From lab-based to in-line: Analytical tools for the characterization of whey protein denaturation and aggregation-A review.

Whey protein denaturation and aggregation have long been areas of research interest to the dairy industry, having significant implications for process performance and final product functionality and quality. As such, a significant number of analytical techniques have been developed or adapted to assess and characterize levels of whey protein denaturation and aggregation, to either maximize processing efficiency or create products with enhanced functionality (both technological and biological). This review aims to collate and critique these approaches based on their analytical principles and outline their application for the assessment of denaturation and aggregation. This review also provides insights into recent developments in process analytical technologies relating to whey protein denaturation and aggregation, whereby some of the analytical methods have been adapted to enable measurements in-line. Developments in this area will enable more live, in-process data to be generated, which will subsequently allow more adaptive processing, enabling improved product quality and processing efficiency. Along with the applicability of these techniques for the assessment of whey protein denaturation and aggregation, limitations are also presented to help assess the suitability of each analytical technique for specific areas of interest.

Application of machine-learning methods to milk mid-infrared spectra for discrimination of cow milk from pasture or total mixed ration diets.

The prevalence of "grass-fed" labeled food products on the market has increased in recent years, often commanding a premium price. To date, the majority of methods used for the authentication of grass-fed source products are driven by auditing and inspection of farm records. As such, the ability to verify grass-fed source claims to ensure consumer confidence will be important in the future. Mid-infrared (MIR) spectroscopy is widely used in the dairy industry as a rapid method for the routine monitoring of individual herd milk composition and quality. Further harnessing the data from individual spectra offers a promising and readily implementable strategy to authenticate the milk source at both farm and processor levels. Herein, a comprehensive comparison of the robustness, specificity, and accuracy of 11 machine-learning statistical analysis methods were tested for the discrimination of grass-fed versus non-grass-fed milks based on the MIR spectra of 4,320 milk samples collected from cows on pasture or indoor total mixed ration-based feeding systems over a 3-yr period. Linear discriminant analysis and partial least squares discriminant analysis (PLS-DA) were demonstrated to offer the greatest level of accuracy for the prediction of cow diet from MIR spectra. Parsimonious strategies for the selection of the most discriminating wavelengths within the spectra are also highlighted.

Effect of bovine feeding system (pasture or concentrate) on the oxidative and sensory shelf life of whole milk powder.

Correlating volatile compounds with the sensory attributes of whole milk powder (WMP) is fundamental for appreciating the effect of lipid oxidation (LO) on sensory perception. LO compounds can adversely affect the sensory perception of WMP by imparting rancid, metallic, and painty notes. Whole milk powders derived from milk produced by cows maintained on a pasture diet (grass and grass-clover mix) versus a nonpasture diet [total mixed ration (TMR); concentrates and silage] were stored at room temperature 21°C (ambient storage) and 37°C (accelerated storage) and analyzed for volatile compounds and sensory attributes every 2 mo for a total of 6 mo. Thirteen volatile compounds originating from LO were chosen to track the volatile profile of the WMP during storage. Color, composition, total fatty acid, and free fatty acid profiling were also carried out. Significant variations in the concentrations of 14 fatty acids were observed in WMP based on diet. Concentrations of free fatty acids increased in all sample types during storage. Similar trends in sensory attributes were observed with an increase in painty attributes, corresponding to an increase in hexanal. Buttery/toffee attributes were found to be more closely correlated with TMR WMP. Those WMP derived from pasture diets were found to be more susceptible to LO from a volatile perspective, particularly in relation to aldehyde development, which is likely due to increased concentrations of conjugated linoleic acid and α-linolenic acid found in these samples.

Raman spectroscopy: A rapid method to assess the effects of pasture feeding on the nutritional quality of butter.

