Changes In Nutrient Status Research Articles

The Effect of Multi-Vitamin/Multi-Mineral Supplementation on Nutritional Status in Older Adults Receiving Drug Therapies: A Double-Blind, Placebo-Controlled Trial

Polypharmacy regimens may increase the susceptibility of older adults to micronutrient inadequacy and deficiency via impairment of nutritional status. We hypothesized that a multi-vitamin-mineral supplement (MVMS) could improve nutritional status in older adults prescribed diuretics, metformin, and/or proton pump inhibitors (PPIs). We conducted a randomized, double-blind, placebo controlled, parallel clinical trial in which eligible subjects were instructed to consume either a MVMS or placebo for 16 wk. Fasting blood was collected at baseline, 8, and 16 wk and the status of selected vitamins and minerals determined. Thirty-five and 19 men and women aged 45–75 yrs in the in MVMS and placebo arms, respectively, completed the trial. The mean total number of medications among the three drug classes taken by participants did not differ between two groups. The status of vitamins B1, B12, C and folate and calcium, copper, magnesium and zinc at baseline were within normal ranges. The MVMS group had a greater change in nutrient status after 16 wk compared to the placebo group for serum folate (7.5 vs. –1.6 ng/mL, p < 0.0001), vitamin B12 (159.2 vs. –33.9 pg/mL, p = 0.007), and plasma vitamin C (0.2 vs. 0.0 mg/dL, p = 0.004). Other measured vitamins and minerals were not significantly changed during the intervention. In conclusion, the status of vitamins B12, C and folate improved with MVMS but remained within normal ranges in older adults taking diuretics, metformin, and/or PPIs.

Chemocline collapse in Lake Kivu as an analogue for nitrogen cycling during Oceanic Anoxic Events

One of the outstanding issues in the study of nutrient dynamics during Oceanic Anoxic Events (OAEs) is the preservation of 15N-depleted nitrogen isotope signals, which are not observed in analogous modern environments. The favored mechanism for δ15N values below 0‰ is utilization of excess ammonium derived from underlying anoxic waters by primary producers. However, there are few modern examples available for testing this hypothesis, due to the overall well-oxygenated state of modern oceans. Here, we present sedimentary δ13Corg and δ15Nbulk data, as well as pigment biomarker ratios, from the sediments of Lake Kivu, a meromictic lake in East Africa. This system serves as a potential analogue for the development of strongly depleted δ15Nbulk in OAE black shales. We focus on intervals of organic carbon enrichment (sapropels) that are interpreted to have been the result of lake water column mixing events. Sediment δ13Corg and δ15Nbulk decrease by up to 6 and 4‰ respectively near the base of sapropel layers. These negative excursions provide evidence for the mixing of 13C-depleted dissolved inorganic carbon and ammonium in excess of photosynthetic need, derived from the deeper anoxic basin of the lake. Support of this model is also provided by photosynthetic pigment biomarkers which show significant fluctuations in phototrophic ecology consistent with water column mixing and changes in nutrient status. Further evidence for the shallowing of the chemocline during sapropel deposition is found in the presence of bacteriochlorophyll derivatives produced by phototrophic sulfide oxidizers.

Temperature and food availability alters the physiology and aerobic capacity of tambaqui (Colossoma macropomum)

Fish of the Amazon experience both daily and seasonal variation in temperature and food availability. In the present work, we investigated the influence of nutrient status changes resulting from feeding Colossoma macropomum five flooded forest fruits on aerobic and swimming performance. To assess the effects of diet, three groups of fish were provided different types of food. One group of was provided with commercial feed, another was given fruit feed, and the last group was not fed. The effects of temperature were tested by keeping half of each group of animals at either 26 °C or 33°C for 30 days. After this period, the animals were transferred to either a respiratory chamber or swimming tunnel. Then, tissues were collected for relevant analyses. Results showed that C. macropomum depresses aerobic metabolism when food is withheld (27% reduction in ṀO2), and observed effects were intensified at the highest temperature (40% reduction in ṀO2 at 33 °C). Further, increased temperature negatively influenced hematological (Ht, Hb, VCM), biochemical (glucose, triglycerides, cholesterol), hepatossomatic index and enzymatic (MDH and CS in white muscle) parameters. The animals feeding commercial and fruits enriched diets, have a physiological and biological advantage when compared to the unfed animals at both temperatures. Metabolic suppression is an important strategy for maintaining swimming capacity in C. macropomum. It is suggested that even after a long period of fasting, carbohydrates are important energetic substrates.

