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In this case study, we describe a client, pseudonymously named Kai, who suffered multiple firearm injuries and was enrolled in a hospital-based violence intervention program (HVIP). Kai required multi-disciplinary care in pediatric and adult Level I Trauma Centers. His care was complicated by behavioral health issues, poverty, and a lack of adequate access to community-based healthcare and social support, leading to deteriorating health, frequent hospitalizations, and high health care utilization. Providers from the HVIP repeatedly worked with Kai, advocated for enhanced care, and provided him with the support necessary to heal and recover. This case report details the exceptional work HVIPs can do to support at-risk individuals, disrupt the cycle of violence, and promote healing and safety. [ABSTRACT FROM AUTHOR]

Although personality disorders (PDs) are more common among persons experiencing homelessness than the general population, few studies have investigated the risk of experiencing homelessness among persons with PDs. This study seeks to identify the demographic, socioeconomic, and behavioral health correlates of past-year homelessness among persons with antisocial, borderline, and schizotypal PDs. Nationally representative data of the civilian, noninstitutionalized population of the United States was used to identify correlates of homelessness. Descriptive statistics and bivariate associations between variables and homeless status were summarized prior to conducting several multivariate logistic regression models to identify correlates of homelessness. Main findings revealed positive associations between poverty, relationship dysfunction, and lifetime suicide attempt with homelessness. In the antisocial PD (ASPD) and borderline PD (BPD) models, comorbid BPD and ASPD, respectively, were associated with higher odds of past-year homelessness. Findings underscore the importance of poverty, interpersonal difficulties, and behavioral health comorbidities on homelessness among persons with ASPD, BPD, and schizotypal PD. Strategies to promote economic security, stable relationships, and interpersonal functioning may buffer against the effects of economic volatility and other systemic factors that could contribute to homelessness and persons with PD. [ABSTRACT FROM AUTHOR]

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Adverse childhood events have been shown to impact individuals through adulthood, particularly the impact on relationships. This study aimed to examine intergenerational trauma exposure among a sample of parents living in a semi-urban Salvadoran community and the relationship between child trauma exposure with maternal perceived discrimination, internal strengths and external support. Survey data was collected from 49 mothers residing in El Salvador. Bivariate analyses and multivariate linear regression analyses were used to examine the relationship between children's exposure to adverse childhood events and parents' exposure to adverse childhood events, while controlling for discrimination. The results of the regression analysis indicate that the maternal number of adverse childhood events and experience of discrimination as an adult explained 52.9% of the variance (R2 = 0.59, F(6, 43) = 10.18, p <.0001). The number of adverse childhood events was significantly predicted by maternal number of adverse events (B = 0.32, 95% CI = 0.17–0.48, p <.0001) and experience of discrimination as adults (B = 5.79, 95% CI = 3.51–8.07, p <.0001). Results suggest that parent exposure to adverse childhood events and parent experience with discrimination are related to the exposure to adverse childhood events of their children. Further research in this area is warranted to better understand the experiences of parents who have been exposed to childhood trauma and the day-to-day parenting challenges. Greater understanding of the impact of childhood trauma also encourages service providers to explore intergenerational interventions. [ABSTRACT FROM AUTHOR]

Immigrant and refugee children often experience stressful or traumatic events that greatly impact their ability to function in school. The dysregulatory and somatic symptoms of trauma such as hyper-arousal and dissociation as well as co-morbid anxiety and depression can have a profound impact on academic and social functioning. Addressing these symptoms requires approaches that help children develop the ability to calm their bodies and achieve a state of emotional regulation and brain-body integration. This pilot study examined the effectiveness of a school-based somatic soothing intervention designed to help children manage dissociative and dysregulatory symptoms. A convenience sample of 34 mostly refugee and immigrant youth who struggled with these symptoms were recruited for this study. The children were between the ages of 6 and 11 and reported experiencing war, interpersonal violence and neglect as well as stressors associated with migration, displacement, and resettlement. Participants in this study scored highly on baseline measures for post-traumatic stress disorder, depression, and anxiety indicating a high amount of comorbid psychiatric symptomology. Participants reported statistically significant improvement in anxiety, depression, psychological functioning, and trauma symptomology post-intervention with medium to large effect sizes ranging from.46 to 1.08. Qualitative results from teacher reports indicated strides in confidence, communication, academic functioning and social interaction for most participants. The positive associational findings suggest that this intervention may hold promise and warrants further investigation using more rigorous designs. [ABSTRACT FROM AUTHOR]

