Transposable Element Populations Shed Light on the Evolutionary History of Wheat and the Complex Co-Evolution of Autonomous and Non-Autonomous Retrotransposons.

Wheat has one of the largest and most repetitive genomes among major crop plants, containing over 85% transposable elements (TEs). TEs populate genomes much in the way that individuals populate ecosystems, diversifying into different lineages, sub-families and sub-populations. The recent availability of high-quality, chromosome-scale genome sequences from ten wheat lines enables a detailed analysis how TEs evolved in allohexaploid wheat, its diploids progenitors, and in various chromosomal haplotype segments.

Novel Optics-Based Approaches for Cardiac Electrophysiology: A Review.

Optical techniques for recording and manipulating cellular electrophysiology have advanced rapidly in just a few decades. These developments allow for the analysis of cardiac cellular dynamics at multiple scales while largely overcoming the drawbacks associated with the use of electrodes. The recent advent of optogenetics opens up new possibilities for regional and tissue-level electrophysiological control and hold promise for future novel clinical applications.

European Expert Consensus on Practical Management of Specific Aspects of Parathyroid Disorders in Adults and in Pregnancy: Recommendations of the ESE Educational Program of Parathyroid Disorders.

This European expert consensus statement provides recommendations for the diagnosis and management of primary hyperparathyroidism (PHPT), chronic hypoparathyroidism in adults (HypoPT), and parathyroid disorders in relation to pregnancy and lactation. Specified areas of interest and unmet needs identified by experts at the second ESE Educational Program of Parathyroid Disorders (PARAT) in 2019, were discussed during two virtual workshops in 2021, and subsequently developed by working groups with interest in the specified areas. PHPT is a common endocrine disease.

Neuroligin-3 Regulates Excitatory Synaptic Transmission and EPSP-Spike Coupling in the Dentate Gyrus In Vivo.

Neuroligin-3 (Nlgn3), a neuronal adhesion protein implicated in autism spectrum disorder (ASD), is expressed at excitatory and inhibitory postsynapses and hence may regulate neuronal excitation/inhibition balance. To test this hypothesis, we recorded field excitatory postsynaptic potentials (fEPSPs) in the dentate gyrus of Nlgn3 knockout (KO) and wild-type mice. Synaptic transmission evoked by perforant path stimulation was reduced in KO mice, but coupling of the fEPSP to the population spike was increased, suggesting a compensatory change in granule cell excitability.

Combining schizophrenia and depression polygenic risk scores improves the genetic prediction of lithium response in bipolar disorder patients.

Lithium is the gold standard therapy for Bipolar Disorder (BD) but its effectiveness differs widely between individuals. The molecular mechanisms underlying treatment response heterogeneity are not well understood, and personalized treatment in BD remains elusive. Genetic analyses of the lithium treatment response phenotype may generate novel molecular insights into lithium's therapeutic mechanisms and lead to testable hypotheses to improve BD management and outcomes.

Protective mucosal immunity against SARS-CoV-2 after heterologous systemic prime-mucosal boost immunization.

Several effective SARS-CoV-2 vaccines are currently in use, but effective boosters are needed to maintain or increase immunity due to waning responses and the emergence of novel variants. Here we report that intranasal vaccinations with adenovirus 5 and 19a vectored vaccines following a systemic plasmid DNA or mRNA priming result in systemic and mucosal immunity in mice. In contrast to two intramuscular applications of an mRNA vaccine, intranasal boosts with adenoviral vectors induce high levels of mucosal IgA and lung-resident memory T cells (T); mucosal neutralization of virus variants of concern is also enhanced.

Linking cognition to ecology in wild sympatric mouse lemur species.

Cognitive abilities covary with both social and ecological factors across animal taxa. Ecological generalists have been attributed with enhanced cognitive abilities, but which specific ecological factors may have shaped the evolution of which specific cognitive abilities remains poorly known. To explore these links, we applied a cognitive test battery (two personality, ten cognitive tests; = 1104 tests) to wild individuals of two sympatric mouse lemur species ( = 120 = 34 ) varying in ecological adaptations but sharing key features of their social systems.

