Does size predict demographic fate? Modular demography and constraints on growth determine response to decreases in size

The modular construction of many plants and animals defies conventional approaches to the study of life histories and population dynamics. An important complication of modular construction is that individuals can rapidly decrease in size when some modules are removed or die or when an individual fragments. Most attempts to describe life histories and population dynamics of modular organisms classify individuals according to their size. This approach relies on the fundamental assumption that fragmentation and module loss have no consequences for an individual apart from a simple decrease in size. Here we experimentally test this assumption. Using a modular marine invertebrate, the encrusting bryozoan Watersipora subtorquata, as a model species, we manipulated colony size and then assessed performance against three potential explanatory models based on size, age, and damage. In a second experiment we disrupted the internal modular demography of colonies to determine whether the performance of a fragment is influenced by the type of modules that remain. Finally, we investigated how constraints on growth in modular organisms uniquely influence growth after module loss. We found that single-state variables such as size or age do not describe performance in our species. Internal constraints substantially reduce growth after a decrease in size, and the age of modules that remain determines the timing of reproductive onset and fecundity. A knowledge of the size history of individuals, including any decreases in size, is necessary to accurately describe life histories and population dynamics in this modular organism. Our results have major consequences for established methods for modeling the demography of modular organisms

Identification of Novel Tumor Antigens With Patient-Derived Immune-Selected Antibodies

The identification of tumor antigens capable of eliciting an immune response in vivo may be an effective method to identify therapeutic cancer targets. We have developed a method to identify such antigens using frozen tumor-draining lymph node samples from breast cancer patients. Immune responses in tumor-draining lymph nodes were identified by immunostaining lymph node sections for B-cell markers (CD20&CD23) and Ki67 which revealed cell proliferation in germinal center zones. Antigen-dependent somatic hypermutation (SH) and clonal expansion (CE) were present in heavy chain variable (VH) domain cDNA clones obtained from these germinal centers, but not from Ki67 negative germinal centers. Recombinant VH single-domain antibodies were used to screen tumor proteins and affinity select potential tumor antigens. Neuroplastin (NPTN) was identified as a candidate breast tumor antigen using proteomic identification of affinity selected tumor proteins with a recombinant VH single chain antibody. NPTN was found to be highly expressed in approximately 20% of invasive breast carcinomas and 50% of breast carcinomas with distal metastasis using a breast cancer tissue array. Additionally, NPTN over-expression in a breast cancer cell line resulted in a significant increase in tumor growth and angiogenesis in vivo which was related to increased VEGF production in the transfected cells. These results validate NPTN as a tumor-associated antigen which could promote breast tumor growth and metastasis if aberrantly expressed. These studies also demonstrate that humoral immune responses in tumor-draining lymph nodes can provide antibody reagents useful in identifying tumor antigens with applications for biomarker screening, diagnostics and therapeutic interventions

Effectiveness of a web-based self-help tool to reduce problem gambling: A randomized controlled trial.

Problem gambling constitutes a public health concern associated with psychopathological comorbidity, substance use, and financial difficulties. Most individuals with gambling problems avoid counseling services due to perceived stigma and their preference for self-reliance. Treatment accessibility could be improved through web-based interventions. We recruited 360 individuals with gambling problems and randomized them to a web-based intervention (n = 185) or an active control group consisting of a self-help manual for problem gambling (n = 175). The primary outcome was the number of days of gambling in the last 30 days. Secondary outcomes included money spent in the last 30 days, time gambling in the last 7 days, gambling-related problems, consumption of alcohol and cigarettes, and psychopathological comorbidity measured at posttreatment and 6-month follow-up. The primary outcome decreased significantly for both groups, with no significant difference between the groups. There were significant group × time interactions according to the Gambling Symptom Assessment Scale (F = 8.83, p <0 .001), the Problem Gambling Severity Index (F = 3.54, p = 0.030), for cigarettes smoked in the last 7 days (F = 26.68, p < 0.001), the Patient Health Questionnaire-9 (F = 19.41, p <0 .001), and the Generalized Anxiety Disorder-7 (F = 41.09, p <0 .001) favoring the intervention group. We experienced an overall high dropout rate (76%). Win Back Control seems to be an effective low-threshold treatment option for individuals with gambling problems that might otherwise be unapproachable for outpatient treatment services. Nevertheless, the high dropout rate should be considered when interpreting the study results, as they may have introduced a degree of variability

