Mid to late Holocene vegetation and land use history in the Weald of south-eastern England: multiple pollen profiles from the Rye area

The High Weald is an unusually well-wooded area in southern England. A high proportion of this woodland is ancient, being formerly exploited as seasonal pasture and coppice. Multiple pollen profiles from the Rye area have been used to elucidate the origins of this cultural landscape. By combining sites with small and large pollen source areas, both local and regional patterns of vegetation change have been determined. The mid-Holocene Tilia-dominated woodlands were subjected to temporary clearance as early as the Neolithic. This woodland was more extensively exploited over a ca. 700 year period from the beginning of the Bronze Age. The main elements of the modern landscape (woodland, pasture and limited cultivation) can be traced back to a more intensive phase of human activity, which commenced in the late Bronze Age. A regional increase in Fagus sylvatica pollen ca. 750 B.C. probably reflects the use of the Wealden woods for pasturage. There is no palynological evidence that the fuel demands of the Roman iron industry resulted in widespread woodland destruction. The early Anglo-Saxon period appears to have been one of land-use continuity, with a second increase in Fagus pollen at ca. A.D. 700 corresponding to historical evidence for the presence of wood-pastures in the Weald.     

Effects of perennial neighbors and nitrogen pulses on growth and nitrogen uptake by Bromus tectorum

An experiment was conducted to determine if growth and biomass responsesof the annual grass Bromus tectorum are affected by themagnitude and timing of nitrogen (N) pulses and if these responses areinfluenced by different perennial neighbor species. Nitrogen(NH₄:NO₃) was applied in three pulse treatments of varyinginterpulse length (3-d, 9-d, or 21-d between N additions). The total amount of Nadded was the same among treatments; hence, both the frequency and magnitude ofN pulses varied (i.e., the longer the interpulse period,the greater the amount of N added for a single pulse).Bromus showed little response to the different N-pulsetreatments. The only characteristic that varied among pulse treatments wasspecific leaf area (SLA), which was significantly greater whenBromus was grown under the 21-d N pulse than when grownunder the 3-d or 9-d N pulses. Bromus height, leaf andtiller numbers, leaf area and aboveground biomass were not affected by theN-pulse treatments nor were tissue-N contents and concentrations. However,Bromus production and tissue-N were significantly differentwhen Bromus was grown with different perennial neighborspecies. Tiller production, aboveground biomass, and seed numbers ofBromus were lowest when the perennial neighbor was thetussock grass Agropyron desertorum, intermediate when theneighbor was the evergreen shrub Artemisia tridentata, andgreatest when the neighbor was the deciduous shrub Chrysothamnusnauseosus. N contents of Bromus leaves were alsolowest when the neighbor was Agropyron. In contrast, root Nuptake capacities were greatest for Agropyron-Bromus rootmixes and lowest for Chrysothamnus-Bromus root mixes. Theseresults suggest that perennial neighbors affect growth, seed production, and Nuptake of Bromus to a greater extent than the timing andmagnitude of N pulses.     

Initiation of fatty acid synthesis in rat mammary glands.

The rate of fatty acid synthesis from [6-14C]glucose in mammary tissue remained low until parturition at 22 days of gestation and increased 10-fold at 1 day post partum. Administration of progesterone on days 20 and 21 or removal of pups at parturition abolished this increase. In the latter case, administration of prolactin, corticosterone or oxytocin had no stimulatory effect; tissue from suckled glands in which the ducts had been ligated at parturition also showed no increased rate in 24 h. Foetoplacentectomy on day 18 did not stimulate fatty acid synthesis but subsequent suckling by foster pups did. Whereas lactose synthesis is initiated by withdrawal of progesterone from the circulation, a further stimulus related to removal of milk by suckling is required to initiate fatty acid synthesis.     

Effect of Global Cardiac Ischemia on Human Ventricular Fibrillation: Insights from a Multi-scale Mechanistic Model of the Human Heart

Acute regional ischemia in the heart can lead to cardiac arrhythmias such as ventricular fibrillation (VF), which in turn compromise cardiac output and result in secondary global cardiac ischemia. The secondary ischemia may influence the underlying arrhythmia mechanism. A recent clinical study documents the effect of global cardiac ischaemia on the mechanisms of VF. During 150 seconds of global ischemia the dominant frequency of activation decreased, while after reperfusion it increased rapidly. At the same time the complexity of epicardial excitation, measured as the number of epicardical phase singularity points, remained approximately constant during ischemia. Here we perform numerical studies based on these clinical data and propose explanations for the observed dynamics of the period and complexity of activation patterns. In particular, we study the effects on ischemia in pseudo-1D and 2D cardiac tissue models as well as in an anatomically accurate model of human heart ventricles. We demonstrate that the fall of dominant frequency in VF during secondary ischemia can be explained by an increase in extracellular potassium, while the increase during reperfusion is consistent with washout of potassium and continued activation of the ATP-dependent potassium channels. We also suggest that memory effects are responsible for the observed complexity dynamics. In addition, we present unpublished clinical results of individual patient recordings and propose a way of estimating extracellular potassium and activation of ATP-dependent potassium channels from these measurements.     

