bluuebunny/crossref_metadata_2025 huggingface dataset:
Snow and ice products from Suomi NPP VIIRS
Authors: Key Jeffrey R. , Mahoney Robert , Liu Yinghui , Romanov Peter , Tschudi Mark , Appel Igor , Maslanik James , Baldwin Dan , Wang Xuanji , Meade Paul
Published: November 2013

The Visible Infrared Imager Radiometer Suite (VIIRS) instrument was launched in October 2011 on the satellite now known as the Suomi National Polar‐orbiting Partnership. VIIRS was designed to improve upon the capabilities of the operational Advanced Very High Resolution Radiometer and provide observation continuity with NASA's Earth Observing System's Moderate Resolution Imaging Spectroradiometer (MODIS). VIIRS snow and ice products include sea ice surface temperature, sea ice concentration, sea ice characterization, a binary snow map, and fractional snow cover. Validation results with these “provisional” level maturity products show that ice surface temperature has a root‐mean‐square error of 0.6–1.0 K when compared to aircraft data and a similar MODIS product, the measurement accuracy and precision of ice concentration are approximately 5% and 15% when compared to passive microwave retrievals, and the accuracy of the binary snow cover (snow/no‐snow) maps is generally above 90% when compared to station data. The ice surface temperature and snow cover products meet their accuracy requirements with respect to the Joint Polar Satellite System Level 1 Requirements Document. Sea Ice Characterization, which consists of two age categories, has not been observed to meet the 70% accuracy requirements of ice classification. Given their current performance, the ice surface temperature, snow cover, and sea ice concentration products should be useful for both research and operational applications, while improvements to the sea ice characterization product are needed before it can be used for these applications.
Chiral N,N′‐Dioxide–Yttrium Triflate Complexes‐Catalyzed Asymmetric Aldol Cyclization of α‐Keto Esters with α‐Isothiocyanato Imide
Authors: Zhao Xiaohu , Xie Mingsheng , Liu Xiaohua , Zhang Yulong , Xiao Xiao , Lin Lili , Feng Xiaoming
Published: November 2013

A highly effective aldol cyclization of α‐isothiocyanato imide to both β,γ‐unsaturated α‐keto esters and aryl‐substituted α‐keto esters has been developed. A chiral N,N′‐dioxide–yttrium triflate complex was used as the catalyst. A series of cyclic thiocarbamates bearing chiral quaternary stereocenters was synthesized in good to high yields, excellent diastereo‐ (up to 25:1 dr) and enantioselectivities (up to 99 % ee). In addition, the reaction could be carried out on a gram‐scale, and other functionalized derivatives are also conveniently transformed. Interestingly, a discrepancy of diastereoselection was observed between the reactions of β,γ‐unsaturated α‐keto esters and aryl‐substituted α‐keto esters. Moreover, a substrate dependency of non‐linear effects was observed in this reaction. On the basis of the experimental results and the absolute configuration of the products, possible catalytic models have been proposed to explain the origin of the asymmetric process.

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Detection of an ABCA1 variant associated with type 2 diabetes mellitus susceptibility for biochemistry and genetic laboratory courses
Authors: Legorreta‐Herrera M. , Mosqueda‐Romo N.A. , Hernández‐Clemente F. , Soto‐Cruz I.
Published: November 2013

We selected diabetes mellitus for this laboratory exercise to provide students with an explicit model for scientific research concerning the association between the R230C polymorphism and susceptibility to type 2 diabetes mellitus, which is highly prevalent in the Mexican population. We used a collaborative project‐based learning to engage students to direct their own learning process. Students worked in small groups with the same learning goal to research, organize data, and present seminars to experimentally genotype the C230 variant and correctly interpret their results. At the conclusion of this laboratory exercise, the students were able to demonstrate a clear understanding of the relevant biological molecular principles to genotype the C230 variant, showed technical competency to carry out the experimental protocols with proficiency, and interpret their results using statistical analyses. The students discussed their understanding of the genetic technologies and the broader social and ethical implications of the research. A randomly selected team was trained to work as a “sentinel” to monitor their classmates and ensure the proper application of techniques. Moreover, the evaluation of this exercise is shared between the students and the instructors; the students evaluate their own work and the performance of their classmates. At the end of the course, the students complete a questionnaire to anonymously provide feedback and information regarding their perception of the learning outcomes. Overall, the student feedback was positive, indicating that the exercise was useful and that it would help to prepare the students for professional practice. © 2013 by The International Union of Biochemistry and Molecular Biology, 41(6):409–418, 2013
Molecular mechanics and dynamics characterization of an in silico mutated protein: A stand‐alone lab module or support activity for in vivo and in vitro analyses of targeted proteins
Authors: Chiang Harry , Robinson Lucy C. , Brame Cynthia J. , Messina Troy C.
Published: November 2013

