Obesity is a world-wide crisis with profound healthcare and socio-economic implications and it is now clear that the central nervous system (CNS) is a target for the complications of metabolic ...disorders like obesity. In addition to decreases in physical activity and sedentary lifestyles, diet is proposed to be an important contributor to the etiology and progression of obesity. Unfortunately, there are gaps in our knowledge base related to how dietary choices impact the structural and functional integrity of the CNS. For example, while chronic consumption of hypercaloric diets (increased sugars and fat) contribute to increases in body weight and adiposity characteristic of metabolic disorders, the mechanistic basis for neurocognitive deficits in obesity remains to be determined. In addition, studies indicate that acute consumption of hypercaloric diets impairs performance in a wide variety of cognitive domains, even in normal non-obese control subjects. These results from the clinical and basic science literature indicate that diet can have rapid, as well as long lasting effects on cognitive function. This review summarizes our symposium at the 2017 Society for the Study of Ingestive Behavior (SSIB) meeting that discussed these effects of diet on cognition. Collectively, this review highlights the need for integrated and comprehensive approaches to more fully determine how diet impacts behavior and cognition under physiological conditions and in metabolic disorders like type 2 diabetes mellitus (T2DM) and obesity.
•Acute intake of hypercaloric diets impairs cognition, even in healthy subjects•High sucrose consumption elicits neuropathological changes in the hippocampus•Fructose ingestion activates brain regions involved in attention and reward•High fat diet decreases impulse control and striatal D2 receptor expression•Brain insulin resistance is a mechanistic link between obesity and dementia
In classical interferometric null test measurements, the measurement and reference beam path should be the same. A difference in the beam paths results in the so called retrace error. One very common ...approach to avoid retrace errors is to adapt the measurement wavefront to the reference wavefront with a computer generated hologram (CGH), which is costly and time consuming. A much more flexible approach is to do non nulltest measurement in combination with mathematical treatment of retrace errors. Most of such methods are based on iterative optimization or calibration of the nominal optical design of the interferometer. While this may be a convenient solution in the context of research, the more common use may be limited due to the need of the optical design of all interferometer components. In many cases, the optical designs of standard off the shelf optical assemblies are not available or disclosed by the manufacturer. This is especially true for transmission spheres of interferometers. We introduce the so called Black Box Model (BBM), used in the well known Tilted Wave Interferometry (TWI), as a mathematical model to account for retrace errors in interferometry. The Black Box Model is based on point characteristic functions which are adapted to the result and behavior of a real interferometer by calibration. With an extended calibration method, the need of a specific optical design of the interferometer is no longer necessary. Thus the method is attractive for a wide field of use in interferometry with standard off the shelf components.
The ability to feed on a wide range of diets has enabled insects to diversify and colonize specialized niches. Carrion, for example, is highly susceptible to microbial decomposers, but is kept ...palatable several days after an animal’s death by carrion-feeding insects. Here we show that the burying beetle Nicrophorus vespilloides preserves carrion by preventing the microbial succession associated with carrion decomposition, thus ensuring a high-quality resource for their developing larvae. Beetle-tended carcasses showed no signs of degradation and hosted a microbial community containing the beetles’ gut microbiota, including the yeast Yarrowia. In contrast, untended carcasses showed visual and olfactory signs of putrefaction, and their microbial community consisted of endogenous and soil-originating microbial decomposers. This regulation of the carcass’ bacterial and fungal community and transcriptomic profile was associated with lower concentrations of putrescine and cadaverine (toxic polyamines associated with carcass putrefaction) and altered levels of proteases, lipases, and free amino acids. Beetle-tended carcasses develop a biofilm-like matrix housing the yeast, which, when experimentally removed, leads to reduced larval growth. Thus, tended carcasses hosted a mutualistic microbial community that promotes optimal larval development, likely through symbiont-mediated extraintestinal digestion and detoxification of carrion nutrients. The adaptive preservation of carrion coordinated by the beetles and their symbionts demonstrates a specialized resource-management strategy through which insects modify their habitats to enhance fitness.
•An overview on catalyst support structures based on fibrous material is given.•Mass transfer and pressure drop properties of several structures are compared.•Fiber based structured materials offer ...advantageous properties for several applications.
This review summarizes the resent research on fiber based structured materials for catalytic application. This material class comprises a wide range of differently structured supports made from ceramic, metal or glass. Within the last decades due to their flexibility fiber based catalysts were applied to several reactions ranging from pollutant control to fuel processing and showed significant advantages in mass and heat transfer, pressure drop and productivity. The review focusses on mass transfer and pressure drop characteristics and the published correlations for them. A classification in comparison to established support structures is done not only showing superior properties but also the demand for further studies in hydrodynamics and transfer processes.
