pinecone/core-2020-05-10-deduplication huggingface dataset:
Copper excess, zinc deficiency, and cognition loss in Alzheimer's disease

In this special issue about biofactors causing cognitive impairment, we present evidence for and discuss two such biofactors. One is excess copper, causing neuronal toxicity. The other is zinc deficiency, causing neuronal damage. We present evidence that Alzheimer's disease (AD) has become an epidemic in developed, but not undeveloped, countries and that the epidemic is a new disease phenomenon, beginning in the early 1900s and exploding in the last 50 years. This leads to the conclusion that something in the developed environment is a major risk factor for AD. We hypothesize that the factor is inorganic copper, leached from the copper plumbing, the use of which coincides with the AD epidemic. We present a web of evidence supporting this hypothesis. Regarding zinc, we have shown that patients with AD are zinc deficient when compared with age‐matched controls. Zinc has critical functions in the brain, and lack of zinc can cause neuronal death. A nonblinded study about 20 years ago showed considerable improvement in AD with zinc therapy, and a mouse AD model study also showed significant cognitive benefit from zinc supplementation. In a small blinded study we carried out,  post hoc  analysis revealed that 6 months of zinc therapy resulted in significant benefit relative to placebo controls in two cognitive measuring systems. These two factors may be linked in that zinc therapy significantly reduced free copper levels. Thus, zinc may act by lowering copper toxicity or by direct benefit on neuronal health, or both
Inhibition of microsomal cortisol production by (–)-epigallocatechin-3-gallate through a redox shift in the endoplasmic reticulum — A potential new target for treating obesity-related diseases

Conversion of cortisone to cortisol by 11β-hydroxysteroid \ud
dehydrogenase type 1 (11βHSD1) in the endoplasmic reticulum (ER) \ud
of the target cells is a major determinant of glucocorticoid \ud
action, and plays an important role in the development of \ud
obesity-related diseases. Inhibition of 11βHSD1 activity is, \ud
therefore, considered as a promising novel strategy for the \ud
treatment of metabolic syndrome and diabetes. Tea flavanols and \ud
their major representative, epigallocatechin gallate are known \ud
as antiobesity and antidiabetic agents. Their impacts on blood \ud
glucose level, hepatic glucose production, and insulin \ud
responsiveness resemble those observed on inhibition or \ud
depletion of 11βHSD1. We aimed to study the effect of \ud
epigallocatechin gallate on 11βHSD1 activity in ER-derived rat \ud
liver microsomes by measuring cortisone and cortisol with HPLC. \ud
Cortisol production was efficiently suppressed in a \ud
concentration dependent manner in intact microsomal vesicles. \ud
However, this effect was abolished by membrane permeabilization; \ud
and the three proteins involved in the overall process (11βHSD1, \ud
hexose 6-phosphate dehydrogenase, and glucose 6-phosphate \ud
transporter) were not or only mildly affected. Further \ud
investigation revealed the oxidation of luminal NADPH to NADP+, \ud
which attenuates cortisone reduction and favors cortisol \ud
oxidation in this compartment. Such a redox shift in the ER \ud
lumen might contribute to the beneficial health effects of tea \ud
flavanols and should be regarded as a promising strategy for the \ud
development of novel selective 11βHSD1 inhibitors to treat \ud
obesity-related diseases. © 2013 BioFactors 39(5):534–541, 201
Piperine alleviates osteoclast formation through the p38/c-Fos/NFATc1 signaling axis

