Lane Medical Library

Patterning and processes: how stomatal development defines physiological potential.

Curr Opin Plant Biol. 2014 Jul 21;21C:67-74

Authors: Dow GJ, Bergmann DC

Abstract
Stomata present an excellent opportunity for connecting scientific disciplines: they are governed by complex genetic controls and unique cell biology, while also possessing a large influence over plant productivity and relationships with the environment. For this reason, stomata have engaged scientists for many centuries and continue to be a central interest for many fields of research. Recent technological advances have enabled interdisciplinary studies of stomata that were previously out of reach, and as a result, we are beginning to realize new insights about stomatal biology that place them at the intersection of our changing world. This review is intended to describe these interdisciplinary connections, discuss the relevant scales at which they are having an influence, and highlight ways we can capitalize on such novel approaches. While we incorporate knowledge about molecular advances, this is not intended to be an extensive review of that field, but rather, we focus on how those systems inform plant physiology and are connected to global scales.

PMID: 25058395 [PubMed - as supplied by publisher]

CT Perfusion of the Liver: Principles and Applications in Oncology.

Radiology. 2014 Aug;272(2):322-344

Authors: Kim SH, Kamaya A, Willmann JK

Abstract
With the introduction of molecularly targeted chemotherapeutics, there is an increasing need for defining new response criteria for therapeutic success because use of morphologic imaging alone may not fully assess tumor response. Computed tomographic (CT) perfusion imaging of the liver provides functional information about the microcirculation of normal parenchyma and focal liver lesions and is a promising technique for assessing the efficacy of various anticancer treatments. CT perfusion also shows promising results for diagnosing primary or metastatic tumors, for predicting early response to anticancer treatments, and for monitoring tumor recurrence after therapy. Many of the limitations of early CT perfusion studies performed in the liver, such as limited coverage, motion artifacts, and high radiation dose of CT, are being addressed by recent technical advances. These include a wide area detector with or without volumetric spiral or shuttle modes, motion correction algorithms, and new CT reconstruction technologies such as iterative algorithms. Although several issues related to perfusion imaging-such as paucity of large multicenter trials, limited accessibility of perfusion software, and lack of standardization in methods-remain unsolved, CT perfusion has now reached technical maturity, allowing for its use in assessing tumor vascularity in larger-scale prospective clinical trials. In this review, basic principles, current acquisition protocols, and pharmacokinetic models used for CT perfusion imaging of the liver are described. Various oncologic applications of CT perfusion of the liver are discussed and current challenges, as well as possible solutions, for CT perfusion are presented. © RSNA, 2014 Online supplemental material is available for this article.

PMID: 25058132 [PubMed - as supplied by publisher]

The Global Burden of Disease Study 2010: Interpretation and Implications for the Neglected Tropical Diseases.

PLoS Negl Trop Dis. 2014 Jul;8(7):e2865

Authors: Hotez PJ, Alvarado M, Basáñez MG, Bolliger I, Bourne R, Boussinesq M, Brooker SJ, Brown AS, Buckle G, Budke CM, Carabin H, Coffeng LE, Fèvre EM, Fürst T, Halasa YA, Jasrasaria R, Johns NE, Keiser J, King CH, Lozano R, Murdoch ME, O'Hanlon S, Pion SD, Pullan RL, Ramaiah KD, Roberts T, Shepard DS, Smith JL, Stolk WA, Undurraga EA, Utzinger J, Wang M, Murray CJ, Naghavi M

PMID: 25058013 [PubMed - as supplied by publisher]

Cerebellar encoding of multiple candidate error cues in the service of motor learning.

J Neurosci. 2014 Jul 23;34(30):9880-90

Authors: Guo CC, Ke MC, Raymond JL

Abstract
For learning to occur through trial and error, the nervous system must effectively detect and encode performance errors. To examine this process, we designed a set of oculomotor learning tasks with more than one visual object providing potential error cues, as would occur in a natural visual scene. A task-relevant visual target and a task-irrelevant visual background both influenced vestibulo-ocular reflex learning in rhesus monkeys. Thus, motor learning does not identify a single error cue based on behavioral relevance, but can be simultaneously influenced by more than one cue. Moreover, the relative weighting of the different cues could vary. If the speed of the visual target's motion on the retina was low (≪1°/s), background motion dominated learning, but if target speed was high, the effects of the background were suppressed. The target and background motion had similar, nonlinear effects on the putative neural instructive signals carried by cerebellar climbing fibers, but with a stronger influence of the background on the climbing fibers than on learning. In contrast, putative neural instructive signals carried by the simple spikes of Purkinje cells were influenced solely by the motion of the visual target. Because they are influenced by different cues during training, joint control of learning by the climbing fibers and Purkinje cells may expand the learning capacity of the cerebellar circuit.

