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Background: Microglia and macrophages (MMs) are the largest component of the inflammatory infiltrate in glioblastoma (GBM). However, whether there are immunophenotypic differences in isocitrate dehydrogenase (IDH)-mutated and -wildtype GBMs is unknown. Studies on specimens of untreated IDH-mutant GBMs are rare given they comprise 10% of all GBMs and often receive treatment at lower grades that can drastically alter MM phenotypes. Methods: We obtained large samples of untreated IDH-mutant and -wildtype GBMs. Using immunofluorescence techniques with single-cell automated segmentation, and comparison between single-cell RNA-sequencing (scRNA-seq) databases of human GBM, we discerned dissimilarities between GBM-associated MMs (GAMMs). Results: There are significantly fewer but more pro-inflammatory GAMMs in IDH-mutant GBMs, suggesting this contributes to the better prognosis of these tumors. Our pro-inflammatory score which combines the expression of inflammatory markers (CD68/HLA-A, -B, -C/TNF/CD163/IL10/TGFB2), Iba1 intensity, and GAMM surface area also indicates more pro-inflammatory GAMMs are associated with longer overall survival independent of IDH status. scRNA-seq analysis demonstrates microglia in IDH-mutants are mainly pro-inflammatory, while anti-inflammatory macrophages that upregulate genes such as FCER1G and TYROBP predominate in IDH-wildtype GBM. Conclusions: Taken together, these observations are the first head-to-head comparison of GAMMs in treatment-naïve IDH-mutant versus -wildtype GBMs that highlight biological disparities that can be exploited for therapeutic purposes.
X-ray microscopy is a field that has developed rapidly in recent years. Two different approaches have been used. Zone plates have been employed to produce focussed beams with sizes as low as 0.07 pm for x-ray energies below 1 keV. Images of biological materials and elemental maps for major and minor low Z have been produced using above and below absorption edge differences. At higher energies collimators and focussing mirrors have been used to make small diameter beams for excitation of characteristic K— or L-x rays of all elements in the periodic
Polyphenol oxidase (PPO) in red clover (RC) has been shown to reduce both lipolysis and proteolysis in silo and implicated (in vitro) in the rumen. However, all in vivo comparisons have compared RC with other forages, typically with lower levels of PPO, which brings in other confounding factors as to the cause for the greater protection of dietary nitrogen (N) and C18 polyunsaturated fatty acids (PUFA) on RC silage. This study compared two RC silages which when ensiled had contrasting PPO activities (RC+ and RC−) against a control of perennial ryegrass silage (PRG) to ascertain the effect of PPO activity on dietary N digestibility and PUFA biohydrogenation. Two studies were performed the first to investigate rumen and duodenal flow with six Hereford×Friesian steers, prepared with rumen and duodenal cannulae, and the second investigating whole tract N balance using six Holstein-Friesian non-lactating dairy cows. All diets were offered at a restricted level based on animal live weight with each experiment consisting of two 3×3 Latin squares using big bale silages ensiled in 2010 and 2011, respectively. For the first experiment digesta flow at the duodenum was estimated using a dual-phase marker system with ytterbium acetate and chromium ethylenediaminetetraacetic acid as particulate and liquid phase markers, respectively. Total N intake was higher on the RC silages in both experiments and higher on RC− than RC+. Rumen ammonia-N reflected intake with ammonia-N per unit of N intake lower on RC+ than RC−. Microbial N duodenal flow was comparable across all silage diets with non-microbial N higher on RC than the PRG with no difference between RC+ and RC−, even when reported on a N intake basis. C18 PUFA biohydrogenation was lower on RC silage diets than PRG but with no difference between RC+ and RC−. The N balance trial showed a greater retention of N on RC+ over RC−; however, this response is likely related to the difference in N intake over any PPO driven protection. The lack of difference between RC silages, despite contrasting levels of PPO, may reflect a similar level of protein-bound-phenol complexing determined in each RC silage. Previously this complexing has been associated with PPOs protection mechanism; however, this study has shown that protection is not related to total PPO activity.