Increased bone fracture is one of the health risk factors in patients with bone loss related disorders such as
osteoporosis and breast cancer metastasis to bone. Over activity of osteoclasts leads to uncoupling of bone
remodeling favoring bone loss over bone formation. Receptor activator of nuclear factor-κβ ligand (RANKL)
triggers the differentiation pathway leading to multinucleated osteoclast formation. Modulation of RANKL or its
downstream signaling pathways involved in osteoclast formation is of significant interest in the development of
anti-resorptive agents. In this study, we investigated the effects of piperine, an alkaloid present in Piper nigrum
L. on osteoclast formation. Piperine inhibited tartrate-resistant acid phosphatase (TRAP)-positive multinucleated
osteoclast formation in murine RAW264.7 macrophages and human CD14+ monocytes induced by RANKL and
breast cancer cells. Piperine attenuated the p38-mitogen activated protein kinase (MAPK) pathway activation,
while the extracellular-signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) or NF-κβ pathways
downstream of RANKL remained unaffected. Concomitantly, expression of c-Fos and nuclear factor of activated
T-cells, cytoplasmic 1 (NFATc1), the key transcription factors involved in osteoclastogenesis were remarkably
inhibited by piperine. Furthermore, piperine disrupted the actin ring structure and bone resorption, a characteristic
hallmark of osteoclasts. Collectively, these results suggest that piperine inhibits osteoclast differentiation by
suppressing the p38/NFATc1/c-Fos signaling axis.RESCOM, University of Pretoria, the University of Pretoria Vice Chancellor’s Postdoctoral Research Fellowship, the University of Pretoria’s Strategic Institutional Research Theme in Food, Nutrition and Well-being and the Struwig-Germeshuysen Research Trust, South Africa.http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1872-80812016-11-30hb201
Selenium supplementation modulates apoptotic processes in thyroid follicular cells

Selenium (Se) is an essential micronutrient modulating several physiopathological processes in the human body. The aim of the study is to characterize the molecular effects determined by Se-supplementation in thyroid follicular cells, using as model the well-differentiated rat thyroid follicular cell line FRTL5. Experiments have been performed to evaluate the effects of Se on cell growth, mortality and proliferation and on modulation of pro- and antiapoptotic pathways. The results indicate that Se-supplementation improves FRTL5 growth rate. Furthermore, Se reduces the proportion of cell death and modulates both proapoptotic (p53 and Bim) and antiapoptotic (NF-kB and Bcl2) mRNA levels. In addition, incubation with high doses of Na-Se might prevent the ER-stress apoptosis induced by tunicamycin, as assessed by membrane integrity maintenance, reduction in caspase 3/7 activities, and reduction in Casp-3 and PARP cleavage. Taken together, these results provide molecular evidences indicating the role of Se supplementation on cell death and apoptosis modulation in thyroid follicular cells. These observations may be useful to understand the effects of this micronutrient on the physiopathology of the thyroid gland. © 2017 The Authors BioFactors published by Wiley Periodicals, Inc. on behalf of International Union of Biochemistry and Molecular Biology, 2017
The endoplasmic reticulum stress signaling pathways in plants.

The unfolded protein response (UPR) is an evolutionarily conserved mechanism by which all eukaryotic cells preserve the homeostasis of the endoplasmic reticulum (ER) in the face of accumulation of unfolded proteins in the ER. Plants possess at least two signaling pathways specific for UPR. ER membrane-bound ER stress sensor/transducers, AtbZIP60 and AtbZIP28, are basic leucine zipper transcription factors that are activated by regulated intramembrane proteolysis systems and regulate transcription of the UPR genes. These signaling pathways play important roles not only in the UPR but also in other biological processes such as the response to pathogens and heat stress
The modifying effects of green tea polyphenols on acute colitis and inflammation-associated colon carcinogenesis in male ICR mice.

Reactive oxygen species (ROS) have been implicated as mediators of intestinal inflammation and carcinogenesis. Although green tea polyphenols (GTP) have anticancer property as antioxidants they also generate ROS in vitro. In this study, we investigated the modifying effects of GTP on dextran sulfate sodium (DSS)-induced acute colitis and on 1,2-dimethylhydrazine (DMH) and DSS-induced colon carcinogenesis in male ICR mice. At sacrifice after 6 days, the colon shortening induced by 2% DSS was unchanged by 0.1% and 0.25% GTP, but increased by 0.5% and 1% GTP-containing diet. The expression of interleukin-1beta and macrophage-migration inhibitory factor in the DSS + 0.1% GTP group were lower than the DSS alone group, whereas the expression levels were increased in the DSS + 0.5% GTP and DSS + 1% GTP groups when compared with the DSS alone group. In a subsequent experiment to determine the effects of 0.01-1% GTP on inflammation-associated colon carcinogenesis induced by DMH/DSS, 0.5 and 1% doses of GTP failed to prevent the development of multiple colon tumors, rather, they tended to increase it. Our results thus indicate that the modifying effects of GTP on DSS-induced acute colitis and DMH/DSS-induced colon carcinogenesis depends upon its dosage and the expression of proinflammatory cytokines
Zinc deficiency and neurodevelopment: the case of neurons

