Human-specific genetic hallmarks in neocortical development: focus on neural progenitors.

The evolutionary expansion of the neocortex in the ape lineage is the basis for the development of higher cognitive abilities. However, the human brain has uniquely increased in size and degree of folding, forming an essential foundation for advanced cognitive functions. This raises the question: what factors distinguish humans from our closest living primate relatives, such as chimpanzees and bonobos, which exhibit comparatively constrained cognitive capabilities? In this review, we focus on recent studies examining (modern) human-specific genetic traits that influence neural progenitor cells, whose behavior and activity are crucial for shaping cortical morphology.

Communication as a Key Performance Indicator in Employer Branding in the Context of the Social Economy-A Quantitative Study.

Performance measurement refers to the systematic evaluation and analysis of the performance and results of business processes, initiatives, or strategies. This study discusses the crucial role of communication using signaling theory in employer branding in the context of the social economy organization (SEO). The aim is to measure employee satisfaction in concrete terms and to determine the status quo of the communication culture of the organization under investigation in order to develop an employer branding strategy based on the results.

Neocortical neurogenesis in development and evolution-Human-specific features.

In this review, we focus on human-specific features of neocortical neurogenesis in development and evolution. Two distinct topics will be addressed. In the first section, we discuss the expansion of the neocortex during human evolution and concentrate on the human-specific gene ARHGAP11B.

The SVZ stem cell niche-components, functions, and modelling.

Neocortical development depends on the intrinsic ability of neural stem and progenitor cells to proliferate and differentiate to generate the different kinds of neurons in the adult brain. These progenitor cells can be distinguished into apical progenitors, which occupy a stem cell niche in the ventricular zone and basal progenitors, which occupy a stem cell niche in the subventricular zone (SVZ). During development, the stem cell niche provided in the subventricular zone enables the increased proliferation and self-renewal of basal progenitors, which likely underlie the expansion of the human neocortex.

Targeted Microinjection and Electroporation of Primate Cerebral Organoids for Genetic Modification.

The cerebral cortex is the outermost brain structure and is responsible for the processing of sensory input and motor output; it is seen as the seat of higher-order cognitive abilities in mammals, in particular, primates. Studying gene functions in primate brains is challenging due to technical and ethical reasons, but the establishment of the brain organoid technology has enabled the study of brain development in traditional primate models (e.g.

PARP14 is a novel target in STAT6 mutant follicular lymphoma.

The variable clinical course of follicular lymphoma (FL) is determined by the molecular heterogeneity of tumor cells and complex interactions within the tumor microenvironment (TME). IL-4 producing follicular helper T cells (T) are critical components of the FL TME. Binding of IL-4 to IL-4R on FL cells activates JAK/STAT signaling.

Monoallelic and biallelic mutations in RELN underlie a graded series of neurodevelopmental disorders.

Reelin, a large extracellular protein, plays several critical roles in brain development and function. It is encoded by RELN, first identified as the gene disrupted in the reeler mouse, a classic neurological mutant exhibiting ataxia, tremors and a 'reeling' gait. In humans, biallelic variants in RELN have been associated with a recessive lissencephaly variant with cerebellar hypoplasia, which matches well with the homozygous mouse mutant that has abnormal cortical structure, small hippocampi and severe cerebellar hypoplasia.

The molecular ontogeny of follicular lymphoma: gene mutations succeeding the BCL2 translocation define common precursor cells.

Relapsed follicular lymphoma (FL) can arise from common progenitor cells (CPCs). Conceptually, CPC-defining mutations are somatic alterations shared by the initial and relapsed tumours, mostly B-cell leukaemia/lymphoma 2 (BCL2)/immunoglobulin heavy locus (IGH) translocations and other recurrent gene mutations. Through complementary approaches for highly sensitive mutation detection, we do not find CPC-defining mutations in highly purified BCL2/IGH-negative haematopoietic progenitor cells in clinical remission samples from three patients with relapsed FL.

COVID-19 in Patients Receiving CD20-depleting Immunochemotherapy for B-cell Lymphoma.

The clinical and immunological impact of B-cell depletion in the context of coronavirus disease 2019 (COVID-19) is unclear. We conducted a prospectively planned analysis of COVID-19 in patients who received B-cell depleting anti-CD20 antibodies and chemotherapy for B-cell lymphomas. The control cohort consisted of age- and sex-matched patients without lymphoma who were hospitalized because of COVID-19.

Human-Specific Genes, Cortical Progenitor Cells, and Microcephaly.

Over the past few years, human-specific genes have received increasing attention as potential major contributors responsible for the 3-fold difference in brain size between human and chimpanzee. Accordingly, mutations affecting these genes may lead to a reduction in human brain size and therefore, may cause or contribute to microcephaly. In this review, we will concentrate, within the brain, on the cerebral cortex, the seat of our higher cognitive abilities, and focus on the human-specific gene and on the gene family comprising the three human-specific genes , , and .

Human-specific increases size and folding of primate neocortex in the fetal marmoset.

The neocortex has expanded during mammalian evolution. Overexpression studies in developing mouse and ferret neocortex have implicated the human-specific gene in neocortical expansion, but the relevance for primate evolution has been unclear. Here, we provide functional evidence that causes expansion of the primate neocortex.

