In silico prediction of housekeeping long intergenic non-coding RNAs reveals HKlincR1 as an essential player in lung cancer cell survival

Prioritising long intergenic noncoding RNAs (lincRNAs) for functional characterisation is a significant challenge. Here we applied computational approaches to discover lincRNAs expected to play a critical housekeeping (HK) role within the cell. Using the Illumina Human BodyMap RNA sequencing dataset as a starting point, we first identified lincRNAs ubiquitously expressed across a panel of human tissues. This list was then further refined by reference to conservation score, secondary structure and promoter DNA methylation status. Finally, we used tumour expression and copy number data to identify lincRNAs rarely downregulated or deleted in multiple tumour types. The resulting list of candidate essential lincRNAs was then subjected to co-expression analyses using independent data from ENCODE and The Cancer Genome Atlas (TCGA). This identified a substantial subset with a predicted role in DNA replication and cell cycle regulation. One of these, HKlincR1, was selected for further characterisation. Depletion of HKlincR1 affected cell growth in multiple lung cancer cell lines, and led to disruption of genes involved in cell growth and viability. In addition, HKlincR1 expression was correlated with overall survival in lung adenocarcinoma patients. Our in silico studies therefore reveal a set of housekeeping noncoding RNAs of interest both in terms of their role in normal homeostasis, and their relevance in tumour growth and maintenance

Benfordness of the Generalized Gamma Distribution

The generalized gamma distribution shows up in many problems related to engineering, hydrology as well as survival analysis. Earlier work has been done that estimated the deviation of the exponential and the Weibull distribution from Benford's Law. We give a mathematical explanation for the Benfordness of the generalized gamma distribution and present a measure for the deviation of the generalized gamma distribution from the Benford distribution

Efficient Mixing at low Reynolds numbers using polymer additives

Mixing in fluids is a rapidly developing field of fluid mechanics \cite{Sreen,Shr,War}, being an important industrial and environmental problem. The mixing of liquids at low Reynolds numbers is usually quite weak in simple flows, and it requires special devices to be efficient. Recently, the problem of mixing was solved analytically for a simple case of random flow, known as the Batchelor regime \cite{Bat,Kraich,Fal,Sig,Fouxon}. Here we demonstrate experimentally that very viscous liquids at low Reynolds number, $Re$. Here we show that very viscous liquids containing a small amount of high molecular weight polymers can be mixed quite efficiently at very low Reynolds numbers, for a simple flow in a curved channel. A polymer concentration of only 0.001% suffices. The presence of the polymers leads to an elastic instability \cite{LMS} and to irregular flow \cite{Ours}, with velocity spectra corresponding to the Batchelor regime \cite{Bat,Kraich,Fal,Sig,Fouxon}. Our detailed observations of the mixing in this regime enable us to confirm sevearl important theoretical predictions: the probability distributions of the concentration exhibit exponential tails \cite{Fal,Fouxon}, moments of the distribution decay exponentially along the flow \cite{Fouxon}, and the spatial correlation function of concentration decays logarithmically.Comment: 11 pages, 5 figure

Control of translation during the unfolded protein response in maize seedlings: Life without PERKs

The accumulation of misfolded proteins in the endoplasmic reticulum (ER) defines a condition called ER stress that induces the unfolded protein response (UPR). The UPR in mammalian cells attenuates protein synthesis initiation, which prevents the piling up of misfolded proteins in the ER. Mammalian cells rely on Protein Kinase RNA‐Like Endoplasmic Reticulum Kinase (PERK) phosphorylation of eIF2α to arrest protein synthesis, however, plants do not have a PERK homolog, so the question is whether plants control translation in response to ER stress. We compared changes in RNA levels in the transcriptome to the RNA levels protected by ribosomes and found a decline in translation efficiency, including many UPR genes, in response to ER stress. The decline in translation efficiency is due to the fact that many mRNAs are not loaded onto polyribosomes (polysomes) in proportion to their increase in total RNA, instead some of the transcripts accumulate in stress granules (SGs). The RNAs that populate SGs are not derived from the disassembly of polysomes because protein synthesis remains steady during stress. Thus, the surge in transcription of UPR genes in response to ER stress is accompanied by the formation of SGs, and the sequestration of mRNAs in SGs may serve to temporarily relieve the translation load during ER stress

Publisher Correction: In silico prediction of housekeeping long intergenic non-coding RNAs reveals HKlincR1 as an essential player in lung cancer cell survival

An amendment to this paper has been published and can be accessed via a link at the top of the paper

Advanced DC zonal marine power system protection

A new Active Impedance Estimation (AIE) based protection strategy which is suitable for utilization in a DC zonal marine power distribution system is presented. This method uses two triangular current "spikes" injections for system impedance estimation and protection when faults are detected. By comparing the estimated impedance with the pre-calibrated value, the fault location can be predicted and fault can be isolated without requiring communication between two injection units. Using co¬operated double injections and line current measurement (directional fault detection), faults in the system with same impedance and different fault positions can be distinguished, located and isolated. The proposed method is validated using experimental test results derived from a 30kW, 400V, twin bus DC marine power system demonstrator. The experimental tests were applied to both faults during normal operation and faults that occur during system restoration

Minimally invasive presacral approach for revision of an Axial Lumbar Interbody Fusion rod due to fall-related lumbosacral instability: a case report

