Immunoglobulin variable-region gene mutational lineage tree analysis: application to autoimmune diseases

Lineage trees have frequently been drawn to illustrate diversification, via somatic hypermutation (SHM), of immunoglobulin variable-region (IGV) genes. In order to extract more information from IGV sequences, we developed a novel mathematical method for analyzing the graphical properties of IgV gene lineage trees, allowing quantification of the differences between the dynamics of SHM and antigen-driven selection in different lymphoid tissues, species, and disease situations. Here, we investigated trees generated from published IGV sequence data from B cell clones participating in autoimmune responses in patients with Myasthenia Gravis (MG), Rheumatoid Arthritis (RA), and Sjögren's Syndrome (SS). At present, as no standards exist for cell sampling and sequence extraction methods, data obtained by different research groups from two studies of the same disease often vary considerably. Nevertheless, based on comparisons of data groups within individual studies, we show here that lineage trees from different individual patients are often similar and can be grouped together, as can trees from two different tissues in the same patient, and even from IgG- and IgA-expressing B cell clones. Additionally, lineage trees from most studies reflect the chronic character of autoimmune diseases

The Role of Neutrophils in Corneal Wound Healing in HO-2 Null Mice

Our studies demonstrated that Heme oxygenase (HO), in particular, the constitutive HO-2, is critical for a self-resolving inflammatory and repair response in the cornea. Epithelial injury in HO-2 null mice leads to impaired wound closure and chronic inflammation in the cornea. This study was undertaken to examine the possible relationship between HO-2 and the recruitment of neutrophils following a corneal surface injury in wild type (WT) and HO-2 knockout (HO-2−/−) mice treated with Gr-1 monoclonal antibody to deplete peripheral neutrophils. Epithelial injury was performed by removing the entire corneal epithelium. Infiltration of inflammatory cell into the cornea in response to injury was higher in HO-2−/− than in WT. However, the rate of corneal wound closure following neutrophil depletion was markedly inhibited in both WT and HO-2−/− mice by 60% and 85%, respectively. Neutropenia induced HO-1 expression in WT but not in HO-2−/− mice. Moreover, endothelial cells lacking HO-2 expressed higher levels of the Midkine and VE-cadherin and displayed strong adhesion to neutrophils suggesting that perturbation in endothelial cell function caused by HO-2 depletion underlies the increased infiltration of neutrophils into the HO-2−/− cornea. Moreover, the fact that neutropenia worsened epithelial healing of the injured cornea in both WT and HO-2−/− mice suggest that cells other than neutrophils contribute to the exaggerated inflammation and impaired wound healing seen in the HO-2 null cornea

Price, Nutrition, Time, and Other Trade-Offs: A Web-Based Food Value Analysis Application to Compare Foods at Different Levels of Preparation and Processing

Consumers choose to eat different forms of foods based on a wide variety of factors such as price, taste, nutrition, and convenience and, in doing so, make trade-offs among them. A Web-based application for use by nutrition educators was developed to help individuals compare foods prepared from home recipes with those for other forms of food (eg, frozen, canned, dry mix). Foods with a home-recipe form in US Department of Agriculture databases were selected to represent a range of commonly consumed entrées, baked goods, side dishes, fruits, vegetables, desserts, and beverages. Multiple US Department of Agriculture and commercial databases along with other public data sources were used to construct prices, nutrient values, food groups and components, preparation and cooking times, shelf life, and food safety concerns for foods in the database. Per-serving and per-100-g values were constructed for 100 individual foods with a home recipe and 1 or more other forms. The data are available in a Web-based application, located at http://www.foodvalueanalysis.org, allowing comparisons of individual foods or a daily diet constructed from foods in the database. Nutrition educators can use the application to advise individuals in selecting foods to consume to meet dietary guidelines while taking into consideration cost, preparation time, food preparation skills, and individual preferences. For example, the application can be used to evaluate differences in prices of fresh or processed foods, whether home recipe or processed foods are less costly when taking into consideration the value of preparation time, and the differences in nutrients across different forms of foods

