Critical review of the impacts of grazing intensity on soil organic carbon storage and other soil quality indicators in extensively managed grasslands.

Livestock grazing intensity (GI) is thought to have a major impact on soil organic carbon (SOC) storage and soil quality indicators in grassland agroecosystems. To critically investigate this, we conducted a global review and meta-analysis of 83 studies of extensive grazing, covering 164 sites across different countries and climatic zones. Unlike previous published reviews we normalized the SOC and total nitrogen (TN) data to a 30 cm depth to be compatible with IPCC guidelines. We also calculated a normalized GI and divided the data into four main groups depending on the regional climate (dry warm, DW; dry cool, DC; moist warm, MW; moist cool, MC). Our results show that taken across all climatic zones and GIs, grazing (below the carrying capacity of the systems) results in a decrease in SOC storage, although its impact on SOC is climate-dependent. When assessed for different regional climates, all GI levels increased SOC stocks under the MW climate (+7.6%) whilst there were reductions under the MC climate (-19%). Under the DW and DC climates, only the low (+5.8%) and low to medium (+16.1%) grazing intensities, respectively, were associated with increased SOC stocks. High GI significantly increased SOC for C4-dominated grassland compared to C3-dominated grassland and C3-C4 mixed grasslands. It was also associated with significant increases in TN and bulk density but had no effect on soil pH. To protect grassland soils from degradation, we recommend that GI and management practices should be optimized according to climate region and grassland type (C3, C4 or C3-C4 mixed).

A parallel-arm phase I trial of the humanised anti-IGF-1R antibody dalotuzumab in combination with the AKT inhibitor MK-2206, the mTOR inhibitor ridaforolimus, or the NOTCH inhibitor MK-0752, in patients with advanced solid tumours.

BACKGROUND: Two strategies to interrogate the insulin growth factor 1 receptor (IGF-1R) pathway were investigated: vertical inhibition with dalotuzumab and MK-2206 or ridaforolimus to potentiate PI3K pathway targeting and horizontal cross-talk inhibition with dalotuzumab and MK-0752 to exert effects against cellular proliferation, angiogenesis, and stem cell propagation. METHODS: A phase I, multi-cohort dose escalation study was conducted in patients with advanced solid tumours. Patients received dalotuzumab (10 mg kg(-1)) and escalating doses of MK-2206 (90-200 mg) or escalating doses of dalotuzumab (7.5-10 mg kg(-1)) and MK-0752 (1800 mg) weekly. Upon maximum tolerated dose determination, patients with low-RAS signature, high-IGF1 expression ovarian cancer were randomised to dalotuzumab/MK-2206 versus dalotuzumab/ridaforolimus, whereas patients with high IGF1/low IGF2 expression colorectal cancer received dalotuzumab/MK-0752. RESULTS: A total of 47 patients were enrolled: 29 in part A (18 in the dalotuzumab/MK-2206 arm and 11 in the dalotuzumab/MK-0752 arm) and 18 in part B (6 in each arm). Dose-limiting toxicities (DLTs) for dalotuzumab/MK-2206 included grade 4 neutropenia and grade 3 serum sickness-like reaction, maculopapular rash, and gastrointestinal inflammation. For dalotuzumab/MK-0752, DLTs included grade 3 dehydration, rash, and diarrhoea. Seven patients remained on study for >4 cycles. CONCLUSIONS: Dalotuzumab/MK-2206 and dalotuzumab/MK-0752 combinations were tolerable. Further developments of prospectively validated predictive biomarkers to aid in patient selection for anti-IGF-1R therapies are needed.

Size discrimination on the skin.

Reasons are given for rejecting the two-point threshold as the standard measure of spatiotactile resolution. As alternative techniques, thresholds were obtained for disc-size and disc-annulus discriminations. Disc-annulus thresholds are comparable to two-point values, but disc-size thresholds are smaller by a factor of 10. Thus, at least part of the cutaneous system is better organized for localization and sizing of a stimulus than for detection of discontinuities in it.

The potential of ecotoxicoproteomics in environmental monitoring: biomarker profiling in mussel plasma using ProteinChip array technology.