PMID: 25057191 [PubMed - in process]

Meta-analysis identifies loci affecting levels of the potential osteoarthritis biomarkers sCOMP and uCTX-II with genome wide significance.

J Med Genet. 2014 Jul 23;

Authors: Ramos YF, Metrustry S, Arden N, Bay-Jensen AC, Beekman M, de Craen AJ, Cupples LA, Esko T, Evangelou E, Felson DT, Hart DJ, Ioannidis JP, Karsdal M, Kloppenburg M, Lafeber F, Metspalu A, Panoutsopoulou K, Slagboom PE, Spector TD, van Spil EW, Uitterlinden AG, Zhu Y, arcOGEN consortium, TreatOA collaborators, Valdes AM, van Meurs JB, Meulenbelt I

Abstract
BACKGROUND: Research for the use of biomarkers in osteoarthritis (OA) is promising, however, adequate discrimination between patients and controls may be hampered due to innate differences. We set out to identify loci influencing levels of serum cartilage oligomeric protein (sCOMP) and urinary C-telopeptide of type II collagen (uCTX-II).
METHODS: Meta-analysis of genome-wide association studies was applied to standardised residuals of sCOMP (N=3316) and uCTX-II (N=4654) levels available in 6 and 7 studies, respectively, from TreatOA. Effects were estimated using a fixed-effects model. Six promising signals were followed up by de novo genotyping in the Cohort Hip and Cohort Knee study (N=964). Subsequently, their role in OA susceptibility was investigated in large-scale genome-wide association studies meta-analyses for OA. Differential expression of annotated genes was assessed in cartilage.
RESULTS: Genome-wide significant association with sCOMP levels was found for a SNP within MRC1 (rs691461, p=1.7×10(-12)) and a SNP within CSMD1 associated with variation in uCTX-II levels with borderline genome-wide significance (rs1983474, p=8.5×10(-8)). Indication for association with sCOMP levels was also found for a locus close to the COMP gene itself (rs10038, p=7.1×10(-6)). The latter SNP was subsequently found to be associated with hip OA whereas COMP expression appeared responsive to the OA pathophysiology in cartilage.
CONCLUSIONS: We have identified genetic loci affecting either uCTX-II or sCOMP levels. The genome wide significant association of MRC1 with sCOMP levels was found likely to act independent of OA subtypes. Increased sensitivity of biomarkers with OA may be accomplished by taking genetic variation into account.

PMID: 25057126 [PubMed - as supplied by publisher]

AACE/ACE Disease State Clinical Review: Medical Management of Cushing Disease.

Endocr Pract. 2014 Jul 1;20(7):746-57

Authors: Hamrahian AH, Yuen KC, Hoffman AR, For The Aace Neuroendocrine And Pituitary Scientific Committee

Abstract
OBJECTIVE: To review available medical therapies for patients with Cushing disease and to provide a roadmap for their use in clinical practice.
METHODS: PubMed searches were performed to identify all of the available published data on medical management of Cushing disease.
RESULTS: Medical therapy is usually not the first-line treatment for patients with Cushing disease but may be used to improve clinical manifestations of Cushing disease in patients who are not suitable candidates for surgery, following unsuccessful surgery or recurrence, or as a "bridge therapy" in those who have undergone radiotherapy. Medical therapy may also be used in preoperative preparation of patients with severe disease. Current available medical options for patients with Cushing disease include centrally acting agents, steroidogenesis inhibitors, and a glucocorticoid receptor antagonists. At present, there are no head-to-head studies comparing the efficacy, tolerability, and safety of different U.S. Food and Drug Administration (FDA)- and non-FDA-approved drugs in patients with Cushing disease. With the initiation of new studies and the completion of ongoing clinical trials, the number of FDA-approved drugs for medical treatment of Cushing disease is expected to increase.
CONCLUSION: Medical therapy has an important adjunctive role in the management of patients with Cushing disease. The decision to initiate medical treatment depends on many factors, including patient characteristics and preference. Long-term studies are needed to better define the clinical efficacy, safety, and tolerability of medical treatment of Cushing disease, including the role of combination therapies.