The animal diet is a critical variable affecting the composition and functionality of dairy products. As "Grass-Fed" labeling becomes more prominent on the market, rapid and label-free methods for verification of feeding systems are required. This work proposes the use of Raman spectroscopy to study the effects of 3 different experimental cow feeding systems-perennial ryegrass pasture, perennial ryegrass with white clover pasture, and an indoor total mixed ration diet (TMR)-on the nutritional quality of sweet cream butter. The results demonstrate that Raman spectroscopy coupled with multivariate analysis is a promising approach to distinguish butter derived from pasture or conventional TMR feeding systems. A Pearson correlation analysis confirmed high positive correlations between the spectral bin at 1,657 cm-1, ascribed to the stretching vibrations of C=C bonds, and concentrations of α-linolenic acid and conjugated linolenic acid (CLA) in butter, and in general with the concentration of n-3 and n-3+CLA fatty acids and polyunsaturated fatty acids in the samples. The yellow color indicative of the presence of carotenoids in butter, which has previously been suggested as a biomarker of pasture or "Grass-Fed" feeding, was also positively correlated with the data obtained from the Raman spectra. Raman spectroscopy could also be used to accurately predict indicators of the nutritional quality of butter, such as the thrombogenic index, which showed a strong negative correlation with the spectral bin at 3,023 cm-1.

Horizontal Gene Transfer as an Indispensable Driver for Evolution of Neocallimastigomycota into a Distinct Gut-Dwelling Fungal Lineage.

Survival and growth of the anaerobic gut fungi (AGF; Neocallimastigomycota) in the herbivorous gut necessitate the possession of multiple abilities absent in other fungal lineages. We hypothesized that horizontal gene transfer (HGT) was instrumental in forging the evolution of AGF into a phylogenetically distinct gut-dwelling fungal lineage. The patterns of HGT were evaluated in the transcriptomes of 27 AGF strains, 22 of which were isolated and sequenced in this study, and 4 AGF genomes broadly covering the breadth of AGF diversity. We identified 277 distinct incidents of HGT in AGF transcriptomes, with subsequent gene duplication resulting in an HGT frequency of 2 to 3.5% in AGF genomes. The majority of HGT events were AGF specific (91.7%) and wide (70.8%), indicating their occurrence at early stages of AGF evolution. The acquired genes allowed AGF to expand their substrate utilization range, provided new venues for electron disposal, augmented their biosynthetic capabilities, and facilitated their adaptation to anaerobiosis. The majority of donors were anaerobic fermentative bacteria prevalent in the herbivorous gut. This study strongly indicates that HGT indispensably forged the evolution of AGF as a distinct fungal phylum and provides a unique example of the role of HGT in shaping the evolution of a high-rank taxonomic eukaryotic lineage.IMPORTANCE The anaerobic gut fungi (AGF) represent a distinct basal phylum lineage (Neocallimastigomycota) commonly encountered in the rumen and alimentary tracts of herbivores. Survival and growth of anaerobic gut fungi in these anaerobic, eutrophic, and prokaryote-dominated habitats necessitates the acquisition of several traits absent in other fungal lineages. We assess here the role of horizontal gene transfer as a relatively fast mechanism for trait acquisition by the Neocallimastigomycota postsequestration in the herbivorous gut. Analysis of 27 transcriptomes that represent the broad diversity of Neocallimastigomycota identified 277 distinct HGT events, with subsequent gene duplication resulting in an HGT frequency of 2 to 3.5% in AGF genomes. These HGT events have allowed AGF to survive in the herbivorous gut by expanding their substrate utilization range, augmenting their biosynthetic pathway, providing new routes for electron disposal by expanding fermentative capacities, and facilitating their adaptation to anaerobiosis. HGT in the AGF is also shown to be mainly a cross-kingdom affair, with the majority of donors belonging to the bacteria. This study represents a unique example of the role of HGT in shaping the evolution of a high-rank taxonomic eukaryotic lineage.

An updated review of clinical methods in the assessment of ageing skin - New perspectives and evaluation for claims support.

