2017
Kfir Sharabi, Lin, Hua , Tavares, Clint DJ, Dominy, John E, Camporez, Joao Paulo , Perry, Rachel J, Schilling, Roger , Rines, Amy K, Lee, Jaemin , Hickey, Marc , Bennion, Melissa , Palmer, Michelle , Nag, Partha P, Bittker, Joshua A, Perez, José , Jedrychowski, Mark P, Ozcan, Umut , Gygi, Steve P, Kamenecka, Theodore M, Shulman, Gerald I, Schreiber, Stuart L, Griffin, Patrick R, ו Puigserver, Pere . 2017.
“Selective Chemical Inhibition Of Pgc-1Α Gluconeogenic Activity Ameliorates Type 2 Diabetes”. Cell, 169, 1, Pp. 148-160.e15. doi:10.1016/j.cell.2017.03.001.
תקציר Type 2 diabetes (T2D) is a worldwide epidemic with a medical need for additional targeted therapies. Suppression of hepatic glucose production (HGP) effectively ameliorates diabetes and can be exploited for its treatment. We hypothesized that targeting PGC-1α acetylation in the liver, a chemical modification known to inhibit hepatic gluconeogenesis, could be potentially used for treatment of T2D. Thus, we designed a high-throughput chemical screen platform to quantify PGC-1α acetylation in cells and identified small molecules that increase PGC-1α acetylation, suppress gluconeogenic gene expression, and reduce glucose production in hepatocytes. On the basis of potency and bioavailability, we selected a small molecule, SR-18292, that reduces blood glucose, strongly increases hepatic insulin sensitivity, and improves glucose homeostasis in dietary and genetic mouse models of T2D. These studies have important implications for understanding the regulatory mechanisms of glucose metabolism and treatment of T2D.
G. Shapiro, Bez, M. , Tawackoli, W. , Gazit, Z. , Gazit, D. , ו Pelled, G.. 2017.
“Semiautomated Longitudinal Microcomputed Tomography-Based Quantitative Structural Analysis Of A Nude Rat Osteoporosis-Related Vertebral Fracture Model”. J Vis Exp. doi:10.3791/55928.
Publisher's Version תקציר Osteoporosis-related vertebral compression fractures (OVCFs) are a common and clinically unmet need with increasing prevalence as the world population ages. Animal OVCF models are essential to the preclinical development of translational tissue engineering strategies. While a number of models currently exist, this protocol describes an optimized method for inducing multiple highly reproducible vertebral defects in a single nude rat. A novel longitudinal semiautomated microcomputed tomography (microCT)-based quantitative structural analysis of the vertebral defects is also detailed. Briefly, rats were imaged at multiple time points post-op. The day 1 scan was reoriented to a standard position, and a standard volume of interest was defined. Subsequent microCT scans of each rat were automatically registered to the day 1 scan so the same volume of interest was then analyzed to assess for new bone formation. This versatile approach can be adapted to a variety of other models where longitudinal imaging-based analysis could benefit from precise 3D semiautomated alignment. Taken together, this protocol describes a readily quantifiable and easily reproducible system for osteoporosis and bone research. The suggested protocol takes 4 months to induce osteoporosis in nude ovariectomized rats and between 2.7 and 4 h to generate, image, and analyze two vertebral defects, depending on tissue size and equipment.
Ido Hadar, Philbin, John P, Panfil, Yossef E, Neyshtadt, Shany , Lieberman, Itai , Eshet, Hagai , Lazar, Sorin , Rabani, Eran , ו Banin, Uri . 2017.
“Semiconductor Seeded Nanorods With Graded Composition Exhibiting High Quantum-Yield, High Polarization, And Minimal Blinking”. Nano Letters, 17, 4, Pp. 2524-2531. .