<p>Abstract</p> <p>Introduction</p> <p>The purpose of this study was to describe procedural details of a minimally invasive presacral approach for revision of an L5-S1 Axial Lumbar Interbody Fusion rod.</p> <p>Case presentation</p> <p>A 70-year-old Caucasian man presented to our facility with marked thoracolumbar scoliosis, osteoarthritic changes characterized by high-grade osteophytes, and significant intervertebral disc collapse and calcification. Our patient required crutches during ambulation and reported intractable axial and radicular pain. Multi-level reconstruction of L1-4 was accomplished with extreme lateral interbody fusion, although focal lumbosacral symptoms persisted due to disc space collapse at L5-S1.</p> <p>Lumbosacral interbody distraction and stabilization was achieved four weeks later with the Axial Lumbar Interbody Fusion System (TranS1 Inc., Wilmington, NC, USA) and rod implantation via an axial presacral approach.</p> <p>Despite symptom resolution following this procedure, our patient suffered a fall six weeks postoperatively with direct sacral impaction resulting in symptom recurrence and loss of L5-S1 distraction. Following seven months of unsuccessful conservative care, a revision of the Axial Lumbar Interbody Fusion rod was performed that utilized the same presacral approach and used a larger diameter implant. Minimal adhesions were encountered upon presacral re-entry. A precise operative trajectory to the base of the previously implanted rod was achieved using fluoroscopic guidance. Surgical removal of the implant was successful with minimal bone resection required. A larger diameter Axial Lumbar Interbody Fusion rod was then implanted and joint distraction was re-established. The radicular symptoms resolved following revision surgery and our patient was ambulating without assistance on post-operative day one. No adverse events were reported.</p> <p>Conclusions</p> <p>The Axial Lumbar Interbody Fusion distraction rod may be revised and replaced with a larger diameter rod using the same presacral approach.</p

Transitions Regulating the Timing of Cytokinesis in Embryonic Cells

AbstractAnaphase, mitotic exit, and cytokinesis proceed in rapid succession, and while mitotic exit is a requirement for cytokinesis in yeast [1, 2], it may not be a direct requirement for furrow initiation in animal cells [3, 4]. In this report, we physically manipulated the proximity of the mitotic apparatus (MA) to the cell cortex in combination with microinjection of effectors of the spindle checkpoint and CDK1 activity to determine how the initiation of cytokinesis is coupled to the onset of anaphase and mitotic exit. Whereas precocious contact between the MA and the cell surface advanced the onset of cytokinesis into early anaphase A, furrowing could not be advanced prior to the metaphase-anaphase transition. Additionally, while cells arrested in anaphase could be induced to initiate cleavage furrows, cells arrested in metaphase could not. Finally, activation of the mitotic checkpoint in one spindle of a binucleate cell failed to arrest cytokinesis induced by the control spindle but did inhibit the formation of furrows between the arrested MA and the control, nonarrested MA. Our experiments suggest that the competence of the mitotic apparatus to initiate cytokinesis is not dependent on cyclin degradation but does require anaphase-promoting complex (APC) activity and, thus, inactivation of the mitotic checkpoint

Proteomic screening and identification of differentially distributed membrane proteins in Escherichia coli

Bacteria show asymmetric subcellular distribution of many proteins involved in diverse cellular processes such as chemotaxis, motility, actin polymerization, chromosome partitioning and cell division. In many cases, the specific subcellular localization of these proteins is critical for proper regulation and function. Although cellular organization of the bacterial cell clearly plays an important role in cell physiology, systematic studies to uncover asymmetrically distributed proteins have not been reported previously. In this study, we undertook a proteomics approach to uncover polar membrane proteins in Escherichia coli . We identified membrane proteins enriched in E. coli minicells using a combination of two-dimensional electrophoresis and mass spectrometry. Among a total of 173 membrane protein spots that were consistently detected, 36 spots were enriched in minicell membranes, whereas 15 spots were more abundant in rod cell membranes. The minicell-enriched proteins included the inner membrane proteins MCPs, AtpA, AtpB, YiaF and AcrA, the membrane-associated FtsZ protein and the outer membrane proteins YbhC, OmpW, Tsx, Pal, FadL, OmpT and BtuB. We immunolocalized two of the minicell-enriched proteins, OmpW and YiaF, and showed that OmpW is a bona fide polar protein whereas YiaF displays a patchy membrane distribution with a polar and septal bias.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72089/1/j.1365-2958.2004.04040.x.pd

Sperm death and dumping in Drosophila

Mating with more than one male is the norm for females of many species. In addition to generating competition between the ejaculates of different males, multiple mating may allow females to bias sperm use. In Drosophila melanogaster, the last male to inseminate a female sires approximately 80% of subsequent progeny. Both sperm displacement, where resident sperm are removed from storage by the incoming ejaculate of the copulating male, and sperm incapacitation, where incoming seminal fluids supposedly interfere with resident sperm, have been implicated in this pattern of sperm use. But the idea of incapacitation is problematic because there are no known mechanisms by which an individual could damage rival sperm and not their own. Females also influence the process of sperm use, but exactly how is unclear. Here we show that seminal fluids do not kill rival sperm and that any 'incapacitation' is probably due to sperm ageing during sperm storage. We also show that females release stored sperm from the reproductive tract (sperm dumping) after copulation with a second male and that this requires neither incoming sperm nor seminal fluids. Instead, males may cause stored sperm to be dumped or females may differentially eject sperm from the previous mating