The experiences of formerly incarcerated mothers are rarely examined despite the sharp rise in female incarceration over the past 2 decades. This project used a transcendental phenomenological approach and in-depth interviews with 12 formerly incarcerated mothers as they reflected on their motherhood experiences before, during and after their incarceration. Mothers described how they struggled to negotiate their own stress, trauma, addiction, and shame, and offer insights for how service systems and professionals can help mothers reunify with their families and re-enter society. Clinical implications for systems of care, policy and practice are explored. [ABSTRACT FROM AUTHOR]

Purpose: To examine illicit drug use and service utilization patterns of US-born and foreign-born Hispanics in the United States.Methods: Hispanic respondents 18 years and older in the NESARC were categorized as being of Mexican (n = 3,556), Puerto Rican (n = 785), Cuban (n = 346), Central American (n = 513), or South American (n = 381) origin. We examined lifetime prevalence of drug use and substance abuse treatment utilization patterns for US-born and Hispanic immigrants across subgroups.Results: Lifetime prevalence of drug use was greater among US-born Hispanics than Hispanic immigrants after controlling for age, gender, income, education, urbanicity, parental history of drug use problems and lifetime DSM-IV mood/anxiety disorders. Both US-born and immigrant Hispanic drug users were less likely than non-Hispanic white drug users to have utilized any form of substance abuse treatment (US-born AOR = 0.89, immigrant AOR = 0.64) and more likely to have utilized family or social services (US-born AOR = 1.17, immigrant AOR = 1.19). Compared to US-born Hispanic drug users, Hispanic immigrant drug users were less likely to have used any form of substance abuse treatment (AOR = 0.81) and were more likely to have utilized family or social services (AOR = 1.22).Conclusion: Strategies to increase engagement and retention of Hispanic drug users in substance abuse treatment include increasing access to linguistically and culturally competent programs that address unmet family and social needs. Further studies examining differences in drug use and service utilization patterns within Hispanic subgroups are needed. [ABSTRACT FROM AUTHOR]

This study explored the integration of peer services into community mental health settings through qualitative interviews with peer-providers and non-peer mental health workers. Results show peer job satisfaction was contingent upon role clarity, autonomy, and acceptance by non-peer coworkers. Mental health workers reported the need for organizational support for peer services and guidance about how to utilize peers, negotiate their professional boundaries and accommodate their mental health needs. Effective peer integration requires organizational readiness, staff preparation and clear policies and procedures. Consultation from consumer-based organizations, enhanced professional competencies, and professional development and career advancement opportunities for peers represent important resources. [ABSTRACT FROM AUTHOR]

Blockade of angiogenesis can retard tumour growth, but may also paradoxically increase metastasis. This paradox may be resolved by vessel normalization, which involves increased pericyte coverage, improved tumour vessel perfusion, reduced vascular permeability, and consequently mitigated hypoxia. Although these processes alter tumour progression, their regulation is poorly understood. Here we show that type 1 T helper (TH1) cells play a crucial role in vessel normalization. Bioinformatic analyses revealed that gene expression features related to vessel normalization correlate with immunostimulatory pathways, especially T lymphocyte infiltration or activity. To delineate the causal relationship, we used various mouse models with vessel normalization or T lymphocyte deficiencies. Although disruption of vessel normalization reduced T lymphocyte infiltration as expected, reciprocal depletion or inactivation of CD4+ T lymphocytes decreased vessel normalization, indicating a mutually regulatory loop. In addition, activation of CD4+ T lymphocytes by immune checkpoint blockade increased vessel normalization. TH1 cells that secrete interferon-γ are a major population of cells associated with vessel normalization. Patient-derived xenograft tumours growing in immunodeficient mice exhibited enhanced hypoxia compared to the original tumours in immunocompetent humans, and hypoxia was reduced by adoptive TH1 transfer. Our findings elucidate an unexpected role of TH1 cells in vasculature and immune reprogramming. TH1 cells may be a marker and a determinant of both immune checkpoint blockade and anti-angiogenesis efficacy. [ABSTRACT FROM AUTHOR]