Publisher's Version תקציר 
Seeded semiconductor nanorods represent a unique family of quantum confined materials that manifest characteristics of mixed dimensionality. They show polarized emission with high quantum yield and fluorescence switching under an electric field, features that are desirable for use in display technologies and other optical applications. So far, their robust synthesis has been limited mainly to CdSe/CdS heterostructures, thereby constraining the spectral tunability to the red region of the visible spectrum. Herein we present a novel synthesis of CdSe/Cd1–xZnxS seeded nanorods with a radially graded composition that show bright and highly polarized green emission with minimal intermittency, as confirmed by ensemble and single nanorods optical measurements. Atomistic pseudopotential simulations elucidate the importance of the Zn atoms within the nanorod structure, in particular the effect of the graded composition. Thus, the controlled addition of Zn influences and improves the nanorods’ optoelectronic performance by providing an additional handle to manipulate the degree confinement beyond the common size control approach. These nanorods may be utilized in applications that require the generation of a full, rich spectrum such as energy-efficient displays and lighting.
Ido Hadar, Philbin, John P. , Panfil, Yossef E. , Neyshtadt, Shany , Lieberman, Itai , Eshet, Hagai , Lazar, Sorin , Rabani, Eran , ו Banin, Uri . 2017.
“Semiconductor Seeded Nanorods With Graded Composition Exhibiting High Quantum-Yield, High Polarization, And Minimal Blinking”. Nano Letters, 17, 4, Pp. 2524-2531. doi:10.1021/acs.nanolett.7b00254.
Publisher's Version תקציר Seeded semiconductor nanorods represent a unique family of quantum confined materials that manifest characteristics of mixed dimensionality. They show polarized emission with high quantum yield and fluorescence switching under an electric field, features that are desirable for use in display technologies and other optical applications. So far, their robust synthesis has been limited mainly to CdSe/CdS heterostructures, thereby constraining the spectral tunability to the red region of the visible spectrum. Herein we present a novel synthesis of CdSe/Cd1–xZnxS seeded nanorods with a radially graded composition that show bright and highly polarized green emission with minimal intermittency, as confirmed by ensemble and single nanorods optical measurements. Atomistic pseudopotential simulations elucidate the importance of the Zn atoms within the nanorod structure, in particular the effect of the graded composition. Thus, the controlled addition of Zn influences and improves the nanorods’ optoelectronic performance by providing an additional handle to manipulate the degree confinement beyond the common size control approach. These nanorods may be utilized in applications that require the generation of a full, rich spectrum such as energy-efficient displays and lighting.
It is alarming that today clinicians are still helpless trying to cope with life-threatening sequelae of severe microbial infections, which very often terminates in sepsis, septic shock and death. According to CDC (The Centers for Disease Control and Prevention) today the annual incidence of sepsis in the USA affects as many as 7,50,000 hospitalized patients and mortality rates are about 40% [1]. As of today, all the clinical trials of sepsis, which had tried the efficacy of only a single antagonist at a time, had failed to protect against septic shock, a disorder obviously caused by multi-factorial processes. Even the “hope of sepsis“, activated protein C (APC), has recently been discontinued. Today, no effective treatment for sepsis is available and the morality rates are climbing steadily also because of the rapid acquisition of antibiotic resistance.
We consider a standard model of judgment aggregation as presented, for example, in Dietrich (2015). For this model we introduce a sequential aggregation procedure (SAP) which uses the majority rule as much as possible. The ordering of the issues is assumed to be exogenous. The exact definition of SAP is given in Section 3. In Section 4 we construct an intuitive relevance relation for our model, closely related to conditional entailment. Unlike Dietrich (2015), where the relevance relation is given exogenously as part of the model, we require that the relevance relation be derived from the agenda. We prove that SAP has the property of independence of irrelevant issues (III) with respect to (the transitive closure of) our relevance relation. As III is weaker than the property of proposition-wise independence (PI) we do not run into impossibility results as does List (2004) who incorporates PI in some parts of his analysis. We proceed to characterize SAP by anonymity, restricted monotonicity, local neutrality, restricted agenda property, and independence of past deliberations (see Section 5 for the precise details). Also, we use this occasion to show that Roberts s (1991) characterization of choice by plurality voting can be adapted to our model.
