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Static correction: Kim ainsi que al. Mobile or portable Floor GRP94 as a Fresh Growing Beneficial Target with regard to Monoclonal Antibody Cancer malignancy Therapy. Tissue 2021, 10, 670.
Our work highlights the degree to which the human footprint and existing protected areas now constrain the distribution of the world's largest terrestrial mammal.9,10 A habitat suitability model, created by evaluating every square kilometer of Africa, predicts that 18,169,219 km2 would be suitable as elephant habitat-62% of the continent. The current elephant distribution covers just 17% of this potential range of which 57.4% falls outside protected areas. To stem the continued extirpation and to secure the elephants' future, effective and expanded protected areas and improved capacity for coexistence across unprotected range are essential.Facial attractiveness confers considerable advantages in social interactions,1,2 with preferences likely reflecting psychobiological mechanisms shaped by natural selection. Theories of universal beauty propose that attractive faces comprise features that are closer to the population average3 while optimizing sexual dimorphism.4 However, emerging evidence questions this model as an accurate representation of facial attractiveness,5-7 including representing the diversity of beauty preferences within and across cultures.8-12 Here, we demonstrate that Western Europeans (WEs) and East Asians (EAs) evaluate facial beauty using culture-specific features, contradicting theories of universality. With a data-driven method, we modeled, at both the individual and group levels, the attractive face features of young females (25 years old) in two matched groups each of 40 young male WE and EA participants. Specifically, we generated a broad range of same- and other-ethnicity female faces with naturally varying shapes and complexions. Participants rated each on attractiveness. We then reverse correlated the face features that drive perception of attractiveness in each participant. From these individual face models, we reconstructed a facial attractiveness representation space that explains preference variations. We show that facial attractiveness is distinct both from averageness and from sexual dimorphism in both cultures. Finally, we disentangled attractive face features into those shared across cultures, culture specific, and specific to individual participants, thereby revealing their diversity. Our results have direct theoretical and methodological impact for representing diversity in social perception and for the design of culturally and ethnically sensitive socially interactive digital agents.Correlation-based (Hebbian) forms of synaptic plasticity are crucial for the initial encoding of associative memories but likely insufficient to enable the stable storage of multiple specific memories within neural circuits. Theoretical studies have suggested that homeostatic synaptic normalization rules provide an essential countervailing force that can stabilize and expand memory storage capacity. Although such homeostatic mechanisms have been identified and studied for decades, experimental evidence that they play an important role in associative memory is lacking. Here, we show that synaptic scaling, a widely studied form of homeostatic synaptic plasticity that globally renormalizes synaptic strengths, is dispensable for initial associative memory formation but crucial for the establishment of memory specificity. We used conditioned taste aversion (CTA) learning, a form of associative learning that relies on Hebbian mechanisms within gustatory cortex (GC), to show that animals conditioned to avoid saccharin initially generalized this aversion to other novel tastants. Specificity of the aversion to saccharin emerged slowly over a time course of many hours and was associated with synaptic scaling down of excitatory synapses onto conditioning-active neuronal ensembles within gustatory cortex. Blocking synaptic scaling down in the gustatory cortex enhanced the persistence of synaptic strength increases induced by conditioning and prolonged the duration of memory generalization. Taken together, these findings demonstrate that synaptic scaling is crucial for sculpting the specificity of an associative memory and suggest that the relative strengths of Hebbian and homeostatic plasticity can modulate the balance between stable memory formation and memory generalization.During mitosis in animal cells, the centrosome acts as a microtubule organizing center (MTOC) to assemble the mitotic spindle. MTOC function at the centrosome is driven by proteins within the pericentriolar material (PCM), however the molecular complexity of the PCM makes it difficult to differentiate the proteins required for MTOC activity from other centrosomal functions. We used the natural spatial separation of PCM proteins during mitotic exit to identify a minimal module of proteins required for centrosomal MTOC function in C. elegans. Using tissue-specific degradation, we show that SPD-5, the functional homolog of CDK5RAP2, is essential for embryonic mitosis, while SPD-2/CEP192 and PCMD-1, which are essential in the one-cell embryo, are dispensable. Surprisingly, although the centriole is known to be degraded in the ciliated sensory neurons in C. elegans,1-3 we find evidence for "centriole-less PCM" at the base of cilia and use this structure as a minimal testbed to dissect centrosomal MTOC function. Super-resolution imaging revealed that this PCM inserts inside the lumen of the ciliary axoneme and directly nucleates the assembly of dendritic microtubules toward the cell body. Tissue-specific degradation in ciliated sensory neurons revealed a role for SPD-5 and the conserved