PMID: 25057099 [PubMed - in process]

Single-molecule analysis of diffusion and trapping of STIM1 and Orai1 at ER-plasma membrane junctions.

Mol Biol Cell. 2014 Jul 23;

Authors: Wu MM, Covington ED, Lewis RS

Abstract
Following ER Ca(2+) depletion, STIM1 and Orai1 complexes assemble autonomously at ER-plasma membrane (PM) junctions to trigger store-operated Ca(2+) influx. One hypothesis to explain this process is a diffusion trap in which activated STIM1 diffusing in the ER becomes trapped at junctions through interactions with the PM, and STIM1 then traps Orai1 in the PM through binding of its CRAC activation domain. We tested this model by analyzing STIM1 and Orai1 diffusion using single-particle tracking, photoactivation of protein ensembles, and Monte Carlo simulations. In resting cells, STIM1 diffusion is Brownian while Orai1 is slightly subdiffusive. After store depletion both proteins slow to the same speeds, consistent with complex formation, and are confined to a corral similar in size to ER-PM junctions. While the escape probability at high STIM:Orai expression ratios is <1%, it is significantly increased by reducing the affinity of STIM1 for Orai1 or by expressing the two proteins at comparable levels. Our results provide direct evidence that STIM-Orai complexes are trapped by their physical connections across the junctional gap, but also reveal that the complexes are surprisingly dynamic, suggesting that readily reversible binding reactions generate free STIM1 and Orai1 which engage in constant diffusional exchange with extrajunctional pools.

PMID: 25057023 [PubMed - as supplied by publisher]

Interpreting the CYP2D6 Results From the International Tamoxifen Pharmacogenetics Consortium.

Clin Pharmacol Ther. 2014 Aug;96(2):144-6

Authors: Province MA, Altman RB, Klein TE

Abstract
UNLABELLED: Meta-analysis of the entire analyzable cohort of 4,935 tamoxifen-treated breast cancer patients by the International Tamoxifen Pharmacogenetics Consortium (ITPC) (criterion 3) revealed no CYP2D6 effect on outcomes but strong heterogeneity across sites.(1) However, a post hoc-defined subgroup (criterion 1: postmenopausal, estrogen receptor positive, receiving 20 mg/day tamoxifen for 5 years; n = 1,996) did find a statistically significant effect of CYP2D6 on both invasive disease-free survival as well as breast cancer-free interval, with little site heterogeneity. How should we interpret these discrepant findings?"
STATISTICS: The only science that enables different experts using the same figures to draw different conclusions."-Evan Esar, humorist"Data do not give up their secrets easily. They must be tortured to confess."-Jeffrey Hooper, Bell Laboratories"Facts are stubborn, but statistics are more pliable."-Mark Twain, humorist.

PMID: 25056393 [PubMed - in process]

Platelet function inhibitors and platelet function testing in neurointerventional procedures.

J Neurointerv Surg. 2014 Jul 23;

Authors: Gandhi CD, Bulsara KR, Fifi J, Kass-Hout T, Grant RA, Almandoz JD, English J, Meyers PM, Abruzzo T, Prestigiacomo CJ, Powers CJ, Lee SK, Albani B, Do HM, Eskey CJ, Patsalides A, Hetts S, Hussain MS, Ansari SA, Hirsch JA, Kelly M, Rasmussen P, Mack W, Pride GL, Alexander MJ, Jayaraman MV, on behalf of the SNIS Standards and Guidelines Committee

PMID: 25056369 [PubMed - as supplied by publisher]

Reprogramming ovarian and breast cancer cells into non-cancerous cells by low-dose metformin or SN-38 through FOXO3 activation.

Sci Rep. 2014;4:5810

Authors: Hu T, Chung YM, Guan M, Ma M, Ma J, Berek JS, Hu MC

Abstract
Cancer is a leading cause of death worldwide. Because the cytotoxic effects of conventional chemotherapies often harm normal tissue cells along with cancer cells, conventional chemotherapies cause many unwanted or intolerable side effects. Thus, there is an unmet medical need to establish a paradigm of chemotherapy-induced differentiation of cancer cells with tolerable side effects. Here we show that low-dose metformin or SN-38 inhibits cell growth or survival in ovarian and breast cancer cells and suppresses their tumor growth in vivo. Low-dose metformin or SN-38 increases FOXO3 nuclear localization as well as the amount of DNA damage markers and downregulates the expression of a cancer-stemness marker CD44 and other stemness markers, including Nanog, Oct-4, and c-Myc, in these cancer cells. This treatment also inhibits spheroid body-formation in 3-dimensional culture. In contrast, silencing FOXO3 diminishes all these cellular events when ovarian/breast cancer cells are treated with the mentioned drugs. These results suggest that low-dose metformin or SN-38 may reprogram these cancer cells into non-cancerous cells in a FOXO3-dependent manner, and may allow patients to overcome these cancers with minimal side effects.

