Intermediate progenitors support migration of neural stem cells into dentate gyrus outer neurogenic niches.

The hippocampal dentate gyrus (DG) is a unique brain region maintaining neural stem cells (NCSs) and neurogenesis into adulthood. We used multiphoton imaging to visualize genetically defined progenitor subpopulations in live slices across key stages of mouse DG development, testing decades old static models of DG formation with molecular identification, genetic-lineage tracing, and mutant analyses. We found novel progenitor migrations, timings, dynamic cell-cell interactions, signaling activities, and routes underlie mosaic DG formation. Intermediate progenitors (IPs, Tbr2+) pioneered migrations, supporting and guiding later emigrating NSCs (Sox9+) through multiple transient zones prior to converging at the nascent outer adult niche in a dynamic settling process, generating all prenatal and postnatal granule neurons in defined spatiotemporal order. IPs (Dll1+) extensively targeted contacts to mitotic NSCs (Notch active), revealing a substrate for cell-cell contact support during migrations, a developmental feature maintained in adults. Mouse DG formation shares conserved features of human neocortical expansion

Horses with equine recurrent uveitis have an activated CD4+ T-cell phenotype that can be modulated by mesenchymal stem cells in vitro.

Equine recurrent uveitis (ERU) is an immune-mediated disease causing repeated or persistent inflammatory episodes which can lead to blindness. Currently, there is no cure for horses with this disease. Mesenchymal stem cells (MSCs) are effective at reducing immune cell activation in vitro in many species, making them a potential therapeutic option for ERU. The objectives of this study were to define the lymphocyte phenotype of horses with ERU and to determine how MSCs alter T-cell phenotype in vitro. Whole blood was taken from 7 horses with ERU and 10 healthy horses and peripheral blood mononuclear cells were isolated. The markers CD21, CD3, CD4, and CD8 were used to identify lymphocyte subsets while CD25, CD62L, Foxp3, IFNγ, and IL10 were used to identify T-cell phenotype. Adipose-derived MSCs were expanded, irradiated (to control proliferation), and incubated with CD4+ T-cells from healthy horses, after which lymphocytes were collected and analyzed via flow cytometry. The percentages of T-cells and B-cells in horses with ERU were similar to normal horses. However, CD4+ T-cells from horses with ERU expressed higher amounts of IFNγ indicating a pro-inflammatory Th1 phenotype. When co-incubated with MSCs, activated CD4+ T-cells reduced expression of CD25, CD62L, Foxp3, and IFNγ. MSCs had a lesser ability to decrease activation when cell-cell contact or prostaglandin signaling was blocked. MSCs continue to show promise as a treatment for ERU as they decreased the CD4+ T-cell activation phenotype through a combination of cell-cell contact and prostaglandin signaling

The Therapeutic Interview Process in Qualitative Research Studies

The purpose of this paper is to describe the systemic strategies used in marriage and family therapy relevant to interviews, via what we call the therapeutic interview process, that expand the meaning of a research study for both the counselor researcher and the participant(s). We outline the therapeutic interview process for conducting transformative - based interviews via similar strategies from a family systems perspective conceptualized by Charlés (2007). The central core of the interview process is the therapeutic conversation itself that involves the systemic whole. This therapeutic conversation is facilitated by debriefing interviews, whereby the counselor researcher is interviewed to promote reflexivit

Gender: An Important Factor in the Implementation of Services for Juvenile Offenders

The Child Welfare League of America (2003) reported that between 1980 and 2000 the arrest rate for boys declined by 11% but increased for girls by 35%. A well tested case management approach being applied more commonly in juvenile justice is the Risk-Needs-Responsivity (RNR) approach, which suggests that interventions and services should be commensurate with ones level of risk and specific dynamic risk factors (criminogenic needs). The RNR model tends to be seen as gender-neutral , based on assumption that it works equally well with both sexes. Few studies have examined whether gender differences exist in the effectiveness of RNR-type case planning. Vitopoulos et al., (2012) examined possible RNR differences between justice-involved boys and girls using the Youth Level of Service/Case Management Inventory (YLS/CMI). Across all of the criminogenic need areas (e.g. antisocial attitudes, peer affiliations), only the personality domain was significantly different by gender, such that more girls than boys seemed to have a problem inthis area. They did not find any gender differences in the matching of services to needs identified; however, a higher match between clinician-recommended needs and assigned treatment services (service-to-needs match) predicted a decrease in boys\u27 re-offending but not in girls\u27 reoffending. Given the paucity of research, we are left to question the applicability of some RNR principles or the quality of their implementation for girl offenders. Using the Structured Assessment of Violence Risk for Youth (SAVRY)) in three probation officies to measure both risk level and dynamic risk factors (criminogenic needs), we examined whether within a large sample of youth there were gender differences in the (a) criminogenic needs identified, (b) ability of probation officers (POs) to match services to needs in their case planning and (c) the association of the serve-need match to recidivism

Repeat prostate biopsy strategies after initial negative biopsy: meta-regression comparing cancer detection of transperineal, transrectal saturation and MRI guided biopsy.