With the advancement of skin research, today's consumer has increased access to an informed understanding of ageing skin and its appendages, together with a plethora of targeted products to meet such needs. In recent years, increased legislative demands for quality evidential claims support have led not only to the development and validation of clinical methods to measure and quantify ageing skin, but also a clearer understanding of the skin ageing process-especially the impact of both its internal and external environments-as well as a tougher stance on clearly unjustifiable claims. Traditional testing methods used to research and evaluate anti-ageing products claim to employ sophisticated instruments. Today, however, since the term anti-ageing can be considered a misnomer, intelligent use of combined more advanced clinical methods has enabled the development of technologically improved consumer products providing enhanced efficacy and targeted performance. Non-invasive methods for the assessment and quantification of the causes of ageing skin provide tools to the clinical researcher as defined by key clinically observed ageing parameters. Where evidence requires additional support, a number of clinical procedures evaluating ageing skin and hair products are combined with invasive procedures, thus enabling an added value to product claims. As discussed herein, given the enhanced understanding of ageing, we provide an update to our previous reviews of clinical methods used in the assessment of skin ageing, to include the wider aspects of environmental exposure; skin pigmentation; microbiome disturbance; surface topography; colour, radiance, and pH; and structural integrity-all requiring a disciplined approach to their use in dermatological investigations and product claims evidence.

Perforated esophageal intervention focus (PERF) study: a multi-center examination of contemporary treatment.

The treatment of esophageal perforation (EP) remains a significant clinical challenge. While a number of investigators have previously documented efficient approaches, these were mostly single-center experiences reported prior to the introduction of newer technologies: specifically endoluminal stents. This study was designed to document contemporary practice in the diagnosis and management of EP at multiple institutions around the world and includes early clinical outcomes. A five-year (2009-2013) multicenter retrospective review of management and outcomes for patients with thoracic or abdominal esophageal perforation was conducted. Demographics, etiology, diagnostic modalities, treatments, subsequent early outcomes as well as morbidity and mortality were captured and analyzed. During the study period, 199 patients from 10 centers in the United States, Canada, and Europe were identified. Mechanisms of perforation included Boerhaave syndrome (60, 30.1%), iatrogenic injury (65, 32.6%), and penetrating trauma (25, 12.6%). Perforation was isolated to the thoracic segment alone in 124 (62.3%), with 62 (31.2%) involving the thoracoabdominal esophagus. Mean perforation length was 2.5 cm. Observation was selected as initial management in 65 (32.7%), with only two failures. Direct operative intervention was initial management in 65 patients (32.6%), while 29 (14.6%) underwent esophageal stent coverage. Compared to operative intervention, esophageal stent patients were significantly more likely to be older (61.3 vs. 48.3 years old, P < 0.001) and have sustained iatrogenic mechanisms of esophageal perforation (48.3% vs.15.4%). Secondary intervention requirement for patients with perforation was 33.7% overall (66). Complications included sepsis (56, 28.1%), pneumonia (34, 17.1%) and multi-organ failure (23, 11.6%). Overall mortality was 15.1% (30). In contemporary practice, diagnostic and management approaches to esophageal perforation vary widely. Despite the introduction of endoluminal strategies, it continues to carry a high risk of mortality, morbidity, and need for secondary intervention. A concerted multi-institutional, prospectively collected database is ideal for further investigation.

The gut microbiome as a virtual endocrine organ with implications for farm and domestic animal endocrinology.

The gut microbiome exerts a marked influence on host physiology, and manipulation of its composition has repeatedly been shown to influence host metabolism and body composition. This virtual endocrine organ also has a role in the regulation of the plasma concentrations of tryptophan, an essential amino acid and precursor to serotonin, a key neurotransmitter within both the enteric and central nervous systems. Control over the hypothalamic-pituitary-adrenal axis also appears to be under the influence of the gut microbiota. This is clear from studies in microbiota-deficient germ-free animals with exaggerated responses to psychological stress that can be normalized by monocolonization with certain bacterial species including Bifidobacterium infantis. Therapeutic targeting of the gut microbiota may thus be useful in treating or preventing stress-related microbiome-gut-brain axis disorders and metabolic diseases, much the same way as redirections of metabolopathies can be achieved through more traditional endocrine hormone-based interventions. Moreover, the implications of these findings need to be considered in the context of farm and domestic animal physiology, behavior, and food safety.

The ontogeny of fairness in seven societies.