New global technologies, allowing simultaneous analysis of thousands of genes, proteins, and metabolites (so-called "omics" technologies), are being adopted rapidly by industry, academia, and regulatory agencies. This study evaluated the potential of proteomics in ecotoxicological research (i.e., ecotoxicoproteomics). Filter-feeding mussels (Mytilus edulis) were exposed continuously for 3 wk to oil, or oil spiked with alkylphenols and extra polycyclic aromatic hydrocarbons. The influence of chronic exposure on mussel plasma protein expression was investigated utilizing ProteinChip array technology in combination with surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI TOF MS). Results indicated that exposure to spiked oil had a more significant effect on protein expression in mussels than oil alone. In total, 83 mass peaks (intact or modified proteins/peptides) were significantly altered by spiked oil, while 49 were altered by oil. In exposed organisms, the majority of peaks were upregulated compared to controls (i.e., 69% in oil and 71% in spiked oil). Some peaks (32 in total) were affected by both treatments; however, the degree of response was higher in the spiked oil group for 25 of the 32 commonly affected features. Additionally, certain peaks revealed exposure- or gender-specific responses. Multivariate analysis with regression tree-based methods detected protein patterns associated with exposure that correctly classified masked samples with 90-95% accuracy. Similarly, 92% of females and 85% of males were correctly classified (independent of exposure). Results indicate that proteomics have the potential to make a valuable contribution to environmental monitoring and risk assessment.

The effect of renovation of long-term temperate grassland on N2O emissions and N leaching from contrasting soils.

Renovation of long-term grassland is associated with a peak in soil organic N mineralisation which, coupled with diminished plant N uptake can lead to large gaseous and leaching N losses. This study reports on the effect of ploughing and subsequent N fertilisation on the N2O emissions and DON/NO3(-) leaching, and evaluates the impact of ploughing technique on the magnitude and profile of N losses. This study was carried out on isolated grassland lysimeters of three Irish soils representing contrasting drainage properties (well-drained Clonakilty, moderately-drained Elton and poorly-drained Rathangan). Lysimeters were manually ploughed simulating conventional (CT) and minimum tillage (MT) as two treatments. Renovation of grassland increased N2O flux to a maximum of 0.9kgN2O-Nha(-1) from poorly-drained soil over four days after treatment. Although there was no difference between CT and MT in the post-ploughing period, the treatment influenced subsequent N2O after fertiliser applications. Fertilisation remained the major driver of N losses therefore reducing fertilisation rate post-planting to account for N mineralised through grassland renovation could reduce the losses in medium to longer term. Leaching was a significant loss pathway, with the cumulative drainage volume and N leached highly influenced by soil type. Overall, the total N losses (N2O+N leached) were lowest from poorly and moderately draining soil and highest for the well draining soil, reflecting the dominance of leaching on total N losses and the paramount importance of soil properties.

Interactions between mitochondrial and nuclear DNA in mammalian cells are non-random.

Chromosome Conformation Capture techniques regularly detect physical interactions between mitochondrial and nuclear DNA (i.e. mito-nDNA interactions) in mammalian cells. We have evaluated mito-nDNA interactions captured by HiC and Circular Chromosome Conformation Capture (4C). We show that these mito-nDNA interactions are statistically significant and shared between biological and technical replicates. The most frequent interactions occur with repetitive DNA sequences, including centromeres in human cell lines and the 18S rDNA in mouse cortical astrocytes. Our results demonstrate a degree of selective regulation in the identity of the interacting mitochondrial partners confirming that mito-nDNA interactions in mammalian cells are not random.

Dynamics of tear film deposition and draining.

This paper investigates the deposition of the tear film on the cornea of the human eye. The tear film is laid down by the motion of the upper eyelid and then subsequently flows and thins. Of particular interest is the stability of the tear layer and the development of dry patches on the cornea. While there has been significant research on the behaviour of tear films between blinks, this paper focuses on understanding the mechanisms which control the shape and thickness of the deposited film and how this affects the subsequent film behaviour. Numerical and analytical methods are applied to a lubrication model which includes the effects of surface tension, viscosity, gravity and evaporation. The model reveals the importance of the eyelid velocity, motion of the surface lipid layer and the storage of tear film between blinks.

