Epigenetic state and gene expression remain stable after CRISPR/Cas-mediated chromosomal inversions.

The epigenetic state of chromatin, gene activity and chromosomal positions are interrelated in plants. In Arabidopsis thaliana, chromosome arms are DNA-hypomethylated and enriched with the euchromatin-specific histone mark H3K4me3, while pericentromeric regions are DNA-hypermethylated and enriched with the heterochromatin-specific mark H3K9me2. We aimed to investigate how the chromosomal location affects epigenetic stability and gene expression by chromosome engineering.

Inferring structure of cortical neuronal networks from activity data: A statistical physics approach.

Understanding the relation between cortical neuronal network structure and neuronal activity is a fundamental unresolved question in neuroscience, with implications to our understanding of the mechanism by which neuronal networks evolve over time, spontaneously or under stimulation. It requires a method for inferring the structure and composition of a network from neuronal activities. Tracking the evolution of networks and their changing functionality will provide invaluable insight into the occurrence of plasticity and the underlying learning process.

Functional monocentricity with holocentric characteristics and chromosome-specific centromeres in a stick insect.

Centromeres are essential for chromosome segregation in eukaryotes, yet their specification is unexpectedly diverse among species and can involve major transitions such as those from localized to chromosome-wide centromeres between monocentric and holocentric species. How this diversity evolves remains elusive. We discovered within-cell variation in the recruitment of the major centromere protein CenH3, reminiscent of variation typically observed among species.

The genetic mechanism of B chromosome drive in rye illuminated by chromosome-scale assembly.

The genomes of many plants, animals, and fungi frequently comprise dispensable B chromosomes that rely upon various chromosomal drive mechanisms to counteract the tendency of non-essential genetic elements to be purged over time. The B chromosome of rye - a model system for nearly a century - undergoes targeted nondisjunction during first pollen mitosis, favouring segregation into the generative nucleus, thus increasing their numbers over generations. However, the genetic mechanisms underlying this process are poorly understood.

Repeat-based holocentromeres of the woodrush Luzula sylvatica reveal insights into the evolutionary transition to holocentricity.

In most studied eukaryotes, chromosomes are monocentric, with centromere activity confined to a single region. However, the rush family (Juncaceae) includes species with both monocentric (Juncus) and holocentric (Luzula) chromosomes, where centromere activity is distributed along the entire chromosome length. Here, we combine chromosome-scale genome assembly, epigenetic analysis, immuno-FISH and super-resolution microscopy to study the transition to holocentricity in Luzula sylvatica.

Fructose restriction has beneficial effects on adipose tissue distribution but not on serum adipokine levels: Post-hoc analysis of a double-blind randomized controlled trial.

We aimed to examine the effects of isocaloric fructose restriction on adipose tissue distribution and serum adipokines. Individuals with BMI >28 kg/m (n = 44) followed a 6-week fructose-restricted diet and were randomly allocated to (double-blind) oral supplementation with fructose (control) or glucose (intervention) powder three times daily. Visceral (VAT) and subcutaneous (SAT) adipose tissue was quantified with MRI.

Multidimensional Rietveld refinement of high-pressure neutron diffraction data of PbNCN.

High-pressure neutron powder diffraction data from PbNCN were collected on the high-pressure diffraction beamline SNAP located at the Spallation Neutron Source (SNS) of Oak Ridge National Laboratory (Tennessee, USA). The diffraction data were analyzed using the novel method of multidimensional (two dimensions for now, potentially more in the future) Rietveld refinement and, for comparison, employing the conventional Rietveld method. To achieve two-dimensional analysis, a detailed description of the SNAP instrument characteristics was created, serving as an instrument parameter file, and then yielding both cell and spatial parameters as refined under pressure for the first time for solid-state cyanamides/carbodi-imides.

Distinct patterns of satDNA distribution in holocentric chromosomes of spike-sedges (, Cyperaceae).

R. Br. (Cyperaceae) species are known for having holocentric chromosomes, which enable rapid karyotype differentiation.

Different Measures of Hyperglycemia Are Negatively Associated With Skin Microvascular Flowmotion: The Maastricht Study.

