Regulation of subcutaneous adipose tissue blood flow during exercise in humans

Regulation of subcutaneous adipose tissue blood flow (ATBF) remains poorly elucidated in humans, especially during exercise. In the present study we tested the role of adenosine in the regulation of ATBF adjacent to active and inactive thigh muscles during intermittent isometric knee-extension exercise (1 s contraction followed by 2 s rest with workloads of 50, 100, and 150 N) in six healthy young women. ATBF was measured using positron emission tomography (PET) without and with unspecific adenosine receptor inhibitor theophylline infused intravenously. Adipose regions were localized from fused PET and magnetic resonance images. Blood flow in subcutaneous adipose tissue adjacent to active muscle increased from rest (1.0 ± 0.3 ml·100 g(-1)·min(-1)) to exercise (P < 0.001) and along with increasing exercise intensity (50 N = 4.1 ± 1.4, 100 N = 5.4 ± 1.8, and 150 N = 6.9 ± 3.0 ml·100 g(-1)·min(-1), P = 0.03 for the increase). In contrast, ATBF adjacent to inactive muscle remained at resting levels with all intensities (～1.0 ± 0.5 ml·100 g(-1)·min(-1)). During exercise theophylline prevented the increase in ATBF adjacent to active muscle especially during the highest exercise intensity (50 N = 4.3 ± 1.8 ml·100 g(-1)·min(-1), 100 N = 4.0 ± 1.5 ml·100 g(-1)·min(-1), and 150 N = 4.9 ± 1.8 ml·100 g(-1)·min(-1), P = 0.06 for an overall effect) but had no effect on blood flow adjacent to inactive muscle or adipose blood flow in resting contralateral leg. In conclusion, we report in the present study that 1) blood flow in subcutaneous adipose tissue of the leg is increased from rest to exercise in an exercise intensity-dependent manner, but only in the vicinity of working muscle, and 2) adenosine receptor antagonism attenuates this blood flow enhancement at the highest exercise intensities.     

Microdomains of endoplasmic reticulum within the sarcoplasmic reticulum of skeletal myofibers

The relationship between the endoplasmic reticulum (ER) and the sarcoplasmic reticulum (SR) of skeletal muscle cells has remained obscure. In this study, we found that ER- and SR-specific membrane proteins exhibited diverse solubility properties when extracted with mild detergents. Accordingly, the major SR-specific protein Ca(2+)-ATPase (SERCA) remained insoluble in Brij 58 and floated in sucrose gradients while typical ER proteins were partially or fully soluble. Sphingomyelinase treatment rendered SERCA soluble in Brij 58. Immunofluorescence staining for resident ER proteins revealed dispersed dots over I bands contrasting the continuous staining pattern of SERCA. Infection of isolated myofibers with enveloped viruses indicated that interfibrillar protein synthesis occurred. Furthermore, we found that GFP-tagged Dad1, able to incorporate into the oligosaccharyltransferase complex, showed the dot-like structures but the fusion protein was also present in membranes over the Z lines. This behaviour mimics that of cargo proteins that accumulated over the Z lines when blocked in the ER. Taken together, the results suggest that resident ER proteins comprised Brij 58-soluble microdomains within the insoluble SR membrane. After synthesis and folding in the ER-microdomains, cargo proteins and non-incorporated GFP-Dad1 diffused into the Z line-flanking compartment which likely represents the ER exit sites.     

The lowering of hepatic fatty acid uptake improves liver function and insulin sensitivity without affecting hepatic fat content in humans

Lipolysis may regulate liver free fatty acid (FFA) uptake and triglyceride accumulation; both are potential causes of insulin resistance and liver damage. We evaluated whether 1) systemic FFA release is the major determinant of liver FFA uptake in fasting humans in vivo and 2) the beneficial metabolic effects of FFA lowering can be explained by a reduction in liver triglyceride content. Sixteen healthy subjects were subdivided in two groups of similar characteristics to undergo positron emission tomography with [(11)C]acetate and [(11)C]palmitate to quantify liver FFA metabolism (n = 8), or magnetic resonance spectroscopy (MRS) to measure hepatic fat content (n = 8), before and after the acute lowering of circulating FFAs by using the antilipolytic agent acipimox. MRS was again repeated after a 1-wk treatment period. Acipimox suppressed FFA levels while stimulating hepatic fractional extraction of FFAs (P < 0.05). As a result, fasting liver FFA uptake was decreased by 79% (P = 0.0002) in tight association with lipolysis (r = 0.996, P < 0.0001). The 1-wk treatment induced a significant improvement in systemic (+30%) and liver (+70%) insulin sensitivity (P < 0.05) and decreased circulating triglycerides (-20%, P = 0.06) and liver enzymes (ALT -20%, P = 0.03). No change in liver fat content was observed after either acute or sustained FFA suppression. We conclude that acute and sustained inhibitions of lipolysis and liver FFA uptake fail to deplete liver fat in healthy human subjects. Liver FFA uptake was decreased in proportion to FFA delivery. As a consequence, liver and systemic insulin sensitivity were improved, together with liver function, independently of changes in hepatic triglyceride accumulation.     