Over the past 20 years, the biological sciences have increasingly incorporated chemistry, physics, computer science, and mathematics to aid in the development and use of mathematical models. Such combined approaches have been used to address problems from protein structure–function relationships to the workings of complex biological systems. Computer simulations of molecular events can now be accomplished quickly and with standard computer technology. Also, simulation software is freely available for most computing platforms, and online support for the novice user is ample. We have therefore created a molecular dynamics laboratory module to enhance undergraduate student understanding of molecular events underlying organismal phenotype. This module builds on a previously described project in which students use site‐directed mutagenesis to investigate functions of conserved sequence features in members of a eukaryotic protein kinase family. In this report, we detail the laboratory activities of a MD module that provide a complement to phenotypic outcomes by providing a hypothesis‐driven and quantifiable measure of predicted structural changes caused by targeted mutations. We also present examples of analyses students may perform. These laboratory activities can be integrated with genetics or biochemistry experiments as described, but could also be used independently in any course that would benefit from a quantitative approach to protein structure–function relationships. © 2013 by The International Union of Biochemistry and Molecular Biology, 41(6):402–408, 2013
Over The Counter Drugs (and Dietary Supplement) Exercise: A Team‐Based Introduction to Biochemistry for Health Professional Students
Authors: Phadtare Sangita , Abali Emine , Brodsky Barbara
Published: November 2013

For successful delivery of basic science topics for health‐professional students, it is critical to reduce apprehension and illustrate relevance to clinical settings and everyday life. At the beginning of the Biochemistry course for Physician Assistants, a team‐based assignment was designed to develop an understanding of the mechanism of action, effectiveness, and toxicity of five common over the counter (OTC) drugs and dietary supplements, and place these familiar medicines in a political and historical context. The objectives of this exercise were to stimulate interest in biochemistry; to provide basic information on enzymes and enzyme inhibitors related to these drugs to be expanded upon later in the course; and to encourage active and interactive learning. Teams of five students were formed, and each student was given an information sheet on aspirin, alpha‐galactosidase, orlistat, dextromethorphan, or simvastatin, a low dose statin, which was previously available without prescription at pharmacies in the UK. After each member of the team acquired information on one OTC drug/dietary supplement by reading an assigned information sheet, the team was asked to go through a series of questions, and then submit answers to a quiz as a group. A high rate of success on the quiz, an overwhelmingly positive response on formal course evaluations, and enthusiastic exchanges during class suggested this team‐based session accomplished its goals. © 2013 by The International Union of Biochemistry and Molecular Biology, 41(6):384–387, 2013
Continuous In Vitro evolution of a ribozyme ligase: A model experiment for the evolution of a biomolecule
Authors: Ledbetter Michael P. , Hwang Tony W. , Stovall Gwendolyn M. , Ellington Andrew D.
Published: November 2013

Evolution is a defining criterion of life and is central to understanding biological systems. However, the timescale of evolutionary shifts in phenotype limits most classroom evolution experiments to simple probability simulations. In vitro directed evolution (IVDE) frequently serves as a model system for the study of Darwinian evolution but produces noticeable phenotypic shifts in a matter of hours. An IVDE demonstration lab would serve to both directly demonstrate how Darwinian selection can act on a pool of variants and introduce students to an essential method of modern molecular biology. To produce an IVDE demonstration lab, continuous IVDE of a T500 ribozyme ligase population has been paired with a fluorescent strand displacement reporter system to visualize the selection of improved catalytic function. A ribozyme population is taken through rounds of isothermal amplification dependent on the self‐ligation of a T7 promoter. As the population is selectively enriched with better ligase activity, the strand displacement system allows for the monitoring of the population's ligation rate. The strand displacement reporter system permits the detection of ligated ribozyme. Once ligated with the T7 promoter, the 5′ end of the ribozyme displaces paired fluorophore‐quencher oligonucleotides, in turn, generating visible signal upon UV light excitation. As the ligation rate of the population increases, due to the selection for faster ligating species, the fluorescent signal develops more rapidly. The pairing of the continuous isothermal system with the fluorescent reporting scheme allows any user, provided with minimal materials, to model the continuous directed evolution of a biomolecule. © 2013 by The International Union of Biochemistry and Molecular Biology, 41(6):433–442, 2013
Tibio‐pedal arterial minimally invasive retrograde revascularization in patients with advanced peripheral vascular disease: The TAMI technique, original case series
Authors: Mustapha J.A. , Saab Fadi , McGoff Theresa , Heaney Carmen , Diaz‐Sandoval Larry , Sevensma Matthew , Karenko Barbara
Published: November 2013

Background

A tibial‐pedal access method is needed for patients with advanced peripheral artery disease (PAD) unable to tolerate common femoral artery (CFA) access and intervention due to body habitus or comorbidities. This is the first case series reporting an alternative technique to revascularize such patients. Using ultrasound (US) and the tibio‐pedal arterial minimally invasive retrograde revascularization (TAMI) technique, operators accessed, and revascularized the lower extremity completely via tibial‐pedal arterial access.

Methods

This retrospective, single‐center, case series recorded on 23 patients who underwent TAMI revascularization during a seven‐month period in 2012, demonstrating the feasibility and safety of the TAMI technique. Eighty‐three percent had Rutherford Classification IV–VI. Ultrasound guidance aided all tibial access. Demographics, vascular symptoms, disease characteristics, success, procedure length, time to discharge, immediate and 30‐day complications were collected. Comparison was sought with 201 unmatched patients treated via traditional CFA access over a similar period.

