate receptor (NMDAR). We hypothesized that lowered d-serine levels associated with schizophrenia would enhance ion flux-independent signaling by the NMDAR, driving destabilization and loss of dendritic spines.

Spike-timing-dependent plasticity rewards synchrony rather than causality.

Spike-timing-dependent plasticity (STDP) is a candidate mechanism for information storage in the brain, but the whole-cell recordings required for the experimental induction of STDP are typically limited to 1 h. This mismatch of time scales is a long-standing weakness in synaptic theories of memory. Here we use spectrally separated optogenetic stimulation to fire precisely timed action potentials (spikes) in CA3 and CA1 pyramidal cells.

Induction of input-specific spine shrinkage on dendrites of rodent hippocampal CA1 neurons using two-photon glutamate uncaging.

Shrinkage and loss of dendritic spines are vital components of the neuronal plasticity that supports learning. To investigate the mechanisms of spine shrinkage and loss, Oh and colleagues established a two-photon glutamate uncaging protocol that reliably induces input-specific spine shrinkage on dendrites of rodent hippocampal CA1 pyramidal neurons. Here, we provide a detailed description of that protocol and also an optimized version that can be used to induce input- and synapse-specific shrinkage of dendritic spines at physiological Ca levels.

ProPIP: a tool for progressive multiple sequence alignment with Poisson Indel Process.

Background: Current alignment tools typically lack an explicit model of indel evolution, leading to artificially short inferred alignments (i.e., over-alignment) due to inconsistencies between the indel history and the phylogeny relating the input sequences.

The Effects of Sperm and Seminal Fluid of Immunized Male Mice on In Vitro Fertilization and Surrogate Mother-Embryo Interaction.

The latest vaccination campaign has actualized the potential impact of antigenic stimuli on reproductive functions. To address this, we mimicked vaccination's effects by administering keyhole limpet hemocyanin (KLH ) to CD1 male mice and used their sperm for in vitro fertilization (IVF). Two-cell embryos after IVF with spermatozoa from control (C) or KLH-treated (Im) male mice were transferred to surrogate mothers mated with vasectomized control (C) or KLH-treated (Im) male mice, resulting in four experimental groups: C-C, Im-C, C-Im, and Im-Im.

Image-based assessment of extracellular mucin-to-tumor area predicts consensus molecular subtypes (CMS) in colorectal cancer.

The backbone of all colorectal cancer classifications including the consensus molecular subtypes (CMS) highlights microsatellite instability (MSI) as a key molecular pathway. Although mucinous histology (generally defined as >50% extracellular mucin-to-tumor area) is a "typical" feature of MSI, it is not limited to this subgroup. Here, we investigate the association of CMS classification and mucin-to-tumor area quantified using a deep learning algorithm, and  the expression of specific mucins in predicting CMS groups and clinical outcome.

Content of circulating tumor DNA depends on the tumor type and the dynamics of tumor size, but is not influenced significantly by physical exercise, time of the day or recent meal.

Purpose: This study aimed to investigate factors, which influence the content of circulating tumor DNA (ctDNA).

Methods: 398 serial plasma samples were collected within 1-7 consecutive days from patients with EGFR-mutated lung cancer (n = 13), RAS/RAF-mutated colorectal cancer (n = 54) and BRAF-mutated melanoma (n = 17), who presented with measurable tumor disease. The amount of ctDNA was determined by ddPCR.