This paper describes a cooperative iron–thiolate catalyst Cp*Fe­(1,2-Ph2PC6H4S)­(NCMe) (Cp*– = C5Me5 –, [1(NCMe)]) for regioselective hydroboration of aryl epoxide by pinacolborane (HBpin). The critical catalytic step involves the direct addition of epoxide to the catalyst rather than activation of the B–H bond of HBpin. Through iron–thiolate cooperation, [1(NCMe)] opens the aryl epoxide rings affording ferrous–alkoxide compounds. Notably, the ferrous–alkoxide intermediate (4) was structurally characterized after its isolation from the reaction of [1(NCMe)] with trans-2,3-diphenyloxirane. The more Lewis acidic hydroboranes such as H3B·THF and 9-BBN (BBN = bora­bicyclo­nonane) can also be captured by [1(NCMe)]. The resulting iron–borane adducts [1H­(BH2)] and [1H­(BBN)] feature an agnostic Fe···B–H interaction. DFT calculations indicate that the addition of HBpin across the iron–thiolate sites is endergonic by 12.9 kcal/mol, whereas it is exergonic by 20.2 kcal/mol with BH3 and 4.6 kcal/mol with 9-BBN. Combining the experimental data with theoretical studies, a mechanism of the substrate activation by [1(NCMe)], followed by HBpin addition, is proposed for the catalysis.

The cadherin EGF LAG seven-pass G-type receptors (CELSRs) are a special subgroup of adhesion G protein-coupled receptors (GPCRs), which are pivotal regulators of many biological processes such as neuronal/endocrine cell differentiation, vessel valve formation and the control of planar cell polarity during embryonic development. All three members of the CELSR family (CELSR1-3) have large ecto-domains that form homophilic interactions and encompass more than 2,000 amino acids. Mutations in the ecto-domain or other gene locations of CELSRs are associated with neural tube defects (NTDs) and other diseases in humans. Celsr knockout (KO) animals have many developmental defects. Therefore, specific agonists or antagonists of CELSR members may have therapeutic potential. Although significant progress has been made regarding the functions and biochemical properties of CELSRs, our knowledge of these receptors is still lacking, especially considering that they are broadly distributed but have few characterized functions in a limited number of tissues. The dynamic activation and inactivation of CELSRs and the presence of endogenous ligands beyond homophilic interactions remain elusive, as do the regulatory mechanisms and downstream signaling of these receptors. Given this motivation, future studies with more advanced cell biology or biochemical tools, such as conditional KO mice, may provide further insights into the mechanisms underlying CELSR function, laying the foundation for the design of new CELSR-targeted therapeutic reagents.

Seminiferous tubules (STs) in the mammalian testes are connected to the rete testis (RT) via a Sertoli valve (SV). Spermatozoa produced in the STs are released into the tubular luminal fluid and passively transported through the SV into the RT. However, the physiological functions of the RT and SV remain unclear. Here, we identified the expression of Sox17 in RT epithelia. The SV valve was disrupted before puberty in RT-specific Sox17 conditional knockout (Sox17-cKO) male mice. This induced a backflow of RT fluid into the STs, which caused aberrant detachment of immature spermatids. RT of Sox17-cKO mice had reduced expression levels of various growth factor genes, which presumably support SV formation. When transplanted next to the Sox17+ RT, Sertoli cells of Sox17-cKO mice reconstructed the SV and supported proper spermiogenesis in the STs. This study highlights the novel and unexpected modulatory roles of the RT in SV valve formation and spermatogenesis in mouse testes, as a downstream action of Sox17.

Integrins are adhesion receptors for components of the extracellular matrix (ECMs) that regulate multiple cellular functions, such as migration, invasion, proliferation, and survival by mediating bidirectional signal transmission. Even though many proteins have been reported to associate with integrins both on and in cells, systemic analyses of the adhesome have not been carried out. In previous studies, we identified proteins associating with a membrane-type protease, MT1-MMP, using nano-flow liquid chromatography/tandem mass spectrometry (nano-LC/MS/MS) of associated proteins prepared by optimized conditions for cell lysis and purification. Since integrins were identified as MT1-MMP-associated proteins, we next applied this method to analyze integrin-associated proteins. In this study, we expressed integrin α2 fused at the C terminus to a FLAG peptide in HT1080 cells. Cells stably expressing the chimeric protein were lysed with 1% Brij-98 and affinity purified using anti-FLAG antibody. Integrin β1 co-purified with integrin α2 confirming the specificity of the purification procedure. Analysis of the purified mixture by nano-LC/MS/MS identified 70 proteins. Nineteen of these were membrane proteins, including adhesion proteins, receptors, transporters, proteinases, and ion-channel receptors, and the balance were cytoplasmic. Interestingly, eight of the proteins had previously been shown to associate with MT1-MMP. We believe the present study provides a platform to facilitate the study of the mechanisms of cell adhesion, migration, and invasion.

Traumatic brain injury (TBI) is a worldwide public health concern without major therapeutic breakthroughs over the past decades. Developing effective treatment options and improving the prognosis of TBI depends on a better understanding of the mechanisms underlying TBI. This study performed a comprehensive analysis of 15 RNA expression datasets of rat TBIs from the GEO database. By integrating the results from the various analyses, this study investigated the biological processes, pathways, and cell types associated with TBI and explored the activity of these cells during various TBI phases. The results showed the response to cytokine, inflammatory response, bacteria-associated response, metabolic and biosynthetic processes, and pathways of neurodegeneration to be involved in the pathogenesis of TBI. The cellular abundance of microglia, perivascular macrophages (PM), and neurons were found to differ after TBI and at different times postinjury. In conclusion, immune- and inflammation-related pathways, as well as pathways of neurodegeneration, are closely related to TBI. Microglia, PM, and neurons are thought to play roles in TBI with different activities that vary by phase of TBI.