Combination therapy with ropivacaine-loaded liposomes and nutrient deprivation for simultaneous cancer therapy and cancer pain relief.

Autophagy allows cancer cells to respond changes in nutrient status by degrading and recycling non-essential intracellular contents. Inhibition of autophagy combined with nutrient deprivation is an effective strategy to treat cancer. Pain is a primary determinant of poor quality of life in advanced cancer patients, but there is currently no satisfactory treatment. In addition, effective treatment of cancer does not efficiently relieve cancer pain, but may increase pain in many cases. Hence, few studies focus on simultaneous cancer therapy and pain relief, and made this situation even worse.Method: Ropivacaine was loaded into tumor-active targeted liposomes. The cytotoxicity of ropivacaine-based combination therapy in B16 and HeLa cells were tested. Moreover, a mice model of cancer pain which was induced by inoculation of melanoma near the sciatic nerve was constructed to assess the cancer suppression and pain relief effects of ropivacaine-based combination therapy.Results: Ropivacaine and ropivacaine-loaded liposomes (Rop-DPRL) were novelly found to damage autophagic degradation. Replicated administration of Rop-DPRL and calorie restriction (CR) could efficiently repress the development of tumor. In addition, administration of Rop-DPRL could relieve cancer pain with its own analgestic ability in a short duration, while repeated administration of Rop-DPRL and CR resulted in continuous alleviation of cancer pain through reduction of VEGF-A levels in advanced cancer mice. Further, dual inhibition of phosphorylation of STAT3 at Tyr705 and Ser727 by Rop-DPRL and CR contribute to the reduction of VEGF-A.Conclusion: Combination therapy with Rop-DPRL and nutrient deprivation simultaneously suppresses cancer growth and relieves cancer pain.

Legacy effects of nitrogen deposition on plant nutrient stoichiometry in a temperate grassland

Nitrogen (N) deposition has negative consequences for plant communities and ecosystem functioning. Nitrogen deposition is declining or is projected to decline in many regions due to the reduction of N-compound emissions. It remains unknown whether the cessation of N deposition will have legacy effects on plant nutrient stoichiometry. If there are stoichiometric legacy effects at the community-level from prior N enrichment, the contribution of changes in community composition relative to the stoichiometric responses of individual functional groups in driving these changes is unknown. We measured plant N:P ratio at both functional group level and community level in a temperate steppe in three consecutive years following cessation of a 7-year N addition experiment with a wide-range of total amount added N in which the total amount of N added ranged from 0 to 350 g m−2. The total amount of N addition was positively correlated with tall rhizomatous grass productivity and negatively correlated with tall bunchgrass productivity. Plant N:P ratios at both functional group and community levels did not change across N addition gradient. Community composition shifts contributed less than intra-group variation to the total variation of community level nutrient status in response to historic N addition. Our results indicated that biological N:P imbalance in response to N deposition can be rapidly ameliorated after the cessation of N deposition. Such legacy effects of N deposition on plant nutrient status are largely driven by the changes of nutrient status of individual plants instead of N-induced shifts in community composition.