Visibility of the nailfold plexus and heredity.

The parents of 37 normal healthy teenagers selected on the basis of nailfold capillary patterns (16 low-plexus children and 21 high-plexus children) were examined by capillary microscopy and rated "blindly" for plexus visualization scores (PVS). The hypothesis that high PVS is a hereditary trait transmitted as a monogenic autosomal dominant is supported by these data. The additional hypothesis that the high PVS may be associated with a higher social class is also confirmed in this sample. The transmission of high PVS in schizophrenics, where it is frequently observed in association with more serious features of this disease, appears to follow the same mode of inheritance as in normal subjects. The importance of detecting a biological hereditary characteristic which appears to have a modifying effect on the schizophrenic process is emphasized.

The effect of olestra on systemic levels of oral contraceptives.

The effect of olestra, a nonabsorbable, noncaloric fat replacement, on the absorption and efficacy of a highly lipophilic oral contraceptive was investigated in a double-blind, placebo-controlled crossover study with 28 women. Subjects consumed 18 gm/day olestra for 28 days while taking an oral contraceptive containing 300 micrograms of norgestrel and 30 micrograms ethinyl estradiol (Lo/Ovral-28). Blood taken on days 12 to 14 of the treatment cycles was analyzed for ethinyl estradiol and norgestrel. There was no statistically significant difference in time to attain maximum concentration, maximum concentration, or area under the concentration-time curve between the olestra and placebo treatments for either drug component. Measurements of serum progesterone indicated that olestra ingestion did not reduce efficacy as indicated by ovulation. The data show that ingestion of 18 gm/day olestra did not affect the absorption or efficacy of the highly lipophilic oral contraceptive.

The UCLA-University of Utah epidemiologic survey of autism: recurrence risk estimates and genetic counseling.

The authors recently reported, in this journal, an epidemiologic survey of autism in Utah. Twenty (9.7%) of the 207 families ascertained had more than one autistic child. Analyses of these data revealed that autism is 215 times more frequent among the siblings of autistic patients than in the general population. The overall recurrence risk estimate (the chance that each sibling born after an autistic child will develop autism) is 8.6%. If the first autistic child is a male the recurrence risk estimate is 7%, and if a female 14.5%. These new recurrence risk estimates should be made available to all individuals who have autistic children and are interested in family planning.

A nuclear Overhauser enhancement study on the imino proton resonances of a DNA pentadecamer comprising the specific target site of the cyclic AMP receptor protein in the ara BAD operon.

A 500 MHz 1H-NMR study on a synthetic DNA pentadecamer comprising the specific target site of the cAMP receptor protein in the ara BAD operon is presented. Using pre-steady state NOE measurements, unambiguous assignments of all the imino proton resonances and associated adenine (H2) resonances are obtained. From the NOE data interbase pair interproton distances involving the imino and adenine (H2) protons are determined. It is shown that these distances are very similar to those expected for classical B DNA (RMS difference of 0.5 A), but are significantly different from those expected for classical A DNA (RMS difference of 1.1 A).

Effects of a nonenergy fat substitute on children's energy and macronutrient intake.

To determine whether children adjusted their energy intake in response to covert manipulations in the proportion of energy from dietary fat, 24-h food intake of 29 2- to 5-y-old children was measured over four 2-d blocks. In this within-subject crossover design, in the first three meals of the first day of each block, children consumed foods containing dietary fat or a nonenergy fat substitute, which provided 10% of total daily energy intake. Children compensated for the missing energy; cumulative energy intake differed by only 100 kJ over 2 d. Substitution for dietary fat reduced the percent of energy from fat from 38.7% to 36.4%. Children's intake at individual meals was highly variable (mean CV 24.7%) relative to the variability of total daily energy intake (CV = 8.6%). To produce this pattern, children adjusted energy intake across successive meals. Use of a fat substitute at 10% of energy from dietary fat did not significantly reduce 24-h energy intake.

Effects of olestra, a noncaloric fat substitute, on daily energy and fat intakes in lean men.