Yaron Bruchim, Ginsburg, Isaac , Segev, Gilad , Mreisat, Ahmad , Avital, Yochai , Aroch, Itamar , ו Horowitz, Michal . 2017.
“Serum Histones As Biomarkers Of The Severity Of Heatstroke In Dogs”. Cell Stress & Chaperones, Epub ahead of print. .
Publisher's Version תקציר Heatstroke is associated with systemic inflammatory response syndrome, leading to multiple organ dysfunction and death. Currently, there is no specific treatment decreasing hyperthermia-induced inflammatory/hemostatic derangements. Emerging studies indicate that histones leaking from damaged cells into the extracellular space are toxic, pro-inflammatory, and pro-thrombotic. We therefore hypothesize that serum histones (sHs) are elevated during heatstroke and are associated with the severity of the disease. Sixteen dogs with heatstroke and seven healthy controls were included in the study. Median serum histones (sHs) upon admission in dogs with heatstroke were significantly higher (P = 0.043) compared to that in seven controls (13.2 vs. 7.3 ng/mL, respectively). sHs level was significantly higher among non-survivors and among dogs with severe hemostatic derangement (P = 0.049, median 21.4 ng/mL vs. median 8.16 ng/mL and P = 0.038, 19.0 vs. 7.0 ng/mL, respectively). There were significant positive correlation between sHs and urea (r = 0.8, P = 0.02); total CO2 (r = 0.661, P = 0.05); CK (r = 0.678, P = 0.04); and prothrombin time (PT) 12 h post presentation (r = 0.888, P = 0.04). The significant positive correlation between sHs and other heatstroke severity biomarkers, and significant increase among severely affected dogs, implies its role in inflammation/oxidation/coagulation during heatstroke. sHs, unlike other prognostic and severity biomarkers in heatstroke, can be pharmacologically manipulated, offering a potential therapeutic target.
Shira Zelber-Sagi, Azar, Shahar , Nemirovski, Alina , Webb, Muriel , Halpern, Zamir , Shibolet, Oren , ו Tam, Joseph . 2017.
“Serum Levels Of Endocannabinoids Are Independently Associated With Nonalcoholic Fatty Liver Disease.”. Obesity (Silver Spring, Md.), 25, 1, Pp. 94–101. doi:10.1002/oby.21687.
תקציר {OBJECTIVE: To evaluate the association between circulating levels of endocannabinoids (eCBs) and non-alcoholic fatty liver disease (NAFLD). METHODS: The serum levels of the main eCBs, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), and their endogenous precursor and breakdown product, arachidonic acid (AA), were analyzed by liquid chromatography/tandem mass spectrometry in 105 volunteers screened for NAFLD. Hepatic ultrasound, fasting blood tests, and anthropometrics were assessed. Liver fat was quantified by the hepato-renal-ultrasound index representing the ratio between the brightness level of the liver and the kidney. RESULTS: Patients with NAFLD had higher levels (pmol/mL) of AA (2,721 ± 1,112 vs. 2,248 ± 977
The WUSCHEL homeobox transcription factor is required to specify stem-cell identity at the shoot apical meristem and its ectopic expression is sufficient to induce de novo shoot meristem formation. Yet, the manner by which WUS promotes stem-cell fate is not yet fully understood. In the present research we address this question by inducing WUS function outside of its domain. We show that activation of WUS function in the root inhibits the responses to exogenous auxin and suppresses the initiation and growth of lateral roots. Using time lapse movies to follow the cell-cycle marker CYCB1;1::GFP, we also show that activation of WUS function suppresses cell division and cell elongation. In addition, activation of WUS represses the auxin-induced expression of the PLETHORA1 root identity gene and promotes shoot fate. Shoot apical meristem formation requires a high cytokinin-to-auxin ratio. Our findings provide evidence for the manner by which WUS specifies stem-cell identity: by affecting auxin responses, by reducing the cell mitotic activity and by repressing other developmental pathways. At the meristem, the stem-cells which are characterized by low division rate are surrounded by the highly proliferative meristematic cells. Our results also provide a model for WUS establishing the differential mitotic rates between two cell populations at the minute structure of the meristem.
