bluuebunny/crossref_metadata_2025 huggingface dataset:
Reward Systems in the Brain and Nutrition
Authors: Rolls Edmund T.
Published: May 2016

The taste cortex in the anterior insula provides separate and combined representations of the taste, temperature, and texture of food in the mouth independently of hunger and thus of reward value and pleasantness. One synapse on, in the orbitofrontal cortex, these sensory inputs are combined by associative learning with olfactory and visual inputs for some neurons, and these neurons encode food reward value in that they respond to food only when hunger is present and in that activations correlate linearly with subjective pleasantness. Cognitive factors, including word-level descriptions and selective attention to affective value, modulate the representation of the reward value of taste, olfactory, and flavor stimuli in the orbitofrontal cortex and a region to which it projects, the anterior cingulate cortex. These food reward representations are important in the control of appetite and food intake. Individual differences in reward representations may contribute to obesity, and there are age-related differences in these reward representations. Implications of how reward systems in the brain operate for understanding, preventing, and treating obesity are described.
Disallowed and Allowed Gene Expression: Two Faces of Mature Islet Beta Cells
Authors: Lemaire Katleen , Thorrez Lieven , Schuit Frans
Published: May 2016

Glucose homeostasis greatly depends on the match between fluctuating insulin demands and adjusted rates of insulin secretion, which is the function of pancreatic beta cells. Emerging evidence suggests that when neonatal beta cells mature, they acquire two faces of differentiated function: an expected “visible face” that depends on specific beta cell proteins needed for regulated insulin release, but also a “hidden face” that represses ubiquitous proteins to prevent inappropriate beta cell function such as elevated basal hormone secretion or insulin release triggered by exercise. This review highlights this novel concept, and we first propose that hidden faces may also be relevant for other specialized tissue functions, such as ketogenesis in the liver. Next, we discuss three scenarios in which aberrant gene expression causes abnormal glucose-induced insulin release and the epigenetic regulation of the hidden face in beta cells. We conclude with perspectives for new research, including beta cell replacement to cure diabetes.
Iron Regulation of Pancreatic Beta-Cell Functions and Oxidative Stress
Authors: Backe Marie Balslev , Moen Ingrid Wahl , Ellervik Christina , Hansen Jakob Bondo , Mandrup-Poulsen Thomas
Published: May 2016

Dietary advice is the cornerstone in first-line treatment of metabolic diseases. Nutritional interventions directed at these clinical conditions mainly aim to (a) improve insulin resistance by reducing energy-dense macronutrient intake to obtain weight loss and (b) reduce fluctuations in insulin secretion through avoidance of rapidly absorbable carbohydrates. However, even in the majority of motivated patients selected for clinical trials, massive efforts using this approach have failed to achieve lasting efficacy. Less attention has been given to the role of micronutrients in metabolic diseases. Here, we review the evidence that highlights (a) the importance of iron in pancreatic beta-cell function and dysfunction in diabetes and (b) the integrative pathophysiological effects of tissue iron levels in the interactions among the beta cell, gut microbiome, hypothalamus, innate and adaptive immune systems, and insulin-sensitive tissues. We propose that clinical trials are warranted to clarify the impact of dietary or pharmacological iron reduction on the development of metabolic disorders.
Hormonal and Metabolite Regulation of Hepatic Glucokinase
Authors: Agius Loranne
Published: May 2016

Liver glucose metabolism is dependent on glucokinase activity. Glucokinase expression is transcriptionally regulated by hormones and metabolites of glucose, and glucokinase activity is dependent on reversible binding of glucokinase to a specific inhibitor protein, glucokinase regulatory protein (GKRP), and to other binding proteins such as 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase (PFK2/FBP2), which functions as an activator. Glucokinase is inhibited in the postabsorptive state by sequestration in the nucleus bound to GKRP, and it is activated postprandially by portal hyperglycemia and fructose through dissociation from GKRP, translocation to the cytoplasm, and binding to PFK2/FBP2. Glucagon dissociates this interaction, promoting translocation back to the nucleus. In humans, changes in glucokinase expression and activity are associated with poorly controlled type 2 diabetes and with nonalcoholic fatty liver disease, and a common variant of GKRP with altered binding affinity for glucokinase is associated with increased blood and liver lipids and other metabolic traits that implicate a role for GKRP in maintaining intrahepatic metabolite homeostasis.
Carbohydrate ingestion induces sex-specific cardiac vagal inhibition, but not vascular sympathetic modulation, in healthy older women
Authors: Cao Lei , Graham Stuart L. , Pilowsky Paul M.
Published: May 2016

The role of vagal function in cardiovascular risk in older women remains unclear. Autonomic modulation following carbohydrate ingestion (CI) and postural stress (PS) were investigated in 14 healthy men and 21 age-matched postmenopausal women (age: 65.0 ± 2.1 vs. 64.1 ± 1.6 years), with normal and comparable insulin sensitivity. Continuous noninvasive finger arterial pressure and ECG were recorded in the lying and the standing positions before and after ingestion of a carbohydrate-rich meal (600 kcal, carbohydrate 78%, protein 13%, and fat 8%). Low-frequency (LF, 0.04–0.15 Hz) and high-frequency (HF, 0.15–0.4 Hz) components (ms2) of heart rate variability (HRV), low-frequency power (mmHg2) of systolic blood pressure variability (SBP LF power), and the sequence method for spontaneous baroreflex sensitivity (BRS, ms/mmHg) were used to quantify autonomic modulation. In response to CI and PS, mean arterial pressure maintained stable, and heart rate increased in women and men in the lying and standing positions. Following CI (60, 90, and 120 min postprandially) in the standing position, SBP LF power increased by 40% in men ( P = 0.02), with unchanged HRV parameters; in contrast, in women, HRV HF power halved ( P = 0.02), with unaltered SBP LF power. During PS before and after CI, similar magnitude of SBP LF power, HRV, and BRS changes was observed in men and women. In conclusion, CI induces sex-specific vascular sympathetic activation in healthy older men, and cardiac vagal inhibition in healthy older women; this CI-mediated efferent vagal inhibition may suggest differential cardiovascular risk factors in women, irrespective of insulin resistance, and impairment of autonomic control.
Inhibitory modulation of optogenetically identified neuron subtypes in the rostral solitary nucleus
Authors: Chen Z. , Travers S. P. , Travers J. B.
Published: May 2016

