Although the first mouse embryonic stem (ES) cell lines were derived 25 years ago using feeder-layer-based blastocyst cultures, subsequent efforts to extend the approach to other mammals, including ...both laboratory and domestic species, have been relatively unsuccessful. The most notable exceptions were the derivation of non-human primate ES cell lines followed shortly thereafter by their derivation of human ES cells. Despite the apparent common origin and the similar pluripotency of mouse and human embryonic stem cells, recent studies have revealed that they use different signalling pathways to maintain their pluripotent status. Mouse ES cells depend on leukaemia inhibitory factor and bone morphogenetic protein, whereas their human counterparts rely on activin (INHBA)/nodal (NODAL) and fibroblast growth factor (FGF). Here we show that pluripotent stem cells can be derived from the late epiblast layer of post-implantation mouse and rat embryos using chemically defined, activin-containing culture medium that is sufficient for long-term maintenance of human embryonic stem cells. Our results demonstrate that activin/Nodal signalling has an evolutionarily conserved role in the derivation and the maintenance of pluripotency in these novel stem cells. Epiblast stem cells provide a valuable experimental system for determining whether distinctions between mouse and human embryonic stem cells reflect species differences or diverse temporal origins.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Ionic liquids are a class of fluids that requires the attentions of experimentalist and theoreticians. In a new project on synthesis and characterization of new and not-so-new ionic liquids, the ...study of several thermophysical properties of these liquids was started, namely binary diffusion, electrical conductivity, heat capacity, surface tension, viscosity and thermal conductivity. Among others we will study 1-
n-butyl-3-methyl-imidazolium bis(trifluoromethanesulfonyl)imide, (C
4mimNTf
2), 1-
n-butyl-3-methyl-imidazolium dicyanamide, (C
4mimdca), 1-ethyl-3-methyl-imidazolium ethylsulfate, (C
2mimEtOSO
3) and methyltrialkylammonium dicyanamide Aliquat
®336-deriveddca, and in the case of diffusion, their mixtures with water.
It is the purpose of this paper to report data on the density, using vibrating tube densimetry, infinite dilution diffusion coefficients, using the Taylor dispersion method, heat capacity, using DSC equipment and surface tension, using the Wilhelmy plate method. Density measurements were performed at atmospheric pressure between 293 and 363
K and several isotherms, depending on the stability of the compound, up to 60
MPa, with an uncertainty of 0.4%. Measurements were performed at 298.03
K for the infinite dilution measurements, with an uncertainty of 1.3–3.5%, for temperatures between 300 and 370
K for heat capacity, with an uncertainty better than 1.5%, and between 292 and 395
K for surface tension, with an uncertainty of 1.5–1.8%.
A brief analysis of the potential of the fluids studied as engineering heat transfer fluids, namely its heat storage capacity was also performed.
Reduction in sirtuin 1 (Sirt-1) is associated with extracellular matrix (ECM) accumulation in the diabetic kidney. Theobromine may reduce kidney ECM accumulation in diabetic rats. In the current ...study, we aimed to unravel, under diabetic conditions, the mechanism of kidney ECM accumulation induced by a reduction in Sirt-1 and the effect of theobromine in these events. In vitro, we used immortalized human mesangial cells (iHMCs) exposed to high glucose (HG; 30 mM), with or without small interfering RNA for NOX4 and Sirt-1. In vivo, spontaneously hypertensive rats (SHR) were rendered diabetic by means of streptozotocin and studied after 12 wk. The effects of treatment with theobromine were investigated under both conditions. HG leads to a decrease in Sirt-1 activity and NAD(+) levels in iHMCs. Sirt-1 activity could be reestablished by treatment with NAD(+), silencing NOX4, and poly (ADP-ribose) polymerase-1 (PARP-1) blockade, or with theobromine. HG also leads to a low AMP/ATP ratio, acetylation of SMAD3, and increased collagen IV, which is prevented by theobromine. Sirt-1 or AMPK blockade abolished these effects of theobromine. In diabetic SHR, theobromine prevented increases in albuminuria and kidney collagen IV, reduced AMPK, elevated NADPH oxidase activity and PARP-1, and reduced NAD(+) levels and Sirt-1 activity. These results suggest that in diabetes mellitus, Sirt-1 activity is reduced by PARP-1 activation and NAD(+) depletion due to low AMPK, which increases NOX4 expression, leading to ECM accumulation mediated by transforming growth factor (TGF)-β1 signaling. It is suggested that Sirt-1 activation by theobromine may have therapeutic potential for diabetic nephropathy.
Introduction
Bipolar disorder (BD) and borderline personality disorder (BPD) appear as prevalent psychiatric conditions, with both being associated with increased morbidity and elevated suicide ...rates.
Borderline personality disorder is characterized by emotional instability and impulsivity, and patients are susceptible to dangerous behaviors such as unsafe sexual behavior, eating disorders and substance abuse. On the other hand, mania in BD patients contributes to impulsivity, hypersexuality and poor judgment, as well as a lack of inhibition. In both cases, individuals are at a higher risk of committing suicide due to emotional dysregulation and impulsive behaviours.