Results

Arterial access was successful in all patients. Thirty‐six lesions were treated. Lesion success (ability to cross lesion and achieve post treatment stenosis <30%) was achieved in 95% of patients. 25% of lesions were above the knee. Average prestenosis was 92.5%; average poststenosis 12%. No major complications were noted. Two patients presented within 30 days with access site pain. Access site peroneal artery pseudo‐aneurysms were diagnosed and treated percutaneously with covered stents. Both recovered with no sequelae.

Conclusion

Retrograde tibio‐pedal intervention appears to be safe and effective. The TAMI technique offers an alternate revascularization method for critically ill advanced PAD patients. © 2013 Wiley Periodicals, Inc.
Significance of the learning curve in left atrial appendage occlusion with two different devices
Authors: Cruz‐Gonzalez Ignacio , Perez‐Rivera Angel , Lopez‐Jimenez Rosana , Rodriguez‐Collado Javier , Martín‐Moreiras Javier , Cascon Manuel , Arribas Antonio , Gomez Jose Carlos , Maree Andrew O. , Martin‐Luengo Candido
Published: November 2013

Objective

To evaluate the impact of learning on outcome with use of two different left atrial appendage (LAA) occlusion devices.

Background

Two self‐expanding devices, the Watchman and the Amplatzer Cardiac Plug (ACP), have been used for LAA occlusion in the last few years. It has been demonstrated that complications associated with implantation decrease in frequency with operator experience. However, the role of operator experience has not been compared across the two device types.

Methods

The study comprises 31 consecutive patients who underwent LAA occlusion. We compare the first 10 patients in whom an ACP was implanted with the subsequent eleven patients who underwent ACP implantation and with 10 cases where a Watcthman device was implanted. The composite safety end point comprised procedure‐related events and excessive bleeding events. We also performed 3 months echocardiographic and clinical follow‐up.

Results

There were not significant differences in the basal clinical and echocardiographical characteristics across the three groups. Cardiac complications only occurred in the ACP initial experience group (9% vs. 0% vs. 0% P = 0.04). Echocardiographic and clinical follow‐up at 3 months was completed in all patients. No significant residual leak was detected. One patient in the ACP initial experience group developed a thrombus on the device. One patient in ACP late experience presented an ischemic stroke.

Conclusions

Complications associated with LAA occlusion cluster early in the peri‐procedural period and significantly decrease in frequency with operator experience. Initial experience gained with one of device may improve outcome with use of alternative LAA occlusion devices. © 2013 Wiley Periodicals, Inc.
Catheter extraction of high risk right atrial clot, technical tips, and lessons learned. successes and failures
Authors: Kassas Safwan
Published: November 2013

Floating right atrial (RA) thrombus in the presence of intracardiac shunting, patent foramen ovale (PFO), or atrial septal defect is a complex clinical challenge. Surgical thrombectomy, thrombolytic therapy, and long‐term anticoagulation are all available management options. However, surgical therapy and thrombolytic therapy both carry significant inherent risk and there is lack of data to support adequacy and efficacy of long‐term anticoagulation. We report for the first time a case of a large free floating RA thrombus in the presence of a large PFO in a patient where surgical intervention and thrombolytic therapy were both felt to be contraindicated. A combined AngioVac thrombectomy procedure and a PFO closure were performed simultaneously and successfully without the fragmentation of the clot or the protrusion and migration of the clot systemically through the large PFO. A second case without the associated presence of a PFO is also being reported where the procedure failed to extract the thrombus. © 2013 Wiley Periodicals, Inc.
The impact of regulatory approval and Medicare coverage on outcomes of carotid stenting
Authors: Gray William A. , Verta Patrick
Published: November 2013

Background

Carotid artery stenting (CAS) was introduced in the United States nearly a decade ago as a novel treatment of severe carotid stenosis. Voluminous and high‐quality prospective data permit analysis of longitudinal trends in CAS outcomes.

Methods

Outcomes from all prospective trials with the Food and Drug Administration (FDA) oversight from 2000–2011 were reviewed, as were the subset of studies using a single CAS system. All studies shared common inclusion/exclusion criteria, endpoints, independent assessment/adjudication of neurological events, and were conducted in accordance with FDA regulations. Death and stroke (DS) rates from FDA‐approved studies in high‐surgical‐risk patients were assessed.

Results

Between 2000 and 2011, two distinct periods with clustered and differentiated outcomes in CAS IDE trials were observed, separated by FDA approval and Centers for Medicare and Medicaid Services (CMS) coverage in 2004–2005. The mean 30‐day DS rate in the first wave (2000–2004) of CAS trials was 5.3% (95% CI: 4.6–6.2%), and fell significantly to 2.6% (95% CI: 1.9–3.7%; P = 0.0001) in the second wave (2006–2011). This decline occurred during a simultaneous, independent 24‐fold increase in monitored CAS activity. This decline in DS rates was observed in symptomatic and asymptomatic patients, alike independent of device tested.

