Making Education Work For Latinas in the U.S.

This study examines the existing knowledge base about promoting Latina educational success, defined as completing high school and then going on to secure a college degree. It also adds to existing research by examining two large data sets - one national, and one California-based for predictors of successful educational outcomes for representative samples of Latina youth who have recently been in high school and college. Finally, after identifying important predictors of success from the existing literature, and the examination of current data, the study incorporates case studies of seven young Latinas who illustrate pathways of women who are finding their way to educational success through high school, community college, and four year universities. Their stories provide a deeper understanding of the challenges that young Latinas encounter in our culture, as well as the promise they represent

Obstructive jaundice secondary to pancreatic head adenocarcinoma in a young teenage boy: a case report

<p>Abstract</p> <p>Introduction</p> <p>Pancreatic adenocarcinoma is extremely rare in childhood. We report a case of metastatic pancreatic adenocarcinoma in a 13-year-old boy, revealed by jaundice.</p> <p>Case presentation</p> <p>A 13-year-old Moroccan boy was admitted with obstructive jaundice to the children's Hospital of Rabat, Department of Pediatric Oncology. Laboratory study results showed a high level of total and conjugated bilirubin. Computerized tomography of the abdomen showed a dilatation of the intra-hepatic and extra-hepatic bile ducts with a tissular heterogeneous tumor of the head of the pancreas and five hepatic lesions. Biopsy of a liver lesion was performed, and a histopathological examination of the sample confirmed the diagnosis of metastatic ductal adenocarcinoma of the pancreas. Our patient underwent a palliative biliary derivation. After that, chemotherapy was administered (5-fluorouracil and epirubicin), however no significant response to treatment was noted and our patient died six months after diagnosis.</p> <p>Conclusion</p> <p>Malignant pancreatic tumors, especially ductal carcinomas, are exceedingly rare in the pediatric age group and their clinical features and treatment usually go unappreciated by most pediatric oncologists and surgeons.</p

Optimization of the IPP-bypass mevalonate pathway and fed-batch fermentation for the production of isoprenol in Escherichia coli.

Isoprenol (3-methyl-3-buten-1-ol) is a drop-in biofuel and a precursor for commodity chemicals. Biological production of isoprenol via the mevalonate pathway has been developed and optimized extensively in Escherichia coli, but high ATP requirements and isopentenyl diphosphate (IPP) toxicity have made it difficult to achieve high titer, yield, and large-scale production. To overcome these limitations, an IPP-bypass pathway was previously developed using the promiscuous activity of diphosphomevalonate decarboxylase, and enabled the production of isoprenol at a comparable yield and titer to the original pathway. In this study, we optimized this pathway, substantially improving isoprenol production. A titer of 3.7 g/L (0.14 g isoprenol per g glucose) was achieved in batch conditions using minimal medium by pathway optimization, and a further optimization of the fed-batch fermentation process enabled an isoprenol titer of 10.8 g/L (yield of 0.105 g/g and maximum productivity of 0.157 g L-1 h-1), which is the highest reported titer for this compound. The substantial increase in isoprenol titer via the IPP-bypass pathway in this study will facilitate progress toward commercialization

A 5-FU precursor designed to evade anabolic and catabolic drug pathways and activated by Pd chemistry in vitro and in vivo