The symptomatic overlap in BPD and BD is prone to discussion and may lead to misdiagnosis. Some studies suggest that BPD and BD may lie on a spectrum, while others advocate them as separate entities that may coexist.
Objectives
To explore the clinical challenges associated with both the differential diagnosis and the comorbidity of BD and BPD.
Methods
We performed a non-systematic review of the literature using the database PubMed and the following keywords:
bipolar disorder borderline personality disorder comorbidity
Results
Patients with borderline personality disorder seem to have significantly greater odds of a previous bipolar misdiagnosis, but no specific borderline criterion was shown unique in predicting this outcome.
Nonetheless, research studies have reported that approximately 20% of BPD were also diagnosed with BD and, similarly, 10% of people with BD I and 20% with BD II were diagnosed with BPD.
Comorbid BPD and BD are associated with marked psychosocial disability, with patients being more impulsive and aggressive than those with BPD and BD alone. They are also highly susceptible to anxiety disorders like obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), and somatoform disorders. Studies have shown that comorbid BPD has a negative impact on the clinical course of Bipolar Disorder, as the patients have an unfavorable illness trajectory, with earlier onset of mood symptoms,higher likelihood of hospitalization, longer treatment duration and worse response to treatment. They are also at higher risk for depression and persistent unemployment, increased risk drug abuse, higher suicide risk, and greater utilization of ECT, compared to patients with BPD or BD alone.
Conclusions
A careful review of the patient’s history must be done to properly distinguish between BPD and BD and to make the right diagnosis. Further studies are needed to clarify the risk factors associated with the comorbidity between these two disorders, in order to develop effective clinical strategies for optimal outcomes for patients with both disorders, improve their clinical course and prevent the increased risk of suicidality.
Disclosure of Interest
None Declared
A systematic molecular dynamics study using large simulation boxes has been performed in order to extend the analysis of the mesoscopic segregation behavior observed in ionic liquids of the ...1,3-dialkyl-imidazolium bis(trifluoromethylsulfonyl)imide homologous series, C n C m imNtf2 (2 ≤ n ≤ 10, 2 ≤ m ≤ n). The analyses include the discussion of the structure factors, S(q), in the low-q range (1.6 ≤ q/nm–1 ≤ 20); the confirmation of the periodicity of the polar network of the ionic liquid and its relation to the so-called intermediate peaks; and the characterization of the polar network and the nonpolar regions that are formed along the series using aggregate analyses by means of five different statistical tools. The analyses confirmed that the percolation of the nonpolar regions into a continuous domain occurs when the total number of carbon atoms in the alkyl chains exceeds six but that this is not a sufficient condition for the emergence of a distinct and intense prepeak. The existence of such a peak also requires that the longer alkyl chain contains more than a critical alkyl length (CAL) of five carbon atoms.
Display omitted
The central nervous system (CNS) is vulnerable to pathologic processes that lead to the development of neurodegenerative disorders like Alzheimer’s, Parkinson’s and Huntington’s ...diseases, Multiple sclerosis or Amyotrophic lateral sclerosis. These are chronic and progressive pathologies characterized by the loss of neurons and the formation of misfolded proteins. Additionally, neurodegenerative diseases are accompanied by a structural and functional dysfunction of the blood–brain barrier (BBB). Although serving as a protection for the CNS, the existence of physiological barriers, especially the BBB, limits the access of several therapeutic agents to the brain, constituting a major hindrance in neurotherapeutics advancement. In this regard, nanotechnology-based approaches have arisen as a promising strategy to not only improve drug targeting to the brain, but also to increase bioavailability. Lipid nanocarriers such as liposomes, solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC), microemulsions and nanoemulsions, have already proven their potential for enhancing brain transport, crossing more easily into the CNS and allowing the administration of medicines that could benefit the treatment of neurological pathologies.
Given the socioeconomic impact of such conditions and the advent of nanotechnology that inevitably leads to more effective and superior therapeutics for their management, it is imperative to constantly update on the current knowledge of these topics. Herein, we provide insight on the BBB and the pathophysiology of the main neurodegenerative disorders. Moreover, this review seeks to highlight the several approaches that can be used to improve the delivery of therapeutic agents to the CNS, while also offering an extensive overview of the latest efforts regarding the use of lipid-based nanocarriers in the management of neurodegenerative diseases.