The neglected foodborne mycotoxin Fusaric acid induces bioenergetic adaptations by switching energy metabolism from mitochondrial processes to glycolysis in a human liver (HepG2) cell line

Metabolic flexibility defines the capacity of cells to respond to changes in nutrient status. Mitochondria are important mediators of metabolic flexibility and dysfunction is associated with metabolic inflexibility and pathology. Foodborne toxins are often overlooked as potential factors contributing to metabolic toxicity. Fusaric acid (FA), a neglected mycotoxin, is known to disrupt mitochondrial function. The aim of this study was to investigate the molecular mechanisms underlying a metabolic switch in response to FA. This study investigated the effects of FA on energy homeostasis in cultured human liver (HepG2) cells. HepG2 cells poised to undergo oxidative and glycolytic metabolism were exposed to a range of FA concentrations (4, 63 and 250 μg/mL) for 6 h. We determined mitochondrial toxicity, acetyl CoA levels and cell viability using luminometric, fluorometric and spectrophotometric methods. Expression of metabolic proteins (PDK1, PKM2, phosphorylated-PDH E1α and HIF-1α) and mRNAs (HIF-1α, PKM2, LDHa and PDK1) were determined using western blot and qPCR respectively. Our data connects a constitutive expression of HIF-1α in response to FA, to the inhibition of pyruvate decarboxylation through up-regulation of PDK-1 and phosphorylation of Pyruvate Dehydrogenase E1α subunit. Moreover, we highlight the potential of FA to induce a glucose “addiction” and phenotype reminiscent of the Warburg effect. The findings provide novel insights into the impact of this neglected foodborne mycotoxin in the dysregulation of energy metabolism.

A conserved role of the insulin-like signaling pathway in diet-dependent uric acid pathologies in Drosophila melanogaster.

Elevated uric acid (UA) is a key risk factor for many disorders, including metabolic syndrome, gout and kidney stones. Despite frequent occurrence of these disorders, the genetic pathways influencing UA metabolism and the association with disease remain poorly understood. In humans, elevated UA levels resulted from the loss of the of the urate oxidase (Uro) gene around 15 million years ago. Therefore, we established a Drosophila melanogaster model with reduced expression of the orthologous Uro gene to study the pathogenesis arising from elevated UA. Reduced Uro expression in Drosophila resulted in elevated UA levels, accumulation of concretions in the excretory system, and shortening of lifespan when reared on diets containing high levels of yeast extract. Furthermore, high levels of dietary purines, but not protein or sugar, were sufficient to produce the same effects of shortened lifespan and concretion formation in the Drosophila model. The insulin-like signaling (ILS) pathway has been shown to respond to changes in nutrient status in several species. We observed that genetic suppression of ILS genes reduced both UA levels and concretion load in flies fed high levels of yeast extract. Further support for the role of the ILS pathway in modulating UA metabolism stems from a human candidate gene study identifying SNPs in the ILS genes AKT2 and FOXO3 being associated with serum UA levels or gout. Additionally, inhibition of the NADPH oxidase (NOX) gene rescued the reduced lifespan and concretion phenotypes in Uro knockdown flies. Thus, components of the ILS pathway and the downstream protein NOX represent potential therapeutic targets for treating UA associated pathologies, including gout and kidney stones, as well as extending human healthspan.

Transcriptome monitoring visualizes growth stage-dependent nutrient status dynamics in rice under field conditions.

Crop plants undergo morpho-physiological changes throughout the growth process in response to both the internal and the external environment, and that eventually determine the yield. The system-level adjustment of the morpho-physiological changes has remained largely unclear, however, especially in field conditions. Here, we reveal changes in nutrient status associated with tiller development and soil conditions based on the leaf transcriptome profile of rice (Oryza sativa) throughout the entire period of growth. We performed gene co-expression network analysis and identified three gene sets as indicators for monitoring the internal nitrogen and phosphorus status. Expression profiling reveals that the phosphorus starvation response is expressed during the tillering stage and is then switched off with the transition to nitrogen deficiency. Coincident with phosphorus status dynamics, the level of phosphate in the leaf is demonstrated to be low during the tillering stage and subsequently increases drastically. The phosphorus dynamics are genetically validated by analysing mutants with a defect in phosphorus homeostasis. Notably, we show that nitrogen limitation directly suppresses the phosphorus starvation response. Finally, the phosphorus starvation response is demonstrated to be activated in soil with a high phosphate retention capacity, without the visible phenotypes associated with phosphorus starvation. Our results reveal a growth stage- and soil condition-dependent reaction that requires phosphorus, which is expressed to promote the phosphorus uptake required for developing tillers and is directly adjusted by nitrogen status. A molecular framework for elucidating nutrient status dynamics under field conditions would provide insights into improving crop productivity.

