B chromosome functions within mammalian spermatogenesis

The goal of limiting global warming to 1.5 °C requires a drastic reduction in CO2 emissions across many sectors of the world economy. Batteries are vital to this endeavor, whether used in electric vehicles, to store renewable electricity, or in aviation. Present lithium-ion technologies are preparing the public for this inevitable change, but their maximum theoretical specific capacity presents a limitation. Their high cost is another concern for commercial viability. Metal-air batteries have the highest theoretical energy density of all possible secondary battery technologies and could yield step changes in energy storage, if their practical difficulties could be overcome. The scope of this review is to provide an objective, comprehensive, and authoritative assessment of the intensive work invested in nonaqueous rechargeable metal-air batteries over the past few years, which identified the key problems and guides directions to solve them. We focus primarily on the challenges and outlook for Li-O2 cells but include Na-O2, K-O2, and Mg-O2 cells for comparison. Our review highlights the interdisciplinary nature of this field that involves a combination of materials chemistry, electrochemistry, computation, microscopy, spectroscopy, and surface science. The mechanisms of O2 reduction and evolution are considered in the light of recent findings, along with developments in positive and negative electrodes, electrolytes, electrocatalysis on surfaces and in solution, and the degradative effect of singlet oxygen, which is typically formed in Li-O2 cells.A novel hybrid plasmonic platform based on the synergetic combination of a molecularly imprinted polymer (MIP) thin film with Au nanoparticle (NPs) assemblies, noted as Au@MIP, was developed for surface-enhanced Raman scattering (SERS) spectroscopy recognition of polycyclic aromatic hydrocarbons (PAHs). While the MIP trapped the PAH close to the Au surface, the plasmonic NPs enhanced the molecule's Raman signal. The Au@MIP fabrication comprises a two-step procedure, first, the layer-by-layer deposition of Au NPs on glass and their further coating with a uniform MIP thin film. Profilometry analysis demonstrated that the thickness and homogeneity of the MIP film could be finely tailored by tuning different parameters such as prepolymerization time or spin-coating rate. Two different PAH molecules, pyrene or fluoranthene, were used as templates for the fabrication of pyrene- or fluoranthene-based Au@MIP substrates. The use of pyrene or fluoranthene, as the template molecule to fabricate the Au@MIP thin films, enabled its ultradetection in the nM regime with a 100-fold improvement compared with the nonimprinted plasmonic sensors (Au@NIPs). The SERS data analysis allowed to estimate the binding constant of the template molecule to the MIP. The selectivity of both pyrene- and fluoranthene-based Au@MIPs was analyzed against three PAHs of different sizes. The results displayed the important role of the template molecule used for the Au@MIPs fabrication in the selectivity of the system. Finally, the practical applicability of pyrene-based Au@MIPs was shown by performing the detection of pyrene in two real samples creek water and seawater. Selleck Bafilomycin A1 The design and optimization of this type of plasmonic platform will pave the way for the detection of other relevant (bio)molecules in a broad range of fields such as environmental control, food safety, or biomedicine.The adenine-sensing riboswitch from the Gram-negative bacterium Vibrio vulnificus is an RNA-based gene regulatory element that acts in response to both its cognate low-molecular weight ligand and temperature. The combined sensitivity to environmental temperature and ligand concentration is maintained by an equilibrium of three distinct conformations involving two ligand-free states and one ligand-bound state. The key structural element that undergoes refolding in the ligand-free states comprises a 35-nucleotide temperature response module. Here, we present the structural characterization of this temperature response module. We employ high-resolution NMR spectroscopy and photocaged RNAs as molecular probes to decipher the kinetic and thermodynamic framework of the secondary structure transition in the apo state of the riboswitch. We propose a model for the transition state adopted during the thermal refolding of the temperature response module that connects two mutually exclusive long-lived and stable conformational states. This transition state is characterized by a comparatively low free activation enthalpy. A pseudoknot conformation in the transition state, as commonly seen in RNA refolding, is therefore unlikely. More likely, the transition state of the adenine-sensing riboswitch temperature response module features a linear conformation.Circulating cancer-derived small extracellular vesicles (EVs) are nanoscale membranous vesicles shed from cancer cells that are released into surrounding body fluids. Small EVs contain biomolecules associated with cancer such as DNA and proteins for cell-to-cell communication. Therefore, small EVs have been regarded as important cancer biomarkers for liquid biopsy-based cancer diagnosis and drug treatment monitoring. However, because of the high heterogeneity and low level of small EVs in body fluids, there is a high demand for sensitive detection and characterization of such vesicles at a molecular level. In this study, we have developed a sensitive and effective approach to simultaneously profile multiple protein biomarkers expressed on cancer-derived small EVs using surface-enhanced Raman spectroscopy (SERS) nanotags in a single test, without complex isolation steps. Rapid and multiplexed phenotypic profiling