Conclusions

Declines in periprocedural DS rates in CAS appear linked to regulatory and coverage approvals leading to increased operator experience along with continued regulatory oversight, and provide insight into the introduction of other novel therapies. © 2013 Wiley Periodicals, Inc.
Subdivisions and connectional networks of the lateral prefrontal cortex in the macaque monkey
Authors: Saleem Kadharbatcha S. , Miller Brad , Price Joseph L.
Published: November 2013

Neuroanatomical studies have long indicated that corticocortical connections are organized in networks that relate distinct sets of areas. Such networks have been emphasized by development of functional imaging methods for correlating activity across the cortex. Previously, two networks were recognized in the orbitomedial prefrontal cortex, the “orbital” and “medial” networks (OPFC and MPFC, respectively). In this study, three additional networks are proposed for the lateral prefrontal cortex: 1) a ventrolateral network (VLPFC) in and ventral to the principal sulcus; 2) a dorsal network (DPFC) in and dorsal to the principal sulcus and in the frontal pole; 3) a caudolateral network (CLPFC) in and rostral to the arcuate sulcus and the caudal principal sulcus. The connections of the first two networks are described here. Areas in each network are connected primarily with other areas in the same network, with overlaps around the principal sulcus. The VLPFC and DPFC are also connected with the OPFC and MPFC, respectively. Outside the prefrontal cortex, the VLPFC connects with specific areas related to somatic/visceral sensation and vision, in the frontoparietal operculum, insula, ventral bank/fundus of the superior temporal sulcus, inferior temporal gyrus, and inferior parietal cortex. In contrast, the DPFC connects with the rostral superior temporal gyrus, dorsal bank of the superior temporal sulcus, parahippocampal cortex, and posterior cingulate and retrosplenial cortex. Area 45a, in caudal VLPFC, is unique, having connections with all the networks. Its extrinsic connections resemble those of the DPFC. In addition, it has connections with both auditory belt/parabelt areas, and visual related areas. J. Comp. Neurol. 522:1641–1690, 2014. © 2013 Wiley Periodicals, Inc.
Connectivity of somatosensory cortical area 1 forms an anatomical substrate for the emergence of multifinger receptive fields and complex feature selectivity in the squirrel monkey (Saimiri sciureus)
Authors: Ashaber Mária , Pálfi Emese , Friedman Robert M. , Palmer Cory , Jákli Balázs , Chen Li Min , Kántor Orsolya , Roe Anna W. , Négyessy László
Published: November 2013

Converging evidence shows that interaction of digit‐specific input, which is required to form global tactile percepts, begins as early as area 3b in the primary somatosensory cortex with the involvement of intrinsic lateral connections. How tactile processing is further elaborated in area 1, the next stage of the somatosensory cortical hierarchy, is less understood. This question was investigated by studying the tangential distribution of intrinsic and interareal connections of finger representations of area 1. Retrogradely labeled cell densities and anterogradely labeled fibers and terminal patches were plotted and quantified with respect to the hand representation by combining tract tracing with electrophysiological mapping and intrinsic signal optical imaging in somatosensory areas. Intrinsic connections of distal finger pad representations of area 1 spanned the representation of multiple digits indicating strong cross‐digit connectivity. Area 1 distal finger pad regions also established high‐density connections with homotopic regions of areas 3b and 2. Although similar to area 3b, connections of area 1 distributed more widely and covered a larger somatotopic representation including more proximal parts of the finger representations. The lateral connectivity pattern of area 1 is a suitable anatomical substrate of the emergence of multifinger receptive fields, complex feature selectivity, and invariant stimulus properties of the neurons. J. Comp. Neurol. 522:1769–1785, 2014. © 2013 Wiley Periodicals, Inc.
PKG in honey bees: Spatial expression, Amfor gene expression, sucrose responsiveness, and division of labor
Authors: Thamm Markus , Scheiner Ricarda
Published: November 2013

Division of labor is a hallmark of social insects. In honey bees, division of labor involves transition of female workers from one task to the next. The most distinct tasks are nursing (providing food for the brood) and foraging (collecting pollen and nectar). The brain mechanisms regulating this form of behavioral plasticity have largely remained elusive. Recently, it was suggested that division of labor is based on nutrition‐associated signaling pathways. One highly conserved gene associated with food‐related behavior across species is the foraging gene, which encodes a cyclic guanosine monophosphate (cGMP)‐dependent protein kinase (PKG). Our analysis of this gene reveals the presence of alternative splicing in the honey bee. One isoform is expressed in the brain. Expression of this isoform is most pronounced in the mushroom bodies, the subesophageal ganglion, and the corpora allata. Division of labor and sucrose responsiveness in honey bees correlate significantly with foraging gene expression in distinct brain regions. Activating PKG selectively increases sucrose responsiveness in nurse bees to the level of foragers, whereas the same treatment does not affect responsiveness to light. These findings demonstrate a direct link between PKG signaling in distinct brain areas and division of labor. Furthermore, they demonstrate that the difference in sensory responsiveness between nurse bees and foragers can be compensated for by activating PKG. Our findings on the function of PKG in regulating specific sensory responsiveness and social organization offer valuable indications for the function of the cGMP/PKG pathway in many other insects and vertebrates. J. Comp. Neurol. 522:1786–1799, 2014. © 2013 Wiley Periodicals, Inc.
Longitudinal in vivo two‐photon fluorescence imaging
Authors: Crowe Sarah E. , Ellis‐Davies Graham C.R.
Published: November 2013