Association between admission temperature and mortality and major morbidity in preterm infants born at fewer than 33weeks\u27 gestation

Importance: Neonatal hypothermia has been associated with higher mortality and morbidity; therefore, thermal control following delivery is an essential part of neonatal care. Identifying the ideal body temperature in preterm neonates in the first few hours of lifemay be helpful to reduce the risk for adverse outcomes. Objectives: To examine the association between admission temperature and neonatal outcomes and estimate the admission temperature associated with lowest rates of adverse outcomes in preterm infants born at fewer than 33 weeks\u27 gestation.. Design, Setting, And Participants: Retrospective observational study at 29 neonatal intensive care units in the Canadian Neonatal Network. Participants included 9833 inborn infants born at fewer than 33 weeks\u27 gestation who were admitted between January 1, 2010, and December 31, 2012.. Exposure: Axillary or rectal body temperature recorded at admission.. Main Outcomes And Measures: The primary outcomewas a composite adverse outcome defined as mortality or any of the following: severe neurological injury, severe retinopathy of prematurity, necrotizing enterocolitis, bronchopulmonary dysplasia, or nosocomial infection. The relationships between admission temperature and the composite outcome as well as between admission temperature and the components of the composite outcome were evaluated using multivariable analyses.. Results: Admission temperatures of the 9833 neonates were distributed as follows: lower than 34.5°C (1%); 34.5°C to 34.9°C (1%); 35.0°C to 35.4°C (3%); 35.5°C to 35.9°C (7%); 36.0°C to 36.4°C (24%); 36.5°C to 36.9°C (38%); 37.0°C to 37.4°C (19%); 37.5°C to 37.9°C (5%); and 38.0°C or higher (2%). After adjustment for maternal and infant characteristics, the rates of the composite outcome, severe neurological injury, severe retinopathy of prematurity, necrotizing enterocolitis, bronchopulmonary dysplasia, and nosocomial infection had a U-shaped relationship with admission temperature (a \u3e 0 [P \u3c .05]). The admission temperature at which the rate of the composite outcome was lowest was 36.8°C (95%CI, 36.7°C-37.0°C). Rates of severe neurological injury, severe retinopathy of prematurity, necrotizing enterocolitis (95%CI, 36.3°C-36.7°C), bronchopulmonary dysplasia, and nosocomial infection (95%CI, 36.9°C-37.3°C) were lowest at admission temperatures ranging from 36.5°C to 37.2°C.. Conclusions And Relevance: The relationship between admission temperature and adverse neonatal outcomes was U-shaped. The lowest rates of adverse outcomes were associated with admission temperatures between 36.5°C and 37.2°C.

IGF-I induced genes in stromal fibroblasts predict the clinical outcome of breast and lung cancer patients

<p>Abstract</p> <p>Background</p> <p>Insulin-like growth factor-1 (IGF-I) signalling is important for cancer initiation and progression. Given the emerging evidence for the role of the stroma in these processes, we aimed to characterize the effects of IGF-I on cancer cells and stromal cells separately.</p> <p>Methods</p> <p>We used an <it>ex vivo </it>culture model and measured gene expression changes after IGF-I stimulation with cDNA microarrays. <it>In vitro </it>data were correlated with <it>in vivo </it>findings by comparing the results with published expression datasets on human cancer biopsies.</p> <p>Results</p> <p>Upon stimulation with IGF-I, breast cancer cells and stromal fibroblasts show some common and other distinct response patterns. Among the up-regulated genes in the stromal fibroblasts we observed a significant enrichment in proliferation associated genes. The expression of the IGF-I induced genes was coherent and it provided a basis for the segregation of the patients into two groups. Patients with tumours with highly expressed IGF-I induced genes had a significantly lower survival rate than patients whose tumours showed lower levels of IGF-I induced gene expression (<it>P </it>= 0.029 - Norway/Stanford and <it>P </it>= 7.96e-09 - NKI dataset). Furthermore, based on an IGF-I induced gene expression signature derived from primary lung fibroblasts, a separation of prognostically different lung cancers was possible (<it>P </it>= 0.007 - Bhattacharjee and <it>P </it>= 0.008 - Garber dataset).</p> <p>Conclusion</p> <p>Expression patterns of genes induced by IGF-I in primary breast and lung fibroblasts accurately predict outcomes in breast and lung cancer patients. Furthermore, these IGF-I induced gene signatures derived from stromal fibroblasts might be promising predictors for the response to IGF-I targeted therapies.</p> <p>See the related commentary by Werner and Bruchim: <url>http://www.biomedcentral.com/1741-7015/8/2</url></p

