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Fibrolamellar hepatocellular carcinoma (FLHCC) is a rare liver malignancy in adolescents and young adults. Surgery is the mainstay of therapy for primary and metastatic disease. Most patients relapse, with development of both local and distant metastases. Brain metastases from solid tumors are rare in the pediatric and young adult population. Here, we document three patients with brain metastases from FLHCC, confirmed by histology and molecular characterization of the chimeric fusion DNAJB1-PRKACA, each necessitating neurosurgical intervention. These observations highlight the ability of FLHCC to metastasize to the brain and suggest the need for surveillance neuroimaging for patients with advanced-stage disease.

Median arcuate ligament (MAL) syndrome is a rare and poorly known cause of abdominal pain. MAL narrows the celiac artery (CA), resulting in true distal aneurysms, including pancreaticoduodenal artery (PDA) aneurysms. These aneurysms often have an aggressive course, as rupture can result in hemorrhagic shock. CT scan appears to be the most effective investigation for the diagnosis of PDA aneurysms and may reveal possible celiac artery compression. In this series, we describe four cases of PDA aneurysm: two ruptured aneurysms treated by an endovascular procedure and two non-ruptured aneurysms treated by surgery. It was also decided to treat CA stenosis in three of the four patients based on the clinical presentation (ruptured or non-ruptured) and the presence of peripancreatic collateral vessels on imaging. This strategy contrasts with the approach commonly reported in the literature, in which MAL section is mandatory due to the high risk of ischemia rather than the potential risk of recurrent aneurysm. Medical teams should be aware of this disease to improve diagnosis and patient management.

A search is presented for the production of vector-like quark pairs, T (T) over bar or Y (Y) over bar, with electric charge of 2/3(T) or -4/3(Y), in proton-proton collisions at root s= 13 TeV. The data were collected by the CMS experiment at the LHC in 2016 and correspond to an integrated luminosity of 35.8 fb(-1). The T and Y quarks are assumed to decay exclusively to a W boson and a b quark. The search is based on events with a single isolated electron or muon, large missing transverse momentum, and at least four jets with large transverse momenta. In the search, a kinematic reconstruction of the final state observables is performed, which would permit a signal to be detected as a narrow mass peak (approximate to 7% resolution). The observed number of events is consistent with the standard model prediction. Assuming strong pair production of the vector-like quarks and a 100% branching fraction to bW, a lower limit of 1295 GeV at 95% confidence level is set on the T and Y quark masses. (c) 2018 The Author(s). Published by Elsevier B.V.

Patients with high-grade serous ovarian carcinoma ( HGSC) exhibit poor 5-year survival rates, which may be significantly improved by early-stage detection. The U.S. Food and Drug Administration-approved biomarkers for HGSC-CA-125 (cancer antigen 125) and HE4 (human epididymis protein 4)-do not generally appear at detectable levels in the serum until advanced stages of the disease. An implantable device placed proximal to disease sites, such as in or near the fallopian tube, ovary, uterine cavity, or peritoneal cavity, may constitute a feasible strategy to improve detection of HGSC. We engineered a prototype optical sensor composed of an antibody-functionalized carbon nanotube complex, which responds quantitatively to HE4 via modulation of the nanotube optical bandgap. The complexes measured HE4 with nanomolar sensitivity to differentiate disease from benign patient biofluids. The sensors were implanted into four models of ovarian cancer, within a semipermeable membrane, enabling the optical detection of HE4 within the live animals. We present the first in vivo optical nanosensor capable of noninvasive cancer biomarker detection in orthotopic models of disease.

Immunity to pathogens and tolerance to self are cardinal features of immune systems. Immunological specificity is encoded by receptors expressed on the surface of lymphocytes that are generated through random assembly of variable, diversity, and joining (VDJ) gene segments during B and T lymphocyte development. In addition, B lymphocytes further diversify this initial repertoire through somatic hypermutation of antibody genes in germinal centers (transient structures that form in lymphoid organs in which high-affinity antibodies arise). On page 223 of this issue, Burnett et al. (1) devise a strategy to track the fate of self-reactive B cells in germinal centers elicited by a foreign antigen that structurally mimics a self-antigen (antigen mimicry). The authors provide evidence that hypermutation of antibody genes in germinal centers can repair self-reactive antibodies. These results have implications for how broadly neutralizing antibodies to HIV-1 may be formed.