Fluorescence microscopy is an essential technique for the basic sciences, especially biomedical research. Since the invention of laser scanning confocal microscopy in the 1980s, which enabled imaging both fixed and living biological tissue with 3D precision, high‐resolution fluorescence imaging has revolutionized biological research. Confocal microscopy, by its very nature, has one fundamental limitation. Due to the confocal pinhole, deep tissue fluorescence imaging is not practical. In contrast (no pun intended), two‐photon fluorescence microscopy allows, in principle, the collection of all emitted photons from fluorophores in the imaged voxel, dramatically extending our ability to see deep into living tissue. Since the development of transgenic mice with genetically encoded fluorescent protein in neocortical cells in 2000, two‐photon imaging has enabled the dynamics of individual synapses to be followed for up to 2 years. Since the initial landmark contributions to this field in 2002, the technique has been used to understand how neuronal structure are changed by experience, learning, and memory and various diseases. Here we provide a basic summary of the crucial elements that are required for such studies, and discuss many applications of longitudinal two‐photon fluorescence microscopy that have appeared since 2002. J. Comp. Neurol. 522:1708–1727, 2014. © 2013 Wiley Periodicals, Inc.
Organization and cellular arrangement of two neurogenic regions in the adult ferret (Mustela putorius furo) brain
Authors: Takamori Yasuharu , Wakabayashi Taketoshi , Mori Tetsuji , Kosaka Jun , Yamada Hisao
Published: November 2013

In the adult mammalian brain, two neurogenic regions have been characterized, the subventricular zone (SVZ) of the lateral ventricle (LV) and the subgranular zone (SGZ) of the dentate gyrus (DG). Despite remarkable knowledge of rodents, the detailed arrangement of neurogenic regions in most mammals is poorly understood. In this study, we used immunohistochemistry and cell type‐specific antibodies to investigate the organization of two germinal regions in the adult ferret, which belongs to the order Carnivora and is widely used as a model animal with a gyrencephalic brain. From the SVZ to the olfactory bulb, doublecortin‐positive cells tended to organize in chain‐like clusters, which are surrounded by a meshwork of astrocytes. This structure is homologous to the rostral migratory stream (RMS) described in other species. Different from rodents, the horizontal limb of the RMS emerges directly from the LV, and the anterior region of the LV extends rostrally and reached the olfactory bulb. In the DG, glial fibrillary acidic protein‐positive cells with long radial processes as well as doublecortin‐positive cells are oriented in the SGZ. In both regions, doublecortin‐positive cells showed characteristic morphology and were positive for polysialylated‐neural cell adhesion molecule, beta‐III tubulin, and lamin B1 (intense staining). Proliferating cells were detected in both regions using antibodies against proliferating cell nuclear antigen and phospho‐histone H3. These observations demonstrate that the two neurogenic regions in ferrets have a similar cellular composition as those of other mammalian species despite anatomical differences in the brain. J. Comp. Neurol. 522:1818–1838, 2014. © 2013 Wiley Periodicals, Inc.
Wnt‐signaling and planar cell polarity genes regulate axon guidance along the anteroposterior axis in C. elegans
Authors: Ackley Brian D.
Published: November 2013

During the development of the nervous system, neurons encounter signals that inform their outgrowth and polarization. Understanding how these signals combinatorially function to pattern the nervous system is of considerable interest to developmental neurobiologists. The Wnt ligands and their receptors have been well characterized in polarizing cells during asymmetric cell division. The planar cell polarity (PCP) pathway is also critical for cell polarization in the plane of an epithelium. The core set of PCP genes include members of the conserved Wnt‐signaling pathway, such as Frizzled and Disheveled, but also the cadherin‐domain protein Flamingo. In Drosophila, the Fat and Dachsous cadherins also function in PCP, but in parallel to the core PCP components. C. elegans also have two Fat‐like and one Dachsous‐like cadherins, at least one of which, cdh‐4, contributes to neural development. In C. elegans Wnt ligands and the conserved PCP genes have been shown to regulate a number of different events, including embryonic cell polarity, vulval morphogenesis, and cell migration. As is also observed in vertebrates, the Wnt and PCP genes appear to function to primarily provide information about the anterior to posterior axis of development. Here, we review the recent work describing how mutations in the Wnt and core PCP genes affect axon guidance and synaptogenesis in C. elegans. © 2013 Wiley Periodicals, Inc. Develop Neurobiol 74: 781–796, 2014
Postnatal development of auditory central evoked responses and thalamic cellular properties
Authors: Venkataraman Yamini , Bartlett Edward L.
Published: November 2013