Castration-resistant prostate cancer (CRPC) is an androgen receptor (AR)-dependent disease expected to cause the death of more than 27,000 Americans in 2015. There are only a few available treatments for CRPC, making the discovery of new drugs an urgent need. We report that CUDC-101 (an inhibitor od HER2/NEU, EGFR and HDAC) inhibits both the full length AR (flAR) and the AR variant AR-V7. This observation prompted experiments to discover which of the known activities of CUDC-101 is responsible for the inhibition of flAR/AR-V7 signaling. We used pharmacologic and genetic approaches, and found that the effect of CUDC-101 on flAR and AR-V7 was duplicated only by other HDAC inhibitors, or by silencing the HDAC isoforms HDAC5 and HDAC10. We observed that CUDC-101 treatment or AR-V7 silencing by RNAi equally reduced transcription of the AR-V7 target gene, PSA, without affecting viability of 22Rv1 cells. However, when cellular proliferation was used as an end point, CUDC-101 was more effective than AR-V7 silencing, raising the prospect that CUDC-101 has additional targets beside AR-V7. In support of this, we found that CUDC-101 increased the expression of the cyclin-dependent kinase inhibitor p21, and decreased that of the oncogene HER2/NEU. To determine if CUDC-101 reduces growth in a xenograft model of prostate cancer, this drug was given for 14 days to castrated male SCID mice inoculated with 22Rv1 cells. Compared to vehicle, CUDC-101 reduced xenograft growth in a statistically significant way, and without macroscopic side effects. These studies demonstrate that CUDC-101 inhibits wtAR and AR-V7 activity and growth of 22Rv1 cells in vitro and in vivo. These effects result from the ability of CUDC-101 to target not only HDAC signaling, which was associated with decreased flAR and AR-V7 activity, but multiple additional oncogenic pathways. These observations raise the possibility that treatment of CRPC may be achieved by using similarly multi-targeted approaches. [ABSTRACT FROM AUTHOR]

This study evaluated a statewide demonstration project to implement a group-based intervention called Procovery in selected inpatient and community mental health centers. Procovery is a facilitated mutual support group designed to build hope and a sense of social inclusion by raising consciousness and helping people develop an understanding of the ways one can move toward recovery in their own lives. This evaluation sought to determine both consumer outcomes and perceptions of the program and implementation efforts held by consumers and the facilitators of the intervention. A multidimensional approach was used, including a quasi-experimental design with consumers, questionnaires and focus groups with the intervention facilitators, and individual interviews with administrators. The Procovery model was shown to have a positive impact on consumers' recoveries and was viewed favorably by consumers, facilitators, and administrators. Several barriers to effective implementation were identified. These findings and their implications for future practice and research are discussed. [ABSTRACT FROM AUTHOR]

Harm reduction in community mental health settings can be effective in engaging persons with co-occurring disorders in services. In this qualitative study, personal interviews and grounded theory methods were used to explore the experiences of 21 mental health practitioners and 15 consumers with co-occurring disorders at a community mental health housing program that uses harm reduction. Results indicate that while harm reduction enhanced therapeutic alliances, ethical and emotional tensions between practitioners and consumers regarding their views on self-determination and tolerance of drug-related behaviors were also evident. These tensions are explored and implications for practice and education are provided. [ABSTRACT FROM AUTHOR]

