142 research outputs found
Zinc Finger Nucleases as tools to understand and treat human diseases
Recent work has shown that it is possible to target regulatory elements to DNA sequences of an investigator's choosing, increasing the armamentarium for probing gene function. In this review, we discuss the development and use of designer zinc finger proteins (ZFPs) as sequence specific tools. While the main focus of this review is to discuss the attachment of the FokI nuclease to ZFPs and the ability of the resulting fusion protein (termed zinc finger nucleases (ZFNs)) to genomically manipulate a gene of interest, we will also cover the utility of other functional domains, such as transcriptional activators and repressors, and highlight how these are being used as discovery and therapeutic tools
A comparison of the malnutrition screening tools, MUST, MNA and bioelectrical impedance assessment in frail older hospital patients
Summary
Background & aims
This cohort study aimed to investigate and compare the ability to predict malnutrition in a group of frail older hospital patients in the United Kingdom using the nutritional risk screening tools, MUST (malnutrition universal screening tool), MNA-SF® (mini nutritional assessment-short form) and bioelectrical impedance assessment (BIA) of body composition.
Methods
MUST and MNA-SF was performed on 78 patients (49 males and 29 females, age: 82 y ± 7.9, body mass index (BMI): 25.5 kg/m2 ± 5.4), categorised by nutritional risk, and statistical comparison and test reliability performed. BIA was performed in 66 patients and fat free mass (FFM), fat mass (FM) and body cell mass (BCM) and index values (kg/m2) calculated and compared against reference values.
Results
MUST scored 77% patients ‘low risk’, 9% ‘medium risk’ and 14% ‘high risk’, compared to MNA-SF categorisation: 9%, 46% and 45%, respectively (P < 0.000001). Reliability assessment found poor reliability between the screening tools (coefficient, r = 0.4). Significant positive correlations were found between most variables (P < 0.05–<0.001); although females exhibited greater variation. FFM index analysis found 40% of males low/depleted, 21% borderline/at risk with 96% categorised by MNA-SF as either malnourished or at risk (MUST-35%). 29% males had low FM index and all appropriately classified by MNA-SF. 30% females had low FFM index or borderline, MNA-SF screening appropriately categorised 86% (compared to MUST-29%).
Conclusions
This preliminary data may have significant clinical implications and highlights the potential ability of the MNA-SF and BIA to accurately assess malnutrition risk over MUST in frail older hospital patients
Protein kinase B phosphorylates AHNAK and regulates its subcellular localization
AHNAK is a ubiquitously expressed giant phosphoprotein that was initially identified as a gene product subject to transcriptional repression in neuroblastoma. AHNAK is predominantly nuclear in cells of nonepithelial origin, but is cytoplasmic or associated with plasma membrane in epithelial cells. In this study we show that the extranuclear localization of AHNAK in epithelial cells depends on the formation of cell–cell contacts. We show that AHNAK is a phosphorylation substrate of protein kinase B (PKB) in vitro and in vivo. Nuclear exclusion of AHNAK is mediated through a nuclear export signal (NES) in a manner that depends on the phosphorylation of serine 5535 of AHNAK by PKB, a process that also plays a major role in determining extranuclear localization of AHNAK. AHNAK is a new PKB substrate whose function, though unknown, is likely to be regulated by its localization, which is in turn regulated by PKB
Corrugated Drop Spine Box
Step-by-step instructions for measuring and assembling a drop-spine box made from a single sheet of corrugated board for the housing or rare books and other materials
Genetic diversity and cross-compatibility of cadagi (Corymbia torelliana): implications for hybrid breeding
Induction of NF-κB by the Akt/PKB kinase
AbstractThe serine/threonine kinase Akt (also known as protein kinase B, PKB) is activated by numerous growth-factor and immune receptors through lipid products of phosphatidylinositol (PI) 3-kinase. Akt can couple to pathways that regulate glucose metabolism or cell survival [1]. Akt can also regulate several transcription factors, including E2F, CREB, and the Forkhead family member Daf-16 [2–4]. Here, we show that Akt can regulate signaling pathways that lead to induction of the NF-κB family of transcription factors in the Jurkat T-cell line. This induction occurs, at least in part, at the level of degradation of the NF-κB inhibitor IκB, and is specific for NF-κB, as other inducible transcription factors are not affected by Akt overexpression. Furthermore, the effect requires the kinase activity and pleckstrin homology (PH) domain of Akt. Also, Akt does not act alone to induce cytokine promoters and NF-κB reporters, because signals from other pathways are required to observe the effect. These studies uncover a previously unappreciated connection between Akt and NF-κB induction that could have implications for the control of T-cell growth and survival
Tuxedo Phase Box (3 variants)
These diagrams depict 3 variants of the tuxedo-style phase box, a simple, low-cost, enclosure made from 20pt acid-free folder stock. It is designed to protect brittle, deteriorated, low priority items
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