The biophysical climate mitigation potential of boreal peatlands during the growing season

Peatlands and forests cover large areas of the boreal biome and are critical for global climate regulation. They also regulate regional climate through heat and water vapour exchange with the atmosphere. Understanding how land-atmosphere interactions in peatlands differ from forests may therefore be crucial for modelling boreal climate system dynamics and for assessing climate benefits of peatland conservation and restoration. To assess the biophysical impacts of peatlands and forests on peak growing season air temperature and humidity, we analysed surface energy fluxes and albedo from 35 peatlands and 37 evergreen needleleaf forests-the dominant boreal forest type-and simulated air temperature and vapour pressure deficit (VPD) over hypothetical homogeneous peatland and forest landscapes. We ran an evapotranspiration model using land surface parameters derived from energy flux observations and coupled an analytical solution for the surface energy balance to an atmospheric boundary layer (ABL) model. We found that peatlands, compared to forests, are characterized by higher growing season albedo, lower aerodynamic conductance, and higher surface conductance for an equivalent VPD. This combination of peatland surface properties results in a similar to 20% decrease in afternoon ABL height, a cooling (from 1.7 to 2.5 degrees C) in afternoon air temperatures, and a decrease in afternoon VPD (from 0.4 to 0.7 kPa) for peatland landscapes compared to forest landscapes. These biophysical climate impacts of peatlands are most pronounced at lower latitudes (similar to 45 degrees N) and decrease toward the northern limit of the boreal biome (similar to 70 degrees N). Thus, boreal peatlands have the potential to mitigate the effect of regional climate warming during the growing season. The biophysical climate mitigation potential of peatlands needs to be accounted for when projecting the future climate of the boreal biome, when assessing the climate benefits of conserving pristine boreal peatlands, and when restoring peatlands that have experienced peatland drainage and mining.Peer reviewe

A global experiment on motivating social distancing during the COVID-19 pandemic

Finding communication strategies that effectively motivate social distancing continues to be a global public health priority during the COVID-19 pandemic. This cross-country, preregistered experiment (n = 25,718 from 89 countries) tested hypotheses concerning generalizable positive and negative outcomes of social distancing messages that promoted personal agency and reflective choices (i.e., an autonomy-supportive message) or were restrictive and shaming (i.e., a controlling message) compared with no message at all. Results partially supported experimental hypotheses in that the controlling message increased controlled motivation (a poorly internalized form of motivation relying on shame, guilt, and fear of social consequences) relative to no message. On the other hand, the autonomy-supportive message lowered feelings of defiance compared with the controlling message, but the controlling message did not differ from receiving no message at all. Unexpectedly, messages did not influence autonomous motivation (a highly internalized form of motivation relying on one’s core values) or behavioral intentions. Results supported hypothesized associations between people’s existing autonomous and controlled motivations and self-reported behavioral intentions to engage in social distancing. Controlled motivation was associated with more defiance and less long-term behavioral intention to engage in social distancing, whereas autonomous motivation was associated with less defiance and more short- and long-term intentions to social distance. Overall, this work highlights the potential harm of using shaming and pressuring language in public health communication, with implications for the current and future global health challenges