Parameterization and validation of an ungulate‐pasture model

Ungulate grazing and trampling strongly affect pastures and ecosystems throughout the world. Ecological population models are used for studying these systems and determining the guidelines for sustainable and economically viable management. However, the effect of trampling and other resource wastage is either not taken into account or quantified with data in earlier models. Also, the ability of models to describe the herbivore impact on pastures is usually not validated. We used a detailed model and data to study the level of winter‐ and summertime lichen wastage by reindeer and the effects of wastage on population sizes and management. We also validated the model with respect to its ability of predicting changes in lichen biomass and compared the actual management in herding districts with model results. The modeling efficiency value (0.75) and visual comparison between the model predictions and data showed that the model was able to describe the changes in lichen pastures caused by reindeer grazing and trampling. At the current lichen biomass levels in the northernmost Finland, the lichen wastage varied from 0 to 1 times the lichen intake during winter and from 6 to 10 times the intake during summer. With a higher value for wastage, reindeer numbers and net revenues were lower in the economically optimal solutions. Higher wastage also favored the use of supplementary feeding in the optimal steady state. Actual reindeer numbers in the districts were higher than in the optimal steady‐state solutions for the model in 18 herding districts out of 20. Synthesis and applications. We show that a complex model can be used for analyzing ungulate‐pasture dynamics and sustainable management if the model is parameterized and validated for the system. Wastage levels caused by trampling and other causes should be quantified with data as they strongly affect the results and management recommendations. Summertime lichen wastage caused by reindeer is higher than expected, which suggests that seasonal pasture rotation should be used to prevent the heavy trampling of winter lichen pastures during summer. In the present situation, reindeer numbers in northernmost Finland are in most cases higher than in the management solutions given by the model.     

Stem wood properties of Populus tremuloides, Betula papyrifera and Acer saccharum saplings after 3 years of treatments to elevated carbon dioxide and ozone

The aim of this study was to examine the effects of elevated carbon dioxide [CO₂] and ozone [O₃] and their interaction on wood chemistry and anatomy of five clones of 3‐year‐old trembling aspen (Populus tremuloides Michx.). Wood chemistry was studied also on paper birch (Betula papyrifera Marsh.) and sugar maple (Acer saccharum Marsh.) seedling‐origin saplings of the same age. Material for the study was collected from the Aspen Free‐Air CO₂ Enrichment (FACE) experiment in Rhinelander, WI, USA, where the saplings had been exposed to four treatments: control (C; ambient CO₂, ambient O₃), elevated CO₂ (560 ppm during daylight hours), elevated O₃ (1.5 × ambient during daylight hours) and their combination (CO₂+O₃) for three growing seasons (1998–2000). Wood chemistry responses to the elevated CO₂ and O₃ treatments differed between species. Aspen was most responsive, while maple was the least responsive of the three tree species. Aspen genotype affected the responses of wood chemistry and, to some extent, wood structure to the treatments. The lignin concentration increased under elevated O₃ in four clones of aspen and in birch. However, elevated CO₂ ameliorated the effect. In two aspen clones, nitrogen in wood samples decreased under combined exposure to CO₂ and O₃. Soluble sugar concentration in one aspen clone and starch concentration in two clones were increased by elevated CO₂. In aspen wood, α‐cellulose concentration changed under elevated CO₂, decreasing under ambient O₃ and slightly increasing under elevated O₃. Hemicellulose concentration in birch was decreased by elevated CO₂ and increased by elevated O₃. In aspen, elevated O₃ induced statistically significant reductions in distance from the pith to the bark and vessel lumen diameter, as well as increased wall thickness and wall percentage, and in one clone, decreased fibre lumen diameter. Our results show that juvenile wood properties of broadleaves, depending on species and genotype, were altered by atmospheric gas concentrations predicted for the year 2050 and that CO₂ ameliorates some adverse effects of elevated O₃ on wood chemistry.     