Inhibition is presumed to play an important role in gustatory processing in the rostral nucleus of the solitary tract (rNST). One source of inhibition, GABA, is abundant within the nucleus and comes both from local, intrasolitary sources and from outside the nucleus. In addition to the receptor-mediated effects of GABA on rNST neurons, the hyperpolarization-sensitive currents, Ihand IA, have the potential to further modulate afferent signals. To elucidate the effects of GABAergic modulation on solitary tract (ST)-evoked responses in phenotypically defined rNST neurons and to define the presence of IAand Ihin the same cells, we combined in vitro recording and optogenetics in a transgenic mouse model. This mouse expresses channelrhodopsin 2 (ChR2) in GAD65-expressing GABAergic neurons throughout the rNST. GABA positive (GABA+) neurons differed from GABA negative (GABA−) neurons in their response to membrane depolarization and ST stimulation. GABA+ neurons had lower thresholds to direct membrane depolarization compared with GABA− neurons, but GABA− neurons responded more faithfully to ST stimulation. Both IAand Ihwere present in subsets of GABA+ and GABA− neurons. Interestingly, GABA+ neurons with Ihwere more responsive to afferent stimulation than inhibitory neurons devoid of these currents, whereas GABA− neurons with IAwere more subject to inhibitory modulation. These results suggest that the voltage-gated channels underlying IAand Ihplay an important role in modulating rNST output through a circuit of feedforward inhibition.
Sleep and memory consolidation: a common mechanism across species?
Authors: Frighetto Giovanni , Cellini Nicola
Published: May 2016

In humans, memory consolidation can be aided by the representation of an odor previously associated with target information during sleep. In an elegant study, Zwaka et al. ( Curr Biol 25: 2869–2874, 2015) have demonstrated that the same process occurs in honeybees, suggesting that the relationship between sleep and memory may be similar across different animal species.
HCN hyperpolarization-activated cation channels strengthen virtual nicotinic EPSPs and thereby elevate synaptic amplification in rat sympathetic neurons
Authors: Kullmann Paul H. M. , Sikora Kristine M. , Clark K. Lyles , Arduini Irene , Springer Mitchell G. , Horn John P.
Published: May 2016

The influence of hyperpolarization-activated cation current (h-current; Ih) upon synaptic integration in paravertebral sympathetic neurons was studied together with expression of hyperpolarization-activated cyclic nucleotide-gated (HCN) subunit isoforms. All four HCN subunits were detected in homogenates of the rat superior cervical ganglion (SCG) using the PCR to amplify reverse-transcribed messenger RNAs (RT-PCR) and using quantitative PCR. Voltage clamp recordings from dissociated SCG neurons at 35°C detected Ih in all cells, with a maximum hyperpolarization-activated cation conductance of 1.2 ± 0.1 nS, half-maximal activation at −87.6 mV, and reversal potential of −31.6 mV. Interaction between Ih and synaptic potentials was tested with virtual fast nicotinic excitatory postsynaptic potentials (EPSPs) created with dynamic clamp. The blocking of Ih with 15 μM ZD7288 hyperpolarized cells by 4.7 mV and increased the virtual synaptic conductance required to stimulate an action potential from 7.0 ± 0.9 nS to 12.1 ± 0.9 nS. In response to stimulation with 40 s long trains of virtual EPSPs, ZD7288 reduced postsynaptic firing from 2.2 to 1.7 Hz and the associated synaptic amplification from 2.2 ± 0.1 to 1.7 ± 0.2. Cyclic nucleotide binding to HCN channels was simulated by blocking native Ih with ZD7288, followed by reconstitution with virtual Ih using a dynamic clamp model of the voltage clamp data. Over a 30-mV range, shifting the half-activation voltage for Ih in 10 mV depolarizing increments always increased synaptic gain. These results indicate that Ih, in sympathetic neurons, can strengthen nicotinic EPSPs and increase synaptic amplification, while also working as a substrate for cyclic nucleotide-dependent modulation.
Knockout of the BK β4-subunit promotes a functional coupling of BK channels and ryanodine receptors that mediate a fAHP-induced increase in excitability
Authors: Wang Bin , Bugay Vladislav , Ling Ling , Chuang Hui-Hsui , Jaffe David B. , Brenner Robert
Published: May 2016

BK channels are large-conductance calcium- and voltage-activated potassium channels with diverse properties. Knockout of the accessory BK β4-subunit in hippocampus dentate gyrus granule neurons causes BK channels to change properties from slow-gated type II channels to fast-gated type I channels that sharpen the action potential, increase the fast afterhyperpolarization (fAHP) amplitude, and increase spike frequency. Here we studied the calcium channels that contribute to fast-gated BK channel activation and increased excitability of β4 knockout neurons. By using pharmacological blockers during current-clamp recording, we find that BK channel activation during the fAHP is dependent on ryanodine receptor activation. In contrast, L-type calcium channel blocker (nifedipine) affects the BK channel-dependent repolarization phase of the action potential but has no effect on the fAHP. Reducing BK channel activation during the repolarization phase with nifedipine, or during the fAHP with ryanodine, indicated that it is the BK-mediated increase of the fAHP that confers proexcitatory effects. The proexcitatory role of the fAHP was corroborated using dynamic current clamp. Increase or decrease of the fAHP amplitude during spiking revealed an inverse relationship between fAHP amplitude and interspike interval. Finally, we show that the seizure-prone ryanodine receptor gain-of-function (R2474S) knockin mice have an unaltered repolarization phase but larger fAHP and increased AP frequency compared with their control littermates. In summary, these results indicate that an important role of the β4-subunit is to reduce ryanodine receptor-BK channel functional coupling during the fAHP component of the action potential, thereby decreasing excitability of dentate gyrus neurons.
Ubiquitin ligase Nedd4-2 modulates Kv1.3 current amplitude and ion channel protein targeting
Authors: Vélez Patricio , Schwartz Austin B. , Iyer Subashini R. , Warrington Anthony , Fadool Debra Ann
Published: May 2016