Modulation of CP2 Family Transcriptional Activity by CRTR-1 and Sumoylation

CRTR-1 is a member of the CP2 family of transcription factors. Unlike other members of the family which are widely expressed, CRTR-1 expression shows specific spatio-temporal regulation. Gene targeting demonstrates that CRTR-1 plays a central role in the maturation and function of the salivary glands and the kidney. CRTR-1 has also recently been identified as a component of the complex transcriptional network that maintains pluripotency in embryonic stem (ES) cells. CRTR-1 was previously shown to be a repressor of transcription. We examine the activity of CRTR-1 in ES and other cells and show that CRTR-1 is generally an activator of transcription and that it modulates the activity of other family members, CP2, NF2d9 and altNF2d9, in a cell specific manner. We also demonstrate that CRTR-1 activity is regulated by sumoylation at a single major site, residue K30. These findings imply that functional redundancy with other family members may mask important roles for CRTR-1 in other tissues, including the blastocyst stage embryo and embryonic stem cells

Nurse practitioner interactions in acute and long-term care : an exploration of the role of knotworking in supporting interprofessional collaboration

BACKGROUND: Interprofessional care ensures high quality healthcare. Effective interprofessional collaboration is required to enable interprofessional care, although within the acute care hospital setting interprofessional collaboration is considered suboptimal. The integration of nurse practitioner roles into the acute and long-term care settings is influencing enhanced care. What remains unknown is how the nurse practitioner role enacts interprofessional collaboration or enables interprofessional care to promote high quality care. The study aim was to understand how nurse practitioners employed in acute and long-term care settings enable interprofessional collaboration and care. METHOD: Nurse practitioner interactions with other healthcare professionals were observed throughout the work day. These interactions were explored within the context of "knotworking" to create an understanding of their social practices and processes supporting interprofessional collaboration. Healthcare professionals who worked with nurse practitioners were invited to share their perceptions of valued role attributes and impacts. RESULTS: Twenty-four nurse practitioners employed at six hospitals participated. 384 hours of observation provided 1,284 observed interactions for analysis. Two types of observed interactions are comparable to knotworking. Rapid interactions resemble the traditional knotworking described in earlier studies, while brief interactions are a new form of knotworking with enhanced qualities that more consistently result in interprofessional care. Nurse practitioners were the most common initiators of brief interactions. CONCLUSIONS: Brief interactions reveal new qualities of knotworking with more consistent interprofessional care results. A general process used by nurse practitioners, where they practice a combination of both traditional (rapid) knotworking and brief knotworking to enable interprofessional care within acute and long-term care settings, is revealed

Adenoviruses in Lymphocytes of the Human Gastro-Intestinal Tract

Objective: Persistent adenoviral shedding in stools is known to occur past convalescence following acute adenoviral infections. We wished to establish the frequency with which adenoviruses may colonize the gut in normal human subjects. Methods: The presence of adenoviral DNA in intestinal specimens obtained at surgery or autopsy was tested using a nested PCR method. The amplified adenoviral DNA sequences were compared to each other and to known adenoviral species. Lamina propria lymphocytes (LPLs) were isolated from the specimens and the adenoviral copy numbers in the CD4+ and CD8+ fractions were determined by quantitative PCR. Adenoviral gene expression was tested by amplification of adenoviral mRNA. Results: Intestinal tissue from 21 of 58 donors and LPLs from 21 of 24 donors were positive for the presence of adenoviral DNA. The majority of the sequences could be assigned to adenoviral species E, although species B and C sequences were also common. Multiple sequences were often present in the same sample. Forty-one non-identical sequences were identified from 39 different tissue donors. Quantitative PCR for adenoviral DNA in CD4+ and CD8+ fractions of LPLs showed adenoviral DNA to be present in both cell types and ranged from a few hundred to several million copies per million cells on average. Active adenoviral gene expression as evidenced by the presence of adenoviral messenger RNA in intestinal lymphocytes was demonstrated in 9 of the 11 donors tested

Recruitment in the sea: bacterial genes required for inducing larval settlement in a polychaete worm

Metamorphically competent larvae of the marine tubeworm Hydroides elegans can be induced to metamorphose by biofilms of the bacterium Pseudoalteromonas luteoviolacea strain HI1. Mutational analysis was used to identify four genes that are necessary for metamorphic induction and encode functions that may be related to cell adhesion and bacterial secretion systems. No major differences in biofilm characteristics, such as biofilm cell density, thickness, biomass and EPS biomass, were seen between biofilms composed of P. luteoviolacea (HI1) and mutants lacking one of the four genes. The analysis indicates that factors other than those relating to physical characteristics of biofilms are critical to the inductive capacity of P. luteoviolacea (HI1), and that essential inductive molecular components are missing in the non-inductive deletion-mutant strains