Several temperature-humidity indexes (THI) have been used to estimate the degree of thermal stress experienced by dairy cows. The present objectives were to develop equations using meteorological ...variables that predicted rectal temperature of lactating cows in a subtropical environment and compare the goodness of fit of these equations to those using 8 different THI. Rectal temperature was measured between 1500 and 1700h in 1,280 lactating Holstein cows in north central Florida between August and December. Meteorological data recorded in the barn where cows were located included dry bulb temperature (Tdb), relative humidity (RH), dew point temperature, and wind speed. Wet bulb temperature was calculated. In the first series of analyses, regression analysis was used to model rectal temperature using the meteorological variables as well as THI. The r2 using Tdb (0.41) was slightly less than for models using all but one THI (r2 between 0.42 and 0.43). The r2 for equations using Tdb could be improved by adding RH (r2=0.43) or RH and RH2 (r2=0.44) to the model. In the second analysis, regression analysis was performed using forward selection, backward elimination, and stepwise selection procedures with the meteorological variables. All models gave a similar goodness of fit (r2=0.44). An analysis of variance with rectal temperature as a class variable was performed to determine the least squares means of meteorological measurements associated with hyperthermia. A Tdb of 29.7°C was associated with rectal temperature of 39°C, and a Tdb of 31.4°C was associated with rectal temperature of 39.5°C. In conclusion, Tdb is nearly as good a predictor of rectal temperatures of lactating Holsteins in a subtropical environment as THI. Estimates of values of meteorological variables associated with specific rectal temperatures should prove valuable in relating environmental conditions to the magnitude of hyperthermia experienced by heat-stressed cows.
Emerging Targets in Photopharmacology Lerch, Michael M.; Hansen, Mickel J.; van Dam, Gooitzen M. ...
Angewandte Chemie (International ed.),
September 5, 2016, Volume:
55, Issue:
37
Journal Article
Peer reviewed
Open access
The field of photopharmacology uses molecular photoswitches to establish control over the action of bioactive molecules. It aims to reduce systemic drug toxicity and the emergence of resistance, ...while achieving unprecedented precision in treatment. By using small molecules, photopharmacology provides a viable alternative to optogenetics. We present here a critical overview of the different pharmacological targets in various organs and a survey of organ systems in the human body that can be addressed in a non‐invasive manner. We discuss the prospects for the selective delivery of light to these organs and the specific requirements for light‐activatable drugs. We also aim to illustrate the druggability of medicinal targets with recent findings and emphasize where conceptually new approaches have to be explored to provide photopharmacology with future opportunities to bring “smart” molecular design ultimately to the realm of clinical use.
Spotlight on the patient: The impressive advances made in the field of photopharmacology in recent years are critically reviewed with respect to the “photodruggability” of medicinal targets and prospects for the selective delivery of light to different organs. This Review is meant to provide a stimulus for chemists to enter this exciting field, with fascinating opportunities to bring “smart” molecular design to the realm of clinical use.
The present study investigated the effect of graded levels of black soldier fly larvae (BSFL) (Hermetia illucens) meal and paste on physical pellet quality, digestibility and utilization of nutrients ...and growth performances in extruded diets for Atlantic salmon (Salmo salar). A total of 1260 Atlantic salmon with 34 g of mean initial weight were randomly distributed into 21 fiberglass tanks and fed with one of seven isonitrogenous, isolipidic and isoenergetic diets for seven weeks. The experimental diets consisted of a control diet based on fishmeal, soy protein concentrate, corn gluten, faba bean and fish oil (Control-1); three diets with increased levels of full-fat BSFL meal, substituting 6.25% (6.25IM), 12.5% (12.5IM) and 25% (25IM) of the protein content of Control-1; two diets with increased levels of full-fat BSFL paste, substituting 3.7% (3.7IP) and 6.7% (6.7IP) of protein from Control-1 and an extra control diet with 0.88% of formic acid (Control-2). Pellet durability and hardness were overall high for all diets. However, the expansion, sinking velocity and water stability of feed pellets were lower with increased inclusion of BSFL meal and paste. Dietary inclusion of BSFL meal or paste did not affect the feed intake of fish. Further, replacing the protein content of the control diet with up to 12.5% and 6.7% of BSFL meal and paste, respectively, did not compromise fish growth rate or feed conversion ratio, although polynomial contrast analysis showed that increasing BSFL meal level in the diet linearly (p < .05) decreased these parameters. However, apparent digestibility coefficient (ADC) of protein and lipid, protein efficiency ratio and lipid retention were reduced linearly (p < .05) with increasing inclusion level of BSFL meal. Further, increasing dietary levels of BSFL paste linearly (p < .05) reduced ADC of protein, protein efficiency ratio and phosphorous retention. Despite the decreased ADC of protein, protein retention was not compromised by the inclusion of BSFL meal or paste. Replacement of 25% of dietary protein with BSFL meal decreased (p < .05) growth rate, accompanied by lower (p < .05) ADC and utilization of lipids and protein efficiency ratio. The present study showed that BSFL meal and paste could replace up to 12.5% and 6.7% of dietary protein, respectively, without compromising growth performance in Atlantic salmon.