Efficacy and Safety of Vilobelimab (IFX-1), a Novel Monoclonal Anti-C5a Antibody, in Patients With Early Severe Sepsis or Septic Shock-A Randomized, Placebo-Controlled, Double-Blind, Multicenter, Phase IIa Trial (SCIENS Study).

Unlabelled: Anaphylatoxin C5a, a proinflammatory complement split product, plays a central role in mediating organ dysfunction.

Objectives: This phase II clinical trial was conducted to study safety, tolerability, pharmacokinetics, and pharmacodynamics of vilobelimab, a recombinant monoclonal antibody against C5a, in patients with severe sepsis or septic shock.

Design: Multicenter, randomized, and placebo-controlled study.

Potential Mechanisms of SGLT2 Inhibitors for the Treatment of Heart Failure With Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) is an unsolved and growing concern in cardiovascular medicine. While no treatment options that improve prognosis in HFpEF patients has been established so far, SGLT2 inhibitors (SGLT2i) are currently being investigated for the treatment of HFpEF patients. SGLT2i have already been shown to mitigate comorbidities associated with HFpEF such as type 2 diabetes and chronic renal disease, however, more recently there has been evidence that they may also directly improve diastolic function.

How challenging RADseq data turned out to favor coalescent-based species tree inference. A case study in Aichryson (Crassulaceae).

Analysing multiple genomic regions while incorporating detection and qualification of discordance among regions has become standard for understanding phylogenetic relationships. In plants, which usually have comparatively large genomes, this is feasible by the combination of reduced-representation library (RRL) methods and high-throughput sequencing enabling the cost effective acquisition of genomic data for thousands of loci from hundreds of samples. One popular RRL method is RADseq.

How collective reward structure impedes group decision making: An experimental study using the HoneyComb paradigm.

This study investigates if and under which conditions humans are able to identify and follow the most advantageous leader who will them provide with the most resources. In an iterated economic game with the aim of earning monetary reward, 150 participants were asked to repeatedly choose one out of four leaders. Unbeknownst to participants, the leaders were computer-controlled and programmed to yield different expected payout values that participants had to infer from repeated interaction over 30 rounds.

Detrimental proarrhythmogenic interaction of Ca/calmodulin-dependent protein kinase II and Na1.8 in heart failure.

An interplay between Ca/calmodulin-dependent protein kinase IIδc (CaMKIIδc) and late Na current (I) is known to induce arrhythmias in the failing heart. Here, we elucidate the role of the sodium channel isoform Na1.8 for CaMKIIδc-dependent proarrhythmia.

A Multi-Perspective Proximity View on the Dynamic Head Region of the Ribosomal 40S Subunit.

A comparison of overlapping proximity captures at the head region of the ribosomal 40S subunit () in from four adjacent perspectives, namely Asc1/RACK1, Rps2/uS5, Rps3/uS3, and Rps20/uS10, corroborates dynamic co-localization of proteins that control activity and fate of both ribosomes and mRNA. Co-locating factors that associate with the are involved in (i) (de)ubiquitination of ribosomal proteins (Hel2, Bre5-Ubp3), (ii) clamping of inactive ribosomal subunits (Stm1), (iii) mRNA surveillance and vesicular transport (Smy2, Syh1), (iv) degradation of mRNA (endo- and exonucleases Ypl199c and Xrn1, respectively), (v) autophagy (Psp2, Vps30, Ykt6), and (vi) kinase signaling (Ste20). Additionally, they must be harmonized with translation initiation factors (eIF3, cap-binding protein Cdc33, eIF2A) and mRNA-binding/ribosome-charging proteins (Scp160, Sro9).

Lactate is an energy substrate for rodent cortical neurons and enhances their firing activity.