Nutrient and energy intakes, hunger, and fullness were examined after the replacement of 36, 20, or 0 g fat in breakfast with olestra, a noncaloric fat substitute. Twenty-four lean, nondieting men (aged 21-30 y) participated in a placebo-controlled, three-condition crossover design. Self-selected, ad libitum intakes at lunch and dinner were monitored in the laboratory. Evening snacks and breakfast the next day were assessed through food diaries. Visual-analog-scale ratings including hunger and fullness were collected throughout the test days. Single-meal olestra substitution produced a significant dose-related reduction in the amount and percentage of energy from fat consumed daily with a reciprocal increase in carbohydrate intake. Daily energy intakes were not significantly different nor did ratings of hunger and fullness vary systematically between conditions. Consumption of olestra can reduce fat intake and increase carbohydrate intake without affecting total daily energy intake or usual patterns of hunger and fullness.

Vitamin K status of free-living subjects consuming olestra.

The potential for 20 g olestra/d to affect vitamin K status was assessed in a 6-wk study involving 202 free-living subjects. Functional prothrombin [Simplastin (S)-Ecarin (E) assay] concentrations and classical clotting times were unaffected by olestra. Initial S:E values were 0.80 and 0.79 for the olestra and placebo groups, respectively, compared with a value of 0.92 for normal reference plasma. At week 6 the value was 0.81 for both groups. Mean phylloquinone serum concentrations, expressed as differences from baseline, were not significantly different between groups. Weekly food diaries indicated that the average phylloquinone intake of the subjects was low, approximately 60 micrograms/d. Sensitive measures of vitamin K status were unaffected in a population where any significant decrease in phylloquinone bioavailability should have been reflected in those measures, indicating that 20 g olestra/d in the diet did not affect vitamin K status.

Serum 25-hydroxyvitamin D concentrations of free-living subjects consuming olestra.

The effect of olestra on vitamin D status was assessed in a 6-wk, double-blind, placebo-controlled study involving 202 free-living adults. Subjects consumed a total of 20 g/d of olestra or triglycerides in cookies eaten at each meal. A 20-micrograms ergocalciferol capsule was taken with each morning meal. Serum 25-hydroxyergocalciferol (25-OHD2) concentrations rose from approximately 5.7 to 39.0 and 31.7 nmol/L in the placebo and olestra groups, respectively, at week 6. At week 6, 25-OHD2 contributed 46-54% to total serum 25-OHD concentration compared with 11% at baseline. The 19% decrease in serum 25-OHD2 concentrations produced by olestra in this study is equivalent to a decrease of approximately 1.2 nmol/L under nonsupplemented dietary conditions. Ingesting 20 g olestra/d in the diet is thus not expected to affect vitamin D nutritional status.

Fatal pulmonary hypertension and resolving immune-complex glomerulonephritis in mixed connective tissue disease. A case report and review of the literature.

Mixed connective tissue disease (MCTD) has been characterized as a benign rheumatic syndrome with a favorable response to immunosuppressive therapy. Serious renal and pulmonary involvement are reported to be rare in MCTD. We are describing a female adolescent with MCTD in whom fatal cor pulmonale developed due to recurrent thromboembolic primary pulmonary hypertension. Death occurred after two years of therapy with prednisone and azathioprine for an immune-complex glomerulonephritis. Paramesangial and intramembranous electron-dense deposits had been identified in several glomeruli at the start of treatment. Improved renal function and apparent histologic improvement were demonstrated four months after the institution of prednisone and azathioprine therapy, and stable renal function was maintained until death. The pulmonary hypertension was progressive and apparently not altered by either the prednisone or azathioprine. At necropsy, there was no evidence of a pulmonary arteritis or vascular immune-complex deposition to account for the recurrent thromboembolic lesions in the small pulmonary arteries and arterioles. This is a clinical course not previously described in patients with MCTD and may represent an extreme of the clinical spectrum of this syndrome.

A randomized, double-blind study of the effect of olestra on disease activity in patients with quiescent inflammatory bowel disease. Olestra in IBD Study Group.