of small EVs is achieved by mixing specific detection antibody-coated SERS nanotags, filtered condieve that this technology enables a comprehensive evaluation of small secreted EV heterogeneity with high sensitivity, offering strong potential for accurate noninvasive cancer diagnosis and monitoring of drug treatment. In addition, this assay provides point-of-care use because of the easy sample preparation and portable nature of the Raman spectrometer.Thorough characterization of protein assemblies is required for the control of structure and robust performance in any given application, especially for the safety and stability of protein therapeutics. Here, we report the use of multiple, orthogonal characterization techniques to enable control over the structure of a multivalent antibody carrier for future use in drug delivery applications. The carrier, known as Hex, contains six antibody binding domains that bind the Fc region of antibodies. Using size exclusion chromatography, analytical ultracentrifugation, and dynamic light scattering, we identified the stoichiometry of assembled Hex-antibody complexes and observed changes in the stoichiometry of nanocarriers when incubated at higher temperatures over time. The characterization data informed the modification of Hex to achieve tighter control over the protein assembly structure for future therapeutic applications. This work demonstrates the importance of using orthogonal characterization techniques and observing protein assembly in different conditions over time to fully understand and control structure and dynamics.ConspectusThis Account highlights recent advances and discusses major challenges in investigations of cryptic (hidden) binding sites by molecular simulations. Cryptic binding sites are not visible in protein targets crystallized without a ligand and only become visible crystallographically upon binding events. These sites have been shown to be druggable and might provide a rare opportunity to target difficult proteins. However, due to their hidden nature, they are difficult to find through experimental screening. Computational methods based on atomistic molecular simulations remain one of the best approaches to identify and characterize cryptic binding sites. However, not all methods are equally efficient. Some are more apt at quickly probing protein dynamics but do not provide thermodynamic or druggability information, while others that are able to provide such data are demanding in terms of time and resources. Here, we review the recent contributions of mixed-solvent simulations, metadynamics, Markov state models, and other enhanced sampling methods to the field of cryptic site identification and characterization. We discuss how these methods were able to provide precious information on the nature of the site opening mechanisms, to predict previously unknown sites which were used to design new ligands, and to compute the free energy landscapes and kinetics associated with the opening of the sites and the binding of the ligands. We highlight the potential and the importance of such predictions in drug discovery, especially for difficult ("undruggable") targets. We also discuss the major challenges in the field and their possible solutions.Micro- and nanotextured surfaces with reconfigurable textures can enable advancements in control of wetting and heat transfer, directed assembly of complex materials, and reconfigurable optics, among many applications. However, reliable and programmable directional shape change in large scale is significant for prescribed applications. Herein, we demonstrate the self-directed fabrication and actuation of large-area elastomer micropillar arrays, using magnetic fields to both program a shape-directed actuation response, and to rapidly and reversibly actuate the arrays. Specifically, alignment of magnetic nanoparticles during casting of microposts arrays with hemicylindrical shapes imparts a deterministic anisotropy that can be exploited to achieve prescribed, large-deformation bending or twisting of the pillars. The actuation coincides with finite element method, and we demonstrate reversible, non-contact magnetic actuation of arrays of tens of thousands pillars over hundreds of cycles with bending and twisting angles of up to 72° and 61°, respectively. Moreover, we demonstrate use of the surfaces to control anisotropic liquid spreading, and show that capillary self-assembly of actuated micropost arrays enables highly complex architectures to be fabricated. The present technique could be scaled to indefinite areas using cost-effective materials and casting techniques, and the principle of shape-directed pillar actuation can be applied to other active material systems.Circulating tumor-related materials (CTRMs) shed from original or metastatic tumors, carry a lot of tumor information and are consid-ered as important markers for cancer diagnosis and metastasis prognosis. Herein, we report a colorimetric detection strategy for CTRMs based on aptamer-based magnetic isolation and endogenous alkaline phosphatase (AP)-signal amplification. This strategy exhibited high sensitivity and selectivity toward the CTRMs that express AP heterodimers (target of aptamer, potential tumor marker). For clinical samples, this CTRM assay significantly discriminated colorectal cancer patients (n = 50) from healthy individuals (n = 39, p less then 0.0001). The receiver operating characteristic (ROC) analysis indicated the sensitivity and specificity reached 92% and 82% re-spectively at the optimal cutoff point, the area under the curve of ROC reached 0.93, suggesting great potential for colorectal cancer diagnosis and therapeutic monitoring. Compared with CTC assays, this strategy is simple and has the potential for point-of-care testing.