Integrating biological data into ocean observing systems: the future role of OBIS

The future data needs of ocean science and ocean resource management will require a more seamless and accessible coupling of biological data with physical oceanographic processes. This bio-physical data framework will be built through the active integration of data from an extensive variety of sensors, observers, platforms and data archives across a wide range of space and time scales. This necessary synthesis of raw biological data into useful information and potentially new understanding is dependent on both new developments in ocean exploration as well as developments in information systems and informatics. The Ocean Biogeographic Information System (OBIS) is poised to play a significant and expanding role in the evolving ocean observation system

CRISPR/Cas9 screen in human iPSC‐derived cortical neurons identifies NEK6 as a novel disease modifier of C9orf72 poly(PR) toxicity

Introduction The most common genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are hexanucleotide repeats in chromosome 9 open reading frame 72 (C9orf72). These repeats produce dipeptide repeat proteins with poly(PR) being the most toxic one. Methods We performed a kinome-wide CRISPR/Cas9 knock-out screen in human induced pluripotent stem cell (iPSC) -derived cortical neurons to identify modifiers of poly(PR) toxicity, and validated the role of candidate modifiers using in vitro, in vivo, and ex-vivo studies. Results Knock-down of NIMA-related kinase 6 (NEK6) prevented neuronal toxicity caused by poly(PR). Knock-down of nek6 also ameliorated the poly(PR)-induced axonopathy in zebrafish and NEK6 was aberrantly expressed in C9orf72 patients. Suppression of NEK6 expression and NEK6 activity inhibition rescued axonal transport defects in cortical neurons from C9orf72 patient iPSCs, at least partially by reversing p53-related DNA damage. Discussion We identified NEK6, which regulates poly(PR)-mediated p53-related DNA damage, as a novel therapeutic target for C9orf72 FTD/ALS

Essential versus accessory aspects of cell death: recommendations of the NCCD 2015

Cells exposed to extreme physicochemical or mechanical stimuli die in an uncontrollable manner, as a result of their immediate structural breakdown. Such an unavoidable variant of cellular demise is generally referred to as ‘accidental cell death’ (ACD). In most settings, however, cell death is initiated by a genetically encoded apparatus, correlating with the fact that its course can be altered by pharmacologic or genetic interventions. ‘Regulated cell death’ (RCD) can occur as part of physiologic programs or can be activated once adaptive responses to perturbations of the extracellular or intracellular microenvironment fail. The biochemical phenomena that accompany RCD may be harnessed to classify it into a few subtypes, which often (but not always) exhibit stereotyped morphologic features. Nonetheless, efficiently inhibiting the processes that are commonly thought to cause RCD, such as the activation of executioner caspases in the course of apoptosis, does not exert true cytoprotective effects in the mammalian system, but simply alters the kinetics of cellular demise as it shifts its morphologic and biochemical correlates. Conversely, bona fide cytoprotection can be achieved by inhibiting the transduction of lethal signals in the early phases of the process, when adaptive responses are still operational. Thus, the mechanisms that truly execute RCD may be less understood, less inhibitable and perhaps more homogeneous than previously thought. Here, the Nomenclature Committee on Cell Death formulates a set of recommendations to help scientists and researchers to discriminate between essential and accessory aspects of cell death

The Interleukin-6 inflammation pathway from cholesterol to aging – Role of statins, bisphosphonates and plant polyphenols in aging and age-related diseases

We describe the inflammation pathway from Cholesterol to Aging. Interleukin 6 mediated inflammation is implicated in age-related disorders including Atherosclerosis, Peripheral Vascular Disease, Coronary Artery Disease, Osteoporosis, Type 2 Diabetes, Dementia and Alzheimer's disease and some forms of Arthritis and Cancer. Statins and Bisphosphonates inhibit Interleukin 6 mediated inflammation indirectly through regulation of endogenous cholesterol synthesis and isoprenoid depletion. Polyphenolic compounds found in plants, fruits and vegetables inhibit Interleukin 6 mediated inflammation by direct inhibition of the signal transduction pathway. Therapeutic targets for the control of all the above diseases should include inhibition of Interleukin-6 mediated inflammation

Resolution of inflammation: a new therapeutic frontier

Dysregulated inflammation is a central pathological process in diverse disease states. Traditionally, therapeutic approaches have sought to modulate the pro- or anti-inflammatory limbs of inflammation, with mixed success. However, insight into the pathways by which inflammation is resolved has highlighted novel opportunities to pharmacologically manipulate these processes — a strategy that might represent a complementary (and perhaps even superior) therapeutic approach. This Review discusses the state of the art in the biology of resolution of inflammation, highlighting the opportunities and challenges for translational research in this field

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

A study of exact methods for container loading problems

The container loading problem, a 3D packing problem, consists of allocating a number of items (usually boxes) inside one or more containers. Different characteristic combinations give rise to different variants of the problem. This study addresses four of these variants: the single knapsack problem (SKP), the single large object placement problem (SLOPP), the multiple heterogeneous large object placement problem (MHLOPP) and the open dimension problem (ODP). The SKP occurs when there exists a single container and a set of strongly heterogeneous boxes to be placed inside the container. By contrast, the SLOPP arises if there is a single container and a set of weakly heterogeneous boxes to be allocated. Finally the MHLOPP concerns a set of boxes requiring placement inside a set of weakly or strongly heterogeneous containers. Although these three problems originate from the same source, the SKP and the SLOPP's objective is to maximize the container's occupied volume, whereas the MHLOPP's is to minimize the number of containers. These three problems assume that containers have fixed dimensions. In the ODP not all dimensions of the container are fixed. The most common scenario in this variant is where two dimensions are fixed (width and height, for example) and the objective is to minimize the remaining dimension. This study compares the most significant exact methods proposed in the literature for the four variants of container loading problems considered. These methods include several discrete and continuous mixed integer programming (MIP) models and a specialized branch-and-bound. Regarding the origin of the MIP models, three were taken from the MHLOPP, two from the SKP and one from the ODP literature. The specialized branch-and-bound was taken from the MHLOPP literature. These methods are adapted so as to enable a clear comparison using classic benchmark datasets from the literature concerning addressed problems. The benchmark datasets consist of different configurations, enabling the evaluation of the methods in distinct situations. Eight benchmark sets are considered, with five consisting of a small number of boxes (up to 15), one from 5 to 100 boxes and the two remaining of a larger number of boxes (at least 100). To analyze the methods, the comparison parameters depend on the particular problem type considered. The number of unallocated boxes and total container volume occupation are the comparison parameters available for the SKP. Since all boxes are already inside the container to begin with in the open dimension problem, the comparison criterion is the value of the minimized dimension. The final results are obtained when the optimal solution is found or the execution time limit is reached. The results obtained suggest which exact methods perform best for each container loading problem category. These results provide further insight and aid in the development of new formulations and matheuristics for the considered problems.Editorial consultation provided by Luke Connolly (KU Leuven).status: publishe