Climate change in Europe between 90 and 50 kyr BP and Neanderthal territorial habitability.

After having lived as the dominant human species in Europe for over 200 kyr, Homo neanderthalensis (the Neanderthals) disappeared around 40 kyr BP (Before Present) Higham T (2014). Competition with Homo sapiens, who arrived in Europe around the same time, is often invoked to explain this extinction. Others have argued that climate change may have reduced the living space of this population making its disappearance more rapid.

Symplastic guard cell connections buffer pressure fluctuations to promote stomatal function in grasses.

Stomata regulate plant gas exchange via repeated turgor-driven changes of guard cell shape, thereby adjusting pore apertures. Grasses, which are among the most widespread plant families on the planet, are distinguished by their unique stomatal structure, which is proposed to have significantly contributed to their evolutionary and agricultural success. One component of their structure, which has received little attention, is the presence of a discontinuous adjoining cell wall of the guard cell pair.

Cellular damage triggers mechano-chemical control of cell wall dynamics and patterned cell divisions in plant healing.

Reactivation of cell division is crucial for the regeneration of damaged tissues, which is a fundamental process across all multicellular organisms. However, the mechanisms underlying the activation of cell division in plants during regeneration remain poorly understood. Here, we show that single-cell endodermal ablation generates a transient change in the local mechanical pressure on neighboring pericycle cells to activate patterned cell division that is crucial for tissue regeneration in Arabidopsis roots.

snRNA-seq stratifies multiple sclerosis patients into distinct white matter glial responses.

Poor understanding of the cellular and molecular basis of clinical and genetic heterogeneity in progressive multiple sclerosis (MS) has hindered the search for new effective therapies. To address this gap, we analyzed 632,000 single-nucleus RNA sequencing profiles from 156 brain tissue samples of MS and control donors to examine inter- and intra-donor heterogeneity. We found distinct cell type-specific gene expression changes between MS gray and white matter, highlighting clear pathology differences.

Improvement of variant reclassification in genetic neurodevelopmental conditions.

Purpose: Limited knowledge about disease mechanisms, few published cases, and the lack of functional assessment of variants for neurodevelopmental genetic disorders challenge diagnostic classification for variants and increase the frequency of variants of uncertain significance (VUS). Because inheritance patterns aid in variant interpretation for neurodevelopmental conditions, genetic testing including only the proband leads to larger numbers of VUS than testing strategies that include the parents.

Methods: We reinterpreted genetic variants submitted to the Simons Searchlight research registry using American College of Medical Genetics and Genomics variant interpretation guidelines, familial cascade testing, and literature curation with annual VUS reevaluation.

Actin-mediated avoidance of tricellular junction influences global topology at the Arabidopsis shoot apical meristem.

Division plane orientation contributes to cell shape and topological organization, playing a key role in morphogenesis, but the precise physical and molecular mechanism influencing these processes remains largely obscure in plants. In particular, it is less clear how the placement of the new walls occurs in relation to the walls of neighboring cells. Here, we show that genetic perturbation of the actin cytoskeleton results in more rectangular cell shapes and higher incidences of four-way junctions, perturbing the global topology of cells in the shoot apical meristem of Arabidopsis thaliana.

Conserved transcriptional regulation by BRN1 and BRN2 in neocortical progenitors drives mammalian neural specification and neocortical expansion.

The neocortex varies in size and complexity among mammals due to the tremendous variability in the number and diversity of neuronal subtypes across species. The increased cellular diversity is paralleled by the expansion of the pool of neocortical progenitors and the emergence of indirect neurogenesis during brain evolution. The molecular pathways that control these biological processes and are disrupted in neurological disorders remain largely unknown.

Combination of MDM2 and Targeted Kinase Inhibitors Results in Prolonged Tumor Control in Lung Adenocarcinomas With Oncogenic Tyrosine Kinase Drivers and Amplification.

Purpose: MDM2, a negative regulator of the TP53 tumor suppressor, is oncogenic when amplified. amplification (MDM2amp) is mutually exclusive with mutation and is seen in 6% of patients with lung adenocarcinoma (LUAD), with significant enrichment in subsets with receptor tyrosine kinase (RTK) driver alterations. Recent studies have shown synergistic activity of MDM2 and MEK inhibition in patient-derived LUAD models with MDM2amp and RTK driver alterations.

Age-associated growth control modifies leaf proximodistal symmetry and enabled leaf shape diversification.

Biological shape diversity is often manifested in modulation of organ symmetry and modification of the patterned elaboration of repeated shape elements. Whether and how these two aspects of shape determination are coordinately regulated is unclear. Plant leaves provide an attractive system to investigate this problem, because they often show asymmetries along the proximodistal (PD) axis of their blades, along which they can also produce repeated marginal outgrowths such as serrations or leaflets.

An incoherent feed-forward loop involving bHLH transcription factors, Auxin and CYCLIN-Ds regulates style radial symmetry establishment in Arabidopsis.

The bilateral-to-radial symmetry transition occurring during the development of the Arabidopsis thaliana female reproductive organ (gynoecium) is a crucial biological process linked to plant fertilization and seed production. Despite its significance, the cellular mechanisms governing the establishment and breaking of radial symmetry at the gynoecium apex (style) remain unknown. To fill this gap, we employed quantitative confocal imaging coupled with MorphoGraphX analysis, in vivo and in vitro transcriptional experiments, and genetic analysis encompassing mutants in two bHLH transcription factors necessary and sufficient to promote transition to radial symmetry, SPATULA (SPT) and INDEHISCENT (IND).

