Effect Of Nanoparticles On The Biochemical And Behavioral Aging Phenotype Of The Nematode Caenorhabditis Elegans

Invertebrate animal models such as the nematode Caenorhabditis elegans (C. elegans) are increasingly used in nanotechnological applications. Research in this area covers a wide range from remote control of worm behavior by nanoparticles (NPs) to evaluation of organismal nanomaterial safety. Despite of the broad spectrum of investigated NP-bio interactions, little is known about the role of nanomaterials with respect to aging processes in C. elegans. We trace NPs in single cells of adult C. elegans and correlate particle distribution with the worm\u27s metabolism and organ function. By confocal microscopy analysis of fluorescently labeled NPs in living worms, we identify two entry portals for the uptake of nanomaterials via the pharynx to the intestinal system and via the vulva to the reproductive system. NPs are localized throughout the cytoplasm and the cell nucleus in single intestinal, and vulval B and D cells. Silica NPs induce an untimely accumulation of insoluble ubiquitinated proteins, nuclear amyloid and reduction of pharyngeal pumping that taken together constitute a premature aging phenotype of C. elegans on the molecular and behavioral level, respectively. Screening of different nanomaterials for their effects on protein solubility shows that polystyrene or silver NPs do not induce accumulation of ubiquitinated proteins suggesting that alteration of protein homeostasis is a unique property of silica NPs. The nematode C. elegans represents an excellent model to investigate the effect of different types of nanomaterials on aging at the molecule, cell, and whole organism level. © 2013 American Chemical Society

Localization of proteasomes and proteasomal proteolysis in the mammalian interphase cell nucleus by systematic application of immunocytochemistry

Proteasomes are ATP-driven, multisubunit proteolytic machines that degrade endogenous proteins into peptides and play a crucial role in cellular events such as the cell cycle, signal transduction, maintenance of proper protein folding and gene expression. Recent evidence indicates that the ubiquitin-proteasome system is an active component of the cell nucleus. A characteristic feature of the nucleus is its organization into distinct domains that have a unique composition of macromolecules and dynamically form as a response to the requirements of nuclear function. Here, we show by systematic application of different immunocytochemical procedures and comparison with signature proteins of nuclear domains that during interphase endogenous proteasomes are localized diffusely throughout the nucleoplasm, in speckles, in nuclear bodies, and in nucleoplasmic foci. Proteasomes do not occur in the nuclear envelope region or the nucleolus, unless nucleoplasmic invaginations expand into this nuclear body. Confirmedly, proteasomal proteolysis is detected in nucleoplasmic foci, but is absent from the nuclear envelope or nucleolus. The results underpin the idea that the ubiquitin-proteasome system is not only located, but also proteolytically active in distinct nuclear domains and thus may be directly involved in gene expression, and nuclear quality control. © 2007 Springer-Verlag

Pollutants Corrupt Resilience Pathways of Aging in the Nematode C. Elegans

Delaying aging while prolonging health and lifespan is a major goal in aging research. One promising strategy is to focus on reducing negative interventions such as pollution and their accelerating effect on age-related degeneration and disease. Here, we used the short-lived model organism C. elegans to analyze whether two candidate pollutants corrupt general aging pathways. We show that the emergent pollutant silica nanoparticles (NPs) and the classic xenobiotic inorganic mercury reduce lifespan and cause a premature protein aggregation phenotype. Comparative mass spectrometry revealed that increased insolubility of proteins with important functions in proteostasis is a shared phenotype of intrinsic- and pollution-induced aging supporting the hypothesis that proteostasis is a central resilience pathway controlling lifespan and aging. The presented data demonstrate that pollutants corrupt intrinsic aging pathways. Reducing pollution is, therefore, an important step to increasing healthy aging and prolonging life expectancies on a population level in humans and animals

Reproductive aging in Caenorhabditis elegans: From molecules to ecology

Aging animals display a broad range of progressive degenerative changes, and one of the most fascinating is the decline of female reproductive function. In the model organis

On the detectability of star-planet interaction

Magnetic (or tidal) interactions between "hot Jupiters" and their host stars can potentially enhance chromospheric and coronal activity. An ideal testbed for investigating this effect is provided by the extreme WASP-18 system, which features a massive (~10 times Jupiter) close-in (~1 day period) transiting planet orbiting a young F6 star. Optical and X-ray observations of WASP-18 were conducted in November 2011. The high-resolution echelle spectrograph MIKE was used on the 6.5m Magellan Clay telescope to obtain 13 spectra spanning planetary orbital phases of 0.7-1.4, while the X-ray Telescope on Swift provided contemporaneous monitoring with a stacked exposure of ~50 ks. The cores of the Ca II H and K lines do not show significant variability over multiple orbits spanning ~8 d, in contrast to the expectation of phase-dependent chromospheric activity enhancements for efficient star-planet interaction. The star is also X-ray faint, with log Lx < 27.6 erg/s (0.3-2 keV), indicating that coronal activity is likewise low. The lack of detectable star-planet interaction in this extreme system requires that any such effect must here be transient, if indeed present. We demonstrate that searches for Ca II H and K variability can potentially mistake a stellar hotspot, if observed over a short segment of the rotation period, for planet-induced activity. Taken together, these results suggest that the utility of star-planet interaction as a robust method of estimating exoplanet magnetic field strengths may be limited.Comment: Accepted to ApJ; 9 pages emulateapj, 5 figures, 1 table (v2: corrected fn15, typos, refs