Zinc is essential for normal brain development. Gestational severe zinc deficiency can lead to overt fetal brain malformations. Although not teratogenic, suboptimal zinc nutrition during gestation can have long-term effects on the offspring's nervous system. This article will review current knowledge on the role of zinc in modulating neurogenesis and neuronal apoptosis as well as the proposed underlying mechanisms. A decrease in neuronal zinc causes cell cycle arrest, which in part involves a deregulation of select signals (ERK1/2, p53, and NF-κB). Zinc deficiency also induces apoptotic neuronal death through the intrinsic (mitochondrial) pathway, which can be triggered by the activation of the zinc-regulated enzyme caspase-3, and as a consequence of abnormal regulation of prosurvival signals (ERK1/2 and NF-κB). Alterations in the finely tuned processes of neurogenesis, neuronal migration, differentiation, and apoptosis, which involve the developmental shaping of the nervous system, could have a long-term impact on brain health. Zinc deficiency during gestation, even at the marginal levels observed in human populations, could increase the risk for behavioral/neurological disorders in infancy, adolescence, and adulthood.Fil: Adamo, Ana María. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Oteiza, Patricia Isabel. University of California at Davis; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin
The effect of additives and mechanical agitation in surface modification of acrylic fibres by cutinase and esterase

The surface of an acrylic fibre containing about 7% of vinyl acetate was modified using Fusarium solani pisi cutinase and a commercial esterase, Texazym PES. The effect of acrylic solvents and stabilising polyols on cutinase operational stability was studied. The half-life time of cutinase increased by 3.5-fold with the addition of 15% N,N-dimethylacetamide (DMA) and by 3-fold with 1M glycerol. The impact of additives and mechanical agitation in the protein adsorption and in the hydrolysis of vinyl acetate from acrylic fabric was investigated. The hydroxyl groups produced on the surface of the fibre were able to react specifically with Remazol Brilliant Blue R (cotton reactive dye) and to increase the colour of the acrylic-treated fabric. The best staining level was obtained with a high level of mechanical agitation and with the addition of 1% DMA. Under these conditions, the raise in the acrylic fabric colour depth was 30% for cutinase and 25% for Texazym. The crystallinity degree, determined by X-ray diffraction, was not significantly changed between control samples and samples treated with cutinase. The results showed that the outcome of the application of these enzymes depends closely on the reaction media conditions
Decolourisation of a synthetic textile effluent using a bacterial consortium

In the present study we examined the performance of a thermoalkalophilic bacterial consortium,
where the predominant strain was Bacillus sp. SF, in the degradation of Reactive Black 5 (RB5).
We used a reactor working in continuous mode and investigated the effects of pH, hydraulic retention
time (HRT) and several added salts on colour and chemical oxygen demand (COD) reductions.
For the chosen operational conditions (pH 9, 55ºC and HRT of 12 h) the efficiencies
achieved were 91.2 ± 0.8 % for colour removal and 81.2% for COD removal. The system tolerated,
with no significant decrease in colour removal efficiency, 30 g/L Na2SO4, Na2CO3 or NaCl. The latter
two salts, however, led to a reduction in COD removal of 30% and 50%, respectively. The system
proved to be very effective in the decolourisation of C.I. RB5 under alkaline conditions and at
a comparatively high temperature
Using a nitrilase for the surface modification of acrylic fibres