We are grateful to the EPSRC (EP/N021134/1) for funding. T.L.B. thanks the CMVM of the University of Edinburgh (Principal's scholarship), and B.R.-R. thanks the EC (H2020MSCA-IF-2014-658833, ChemoBOOM) for financial support. A.U.-B. and D.J.B. thank Medical Research Scotland (PHD-1046-2016) for funding. We acknowledge support from the MRC Confidence in Concept scheme (MRC/CIC6/52) and EPSRC Impact Acceleration Account (PIII024).5-Fluorouracil (5-FU) is an antineoplastic antimetabolite that is widely administered to cancer patients by bolus injection, especially to those suffering from colorectal and pancreatic cancer. Because of its suboptimal route of administration and dose-limiting toxicities, diverse 5-FU prodrugs have been developed to confer oral bioavailability and increase the safety profile of 5-FU chemotherapy regimens. Our contribution to this goal is presented herein with the development of a novel palladium-activated prodrug designed to evade the metabolic machinery responsible for 5-FU anabolic activation and catabolic processing. The new prodrug is completely innocuous to cells and highly resistant to metabolization by primary hepatocytes and liver S9 fractions (the main metabolic route for 5-FU degradation), whereas it is rapidly converted into 5-FU in the presence of a palladium (Pd) source. In vivo pharmokinetic analysis shows the prodrug is rapidly and completely absorbed after oral administration and exhibits a longer half-life than 5-FU. In vivo efficacy studies in a xenograft colon cancer model served to prove, for the first time, that orally administered prodrugs can be locally converted to active drugs by intratumorally inserted Pd implants.UK Research & Innovation (UKRI) Engineering & Physical Sciences Research Council (EPSRC) EP/N021134/1CMVM of the University of EdinburghEuropean Commission European Commission Joint Research Centre H2020MSCA-IF-2014-658833Medical Research Scotland PHD-1046-2016UK Research & Innovation (UKRI) Medical Research Council UK (MRC) MRC/CIC6/52 UK Research & Innovation (UKRI)Engineering & Physical Sciences Research Council (EPSRC) PIII02

Genetical genomics: spotlight on QTL hotspots

No abstract available

Biopsy confirmation of metastatic sites in breast cancer patients:clinical impact and future perspectives

Determination of hormone receptor (estrogen receptor and progesterone receptor) and human epidermal growth factor receptor 2 status in the primary tumor is clinically relevant to define breast cancer subtypes, clinical outcome,and the choice of therapy. Retrospective and prospective studies suggest that there is substantial discordance in receptor status between primary and recurrent breast cancer. Despite this evidence and current recommendations,the acquisition of tissue from metastatic deposits is not routine practice. As a consequence, therapeutic decisions for treatment in the metastatic setting are based on the features of the primary tumor. Reasons for this attitude include the invasiveness of the procedure and the unreliable outcome of biopsy, in particular for biopsies of lesions at complex visceral sites. Improvements in interventional radiology techniques mean that most metastatic sites are now accessible by minimally invasive methods, including surgery. In our opinion, since biopsies are diagnostic and changes in biological features between the primary and secondary tumors can occur, the routine biopsy of metastatic disease needs to be performed. In this review, we discuss the rationale for biopsy of suspected breast cancer metastases, review issues and caveats surrounding discordance of biomarker status between primary and metastatic tumors, and provide insights for deciding when to perform biopsy of suspected metastases and which one (s) to biopsy. We also speculate on the future translational implications for biopsy of suspected metastatic lesions in the context of clinical trials and the establishment of bio-banks of biopsy material taken from metastatic sites. We believe that such bio-banks will be important for exploring mechanisms of metastasis. In the future,advances in targeted therapy will depend on the availability of metastatic tissue

Phenotypic and molecular characterization of Staphylococcus aureus isolates expressing low- and high-level mupirocin resistance in Nigeria and South Africa