PMID: 25056111 [PubMed - in process]

Late acute myopia syndrome induced by combination of sulfonamide drugs.

J Glaucoma. 2014 Feb;23(2):e119-21

Authors: Kozner P, Simonova K, Brozek B, Singh K

Abstract
We present a case of late acute myopia syndrome following discontinuation of treatment with a combination of sulphonamide drugs. To the best of our knowledge, this is the first reported case with such a presentation, and suggests that the pathophysiological basis for the acute myopia syndrome is a rapid decrease in serum carbonic anhydrase inhibitors levels which may lead to a rebound increase in the production of aqueous humor and accumulation of suprachoroidal fluid. It is further postulated that there may be a cumulative effect of sulphonamide drug use on carbonic anhydrase activity in the ciliary body epithelium of susceptible individuals.

PMID: 23661047 [PubMed - indexed for MEDLINE]

Three-dimensional dixon fat-water separated rapid breathheld imaging of myocardial infarction.

J Magn Reson Imaging. 2013 Dec;38(6):1362-8

Authors: Saranathan M, Glockner J

Abstract
PURPOSE: To develop a breathhold three-dimensional (3D) Dixon technique for fat suppressed imaging of myocardial infarction.
MATERIALS AND METHODS: A pulse sequence was developed that uses a radial fan-beam k-space segmentation scheme for efficient coverage of k-space, enabling 3D scans in a single breathhold. The sequence uses a dual-echo bipolar readout to enable Dixon fat-water separation for improved visualization of epicardial and pericardial delayed enhancement. The 3D Dixon method was compared with a conventional 2D fast gradient recalled echo (FGRE) -based technique in 25 patients.
RESULTS: Pericardial visualization scores and confidence were higher while overall image quality and artifacts were slightly worse for 3D Dixon compared with 2D FGRE. Robust fat suppression was achieved in 21 of 25 cases using the 3D Dixon method.
CONCLUSION: A 3D breathhold method for fat-water separated imaging of myocardial delayed enhancement was developed and validated.

PMID: 23559381 [PubMed - indexed for MEDLINE]

Respiratory-induced 3D deformations of the renal arteries quantified with geometric modeling during inspiration and expiration breath-holds of magnetic resonance angiography.

J Magn Reson Imaging. 2013 Dec;38(6):1325-32

Authors: Suh GY, Choi G, Draney MT, Herfkens RJ, Dalman RL, Cheng CP

Abstract
PURPOSE: To quantify renal artery deformation due to respiration using magnetic resonance (MR) image-based geometric analysis.
MATERIALS AND METHODS: Five males were imaged with contrast-enhanced MR angiography during inspiratory and expiratory breath-holds. From 3D models of the abdominal aorta, left and right renal arteries (LRA and RRA), we quantified branching angle, curvature, peak curve angle, axial length, and locations of branch points.
RESULTS: With expiration, maximum curvature changes were 0.054 ± 0.025 mm(-1) (P < 0.01), and curve angle at the most proximal curvature peak increased by 8.0 ± 4.5° (P < 0.05) in the LRA. Changes in maximum curvature and curve angles were not significant in the RRA. The first renal bifurcation point translated superiorly and posteriorly by 9.7 ± 3.6 mm (P < 0.005) and 3.5 ± 2.1 mm (P < 0.05), respectively, in the LRA, and 10.8 ± 6.1 mm (P < 0.05) and 3.6 ± 2.5 mm (P < 0.05), respectively, in the RRA. Changes in branching angle, axial length, and renal ostia locations were not significant.
CONCLUSION: The LRA and RRA deformed and translated significantly. Greater deformation of the LRA as compared to the RRA may be due to asymmetric anatomy and mechanical support by the inferior vena cava. The presented methodology can extend to quantification of deformation of diseased and stented arteries to help renal artery implant development.

PMID: 23553967 [PubMed - indexed for MEDLINE]