During development, the sense of hearing changes rapidly with age, especially around hearing onset. During this period, auditory structures are highly sensitive to alterations of the acoustic environment, such as hearing loss or background noise. This sensitivity includes auditory temporal processing, which is important for processing complex sounds, and for acquiring reading and language skills. Developmental changes can be observed at multiple levels of brain organization—from behavioral responses to cellular responses, and at every auditory nucleus. Neuronal properties and sound processing change dramatically in auditory cortex neurons after hearing onset. However, development of its primary source, the auditory thalamus, or medial geniculate body (MGB), has not been well studied over this critical time window. Furthermore, to understand how temporal processing develops, it is important to determine the relative maturation of temporal processing not only in the MGB, but also in its inputs. Cellular properties of rat MGB neurons were studied using in vitro whole‐cell patch‐clamp recordings, at ages postnatal day (P) 7–9; P15–17, and P22–32. Auditory evoked potentials were measured in P14–17 and P22–32 rats. MGB action potentials became about five times faster, and the ability to generate spike trains increased with age, particularly at frequencies of 50 Hz and higher. Evoked potential responses, including auditory brainstem responses (ABR), middle latency responses (MLR), and amplitude modulation following responses, showed increased amplitudes with age, and ABRs and MLRs additionally showed decreased latencies with age. Overall, temporal processing at subthalamic nuclei is concurrently maturing with MGB cellular properties. © 2013 Wiley Periodicals, Inc. Develop Neurobiol 74: 541–555, 2014
Evaluating the carbon balance estimate from an automated ground‐level flux chamber system in artificial grass mesocosms
Authors: Heinemeyer Andreas , Gornall Jemma , Baxter Robert , Huntley Brian , Ineson Phil
Published: November 2013

Measuring and modeling carbon (C) stock changes in terrestrial ecosystems are pivotal in addressing global C‐cycling model uncertainties. Difficulties in detecting small short‐term changes in relatively large C stocks require the development of robust sensitive flux measurement techniques. Net ecosystem exchange (NEE) ground‐level chambers are increasingly used to assess C dynamics in low vegetation ecosystems but, to date, have lacked formal rigorous field validation against measured C stock changes. We developed and deployed an automated and multiplexed C‐flux chamber system in grassland mesocosms in order rigorously to compare ecosystem total C budget obtained using hourly C‐flux measurements versus destructive net C balance. The system combines transparent NEE and opaque respiration chambers enabling partitioning of photosynthetic and respiratory fluxes. The C‐balance comparison showed good agreement between the two methods, but only after NEE fluxes were corrected for light reductions due to chamber presence. The dark chamber fluxes allowed assessing temperature sensitivity of ecosystem respiration (Reco) components (i.e., heterotrophic vs. autotrophic) at different growth stages. We propose that such automated flux chamber systems can provide an accurate C balance, also enabling pivotal partitioning of the different C‐flux components (e.g., photosynthesis and respiration) suitable for model evaluation and developments.
Vertical patterns of soil water acquisition by non‐native rubber trees (Hevea brasiliensis) in Xishuangbanna, southwest China
Authors: Liu Wenjie , Li Jintao , Lu Hongjian , Wang Pingyuan , Luo Qinpu , Liu Wenyao , Li Hongmei
Published: November 2013

The rubber tree (Hevea brasiliensis) has been extensively cultivated in Xishuangbanna, southwest (SW) China. It shows strong synchronicity for flushing and shedding, displaying a very different phenology to the native vegetation. However, little is known about the water‐use patterns of the plant in this area. We assessed seasonal water‐use strategies of rubber trees over the course of a rainy/dry season cycle. Stable isotope compositions of water in xylem, soil, rain and groundwater were sampled on seasonally distinct dates, and soil water content, root distribution and leaf water potential on sunny days were measured in order to determine the proportion of water derived from different soil layers. Midday leaf water potential of rubber trees was relatively stable throughout the year and did not drop significantly during the late dry season, displaying isohydric behaviour. Soil and stem water isotope signatures along with rooting distributional patterns revealed that rubber trees extracted their water mostly from the top 30 cm and less from below 70 cm of the soil profile during the late rainy season when soil water was plentiful. During the late dry season, as the moisture in the middle soil layers (30–70 cm) was gradually depleted, the depth of water uptake shifted to deeper soil levels. Model calculations showed that the proportion of water uptake from the shallow soil layer (<30 cm) increased markedly after the most recent rainfall in the late dry season and the early rainy season (varying between 65% and 71%), indicating significant plasticity in sources of water uptake in this dimorphic‐rooted species. This ability to take up a large proportion of shallow soil water after rainfall is likely the key feature enabling rubber trees to thrive through the period of greatest water demand. Our results suggest that rubber trees are able to adjust the allocation of resources and thus acclimate to the spatiotemporal changes to water conditions in the soil profile. Copyright © 2013 John Wiley & Sons, Ltd.
Augmenting aquatic species sensitivity distributions with interspecies toxicity estimation models
Authors: Awkerman Jill A. , Raimondo Sandy , Jackson Crystal R. , Barron Mace G.
Published: November 2013