Glucose is the mandatory fuel for the brain, yet the relative contribution of glucose and lactate for neuronal energy metabolism is unclear. We found that increased lactate, but not glucose concentration, enhances the spiking activity of neurons of the cerebral cortex. Enhanced spiking was dependent on ATP-sensitive potassium (K) channels formed with KCNJ11 and ABCC8 subunits, which we show are functionally expressed in most neocortical neuronal types.

CRM1 Promotes Capsid Disassembly and Nuclear Envelope Translocation of Adenovirus Independently of Its Export Function.

After receptor-mediated endocytosis and endosomal escape, adenoviral capsids can travel via microtubule organizing centers to the nuclear envelope. Upon capsid disassembly, viral genome import into nuclei of interphase cells then occurs through nuclear pore complexes, involving the nucleoporins Nup214 and Nup358. Import also requires the activity of the classic nuclear export receptor CRM1, as it is blocked by the selective inhibitor leptomycin B.

Stereophotogrammetric head shape assessment in neonates is feasible and can identify distinct differences between term-born and very preterm infants at term equivalent age.

The development of head shape and volume may reflect neurodevelopmental outcome and therefore is of paramount importance in neonatal care. Here, we compare head morphology in 25 very preterm infants with a birth weight of below 1500 g and / or a gestational age (GA) before 32 completed weeks to 25 term infants with a GA of 37-42 weeks at term equivalent age (TEA) and identify possible risk factors for non-synostotic head shape deformities. For three-dimensional head assessments, a portable stereophotogrammetric device was used.

Olfactory cues of large carnivores modify red deer behavior and browsing intensity.

This study examined the effect of perceived predation risk imposed by lynx and wolf on red deer foraging behavior under experimental conditions. We hypothesized that in response to large carnivore scent red deer would increase their vigilance, although reducing the frequency and duration of visits to foraging sites. Consequently, browsing intensity on tree saplings was expected to decrease, whereas a higher proportion of more preferred species was expected to be browsed to compensate for higher foraging costs.

Association of snR190 snoRNA chaperone with early pre-60S particles is regulated by the RNA helicase Dbp7 in yeast.

Synthesis of eukaryotic ribosomes involves the assembly and maturation of precursor particles (pre-ribosomal particles) containing ribosomal RNA (rRNA) precursors, ribosomal proteins (RPs) and a plethora of assembly factors (AFs). Formation of the earliest precursors of the 60S ribosomal subunit (pre-60S r-particle) is among the least understood stages of ribosome biogenesis. It involves the Npa1 complex, a protein module suggested to play a key role in the early structuring of the pre-rRNA.

Increasing the Gas Barrier Properties of Polyethylene Foils by Coating with Poly(methyl acrylate)-Grafted Montmorillonite Nanosheets.

Low-density polyethylene (LDPE) foils were coated with a thin film of polymer-grafted Montmorillonite (MMT) nanosheets, which form a barrier against gas diffusion due to their unique brick-and-mortar arrangement. The MMT nanosheets were grafted with poly(methyl acrylate) (PMA), a soft and flexible polymer. Already very thin films of this nanocomposite could reduce gas permeability significantly.

App-SpaM: phylogenetic placement of short reads without sequence alignment.

Motivation: Phylogenetic placement is the task of placing a query sequence of unknown taxonomic origin into a given phylogenetic tree of a set of reference sequences. A major field of application of such methods is, for example, the taxonomic identification of reads in metabarcoding or metagenomic studies. Several approaches to phylogenetic placement have been proposed in recent years.

A novel class of TMPRSS2 inhibitors potently block SARS-CoV-2 and MERS-CoV viral entry and protect human epithelial lung cells.

The host cell serine protease TMPRSS2 is an attractive therapeutic target for COVID-19 drug discovery. This protease activates the Spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and of other coronaviruses and is essential for viral spread in the lung. Utilizing rational structure-based drug design (SBDD) coupled to substrate specificity screening of TMPRSS2, we have discovered covalent small-molecule ketobenzothiazole (kbt) TMPRSS2 inhibitors which are structurally distinct from and have significantly improved activity over the existing known inhibitors Camostat and Nafamostat.