The surface of an acrylic fibre was modified with a commercial nitrilase (EC 3.5.5.1). The effect of fibre solvents and polyols on nitrilase catalysis efficiency and stability was investigated. The nitrilase action on the acrylic fabric was improved by the combined addition of 1 M sorbitol and 4% N, N-dimethylacetamide. The colour levels for samples treated with nitrilase increased 156% comparing to the control samples. When the additives were introduced in the treatment media, the colour levels increased 199%. The enzymatic conversion of nitrile groups into the corresponding carboxylic groups, on the fibre surface, was followed by the release of ammonia and polyacrylic acid. A surface erosion phenomenon took place and determined the “oscillatory” behaviour of the amount of dye uptake with time of treatment. These results showed that the outcome of the application of the nitrilase for the acrylic treatment is intimately dependent on reaction media parameters, such as time, enzyme activity and formulation
Comparative transcriptome analysis between original and evolved recombinant lactose-consuming Saccharomyces cerevisiae strains

The engineering of Saccharomyces cerevisiae strains for lactose utilization has been attempted with
the intent of developing high productivity processes for alcoholic fermentation of cheese whey. A
recombinant S. cerevisiae flocculent strain that efficiently ferments lactose to ethanol was previously
obtained by evolutionary engineering of an original recombinant that displayed poor lactose
fermentation performance. We compared the transcriptomes of the original and the evolved recombinant
strains growing in lactose, using cDNA microarrays. Microarray data revealed 173
genes whose expression levels differed more than 1.5-fold. About half of these genes were related
to RNA-mediated transposition. We also found genes involved in DNA repair and recombination
mechanisms, response to stress, chromatin remodeling, cell cycle control, mitosis regulation, glycolysis
and alcoholic fermentation. These transcriptomic data are in agreement with some of the
previously identified physiological and molecular differences between the recombinants, and point
to further hypotheses to explain those differences
Expression system of CotA-laccase for directed evolution and high-throughput screenings for the oxidation of high-redox potential dyes

Laccases are useful biocatalysts for many diverse biotechnological applications. In this study we have established efficient and reliable expression systems and high-throughput screenings for the recombinant CotA-laccase from Bacillus subtilis. The expression levels of cotA-laccase were compared in five different Escherichia coli host strains growing in 96-well microtiter plates under different culture conditions. Lower coefficients of variance (around 15%) were achieved using crude cell lysates of BL21 and KRX host strains growing under microaerobic conditions. Reproducible high-throughput screenings for the decolorization of high redox potential azo and anthraquinonic dyes were developed and optimized for identification of variants with increased redox potential. The enzymatic assays developed were tested for the screening of one mutant library from CotA-laccase created by error-prone PCR
Improved donor/acceptor BRET couples for monitoring ß-arrestin recruitment to G protein-coupled receptors

International audienceWe report highly sensitive Bioluminescence Resonance Energy Transfer (BRET) assays with optimized donor/acceptor couples. We combined the energy donors Renilla luciferase (Rluc) and the Rluc8 variant with the energy acceptors yellow fluorescent protein (YFP), the YPet variant and the Renilla green fluorescent protein (RGFP). Different donor/acceptor couples were tested in well-established assays measuring ligand-induced ß-arrestin (ßARR) intramolecular rearrangements and recruitment to G protein-coupled receptors (GPCRs). We show increased sensitivity with Rluc8/YPet and Rluc8/RGFP couples and measured previously undetectable BRET signals. These tools improve existing ßARR assays and offer new options for the development of future BRET assays
Treatment of cotton with an alkaline Bacillus spp cellulase : activity towards crystalline cellulose

We analysed the influence of several enzymatic treatment processes using an alkaline cellulase enzyme from Bacillus spp. on the sorption properties of cotton fabrics. Although cellulases are commonly applied in detergent formulations due to their anti-redeposition and depilling benefits, determining the mechanism of action of alkaline cellulases on cotton fibres requires a deeper understanding of the morphology and structure of cotton fibres in terms of fibre cleaning. The accessibility of cellulose fibres was studied by evaluating the iodine sorption value and by fluorescent-labelled enzyme microscopy; the surface morphology of fabrics was analysed by scanning microscopy. The action of enzyme hydrolysis over short time periods can produce fibrillation on cotton fibre surface without any release of cellulosic material. The results indicate that several short consecutive treatments were more effective in increasing the fibre accessibility than one long treatment. In addition, no detectable hydrolytic activity, in terms of reducing sugar production, was found.This work is funded by European Union funds through the Marie Curie Fellowships (MEST-CT-2005-019885) from the Sixth Framework Programme (FP6)
The zero-sum game of pathway optimization: Emerging paradigms for tuning gene expression