Species sensitivity distributions (SSDs) are cumulative distribution functions of species toxicity values. The SSD approach is being used increasingly in ecological risk assessment but is often limited by available toxicity data needed for diverse species representation. In the present study, the authors evaluate augmenting aquatic species databases limited to standard test species using toxicity values extrapolated from interspecies correlation estimation (ICE) models for SSD development. The authors compared hazard concentrations at the 5th centile (HC5) of SSDs developed using limited measured data augmented with ICE toxicity values (augmented SSDs) with those estimated using larger measured toxicity datasets of diverse species (reference SSDs). When SSDs had similar species composition to the reference SSDs, 0.76 of the HC5 estimates were closer to the reference HC5; however, the proportion of augmented HC5s that were within 5-fold of the reference HC5s was 0.94, compared with 0.96 when predicted SSDs had random species assemblages. The range of toxicity values among represented species in all SSDs also depended on a chemical's mode of action. Predicted HC5 estimations for acetylcholinesterase inhibitors showed the greatest discrepancies from the reference HC5 when SSDs were limited to commonly tested species. The results of the present study indicate that ICE models used to augment datasets for SSDs do not greatly affect HC5 uncertainty. Uncertainty analysis of risk assessments using SSD hazard concentrations should address species composition, especially for chemicals with known taxa-specific differences in toxicological effects. Environ Toxicol Chem 2014;33:688–695. © 2013 SETAC. This article is a US Government work and is in the public domain in the USA.
T-cell factor 4 and β-catenin chromatin occupancies pattern zonal liver metabolism in mice
Authors: Gougelet Angélique , Torre Cyril , Veber Philippe , Sartor Chiara , Bachelot Laura , Denechaud Pierre-Damien , Godard Cécile , Moldes Marthe , Burnol Anne-Françoise , Dubuquoy Céline , Terris Benoit , Guillonneau François , Ye Tao , Schwarz Michael , Braeuning Albert , Perret Christine , Colnot Sabine
Published: November 2013

β-catenin signaling can be both a physiological and oncogenic pathway in the liver. It controls compartmentalized gene expression, allowing the liver to ensure its essential metabolic function. It is activated by mutations in 20%-40% of hepatocellular carcinomas (HCCs) with specific metabolic features. We decipher the molecular determinants of β-catenin-dependent zonal transcription using mice with β-catenin-activated or -inactivated hepatocytes, characterizing in vivo their chromatin occupancy by T-cell factor (Tcf)−4 and β-catenin, transcriptome, and metabolome. We find that Tcf-4 DNA bindings depend on β-catenin. Tcf-4/β-catenin binds Wnt-responsive elements preferentially around β-catenin-induced genes. In contrast, genes repressed by β-catenin bind Tcf-4 on hepatocyte nuclear factor 4 (Hnf-4)-responsive elements. β-Catenin, Tcf-4, and Hnf-4α interact, dictating β-catenin transcription, which is antagonistic to that elicited by Hnf-4α. Finally, we find the drug/bile metabolism pathway to be the one most heavily targeted by β-catenin, partly through xenobiotic nuclear receptors. Conclusions: β-catenin patterns the zonal liver together with Tcf-4, Hnf-4α, and xenobiotic nuclear receptors. This network represses lipid metabolism and exacerbates glutamine, drug, and bile metabolism, mirroring HCCs with β-catenin mutational activation. (Hepatology 2014;59:2344–2357)
Using surveillance data to determine treatment rates and outcomes for patients with chronic hepatitis C virus infection
Authors: Lattimore Sam , Irving Will , Collins Sarah , Penman Celia , Ramsay Mary
Published: November 2013

The aim of this work was to develop and validate an algorithm to monitor rates of, and response to, treatment of patients infected with hepatitis C virus (HCV) across England using routine laboratory HCV RNA testing data. HCV testing activity between January 2002 and December 2011 was extracted from the local laboratory information systems of a sentinel network of 23 laboratories across England. An algorithm based on frequency of HCV RNA testing within a defined time period was designed to identify treated patients. Validation of the algorithm was undertaken for one center by comparison with treatment data recorded in a clinical database managed by the Trent HCV Study Group. In total, 267,887 HCV RNA test results from 100,640 individuals were extracted. Of these, 78.9% (79,360) tested positive for viral RNA, indicating an active infection, 20.8% (16,538) of whom had a repeat pattern of HCV RNA testing suggestive of treatment monitoring. Annual numbers of individuals treated increased rapidly from 468 in 2002 to 3,295 in 2009, but decreased to 3,110 in 2010. Approximately two thirds (63.3%; 10,468) of those treated had results consistent with a sustained virological response, including 55.3% and 67.1% of those with a genotype 1 and non-1 virus, respectively. Validation against the Trent clinical database demonstrated that the algorithm was 95% sensitive and 93% specific in detecting treatment and 100% sensitive and 93% specific for detecting treatment outcome. Conclusions: Laboratory testing activity, collected through a sentinel surveillance program, has enabled the first country-wide analysis of treatment and response among HCV-infected individuals. Our approach provides a sensitive, robust, and sustainable method for monitoring service provision across England. (HEPATOLOGY 2014;59:1343-1350)
Withholding Parenteral Nutrition During Critical Illness Increases Plasma Bilirubin but Lowers the Incidence of Biliary Sludge
Authors: Vanwijngaerden Yoo-Mee , Langouche Lies , Brunner Richard , Debaveye Yves , Gielen Marijke , Casaer Michael , Liddle Christopher , Coulter Sally , Wouters Pieter J. , Wilmer Alexander , Van den Berghe Greet , Mesotten Dieter
Published: November 2013