Passive myocardial mechanical properties: meaning,measurement, models

Passive mechanical tissue properties are major determinants of myocardial contraction and relaxation and, thus, shape cardiac function. Tightly regulated, dynamically adapting throughout life, and affecting a host of cellular functions, passive tissue mechanics also contribute to cardiac dysfunction. Development of treatments and early identification of diseases requires better spatio-temporal characterisation of tissue mechanical properties and their underlying mechanisms. With this understanding, key regulators may be identified, providing pathways with potential to control and limit pathological development. Methodologies and models used to assess and mimic tissue mechanical properties are diverse, and available data are in part mutually contradictory. In this review, we define important concepts useful for characterising passive mechanical tissue properties, and compare a variety of in vitro and in vivo techniques that allow one to assess tissue mechanics. We give definitions of key terms, and summarise insight into determinants of myocardial stiffness in situ. We then provide an overview of common experimental models utilised to assess the role of environmental stiffness and composition, and its effects on cardiac cell and tissue function. Finally, promising future directions are outlined.     

Role of Protein Farnesylation in Burn-Induced Metabolic Derangements and Insulin Resistance in Mouse Skeletal Muscle

Objective

Metabolic derangements, including insulin resistance and hyperlactatemia, are a major complication of major trauma (e.g., burn injury) and affect the prognosis of burn patients. Protein farnesylation, a posttranslational lipid modification of cysteine residues, has been emerging as a potential component of inflammatory response in sepsis. However, farnesylation has not yet been studied in major trauma. To study a role of farnesylation in burn-induced metabolic aberration, we examined the effects of farnesyltransferase (FTase) inhibitor, FTI-277, on burn-induced insulin resistance and metabolic alterations in mouse skeletal muscle.

Methods

A full thickness burn (30% total body surface area) was produced under anesthesia in male C57BL/6 mice at 8 weeks of age. After the mice were treated with FTI-277 (5 mg/kg/day, IP) or vehicle for 3 days, muscle insulin signaling, metabolic alterations and inflammatory gene expression were evaluated.

Results

Burn increased FTase expression and farnesylated proteins in mouse muscle compared with sham-burn at 3 days after burn. Simultaneously, insulin-stimulated phosphorylation of insulin receptor (IR), insulin receptor substrate (IRS)-1, Akt and GSK-3β was decreased. Protein expression of PTP-1B (a negative regulator of IR-IRS-1 signaling), PTEN (a negative regulator of Akt-mediated signaling), protein degradation and lactate release by muscle, and plasma lactate levels were increased by burn. Burn-induced impaired insulin signaling and metabolic dysfunction were associated with increased inflammatory gene expression. These burn-induced alterations were reversed or ameliorated by FTI-277.

Conclusions

Our data demonstrate that burn increased FTase expression and protein farnesylation along with insulin resistance, metabolic alterations and inflammatory response in mouse skeletal muscle, all of which were prevented by FTI-277 treatment. These results indicate that increased protein farnesylation plays a pivotal role in burn-induced metabolic dysfunction and inflammatory response. Our study identifies FTase as a novel potential molecular target to reverse or ameliorate metabolic derangements in burn patients.     

A cetylated fatty acid topical cream with menthol reduces pain and improves functional performance in individuals with arthritis

This investigation was an extension of a previous study conducted in our laboratory in which we showed that 1 month of treatment with a topical cream (Celadrin) consisting of cetylated fatty acids was effective for reducing pain and improving functional performance in individuals with osteoarthritis (OA) of the knee (Kraemer et al., Journal of Rheumatology, 2004). We wanted to verify that the addition of menthol to the compound would produce a similar percentage of improvement in therapeutic effects. We used a single treatment group with a pre-post experimental design to examine % treatment changes. Individuals diagnosed with OA of the knee (N = 10; age, 66.4 +/- 11.5 years) and severe pain (e.g., OA, rheumatoid arthritis) of the elbow (N = 8; age, 59.1 +/- 18.2 years) and wrist (N = 10; age, 60.3 +/- 16.8 years) were tested for pain and functional performance before and after 1 week of treatment with a topical cream consisting of cetylated fatty acids and menthol applied twice per day. In individuals with knee OA, significant improvements in stair-climbing ability (about 12%), "up-and-go" performance (about 12%), balance and strength (about 16.5%), and range of motion (about 3.5%) were observed, as were reductions in pain. In individuals with severe pain of the elbow and wrist, significant improvements in dynamic (about 22 and 24.5%, respectively) and isometric (about 33 and 42%, respectively) local muscular endurance were observed, as was a reduction in pain. Neither group demonstrated significant changes in maximal grip strength or maximal force production. One week of treatment with a topical cream consisting of cetylated fatty acids and menthol was similarly effective for reducing pain and improving functional performance in individuals with arthritis of the knee, elbow, and wrist. The % changes were consistent with our prior work on the compound without menthol. Further work is needed to determine the impact of menthol in such a cream. Nevertheless, our data support the use of a topical cream consisting of cetylated fatty acids (with or without menthol) for enhancing the potential for exercise training in this population.