Voltage-dependent potassium channels (Kv) go beyond the stabilization of the resting potential and regulate biochemical pathways, regulate intracellular signaling, and detect energy homeostasis. Because targeted deletion and pharmacological block of the Kv1.3 channel protein produce marked changes in metabolism, resistance to diet-induced obesity, and changes in olfactory structure and function, this investigation explored Nedd4-2-mediated ubiquitination and degradation to regulate Kv1.3 channel density. Heterologous coexpression of Nedd4-2 ligase and Kv1.3 in HEK 293 cells reduced Kv1.3 current density without modulation of kinetic properties as measured by patch-clamp electrophysiology. Modulation of current density was dependent on ligase activity and was lost through point mutation of cysteine 938 in the catalytic site of the ligase (Nedd4-2CS). Incorporation of adaptor protein Grb10 relieved Nedd4-2-induced current suppression as did application of the proteasome inhibitor Mg-132. SDS-PAGE and immunoprecipitation strategies demonstrated a channel/adaptor/ligase signalplex. Pixel immunodensity was reduced for Kv1.3 in the presence of Nedd4-2, which was eliminated upon additional incorporation of Grb10. We confirmed Nedd4-2/Grb10 coimmunoprecipitation and observed an increased immunodensity for Nedd4-2 in the presence of Kv1.3 plus Grb10, regardless of whether the catalytic site was active. Kv1.3/Nedd4-2 were reciprocally coimmunoprecipated, whereby mutation of the COOH-terminal, SH3-recognition (493–498), or ubiquitination sites on Kv1.3 (lysines 467, 476, 498) retained coimmunoprecipitation, while the latter prevented the reduction in channel density. A model is presented for which an atypical interaction outside the canonical PY motif may permit channel/ligase interaction to lead to protein degradation and reduced current density, which can involve Nedd4-2/Grb10 interactions to disrupt Kv1.3 loss of current density.
Hybrid Multistarting GA-Tabu Search Method for the Placement of BtB Converters for Korean Metropolitan Ring Grid
Authors: Labios Remund J. , Kim Seungjin , Song Hwachang , Lee Byongjun
Published: May 2016

This paper presents a method to determine the optimal locations for installing back-to-back (BtB) converters in a power grid as a countermeasure to reduce fault current levels. The installation of BtB converters can be regarded as network reconfiguration. For the purpose, a hybrid multistarting GA-tabu search method was used to determine the best locations from a preselected list of candidate locations. The constraints used in determining the best locations include circuit breaker fault current limits, proximity of proposed locations, and capability of the solution to reach power flow convergence. A simple power injection model after applying line-opening on selected branches was used as a means for power flows with BtB converters. Kron reduction was also applied as a method for network reduction for fast evaluation of fault currents with a given topology. Simulations of the search method were performed on the Korean power system, particularly the Seoul metropolitan area.
Protective Effects of Carvedilol and Vitamin C against Azithromycin‐Induced Cardiotoxicity in Rats via Decreasing ROS, IL1‐β, and TNF‐α Production and Inhibiting NF‐κB and Caspase‐3 Expression
Authors: El-Shitany Nagla A. , El-Desoky Karema
Published: May 2016

The Food and Drug Administration recently warned of the fatal cardiovascular risks of azithromycin in humans. In addition, a recently published study documented azithromycin‐induced cardiotoxicity in rats. This study aimed to justify the exact cardiovascular events accompanying azithromycin administration in rats, focusing on electrocardiographic, biochemical, and histopathological changes. In addition, the underlying mechanisms were studied regarding reactive oxygen species production, cytokine release, and apoptotic cell‐death. Finally, the supposed protective effects of both carvedilol and vitamin C were assessed. Four groups of rats were used: (1) control, (2) azithromycin, (3) azithromycin + carvedilol, and (4) azithromycin + vitamin C. Azithromycin resulted in marked atrophy of cardiac muscle fibers and electrocardiographic segment alteration. It increased the heart rate, lactate dehydrogenase, creatine phosphokinase, malondialdehyde, nitric oxide, interleukin‐1 beta (IL1‐β), tumor necrosis factor alpha (TNF‐α), nuclear factor kappa beta (NF‐κB), and caspase‐3. It decreased reduced glutathione, glutathione peroxidase, and superoxide dismutase. Carvedilol and vitamin C prevented most of the azithromycin‐induced electrocardiographic and histopathological changes. Carvedilol and vitamin C decreased lactate dehydrogenase, malondialdehyde, IL1‐β, TNF‐α, NF‐κB, and caspase‐3. Both agents increased glutathione peroxidase. This study shows that both carvedilol and vitamin C protect against azithromycin‐induced cardiotoxicity through antioxidant, immunomodulatory, and antiapoptotic mechanisms.
Feedback Gating Control for Network Based on Macroscopic Fundamental Diagram
Authors: Ji YangBeibei , Mo Chao , Ma Wanjing , Liao Dabin
Published: May 2016

Empirical data from Yokohama, Japan, showed that a macroscopic fundamental diagram (MFD) of urban traffic provides for different network regions a unimodal low-scatter relationship between network vehicle density and network space-mean flow. This provides new tools for network congestion control. Based on MFD, this paper proposed a feedback gating control policy which can be used to mitigate network congestion by adjusting signal timings of gating intersections. The objective of the feedback gating control model is to maximize the outflow and distribute the allowed inflows properly according to external demand and capacity of each gating intersection. An example network is used to test the performance of proposed feedback gating control model. Two types of background signalization types for the intersections within the test network, fixed-time and actuated control, are considered. The results of extensive simulation validate that the proposed feedback gating control model can get a Pareto improvement since the performance of both gating intersections and the whole network can be improved significantly especially under heavy demand situations. The inflows and outflows can be improved to a higher level, and the delay and queue length at all gating intersections are decreased dramatically.
Adaptive Robust Backstepping Control of Permanent Magnet Synchronous Motor Chaotic System with Fully Unknown Parameters and External Disturbances
Authors: Yu Yang , Guo Xudong , Mi Zengqiang
Published: May 2016