Effect of trophic status of a deep-water lake on breeding Great Crested Grebes Podiceps cristatus during a phase of recovery from eutrophication: a long-term study

ABSTRACTCapsule: Trophic status of a deep-water lake was the main driver of changes in breeding population size of Great Crested Grebes Podiceps cristatus while reproductive success was also strongly affected by weather parameters.Aims: To determine the effects of changes in nutrient status of a formerly highly-eutrophicated deep-water lake and other environmental parameters on a Great Crested Grebe population during a phase of re-oligotrophication.Methods: Annual surveys were carried out on a natural lake in Switzerland over a period of 25 years to determine breeding population size and reproductive success. The effects of phosphorus content, other limnological parameters and weather variables were analysed with quasi-Poisson models.Results: The breeding population increased from 80 pairs in 1992 to 417 pairs in 2001, after which numbers showed strong fluctuations. Total phosphorus content in the lake had a strong negative effect on breeding population size. A significant positive correlation was found with the national population index. Reproductive success fluctuated strongly but showed an overall decline. The model indicated positive effects on reproductive success of phosphorus and negative effects of the number of days with strong wind. Rapid water-level increases in early summer and water transparency in June led to higher proportions of late broods.Conclusion: Phosphorus concentration was identified as the main driver affecting the breeding population of Great Crested Grebes during the phase of recovery of the lake from a highly-eutrophic state. Results indicate that mesotrophic to eutrophic conditions enabled a large population and high breeding success. Reproductive output was further negatively affected by strong wind during a critical breeding phase.

The Krüppel-Like Factors and Control of Energy Homeostasis.

Nutrient handling by higher organisms is a complex process that is regulated at the transcriptional level. Studies over the past 15 years have highlighted the critical importance of a family of transcriptional regulators termed the Krüppel-like factors (KLFs) in metabolism. Within an organ, distinct KLFs direct networks of metabolic gene targets to achieve specialized functions. This regulation is often orchestrated in concert with recruitment of tissue-specific transcriptional regulators, particularly members of the nuclear receptor family. Upon nutrient entry into the intestine, gut, and liver, KLFs control a range of functions from bile synthesis to intestinal stem cell maintenance to effect nutrient acquisition. Subsequently, coordinated KLF activity across multiple organs distributes nutrients to sites of storage or liberates them for use in response to changes in nutrient status. Finally, in energy-consuming organs like cardiac and skeletal muscle, KLFs tune local metabolic programs to precisely match substrate uptake, flux, and use, particularly via mitochondrial function, with energetic demand; this is achieved in part via circulating mediators, including glucocorticoids and insulin. Here, we summarize current understanding of KLFs in regulation of nutrient absorption, interorgan circulation, and tissue-specific use.

Biochemical and physiological responses to long‐term Citrus tristeza virus infection in Mexican lime plants

Reactions that occur when a plant is subjected to Citrus tristeza virus (CTV) infection often result in triggering of numerous defence mechanisms to fight the infection. The reactions vary according to virus strain, host genotype, time of exposure to the infection and environmental conditions. To date, no study has examined in detail the consequences of 10‐year exposure to CTV infection on the biochemical and physiological status of susceptible Mexican lime plants (Citrus aurantifolia). To understand the reaction of such plants, changes in nutrient status, total proteins, enzyme activity involved in scavenging of reactive oxygen species, photosynthetic and transpiration rates, chlorophyll content, membrane permeability and water content were analysed in plants infected with different CTV isolates and in healthy plants. The activity of superoxide dismutase and polyphenol oxidase significantly decreased in the infected leaves, and membrane permeability was lower in the infected plants. Macro‐ and micronutrient elements were significantly changed: concentrations of leaf nitrogen, zinc, magnesium and iron were elevated but potassium concentration depressed in comparison to noninfected control leaves. Levels of other analysed nutrient elements, enzymes, photosynthesis and stomatal conductance, chlorophyll content and relative water content were unchanged. Clear physiological changes were found among infected and noninfected control plants but none between plants infected with different CTV isolates. The data suggest that some of the defence mechanisms investigated here were suppressed due to the continuous and long‐term pressure of biotic stress.