A 25% increase in bidimensional products (BPs) of tumor diameter has been used as a criterion for brain tumor progression. We studied intra-observer variability in measurements of BPs. Ten patients with contrast-enhancing glioblastoma multiforme underwent baseline and follow-up MR imaging. Seven observers measured BPs in various planes. Differences in BPs between scans were expressed as a percentage of baseline. This calculation was performed for both readings of the baseline and follow-up scans. Differences between change from baseline to follow-up on each reading (termed D values) were calculated for each reader (total of 196 D values). Median D value in each plane was calculated for each reader. Range of D values was 12.36-33.64% in axial plane (average 10.63%), 12.18-38.62% in coronal plane (average 26.84%) and 15.12-35.48% in sagittal plane (average 26.11%). Across all planes, 88 (45%) D values were >25%. When all imaging planes for any single observation were combined, in 76% of cases, at least one D value of >25% was seen. Based on the high degree of intra-observer variability, tumor measurements producing an increase in BP of >25% can routinely be obtained solely by chance. [ABSTRACT FROM AUTHOR]

Estrogens play a crucial role in breast tumor growth, which is the rationale for the use of antiestrogens, such as tamoxifen, in women with estrogen receptor (ER)-α-positive breast cancer. However, hormone resistance is a major clinical problem. Altered growth factor signaling to the ERα pathway has been shown to be associated with the development of clinical resistance. We previously have identified a mutation that replaces arginine for lysine at residue 303 (K303R) of ERα, which confers hypersensitive growth in low levels of estrogen. To determine if the K303R mutation could participate in the evolution of hormone resistance, we generated MCF-7 breast cancer cells stably transfected with either wild-type (WT) or K303R ERα. We found that the mutation confers decreased sensitivity to tamoxifen in the presence of the growth factor heregulin, using anchorage-independent growth assays. K303R ERα-expressing cells were hypersensitive to growth factor signals. Our data suggest that phosphorylation of serine 305 within the hinge domain of ERα might play a key role in increasing ligand-independent activity of the mutant receptor. We hypothesize that the mutation adapts the receptor for enhanced bidirectional cross-talk with the HER2 growth factor receptor pathway, which then impacts on responsiveness to tamoxifen. [ABSTRACT FROM AUTHOR]

Nuclear mitotic apparatus protein-retinoic acid receptor α (NuMA-RARα) is the fourth of five fusion proteins identified in acute promyelocytic leukemia (APL) patients. The molecular basis for its oncogenic activity has not been delineated. In gel-shift assays, NuMA-RARα bound to retinoic acid response elements (RAREs) both as a homodimer and as a heterodimer with RXRα. The binding profile of NuMA-RARα to a panel of RAREs was very similar to PML-RARα and PLZF-RARα. In transient transfection assays using HepG2 cells, NuMA-RARα inhibited wild-type RARα transcriptional activity, while it augmented STAT3 transcriptional activity. In GST-pull down experiments, NuMA-RARα formed a complex with the corepressor SMRT, was released from the NuMA-RARα/SMRT complexes by all-trans retinoic acid (ATRA) at 10-7–10-6 M and became associated with the coactivator TRAM-1 at 10-8 M ATRA. Studies comparing NuMA-RARα with NuMA-RARα(ΔCC) demonstrated that the dimerization or α-helical coiled-coil domain of NuMA was required for homodimer formation, transcriptional repression of wild-type RARα, transcriptional activation of STAT3, and stability of the NuMA-RARα/SMRT complex. Confocal fluorescent microscopy of HeLa cells was performed following transient expression of cyan fluorescent protein (CFP)-tagged proteins and incubation of cells with or without ATRA. Within the nucleus, CFP-NuMA-RARα exhibited a speckled pattern identical to that observed in cells transfected with CFP-NuMA. Furthermore, CFP-NuMA-RARα colocalized with yellow fluorescent protein-tagged (YFP)-NuMA. In contrast, CFP-NuMA-RARα(ΔCC) exhibited a diffuse granular pattern within the nucleus, similar to RARα. These results indicate that the dimerization domain of NuMA-RARα is critical for each of the known oncogenic activities of NuMA fusion proteins as well as its... [ABSTRACT FROM AUTHOR]