With increasing price volatility and growing awareness of the lack of sustainability of traditional chemical synthesis, microbial chemical production has been tapped as a promising renewable alternative for the generation of diverse, stereospecific compounds. Nonetheless, many attempts to generate them are not yet economically viable. Due to the zero-sum nature of microbial resources, traditional strategies of pathway optimization are attaining minimal returns. This result is in part a consequence of the gross changes in host physiology resulting from such efforts and underscores the need for more precise and subtle forms of gene modulation. In this review, we describe alternative strategies and emerging paradigms to address this problem and highlight potential solutions from the emerging field of synthetic biology.National Science Foundation (U.S.) (Synthetic Biology Engineering Research Center (SynBERC), grant number EEC-0540879)National Science Foundation (U.S.) (NSF CAREER Award (grant number CBET-0954986))Natural Sciences and Engineering Research Council of Canada (Fellowship
Changes in the bacterial community structure and diversity during bamboo retting

Microbial retting is a critical step in obtaining fiber bundles from bamboo culm using indigenous microorganisms. A cultivation-independent technique for monitoring the changes in bacteria community during bamboo retting was applied in this work. This technique involves genetic profiling of PCR-amplified small-subunit rRNA and the single-strand conformation polymorphism (SSCP) gel analysis of the PCR-amplified 16S rDNA fragments. The study revealed that both the structure and the diversity of investigated communities varied with the incubation periods and sample locations. The bacteria bands from SCCP gel profiles related to Bacillus sp. decreased in intensity, and Phaeospirillum sp. and Azospirillum brasilense completely disappeared during the 4th and 5th month of incubation, while the bands related to the Sphingomonas japonica, Alphaproteobacterium Ellin335 and Microbacterium sp. increased. The bands closely related to Sphingomonads, Brevundimonas brasilense, Pseudoclavibacter sp., Agrococcus jenensis and Oxalophagus oxalicus remained dominant during the whole incubation period. This study showed that the use of PCR assay targeting 16S rRNA and SCCP profiling provided valuable information on monitoring the bacteria dynamic changes occurring in the bacteria community during bamboo retting, which is crucial for controlling the quality of the retting process and improving the retting efficiency, and thus benefits for fiber recovery.This work was made possible by the support from the earmarked fund for Modern Agro-industry Technology Research System (nycytx-19-E23), the European Union Biorenew Project [Sixth Framework Programme (FP6-2004-NMP-NI-4)] and China Scholarship Council. The authors would like to thank Florian Schmid, Herbert Pobeheim, Stefan Wei\l=ss\, Michael Furnkranz, Christoph Schmidt and Endry Nugroho Prasetyo for a number of insightful comments and suggestions
In situ laccase-assisted overdyeing of denim using flavonoids

A laccase-mediated system for denim overdyeing using phenolic compounds was developed. Laccase from ascomycete Myceliophthora thermophila was able to oxidize phenolic compounds such as catechol and catechin and mediate their attachment to denim surfaces. Laccase-generated polymers gave rise to new coloration states from dark brown to green–yellow and replaced dyes in the overdyeing process. Process parameters, such as enzyme dosage, incubation time and presence of mediator, were studied by considering a compromise between the highest overdyeing level and lower energy/products consumption (2 U/mL laccase; 4 h incubation in the absence of mediator). Enzyme-generated polymers were followed by UV/Vis spectrophotometry and their level of attachment to denim surfaces was evaluated by means of spectral values quantification [k/s, Kubelka–Munk relationship (k=absorption coefficient, s=scattering coefficient)]. Overdyeing of denim with phenolics, such as catechol or catechin, was successfully achieved with acceptable levels in terms of durability.S.Y.K. would like to acknowledge the BIORENEW European Project - Sixth Framework European Program. C.S. would like to acknowledge the Portuguese Fundacao para a Ciencia e a Tecnologia (FCT) for funding under the scholarship SFRH/BPD/46515/2008