Let n be a fixed positive integer, and consider an alphabet consisting of the numbers 1, 2, … , n. With this alphabet form all possible k-letter words (a1a2 … ak), where k is also fixed. There are evidently nk such words in all.
Scientists have long known that certain pesticides, industrial chemicals and heavy metals have a detrimental impact on the reproductive health of a wide range of species (including humans) by disrupting the endocrine system. As exposure to, and the effects of, ‘endocrine disrupters’ are likely to be more pronounced in wild species with a short gestation period and life-cycle we have chosen to develop non-invasive tools based upon faecal steroid analysis to monitor the reproductive status of the short-tailed field vole (Microtus agrestis). This approach is hoped to eventually provide a sensitive means of detecting environmental disturbances that could adversely affect humans, livestock and wildlife by establishing the the field vole as a terrestrial biomarker. Faecal steroid hormone analysis has already been demonstrated as being a convenient and reliable means of diagnosing reproductive state in a large range of mammalian species (including gazelle, rhino, macaque and mice), however, as of yet little is known regarding the hormonal changes that occur during pregnancy in M. agrestis.
The pre-requisites for nutritional management of dairy cows are information about how much feed is being consumed as well as the nutrients that are being derived from that feed. Studies of feed intake and nutrient supply have been limited by difficult experimental techniques, particularly with grazing animals. The models derived from much earlier work are of only general applicability and there is a need for more site-specific information in order to benefit further from conceptual advances.
We have adopted a different approach to studying herbage intake and nutrient supply, using less-invasive approaches as well as techniques that monitor more accessible aspects of these processes, such as jaw movements. These techniques have a major advantage, in addition to their value as research tools, because they could translate directly into commercial applications in on-farm monitoring. The use of diagnostics and behavioural recording is well explored in relation to health monitoring; here we argue for its potential to advance the application of knowledge about grazing and nutrition. We will illustrate this approach using our experiences in measuring grazing behaviour, using IGER behaviour recorders and assessing rumen function, using a series of non-invasive techniques.
The IGER grazing behaviour recorder allows us to record jaw movements and hence grazing and ruminating time and bite dynamics. It also allows the recording of steps and is now being developed to incorporate non-invasive rumen state sensors. It has made a major contribution to our understanding of the foraging strategies of grazing animals and their effect on herbage intake. This technology has the potential to be developed for on-farm monitoring of foraging behaviour providing valuable inputs to the prediction of herbage intake, in decision support systems for grazing.
The introduction of concept of protein degradation and microbial synthesis in the rumen are significant advances in protein rationing schemes. However, real progress has been limited because the lack of consistent experimental results means that models have little relevance to specific farm situations. We foresee considerable opportunities to monitor products of rumen degradation and synthesis that appear in milk (e.g. odd-chain fatty acids) or breath (e.g. sulphides).
Taken together these technologies open the possibilities of an entirely new approach to nutritional management of dairy cows, with site-specific recommendations based on information gathered using new sensors that are incorporated into computerised feeding equipment and milking parlours.
This experiment was conducted to evaluate the effect of adding some herbal feed additives (HF A) [thyme (T, Thymus Vulgaris L.), dianthus (D, Delphinum Ajaews), and fennel (F, Foeniculum Vulgare L.)] at a level of 10g/kg to Japanese quail diets on performance and some metabolic functions. Adding HFA to the control diet improved (P<0.05) body gain, feed intake and feed conversion (feed/gain) efficiency. The birds fed dietary F additive exhibited the best (P<0.05) values of these parameters during the entire period (0 to 6 weeks of age), compared with other dietary treatments. There was an improvement (P<0.05) in total protein, globulin, and albumin for birds fed dietary T or F at six weeks of age. Birds fed on dietary F recorded the lowest (P<0.05) value of these components compared with other dietary treatments.