INTRODUCTION: There is no consensus on how to investigate men with negative transrectal ultrasound guided prostate biopsy (TRUS-B) but ongoing suspicion of cancer. Three strategies used are transperineal (TP-B), transrectal saturation (TS-B) and MRI-guided biopsy (MRI-B). We compared cancer yields of these strategies. METHODS: Papers were identified by search of Pubmed, Embase and Ovid Medline. Included studies investigated biopsy diagnostic yield in men with at least one negative TRUS-B and ongoing suspicion of prostate cancer. Data including age, PSA, number of previous biopsy episodes, number of cores at re-biopsy, cancer yield, and Gleason score of detected cancers were extracted. Meta-regression analyses were used to analyse the data. RESULTS: Forty-six studies were included; 12 of TS-B, 14 of TP-B, and 20 of MRI-B, representing 4,657 patients. Mean patient age, PSA and number of previous biopsy episodes were similar between the strategies. The mean number of biopsy cores obtained by TP-B and TS-B were greater than MRI-B. Cancer detection rates were 30·0%, 36·8%, and 37·6% for TS-B, TP-B, and MRI-B respectively. Meta-regression analysis showed that MRI-B had significantly higher cancer detection than TS-B. There were no significant differences however between MRI-B and TP-B, or TP-B and TS-B. In a sensitivity analysis incorporating number of previous biopsy episodes (36 studies) the difference between MRI-B and TP-B was not maintained resulting in no significant difference in cancer detection between the groups. There were no significant differences in median Gleason scores detected comparing the three strategies. CONCLUSIONS: In the re-biopsy setting, it is unclear which strategy offers the highest cancer detection rate. MRI-B may potentially detect more prostate cancers than other modalities and can achieve this with fewer biopsy cores. However, well-designed prospective studies with standardised outcome measures are needed to accurately compare modalities and define an optimum re-biopsy approach

Vaginal biogenic amines: biomarkers of bacterial vaginosis or precursors to vaginal dysbiosis?

Bacterial vaginosis (BV) is the most common vaginal disorder among reproductive age women. One clinical indicator of BV is a "fishy" odor. This odor has been associated with increases in several biogenic amines (BAs) that may serve as important biomarkers. Within the vagina, BA production has been linked to various vaginal taxa, yet their genetic capability to synthesize BAs is unknown. Using a bioinformatics approach, we show that relatively few vaginal taxa are predicted to be capable of producing BAs. Many of these taxa (Dialister, Prevotella, Parvimonas, Megasphaera, Peptostreptococcus, and Veillonella spp.) are more abundant in the vaginal microbial community state type (CST) IV, which is depleted in lactobacilli. Several of the major Lactobacillus species (L. crispatus, L. jensenii, and L. gasseri) were identified as possessing gene sequences for proteins predicted to be capable of putrescine production. Finally, we show in a small cross sectional study of 37 women that the BAs putrescine, cadaverine and tyramine are significantly higher in CST IV over CSTs I and III. These data support the hypothesis that BA production is conducted by few vaginal taxa and may be important to the outgrowth of BV-associated (vaginal dysbiosis) vaginal bacteria

Social ecological influences on treatment decision-making in men diagnosed with low risk, localised prostate cancer

Objective: Individuals diagnosed with low risk, localised prostate cancer (PCa) face a difficult decision between active surveillance (AS) and definitive treatment. We aimed to explore perceived influences on treatment decision-making from the patient and partner\u27s perspectives. Methods: Patients (and partners) who met AS criteria and had chosen their treatment were recruited. Semi-structured individual interviews were conducted via telephone to explore experiences of diagnosis, impact on patient lifestyle, experiences with physicians, treatment preferences/choice, treatment information understanding and needs, and overall decision-making process. Interviews were audio recorded, transcribed verbatim, and analysed using Reflexive Thematic Analysis. Results: Twenty-four male patients (18 chose AS) and 12 female partners participated. Five themes relating to social-ecological influences on treatment choice were identified: (1) partner support and direct influence on patient treatment choice, (2) patient and partner vicarious experiences may influence treatment decisions, (3) the influence of the patient\u27s life circumstances, (4) disclosing to wider social networks: friends, family, and co-workers, and (5) the importance of a good relationship and experience with physicians. Additionally, two themes were identified relating to information patients and partners received about the treatment options during their decision-making process. Conclusions: A range of individual and social influences on treatment decision-making were reported. Physicians providing treatment recommendations should consider and discuss the patient and partner\u27s existing beliefs and treatment preferences and encourage shared decision-making. Further research on treatment decision-making of partnered and non-partnered PCa patients is required. We recommend research considers social ecological factors across the personal, interpersonal, community, and policy levels