A sense of fairness plays a critical role in supporting human cooperation. Adult norms of fair resource sharing vary widely across societies, suggesting that culture shapes the acquisition of fairness behaviour during childhood. Here we examine how fairness behaviour develops in children from seven diverse societies, testing children from 4 to 15 years of age (n = 866 pairs) in a standardized resource decision task. We measured two key aspects of fairness decisions: disadvantageous inequity aversion (peer receives more than self) and advantageous inequity aversion (self receives more than a peer). We show that disadvantageous inequity aversion emerged across all populations by middle childhood. By contrast, advantageous inequity aversion was more variable, emerging in three populations and only later in development. We discuss these findings in relation to questions about the universality and cultural specificity of human fairness.

Plerixafor is superior to conventional chemotherapy for first-line stem cell mobilisation, and is effective even in heavily pretreated patients.

This study (PHANTASTIC) compares first-line plerixafor with granulocyte colony-stimulating factor (G-CSF) in 98 myeloma and lymphoma patients with 151 historic controls mobilised by conventional chemotherapy+G-CSF. Eleven patients developed mild transient symptoms possibly related to plerixafor. No serious adverse events were seen. Seventy (71%) plerixafor-mobilised patients achieved both ⩾ 4 × 10(6) CD34(+) cells/kg in ⩽ 2 aphereses and no neutropenia (<1.0 × 10(9)/l). This is significantly > 48 (32%) of 151 historical chemotherapy+G-CSF-mobilised control patients achieving this end point (P<0.001). Ninety-six (98%) plerixafor-mobilised patients achieved ⩾ 2 × 10(6) CD34(+) cells/kg within one harvest round compared with 114 (75%) of controls (P=0.001). Engraftment times and 12-month outcome were comparable in both groups. Prior treatment was summarised by two scoring systems. Controls mobilising either >2.0 or >4.0 × 10(6) CD34(+) cells/kg have significantly lower scores than mobilisation failures (P=0.002), but this relationship was not seen for plerixafor-mobilised patients. Plerixafor is a more effective and less toxic mobilising agent than conventional chemotherapy (especially in heavily pretreated patients), with comparable subsequent outcome, and merits consideration as the first-line standard of care for stem cell mobilisation.

Seasonal climate manipulations have only minor effects on litter decomposition rates and N dynamics but strong effects on litter P dynamics of sub-arctic bog species.

Litter decomposition and nutrient mineralization in high-latitude peatlands are constrained by low temperatures. So far, little is known about the effects of seasonal components of climate change (higher spring and summer temperatures, more snow which leads to higher winter soil temperatures) on these processes. In a 4-year field experiment, we manipulated these seasonal components in a sub-arctic bog and studied the effects on the decomposition and N and P dynamics of leaf litter of Calamagrostis lapponica, Betula nana, and Rubus chamaemorus, incubated both in a common ambient environment and in the treatment plots. Mass loss in the controls increased in the order Calamagrostis < Betula < Rubus. After 4 years, overall mass loss in the climate-treatment plots was 10 % higher compared to the ambient incubation environment. Litter chemistry showed within each incubation environment only a few and species-specific responses. Compared to the interspecific differences, they resulted in only moderate climate treatment effects on mass loss and these differed among seasons and species. Neither N nor P mineralization in the litter were affected by the incubation environment. Remarkably, for all species, no net N mineralization had occurred in any of the treatments during 4 years. Species differed in P-release patterns, and summer warming strongly stimulated P release for all species. Thus, moderate changes in summer temperatures and/or winter snow addition have limited effects on litter decomposition rates and N dynamics, but summer warming does stimulate litter P release. As a result, N-limitation of plant growth in this sub-arctic bog may be sustained or even further promoted.

High sensitivity troponin T provides useful prognostic information in non-acute chest pain.