The chaotic behavior of permanent magnet synchronous motor is directly related to the parameters of chaotic system. The parameters of permanent magnet synchronous motor chaotic system are frequently unknown. Hence, chaotic control of permanent magnet synchronous motor with unknown parameters is of great significance. In order to make the subject more general and feasible, an adaptive robust backstepping control algorithm is proposed to address the issues of fully unknown parameters estimation and external disturbances inhibition on the basis of associating backstepping control with adaptive control. Firstly, the mathematical model of permanent magnet synchronous motor chaotic system with fully unknown parameters is constructed, and the external disturbances are introduced into the model. Secondly, an adaptive robust backstepping control technology is employed to design controller. In contrast with traditional backstepping control, the proposed controller is more concise in structure and avoids many restricted problems. The stability of the control approach is proved by Lyapunov stability theory. Finally, the effectiveness and correctness of the presented algorithm are verified through multiple simulation experiments, and the results show that the proposed scheme enables making permanent magnet synchronous motor operate away from chaotic state rapidly and ensures the tracking errors to converge to a small neighborhood within the origin rapidly under the full parameters uncertainties and external disturbances.
Bilateral, Simultaneous, Acute Angle Closure Glaucoma in Pseudophakia Induced by Chlorthalidone
Authors: Durai Indra , Mohan Dhavalikar Mrunali , Anand Chandran Prem , Ganesh Venkatraman , Krishnadas Ramaswami
Published: May 2016

Purpose. To report two persons with acute, bilateral, and simultaneous angle closure glaucoma in pseudophakia secondary to uveal effusions induced by administration of chlorthalidone.Methods. Case reports.Results. Bilateral shallow anterior chambers and high intraocular pressure with decline in visual acuity were reported in two patients within days of intake of chlorthalidone for systemic hypertension. Gonioscopy confirmed appositional angle closure while choroidal detachment and ciliochoroidal detachment were revealed on ultrasonographic studies. Discontinuing chlorthalidone and institution of aqueous suppressants to reduce IOP and cycloplegics reversed angle closure and glaucoma.Conclusions. Reports of angle closure glaucoma in pseudophakic eyes induced by idiosyncratic reaction to chlorthalidone confirms that osmotic changes in the crystalline lens has no role in the pathogenesis of drug induced glaucoma and reaffirms that glaucoma is secondary to ciliochoroidal detachment and ciliary body rotation and edema.
An Analysis of the Thermal Conductivity of Composite Materials (CPC-30R/Charcoal from Sugarcane Bagasse) Using the Hot Insulated Plate Technique
Authors: Salgado-Delgado René , Olarte-Paredes Alfredo , Salgado-Delgado Areli Marlen , Vargas-Galarza Zully , Lopez-Lara Teresa , Hernández-Zaragoza Juan Bosco , Rico-Rodríguez Israel , Martínez-Barrera Gonzalo
Published: May 2016

The production of new thermally insulating composite materials from solid residues such as charcoal from sugarcane bagasse (CSB) is of great importance because it takes advantage of materials that might otherwise pollute the environment. Therefore, for this study, we obtained composite materials based on a portland cement (CPC-30R) matrix and CSB particles with a 4 : 1 water-cement ratio and CSB concentrations of 5%, 10%, and 15% by weight. The thermal conductivities of these materials were characterized following ASTM guideline C177, their CSB morphological properties were analyzed using scanning electron microscopy (SEM), and their compositions were determined using energy-dispersive spectrometer (EDS). The results show that the composite materials have reduced thermal conductivities. The metallic oxide percentage composition of the CSB was also determined. It was observed that there was a reduction in thermal conductivity when CSB was used as compared to 100% CPC-30R, and the influence of the CSB concentration on thermal conductivity was measured.
Evaluation of Performance of Different Methods in Detecting Abrupt Climate Changes
Authors: Zhao Chunyu , Cui Yan , Zhou Xiaoyu , Wang Ying
Published: May 2016

We compared and evaluated the performance of five methods for detecting abrupt climate changes using a time series with artificially generated abrupt characteristics. Next, we analyzed these methods using annual mean surface air temperature records from the Shenyang meteorological station. Our results show that the movingt-test (MTT), Yamamoto (YAMA), and LePage (LP) methods can correctly and effectively detect abrupt changes in means, trends, and dynamic structure; however, they cannot detect changes in variability. We note that the sample size of the subseries used in these tests can affect their results. When the sample size of the subseries ranges from one-quarter to three-quarters of the jump scale, these methods can effectively detect abrupt changes; they perform best when the sample size is one-half of the jump scale. The Cramer method can detect abrupt changes in the mean and trend of a series but not changes in variability or dynamic structure. Finally, we found that the Mann-Kendall test could not detect any type of abrupt change. We found no difference in the results of any of the methods following removal of the mean, creation of an anomaly series, or normalization. However, detrending and study period selection affected the results of the Cramer and Mann-Kendall methods; in the latter case, they could lead to a completely different result.
Energy Optimization for Outdoor Activity Recognition
Authors: Boukhechba Mehdi , Bouzouane Abdenour , Bouchard Bruno , Gouin-Vallerand Charles , Giroux Sylvain
Published: May 2016

The mobile phone is no longer only a communication device, but also a powerful environmental sensing unit that can monitor a user’s ambient context. Mobile users take their devices with them everywhere which increases the availability of persons’ traces. Extracting and analyzing knowledge from these traces represent a strong support for several applications domains, ranging from traffic management to advertisement and social studies. However, the limited battery capacity of mobile devices represents a big hurdle for context detection, no matter how useful the service may be. We present a novel approach to online recognizing users’ outdoor activities without depleting the mobile resources. We associate the places visited by individuals during their movements with meaningful human activities using a novel algorithm that clusters incrementally user’s moves into different types of activities. To optimize the battery consumption, the algorithm behaves variably on the basis of users’ behaviors and the remaining battery level. Studies using real GPS records from two big datasets demonstrate that the proposal is effective and is capable of inferring human activities without draining the phone resources.
LncRNA GClnc1 Promotes Gastric Carcinogenesis and May Act as a Modular Scaffold of WDR5 and KAT2A Complexes to Specify the Histone Modification Pattern
Authors: Sun Tian-Tian , He Jie , Liang Qian , Ren Lin-Lin , Yan Ting-Ting , Yu Ta-Chung , Tang Jia-Yin , Bao Yu-Jie , Hu Ye , Lin Yanwei , Sun Danfeng , Chen Ying-Xuan , Hong Jie , Chen Haoyan , Zou Weiping , Fang Jing-Yuan
Published: May 2016