Analysis of DNA from brain tissue on stereo-EEG electrodes reveals mosaic epilepsy-related variants.

Somatic mosaic variants contribute to focal epilepsy, but genetic analysis has been limited to patients with drug-resistant epilepsy (DRE) who undergo surgical resection, as the variants are mainly brain-limited. Stereoelectroencephalography (sEEG) has become part of the evaluation for many patients with focal DRE, and sEEG electrodes provide a potential source of small amounts of brain-derived DNA. We aimed to identify, validate, and assess the distribution of potentially clinically relevant mosaic variants in DNA extracted from trace brain tissue on individual sEEG electrodes.

The ecology of giant kelp colonization and its implications for kelp forest restoration.

The success and cost-effectiveness of kelp forest restoration hinges on understanding the colonization ecology of kelps, particularly with respect to dispersal potential, recruitment success, and subsequent establishment. To gain needed insight into these processes we examined spatial patterns and temporal trajectories of the colonization of a large artificial reef by the giant kelp Macrocystis pyrifera. The 151 ha artificial reef complex was constructed in three phases over 21 years, enabling dispersal, recruitment, and subsequent establishment to be examined for a wide range of environmental conditions, dispersal distances, and source population sizes.

Arabidopsis floral buds are locked through stress-induced sepal tip curving.

In most plant species, sepals-the outermost floral organs-provide a protective shield for reproductive organs. How the floral bud becomes sealed is unknown. In Arabidopsis, we identified a small region at the sepal tip that is markedly curved inward early on and remains curved even after anthesis.

A deep learning-based toolkit for 3D nuclei segmentation and quantitative analysis in cellular and tissue context.

We present a new set of computational tools that enable accurate and widely applicable 3D segmentation of nuclei in various 3D digital organs. We have developed an approach for ground truth generation and iterative training of 3D nuclear segmentation models, which we applied to popular CellPose, PlantSeg and StarDist algorithms. We provide two high-quality models trained on plant nuclei that enable 3D segmentation of nuclei in datasets obtained from fixed or live samples, acquired from different plant and animal tissues, and stained with various nuclear stains or fluorescent protein-based nuclear reporters.

Tradeoff between speed and robustness in primordium initiation mediated by auxin-CUC1 interaction.

Robustness is the reproducible development of a phenotype despite stochastic noise. It often involves tradeoffs with other performance metrics, but the mechanisms underlying such tradeoffs were largely unknown. An Arabidopsis flower robustly develops four sepals from four precisely positioned auxin maxima.

An HSF1-JMJD6-HSP feedback circuit promotes cell adaptation to proteotoxic stress.

Heat Shock Factor 1 (HSF1) is best known as the master transcriptional regulator of the heat-shock response (HSR), a conserved adaptive mechanism critical for protein homeostasis (proteostasis). Combining a genome-wide RNAi library with an HSR reporter, we identified Jumonji domain-containing protein 6 (JMJD6) as an essential mediator of HSF1 activity. In follow-up studies, we found that JMJD6 is itself a noncanonical transcriptional target of HSF1 which acts as a critical regulator of proteostasis.

Chain-Length Dependence of Peptide-Lipid Bilayer Interaction Strength and Binding Kinetics: A Combined Theoretical and Experimental Approach.

Physical interactions between polypeptide chains and lipid membranes underlie critical cellular processes. Yet, despite fundamental importance, key mechanistic aspects of these interactions remain elusive. Bulk experiments have revealed a linear relationship between free energy and peptide chain length in a model system, but does this linearity extend to the interaction strength and to the kinetics of lipid binding? To address these questions, we utilized a combination of coarse-grained molecular dynamics (CG MD) simulations, analytical modeling, and atomic force microscopy (AFM)-based single molecule force spectroscopy.

A mechanical transition from tension to buckling underlies the jigsaw puzzle shape morphogenesis of histoblasts in the Drosophila epidermis.

The polygonal shape of cells in proliferating epithelia is a result of the tensile forces of the cytoskeletal cortex and packing geometry set by the cell cycle. In the larval Drosophila epidermis, two cell populations, histoblasts and larval epithelial cells, compete for space as they grow on a limited body surface. They do so in the absence of cell divisions.

Skeletal muscle desmin alterations following revascularization in peripheral artery disease claudicants.

Peripheral artery disease (PAD) is characterized by varying severity of arterial stenosis, exercise induced claudication, malperfused tissue precluding normal healing and skeletal muscle dysfunction. Revascularization interventions improve circulation, but post-reperfusion changes within the skeletal muscle are not well characterized. This study investigates if revascularization enhanced hemodynamics increases walking performance with concurrent improvement of mitochondrial function and reverses abnormal skeletal muscle morphological features that develop with PAD.

PRDM16 co-operates with LHX2 to shape the human brain.

PRDM16 is a dynamic transcriptional regulator of various stem cell niches, including adipocytic, hematopoietic, cardiac progenitors, and neural stem cells. PRDM16 has been suggested to contribute to 1p36 deletion syndrome, one of the most prevalent subtelomeric microdeletion syndromes. We report a patient with a nonsense mutation in the PRDM16 coding sequence, accompanied by lissencephaly and microcephaly features.

Growth and tension in explosive fruit.

Exploding seed pods of the common weed Cardamine hirsuta have the remarkable ability to launch seeds far from the plant. The energy for this explosion comes from tension that builds up in the fruit valves. Above a critical threshold, the fruit fractures along its dehiscence zone and the two valves coil explosively, ejecting the seeds.