The aim of this study was to evaluate the effects on feed intake, calf performance, feed efficiency, fecal score, passage rate, apparent nutrient digestibility, development of rumen and other organs, ...and body composition of increasing the total solids content of liquid feed (whole milk) by adding increasing amounts of milk replacer powder during the preweaning period. Crossbred Holstein-Gyr calves (n=32) were assigned to 1 of 4 treatments (n=8 per group), which consisted of different total solids concentrations: 12.5, 15.0, 17.5, and 20.0% of liquid feed. Calves received 6 L of liquid per day, divided into 2 equal meals (0800 and 1600 h) and provided in buckets, from 5 to 55d of age. Starter and water were provided ad libitum during the entire experiment. At 56d of age, animals were killed. Laboratory analysis determined that the actual total solids contents of the liquid feed were 13.5, 16.1, 18.2, and 20.4%, for the proposed 12.5, 15.0, 17.5, and 20.0% total solids treatments, respectively. The osmolality of liquid feed treatments was 265 to 533 mOsm/L. Fecal score was similar among treatments, except for wk 2 and 7. Intake of liquid feed was similar among treatments from 6wk of age. During wk 4, 5, and 6, we detected a linear decrease in starter intake. After wk 7, we observed greater starter intake for calves fed approximately 16.1% total solids. Water intake, feed efficiency, and withers height were similar among treatments. Increasing concentrations of total solids in liquid feed quadratically affected average daily gain, final body weight, and empty body weight. We observed a greater average daily gain for calves fed approximately 20.4% total solids. Passage rate, nutrient digestibility, development of pre-stomachs and intestine, and body composition were similar among treatments. Increasing the concentration of total solids in liquid feed up to 20.4% reduced starter intake between 4 and 6wk of life, but increased average daily gain. It did not affect passage rate, nutrient digestibility, ruminal and organ development, or body composition in calves during the preweaning period, indicating that this strategy may be a viable alternative for feeding without increasing the total volume of liquid feed provided to dairy calves.
The objective of this work was to evaluate the effectiveness of antimicrobial edible coatings to wrap cheeses, throughout 60d of storage, as an alternative to commercial nonedible coatings. Coatings ...were prepared using whey protein isolate, glycerol, guar gum, sunflower oil, and Tween 20 as a base matrix, together with several combinations of antimicrobial compounds—natamycin and lactic acid, natamycin and chitooligosaccharides (COS), and natamycin, lactic acid, and COS. Application of coating on cheese decreased water loss (~10%, wt/wt), hardness, and color change; however, salt and fat contents were not significantly affected. Moreover, the antimicrobial edible coatings did not permit growth of pathogenic or contaminant microorganisms, while allowing regular growth of lactic acid bacteria throughout storage. Commercial nonedible coatings inhibited only yeasts and molds. The antimicrobial edible coating containing natamycin and lactic acid was the best in sensory terms. Because these antimicrobial coatings are manufactured from food-grade materials, they can be consumed as an integral part of cheese, which represents a competitive advantage over nonedible coatings.
Aims
Increased N deposition may cause nutritional imbalances in tropical ecosystems, by shifting N:P stoichiometry (as they are typically P-limited) and NH
4
-N:NO
3
-N ratios throughout their ...compartments. Based on this assumption, we aimed at verifying if the anthropogenic N deposition are inducing nutritional imbalances in trees, litter and soil in the remaining Atlantic Forest in SE Brazil.
Methods
Three forest remnants were selected, one of them supposedly exposed to lower levels anthropogenic N deposition (peri-urban forest) than the other two (urban and agricultural-urban forests). We measured NO
2
concentrations, wet and dry deposition of NH
4
-N, NO
3
-N and PO
4
-P and determined total/soluble N and P contents in samples of pioneer and non-pioneer trees, litter and soil. NH
4
-N:NO
3
-N and N:P ratios were calculated in all compartments.
Results
Multivariate analysis indicated associations between NH
4
-N, PO
4
-P and NH
4
:NO
3
ratios in atmospheric deposition or NO
2
concentrations and N and P contents in trees, litter and soil of all forest remnants. The comparison of N:P ratios in tree species and litter with those from studies conducted in the 1980–2000 indicated a tendency of N enrichment and increasing P scarcity in the Atlantic Forest remnants studied.
Conclusions
Confirming the hypothesis, anthropogenic N deposition increases nutritional imbalances in the ecosystem compartments of forest remnants studied. The peri-urban forest showed to be more vulnerable to nutritional imbalances than the other forests, based on the comparisons with data from 30 to 40 years ago.
Until recently, human embryonic stem cells (hESCs) were shown to exist in a state of primed pluripotency, while mouse embryonic stem cells (mESCs) display a naive or primed pluripotent state. Here we ...show the rapid conversion of in-house-derived primed hESCs on mouse embryonic feeder layer (MEF) to a naive state within 5-6 days in naive conversion media (NCM-MEF), 6-10 days in naive human stem cell media (NHSM-MEF) and 14-20 days using the reverse-toggle protocol (RT-MEF). We further observe enhanced unbiased lineage-specific differentiation potential of naive hESCs converted in NCM-MEF, however, all naive hESCs fail to differentiate towards functional cell types. RNA-seq analysis reveals a divergent role of PI3K/AKT/mTORC signalling, specifically of the mTORC2 subunit, in the different naive hESCs. Overall, we demonstrate a direct evaluation of several naive culture conditions performed in the same laboratory, thereby contributing to an unbiased, more in-depth understanding of different naive hESCs.
PDF
