development of multiple malignant neoplasms without PTEN germline mutations, we confirmed the function of WWP1 as a cancer-susceptibility gene through direct aberrant regulation of the PTEN-PI3K signaling axis. (Funded by the National Institutes of Health and others.).A key goal of whole-genome sequencing (WGS) for human genetics studies is to interrogate all forms of variation, including single nucleotide variants (SNV), small insertion/deletion (indel) variants and structural variants (SV). However, tools and resources for the study of SV have lagged behind those for smaller variants. Here, we used a scalable pipeline22 to map and characterize SV in 17,795 deeply sequenced human genomes. We publicly release site-frequency data to create the largest WGS-based SV resource to date. On average, individuals carry 2.9 rare SVs that alter coding regions, affecting the dosage or structure of 4.2 genes and accounting for 4.0-11.2% of rare high-impact coding alleles. Based on a computational model, we estimate that SVs account for 17.2% of rare alleles genome-wide with predicted deleterious effects equivalent to loss-of-function coding alleles; approximately 90% of such SVs are non-coding deletions (mean 19.1 per genome). We report 158,991 ultra-rare SVs and show that around 2% of individuals carry ultra-rare megabase-scale SVs, nearly half of which are balanced or complex rearrangements. Finally, we infer the dosage sensitivity of genes and non-coding elements, revealing trends related to element class and conservation. This work will help guide SV analysis and interpretation in the era of WGS.The emergence of the coronavirus disease 2019 (COVID-19) heralded a new era in the cross-species transmission of severe respiratory illness leading to rapid spread in mainland China and around the world with a case fatality rate of 2.3% in China and 1.8-7.2% outside China (Wu & McGoogan, 2019; Centers for Disease Control and Prevention, 2020; Onder Rezza, & Brusaferro, 2020; World Health Organization, 2020). As of May 15, 2020, a total of 4,338,658 confirmed cases of COVID-19 and 297,119 death cases have been documented globally (World Health Organization, 2020). Several strategies have been adopted to contain the outbreak including classic infection-control and public health measures, nevertheless these measures may not be effective for tackling the scale of COVID-19.Background Solid organ transplant (SOT) recipients may be at risk for severe COVID-19. Data on the clinical course of COVID-19 in immunosuppressed patients are limited and the effective treatment strategy for these patients is unknown. Methods We describe our institutional experience with COVID-19 in SOT. Demographic, clinical and treatment data were extracted from the electronic patient files. Results A total of 23 SOT transplant recipients suffering from COVID-19 were identified (n = 3 heart; n =15 kidney; n = 1 kidney-after-heart; n = 3 lung and n = 1 liver transplant recipient). The presenting symptoms were similar to non-immunocompromised patients Eighty-three percent (19/23) of the patients required hospitalization but only two of these were transferred to the intensive care unit. Five patients died from COVID-19; all had high Clinical Frailty scores. In four of these patients, mechanical ventilation was deemed futile. In 57% of patients, the immunosuppressive therapy was not changed and only 3 patients were treated with chloroquine. Most patients recovered without experimental anti-viral therapy. Conclusions Modification of the immunosuppressive regimen alone could be a therapeutic option for SOT recipients suffering from moderate to severe COVID-19. Pre-existent frailty is associated with death from COVID-19.Small GTPases of the RAS and RHO families are related signaling proteins that, when activated by growth factors or by mutation, drive oncogenic processes. While activating mutations in KRAS, NRAS, and HRAS genes have long been recognized and occur in many types of cancer, similar mutations in RHO family genes, such as RAC1 and RHOA, have only recently been detected as the result of extensive cancer genome-sequencing efforts and are linked to a restricted set of malignancies. In this review, we focus on the role of RAC1 signaling in malignant melanoma, emphasizing recent advances that describe how this oncoprotein alters melanocyte proliferation and motility and how these findings might lead to new therapeutics in RAC1-mutant tumors.Three freshwater scuticociliates, Apouronema harbinensis gen. nov. spec. nov., Cyclidium vorax spec. nov., and C. glaucomaMüller, 1773, collected from rivers in Hulan District, Harbin, northeastern China, were investigated using morphological and phylogenetic criteria. Apouronema gen. nov., assigned to the family Uronematidae, is mainly distinguished from the other genera of the family by its paroral membrane extending anteriorly to the middle of membranelle 1. Apouronema harbinensis spec. nov. is defined by body size in vivo about 45-55 × 20-25 μm, buccal field about 70-80% of cell length; 12 or 13 somatic kineties; membranelle 1 having two rows, with 16-18 basal bodies in each kinety; membranelle 2 and membranelle 3 both having two rows each; scutica X-shaped with five pairs of basal bodies.  https://www.selleckchem.com/products/ABT-888.html  Cyclidium vorax spec. nov. is characterized by the following features body size 35-40 × 18-20 μm in vivo; 9 or 10 somatic kineties; membranelle 1 having two longitudinal rows, much shorter than M2; M2 triangle-shaped. The phylogenetic analyses show that (1) Apouronema clustered in the Uronematidae clade, and grouped with genera Uronemita and Uronema; (2) Cyclidium vorax spec. nov. grouped with C. glaucoma and C. sinicum, which supports the assignment of the new species to the genus Cyclidium; (3) Cyclidium remains non-monophyletic with the addition of the new sequence.Chemoresistance is a major factor driving tumour relapse and the high rates of cancer-related deaths. Understanding how cancer cells overcome chemotherapy-induced cell death is critical in promoting patient survival. One emerging mechanism of chemoresistance is the tumour cell secretome (TCS), an array of protumorigenic factors released by tumour cells. Chemotherapy exposure can also alter the composition of the TCS, known as therapy-induced TCS, and can promote tumour relapse and the formation of an immunosuppressive tumour microenvironment (TME). Here, we outline how the TCS can protect cancer cells from chemotherapy-induced cell death. We also highlight recent evidence describing how therapy-induced TCS can impact cancer stem cell (CSC) expansion and tumour-associated immune cells to enable tumour regrowth and antitumour immunity.