This study compared the effect of feeding AmyPlus, a moist feed, as opposed to rolled wheat on the yield and composition of milk from dairy cows consuming grass silage based total mixed ration (TMR). Seventy-two Holstein-Friesian cows were distributed into AmyPlus (Treatment) and Wheat (Control) groups and loose housed on straw in an open shed. Each kg Wheat based concentrate contained 345g rolled wheat, 230g rapeseed meal, 115g sugarbeet pulp, 115g Molaferm 20, 115g soybean meal, 56g barley straw and 24g vitamin-minerals. In contrast, each kg AmyPlus based concentrate contained 501g AmyPlus (480g DM /kg), 105g rapeseed meal, 126g sugarbeet pulp, 126g Molaferm 20, 84g soybean meal, 41g barley straw and 17g vitamin-minerals. Here, AmyPlus was loaded directly into the mixer wagon to prepare fresh AmyPlus based TMR with a silage to concentrate ratio of 68:32. Each TMR was fed once daily to the corresponding group of cows also receiving 2kg of Distillers’ grains per cow in the parlour during milking. Daily milk yield and composition was recorded from November 1999 to February 2000. The overall daily Dry matter intake (DMI) of each TMR per cow remained uniform (20.19 vs 20.15 kg for Treatment and Control group respectively) across both groups. Daily milk yield and total cell counts per cow did not vary significantly (P>0.05) between groups during various months. While, milk fat and protein contents were greater in Treatment than Control group during each month, the differences were significant (P<0.05) only during November and December for fat and in January for protein. On average, the Treatment group tended to show a non-significant increase (P>0.05) in daily milk yield per cow by 0.144 kg than the Control group. The fat (46.2 vs 43.7) and protein (34.5 vs 33.5) contents in g /kg milk were also increased significantly (P<0.001) in Treatment compared with Control group. Total cell counts did not vary significantly (P>0.05) and remained within the acceptable limits. The cows consuming AmyPlus maintained their health as indicated by their intake, production, cell counts and general appearance. It would appear that AmyPlus can replace rolled wheat in TMR. However, it may be necessary to evaluate the storage, economic and environmental implications of using such moist co-products in silage based dairy rations.
One of the cornerstones in the development of a new feed rationing system for dairy cows must involve a reappraisal of both the concepts and ‘numbers’ adopted in defining the energy requirements for dairy cows. This is particularly important in the present scenario where increasingly high levels of animal output are being achieved from very different animal genotypes to those used in UK dairying 20 - 30 years ago. One of the tasks within the Feed Into Milk (FIM) project was to develop a new system to predict the energy requirements of todays dairy cow. The objective of the present study was to collate all available energy metabolism data with dairy cows in the UK and to develop relationships for describing metabolisable energy (ME) requirement for maintenance (MEm) and efficiency of ME use for lactation (kl) using both existing and new methodologies.
The Feed into Milk (FIM) project in the United Kingdom has developed a Mitscherlich equation from calorimetric data for energy rationing of dairy cattle (Agnew et al., 2004). The objective of the present study was to evaluate this equation using independent data sets obtained in both calorimetric and production studies.