β-Cell Control of Insulin Production During Starvation-Refeeding in Male Rats.

Mammalian metabolism has evolved to adapt to changes in nutrient status. Insulin, the key anabolic hormone, facilitates intracellular storage of nutrient fuels and plays a pivotal role in the transition away from catabolism upon refeeding. Although circulating insulin relative to nutrient levels has been well characterized during fasting and refeeding, how pancreatic β-cell biology caters to acute changes in insulin demand has not been sufficiently addressed. Here, we examined the dynamics of (pro)insulin production and associated changes in β-cell ultrastructure during refeeding after a 72-hour fast in male rats. We found that fasted β-cells had marked degranulation, which inversely coordinated with the upregulation of autophagolysomal and lysosomal organelles. There was also expanded Golgi that correlated with enhanced (pro)insulin biosynthetic capacity but, conversely, blunted in vivo insulin secretion. Within 4 to 6 hours of refeeding, proinsulin biosynthesis, cellular ultrastructure, in vivo insulin secretion, and glucose tolerance normalized to levels near those of fed control animals, indicating a rapid replenishment of normal insulin secretory capacity. Thus, during a prolonged fast, the β-cell protects against hypoglycemia by markedly reducing insulin secretory capacity in vivo but is simultaneously poised to efficiently increase (pro)insulin production upon refeeding to effectively return normal insulin secretory capacity within hours.

The Regulation of NRF2 by Nutrient-Responsive Signaling and Its Role in Anabolic Cancer Metabolism.

The stress responsive transcription factor nuclear factor erythroid 2 p45-related factor 2, or NRF2, regulates the expression of many cytoprotective enzymes to mitigate oxidative stress under physiological conditions. NRF2 is activated in response to oxidative stress, growth factor signaling, and changes in nutrient status. In addition, somatic mutations that disrupt the interaction between NRF2 and its negative regulator Kelch-like erythroid cell-derived protein with CNC homology (ECH)-associated 1 (KEAP1) commonly occur in cancer and are thought to promote tumorigenesis. Recent Advances: While it is well established that aberrant NRF2 activation results in enhanced antioxidant capacity in cancer cells, recent exciting findings demonstrate a role for NRF2-mediated metabolic deregulation that supports cancer cell proliferation. In this review, we describe how the NRF2-KEAP1 signaling pathway is altered in cancer, how NRF2 is regulated by changes in cellular metabolism, and how NRF2 reprograms cellular metabolism to support proliferation. Future studies will delineate the NRF2-regulated processes critical for metabolic adaptation to nutrient availability, cellular proliferation, and tumorigenesis. Antioxid. Redox Signal. 00, 000-000.

Glyphosate effects on soil rhizosphere-associated bacterial communities

Glyphosate is one of the most widely used herbicides in agriculture with predictions that 1.35millionmetric tons will be used annually by 2017. With the advent of glyphosate tolerant (GT) cropping more than 10years ago, there is now concern for non-target effects on soil microbial communities that has potential to negatively affect soil functions, plant health, and crop productivity. Although extensive research has been done on short-term response to glyphosate, relatively little information is available on long-term effects. Therefore, the overall objective was to investigate shifts in the rhizosphere bacterial community following long-term glyphosate application on GT corn and soybean in the greenhouse. In this study, rhizosphere soil was sampled from rhizoboxes following 4 growth periods, and bacterial community composition was compared between glyphosate treated and untreated rhizospheres using next-generation barcoded sequencing. In the presence or absence of glyphosate, corn and soybean rhizospheres were dominated by members of the phyla Proteobacteria, Acidobacteria, and Actinobacteria. Proteobacteria (particularly gammaproteobacteria) increased in relative abundance for both crops following glyphosate exposure, and the relative abundance of Acidobacteria decreased in response to glyphosate exposure. Given that some members of the Acidobacteria are involved in biogeochemical processes, a decrease in their abundance could lead to significant changes in nutrient status of the rhizosphere. Our results also highlight the need for applying culture-independent approaches in studying the effects of pesticides on the soil and rhizosphere microbial community.

