Post-Transcriptional Regulation of 5-Lipoxygenase mRNA Expression via Alternative Splicing and Nonsense-Mediated mRNA Decay

5-Lipoxygenase (5-LO) catalyzes the two initial steps in the biosynthesis of leukotrienes (LT), a group of inflammatory lipid mediators derived from arachidonic acid. Here, we investigated the regulation of 5-LO mRNA expression by alternative splicing and nonsense-mediated mRNA decay (NMD). In the present study, we report the identification of 2 truncated transcripts and 4 novel 5-LO splice variants containing premature termination codons (PTC). The characterization of one of the splice variants, 5-LOΔ3, revealed that it is a target for NMD since knockdown of the NMD factors UPF1, UPF2 and UPF3b in the human monocytic cell line Mono Mac 6 (MM6) altered the expression of 5-LOΔ3 mRNA up to 2-fold in a cell differentiation-dependent manner suggesting that cell differentiation alters the composition or function of the NMD complex. In contrast, the mature 5-LO mRNA transcript was not affected by UPF knockdown. Thus, the data suggest that the coupling of alternative splicing and NMD is involved in the regulation of 5-LO gene expression

Bone mineral density in partially recovered early onset anorexic patients - a follow-up investigation

<p>Abstract</p> <p>Background and aims</p> <p>There still is a lack of prospective studies on bone mineral development in patients with a history of early onset Anorexia nervosa (AN). Therefore we assessed associations between bone mass accrual and clinical outcomes in a former clinical sample. In addition to an expected influence of regular physical activity and hormone replacement therapy, we explored correlations with nutritionally dependent hormones.</p> <p>Methods</p> <p>3-9 years (mean 5.2 ± 1.7) after hospital discharge, we re-investigated 52 female subjects with a history of early onset AN. By means of a standardized approach, we evaluated the general outcome of AN. Moreover, bone mineral content (BMC) and bone mineral density (BMD) as well as lean and fat mass were measured by dual-energy x-ray absorptiometry (DXA). In a substudy, we measured the serum concentrations of leptin and insulin-like growth factor-I (IGF-I).</p> <p>Results</p> <p>The general outcome of anorexia nervosa was good in 50% of the subjects (BMI ≥ 17.5 kg/m², resumption of menses). Clinical improvement was correlated with BMC and BMD accrual (χ²= 5.62/χ²= 6.65, p = 0.06 / p = 0.036). The duration of amenorrhea had a negative correlation with BMD (r = -.362; p < 0.01), but not with BMC. Regular physical activity tended to show a positive effect on bone recovery, but the effect of hormone replacement therapy was not significant. Using age-related standards, the post-discharge sample for the substudy presented IGF-I levels below the 5^thpercentile. IGF-I serum concentrations corresponded to the general outcome of AN. By contrast, leptin serum concentrations showed great variability. They correlated with BMC and current body composition parameters.</p> <p>Conclusions</p> <p>Our results from the main study indicate a certain adaptability of bone mineral accrual which is dependent on a speedy and ongoing recovery. While leptin levels in the substudy tended to respond immediately to current nutritional status, IGF-I serum concentrations corresponded to the individual's age and general outcome of AN.</p

Multivariate Prediction of Total Water Storage Changes Over West Africa from Multi-Satellite Data

West African countries have been exposed to changes in rainfall patterns over the last decades, including a significant negative trend. This causes adverse effects on water resources of the region, for instance, reduced freshwater availability. Assessing and predicting large-scale total water storage (TWS) variations are necessary for West Africa, due to its environmental, social, and economical impacts. Hydrological models, however, may perform poorly over West Africa due to data scarcity. This study describes a new statistical, data-driven approach for predicting West African TWS changes from (past) gravity data obtained from the gravity recovery and climate experiment (GRACE), and (concurrent) rainfall data from the tropical rainfall measuring mission (TRMM) and sea surface temperature (SST) data over the Atlantic, Pacific, and Indian Oceans. The proposed method, therefore, capitalizes on the availability of remotely sensed observations for predicting monthly TWS, a quantity which is hard to observe in the field but important for measuring regional energy balance, as well as for agricultural, and water resource management.Major teleconnections within these data sets were identified using independent component analysis and linked via low-degree autoregressive models to build a predictive framework. After a learning phase of 72 months, our approach predicted TWS from rainfall and SST data alone that fitted to the observed GRACE-TWS better than that from a global hydrological model. Our results indicated a fit of 79 % and 67 % for the first-year prediction of the two dominant annual and inter-annual modes of TWS variations. This fit reduces to 62 % and 57 % for the second year of projection. The proposed approach, therefore, represents strong potential to predict the TWS over West Africa up to 2 years. It also has the potential to bridge the present GRACE data gaps of 1 month about each 162days as well as a—hopefully—limited gap between GRACE and the GRACE follow-on mission over West Africa. The method presented could also be used to generate a near real-time GRACE forecast over the regions that exhibit strong teleconnections

Assessing the Effects of Climate on Host-Parasite Interactions: A Comparative Study of European Birds and Their Parasites