•Insect meal and paste gave high pellet durability but reduced water stability.•Up to 12.5% insect meal and 6.7% paste supported high growth performance.•Insect meal reduced protein and lipid digestibility and lipid retention.•Insect paste reduced protein digestibility and efficiency ratio and P retention.
Land use is expanding and intensifying in the unprotected lands surrounding many of the world's protected areas. The influence of this land use change on ecological processes is poorly understood. ...The goal of this paper is to draw on ecological theory to provide a synthetic framework for understanding how land use change around protected areas may alter ecological processes and biodiversity within protected areas and to provide a basis for identifying scientifically based management alternatives. We first present a conceptual model of protected areas embedded within larger ecosystems that often include surrounding human land use. Drawing on case studies in this Invited Feature, we then explore a comprehensive set of ecological mechanisms by which land use on surrounding lands may influence ecological processes and biodiversity within reserves. These mechanisms involve changes in ecosystem size, with implications for minimum dynamic area, species-area effect, and trophic structure; altered flows of materials and disturbances into and out of reserves; effects on crucial habitats for seasonal and migration movements and population source/sink dynamics; and exposure to humans through hunting, poaching, exotics species, and disease. These ecological mechanisms provide a basis for assessing the vulnerability of protected areas to land use. They also suggest criteria for designing regional management to sustain protected areas in the context of surrounding human land use. These design criteria include maximizing the area of functional habitats, identifying and maintaining ecological process zones, maintaining key migration and source habitats, and managing human proximity and edge effects.
Growing evidence supports a role for extracellular vesicles (EVs) in haemostasis and thrombosis due to exposure of negatively charged procoagulant phospholipids (PPL). Current commercial ...PPL-dependent clotting assays use chemically phospholipid depleted plasma to measure PPL activity. The purpose of our study was to modify the PPL assay by substituting the chemically phospholipid depleted plasma with PPL depleted plasma obtained by ultracentrifugation This in order to get readily access to a sensitive and reliable assay to measure PPL activity in human plasma and cell supernatants. The performance of the assay was tested, including the influence of individual coagulation factors and postprandial lipoproteins and compared to a commercial PPL assay (STA-Procoag-PPL). The two PPL assays displayed similar sensitivity to exogenously added standardized phospholipids. The PPL activity measured by the modified assay strongly correlates with the results from the commercial assay. The intraday- and between-days coefficients of variation ranged from 2-4% depending on the PPL activity in the sample. The modified PPL assay was insensitive to postprandial lipoprotein levels in plasma, as well as to tissue factor (TF) positive EVs from stimulated whole blood. Our findings showed that the modified assay performed equal to the comparator, and was insensitive to postprandial lipoproteins and TF
EVs.