OBJECTIVE: To evaluate the prognostic value of high-sensitivity troponin T (hs-cTnT) in patients who present to General Practitioners (GPs) with non-acute chest pain. DESIGN, SETTING AND PATIENTS: A total of 625 patients who were referred by their GPs to a regional Rapid Access Chest Pain Clinic in Tayside, Scotland were consented and recruited. Diamond-Forrester pretest probability of coronary artery disease (CAD) was used to select patients with intermediate and high-pretest probability. Hs-cTnT and B-type Natriuretic Peptide (BNP) were measured and final diagnosis recorded. Twelve-month follow-up for cardiac events and hospital admission data was collected. Sensitivity, specificity, positive predictive value and negative predictive value (NPV), for both prognosis and diagnosis, were produced using various pre-specified cut-off values for hs-cTnT and BNP. RESULTS: A total of 579 patients were included in the final analysis. Of these, 477 had intermediate/high-pretest probability of CAD. A total of 431 (90.4%) of patients had a hs-cTnT ≤14 ng/l. In this study, hs-cTnT of 14 ng/l was the best cut-off for ruling out if a patient would have an admission for cardiac chest pain in the following 12 months (specificity 90%, NPV 91.4%). It performed well as a predictor of a subsequent negative diagnosis of cardiac chest pain with a specificity of 92.4% and NPV of 83.5%. CONCLUSIONS: Hs-cTnT, at the same level currently used in clinical practice as a diagnostic cut-off for myocardial infarction and acute coronary syndromes, is also a clinically-meaningful indicator for further 12-month cardiac chest pain hospital admissions in patients with non-acute chest pain referred to chest pain clinics by GPs.

Impacts of long-term enhanced UV-B radiation on bryophytes in two sub-Arctic heathland sites of contrasting water availability.

BACKGROUND AND AIMS: Anthropogenic depletion of stratospheric ozone in Arctic latitudes has resulted in an increase of ultraviolet-B radiation (UV-B) reaching the biosphere. UV-B exposure is known to reduce above-ground biomass and plant height, to increase DNA damage and cause accumulation of UV-absorbing compounds in polar plants. However, many studies on Arctic mosses tended to be inconclusive. The importance of different water availability in influencing UV-B impacts on lower plants in the Arctic has been poorly explored and might partially explain the observed wide variation of responses, given the importance of water in controlling bryophyte physiology. This study aimed to assess the long-term responses of three common sub-Arctic bryophytes to enhanced UV-B radiation (+UV-B) and to elucidate the influence of water supply on those responses. METHODS: Responses of three sub-Arctic bryophytes (the mosses Hylocomium splendens and Polytrichum commune and the liverwort Barbilophozia lycopodioides) to +UV-B for 15 and 13 years were studied in two field experiments using lamps for UV-B enhancement with identical design and located in neighbouring areas with contrasting water availability (naturally mesic and drier sites). Responses evaluated included bryophyte abundance, growth, sporophyte production and sclerophylly; cellular protection by accumulation of UV-absorbing compounds, ß-carotene, xanthophylls and development of non-photochemical quenching (NPQ); and impacts on photosynthesis performance by maximum quantum yield (F(v) /F(m)) and electron transport rate (ETR) through photosystem II (PSII) and chlorophyll concentrations. RESULTS: Responses were species specific: H. splendens responded most to +UV-B, with reduction in both annual growth (-22 %) and sporophyte production (-44 %), together with increased ß-carotene, violaxanthin, total chlorophyll and NPQ, and decreased zeaxanthin and de-epoxidation of the xanthophyll cycle pool (DES). Barbilophozia lycopodioides responded less to +UV-B, showing increased ß-carotene and sclerophylly and decreased UV-absorbing compounds. Polytrichum commune only showed small morphogenetic changes. No effect of UV-B on bryophyte cover was observed. Water availability had profound effects on bryophyte ecophysiology, and plants showed, in general, lower growth and ETR, together with a higher photoprotection in the drier site. Water availability also influenced bryophyte responses to +UV-B and, in particular, responses were less detectable in the drier site. CONCLUSIONS: Impacts of UV-B exposure on Arctic bryophytes were significant, in contrast to modest or absent UV-B effects measured in previous studies. The impacts were more easily detectable in species with high plasticity such as H. splendens and less obvious, or more subtle, under drier conditions. Species biology and water supply greatly influences the impact of UV-B on at least some Arctic bryophytes and could contribute to the wide variation of responses observed previously.

A review of ageing and an examination of clinical methods in the assessment of ageing skin. Part I: Cellular and molecular perspectives of skin ageing.