Long noncoding RNAs (lncRNA) play a role in carcinogenesis. However, the function of lncRNAs in human gastric cancer remains largely unknown. In this study, we identified a novel lncRNA, GClnc1, which was upregulated and associated with tumorigenesis, tumor size, metastasis, and poor prognosis in gastric cancer. GClnc1 affected gastric cancer cell proliferation, invasiveness, and metastasis in multiple gastric cancer models. Mechanistically, GClnc1 bound WDR5 (a key component of histone methyltransferase complex) and KAT2A histone acetyltransferase, acted as a modular scaffold of WDR5 and KAT2A complexes, coordinated their localization, specified the histone modification pattern on the target genes, including SOD2, and consequently altered gastric cancer cell biology. Thus, GClnc1 is mechanistically, functionally, and clinically oncogenic in gastric cancer. Targeting GClnc1 and its pathway may be meaningful for treating patients with gastric cancer.

Significance: This report documents a novel lncRNA, GClnc1, which may act as a scaffold to recruit the WDR5 and KAT2A complex and modify the transcription of target genes. This study reveals that GClnc1 is an oncogenic lncRNA in human gastric cancer. Cancer Discov; 6(7); 784–801. ©2016 AACR.

This article is highlighted in the In This Issue feature, p. 681
Systematic Functional Interrogation of Rare Cancer Variants Identifies Oncogenic Alleles
Authors: Kim Eejung , Ilic Nina , Shrestha Yashaswi , Zou Lihua , Kamburov Atanas , Zhu Cong , Yang Xiaoping , Lubonja Rakela , Tran Nancy , Nguyen Cindy , Lawrence Michael S. , Piccioni Federica , Bagul Mukta , Doench John G. , Chouinard Candace R. , Wu Xiaoyun , Hogstrom Larson , Natoli Ted , Tamayo Pablo , Horn Heiko , Corsello Steven M. , Lage Kasper , Root David E. , Subramanian Aravind , Golub Todd R. , Getz Gad , Boehm Jesse S. , Hahn William C.
Published: May 2016

Cancer genome characterization efforts now provide an initial view of the somatic alterations in primary tumors. However, most point mutations occur at low frequency, and the function of these alleles remains undefined. We have developed a scalable systematic approach to interrogate the function of cancer-associated gene variants. We subjected 474 mutant alleles curated from 5,338 tumors to pooled in vivo tumor formation assays and gene expression profiling. We identified 12 transforming alleles, including two in genes (PIK3CB, POT1) that have not been shown to be tumorigenic. One rare KRAS allele, D33E, displayed tumorigenicity and constitutive activation of known RAS effector pathways. By comparing gene expression changes induced upon expression of wild-type and mutant alleles, we inferred the activity of specific alleles. Because alleles found to be mutated only once in 5,338 tumors rendered cells tumorigenic, these observations underscore the value of integrating genomic information with functional studies.

Significance: Experimentally inferring the functional status of cancer-associated mutations facilitates the interpretation of genomic information in cancer. Pooled in vivo screen and gene expression profiling identified functional variants and demonstrated that expression of rare variants induced tumorigenesis. Variant phenotyping through functional studies will facilitate defining key somatic events in cancer. Cancer Discov; 6(7); 714–26. ©2016 AACR.

See related commentary by Cho and Collisson, p. 694.

This article is highlighted in the In This Issue feature, p. 681
ПЕРВИННА ПРОФІЛАКТИКА АТОПІЧНИХ ЗАХВОРЮВАНЬ У ДІТЕЙ РАННЬОГО ВІКУ НА АНТЕНАТАЛЬНОМУ ЕТАПІ.
Authors: Vrublevska S. V.
Published: May 2016

Материнські алогенні та ксеногенні імуногени можуть спричинити сенсибілізацію плода за рахунок контакту його шкіри і
шлунково-кишкового тракту з амніотичною рідиною вже з 19-го тижня вагітності, таким чином підвищуючи ризик розвитку
гіперчутливості I та II типів. Відсутність доказів превентивного ефекту гіпоалергенної дієти в період вагітності відносно
алергічних захворювань у дітей не дозволяє рекомендувати виключення певних харчових продуктів з раціону вагітних при
наявності генетичного ризику атопії в дітей. Ми пропонуємо на антенатальному етапі комплекс профілактичних засобів,
який базується на виключенні контакту вагітних жінок, хворих на атопічне захворювання, тільки з причинно-вагомими
алергенами, та своєчасне лікування загострень алергічних захворювань у них. Споживання жінками різноманітних якісних
харчових продуктів під час вагітності тільки сприяє формуванню харчової толерантності в майбутніх немовлят і, тим самим,
є дієвим засобом профілактики атопії у дітей раннього віку.
КЛІНІЧНІ ПРОЯВИ КЛІМАКТЕРІЮ У ЖІНОК ІЗ ФІЗІОЛОГІЧНОЮ МЕНОПАУЗОЮ ПРИ ЗАСТОСУВАННІ НЕГОРМО - НАЛЬНИХ ПРЕПАРАТІВ.
Authors: Henyk N. I. , Hinchytska L. V. , Levytskyi I. V. , Neiko O. V. , Orishchak I. K.
Published: May 2016

Проведено клінічне та лабораторне обстеження пацієнток із фізіологічною менопаузою, з метою
визначення нейровегетативних, психоемоційних та обмінно-ендокринних порушень. Представлено результати клінічних
проявів клімаксу до та після застосування негормональних препаратів протягом трьох місяців.
ОЦІНКА ЕФЕКТИВНОСТІ ПРОФІЛАКТИКИ ПЕРВИННОЇ ПЛАЦЕНТАРНОЇ ДИСФУНКЦІЇ В РАННІ ТЕРМІНИ ГЕСТАЦІЇ ПРИ АНОМАЛЬНОМУ РОЗТАШУВАННІ ПЛАЦЕНТИ.
Authors: Kravchenko O. V. , Pecheriaha S. V.
Published: May 2016