<p>Abstract</p> <p>Background</p> <p>Mupirocin is a topical antimicrobial agent which is used for the treatment of skin and postoperative wound infections, and the prevention of nasal carriage of methicillin-resistant <it>Staphylococcus aureus </it>(MRSA). However, the prevalence of mupirocin resistance in <it>S. aureus</it>, particularly in MRSA, has increased with the extensive and widespread use of this agent in hospital settings. This study characterized low- and high-level mupirocin-resistant <it>S. aureus </it>isolates obtained from Nigeria and South Africa.</p> <p>Methods</p> <p>A total of 17 mupirocin-resistant <it>S. aureus </it>isolates obtained from two previous studies in Nigeria and South Africa, were characterized by antibiogram, PCR-RFLP of the coagulase gene and PFGE. High-level mupirocin resistant isolates were confirmed by PCR detection of the <it>mupA </it>gene. The genetic location of the resistance determinants was established by curing and transfer experiments.</p> <p>Results</p> <p>All the low-level mupirocin resistant isolates were MRSA and resistant to gentamicin, tetracycline and trimethoprim. PFGE identified a major clone in two health care institutions located in Durban and a health care facility in Pietermaritzburg, Greytown and Empangeni. Curing and transfer experiments indicated that high-level mupirocin resistance was located on a 41.1 kb plasmid in the South African strain (A15). Furthermore, the transfer of high-level mupirocin resistance was demonstrated by the conjugative transfer of the 41.1 kb plasmid alone or with the co-transfer of a plasmid encoding resistance to cadmium. The size of the mupirocin-resistance encoding plasmid in the Nigerian strain (35 IBA) was approximately 35 kb.</p> <p>Conclusion</p> <p>The emergence of mupirocin-resistant <it>S. aureus </it>isolates in Nigeria and South Africa should be of great concern to medical personnel in these countries. It is recommended that methicillin-susceptible <it>S. aureus </it>(MSSA) and MRSA should be routinely tested for mupirocin resistance even in facilities where the agent is not administered. Urgent measures, including judicious use of mupirocin, need to be taken to prevent clonal dissemination of the mupirocin/methicillin resistant <it>S. aureus </it>in KZN, South Africa and the transfer of the conjugative plasmid encoding high-level mupirocin resistance identified in this study.</p

Assisted evolution enables HIV-1 to overcome a high trim5α-imposed genetic barrier to rhesus macaque tropism

Diversification of antiretroviral factors during host evolution has erected formidable barriers to cross-species retrovirus transmission. This phenomenon likely protects humans from infection by many modern retroviruses, but it has also impaired the development of primate models of HIV-1 infection. Indeed, rhesus macaques are resistant to HIV-1, in part due to restriction imposed by the TRIM5α protein (rhTRIM5α). Initially, we attempted to derive rhTRIM5α-resistant HIV-1 strains using two strategies. First, HIV-1 was passaged in engineered human cells expressing rhTRIM5α. Second, a library of randomly mutagenized capsid protein (CA) sequences was screened for mutations that reduced rhTRIM5α sensitivity. Both approaches identified several individual mutations in CA that reduced rhTRIM5α sensitivity. However, neither approach yielded mutants that were fully resistant, perhaps because the locations of the mutations suggested that TRIM5α recognizes multiple determinants on the capsid surface. Moreover, even though additive effects of various CA mutations on HIV-1 resistance to rhTRIM5α were observed, combinations that gave full resistance were highly detrimental to fitness. Therefore, we employed an 'assisted evolution' approach in which individual CA mutations that reduced rhTRIM5α sensitivity without fitness penalties were randomly assorted in a library of viral clones containing synthetic CA sequences. Subsequent passage of the viral library in rhTRIM5α-expressing cells resulted in the selection of individual viral species that were fully fit and resistant to rhTRIM5α. These viruses encoded combinations of five mutations in CA that conferred complete or near complete resistance to the disruptive effects of rhTRIM5α on incoming viral cores, by abolishing recognition of the viral capsid. Importantly, HIV-1 variants encoding these CA substitutions and SIVmac239 Vif replicated efficiently in primary rhesus macaque lymphocytes. These findings demonstrate that rhTRIM5α is difficult to but not impossible to evade, and doing so should facilitate the development of primate models of HIV-1 infection

Mammalian interspecies substitution of immune modulatory alleles by genome editing

We describe a fundamentally novel feat of animal genetic engineering: the precise and efficient substitution of an agronomic haplotype into a domesticated species. Zinc finger nuclease in-embryo editing of the RELA locus generated live born domestic pigs with the warthog RELA orthologue, associated with resilience to African Swine Fever. The ability to efficiently achieve interspecies allele introgression in one generation opens unprecedented opportunities for agriculture and basic research