The ageing process is noticeable within all organs of the body and manifests itself visibly in the skin. Skin ageing is influenced by several factors including genetics, environmental exposure, hormonal changes and metabolic processes. Together these factors lead to cumulative alterations of skin structure, function and appearance. The functioning of the central nervous, immune, endocrine and cardiovascular systems, as well as the skin is also impaired with age. Chronologically, aged skin is thin, relatively flattened, dry and unblemished, with some loss of elasticity and age-related loss of architectural regularity. General atrophy of the extracellular matrix is reflected by a decrease in the number of fibroblasts. Reduced levels of collagen and elastin, with impaired organization are primarily because of decreased protein synthesis affecting types I and III collagen in the dermis, with an increased breakdown of extracellular matrix proteins. Oxidative stress is considered of primary importance in driving the ageing process. The original free radical theory of ageing purported that the molecular basis of ageing was derived from a lifetime accumulation of oxidative damage to cells resulting from excess reactive oxygen species (ROS) produced as a consequence of aerobic metabolism. Although the skin possesses extremely efficient anti-oxidant activities, during ageing, ROS levels rise and anti-oxidant activities decline. The ROS are necessary in multiple MAP kinase pathways and the induction of AP-1, in turn, up-regulates expression of matrix-metalloproteinases providing a plausible mechanism for the increased collagen degradation in aged human skin.

A review of ageing and an examination of clinical methods in the assessment of ageing skin. Part 2: Clinical perspectives and clinical methods in the evaluation of ageing skin.

With the advancement of skin research, today's consumer has increased access to technological information about ageing skin and hair care products. As a result, there is a rapidly increasing demand for proof of efficacy of these products. Recognizing these demands has led to the development and validation of many clinical methods to measure and quantify ageing skin and the effects of anti-ageing treatments. Many of the current testing methods used to research and evaluate anti-ageing product claim to employ sophisticated instruments alongside more traditional clinical methods. Intelligent use of combined clinical methods has enabled the development of technologically advanced consumer products providing enhanced efficacy and performance. Of non-invasive methods for the assessment and quantification of ageing skin, there is a plethora of tools available to the clinical researcher as defined by key clinically observed ageing parameters: skin roughness and surface texture; fine lines and wrinkles; skin pigmentation; skin colour; firmness and elasticity; hair loss; and proliferative lesions. Furthermore, many clinical procedures for the evaluation of ageing skin treatments are combined with invasive procedures, which enable added-value to claims (such as identification and alteration of biochemical markers), particularly in those cases where perception of product effect needs additional support. As discussed herein, clinical methods used in the assessment of skin ageing are many and require a disciplined approach to their use in such investigations.

A catchment-scale carbon and greenhouse gas budget of a subarctic landscape.

This is the first attempt to budget average current annual carbon (C) and associated greenhouse gas (GHG) exchanges and transfers in a subarctic landscape, the Lake Torneträsk catchment in northern Sweden. This is a heterogeneous area consisting of almost 4000 km2 of mixed heath, birch and pine forest, and mires, lakes and alpine ecosystems. The magnitudes of atmospheric exchange of carbon in the form of the GHGs, CO2 and CH4 in these various ecosystems differ significantly, ranging from little or no flux in barren ecosystems over a small CO2 sink function and low rates of CH4 exchange in the heaths to significant CO2 uptake in the forests and also large emissions of CH4 from the mires and small lakes. The overall catchment budget, given the size distribution of the individual ecosystem types and a first approximation of run-off as dissolved organic carbon, reveals a landscape currently with a significant sink capacity for atmospheric CO2. This sink capacity is, however, extremely sensitive to environmental changes, particularly those that affect the birch forest ecosystem. Climatic drying or wetting and episodic events such as insect outbreaks may cause significant changes in the sink function. Changes in the sources of CH4 through increased permafrost melting may also easily change the sign of the current radiative forcing, due to the stronger impact per gram of CH4 relative to CO2. Hence, to access impacts on climate, the atmospheric C balance alone has to be weighed in a radiative forcing perspective. When considering the emissions of CH4 from the mires and lakes as CO2 equivalents, the Torneträsk catchment is currently a smaller sink of radiative forcing, but it can still be estimated as representing the equivalent of approximately 14000 average Swedish inhabitants' emissions of CO2. This can be compared with the carbon emissions of less than 200 people who live permanently in the catchment, although this comparison disregards substantial emissions from the non-Swedish tourism and transportation activities.

Climate change has only a minor impact on nutrient resorption parameters in a high-latitude peatland.

