The effect of thermal manipulations during the development of the thyroid and adrenal axes on in-hatch and post-hatch thermoregulation

This study aimed to elucidate the effects of thermal manipulation (TM) during the development and maturation of the thyroid and adrenal axis on broiler chicks hatchability and thermoregulation during hatch, and to evaluate the improvement of thermotolerance acquisition of TM chicks by thermally challenging them post-hatch. Fertile Cobb eggs were divided into three treatments: control, 12 and 24 H. The control eggs were incubated under standard conditions, whereas the 12 and 24 H eggs were incubated from 7 d of incubation (E7) until E16 (inclusive) at 39.5 °C and 65% RH for 12 h/d (12 H) or continuously (24 H). Hatchability, BW and quality of the hatched 24 H chicks were negatively affected, but exhibited significantly improved thermotolerance on heat stress at 3 and 10 d of age for males and females, respectively. It can be concluded that continuous TM during embryogenesis impaired broiler chick performance, but improved their ability to thermoregulate in response to thermal challenge mainly by reducing heat production.     

Reference‐independent wide field fluorescence lifetime measurements using Frequency‐Domain (FD) technique based on phase and amplitude crossing point

Fluorescence lifetime imaging microscopy (FLIM) is an essential tool in many scientific fields such as biology and medicine thanks to the known advantages of the fluorescence lifetime (FLT) over the classical fluorescence intensity (FI). However, the frequency domain (FD) FLIM technique suffers from its strong dependence on the reference and its compliance to the sample. In this paper, we suggest a new way to calculate the FLT by using the crossing point (CRPO) between the modulation and phase FLTs measured over several light emitting diode (LED) DC currents values instead of either method alone. This new technique was validated by measuring homogeneous substances with known FLT, where the CRPO appears to be the optimal measuring point. Furthermore, the CRPO method was applied in heterogeneous samples. It was found that the CRPO in known mixed solutions is the weighted average of the used solutions. While measuring B16 and lymphocyte cells, the CRPO of the DAPI compound in single FLT regions was measured at 3.5 ± 0.06 ns and at 2.83 ± 0.07 ns, respectively, both of which match previous reports and multi‐frequency analyses. This paper suggests the CRPO as a new method to extract the FLT in problematic cases such as high MCP gains and heterogeneous environments.

In traditional FD FLIM measurements, the variation in phase angle and modulation are measured. By measuring over varying DC currents, another variation is detected in the FLT determined through the phase and modulation methods, with the CRPO indicating the true FLT.     

Relevance of intra-hospital patient movements for the spread of healthcare-associated infections within hospitals - a mathematical modeling study

The aim of this study is to analyze patient movement patterns between hospital departments to derive the underlying intra-hospital movement network, and to assess if movement patterns differ between patients at high or low risk of colonization. For that purpose, we analyzed patient electronic medical record data from five hospitals to extract information on risk stratification and patient intra-hospital movements. Movement patterns were visualized as networks, and network centrality measures were calculated. Next, using an agent-based model where agents represent patients and intra-hospital patient movements were explicitly modeled, we simulated the spread of multidrug resistant enterobacteriacae (MDR-E) inside a hospital. Risk stratification of patients according to certain ICD-10 codes revealed that length of stay, patient age, and mean number of movements per admission were higher in the high-risk groups. Movement networks in all hospitals displayed a high variability among departments concerning their network centrality and connectedness with a few highly connected departments and many weakly connected peripheral departments. Simulating the spread of a pathogen in one hospital network showed positive correlation between department prevalence and network centrality measures. This study highlights the importance of intra-hospital patient movements and their possible impact on pathogen spread. Targeting interventions to departments of higher (weighted) degree may help to control the spread of MDR-E. Moreover, when the colonization status of patients coming from different departments is unknown, a ranking system based on department centralities may be used to design more effective interventions that mitigate pathogen spread.     

Thermal manipulations during broiler embryogenesis improves post-hatch performance under hot conditions

