Source, production and export of dissolved organic carbon and nitrogen

The purpose of this research was to quantify the major sources of dissolved organic carbon (DOC) and nitrogen (DON) in forest soils and ascertain mechanisms for their production and export to surface waters. To quantify the source of DOC we made use of the on-going litter manipulation study (DIRT) at Harvard Forest, Massachusetts. The organic horizon supplies 74% of DOC to bulk soil solution, 12% is supplied by leaf litter, and 13% from root exudate and decay. In plots with no inputs, DON concentrations were 9% higher than the control plots. When either roots or litter were excluded, DON concentrations increased by 17% and 12% respectively. Both DON and DOC concentrations were significantly related to fungal biomass (R2 = 0.99 and 0.90; p \u3c 0.01). We investigated the mechanisms of DOC and DON production and their relationship with CO2 and soil C:N ratio and the effect of chronic carbon and nitrogen manipulation on these relationships. DOC was significantly related to soil respiration in the hardwood plots (R2 = 0.61; p \u3c 0.05), chronic carbon and nitrogen manipulation did not affect this relationship. In the coniferous control plots, the relationship between DOC and soil respiration was strong and significant (R2 = 0.93 p \u3c 0.05) but nitrogen fertilization affected the relationship. DOC was significantly related to soil C:N among forest type and treatment suggesting that the overall mechanisms of DOC production are unaffected by either carbon or nitrogen manipulation. We examined the effect of cold and warm temperature on the relationships between DOC, DON soil respiration and soil C:N in a laboratory controlled study. Temperature had no significant effect on the relationships between DOC and soil C:N, DOC and DON, DON and soil C:N but a significant temperature effect was apparent between both DOC and DON and soil respiration. We used mean biome soil C:N ratio and mean biome DOC export to derive an empirical model (R2 = 0.99 p \u3c 0.001). The model predicted DOC export from contrasting forest types to within 4.5% of their observed exports. We estimated global annual riverine DOC export to be between 0.41--0.48 Pg yr-1

Structures of Two Melanoma-Associated Antigens Suggest Allosteric Regulation of Effector Binding

The MAGE (melanoma associated antigen) protein family are tumour-associated proteins normally present only in reproductive tissues such as germ cells of the testis. The human genome encodes over 60 MAGE genes of which one class (containing MAGE-A3 and MAGE-A4) are exclusively expressed in tumours, making them an attractive target for the development of targeted and immunotherapeutic cancer treatments. Some MAGE proteins are thought to play an active role in driving cancer, modulating the activity of E3 ubiquitin ligases on targets related to apoptosis. Here we determined the crystal structures of MAGE- A3 and MAGE-A4. Both proteins crystallized with a terminal peptide bound in a deep cleft between two tandem-arranged winged helix domains. MAGE-A3 (but not MAGE-A4), is pre- dominantly dimeric in solution. Comparison of MAGE-A3 and MAGE-A3 with a structure of an effector-bound MAGE-G1 suggests that a major conformational rearrangement is required for binding, and that this conformational plasticity may be targeted by allosteric binders

Gypsophile chemistry unveiled: Fourier transform infrared (FTIR) spectroscopy provides new insight into plant adaptations to gypsum soils

Gypsum soils are among the most restrictive and widespread substrates for plant life. Plants living on gypsum are classified as gypsophiles (exclusive to gypsum) and gypsovags (non-exclusive to gypsum). The former have been separated into wide and narrow gypsophiles, each with a putative different ecological strategy. Mechanisms displayed by gypsum plants to compete and survive on gypsum are still not fully understood. The aim of this study was to compare the main chemical groups in the leaves of plants with different specificity to gypsum soils and to explore the ability of Fourier transform infrared (FTIR) spectra analyzed with neural network (NN) modelling to discriminate groups of gypsum plants. Leaf samples of 14 species with different specificity to gypsum soils were analysed with FTIR spectroscopy coupled to neural network (NN) modelling. Spectral data were further related to the N, C, S, P, K, Na, Ca, Mg and ash concentrations of samples. The FTIR spectra of the three groups analyzed showed distinct features that enabled their discrimination through NN models. Wide gypsophiles stood out for the strong presence of inorganic compounds in their leaves, particularly gypsum and, in some species, also calcium oxalate crystals. The spectra of gypsovags had less inorganic chemical species, while those of narrow gypsum endemisms had low inorganics but shared with wide gypsophiles the presence of oxalate. Gypsum and calcium oxalate crystals seem to be widespread amongst gypsum specialist plants, possibly as a way to tolerate excess Ca and sulphate. However, other mechanisms such as the accumulation of sulphates in organic molecules are also compatible with plant specialization to gypsum. While gypsovags seem to be stress tolerant plants that tightly regulate the uptake of S and Ca, the ability of narrow gypsum endemisms to accumulate excess Ca as oxalate may indicate their incipient specialization to gypsum