Cathepsin S Alterations Induce a Tumor-Promoting Immune Microenvironment in Follicular Lymphoma.

Tumor cells orchestrate their microenvironment. Here, we provide biochemical, structural, functional, and clinical evidence that Cathepsin S (CTSS) alterations induce a tumor-promoting immune microenvironment in follicular lymphoma (FL). We found CTSS mutations at Y132 in 6% of FL (19/305).

Genetic Modification of Brain Organoids.

Brain organoids have become increasingly used systems allowing 3D-modeling of human brain development, evolution, and disease. To be able to make full use of these modeling systems, researchers have developed a growing toolkit of genetic modification techniques. These techniques can be applied to mature brain organoids or to the preceding embryoid bodies (EBs) and founding cells.

Organoid single-cell genomic atlas uncovers human-specific features of brain development.

The human brain has undergone substantial change since humans diverged from chimpanzees and the other great apes. However, the genetic and developmental programs that underlie this divergence are not fully understood. Here we have analysed stem cell-derived cerebral organoids using single-cell transcriptomics and accessible chromatin profiling to investigate gene-regulatory changes that are specific to humans.

Brain organoids as models to study human neocortex development and evolution.

Since their recent development, organoids that emulate human brain tissue have allowed in vitro neural development studies to go beyond the limits of monolayer culture systems, such as neural rosettes. We present here a review of organoid studies that focuses on cortical wall development, starting with a technical comparison between pre-patterning and self-patterning brain organoid protocols. We then follow neocortex development in space and time and list those aspects where organoids have succeeded in emulating in vivo development, as well as those aspects that continue to be pending tasks.

Evolution and cell-type specificity of human-specific genes preferentially expressed in progenitors of fetal neocortex.

Understanding the molecular basis that underlies the expansion of the neocortex during primate, and notably human, evolution requires the identification of genes that are particularly active in the neural stem and progenitor cells of the developing neocortex. Here, we have used existing transcriptome datasets to carry out a comprehensive screen for protein-coding genes preferentially expressed in progenitors of fetal human neocortex. We show that 15 human-specific genes exhibit such expression, and many of them evolved distinct neural progenitor cell-type expression profiles and levels compared to their ancestral paralogs.

Novel gene function and regulation in neocortex expansion.

The expansion of the neocortex during human evolution is due to changes in our genome that result in increased and prolonged proliferation of neural stem and progenitor cells during neocortex development. Three principal types of such genomic changes can be distinguished, first, novel gene regulation in human, second, novel function in human of genes existing in both human and non-human species, and third, novel, human-specific genes. The latter comprise both, increases in the copy number of genes existing also in non-human species, and the emergence of genes giving rise to unique, human-specific gene products.

A tunable refractive index matching medium for live imaging cells, tissues and model organisms.

In light microscopy, refractive index mismatches between media and sample cause spherical aberrations that often limit penetration depth and resolution. Optical clearing techniques can alleviate these mismatches, but they are so far limited to fixed samples. We present Iodixanol as a non-toxic medium supplement that allows refractive index matching in live specimens and thus substantially improves image quality in live-imaged primary cell cultures, planarians, zebrafish and human cerebral organoids.

LIM homeobox protein 5 (Lhx5) is essential for mamillary body development.

The mamillary body (MM) is a group of hypothalamic nuclei related to memory and spatial navigation that interconnects hippocampal, thalamic, and tegmental regions. Here we demonstrate that Lhx5, a LIM-HD domain transcription factor expressed early in the developing posterior hypothalamus, is required for the generation of the MM and its derived tracts. The MM markers Foxb1, Sim2, and Lhx1 are absent in Lhx5 knock-out mice from early embryonic stages, suggesting abnormal specification of this region.

Lhx5 controls mamillary differentiation in the developing hypothalamus of the mouse.

Acquisition of specific neuronal identity by individual brain nuclei is a key step in brain development. However, how the mechanisms that confer neuronal identity are integrated with upstream regional specification networks is still mysterious. Expression of Sonic hedgehog (Shh), is required for hypothalamic specification and is later downregulated by Tbx3 to allow for the differentiation of the tubero-mamillary region.

Probe-based confocal laser endomicroscopy (pCLE) - a new imaging technique for in situ localization of spermatozoa.

In azoospermic patients, spermatozoa are routinely obtained by testicular sperm extraction (TESE). However, success rates of this technique are moderate, because the site of excision of testicular tissue is determined arbitrarily. Therefore the aim of this study was to establish probe-based laser endomicroscopy (pCLE) a noval biomedical imaging technique, which provides the opportunity of non-invasive, real-time visualisation of tissue at histological resolution.

Mouse thalamic differentiation: gli-dependent pattern and gli-independent prepattern.

Sonic hedgehog (Shh) signaling is essential for thalamic development. The Gli transcription factors act downstream of Shh - while Gli2 is the major activator (GliA), Gli3 acts primarily as a repressor (GliR). The thalamus is remarkable among dorsal structures because of its proximity to the mid-diencephalic organizer, a unique dorsal Shh source.