[Background] Climate change potentially has important effects on distribution, abundance, transmission and virulence of parasites in wild populations of animals. [Methodology/Principal Finding] Here we analyzed paired information on 89 parasite populations for 24 species of bird hosts some years ago and again in 2010 with an average interval of 10 years. The parasite taxa included protozoa, feather parasites, diptera, ticks, mites and fleas. We investigated whether change in abundance and prevalence of parasites was related to change in body condition, reproduction and population size of hosts. We conducted analyses based on the entire dataset, but also on a restricted dataset with intervals between study years being 5–15 years. Parasite abundance increased over time when restricting the analyses to datasets with an interval of 5–15 years, with no significant effect of changes in temperature at the time of breeding among study sites. Changes in host body condition and clutch size were related to change in temperature between first and second study year. In addition, changes in clutch size, brood size and body condition of hosts were correlated with change in abundance of parasites. Finally, changes in population size of hosts were not significantly related to changes in abundance of parasites or their prevalence. [Conclusions/Significance] Climate change is associated with a general increase in parasite abundance. Variation in laying date depended on locality and was associated with latitude while body condition of hosts was associated with a change in temperature. Because clutch size, brood size and body condition were associated with change in parasitism, these results suggest that parasites, perhaps mediated through the indirect effects of temperature, may affect fecundity and condition of their hosts. The conclusions were particularly in accordance with predictions when the restricted dataset with intervals of 5–15 years was used, suggesting that short intervals may bias findings.The Academy of Finland is acknowledged for a grant to TE (project 8119367) and EK (project 250709). PLP was supported by a research grant (TE_291/2010) offered by the Romanian Ministry of Education and Science. T. Szép received funding from OTKA K69068 and JT from OTKA 75618. JMP was supported by a JAE grant from Consejo Superior de Investigaciones Científicas. SM-JM, FdL-AM, JF, JJS and FV were respectively supported by projects CGL2009-09439, CGL2012-36665, CGL2009- 11445, CGL2010-19233-C03-01 and CGL2008-00562 by the Spanish Ministry of Science and Innovation and FEDER and project EVITAR by the Spanish Ministry of Health. FV was also supported by the European Regional Development Fund. MACT was funded by a predoctoral FPU grant from the Spanish Ministry of Education (AP20043713). PM was supported by grant from the Polish Ministry of Science and Higher Education (project 2P04F07030), and the Foundation for Polish Science

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field

Novel probes for pH and dissolved oxygen measurements in cultivations from millilitre to benchtop scale

Erworben im Rahmen der Schweizer Nationallizenzen (http://www.nationallizenzen.ch)pH value and the concentration of dissolved oxygen (DO) are key parameters to monitor and control cell growth in cultivation studies. Reliable, robust and accurate methods to measure these parameters in cultivation systems in real time guarantee high product yield and quality. This mini-review summarises the current state of the art of pH and DO sensors that are applied to bioprocesses from millilitre to benchtop scale by means of a short introduction on measuring principles and selected applications. Special emphasis is placed on single-use bioreactors, which have been increasingly employed in bioprocess development and production in recent years. Working principles, applications and the particular requirements of sensors in these cultivation systems are given. In such processes, optical sensors for pH and DO are often preferred to electrochemical probes, as they allow semi-invasive measurements and can be miniaturised to micrometre scale or lower. In addition, selected measuring principles of novel sensing technologies for pH and DO are discussed. These include solid-state sensors and miniaturised devices that are not yet commercially available, but show promising characteristics for possible use in bioprocesses in the near future

A new model of development of the mammalian ovary and follicles

Ovarian follicular granulosa cells surround and nurture oocytes, and produce sex steroid hormones. It is believed that during development the ovarian surface epithelial cells penetrate into the ovary and develop into granulosa cells when associating with oogonia to form follicles. Using bovine fetal ovaries (n = 80) we identified a novel cell type, termed GREL for Gonadal Ridge Epithelial-Like. Using 26 markers for GREL and other cells and extracellular matrix we conducted immunohistochemistry and electron microscopy and chronologically tracked all somatic cell types during development. Before 70 days of gestation the gonadal ridge/ovarian primordium is formed by proliferation of GREL cells at the surface epithelium of the mesonephros. Primordial germ cells (PGCs) migrate into the ovarian primordium. After 70 days, stroma from the underlying mesonephros begins to penetrate the primordium, partitioning the developing ovary into irregularly-shaped ovigerous cords composed of GREL cells and PGCs/oogonia. Importantly we identified that the cords are always separated from the stroma by a basal lamina. Around 130 days of gestation the stroma expands laterally below the outermost layers of GREL cells forming a sub-epithelial basal lamina and establishing an epithelial-stromal interface. It is at this stage that a mature surface epithelium develops from the GREL cells on the surface of the ovary primordium. Expansion of the stroma continues to partition the ovigerous cords into smaller groups of cells eventually forming follicles containing an oogonium/oocyte surrounded by GREL cells, which become granulosa cells, all enclosed by a basal lamina. Thus in contrast to the prevailing theory, the ovarian surface epithelial cells do not penetrate into the ovary to form the granulosa cells of follicles, instead ovarian surface epithelial cells and granulosa cells have a common precursor, the GREL cell.Katja Hummitzsch, Helen F. Irving-Rodgers, Nicholas Hatzirodos, Wendy Bonner, Laetitia Sabatier, Dieter P. Reinhardt, Yoshikazu Sado, Yoshifumi Ninomiya, Dagmar Wilhelm and Raymond J. Rodger