Проаналізований перебіг вагітностей та пологів 64 вагітних із низьким
розташуванням хоріона, яким проводилася профілактика дисфункції плаценти в ранніх термінах гестації, та 55 жінок із низь-
кою плацентацією, яким не були призначені профілактичні заходи. Встановлено, що з метою покращення прогнозу перебігу
вагітності, а також профілактики ускладнень в ІІ та ІІІ триместрах гестації слід проводити лікувально-профілактичні заходи,
які спрямовані на попередження формування порушень фетоплацентарного комплексу в ранніх термінах вагітності.
ОЦІНКА ПОКАЗНИКІВ СПЕЦИФІЧНИХ БІЛКІВ ВАГІТНОСТІ ТА ДИНАМІКА ЇХ РІВНЯ В СИРОВАТЦІ КРОВІ У ВАГІТНИХ ІЗ ЛОКАЛЬНИМ НЕПРОГРЕСУЮЧИМ ВІДШАРУВАННЯМ ХОРІОН А ТА ПЛАЦЕНТИ.
Authors: Makarchuk O. M. , Rymarchuk M. I. , Vakalyuk L. M. , Drohomyretskyi L. V. , Cheredarchuk A. R.
Published: May 2016

 Існують повідомлення щодо певної діагностичної цінності специфічних білків плаценти як материнської, так і плодової її частини, що дозволяють всебічно оцінити взаємовідносини у фетоплацентарному комплексі. Було обстежено 120 жінок з епізодами відшарування плаценти в анамнезі або діагностованими ретрохоріальними та ретроплацентарними гематомами при даній вагітності, які входили в групу ризику щодо невиношування вагітності. Контрольну групу склали 30 жінок з неускладненим перебігом вагітності. Оцінювали рівень специфічних білків вагітності (вільного естріолу, хоріонічного гонадотропіну та РАРР-А) в сироватці крові пацієнток з
фізіологічною вагітністю та вагітністю, яка ускладнилася локальним непрогресуючим відшаруванням хоріона та плаценти, та їх коливання протягом першої половини гестаційного періоду. Що стосується концентрації білка вагітності РАРР-А в крові вагітних досліджуваних груп, варто відмітити у терміни 8–9 тижнів вагітності у 48,5 % пацієнток підвищення його вмісту
майже вдвічі порівняно з контролем. Отримані результати дозволяють трактувати, що фізіологічному перебігу вагітності властиві односпрямовані зміни даних маркерів: низьким концентраціям РАРР-А відповідають низькі рівні β-ХГЛ, у той час як високі рівні РАРР-А супроводжуються підвищеним вмістом β-ХГЛ і тільки різноспрямовані зміни, насамперед РАРР-А та
β-ХГЛ, дозволяють прогнозувати ускладнений перебіг вагітності.
БІОФІЗИЧНІ ПАРАМЕТРИ ФУНКЦІОНАЛЬНОЇ СИСТЕМИ МАТКА–ПЛАЦЕНТА–ПЛІД ПРИ ФІЗІОЛОГІЧНОМУ ПЕРЕБІГУ ЛАТЕНТНОЇ ФАЗИ ПЕРШОГО ПЕРІОДУ ПЕРЕДЧАСНИХ ПОЛОГІВ.
Authors: Markin L. B. , Hychka N. M.
Published: May 2016

 Вивчено основні біофізичні параметри, які відображають стан фетоплацентарної системи при фізіологічному перебігу латентної фази першого періоду передчасних пологів. Встановлено особливості скоротливої діяльності матки, внутрішньоматкової гемодинаміки, контрактильних змін нижнього маткового сегмента, стану матково-плацентарного кровообігу, життєдіяльності недоношеного плода при неускладнених передчасних пологах.
КОНТРАВЕРСІЙНІ ПОЗИЦІЇ В ДІАГНОСТИЦІ БАКВАГІНОЗУ У ВАГІТНИХ.
Authors: Nahornа V. F. , Hrytsenko A. A. , Moskalenko T. Ya.
Published: May 2016

Авторами на підставі обстеження 60 вагітних
із баквагінозом наведені значні розбіжності результатів різних діагностичних методів. Найбільш достовірним визнано вимірювання рН піхвового вмісту та виявлення збудників Gardherella vaginalis, Atopobium vaginalis за допомогою методів ДНК-технологій.
ЛІКУВАЛЬНО-ПРОФІЛАКТИЧНІ ЗАХОДИ ЩОДО ПОЛІПШЕННЯ КАЛЬЦІЙ-ФОСФОРНОГО ОБМІНУ ТА КІСТКОВОГО МЕТАБОЛІЗМУ У ЖІНОК З ДЕФІЦИТОМ МАСИ ТІЛА, ЯКІ ПЛАНУЮТЬ ВАГІТНІСТЬ.
Authors: Shelestovа L. P. , Allakhverdiyev R. S.
Published: May 2016

Включення карбонату кальцію та холекальциферолу і лікувального харчування до комплексу лікувально-профілактичних заходів щодо жінок з дефіцитом
маси тіла, які планують вагітність, має позитивний вплив на вміст загального кальцію і кальцієрегулювальних гормонів
(паратгормону, остеокальцину і вітаміну D), тобто спостерігається їх нівелювання з показниками жінок за нормальної маси тіла, чого не відбувається при традиційному веденні пацієнток.
АКТУАЛЬНІ ПИТАННЯ ОРГАНІЗАЦІЇ ПІДГОТОВКИ КАДРІВ У СФЕРІ ОХОРОНИ ЗДОРОВ’Я
Authors: Hryhorovska S. V. , Pyatnytskyi Yu. S. , Volosovets O. P. , Hasiuk H. I. , Petrova K. I.
Published: May 2016

