Chromophobe renal cell carcinoma (ChRCC) accounts for 5% to 7% of all renal cell carcinomas. It was thought for many years that ChRCC exhibits a hypodiploid genome. Recent studies using advanced molecular genetics techniques have shown more complex and heterogenous pattern with frequent chromosomal gains. Historically, multiple losses of chromosomes 1, 2, 6, 10, 13, 17, and 21 have been considered a genetic hallmark of ChRCC, both for classic and eosinophilic ChRCC variants. In the last 2 decades, multiple chromosomal gains in ChRCCs have also been documented, depicting a considerably broader genetic spectrum than previously thought. Studies of rare morphologic variants including ChRCC with pigmented microcystic adenomatoid/multicystic growth, ChRCC with neuroendocrine differentiation, ChRCC with papillary architecture, and renal oncocytoma-like variants also showed variable chromosomal numerical aberrations, including multiple losses (common), gains (less common), or chromosomal changes overlapping with renal oncocytoma. Although not the focus of the review, The Cancer Genome Atlas (TCGA) data in ChRCC show TP53, PTEN, and CDKN2A to be the most mutated genes. Given the complexity of molecular genetic alterations in ChRCC, this review analyzed the existing published data, aiming to present a comprehensive up-to-date survey of the chromosomal abnormalities in classic ChRCC and its variants. The potential role of chromosomal numerical aberrations in the differential diagnostic evaluation may be limited, potentially owing to its high variability.COVID-19 spans a wide range of symptoms, sometimes with profound immune system involvement. How immune cell subsets change during the disease course and with disease severity needs further study. While myeloid cells have been shown to initiate and maintain responses to pneumonia and lung inflammation, often playing a role in resolution, their involvement with COVID-19 remains unknown. In this issue of the JCI, Sánchez-Cerrillo and Landete et al. investigated DCs and monocytes from blood and bronchial secretions of patients with varying COVID-19 severity and with healthy controls. The authors conclude that circulating monocytes and DCs migrate from the blood into the inflamed lungs. While sampling differences in sex, collection timing, bacteria/fungal infection, and corticosteroid treatment limit interpretation, we believe that reprogramming monocyte or macrophages by targeting immunometabolism, epigenetics, or the cytokine milieu holds promise in resolving lung inflammation associated with COVID-19.CXCL13 is the cognate chemokine agonist of CXCR5, a class A G-protein-coupled receptor (GPCR) that is essential for proper humoral immune responses. Using a `methionine scanning' mutagenesis method on the N-terminus of CXCL13, which is the chemokine signaling region, it was shown that minor length alterations and side-chain substitutions still result in CXCR5 activation. This observation indicates that the orthosteric pocket of CXCR5 can tolerate these changes without severely affecting the activity. The introduction of bulk on the ligand was well tolerated by the receptor, whereas a loss of contacts was less tolerated. Furthermore, two crystal structures of CXCL13 mutants were solved, both of which represent the first uncomplexed structures of the human protein. These structures were stabilized by unique interactions formed by the N-termini of the ligands, indicating that CXCL13 exhibits substantial N-terminal flexibility while the chemokine core domain remains largely unchanged. Additionally, it was observed that CXCL13 harbors a large degree of flexibility in the C-terminal extension of the ligand. Comparisons with other published structures of human and murine CXCL13 validate the relative rigidity of the core domain as well as the N- and C-terminal mobilities. Collectively, these mutants and their structures provide the field with additional insights into how CXCL13 interacts with CXCR5.The structure and function of proteins are strongly affected by the surrounding solvent water, for example through hydrogen bonds and the hydrophobic effect. These interactions depend not only on the position, but also on the orientation, of the water molecules around the protein. Therefore, it is often vital to know the detailed orientations of the surrounding ordered water molecules. Such information can be obtained by neutron crystallography. However, it is tedious and time-consuming to determine the correct orientation of every water molecule in a structure (there are typically several hundred of them), which is presently performed by manual evaluation. Here, a method has been developed that reliably automates the orientation of a water molecules in a simple and relatively fast way. Firstly, a quantitative quality measure, the real-space correlation coefficient, was selected, together with a threshold that allows the identification of water molecules that are oriented. Secondly, the refinement procedure was optimized by varying the refinement method and parameters, thus finding settings that yielded the best results in terms of time and performance. MYCMI-6 mouse It turned out to be favourable to employ only the neutron data and a fixed protein structure when reorienting the water molecules. Thirdly, a method has been developed that identifies and reorients inadequately oriented water molecules systematically and automatically. The method has been tested on three proteins, galectin-3C, rubredoxin and inorganic pyrophosphatase, and it is shown that it yields improved orientations of the water molecules for all three proteins in a shorter time than manual model building. It also led to an increased number of hydrogen bonds involving water molecules for all proteins.In eukaryotes, numerous fundamental processes are controlled by the WAVE regulatory complex (WRC) that regulates cellular actin polymerization, crucial for cell motility, cell-cell adhesion and epithelial differentiation. Actin assembly is triggered by interaction of the small GTPase Rac1 with CYFIP1, a key component of the WRC. Previously known as FAM49B, CYRI-B is a protein that is highly conserved across the Eukaryota and has recently been revealed to be a key regulator of Rac1 activity. Mutation of CYRI-B or alteration of its expression therefore leads to altered actin nucleation dynamics, with impacts on lamellipodia formation, cell migration and infection by intracellular pathogens. In addition, knockdown of CYRI-B expression in cancer cell lines results in accelerated cell proliferation and invasiveness. Here, the structure of Rhincodon typus (whale shark) CYRI-B is presented, which is the first to be reported of any CYRI family member. Solved by X-ray crystallography, the structure reveals that CYRI-B comprises three distinct α-helical subdomains and is highly structurally related to a conserved domain present in CYFIP proteins.