Temporal development of coastal ecosystems in the Baltic Sea over the past two decades

Abstract Coastal areas are among the most biologically productive aquatic systems worldwide, but face strong and variable anthropogenic pressures. Few studies have, however, addressed the temporal development of coastal ecosystems in an integrated context. This study represents an assessment of the development over time in 13 coastal ecosystems in the Baltic Sea region during the past two decades. The study covers between two to six trophic levels per system and time-series dating back to the early 1990s. We applied multivariate analyses to assess the temporal development of biological ecosystem components and relate these to potential driving variables associated with changes in climate, hydrology, nutrient status, and fishing pressure. Our results show that structural change often occurred with similar timing in the assessed coastal systems. Moreover, in 10 of the 13 systems, a directional development of the ecosystem components was observed. The variables representing key ecosystem components generally differed across systems, due to natural differences and limitation to available data. As a result of this, the correlation between the temporal development of the biological components in each area and the driving variables assessed was to some extent area-specific. However, change in nutrient status was a common denominator of the variables most often associated with changes in the assessed systems. Our results, additionally, indicate existing strengths as well as future challenges in the capacity of currently available monitoring data to support integrated assessments and the implementation of an integrated ecosystem-based approach to the management of the Baltic Sea coastal ecosystems.

Assessing changes in carbon stocks of Scottish soils: lessons learnt

Between 1978 and 1988, the soils at 721 locations throughout Scotland were sampled at intervals 10 km apart. They were described, characterised and samples were taken from each of the main horizons. Material not used for analysis was stored in the National Soils Archive. Between 2007 and 2009, 183 of these locations were re-visited (20 km intervals) and fresh samples taken to identify changes in nutrient status, pH and, in particular, soil carbon concentrations and stocks over the 19-31 year period. The archived soil samples from this time were re-analysed alongside those from the recent sampling to determine carbon concentrations. Near Infrared (NIR) spectroscopy was used to estimate their bulk density so that carbon stocks could be calculated as this was not measured at the original sampling. The results showed no statistically significant change in soil carbon stocks to 1 m depth for the main, broad land use types in Scotland apart from a small but significant increase (P=0.035) in soils under woodland. There was approximately 11.5% difference in carbon concentration between the reanalysed, archived soil and values originally obtained, but this was attributed to an artefact of differences in analytical methods. Between the two sampling periods, a decrease in carbon concentration of 2.4 g kg−1 was detected in cultivated soils. However, a significant increase in topsoil thickness of 2.9 cm (P=0.024) was sufficient to compensate for these changes in arable soils such that there was no detectable change in carbon stocks. The work shows the value of soil archives and of measuring horizon thickness.

Seasonal changes in soil organic matter after a decade of nutrient addition in a lowland tropical forest

Soil organic matter is an important pool of carbon and nutrients in tropical forests. The majority of this pool is assumed to be relatively stable and to turn over slowly over decades to centuries, although changes in nutrient status can influence soil organic matter on shorter timescales. We measured carbon, nitrogen, and phosphorus concentrations in soil organic matter and leaf litter over an annual cycle in a long-term nutrient addition experiment in lowland tropical rain forest in the Republic of Panama. Total soil carbon was not affected by a decade of factorial combinations of nitrogen, phosphorus, or potassium. Nitrogen addition increased leaf litter nitrogen concentration by 7 % but did not affect total soil nitrogen. Phosphorus addition doubled the leaf litter phosphorus concentration and increased soil organic phosphorus by 50 %. Surprisingly, concentrations of carbon, nitrogen, and phosphorus in soil organic matter declined markedly during the four-month dry season, and then recovered rapidly during the following wet season. Between the end of the wet season and the late dry season, total soil carbon declined by 16 %, total nitrogen by 9 %, and organic phosphorus by between 19 % in control plots and 25 % in phosphorus addition plots. The decline in carbon and nitrogen was too great to be explained by changes in litter fall, bulk density, or the soil microbial biomass. However, a major proportion of the dry-season decline in soil organic phosphorus was explained by a corresponding decline in the soil microbial biomass. These results have important implications for our understanding of the stability and turnover of organic matter in tropical forest soils, because they demonstrate that a considerable fraction of the soil organic matter is seasonally transient, despite the overall pool being relatively insensitive to long-term changes in nutrient status.

