In experimental research a scientific conclusion is always drawn from the statistical testing of hypothesis, in which an acceptable cutoff of probability, such as 0.05 or 0.01, is used for decision-making.However, the probability of committing false statistical inferences would considerably increase when more than one hypothesis is simultaneously tested (namely the multiple comparisons), which therefore requires proper adjustment. Although the adjustment for multiple comparisons is proposed to be mandatory in some journals, it still remains difficult to select a proper method suitable for the various experimental properties and study purposes, especially for researchers without good background in statistics. In the present paper, we provide a brief review on mathematical framework, general concepts and common methods of adjustment for multiple comparisons, which is expected to facilitate the understanding and selection of adjustment methods.

SummaryCentrosomes are important cell organizers. They consist of a pair of centrioles surrounded by pericentriolar material (PCM) that expands dramatically during mitosis—a process termed centrosome maturation. How centrosomes mature remains mysterious. Here, we identify a domain in Drosophila Cnn that appears to be phosphorylated by Polo/Plk1 specifically at centrosomes during mitosis. The phosphorylation promotes the assembly of a Cnn scaffold around the centrioles that is in constant flux, with Cnn molecules recruited continuously around the centrioles as the scaffold spreads slowly outward. Mutations that block Cnn phosphorylation strongly inhibit scaffold assembly and centrosome maturation, whereas phosphomimicking mutations allow Cnn to multimerize in vitro and to spontaneously form cytoplasmic scaffolds in vivo that organize microtubules independently of centrosomes. We conclude that Polo/Plk1 initiates the phosphorylation-dependent assembly of a Cnn scaffold around centrioles that is essential for efficient centrosome maturation in flies.

Designing an incentive compatible auction that maximizes expected revenue is an intricate task. The single-item case was resolved in a seminal piece of work by Myerson in 1981. Even after 30--40 years of intense research, the problem remains unsolved for settings with two or more items. We overview recent research results that show how tools from deep learning are shaping up to become a powerful tool for the automated design of near-optimal auctions auctions. In this approach, an auction is modeled as a multilayer neural network, with optimal auction design framed as a constrained learning problem that can be addressed with standard machine learning pipelines. Through this approach, it is possible to recover to a high degree of accuracy essentially all known analytically derived solutions for multi-item settings and obtain novel mechanisms for settings in which the optimal mechanism is unknown.

SummaryIn flies, Centrosomin (Cnn) forms a phosphorylation-dependent scaffold that recruits proteins to the mitotic centrosome, but how Cnn assembles into a scaffold is unclear. We show that scaffold assembly requires conserved leucine zipper (LZ) and Cnn-motif 2 (CM2) domains that co-assemble into a 2:2 complex in vitro. We solve the crystal structure of the LZ:CM2 complex, revealing that both proteins form helical dimers that assemble into an unusual tetramer. A slightly longer version of the LZ can form micron-scale structures with CM2, whose assembly is stimulated by Plk1 phosphorylation in vitro. Mutating individual residues that perturb LZ:CM2 tetramer assembly perturbs the formation of these micron-scale assemblies in vitro and Cnn-scaffold assembly in vivo. Thus, Cnn molecules have an intrinsic ability to form large, LZ:CM2-interaction-dependent assemblies that are critical for mitotic centrosome assembly. These studies provide the first atomic insight into a molecular interaction required for mitotic centrosome assembly.

Edited by Paul E. FraserLiquid-liquid phase separation (LLPS) facilitates the formation of condensed biological assemblies with well-delineated physical boundaries, but without lipid membrane barriers. LLPS is increasingly recognized as a common mechanism for cells to organize and maintain different cellular compartments in addition to classical membrane-delimited organelles. Membraneless condensates have many distinct features that are not present in membrane-delimited organelles and that are likely indispensable for the viability and function of living cells. Malformation of membraneless condensates is increasingly linked to human diseases. In this review, we summarize commonly used methods to investigate various forms of LLPS occurring both in 3D aqueous solution and on 2D membrane bilayers, such as LLPS condensates arising from intrinsically disordered proteins or structured modular protein domains. We then discuss, in the context of comparisons with membrane-delimited organelles, the potential functional implications of membraneless condensate formation in cells. We close by highlighting some challenges in the field devoted to studying LLPS-mediated membraneless condensate formation.In eukaryotic cells, reaction components are spatiotemporally compartmentalized so that materials are concentrated and activities are localized and protected from damaging activities, such as proteolysis, changes in pH, and undesired covalent modifications. Classical organelles are membrane-enclosed where the lipid bilayer provides a physical barrier to separate their interior contents from the exterior environment. Examples include Golgi apparatus, mitochondria, and endoplasmic reticulum (ER). 3 However, many organelles are not membrane-enclosed (often referred to as membraneless compartments in the literature), and such organelles include but are not limited to germ granules, stress granules, nucleoli, centrosomes, and synapses in neurons. In these membraneless compartments, due to the lack of physical separation, molecules can freely exchange with their counterparts in the surrounding bulk solution. Sharp concentration gradients are maintained between the proteinaceous (and sometimes protein and nucleic acid mixtures) interior and the much more diluted exterior. Reaction machineries can reversibly assemble and disassemble within a short time window, as fast as a few seconds. Reaction constituents can be integrated or removed to control specific activities. While recognized for many years, the mechanisms governing the formation of membraneless organelles have remained unclear until about 10 years ago. The first direct experimental evidence came from the study of P granules in germ cells of Caenorhabditis elegans (1). P granule is a collection of RNA and RNA-binding proteins (RBPs) localized at the posterior cortex of a dividing embryo. P granules appear as spherical droplets with liquid-like properties, and they fuse with one another, deform under shear stress, and flow off the surface of the nucleus. Fluorescence recovery afte...

Eye tracking (ET) holds potential for the early detection of autism spectrum disorder (ASD). To overcome the difficulties of working with young children, developing a short and informative paradigm is crucial for ET. We investigated the fixation times of 37 ASD and 37 typically developing (TD) children ages 4-6 watching a 10-second video of a female speaking. ASD children showed significant reductions in fixation time at six areas of interest. Furthermore, discriminant analysis revealed fixation times at the mouth and body could significantly discriminate ASD from TD with a classification accuracy of 85.1%, sensitivity of 86.5%, and specificity of 83.8%. Our study suggests that a short video clip may provide enough information to distinguish ASD from TD children.

Formation of biomolecular condensates that are not enclosed by membranes via liquid-liquid phase separation (LLPS) is a general strategy that cells adopt to organize membraneless subcellular compartments for diverse functions. Neurons are highly polarized with elaborate branching and functional compartmentalization of their neurites, thus, raising additional demand for the proper subcellular localization of both membraneless and membrane-based organelles. Recent studies have provided evidence that several protein assemblies involved in the establishment of neuronal stem cell (NSC) polarity and in the asymmetric division of NSCs form distinct molecular condensates via LLPS. In synapses of adult neurons, molecular apparatuses controlling presynaptic neurotransmitter release and postsynaptic signaling transmission are also likely formed via LLPS. These molecular condensates, though not enclosed by lipid bilayers, directly associate with plasma membranes or membrane-based organelles, indicating that direct communication between membraneless and membrane-based organelles is a common theme in neurons and other types of cells. ll ll

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