Abstract Freeze-drying is the preferred method for stabilizing live, attenuated virus vaccines. After decades of research on several aspects of the process like the stabilization and destabilization ...mechanisms of the live, attenuated viruses during freeze-drying, the optimal formulation components and process settings are still matter of research. The molecular complexity of live, attenuated viruses, the multiple destabilization pathways and the lack of analytical techniques allowing the measurement of physicochemical changes in the antigen's structure during and after freeze-drying mean that they form a particular lyophilization challenge. The purpose of this review is to overview the available information on the development of the freeze-drying process of live, attenuated virus vaccines, herewith focusing on the freezing and drying stresses the viruses can undergo during processing as well as on the mechanisms and strategies (formulation and process) that are used to stabilize them during freeze-drying.
The purpose of this paper is threefold. First, we review the existing literature on flow rates of water in carbon nanotubes. Data for the slip length which characterizes the flow rate are scattered ...over 5 orders of magnitude for nanotubes of diameter 0.81-10 nm. Second, we precisely compute the slip length using equilibrium molecular dynamics (EMD) simulations, from which the interfacial friction between water and carbon nanotubes can be found, and also via external field driven non-equilibrium molecular dynamics simulations (NEMD). We discuss some of the issues in simulation studies which may be reasons for the large disagreements reported. By using the EMD method friction coefficient to determine the slip length, we overcome the limitations of NEMD simulations. In NEMD simulations, for each tube we apply a range of external fields to check the linear response of the fluid to the field and reliably extrapolate the results for the slip length to values of the field corresponding to experimentally accessible pressure gradients. Finally, we comment on several issues concerning water flow rates in carbon nanotubes which may lead to some future research directions in this area.
The traditional view of the planktonic food web describes consumption of inorganic nutrients by photoautotrophic phytoplankton, which in turn supports zooplankton and ultimately higher trophic ...levels. Pathways centred on bacteria provide mechanisms for nutrient recycling. This structure lies at the foundation of most models used to explore biogeochemical cycling, functioning of the biological pump, and the impact of climate change on these processes. We suggest an alternative new paradigm, which sees the bulk of the base of this food web supported by protist plankton communities that are mixotrophic - combining phototrophy and phagotrophy within a single cell. The photoautotrophic eukaryotic plankton and their heterotrophic microzooplankton grazers dominate only during the developmental phases of ecosystems (e.g. spring bloom in temperate systems). With their flexible nutrition, mixotrophic protists dominate in more-mature systems (e.g. temperate summer, established eutrophic systems and oligotrophic systems); the more-stable water columns suggested under climate change may also be expected to favour these mixotrophs. We explore how such a predominantly mixotrophic structure affects microbial trophic dynamics and the biological pump. The mixotroph-dominated structure differs fundamentally in its flow of energy and nutrients, with a shortened and potentially more efficient chain from nutrient regeneration to primary production. Furthermore, mixotrophy enables a direct conduit for the support of primary production from bacterial production. We show how the exclusion of an explicit mixotrophic component in studies of the pelagic microbial communities leads to a failure to capture the true dynamics of the carbon flow. In order to prevent a misinterpretation of the full implications of climate change upon biogeochemical cycling and the functioning of the biological pump, we recommend inclusion of multi-nutrient mixotroph models within ecosystem studies.
DNA-encoded small molecule libraries (DELs) have facilitated the discovery of novel modulators of many different therapeutic protein targets. We report the first successful screening of a ...multimillion membered DEL inside a living cell. We demonstrate a novel method using oocytes from the South African clawed frog Xenopus laevis. The large size of the oocytes of 1 μL, or 100 000 times bigger than a normal somatic cell, permits simple injection of DELs, thus resolving the fundamental problem of delivering DELs across cell membranes for in vivo screening. The target protein was expressed in the oocytes fused to a prey protein, to allow specific DNA labeling and hereby discriminate between DEL members binding to the target protein and the endogenous cell proteins. The 194 million member DEL was screened against three pharmaceutically relevant protein targets, p38α, ACSS2, and DOCK5. For all three targets multiple chemical clusters were identified. For p38α, validated hits with single digit nanomolar potencies were obtained. This work demonstrates a powerful new approach to DEL screening, which eliminates the need for highly purified active target protein and which performs the screening under physiological relevant conditions and thus is poised to increase the DEL amenable target space and reduce the attrition rates.
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