microtubule nucleator γ-TuRC, but not SPD-2 or PCMD-1, in MTOC function at centriole-less PCM. This MTOC function was in the absence of regulation by mitotic kinases, highlighting the intrinsic ability of these proteins to drive microtubule growth and organization and further supporting a model that SPD-5 is the primary driver of MTOC function at the PCM.In animal cells, the functions of the microtubule cytoskeleton are coordinated by centriole-based centrosomes via γ-tubulin complexes embedded in the pericentriolar material or PCM.1 PCM assembly has been best studied in the context of mitosis, where centriolar SPD-2 recruits PLK-1, which in turn phosphorylates key scaffolding components like SPD-5 and CNN to promote expansion of the PCM polymer.2-4 To what extent these mechanisms apply to centrosomes in interphase or in differentiated cells remains unclear.5 Here, we examine a novel type of centrosome found at the ciliary base of C. elegans sensory neurons, which we show plays important roles in neuronal morphogenesis, cellular trafficking, and ciliogenesis. These centrosomes display similar dynamic behavior to canonical, mitotic centrosomes, with a stable PCM scaffold and dynamically localized client proteins. Unusually, however, they are not organized by centrioles, which degenerate early in terminal differentiation.6 Yet, PCM not only persists but continues to grow with key scaffolding proteins including SPD-5 expressed under control of the RFX transcription factor DAF-19. This assembly occurs in the absence of the mitotic regulators SPD-2, AIR-1 and PLK-1, but requires tethering by PCMD-1, a protein which also plays a role in the initial, interphase recruitment of PCM in early embryos.7 These results argue for distinct mechanisms for mitotic and non-mitotic PCM assembly, with only the former requiring PLK-1 phosphorylation to drive rapid expansion of the scaffold polymer.Jecrois et al. (2020) use cryoelectron microscopy to illuminate the tetrameric conformation of the CtBP2 transcriptional corepressor, a protein frequently overexpressed in human cancers. The in vivo functional characterization of tetramer-destabilizing mutants indicates that tetramerization is a physiologically important process, critical for CtBP control of gene regulation and cell migration.In this issue of Structure, Cho et al. (2020) identified an intermolecular interaction between two RIAM pleckstrin homology (PH) domains that masks the phosphoinositide-binding site, and that phosphorylation by Src unmasks the PH domain. This provides an explanation of how RIAM plasma membrane translocation is regulated to promote integrin activation.What you see is what you get-imaging techniques have long been essential for visualization and understanding of tissue development, homeostasis, and regeneration, which are driven by stem cell self-renewal and differentiation. Advances in molecular and tissue modeling techniques in the last decade are providing new imaging modalities to explore tissue heterogeneity and plasticity. Here we describe current state-of-the-art imaging modalities for tissue research at multiple scales, with a focus on explaining key tradeoffs such as spatial resolution, penetration depth, capture time/frequency, and moieties. We explore emerging tissue modeling and molecular tools that improve resolution, specificity, and throughput.COVID-19 has unfortunately halted lab work, conferences, and in-person networking, which is especially detrimental to researchers just starting their labs. Through social media and our reviewer networks, we met some early-career stem cell investigators impacted by the closures. Here, they introduce themselves and their research to our readers.In a recent report in Nature Medicine, Tao et al. (2021) demonstrate that MPTP-treated monkeys receiving autologous, but not allogeneic, transplantation showed significant long-term improvement in motor and depressive behaviors, supporting the feasibility of autologous cell therapy for Parkinson's disease (PD).Cellular cartography of human tissues has provided unprecedented insight into health and disease. In a recent issue of Science, Reynolds et al. (2021) use single-cell transcriptomics to define cell states and gene programs in human skin and uncover fetal programs in dermatological diseases that may fuel inflammatory pathology.The response of adipose progenitors to metabolic states is a crucial, but poorly understood, determinant of metabolic health. The back-to-back papers by Joffin et al. (2021) and Shao et al. (2021) in this issue of Cell Stem Cell reveal how adipose-tissue-resident PDGFRβ+precursor cell fate is regulated by mitochondrial bioenergetic state and how such processes go wrong in obesity.Methods for deriving the ureteric epithelium (UE) in vitro could improve understanding of kidney development and patterning. In this issue of Cell Stem Cell, Howden et al. (2021) identified transcriptionally distinct cell populations in human induced pluripotent stem cell (iPSC)-derived distal nephron (DN) epithelia that were inducible to UE phenotype within kidney organoids.Accumulation of undifferentiated myeloid progenitors is a hallmark of AML, and targeting differentiation blockade represents a promising therapeutic strategy for AML. In this issue of Cell Stem Cell, Wang et al. Nafamostat cost (2021) conducted surface antigen-guided CRISPR screening and identified ZFP36L2 as a myeloid leukemia differentiation regulator and new therapeutic target.Using a forward-genetic screening of macrophages from randomly mutagenized mice, Kayagaki et al. (2021) identify NINJ1 that mediates plasma membrane rupture following various types of programmed cell death, an event previously thought to be passive.
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