Structural insights into the autoregulation and cooperativity of the human transcription factor Ets-2

Ets-2, like its closely related homologue Ets-1, is a member of the Ets family of DNA binding transcription factors. Both proteins are subject to multiple levels of regulation of their DNA binding and transactivation properties. One such regulatory mechanism is the presence of an autoinhibitory module, which in Ets-1 allosterically inhibits the DNA binding activity. This inhibition can be relieved by interaction with protein partners or cooperative binding to closely separated Ets binding sites in a palindromic arrangement. In this study we describe the 2.5 Å resolution crystal structure of a DNA complex of the Ets-2 Ets domain. The Ets domain crystallized with two distinct species in the asymmetric unit, which closely resemble the autoinhibited and DNA bound forms of Ets-1. This discovery prompted us to re-evaluate the current model for the autoinhibitory mechanism and the structural basis for cooperative DNA binding. In contrast to Ets-1, in which the autoinhibition is caused by a combination of allosteric and steric mechanisms, we were unable to find clear evidence for the allosteric mechanism in Ets-2. We also demonstrated two possibly distinct types of cooperative binding to substrates with Ets binding motifs separated by four and six base pairs and suggest possible molecular mechanisms for this behavior

Caffeine ingestion compromises thermoregulation and does not improve cycling time to exhaustion in the heat among males

Purpose Caffeine is a commonly used ergogenic aid for endurance events; however, its efficacy and safety have been questioned in hot environmental conditions. The aim of this study was to investigate the effects of acute caffeine supplementation on cycling time to exhaustion and thermoregulation in the heat. Methods In a double-blind, randomised, cross-over trial, 12 healthy caffeine-habituated and unacclimatised males cycled to exhaustion in the heat (35 \ub0C, 40% RH) at an intensity associated with the thermoneutral gas exchange threshold, on two separate occasions, 60 min after ingesting caffeine (5 mg/kg) or placebo (5 mg/kg). Results There was no effect of caffeine supplementation on cycling time to exhaustion (caffeine; 28.5 \ub1 8.3 min vs. placebo; 29.9 \ub1 8.8 min, P = 0.251). Caffeine increased pulmonary oxygen uptake by 7.4% (P = 0.003), heat production by 7.9% (P = 0.004), whole-body sweat rate by 21% (P = 0.008), evaporative heat transfer by 16.5% (P = 0.006) and decreased estimated skin blood flow by 14.1% (P < 0.001) compared to placebo. Core temperature was higher by 0.6% (P = 0.013) but thermal comfort decreased by -18.3% (P = 0.040), in the caffeine condition, with no changes in rate of perceived exertion (P > 0.05). Conclusion The greater heat production and storage, as indicated by a sustained increase in core temperature, corroborate previous research showing a thermogenic effect of caffeine ingestion. When exercising at the pre-determined gas exchange threshold in the heat, 5 mg/kg of caffeine did not provide a performance benefit and increased the thermal strain of participants

OPTIma:a tracking solution for proton computed tomography in high proton flux environments

Currently there is a large discrepancy between the currents that are used for treatments in proton beam therapy facilities and the ultra low beam currents required for many proton CT imaging systems. Here we provide details of the OPTIma silicon strip based tracking system, which has been designed for performing proton CT imaging in conditions closer to the high proton flux environments of modern spot scanning treatment facilities. Details on the physical design, sensor testing, modelling, and track reconstruction are provided along with Monte-Carlo simulation studies of the expected performance for proton beam currents of up to 50 pA at the nozzle when using a σ = ∼10 mm spot scanning cyclotron system. Using a detailed simulation of the proposed OPTIma system, a discrepancy of less than 1% on the Relative Stopping Power is found for various tissues when embedded within a 150 mm diameter Perspex sphere. It is found that by accepting up to 7 protons per bunch it is possible to operate at cyclotron beam currents up to 5 times higher than would be possible with a single proton based readout, significantly reducing the total beam time required to produce an image, while also reducing the discrepancy between the beam currents required for treatment and those used for proton CT