У статті окреслено основні завдання, які стоять перед Міністерством охорони здоров’я та вищою медичною освітою щодо належного кадрового забезпечення системи охорони здоров’я та якості підготовки медичного персоналу. Вони можуть бути вирішені за умови впровадження сучасних стандартів підготовки медичних та фармацевтичних кадрів, розвитку віртуальної освіти та самоосвіти медиків, подальшого створення мережі університетських клінік та лікарень. Розподіл випускників здійснюється МОЗ України відповідно до потреб та пріоритетів галузі для першочергового забезпечення первинної та вторинної ланок сфери охорони здоров’я лікарськими кадрами. Ефективне використання наявних кадрових ресурсів в охороні здоров’я є спільним завданням регіонів та Міністерства охорони здоров’я України.
РАЦІОНАЛЬНІ НАВЧАЛЬНІ ПЛАНИ ЯК ЗАПОРУКА ЯКІСНОЇ ПІДГОТОВКИ МАГІСТРІВ ЗА СПЕЦІАЛЬНІСТЮ “МЕДИЦИНА”
Authors: Dumanskyi Yu. V. , Kondratenko P. H. , Konkova M. V. , Kietinh O. V.
Published: May 2016

Основним пріоритетом розвитку сучасної медичної освіти є постійне вдосконалення навчально-методичних підходів до підготовки лікарів, внесення доповнень та змін до робочих навчальних планів і програм відповідно до потреб практичної охорони здоров’я. Скорочення кількості аудиторних годин відповідно до Закону України “Про вищу освіту” зумовлює необхідність відповідального ставлення до їх розподілу між навчальними дисциплінами. Вища медична освіта – досить специфічний та несхожий на інші освітній процес. Вже з 1 курсу студенти-медики повинні отримувати великий обсяг базисних медичних знань та вмінь.

У роботі висвітлено основні проблеми розподілу аудиторних годин між курсами та навчальними дисциплінами: штучно збільшена або, навпаки, недостатня кількість виділених на предмет годин, дублювання однієї і тієї ж тематики на різних кафедрах при її викладанні у складі різних дисциплін, відсутність послідовності подачі матеріалу, недостатня сучасність та розірваність отриманих студентами медичних знань. Вказане нераціональне використання аудиторних годин є неприпустимим. Автори припускають, що частковий перерозподіл годин може виявитися дуже корисним.

Якісна підготовка лікарів значною мірою залежить від раціонального використання наявних аудиторних годин, що можливо тільки за умови перегляду робочих навчальних планів підготовки фахівців з урахуванням принципу послідовного, логічного та сучасного викладання дисциплін у медичному університеті.
КОМПЕТЕНТНІСНИЙ ПІДХІД У СТВОРЕННІ СТАНДАРТУ ВИЩОЇ ОСВІТИ СПЕЦІАЛЬНОСТІ “ФАРМАЦІЯ”
Authors: Chernykh V. P. , Kotvitska A. A. , Ohar S. V.
Published: May 2016

 Створення галузевих стандартів вищої фармацевтичної освіти нового покоління на основі компетентнісного підходу є необхідним етапом на шляху підготовки сучасного фахівця, якого потребує практична фармація.

До роботи над стандартом, крім робочої групи, визначеної наказом МОЗ України від 06.11.2015 р. № 733, були залучені фахівці практичної фармації, чия думка є невід’ємним компонентом при створенні державного стандарту, що відповідав би усім європейським вимогам. Проведено соціологічне опитування фахівців практичної фармації щодо загальних та професійних компетентностей випускника, результати якого впроваджено до стандарту вищої освіти спеціальності “Фармація”.
ВИКОРИСТАННЯ МЕТОДИК СИМУЛЯЦІЙНОГО НАВЧАННЯ У ПІДВИЩЕННІ ПРОФЕСІЙНОЇ КОМПЕТЕНЦІЇ ЛІКАРІВ ТА ПАРАМЕДИКІВ НА КАФЕДРАХ ДЗ “ЗМАПО МОЗ УКРАЇНИ”
Authors: Nykonenko O. S. , Shapoval S. D. , Dmytriyeva S. M. , Hrytsun T. O.
Published: May 2016

У статті представлено аналіз та роль симуляційних методик, впроваджених на кафедрах ДЗ “ЗМАПО МОЗ України”, та оцінку отриманих лікарями компетенцій за класифікацією Блума. Показано, що використання симуляційних методик дозволяє відтворити тісний зв’язок навчального процесу з практикою і максимальну реалістичність клінічної ситуації у післядипломній освіті лікарів.
ДЕЯКІ АСПЕКТИ СУЧАСНОЇ ПЕДАГОГІКИ МЕДИЧНОЇ ОСВІТИ
Authors: Dereziuk A. V.
Published: May 2016

У статті узагальнено матеріали педагогічних видань 2012–2014 років. Основну увагу звернено на публікації учасників ІХ Міжнародної науково-методичної конференції “Духовна культура особистості та її інноваційні основні технології: виклики ХХІ століття”. Для дослідження обрано виступи викладачів вищих медичних навчальних закладів, у яких наголошено на таких аспектах педагогічної освіти як: роль інноваційних засобів і технологій у процесі навчально-виховної роботи, психолого-педагогічна компетентність і мобільність майбутнього лікаря, вимоги до викладача сучасного вузу та ін.
ЄВРОПЕЙСЬКІ СТАНДАРТИ ПІДГОТОВКИ СУЧАСНИХ ФАХІВЦІВ-МЕДИКІВ ВІДПОВІДНО ДО ВИМОГ БОЛОНСЬКОЇ ДЕКЛАРАЦІЇ
Authors: Malakhova S. М.
Published: May 2016

У статті розглянуто питання самостійної роботи студентів, як важливої складової сучасної вищої медичної освіти. Розглянуто види самостійної роботи, проблемні питання.
КЕЙС-МЕТОД НАВЧАННЯ У МЕДИЧНІЙ ОСВІТІ
Authors: Pavlyshyn H. A. , Bihunyak T. V. , Savaryn T. V.
Published: May 2016