Inactivation of mouse transmembrane prolyl 4-hydroxylase increases blood brain barrier permeability and ischemia-induced cerebral neuroinflammation

Hypoxia-inducible factor prolyl 4-hydroxylases (HIF-P4Hs) regulate the hypoxic induction of >300 genes required for survival and adaptation under oxygen deprivation. Inhibition of HIF-P4H-2 has been shown to be protective in focal cerebral ischemia rodent models, while that of HIF-P4H-1 has no effects and inactivation of HIF-P4H-3 has adverse effects. A transmembrane prolyl 4-hydroxylase (P4H-TM) is highly expressed in the brain and contributes to the regulation of HIF, but the outcome of its inhibition on stroke is yet unknown. To study this, we subjected WT and P4htm^−/− mice to permanent middle cerebral artery occlusion (pMCAO). Lack of P4H-TM had no effect on lesion size following pMCAO, but increased inflammatory microgliosis and neutrophil infiltration was observed in the P4htm^−/− cortex. Furthermore, both the permeability of blood brain barrier and ultrastructure of cerebral tight junctions were compromised in P4htm^−/− mice. At the molecular level, P4H-TM deficiency led to increased expression of proinflammatory genes and robust activation of protein kinases in the cortex, while expression of tight junction proteins and the neuroprotective growth factors erythropoietin and vascular endothelial growth factor was reduced. Our data provide the first evidence that P4H-TM inactivation has no protective effect on infarct size and increases inflammatory microgliosis and neutrophil infiltration in the cortex at early stage after pMCAO. When considering HIF-P4H inhibitors as potential therapeutics in stroke, the current data support that isoenzyme-selective inhibitors that do not target P4H-TM or HIF-P4H-3 would be preferred.     

Direct observation of hematopoietic progenitor chimerism in fetal freemartin cattle

Background

Cattle twins are well known as blood chimeras. However, chimerism in the actual hematopoietic progenitor compartment has not been directly investigated. Here, we analyzed fetal liver of chimeric freemartin cattle by combining a new anti-bovine CD34 antibody and Y-chromosome specific in situ hybridization.

Results

Bull-derived CD34⁺ cells were detected in the liver of the female sibling (freemartin) at 60 days gestation. The level of bull-derived CD34⁺ cells was lower in the freemartin than in its male siblings. Bull (Y⁺) and cow hematopoietic cells often occurred in separate clusters. Around clusters of Y⁺CD34⁺ cells, Y⁺CD34^- cells were typically observed. The thymi were also strongly chimeric at 60 days of gestation.

Conclusion

The fetal freemartin liver contains clusters of bull-derived hematopoietic progenitors, suggesting clonal expansion and differentiation. Even the roots of the hematopoietic system in cattle twins are thus strongly chimeric from the early stages of fetal development. However, the hematopoietic seeding of fetal liver apparently started already before the onset of functional vascular anastomosis.     

中国晚中新世陆相哺乳动物群序列:陕西蓝田的新证据(英文)

自 2 0世纪 60年代 ,陕西蓝田地区就以连续的晚新生代地层及丰富的哺乳动物化石而成为研究中国晚新生代哺乳动物与地层划分对比的经典地区之一。李传夔等 ( 1 984)根据灞河组发现的哺乳动物化石建立了灞河期 ,并与欧洲的Vallesian期对比。邱占祥等( 1 990 ,1 995)认为化石证据不充分 ,而将其与保德期合并。近年来 ,黄土高原三趾马红粘土大量的年代学资料表明 ,红粘土沉积最早可能开始于约 8Ma前。因此 ,狭义的保德期可能只代表了晚中新世晚期 ,晚中新世哺乳动物分期的再划分问题又重新被提出。自 1 997年以来 ,我们课题组在蓝田地区共发现 52个化石地点 ,其中的 2 6个含有哺乳动物化石 ,大哺乳动物化石标本共计 1 666件。经过详细野外地层测量 ,绘制了综合地层剖面 ,并将主要含哺乳动物化石的地点对比标定到综合地层剖面上。经过对各门类化石的初步研究 ,以及对已有化石材料的初步修订 ,到目前为止 ,陕西蓝田灞河组共计发现哺乳动物化石 45种 ,蓝田组 2 0种。新的化石证据表明 ,灞河组发现的哺乳动物化石组合完全不同于典型意义上的保德三趾马动物群。大哺乳动物化石以灞河三趾马与贾氏三趾马为代表 ,牛科化石组合在种级甚至属级上有明显的区别。大量的陕西转角羚羊 ,小型的Protoryx、Dorcadoryx以及Ga