Increasing our understanding of Earth's biodiversity and responsibly stewarding its resources are among the most crucial scientific and social challenges of the new millennium. These challenges require fundamental new knowledge of the organization, evolution, functions, and interactions among millions of the planet's organisms. Herein, we present a perspective on the Earth BioGenome Project (EBP), a moonshot for biology that aims to sequence, catalog, and characterize the genomes of all of Earth's eukaryotic biodiversity over a period of 10 years. The outcomes of the EBP will inform a broad range of major issues facing humanity, such as the impact of climate change on biodiversity, the conservation of endangered species and ecosystems, and the preservation and enhancement of ecosystem services. We describe hurdles that the project faces, including data-sharing policies that ensure a permanent, freely available resource for future scientific discovery while respecting access and benefit sharing guidelines of the Nagoya Protocol. We also describe scientific and organizational challenges in executing such an ambitious project, and the structure proposed to achieve the project's goals. The far-reaching potential benefits of creating an open digital repository of genomic information for life on Earth can be realized only by a coordinated international effort.

Midaortic syndrome (MAS) is a rare cause of severe childhood hypertension characterized by narrowing of the abdominal aorta in children and is associated with extensive vascular disease. It may occur as part of a genetic syndrome, such as neurofibromatosis, or as consequence of a pathological inflammatory disease. However, most cases are considered idiopathic. We hypothesized that in a high percentage of these patients, a monogenic cause of disease may be detected by evaluating whole exome sequencing data for mutations in 1 of 38 candidate genes previously described to cause vasculopathy. We studied a cohort of 36 individuals from 35 different families with MAS by exome sequencing. In 15 of 35 families (42.9%), we detected likely causal dominant mutations. In 15 of 35 (42.9%) families with MAS, whole exome sequencing revealed a mutation in one of the genes previously associated with vascular disease (NF1, JAG1, ELN, GATA6, and RNF213). Ten of the 15 mutations have not previously been reported. This is the first report of ELN, RNF213, or GATA6 mutations in individuals with MAS. Mutations were detected in NF1 (6/15 families), JAG1 (4/15 families), ELN (3/15 families), and one family each for GATA6 and RNF213. Eight individuals had syndromic disease and 7 individuals had isolated MAS. Whole exome sequencing can provide conclusive molecular genetic diagnosis in a high fraction of individuals with syndromic or isolated MAS. Establishing an etiologic diagnosis may reveal genotype/phenotype correlations for MAS in the future and should, therefore, be performed routinely in MAS.

Hybridization in ants can have consequences different from those observed in most other species, with many of the potential deleterious effects being mitigated due to haplodiploidy and eusociality. In some species where colonies are either headed by multiple queens or single queens that mate with many males, hybridization is associated with genetic caste determination, where hybrids develop into workers and purebred individuals develop into queens. A previous study suggested that hybridization occurs between two Dorylus army ant species with multiply mated queens. However, the extent and exact pattern of hybridization have remained unclear, and its possible effect on caste determination has not been investigated. In this study, we aimed to determine the extent and direction of hybridization by measuring how frequently hybrids occur in colonies of both species, and to investigate the possibility of genetic caste determination. We show that hybridization is bidirectional and occurs at equal rates in both species. Hybrid workers make up only 1-2% of the population, and successful interspecific matings represent approximately 2% of all matings in both species. This shows that, although interspecific matings that give rise to worker offspring occur regularly, they are much rarer than intraspecific mating. Finally, we find no evidence of an association between hybridization and genetic caste determination in this population. This means that genetic caste determination is not a necessary outcome of hybridization in ants, even in species where queens mate with multiple males.

Immunodeficient mice transplanted with human cell populations or tissues, also known as human immune system (HIS) mice, have emerged as an important and versatile tool for the in vivo study of human immunodeficiency virus-type 1 (HIV-1) pathogenesis, treatment, and persistence in various biological compartments. Recent work in HIS mice has demonstrated their ability to recapitulate critical aspects of human immune responses to HIV-1 infection, and such studies have informed our knowledge of HIV-1 persistence and latency in the context of combination antiretroviral therapy. The central nervous system (CNS) is a unique, immunologically privileged compartment susceptible to HIV-1 infection, replication, and immune-mediated damage. The unique, neural, and glia-rich cellular composition of this compartment, as well as the important role of infiltrating cells of the myeloid lineage in HIV-1 seeding and replication makes its study of paramount importance, particularly in the context of HIV-1 cure research. Current work on the replication and persistence of HIV-1 in the CNS, as well as cells of the myeloid lineage thought to be important in HIV-1 infection of this compartment, has been aided by the expanded use of these HIS mouse models. In this review, we describe the major HIS mouse models currently in use for the study of HIV-1 neuropathogenesis, recent insights from the field, limitations of the available models, and promising advances in HIS mouse model development.