E. Troja, Lipunov, V. M, Mundell, C. G, Butler, N. R, Watson, A. M, Kobayashi, S. , Cenko, S. B, Marshall, F. E, Ricci, R. , Fruchter, A. , Wieringa, M. H, Gorbovskoy, E. S, Kornilov, V. , Kutyrev, A. , Lee, W. H, Toy, V. , Tyurina, N. V, Budnev, N. M, Buckley, D. AH, González, J. , Gress, O. , Horesh, A. , Panasyuk, M. I, Prochaska, J. X, Ramirez-Ruiz, E. , R. Lopez, Rebolo , Richer, M. G, Roman-Zuniga, C. , Serra-Ricart, M. , Yurkov, V. , ו Gehrels, N. . 2017.
“Significant And Variable Linear Polarization During The Prompt Optical Flash Of Grb 160625B.”. \Nat, 547, Pp. 425-427. doi:10.1038/nature23289.
Plants take up silicon as mono-silicic acid, which is released to soil by the weathering of silicate minerals. Silicic acid can be taken up by plant roots passively or actively, and later it is deposited in its polymerized form as amorphous hydrated silica. Major silica depositions in grasses occur in root endodermis, leaf epidermal cells, and outer epidermal cells of inflorescence bracts. Debates are rife about the mechanism of silica deposition, and two contrasting scenarios are often proposed to explain it. According to the passive mode of silicification, silica deposition is a result of silicic acid condensation due to dehydration, such as during transpirational loss of water from the aboveground organs. In general, silicification and transpiration are positively correlated, and continued silicification is sometimes observed after cell and tissue maturity. The other mode of silicification proposes the involvement of some biological factors, and is based on observations that silicification is not necessarily coupled with transpiration. Here, we review evidence for both mechanisms of silicification, and propose that the deposition mechanism is specific to the cell type. Considering all the cell types together, our conclusion is that grass silica deposition can be divided into three modes: spontaneous cell wall silicification, directed cell wall silicification, and directed paramural silicification in silica cells.
Oshry Markovich, Steiner, Evyatar , Kouřil, Štěpán, Tarkowski, Petr , Aharoni, Asaph , ו Elbaum, Rivka . 2017.
“Silicon Promotes Cytokinin Biosynthesis And Delays Senescence In Arabidopsis And Sorghum.”. Plant Cell Environ, 40, 7, Pp. 1189-1196. doi:10.1111/pce.12913.
תקציר Silicate minerals are dominant soil components. Thus, plant roots are constantly exposed to silicic acid. High silicon intake, enabled by root silicon transporters, correlates with increased tolerance to many biotic and abiotic stresses. However, the underlying protection mechanisms are largely unknown. Here, we tested the hypothesis that silicon interacts with the plant hormones, and specifically, that silicic acid intake increases cytokinin biosynthesis. The reaction of sorghum (Sorghum bicolor) and Arabidopsis plants, modified to absorb high versus low amounts of silicon, to dark-induced senescence was monitored, by quantifying expression levels of genes along the senescence pathway and measuring tissue cytokinin levels. In both species, detached leaves with high silicon content senesced more slowly than leaves that were not exposed to silicic acid. Expression levels of genes along the senescence pathway suggested increased cytokinin biosynthesis with silicon exposure. Mass spectrometry measurements of cytokinin suggested a positive correlation between silicon exposure and active cytokinin concentrations. Our results indicate a similar reaction to silicon treatment in distantly related plants, proposing a general function of silicon as a stress reliever, acting via increased cytokinin biosynthesis.