The Taipan galaxy survey (hereafter simply ‘Taipan’) is a multi-object spectroscopic survey starting in 2017 that will cover 2π steradians over the southern sky (δ ≲ 10°, |b| ≳ 10°), and obtain optical spectra for about two million galaxies out to z < 0.4. Taipan will use the newly refurbished 1.2-m UK Schmidt Telescope at Siding Spring Observatory with the new TAIPAN instrument, which includes an innovative ‘Starbugs’ positioning system capable of rapidly and simultaneously deploying up to 150 spectroscopic fibres (and up to 300 with a proposed upgrade) over the 6° diameter focal plane, and a purpose-built spectrograph operating in the range from 370 to 870 nm with resolving power R ≳ 2000. The main scientific goals of Taipan are (i) to measure the distance scale of the Universe (primarily governed by the local expansion rate, H0) to 1% precision, and the growth rate of structure to 5%; (ii) to make the most extensive map yet constructed of the total mass distribution and motions in the local Universe, using peculiar velocities based on improved Fundamental Plane distances, which will enable sensitive tests of gravitational physics; and (iii) to deliver a legacy sample of low-redshift galaxies as a unique laboratory for studying galaxy evolution as a function of dark matter halo and stellar mass and environment. The final survey, which will be completed within 5 yrs, will consist of a complete magnitude-limited sample (i ⩽ 17) of about 1.2 × 106 galaxies supplemented by an extension to higher redshifts and fainter magnitudes (i ⩽ 18.1) of a luminous red galaxy sample of about 0.8 × 106 galaxies. Observations and data processing will be carried out remotely and in a fully automated way, using a purpose-built automated ‘virtual observer’ software and an automated data reduction pipeline. The Taipan survey is deliberately designed to maximise its legacy value by complementing and enhancing current and planned surveys of the southern sky at wavelengths from the optical to the radio; it will become the primary redshift and optical spectroscopic reference catalogue for the local extragalactic Universe in the southern sky for the coming decade.
Plateau icefields occur commonly in glacierized areas and not uncommonly in glaciated mountains. We report on a glacierized area of plateaux and valleys centred round the highest peak Jiehkkevárri (1833 m) in the maritime Lyngen Alps, North Norway. Some valley glaciers are fed by steep, narrow plateau glacier outlets and/or ice avalanching from the plateaux over precipitous cliffs. Plateaux must therefore be considered as “contributing areas”, if they supply ice to valley systems below. Equilibrium line altitudes (ELAs) are calculated for the valley glaciers during the Little Ice Age (LIA), accounting for both input and no input of ice from plateaux above. The results show that ELAs may be at significantly higher altitudes when plateau/x are contributing ice mass. The response of plateau glaciers to climate amelioration since the end of the LIA is somewhat different to that of valley glaciers, which appear to be retreating markedly. These findings have significant implications for the interpretation of moraine systems, glacier dynamics, the construction and reconstruction of present and former ELAs, and palaeoclimates in glacierized and glaciated mountain plateau areas.
In 1944 Fritz Heider and Marianne Simmel published the results of a novel experiment conducted at Smith College in Northampton, Massachusetts. In “An experimental study of apparent behavior” Heider and Simmel (1944) prepared a brief film depicting the movements of a two triangles and a circle in and around a shape made to look like a room with a door. The film was shown to 114 undergraduate women at Smith College divided into three experimental groups. In the first, subjects were given the general instruction to “write down what happened in the picture.” In the second, subjects were instructed to interpret the movements of the figures as actions of persons and to answer ten questions in a written questionnaire. The third group was shown the film in reverse, by running the filmstrip backwards through the projector, and asked a subset of the same questions.
The Heider–Simmel film, which is today readily viewable on online video websites, is not particularly remarkable as a piece of animated cinematography. Compared to Walt Disney's films of the same era, including Pinocchio, Fantasia, and Bambi, the film must have appeared anachronistic even to the original Smith College subjects. Each frame in the film was produced as a photo of geometric shapes cut from cardboard and placed on a horizontal translucent-glass plate illuminated from above. The careful placement of the shapes in each frame created a narrative stream of events, evidenced only by the silent trajectories of each shape and its position in relation to the others. As expected, the subjects in the three experimental groups interpreted these events as a coherent narrative and described them in terms of the interrelated behaviors of three intentional characters, in and around a room defined by four walls and a door. Somewhat surprising is the degree to which these descriptions attributed mental states to these nondescript shapes. Heider and Simmel provide the following as representative of the descriptions produced by the first experimental group:
A man has planned to meet a girl and the girl comes along with another man. The first man tells the second to go; the second tells the first, and he shakes his head. Then the two men have a fight, and the girl starts to go into the room to get out of the way and hesitates and finally goes in.