Pancreatic ductal adenocarcinoma (PDA) is among the most lethal human cancers in part because it is insensitive to many chemotherapeutic drugs. Studying a mouse model of PDA that is refractory to the ...clinically used drug gemcitabine, we found that the tumors in this model were poorly perfused and poorly vascularized, properties that are shared with human PDA. We tested whether the delivery and efficacy of gemcitabine in the mice could be improved by coadministration of IPI-926, a drug that depletes tumor-associated stromal tissue by inhibition of the Hedgehog cellular signaling pathway. The combination therapy produced a transient increase in intratumoral vascular density and intratumoral concentration of gemcitabine, leading to transient stabilization of disease. Thus, inefficient drug delivery may be an important contributor to chemoresistance in pancreatic cancer.
New Findings
What is the central question of this study?
What are the cardiovascular consequences of periconceptual ethanol on offspring throughout the lifespan?
What is the main finding and its ...importance?
It is shown for the first time that periconceptional alcohol has sex‐specific effects on heart growth, with ageing female offspring exhibiting decreased cardiac output. Altered in vivo cardiac function in ageing female offspring may be linked to changes in cardiac oestrogen receptor expression.
Alcohol exposure throughout gestation is detrimental to cardiac development and function. Although many women decrease alcohol consumption once aware of a pregnancy, exposure prior to recognition is common. We, therefore, examined the effects of periconceptional alcohol exposure (PC:EtOH) on heart function, and explored mechanisms that may contribute. Female Sprague–Dawley rats received a liquid diet ±12.5% v/v ethanol from 4 days prior to mating until 4 days after mating (PC:EtOH). Cardiac function was assessed via echocardiography, and offspring were culled at multiple time points for assessment of morphometry, isolated heart and aortic ring function, protein and transcriptional changes. PC:EtOH‐exposed embryonic day 20 fetuses (but not postnatal offspring) had larger hearts relative to body weight. Ex vivo analysis of hearts at 5–7 months old (mo) indicated no changes in coronary function or cardiac ischaemic tolerance, and apparently improved ventricular compliance in PC:EtOH females (compared to controls). At 12 mo, vascular responses in isolated aortic rings were unaltered by PC:EtOH, whilst echocardiography revealed reduced cardiac output in female but not male PC:EtOH offspring. At 19 mo, left ventricular transcript and protein for type 1 oestrogen receptor (ESR1), HSP90 transcript and plasma oestradiol levels were all elevated in female PC:EtOH exposed offspring. Summarising, PC:EtOH adversely impacts in vivo heart function in mature female offspring, associated with increased ventricular oestrogen‐related genes. PC:EtOH may thus influence age‐related heart dysfunction in females through modulation of oestrogen signalling.
Phenotypic and transcriptomic evidence of early cardiac aging, and associated mechanisms, were investigated in young to middle-aged male mice (C57Bl/6; ages 8, 16, 32, 48 wks). Left ventricular gene ...expression (profiled via Illumina MouseWG-6 BeadChips), contractile and coronary function, and stress-resistance were assessed in Langendorff perfused hearts under normoxic conditions and following ischemic insult (20 min global ischemia-45 min reperfusion; I-R). Baseline or normoxic contractile function was unaltered by age, while cardiac and coronary ‘reserves’ (during β-adrenoceptor stimulation; 1 μM isoproterenol) declined by 48 wks. Resistance to I-R injury fell from 16 to 32 wks. Age-dependent transcriptional changes In un-stressed hearts were limited to 104 genes (>1.3-fold; 0.05 FDR), supporting: up-regulated innate defenses (glutathione and xenobiotic metabolism, chemotaxis, interleukins) and catecholamine secretion; and down-regulated extracellular matrix (ECM), growth factor and survival (PI3K/Akt) signaling. In stressed (post-ischemic) myocardium, ∼15-times as many genes (1528) were age-dependent, grouped into 6 clusters (>1.3-fold change; 0.05 FDR): most changing from 16 wks (45 % up/44 % down), a further 5 % declining from 32 wks. Major age-dependent Biological Processes in I-R hearts reveal: declining ATP metabolism, oxidative phosphorylation, cardiac contraction and morphogenesis, phospholipid metabolism and calcineurin signaling; increasing proteolysis and negative control of MAPK; and mixed changes in nuclear transport and angiogenic genes. Pathway analysis supports reductions in: autophagy, stress response, ER protein processing, mRNA surveillance and ribosome/translation genes; with later falls in mitochondrial biogenesis, oxidative phosphorylation and proteasome genes in I-R hearts. Summarizing, early cardiac aging is evident from 16 to 32 wks in male mice, characterized by: declining cardiovascular reserve and stress-resistance, transcriptomic evidence of constitutive stress and altered catecholamine and survival/growth signaling in healthy hearts; and declining stress response, quality control, mitochondrial energy metabolism and cardiac modeling processes in stressed hearts. These very early changes, potentially key substrate for advanced aging, may inform approaches to healthy aging and cardioprotection in the adult heart.