A hallmark of neurodegenerative diseases caused by polyglutamine expansion is the abnormal accumulation of mutant proteins into ubiquitin-positive inclusions. The local build-up of these ubiquitinated proteins suggests that the proteasome machinery inadequately clears misfolded proteins, resulting in their increase to potentially toxic levels. Inclusions may disrupt normal cell homeostasis by sequestering vital cellular factors, such as chaperones, proteasomes and transcription components. Here, we used fluorescence recovery after photobleaching (FRAP) to examine the intranuclear dynamics of polyglutamine-expanded ataxin1 and inclusion-associated proteins. These experiments demonstrated that at least two types of ataxin1 inclusions exist; those that undergo rapid and complete exchange with a nucleoplasmic pool and those that contain varying levels of slowexchanging ataxin1. Slow-exchanging inclusions contain high ubiquitin levels, but surprisingly low proteasome levels, suggesting an impairment in the ability of proteasomes to recognize ubiquitinated substrates. Proteasomes and CBP remained highly dynamic components of inclusions, indicating that although enriched with ataxin1, they are not irreversibly trapped. These results redefine our perception of polyglutamine inclusions and demonstrate the usefulness of FRAP and live cell imaging to study factors that modulate their behaviour. [ABSTRACT FROM AUTHOR]

Here we report the use of fluorescence recovery after photobleaching (FRAP) to examine the intranuclear dynamics of fluorescent oestrogen receptor-α (ER). After bleaching, unliganded ER exhibits high mobility (recovery t1/2 < 1 s). Agonist (oestradiol; E2) or partial antagonist (4-hydroxytamoxifen) slows ER recovery (t1/2 ∼5?6 s), whereas the pure antagonist (ICI 182,780) and, surprisingly, proteasome inhibitors each immobilize ER to the nuclear matrix. Dual FRAP experiments show that fluorescent ER and SRC-1 exhibit similar dynamics only in the presence of E2. In contrast to reports that several nuclear proteins show uniform dynamics, ER exhibits differential mobility depending upon several factors that are linked to its transcription function. [ABSTRACT FROM AUTHOR]

Centromere protein B (CENP-B) is a centromeric DNA-binding protein that binds to α-satellite DNA at the 17 bp CENP-B box sequence. The binding of CENP-B, along with other proteins, to α-satellite DNA sequences at the centromere, is thought to package the DNA into heterochromatin subjacent to the kinetochore of mitotic chromosomes. To determine the importance of CENP-B to kinetochore assembly and function, we generated a mouse null for the cenpB gene. The deletion removed part of the promoter and the entire coding sequence except for the carboxyl-terminal 35 amino acids of the CENP-B polypeptide. Mice heterozygous or homozygous for the cenpB null mutation are viable and healthy, with no apparent defect in growth and morphology. We have established mouse embryo fibroblasts from heterozygous and homozygous cenpB null littermates. Microscopic analysis, using immunofluorescence and electron microscopy of the cultured cells, indicated that the centromere-kinetochore complex was intact and identical to control cells. Mitosis was identical in fibroblasts derived from cenpB wild-type, heterozygous and null animals. Our studies demonstrate that CENP-B is not required for the assembly of heterochromatin or the kinetochore, or for completion of mitosis. [ABSTRACT FROM AUTHOR]

Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurodegenerative disorder caused by expansion of a polyglutamine tract in ataxin-1. In affected neurons of SCA1 patients and transgenic mice, mutant ataxin-1 accumulates in a single, ubiquitin-positive nuclear inclusion. In this study, we show that these inclusions stain positively for the 20S proteasome and the molecular chaperone HDJ-2/HSDJ. Similarly, HeLa cells transfected with mutant ataxin-1 develop nuclear aggregates which colocalize with the 20S proteasome and endogenous HDJ-2/HSDJ. Overexpression of wild-type HDJ-2/HSDJ in HeLa cells decreases the frequency of ataxin-1 aggregation. These data suggest that protein misfolding is responsible for the nuclear aggregates seen in SCA1, and that overexpression of a DnaJ chaperone promotes the recognition of a misfolded polyglutamine repeat protein, allowing its refolding and/or ubiquitin-dependent degradation. [ABSTRACT FROM AUTHOR]

Ginkgo biloba cells were cultured in two 500 mL shake flasks and in 2 L and 6 L immobilization bioreactors using MS medium supplemented with 1 mg.L NAA, 0.1 mg.L K and 30 g.L sucrose. Specific growth rates were 0.06 d, 0.11 d and 0.07 d for the 2 L and 6 L bioreactors and shake flask cultures, respectively. Extracellular phosphate, nitrate, ammonium and carbohydrate uptake rates of the bio reactor cultures were approximately 17 to 39% slower than those of shake flask cultures. The specific oxygen uptake and carbon dioxide transfer rates of immobilized Ginkgo biloba cells ranged from 0.027 to 0.041 mmol O.g.d.w.hr (maximum uptake at 14 days) and 0.020 to 0.057 mmol COg. .d.w.hr (maximum production at 14 days). Extracts from the biomass of the two immobilized and shake flask suspension cultures were analysed for ginkgolide A by GC-MS. Yields of 7, 17, 19 and 7 ng.g. d.w. of ginkgolide A were determined for shake flask 1, shake flask 2 and the 2 L and 6 L immobilized cultures, respectively. Traces of ginkgolide B were detected with the signal to noise ratio, however, being too low for positive confirmation of this last product. [ABSTRACT FROM AUTHOR]

83 strains of Pseudomonas aeruginosa were unable to utilize l-threonine as carbon-energy source, although this compound served as sole nitrogen source. Auxotrophs of P. aeruginosa 9-D2 that required l-serine or glycine for growth could grow in the presence of l-threonine. Extracts of P. aeruginosa 9-D2 grown in the presence of l-threonine contained threonine dehydrogenase and alpha-amino beta-ketobutyrate: CoA ligase activities; threonine aldolase was not detectable. Cells grown in the absence of l-threonine produced no detectable threonine dehydrogenase. l-Leucine neither stimulated nor repressed threonine dehydrogenase levels. Glycine, and to a lesser extent l-serine, repressed l-threonine-mediated threonine dehydrogenase synthesis. A mutant of strain 9-D2 was isolated that could utilize l-threonine as sole carbon-energy source. This strain produced elevated levels of threonine dehydrogenase, but only slightly higher levels of alpha-amino beta-ketobutyrate: CoA ligase activities. [ABSTRACT FROM AUTHOR]

We have generated and characterized a novel site-specific antibody highly specific for the phosphorylated form of the amino-terminus of histone H3 (Ser10). In this study, we used this antibody to examine in detail the relationship between H3 phosphorylation and mitotic chromosome condensation in mammalian cells. Our results extend previous biochemical studies by demonstrating that mitotic phosphorylation of H3 initiates nonrandomly in pericentromeric heterochromatin in late G2 interphase cells. Following initiation, H3 phosphorylation appears to spread throughout the condensing chromatin and is complete in most cell lines just prior to the formation of prophase chromosomes, in which a phosphorylated, but nonmitotic, chromosomal organization is observed. In general, there is a precise spatial and temporal correlation between H3 phosphorylation and initial stages of chromatin condensation. Dephosphorylation of H3 begins in anaphase and is complete immediately prior to detectable chromosome decondensation in telophase cells. We propose that the singular phosphorylation of the amino-terminus of histone H3 may be involved in facilitating two key functions during mitosis: (1) regulate protein-protein interactions to promote binding of trans-acting factors that “drive” chromatin condensation as cells enter M-phase and (2) coordinate chromatin decondensation associated with M-phase. [ABSTRACT FROM AUTHOR]