Nutrient resorption from senescing plant tissues is an important determinant of the fitness of plant populations in nutrient-poor ecosystems, because it makes plants less dependent on current nutrient uptake. Moreover, it can have significant "afterlife" effects through its impact on litter chemistry and litter decomposability. Little is known about the effects of climate change on nutrient resorption. We studied the effects of climate change treatments (including winter snow addition, and spring and/or summer warming) on nutrient resorption of four dominant species in a nutrient-poor subarctic peatland. These species were Betula nana (woody deciduous), Vaccinium uliginosum (woody deciduous), Calamagrostis lapponica (graminoid) and Rubus chamaemorus (forb). After five years of treatments both mature and senesced leaf N concentrations showed a small but significant overall reduction in response to the climate treatments. However, the effects were species-specific. For example, in the controls the N concentration in senesced leaves of Calamagrostis (3.0+/-0.2 mg N g(-1)) was about four times lower than for Rubus (11.2+/-0.2 mg N g(-1)). There were no significant treatment effects on N resorption efficiency (% of the N pool in mature leaves that is resorbed during senescence). The nitrogen resorption efficiency of Calamagrostis (about 80%) was higher than in the other three species (about 60%). Thus, climate change has only a minor impact on nutrient resorption parameters. However, given the substantial interspecific differences in these parameters, substantial changes in plant-soil feedbacks may be expected as a result of the observed changes in the species composition of high-latitude vegetation. These changes are species-specific and thus difficult to predict.

[Hematological aspects of Gaucher disease]. / Aspects hématologiques de la maladie de Gaucher.

PURPOSE: Gaucher disease is the most frequent lysosomal storage disease, and corresponds to an inherited deficiency of glucocerebrosidase. Due to excessive accumulation of glucocerebroside in bone marrow, cytopenia and bone lesions occur. KEY POINTS: The clinical signs at diagnosis include frequently anaemia, thrombopenia and splenomegaly. The hematologist is often in first line of the diagnosis, but it must avoid certain diagnostic traps (pseudo-Gaucher cells or even pseudo-pseudo-Gaucher cells in certain crystal storage diseases). The treatment of substitution when adequately carried out generally makes it possible to quickly improve the hematologic parameters. Another hematologic aspect must be evoked in Gaucher disease, i.e. the incidence of associated malignant pathologies and more particularly of multiple myeloma. Many cases of association between multiple myeloma and Gaucher disease have been reported in the literature. Recently two important series demonstrated the nonfortuitous character of this association. PROJECTS: The physiopathological links which could connect myeloma and Gaucher disease are not known to date. Immune network imbalance could be an interesting hypothesis that should require further investigations.

Alterations in transporter expression in liver, kidney, and duodenum after targeted disruption of the transcription factor HNF1alpha.

The transcription factor hepatocyte nuclear factor 1alpha (HNF1alpha) is involved in regulation of glucose metabolism and transport, and in the expression of several drug and bile acid metabolizing enzymes. Targeted disruption of the HNF1alpha gene results in decreased Cyp1a2, and Cyp2e1 expression, and increased Cyp4a1 and Cyp7a1 expression, suggesting these enzymes are HNF1alpha target genes. Since hepatic metabolism can be coordinately linked with drug and metabolite transport, this study aims to demonstrate whether HNF1alpha regulates expression of a variety of organic anion and cation transporters through utilization of an HNF1alpha-null mouse model. Expression of 32 transporters, including members of the Oat, Oatp, Oct, Mrp, Mdr, bile acid and sterolin families, was quantified in three different tissues: liver, kidney, and duodenum. The expression of 17 of 32 transporters was altered in liver, 21 of 32 in kidney, and 6 of 32 in duodenum of HNF1alpha-null mice. This includes many novel observations, including marked downregulation of Oats in kidney, as well as upregulation of many Mrp and Mdr family members in all three tissues. These data indicate that disruption of HNF1alpha causes a marked attenuation of several Oat and Oatp uptake transporters in liver and kidney, and increased expression of efflux transporters such as Mdrs and Mrps, thus suggesting that HNF1alpha is a central mediator in regulating hepatic, renal, and intestinal transporters.