Variable responses of human and non-human primate gut microbiomes to a Western diet

BACKGROUND: The human gut microbiota interacts closely with human diet and physiology. To better understand the mechanisms behind this relationship, gut microbiome research relies on complementing human studies with manipulations of animal models, including non-human primates. However, due to unique aspects of human diet and physiology, it is likely that host-gut microbe interactions operate differently in humans and non-human primates. RESULTS: Here, we show that the human microbiome reacts differently to a high-protein, high-fat Western diet than that of a model primate, the African green monkey, or vervet (Chlorocebus aethiops sabaeus). Specifically, humans exhibit increased relative abundance of Firmicutes and reduced relative abundance of Prevotella on a Western diet while vervets show the opposite pattern. Predictive metagenomics demonstrate an increased relative abundance of genes associated with carbohydrate metabolism in the microbiome of only humans consuming a Western diet. CONCLUSIONS: These results suggest that the human gut microbiota has unique properties that are a result of changes in human diet and physiology across evolution or that may have contributed to the evolution of human physiology. Therefore, the role of animal models for understanding the relationship between the human gut microbiota and host metabolism must be re-focused.P40 OD010965 - NIH HHS; P40 RR019963 - NCRR NIH HHS; P51 OD011132 - NIH HHS; R01 RR016300 - NCRR NIH HHS; 5R01RR016300 - NCRR NIH HH

Resistance loci affecting distinct stages of fungal pathogenesis: use of introgression lines for QTL mapping and characterization in the maize - Setosphaeria turcica pathosystem

<p>Abstract</p> <p>Background</p> <p>Studies on host-pathogen interactions in a range of pathosystems have revealed an array of mechanisms by which plants reduce the efficiency of pathogenesis. While R-gene mediated resistance confers highly effective defense responses against pathogen invasion, quantitative resistance is associated with intermediate levels of resistance that reduces disease progress. To test the hypothesis that specific loci affect distinct stages of fungal pathogenesis, a set of maize introgression lines was used for mapping and characterization of quantitative trait loci (QTL) conditioning resistance to <it>Setosphaeria turcica</it>, the causal agent of northern leaf blight (NLB). To better understand the nature of quantitative resistance, the identified QTL were further tested for three secondary hypotheses: (1) that disease QTL differ by host developmental stage; (2) that their performance changes across environments; and (3) that they condition broad-spectrum resistance.</p> <p>Results</p> <p>Among a set of 82 introgression lines, seven lines were confirmed as more resistant or susceptible than B73. Two NLB QTL were validated in BC₄F₂segregating populations and advanced introgression lines. These loci, designated <it>qNLB1.02 </it>and <it>qNLB1.06</it>, were investigated in detail by comparing the introgression lines with B73 for a series of macroscopic and microscopic disease components targeting different stages of NLB development. Repeated greenhouse and field trials revealed that <it>qNLB1.06_Tx303</it>(the Tx303 allele at bin 1.06) reduces the efficiency of fungal penetration, while <it>qNLB1.02_B73</it>(the B73 allele at bin 1.02) enhances the accumulation of callose and phenolics surrounding infection sites, reduces hyphal growth into the vascular bundle and impairs the subsequent necrotrophic colonization in the leaves. The QTL were equally effective in both juvenile and adult plants; <it>qNLB1.06_Tx303</it>showed greater effectiveness in the field than in the greenhouse. In addition to NLB resistance, <it>qNLB1.02_B73</it>was associated with resistance to Stewart's wilt and common rust, while <it>qNLB1.06_Tx303</it>conferred resistance to Stewart's wilt. The non-specific resistance may be attributed to pleiotropy or linkage.</p> <p>Conclusions</p> <p>Our research has led to successful identification of two reliably-expressed QTL that can potentially be utilized to protect maize from <it>S. turcica </it>in different environments. This approach to identifying and dissecting quantitative resistance in plants will facilitate the application of quantitative resistance in crop protection.</p