Casein Α S1 Is Expressed By Human Monocytes And Upregulates The Production Of GM-CSF Via P38 MAPK

Caseins are major constituents of mammalian milks that are thought to be exclusively expressed in mammary glands and to function primarily as a protein source, as well as to ameliorate intestinal calcium uptake. In addition, proinflammatory and immunomodulatory properties have been reported for bovine caseins. Our aim was to investigate whether human casein α s1 (CSN1S1) is expressed outside the mammary gland and possesses immunomodulatory functions in humans as well. For this purpose, CSN1S1 mRNA was detected in primary human monocytes and CD4+ and CD8+ T cells, but not in CD19 + B cells. CSN1S1 protein was traceable in supernatants of cultured primary human CD14+ monocytes by ELISA. Similarly, CSN1S1 mRNA and protein were detected in the human monocytic cell lines HL60, U937, and THP1 but not in Mono Mac 6 cells. Moreover, permeabilized human monocytes and HL60 cells could be stained by immunofluorescence, indicating intracellular expression. Recombinant human CSN1S1 was bound to the surface of Mono Mac 6 cells and upregulated the expression of GM-CSF mRNA in primary human monocytes and Mono Mac 6 cells in a time- and concentration-dependent manner. A similar increase in GM-CSF protein was found in the culture supernatants. CSN1S1-dependent upregulation of GM-CSF was specifically blocked by the addition of the p38 MAPK inhibitor ML3403. Our results indicated that human CSN1S1 may possess an immunomodulatory role beyond its nutritional function in milk. It is expressed in human monocytes and stimulates the expression of the proinflammatory cytokine GM-CSF. Copyright © 2010 by The American Association of Immunologists, Inc

White Matter Hyperintensity Longitudinal Morphometric Analysis In Association With Alzheimer Disease

INTRODUCTION: Vascular damage in Alzheimer\u27s disease (AD) has shown conflicting findings particularly when analyzing longitudinal data. We introduce white matter hyperintensity (WMH) longitudinal morphometric analysis (WLMA) that quantifies WMH expansion as the distance from lesion voxels to a region of interest boundary. METHODS: WMH segmentation maps were derived from 270 longitudinal fluid-attenuated inversion recovery (FLAIR) ADNI images. WLMA was performed on five data driven WMH patterns with distinct spatial distributions. Amyloid accumulation was evaluated with WMH expansion across the five WMH patterns. RESULTS: The preclinical group had significantly greater expansion in the posterior ventricular WM compared to controls. Amyloid significantly associated with frontal WMH expansion primarily within AD individuals. WLMA outperformed WMH volume changes for classifying AD from controls primarily in periventricular and posterior WMH. DISCUSSION: These data support the concept that localized WMH expansion continues to proliferate with amyloid accumulation throughout the entirety of the disease in distinct spatial locations

Long-term improvement of quality of life in patients with breast cancer: supporting patient-physician communication by an electronic tool for inpatient and outpatient care

Purpose The effectiveness of a pathway with quality of life (QoL) diagnosis and therapy has been already demonstrated in an earlier randomized trial (RCT) in patients with breast cancer. We refined the pathway by developing and evaluating an electronic tool for QoL assessment in routine inpatient and outpatient care. Methods In a single-arm study, patients with breast cancer with surgical treatment in two German hospitals were enrolled. QoL (EORTC QLQ-C30, QLQ-BR23) was measured with an electronic tool after surgery and during aftercare in outpatient medical practices (3, 6, 9, 12, 18, and 24 months) so that results (QoL-profile) were available immediately. Feedback by patients and physicians was analyzed to evaluate feasibility and impact on patient-physician communication. Results Between May 2016 and July 2018, 56 patients were enrolled. Physicians evaluated the QoL pathway as feasible. Patients whose physician regularly discussed QoL-profiles with them reported significantly more often that their specific needs were cared for (p < .001) and that their physician had found the right treatment strategy for these needs (p < .001) compared with patients whose doctor never/rarely discussed QoL-profiles. The latter significantly more often had no benefit from QoL assessments (p < .001). Conclusion The QoL pathway with electronic QoL assessments is feasible for inpatient and outpatient care. QoL results should be discussed directly with the patient. Clinical trial information NCT04334096, date of registration 06.04.202

Junctional Nevus and Early Melanoma on Sun-Damaged Skin of the Head/Neck: A Clinico-Pathologic Challenge

Introduction: Melanoma on the head/neck area can show subtle clinical, dermoscopic and histologic features at early stages, being difficult to differentiate from junctional nevi. Objectives: This case series aims to raise awareness on the topic of misdiagnosis of early lentigo maligna as junctional nevi. Methods: From the databases of three pigmented lesion clinics in Italy, Australia, and France, we retrieved all cases of lesions of the head/neck area with an initial histopathologic diagnosis of junctional nevus (JN) or dysplastic junctional nevus (DJN) which subsequently recurred and were ultimately diagnosed as melanoma. Moreover, we also retrieved those cases with an initial diagnosis of JN/DJN made on a partial biopsy that were diagnosed as melanoma after complete surgical removal. Results: Here we report 14 cases in which the initial histologic diagnosis was junctional nevus or dysplastic junctional nevus. The lesions recurred over time with a final diagnosis of lentigo maligna. Conclusions: Clinicians should critically question a given histologic diagnosis of junctional or dysplastic junctional nevus on the head/neck area if the clinical or dermoscopic features are discordant. Clinico-pathologic correlation is the best way to increase diagnostic accuracy and optimize management for the patient