•Evidence of cardiac aging emerges from early adulthood (16–32 wks) in male mice.•Phenotypic changes include declining cardiovascular reserve and ischemic tolerance.•Constitutive stress, altered catecholamine and kinase paths evident in normoxic hearts•Defense, quality control and energy metabolism paths fall with age in ischemic hearts.•Gene changes are consistent with evolutionary (eg. disposable soma) theories of aging.
This study provides new information on the effects of various concentrations of the trace metals copper, lead, zinc, cadmium, and nickel on fertilization success of gametes from the scleractinian ...reef corals Goniastrea aspera,Goniastrea retiformis, Acropora tenuis, and Acropora longicyathus. The EC50 values (the concentration that reduces the fertilization rate by 50% relative to the control fertilization) for copper effects on fertilization success of these coral species range from 15 to 40 mu g/L, which is similar to responses of other marine invertebrates. The EC50 values for lead were 1450-1800 mu g/L for the Acropora species, and >2400 mu g/L for G. aspera gametes, which indicates that lead was much less toxic than copper. Fertilization responses to zinc and nickel were variable and a significant reduction in fertilization success for A. tenuis gametes was found only at very high cadmium concentrations. The data from this study and other recent research clearly demonstrate that some trace metals impair the fertilization success of gametes from faviid and acroporiid reef corals. Trace metal inputs into reef waters should be limited and controlled to avoid potential interference with sexual reproductive processes of reef corals.
Prevailing dogma holds that cell-cell communication through Notch ligands and receptors determines binary cell fate decisions during progenitor cell divisions, with differentiated lineages remaining ...fixed. Mucociliary clearance in mammalian respiratory airways depends on secretory cells (club and goblet) and ciliated cells to produce and transport mucus. During development or repair, the closely related Jagged ligands (JAG1 and JAG2) induce Notch signalling to determine the fate of these lineages as they descend from a common proliferating progenitor. In contrast to such situations in which cell fate decisions are made in rapidly dividing populations, cells of the homeostatic adult airway epithelium are long-lived, and little is known about the role of active Notch signalling under such conditions. To disrupt Jagged signalling acutely in adult mammals, here we generate antibody antagonists that selectively target each Jagged paralogue, and determine a crystal structure that explains selectivity. We show that acute Jagged blockade induces a rapid and near-complete loss of club cells, with a concomitant gain in ciliated cells, under homeostatic conditions without increased cell death or division. Fate analyses demonstrate a direct conversion of club cells to ciliated cells without proliferation, meeting a conservative definition of direct transdifferentiation. Jagged inhibition also reversed goblet cell metaplasia in a preclinical asthma model, providing a therapeutic foundation. Our discovery that Jagged antagonism relieves a blockade of cell-to-cell conversion unveils unexpected plasticity, and establishes a model for Notch regulation of transdifferentiation.
The glucosinolate content of various organs of the model plant
Arabidopsis thaliana was analysed at different stages during its life cycle. Seeds had the highest concentration (2.5% by dry weight), ...followed by inflorescences, siliques (fruits), leaves and roots. Seeds also had a very distinct glucosinolate composition, including much higher concentrations of methylthioalkyl glucosinolates, hydroxyalkyl glucosinolates and compounds with benzoate esters than other organs. During seed germination and leaf senescence, there were significant declines in glucosinolate concentration.
The glucosinolate content of various organs of the model plant
Arabidopsis thaliana (L.) Heynh., Columbia (Col-0) ecotype, was analyzed at different stages during its life cycle. Significant differences were noted among organs in both glucosinolate concentration and composition. Dormant and germinating seeds had the highest concentration (2.5–3.3% by dry weight), followed by inflorescences, siliques (fruits), leaves and roots. While aliphatic glucosinolates predominated in most organs, indole glucosinolates made up nearly half of the total composition in roots and late-stage rosette leaves. Seeds had a very distinctive glucosinolate composition. They possessed much higher concentrations of several types of aliphatic glucosinolates than other organs, including methylthioalkyl and, hydroxyalkyl glucosinolates and compounds with benzoate esters than other organs. From a developmental perspective, older leaves had lower glucosinolate concentrations than younger leaves, but this was not due to decreasing concentrations in individual leaves with age (glucosinolate concentration was stable during leaf expansion). Rather, leaves initiated earlier in development simply had much lower rates of glucosinolate accumulation per dry weight gain throughout their lifetimes. During seed germination and leaf senescence, there were significant declines in glucosinolate concentration. The physiological and ecological significance of these findings is briefly discussed.
PDF
