A Latent Class Analysis of Community Violence Exposure and Peer Delinquency in African American Adolescents

Aims Person-based analyses have demonstrated wide variability among the levels of exposure to community violence (ECV) experienced by youth in disadvantaged communities. In addition, social network research has found that violence victimization tends to occur primarily among a small social group, demonstrating that levels of peer delinquency may be a factor that distinguishes among youth who experience high and low levels of ECV. Methods The current study utilized latent class analysis to examine profiles of ECV and peer delinquency in a sample of 618 African American adolescents (54.7% female; mean age = 15.8, SD = 1.41), and the relationship these profiles have to adaptive and maladaptive outcomes. Results Results demonstrated that levels of ECV and peer delinquency vary significantly among these youth, and profile membership predicts levels of delinquency, aggression, future orientation, and self-esteem. Conclusion Research and clinical implications are discussed

Cyclic AMP signaling in Dictyostelium promotes the translocation of the copine family of calcium-binding proteins to the plasma membrane

Abstract Background Copines are calcium-dependent phospholipid-binding proteins found in many eukaryotic organisms and are thought to be involved in signaling pathways that regulate a wide variety of cellular processes. Copines are characterized by having two C2 domains at the N-terminus accompanied by an A domain at the C-terminus. Six copine genes have been identified in the Dictyostelium genome, cpnA – cpnF. Results Independent cell lines expressing CpnA, CpnB, CpnC, CpnE, or CpnF tagged with green fluorescent protein (GFP) were created as tools to study copine protein membrane-binding and localization. In general, the GFP-tagged copine proteins appeared to localize to the cytoplasm in live cells. GFP-tagged CpnB, CpnC, and CpnF were also found in the nucleus. When cells were fixed or when live cells were treated with calcium ionophore, the GFP-tagged copine proteins were found associated with the plasma membrane and vesicular organelles. When starved Dictyostelium cells were stimulated with cAMP, which causes a transitory increase in calcium concentration, all of the copines translocated to the plasma membrane, but with varying magnitudes and on and off times, suggesting each of the copines has distinct calcium-sensitivities and/or membrane-binding properties. In vitro membrane binding assays showed that all of the GFP-tagged copines pelleted with cellular membranes in the presence of calcium; yet, each copine displayed distinct calcium-independent membrane-binding in the absence of calcium. A lipid overlay assay with purified GFP-tagged copine proteins was used to screen for specific phospholipid-binding targets. Similar to other proteins that contain C2 domains, GFP-tagged copines bound to a variety of acidic phospholipids. CpnA, CpnB, and CpnE bound strongly to PS, PI(4)P, and PI(4,5)P2, while CpnC and CpnF bound strongly to PI(4)P. Conclusions Our studies show that the Dictyostelium copines are soluble cytoplasmic and nuclear proteins that have the ability to bind intracellular membranes. Moreover, copines display different membrane-binding properties suggesting they play distinct roles in the cell. The transient translocation of copines to the plasma membrane in response to cAMP suggests copines may play a specific role in chemotaxis signaling.https://deepblue.lib.umich.edu/bitstream/2027.42/145158/1/12860_2018_Article_160.pd

Cyclic AMP signaling in Dictyostelium promotes the translocation of the copine family of calcium-binding proteins to the plasma membrane

Abstract Background Copines are calcium-dependent phospholipid-binding proteins found in many eukaryotic organisms and are thought to be involved in signaling pathways that regulate a wide variety of cellular processes. Copines are characterized by having two C2 domains at the N-terminus accompanied by an A domain at the C-terminus. Six copine genes have been identified in the Dictyostelium genome, cpnA – cpnF. Results Independent cell lines expressing CpnA, CpnB, CpnC, CpnE, or CpnF tagged with green fluorescent protein (GFP) were created as tools to study copine protein membrane-binding and localization. In general, the GFP-tagged copine proteins appeared to localize to the cytoplasm in live cells. GFP-tagged CpnB, CpnC, and CpnF were also found in the nucleus. When cells were fixed or when live cells were treated with calcium ionophore, the GFP-tagged copine proteins were found associated with the plasma membrane and vesicular organelles. When starved Dictyostelium cells were stimulated with cAMP, which causes a transitory increase in calcium concentration, all of the copines translocated to the plasma membrane, but with varying magnitudes and on and off times, suggesting each of the copines has distinct calcium-sensitivities and/or membrane-binding properties. In vitro membrane binding assays showed that all of the GFP-tagged copines pelleted with cellular membranes in the presence of calcium; yet, each copine displayed distinct calcium-independent membrane-binding in the absence of calcium. A lipid overlay assay with purified GFP-tagged copine proteins was used to screen for specific phospholipid-binding targets. Similar to other proteins that contain C2 domains, GFP-tagged copines bound to a variety of acidic phospholipids. CpnA, CpnB, and CpnE bound strongly to PS, PI(4)P, and PI(4,5)P2, while CpnC and CpnF bound strongly to PI(4)P. Conclusions Our studies show that the Dictyostelium copines are soluble cytoplasmic and nuclear proteins that have the ability to bind intracellular membranes. Moreover, copines display different membrane-binding properties suggesting they play distinct roles in the cell. The transient translocation of copines to the plasma membrane in response to cAMP suggests copines may play a specific role in chemotaxis signaling.https://deepblue.lib.umich.edu/bitstream/2027.42/145158/1/12860_2018_Article_160.pd