Статтю присвячено проблемі використання кейс-методу як інтерактивного методу навчання у медичній освіті. Розглядається історія виникнення, класифікація та види демонстрації кейсів, етапи роботи з сase-study методом, проблема інтерактивності та доцільності використання даного методу під час навчання студентів-медиків.
Relendo Walter Benjamin: etnografia da música, disco e inconsciente auditivo
Authors: Schouten André-Kees De Moraes , Cirino Giovanni
Published: May 2016

Conforme Walter Benjamin apontouem seu ensaio “A obra de arte na era da sua reprodu- tibilidade técnica”, diante das modernas técnicas de reprodução a arte vê-se destituída de sua aura, fun- damento de sua autenticidade. Para o autor, só seria possível mostrar as condições sociais de tal decadên- cia entendendo-a não como perda de importância da arte no mundo moderno, mas sim como alte- rações no medium de percepção contemporâneo. Tratando do cinema e da fotografia, diz Benjamin que a reprodução técnica tanto autonomiza a arte de sua existência no ritual, inserido-a agora numa práxis política, como as obras que reproduz permi- tem acessar o inconsciente óptico da sociedade mo- derna. Partindo das sugestivas idéias deste autor, e tomando como objeto de reflexão o disco, procura- mos nesse trabalho explorar algumas possibilidades de tratamento etnográfico do material fonográfico no âmbito de uma etnografia da música, procuran- do neste material algo além de sua capacidade de testar hipóteses.
The Time and the Other: how anthropology makes its object
Authors: Lobão Ronaldo
Published: May 2016

FABIAN, Johannes. The Time and the Other: how anthropology makes its object.Por que fazer a resenha da segunda edição em língua inglesa de um texto publicado pela primeira vez em 1983? De alguma forma a resposta está contida na própria pergunta, pois já se passaram mais de 20 anos e este livro seminal de Johannes Fabian ainda não foi publicado em português! Não que ele não circule nos meios acadêmicos nacionais, mas se mantém restrito a um público necessariamente bilíngüe, quem sabe para que o poder de sua crítica não ameace formações não consolidadas.
“Filhos do Rei Sebastião”, “Filhos da Lua”: construções simbólicas sobre os nativos da Ilha dos Lençóis
Authors: Pereira Madian De Jesus Frazão
Published: May 2016

Este artigo aborda a construção doimaginário de uma ilha considerada “encantada”: a Ilha dos Lençóis, no Estado do Maranhão. Apresen- ta uma simbologia sobre os ilhéus, principalmente acerca daqueles singularizados por marcas corporais, os albinos. Enfatiza a compreensão explicativa das práticas discursivas do “universo de fora” (sobretu- do matérias veiculadas na imprensa de uma manei- ra geral) e do “universo de dentro” (representações nativas) sobre duas denominações que sintetizam o imaginário sobre os albinos da Ilha dos Lençóis: “fi- lhos da Lua” e “filhos do Rei Sebastião”.
Adipose Tissue Depots and Their Cross‐Sectional Associations With Circulating Biomarkers of Metabolic Regulation
Authors: Lee Jane J. , Britton Kathryn A. , Pedley Alison , Massaro Joseph M. , Speliotes Elizabeth K. , Murabito Joanne M. , Hoffmann Udo , Ingram Cheryl , Keaney John F. , Vasan Ramachandran S. , Fox Caroline S.
Published: May 2016

Background

Visceral adipose tissue (
VAT
) and fatty liver differ in their associations with cardiovascular risk compared with subcutaneous adipose tissue (
SAT
). Several biomarkers have been linked to metabolic derangements and may contribute to the pathogenicity of fat depots. We examined the association between fat depots on multidetector computed tomography and metabolic regulatory biomarkers.

Methods and Results

Participants from the Framingham Heart Study (n=1583, 47% women) underwent assessment of
SAT
,
VAT
, and liver attenuation. We measured circulating biomarkers secreted by adipose tissue or liver (adiponectin, leptin, leptin receptor, fatty acid binding protein 4, fetuin‐A, and retinol binding protein 4). Using multivariable linear regression models, we examined relations of fat depots with biomarkers. Higher levels of fat depots were positively associated with leptin and fatty acid binding protein 4 but negatively associated with adiponectin (all
P
<0.001). Associations with leptin receptor, fetuin‐A, and retinol binding protein 4 varied according to fat depot type or sex. When comparing the associations of
SAT
and
VAT
with biomarkers,
VAT
was the stronger correlate of adiponectin (β=−0.28 [women]; β=−0.30 [men]; both
P
<0.001), whereas
SAT
was the stronger correlate of leptin (β=0.62 [women]; β=0.49 [men]; both
P
<0.001;
P
<0.001 for comparing
VAT
versus
SAT
). Although fetuin‐A and retinol binding protein 4 are secreted by the liver in addition to adipose tissue, associations of liver attenuation with these biomarkers was not stronger than that of
SAT
or
VAT
.

Conclusions

SAT
,
VAT
, and liver attenuation are associated with metabolic regulatory biomarkers with differences in the associations by fat depot type and sex. These findings support the possibility of biological differences between fat depots.
Deal or No Deal? The End of the Cold War and the U.S. Offer to Limit NATO Expansion
Authors: Shifrinson Joshua R. Itzkowitz
Published: May 2016

Did the United States promise the Soviet Union during the 1990 negotiations on German reunification that NATO would not expand into Eastern Europe? Since the end of the Cold War, an array of Soviet/Russian policymakers have charged that NATO expansion violates a U.S. pledge advanced in 1990; in contrast, Western scholars and political leaders dispute that the United States made any such commitment. Recently declassified U.S. government documents provide evidence supporting the Soviet/Russian position. Although no non-expansion pledge was ever codified, U.S. policymakers presented their Soviet counterparts with implicit and informal assurances in 1990 strongly suggesting that NATO would not expand in post–Cold War Europe if the Soviet Union consented to German reunification. The documents also show, however, that the United States used the reunification negotiations to exploit Soviet weaknesses by depicting a mutually acceptable post–Cold War security environment, while actually seeking a system dominated by the United States and opening the door to NATO's eastward expansion. The results of this analysis carry implications for international relations theory, diplomatic history, and current U.S.-Russian relations.