Objective: Diabetes can lead to microvascular complications such as diabetic neuropathy, nephropathy, and retinopathy. Hyperglycemia may initiate microvascular function impairment early in the course of diabetes, even prior to its clinical establishment during the pre-diabetes stage. Microvascular vasomotion, that is, the rhythmic arteriolar constriction and dilation, is an important function that regulates oxygen and nutrient delivery within the tissue and regulates peripheral resistance.

The potential of ALFA-tag and tyramide-based fluorescence signal amplification to expand the CRISPR-based DNA imaging toolkit.

Understanding the spatial organization of genomes within chromatin is crucial for deciphering gene regulation. A recently developed CRISPR-dCas9-based genome labeling tool, known as CRISPR-FISH, allows efficient labeling of repetitive sequences. Unlike standard fluorescence in situ hybridization (FISH), CRISPR-FISH eliminates the need for global DNA denaturation, allowing for superior preservation of chromatin structure.

Unravelling the unusual: chromosome elimination, nondisjunction and extra pollen mitosis characterize the B chromosome in wild sorghum.

The B chromosomes exhibit diverse behaviour compared with conventional genetic models. The capacity of the B chromosome either to accumulate or to be eliminated in a tissue-specific manner is dependent on biological processes related to aberrant cell division(s), but here yet remains compatible with normal development. We studied B chromosome elimination in Sorghum purpureosericeum embryos through cryo-sections and demonstrated the B chromosome instability during plant growth using flow cytometry, molecular markers and fluorescent in situ hybridization techniques.

Centromere sequence-independent but biased loading of subgenome-specific CENH3 variants in allopolyploid Arabidopsis suecica.

Centromeric nucleosomes are determined by the replacement of the canonical histone H3 with the centromere-specific histone H3 (CENH3) variant. Little is known about the centromere organization in allopolyploid species where different subgenome-specific CENH3s and subgenome-specific centromeric sequences coexist. Here, we analyzed the transcription and centromeric localization of subgenome-specific CENH3 variants in the allopolyploid species Arabidopsis suecica.

Integrated information decomposition unveils major structural traits of in silico and in vitro neuronal networks.

The properties of complex networked systems arise from the interplay between the dynamics of their elements and the underlying topology. Thus, to understand their behavior, it is crucial to convene as much information as possible about their topological organization. However, in large systems, such as neuronal networks, the reconstruction of such topology is usually carried out from the information encoded in the dynamics on the network, such as spike train time series, and by measuring the transfer entropy between system elements.

Preclinical efficacy and pharmacokinetics of an RNA-encoded T cell-engaging bispecific antibody targeting human claudin 6.

We present the preclinical pharmacology of BNT142, a lipid nanoparticle (LNP)-formulated RNA (RNA-LNP) encoding a T cell-engaging bispecific antibody that monovalently binds the T cell marker CD3 and bivalently binds claudin 6 (CLDN6), an oncofetal antigen that is absent from normal adult tissue but expressed on various solid tumors. Upon BNT142 RNA-LNP delivery in cell culture, mice, and cynomolgus monkeys, RNA is translated, followed by self-assembly into and secretion of the functional bispecific antibody RiboMab02.1.

Associations of between- and within-day patterns of physical activity accumulation with arterial stiffness and indices of microvascular health-Evidence from The Maastricht study.

While physical activity (PA) is understood to promote vascular health, little is known about whether the daily and weekly patterns of PA accumulation associate with vascular health. Accelerometer-derived (activPAL3) 6- or 7-day stepping was analyzed for 6430 participants in The Maastricht Study (50.4% women; 22.

Major chromosome rearrangements in intergeneric wheat × rye hybrids in compatible and incompatible crosses detected by GBS read coverage analysis.

The presence of incompatibility alleles in primary amphidiploids constitutes a reproductive barrier in newly synthesized wheat-rye hybrids. To overcome this barrier, the genome stabilization process includes large-scale chromosome rearrangements. In incompatible crosses resulting in fertile amphidiploids, the elimination of one of the incompatible alleles Eml-A1 or Eml-R1b can occur already in the somatic tissue of the wheat × rye hybrid embryo.