Steroid receptor coactivator-2 (SRC-2) is a transcriptional coregulator that modulates the activity of many transcription factors. Levels of SRC-2 are elevated in endometrial biopsies from polycystic ovary syndrome patients, a population predisposed to endometrial cancer (EC). Increased expression of SRC-2 is also detected in neoplastic endometrium suggesting a causal link between elevated SRC-2 expression and the emergence of endometrial disorders that can lead to cancer. Here, we reveal that SRC-2 knockdown reduces EC cell proliferation and anchorage-independence. Additionally, SRC-2 is required to maintain cellular glycolytic capacity and oxidative phosphorylation, processes essential for EC cell proliferation. Importantly, SRC-2 is critical for the normal performance of the pentose phosphate pathway (PPP). Perturbation of the PPP due to loss of SRC-2 expression may result from the depletion of ribose-5-P isomerase (RPIA), a key enzyme of the PPP. As with SRC-2, RPIA knockdown reduces EC cell proliferation, which is accompanied by a decrease in glycolytic capacity and oxidative phosphorylation. Glucose metabolite tracking experiments confirmed that knockdown of SRC-2 and RPIA downregulates the metabolic rate of both glycolysis and the PPP, highlighting a novel regulatory cross-talk between glycolysis and the PPP modulated by SRC-2. [ABSTRACT FROM AUTHOR]

The majority of breast cancer models for drug discovery are based on orthotopic or subcutaneous tumours. Therapeutic responses of metastases, especially microscopic metastases, are likely to differ from these tumours due to distinct cancer-microenvironment crosstalk in distant organs. Here, to recapitulate such differences, we established an ex vivo bone metastasis model, termed bone-in-culture array or BICA, by fragmenting mouse bones preloaded with breast cancer cells via intra-iliac artery injection. Cancer cells in BICA maintain features of in vivo bone micrometastases regarding the microenvironmental niche, gene expression profile, metastatic growth kinetics and therapeutic responses. Through a proof-of-principle drug screening using BICA, we found that danusertib, an inhibitor of the Aurora kinase family, preferentially inhibits bone micrometastases. In contrast, certain histone methyltransferase inhibitors stimulate metastatic outgrowth of indolent cancer cells, specifically in the bone. Thus, BICA can be used to investigate mechanisms involved in bone colonization and to rapidly test drug efficacies on bone micrometastases. [ABSTRACT FROM AUTHOR]

Zika virus (ZIKV) is an emerging mosquito-borne (Aedes genus) arbovirus of the Flaviviridae family. Although ZIKV has been predominately associated with a mild or asymptomatic dengue-like disease, its appearance in the Americas has been accompanied by a multi-fold increase in reported incidence of fetal microcephaly and brain malformations. The source and mode of vertical transmission from mother to fetus is presumptively transplacental, although a causal link explaining the interval delay between maternal symptoms and observed fetal malformations following infection has been missing. In this study, we show that primary human placental trophoblasts from non-exposed donors (n = 20) can be infected by primary passage ZIKV-FLR isolate, and uniquely allowed for ZIKV viral RNA replication when compared to dengue virus (DENV). Consistent with their being permissive for ZIKV infection, primary trophoblasts expressed multiple putative ZIKV cell entry receptors, and cellular function and differentiation were preserved. These findings suggest that ZIKV-FLR strain can replicate in human placental trophoblasts without host cell destruction, thereby serving as a likely permissive reservoir and portal of fetal transmission with risk of latent microcephaly and malformations. [ABSTRACT FROM AUTHOR]

The article focuses on a study conducted by Hongjie Dai and colleagues at Stanford University and Soochow University in China which examines a method of producing biocompatible fluorescent single-walled carbon nanotubes. Since single-walled carbon nanotubes are created on solid substrates, researchers detached, debundled and coated them with hydrophilic layer before using as soluble fluorophores. They found that coating tubes with a layer of biocompatible phospholipids reduces the tubes and produces defects.