Dissecting X-ray-emitting Gas around the Center of our Galaxy

Most supermassive black holes (SMBHs) are accreting at very low levels and are difficult to distinguish from the galaxy centers where they reside. Our own Galaxy's SMBH provides a uniquely instructive exception, and we present a close-up view of its quiescent X-ray emission based on 3 mega-second of Chandra observations. Although the X-ray emission is elongated and aligns well with a surrounding disk of massive stars, we can rule out a concentration of low-mass coronally active stars as the origin of the emission based on the lack of predicted Fe Kalpha emission. The extremely weak H-like Fe Kalpha line further suggests the presence of an outflow from the accretion flow onto the SMBH. These results provide important constraints for models of the prevalent radiatively inefficient accretion state.Comment: 18 pages, 5 PDF figures, pdflatex format; Final version, published in Scienc

Ficus insipida subsp. insipida (Moraceae) reveals the role of ecology in the phylogeography of widespread Neotropical rain forest tree species

Aim: To examine the phylogeography of Ficus insipida subsp. insipida in order to investigate patterns of spatial genetic structure across the Neotropics and within Amazonia. Location: Neotropics. Methods: Plastid DNA (trnH-psbA; 410 individuals from 54 populations) and nuclear ribosomal internal transcribed spacer (ITS; 85 individuals from 27 populations) sequences were sampled from Mexico to Bolivia, representing the full extent of the taxon's distribution. Divergence of plastid lineages was dated using a Bayesian coalescent approach. Genetic diversity was assessed with indices of haplotype and nucleotide diversities, and genetic structure was examined using spatial analysis of molecular variance (SAMOVA) and haplotype networks. Population expansion within Amazonia was tested using neutrality and mismatch distribution tests. Results: trnH-psbA sequences yielded 19 haplotypes restricted to either Mesoamerica or Amazonia; six haplotypes were found among ITS sequences. Diversification of the plastid DNA haplotypes began c. 14.6 Ma. Haplotype diversity for trnH-psbA was higher in Amazonia. Seven genetically differentiated SAMOVA groups were described for trnH-psbA, of which two were also supported by the presence of unique ITS sequences. Population expansion was suggested for both markers for the SAMOVA group that contains most Amazonian populations. Main conclusions: Our results show marked population genetic structure in F. insipida between Mesoamerica and Amazonia, implying that the Andes and seasonally dry areas of northern South America are eco-climatic barriers to its migration. This pattern is shared with other widespread pioneer species affiliated to wet habitats, indicating that the ecological characteristics of species may impact upon large-scale phylogeography. Ficus insipida also shows genetic structure in north-western Amazonia potentially related to pre-Pleistocene historical events. In contrast, evident population expansion elsewhere in Amazonia, in particular the presence of genetically uniform populations across the south-west, indicate recent colonization. Our findings are consistent with palaeoecological data that suggest recent post-glacial expansion of Amazonian forests in the south

A regional informatics platform for coordinated antibiotic resistant infection tracking, alerting and prevention

Background. We developed and assessed the impact of a patient registry and electronic admission notification system relating to regional antimicrobial resistance (AMR) on regional AMR infection rates over time. We conducted an observational cohort study of all patients identified as infected or colonized with methicillin-resistant Staphylococcus aureus (MRSA) and/or vancomycin-resistant enterococci (VRE) on at least 1 occasion by any of 5 healthcare systems between 2003 and 2010. The 5 healthcare systems included 17 hospitals and associated clinics in the Indianapolis, Indiana, region. Methods. We developed and standardized a registry of MRSA and VRE patients and created Web forms that infection preventionists (IPs) used to maintain the lists. We sent e-mail alerts to IPs whenever a patient previously infected or colonized with MRSA or VRE registered for admission to a study hospital from June 2007 through June 2010. Results. Over a 3-year period, we delivered 12 748 e-mail alerts on 6270 unique patients to 24 IPs covering 17 hospitals. One in 5 (22%–23%) of all admission alerts was based on data from a healthcare system that was different from the admitting hospital; a few hospitals accounted for most of this crossover among facilities and systems. Conclusions. Regional patient registries identify an important patient cohort with relevant prior antibiotic-resistant infection data from different healthcare institutions. Regional registries can identify trends and interinstitutional movement not otherwise apparent from single institution data. Importantly, electronic alerts can notify of the need to isolate early and to institute other measures to prevent transmission

A study of ovarian cancer patients treated with dose-intensive chemotherapy supported with peripheral blood progenitor cells mobilised by filgrastim and cyclophosphamide.

We have shown that large numbers of haemopoietic progenitor cells are mobilised into the blood after filgrastim [granulocyte colony-stimulating factor (G-CSF)] alone and filgrastim following cyclophosphamide chemotherapy in previously untreated patients with ovarian cancer. These cells may be used to provide safe and effective haemopoietic rescue following dose-intensive chemotherapy. Using filgrastim alone (10 micrograms kg-1), the apheresis harvest contained a median CFU-GM count of 45 x 10(4) kg-1 and 2 x 10(6) kg-1 CD34+ cells. Treatment with filgrastim (5 micrograms kg-1) following cyclophosphamide (3 g m-2) resulted in a harvest containing 66 x 10(4) kg-1 CFU-GM and 2.4 x 10(6) kg-1 CD34+ cells. There was no statistically significant difference between these two mobilising regimens. We have also demonstrated that dose-intensive carboplatin and cyclophosphamide chemotherapy can be delivered safely to patients with ovarian cancer when supported by peripheral blood progenitor cells and filgrastim. Carboplatin (AUC 7.5) and cyclophosphamide (900 mg m-2) given at 3 weekly intervals with progenitor cell and growth factor support was well tolerated in terms of haematological and systemic side-effects. Double the dose intensity of chemotherapy was delivered compared with our standard dose regimen when the treatment was given at 3 weekly intervals. Median dose intensity could be further escalated to 2.33 compared with our standard regimen by decreasing the interval between treatment cycles to 2 weeks. However, at this dose intensity less than a third of patients received their planned treatment on time. All the delays were due to thrombocytopenia