The holocentricity in the dioecious nutmeg (Myristica fragrans) is not based on major satellite repeats.

Holocentric species are characterized by the presence of centromeres throughout the length of the chromosomes. We confirmed the holocentricity of the dioecious, small chromosome-size species Myristica fragrans based on the chromosome-wide distribution of the centromere-specific protein KNL1, α-tubulin fibers, and the cell cycle-dependent histone H3 serine 28 phosphorylation (H3S28ph) mark. Each holocentromere is likely composed of, on average, ten centromere units, but none of the identified and in situ hybridized high-copy satellite repeats is centromere-specific.

Centromere diversity: How different repeat-based holocentromeres may have evolved.

In addition to monocentric eukaryotes, which have a single localized centromere on each chromosome, there are holocentric species, with extended repeat-based or repeat-less centromeres distributed over the entire chromosome length. At least two types of repeat-based holocentromeres exist, one composed of many small repeat-based centromere units (small unit-type), and another one characterized by a few large centromere units (large unit-type). We hypothesize that the transposable element-mediated dispersal of hundreds of short satellite arrays formed the small centromere unit-type holocentromere in Rhynchospora pubera.

Retinal microvascular function and incidence and trajectories of clinically relevant depressive symptoms: the Maastricht Study.

Background: Cerebral microvascular dysfunction may contribute to depression via disruption of brain structures involved in mood regulation, but evidence is limited. We investigated the association of retinal microvascular function, a proxy for microvascular function in the brain, with incidence and trajectories of clinically relevant depressive symptoms.

Methods: Longitudinal data are from The Maastricht Study of 5952 participants (59.

How diverse a monocentric chromosome can be? Repeatome and centromeric organization of Juncus effusus (Juncaceae).

Juncus is the largest genus of Juncaceae and was considered holocentric for a long time. Recent findings, however, indicated that 11 species from different clades of the genus have monocentric chromosomes. Thus, the Juncus centromere organization and evolution need to be reassessed.

Microvascular Dysfunction and Whole-Brain White Matter Connectivity: The Maastricht Study.

Background: Microvascular dysfunction is involved in the development of various cerebral disorders. It may contribute to these disorders by disrupting white matter tracts and altering brain connectivity, but evidence is scarce. We investigated the association between multiple biomarkers of microvascular function and whole-brain white matter connectivity.

Preoperative continuation of aspirin before isolated heart valve surgery and postoperative bleeding and transfusion: a single-center retrospective study.

Background: The risks and benefits of preoperative aspirin continuation in patients undergoing isolated heart valve replacement surgery are unclear. We investigated the effect of aspirin continuation on the risk of bleeding and transfusion in these patients.

Methods: In this single center, retrospective study, among 474 adult patients who underwent isolated heart valve surgery between April 2013 and June 2018, 269 continued aspirin within 5 days before surgery (aspirin group) and 205 patients did not take or stopped aspirin no later than 5 days before surgery (non-aspirin group).

Epigenetic histone H3 phosphorylation marks discriminate between univalent- and bivalent-forming chromosomes during canina asymmetrical meiosis.

Background And Aims: Dogroses (Rosa sect. Caninae) are mostly pentaploid, bearing 2n = 5x = 35 chromosomes in somatic cells. They evolved a unique form of asymmetrical meiosis characterized by two types of chromosomes: (1) chromosomes forming bivalents and distributed in the normal sexual way; and (2) chromosomes occurring as univalents and transferred by a female gamete only.

Type II Muscle Fiber Capillarization Is an Important Determinant of Post-Exercise Microvascular Perfusion in Older Adults.

Introduction: Microvascular perfusion is essential for post-exercise skeletal muscle recovery to ensure adequate delivery of nutrients and growth factors. This study assessed the relationship between various indices of muscle fiber capillarization and microvascular perfusion assessed by contrast-enhanced ultrasound (CEUS) at rest and during recovery from a bout of resistance exercise in older adults.

Methods: Sixteen older adults (72 ± 6 y, 5/11 male/female) participated in an experimental test day during which a muscle biopsy was collected from the vastus lateralis and microvascular perfusion was determined by CEUS at rest and at 10 and 40 min following a bout of resistance exercise.