PURPOSE: To determine the effects of olestra, a zero-calorie fat substitute that is neither digested nor absorbed, on the well-being and disease state of persons with chronic inflammatory bowel disease (IBD) in remission. PATIENTS AND METHODS: Eighty-nine patients with mild to moderate ulcerative colitis (n = 43) or Crohn's disease (n = 46) in remission, with a history of disease of 2 years or longer, were enrolled in this prospective study from nine private practices, three university-based medical centers, and one Veterans Administration medical center in the United States. Forty-four patients were randomly assigned to receive olestra and 45 to receive triglycerides in chips or cookies daily for 4 weeks. At Week 4, patients were classified as in remission, worsened, or relapsed according to an investigator's global assessment based on sigmoidoscopy (for ulcerative colitis) or the Crohn's disease activity index, laboratory findings, and clinical course. RESULTS: At Week 4, the olestra and triglyceride groups did not differ significantly with respect to the percentages of patients who relapsed (P = 0.494; difference = 2.4%; upper 95% CL = 8.8%) or with respect to the percentages of patients who experienced any worsening of their symptoms (P = 0.630; difference = 0.2%; upper 95% CL = 13.3%). Of evaluable patients, 90% (37 of 41) given olestra remained in remission with no worsening, compared with 90% (38 of 42) given triglycerides. Gastrointestinal symptoms were comparable between the treatment groups, and there were no treatment-related laboratory abnormalities. Six patients were excluded from analysis for reasons unrelated to treatment. CONCLUSION: Olestra did not affect the activity of quiescent mild to moderate IBD.

Comparative responses to water stress in stay-green, rapid- and slow senescing genotypes of the biomass crop, Miscanthus.

• Although hybrids of the perennial rhizomatous grass Miscanthus give high yields under irrigation, their use as a biomass crop in many locations is limited by inadequate water availability. Here, the effects of reduced water availability on growth are reported for three Miscanthus genotypes with differing responses to drought. • In a controlled environment experiment during a drought treatment M. sinensis hybrid (Sin-H6) had no detectable photosynthesis and negligible leaf conductance, whereas M. × giganteus (Gig-3) continued to photosynthesize and transpire but it shed leaf area through senescence. A M. sacchariflorus line (Sac-5) was generally intermediate in its response. Measurements on 3-y-old stands of Gig-3 and Sin-H6 in the field during a short summer drought in August 1999 confirmed the controlled environment observations. • Stay-green characteristics in Sin-H6 appeared to rely on tight control of transpiration through lowered leaf conductance, although the highest leaf ABA concentrations were not found in this genotype. • Stay-green genotypes, such as Sin-H6, are likely to be important for further breeding of Miscanthus because they appear to make the most effective use of available water.

Parents and collateral relatives of children with pervasive developmental disorders: a family history study.

The objective of this study was to see whether, using the family history method, the risk for pervasive developmental disorder (PDD), cognitive impairments, and other psychiatric symptoms is greater in the parents and collateral relatives of probands with PDD compared to a control group. A semistructured family history interview was carried out with the parents of 52 probands with PDD and 33 parents of controls. Rates of cognitive impairments and psychiatric problems were not found more frequently in parents or relatives of PDD probands compared to relatives of controls, but four cases of PDD were reported among the extended families of the PDD probands. The relatives with PDD were related to the probands through the maternal line, possibly suggesting some form of maternal influence on inheritance or reduced penetrance in females with the PDD genotype.

High phenotypic correlations among siblings with autism and pervasive developmental disorders.

The objective of this study was to examine familial factors influencing clinical variation in sibships that contained at least 2 children affected with autism or another form of pervasive developmental disorder (PDD). The sample included a total of 60 families, 23 with multiple cases of PDD and 37 with a single affected child. Measurements of IQ, adaptive behaviors in socialization and communication, and autistic symptoms were taken on all affected children. A high intraclass correlation, especially on IQ and an index of social behaviors, was observed between affected children from the same family. In contrast, low correlations were observed on measurements of IQ and adaptive behavior between affected and unaffected children from the same family. These data indicate that variation in severity of PDD is influenced by familial, and probably genetic, mechanisms. The results are discussed in relation to current theories on the genetics of autism and the heritable mechanisms underlying variations in clinical severity.