Intracellular protein O-GlcNAc modification integrates nutrient status with transcriptional and metabolic regulation.

The inducible, nutrient-sensitive posttranslational modification of protein Ser/Thr residues with O-linked β-N-acetylglucosamine (O-GlcNAc) occurs on histones, transcriptional regulators, metabolic enzymes, oncogenes, tumor suppressors, and many critical intermediates of growth factor signaling. Cycling of O-GlcNAc modification on and off of protein substrates is catalyzed by the actions of O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), respectively. To date, there are less than 150 publications addressing the role of O-GlcNAc modification in cancer and over half were published in the last 2 years. These studies have clearly established that increased expression of OGT and hyper-O-GlcNAcylation is common to human cancers of breast, prostate, colon, lung, and pancreas. Furthermore, attenuating OGT activity reduces tumor growth in vitro and metastasis in vivo. This chapter discusses the structure and function of the O-GlcNAc cycling enzymes, mechanisms by which protein O-GlcNAc modification sense changes in nutrient status, the influence of O-GlcNAc cycling enzymes on glucose metabolism, and provides an overview of recent observations regarding the role of O-GlcNAcylation in cancer.

Combinatorial regulation of a signal-dependent activator by phosphorylation and acetylation.

In the fasted state, increases in catecholamine signaling promote adipocyte function via the protein kinase A-mediated phosphorylation of cyclic AMP response element binding protein (CREB). CREB activity is further up-regulated in obesity, despite reductions in catecholamine signaling, where it contributes to the development of insulin resistance. Here we show that obesity promotes the CREB binding protein (CBP)-mediated acetylation of CREB at Lys136 in adipose. Under lean conditions, CREB acetylation was low due to an association with the energy-sensing NAD(+)-dependent deacetylase SirT1; amounts of acetylated CREB were increased in obesity, when SirT1 undergoes proteolytic degradation. Whereas CREB phosphorylation stimulated an association with the KIX domain of CBP, Lys136 acetylation triggered an interaction with the CBP bromodomain (BRD) that augmented recruitment of this coactivator to the promoter. Indeed, coincident Ser133 phosphorylation and Lys136 acetylation of CREB stimulated the formation of a ternary complex with the KIX and BRD domains of CBP by NMR analysis. As disruption of the CREB:BRD complex with a CBP-specific BRD inhibitor blocked effects of CREB acetylation on target gene expression, our results demonstrate how changes in nutrient status modulate cellular gene expression in response to hormonal signals.

The Late Vistulian and Holocene evolution of Jezioro Lake: a record of environmental change in southern Poland found in deposits and landforms

Jezioro Lake is the only natural lake in southern Poland outside mountainous areas to have existed continuously since the Pleistocene. The record of environmental change in the Late Vistulian (Weichselian) and Holocene is preserved in the deposits and landforms around the lake. This paper presents the results of paleogeographical and paleoecological research that emabled us to reconstruct the history of the Jezioro Lake. At the end of the Vistulian period, the outlet of the lake was blocked by a parabolic dune moving in from the west. Limnic sedimentation was evident in the sediment core at all levels from the Holocene, with remains of Cladocera, Chironomidae larvae, and aquatic plants. The lake did not disappear at that time, although its area decreased by a factor of 12 by the end of the period. Paleobotanical research permitted the reconstruction of sequences of plant communities and changes in nutrient status and water level. An initial oligotrophic lake, as indicated by the presence of Isoetes lacustris L., changed to a eutrophic lake, as indicated by the presence of Potamogeton natans L. and Nuphar sp., then the lake progressed to the present-day dystrophic lake that is surrounded by a swamp. The profile of organic deposits contains a record of environmental change at least since the Younger Dryas in southern Poland.