Cholestatic liver dysfunction (CLD) and biliary sludge often occur during critical illness and are allegedly aggravated by parenteral nutrition (PN). Delaying initiation of PN beyond day 7 in the intensive care unit (ICU) (late PN) accelerated recovery as compared with early initiation of PN (early PN). However, the impact of nutritional strategy on biliary sludge and CLD has not been fully characterized. This was a preplanned subanalysis of a large randomized controlled trial of early PN versus late PN (n = 4,640). In all patients plasma bilirubin (daily) and liver enzymes (alanine aminotransferase [ALT], aspartate aminotransferase [AST], gamma-glutamyl transpeptidase [GGT], alkaline phosphatase [ALP], twice weekly; n = 3,216) were quantified. In a random predefined subset of patients, plasma bile acids (BAs) were also quantified at baseline and on days 3, 5, and last ICU-day (n = 280). Biliary sludge was ultrasonographically evaluated on ICU-day 5 (n = 776). From day 1 after randomization until the end of the 7-day intervention window, bilirubin was higher in the late PN than in the early PN group (

P

< 0.001). In the late PN group, as soon as PN was started on day 8 bilirubin fell and the two groups became comparable. Maximum levels of GGT, ALP, and ALT were lower in the late PN group (

P

< 0.01). Glycine/taurine-conjugated primary BAs increased over time in ICU (

P

< 0.01), similarly for the two groups. Fewer patients in the late PN than in the early PN group developed biliary sludge on day 5 (37% versus 45%;

P

= 0.04).

Conclusion :

Tolerating substantial caloric deficit by withholding PN until day 8 of critical illness increased plasma bilirubin but reduced the occurrence of biliary sludge and lowered GGT, ALP, and ALT. These results suggest that hyperbilirubinemia during critical illness does not necessarily reflect cholestasis and instead may be an adaptive response that is suppressed by early PN. (Hepatology 2014;60:202–210)
Ribonucleotide reductase M2B inhibits cell migration and spreading by early growth response protein 1-mediated phosphatase and tensin homolog/Akt1 pathway in hepatocellular carcinoma
Authors: Tian Hua , Ge Chao , Li Hong , Zhao Fangyu , Hou Helei , Chen Taoyang , Jiang Guoping , Xie Haiyang , Cui Ying , Yao Ming , Li Jinjun
Published: November 2013

Ribonucleotide reductase (RR)M2B is an enzyme belonging to the ribonucleotide reductase enzyme family, which is essential for DNA synthesis and repair. RRM2B plays an important role in tumor progression and metastasis; however, little is known about the expression and underlying molecular mechanisms of RRM2B in hepatocellular carcinoma (HCC). In the present study, we report that down-regulation of RRM2B in HCC is negatively associated with intrahepatic metastasis, regardless of p53 status. Moreover, the ectopic overexpression of RRM2B decreased HCC cell migration and invasion in vitro, whereas silencing RRM2B expression resulted in increased migration and invasion in vitro and intrahepatic and lung metastasis in vivo. Additionally, knockdown of RRM2B by short hairpin RNA (shRNA) in HCC cells was associated with epithelial-mesenchymal transition (EMT), including the down-regulation of E-cadherin, and the concomitant up-regulation of N-cadherin and slug. A further experiment showed that RRM2B inhibited cell migration and spreading through regulation of the early growth response protein 1 (Egr-1) / phosphatase and tensin homolog (PTEN) / Akt1 pathway. Consistently, we also detected a significant correlation between RRM2B and E-cadherin protein expression in HCC tissues. Furthermore, Egr-1 also directly bound to the RRM2B promoter and repressed RRM2B transcription, thereby establishing a negative regulatory feedback loop. Conclusion: These findings indicate that RRM2B suppresses cell migration and spreading by way of modulation of the Egr-1/PTEN/Akt1 pathway. (HEPATOLOGY 2014;59:1459-1470)
Inhibition of Niemann-Pick-type C1-like1 by ezetimibe activates autophagy in human hepatocytes and reduces mutant α1-antitrypsin Z deposition
Authors: Yamamura Takeshi , Ohsaki Yuki , Suzuki Michitaka , Shinohara Yuki , Tatematsu Tsuyako , Cheng Jinglei , Okada Masato , Ohmiya Naoki , Hirooka Yoshiki , Goto Hidemi , Fujimoto Toyoshi
Published: November 2013

Autophagy can degrade aggregate-prone proteins, but excessive autophagy can have adverse effects. It would be beneficial if autophagy could be enhanced in a cell type-specific manner, but this has been difficult because the basic mechanism of autophagy is common. In the present study we found that inhibition of Niemann-Pick-type C1-like 1 (NPC1L1) by ezetimibe activates autophagy only in hepatocytes and small intestinal epithelia, but not in other cells. Ezetimibe induced accumulation of free cholesterol in the late endosome/lysosome and increased partitioning of a Ragulator component, LAMTOR1, in rafts. The latter change led to down-regulation of mammalian target of rapamycin (mTOR)C1 activity by decreasing mTOR recruitment to the late endosome/lysosome and activated autophagy. A primary effect of ezetimibe was found to be a decrease of free cholesterol in the plasma membrane, because all the results caused by ezetimibe were suppressed by supplementation of cholesterol as a methyl-β-cyclodextrin complex. By enhancing autophagy in human primary hepatocytes with ezetimibe, insoluble mutant α1-antitrypsin Z was reduced significantly. Conclusion: Inhibition of NPC1L1 by ezetimibe activates autophagy in human hepatocytes by modulating cholesterol homeostasis. Ezetimibe may be used to ameliorate liver degeneration in α1-antitrypsin deficiency. (HEPATOLOGY 2014;59:1591-1599)