Previous studies on broilers conducted in our laboratory showed that intermittent thermal manipulation (TM) of 39.5 °C every 12 h during embryonic days E7–E16 improved thermoregulative parameters in the embryo and post-hatch, as well as the broilers' ability to cope with heat challenge at marketing age. The aim of this study was to investigate the effect of intermittent TM of 39.5 °C (65% RH) for 12 h/d (12 H), during E7–E16, on post-hatch performance and thermoregulation under both optimal and hot conditions. Chicks from the control and TM treatments were raised under “regular” conditions until 21 d of age. Then, each treatment was divided into 2 sub-treatments (growth conditions) – optimal conditions (25 °C) and hot conditions of 32 °C for 12 h/d – until 35 d of age. Under optimal conditions, no difference in growth rates was found between TM and control throughout the growth period, but TM had significantly larger relative breast muscle weight, and on days 13, 25, and 35 breast muscle in the TM treatment contained a higher percentage of large-diameter fibers than controls. Consequently, average fiber diameter was significantly larger in TM than in control. Relative weight of the abdominal fat pad was significantly lower in the TM treatment than in control, under both environmental conditions. Hot conditions negatively affected growth rates of broilers in both treatments. The TM chickens showed no body-weight advantage over controls, nevertheless, feed conversion between days 21 and 35 was lower in the TM chickens of both sexes than in controls. This could be attributed to lower body temperature and lower plasma thyroid hormone levels found in the TM chickens, indicating lower heat production rates. Greater muscle growth and lower relative weight of abdominal fat pad were found in the TM chickens than in controls, under hot conditions. It can be concluded that TM during embryonic development improves performance as well as thermoregulation.     

Cryo-electron tomography: gaining insight into cellular processes by structural approaches

Visualization of cellular processes at a resolution of the individual protein should involve integrative and complementary approaches that can eventually draw realistic functional and cellular landscapes. Electron tomography of vitrified but otherwise unaltered cells emerges as a central method for three-dimensional reconstruction of cellular architecture at a resolution of 2-6 nm. While a combination of correlative light-based microscopy with cryo-electron tomography (cryo-ET) provides medium-resolution insight into pivotal cellular processes, fitting high-resolution structural approaches, for example, X-ray crystallography, into reconstructed macromolecular assemblies provides unprecedented information on native protein assemblies. Thus, cryo-ET bridges the resolution gap between cellular and structural biology. In this article, we focus on the study of eukaryotic cells and macromolecular complexes in a close-to-life-state. We discuss recent developments and structural findings enabling major strides to be made in understanding complex physiological functions.     

Visual exploration across biomedical databases

Though biomedical research often draws on knowledge from a wide variety of fields, few visualization methods for biomedical data incorporate meaningful cross-database exploration. A new approach is offered for visualizing and exploring a query-based subset of multiple heterogeneous biomedical databases. Databases are modeled as an entity-relation graph containing nodes (database records) and links (relationships between records). Users specify a keyword search string to retrieve an initial set of nodes, and then explore intra- and interdatabase links. Results are visualized with user-defined semantic substrates to take advantage of the rich set of attributes usually present in biomedical data. Comments from domain experts indicate that this visualization method is potentially advantageous for biomedical knowledge exploration.     

An In Vivo Metabolic Approach for Deciphering the Product Specificity of Glycerate Kinase Proves that Both E. coli’s Glycerate Kinases Generate 2-Phosphoglycerate

Apart from addressing humanity’s growing demand for fuels, pharmaceuticals, plastics and other value added chemicals, metabolic engineering of microbes can serve as a powerful tool to address questions concerning the characteristics of cellular metabolism. Along these lines, we developed an in vivo metabolic strategy that conclusively identifies the product specificity of glycerate kinase. By deleting E. coli’s phosphoglycerate mutases, we divide its central metabolism into an ‘upper’ and ’lower’ metabolism, each requiring its own carbon source for the bacterium to grow. Glycerate can serve to replace the upper or lower carbon source depending on the product of glycerate kinase. Using this strategy we show that while glycerate kinase from Arabidopsis thaliana produces 3-phosphoglycerate, both E. coli’s enzymes generate 2-phosphoglycerate. This strategy represents a general approach to decipher enzyme specificity under physiological conditions.     

A locus for an autosomal dominant form of progressive renal failure and hypertension at chromosome 1q21

Linkage studies were performed in a large family with an autosomal dominant phenotype characterized by nephropathy and hypertension. In this family of Iraqi Jewish origin, the nephropathy develops into progressive renal failure. By performing a genomewide linkage search, we localized the disease gene to chromosome 1q21; the highest LOD score was obtained for the marker at locus D1S305, which yielded a maximum LOD score of 4.71 at a recombination fraction of 0. Recombination mapping defined an interval of approximately 11.6 cM, between the markers at loci D1S2696 and D1S2635, that contains the disease gene. Localization of the disease-causing gene in this family represents a necessary step toward isolation of the defective gene and toward a deeper understanding of the mechanisms of hypertension and progressive renal failure.     

Signalling pathways in vascular endothelium activated by shear stress: relevance to atherosclerosis

Major advances in our understanding of how endothelial cells sense and respond to haemodynamic forces and, more specifically, to fluid shear stress have been achieved during the past 3 years. These include definition of potential shear stress receptors and multiple signalling pathways that mediate shear stress regulation of gene expression. A few studies have also pointed to the unique effects of complex shear stress on endothelial activation, thus leading to better understanding of the mechanisms that lead to the development of atherosclerosis.