bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anatomy of RISC: how do small RNAs and chaperones activate Argonaute proteins?
Authors: Nakanishi Kotaro 
Published: May 2016

RNA silencing is a eukaryote‐specific phenomenon in which microRNAs and small interfering RNAs degrade messenger RNAs containing a complementary sequence. To this end, these small RNAs need to be loaded onto an Argonaute protein (AGO protein) to form the effector complex referred to as RNA‐induced silencing complex (RISC). RISC assembly undergoes multiple and sequential steps with the aid of Hsc70/Hsp90 chaperone machinery. The molecular mechanisms for this assembly process remain unclear, despite their significance for the development of gene silencing techniques and RNA interference‐based therapeutics. This review dissects the currently available structures of AGO proteins and proposes models and hypotheses for RISC assembly, covering the conformation of unloaded AGO proteins, the chaperone‐assisted duplex loading, and the slicer‐dependent and slicer‐independent duplex separation. The differences in the properties of RISC between prokaryotes and eukaryotes will also be clarified. WIREs RNA 2016, 7:637–660. doi: 10.1002/wrna.1356This article is categorized under:

RNA Interactions with Proteins and Other Molecules > Protein–RNA Recognition
Regulatory RNAs/RNAi/Riboswitches > Biogenesis of Effector Small RNAs
Regulatory RNAs/RNAi/Riboswitches > RNAi: Mechanisms of Action
Postmenopausal Breast Cancer, Aromatase Inhibitors, and Bone Health: What the Surgeon Should Know
Authors: Baatjes K. J. , Apffelstaedt J. P. , Kotze M. J. , Conradie M. 
Published: May 2016

AbstractBreast cancer, as the most common malignancy in women, remains a major public health issue despite countless advances across decades. Endocrine therapy is the cornerstone of treatment of the hormone‐sensitive subtype of breast cancer. The use of aromatase inhibitors (AIs) in the postmenopausal women has extended the survival beyond that of Tamoxifen, but harbors a subset of side effects, most notably accelerated bone loss. This, however, does not occur in all women undergoing treatment. It is vital to identify susceptible patients early, to limit such events, employ early treatment thereof, or alter drug therapy. International trials on AIs, predominantly performed in North American and European females, provide little information on what to expect in women in developing countries. Here, surgeons often prescribe and manage endocrine therapy. The prescribing surgeon should be aware of the adverse effect of the endocrine therapy and be able to attend to side effects. This review highlights clinical and biochemical factors associated with decrease in bone mineral density in an, as yet, unidentified subgroup of postmenopausal women. In the era of personalized medical care, appropriate management of bone health by surgeons based on these factors becomes increasingly important.
Vats Versus Axillary Minithoracotomy in the Management of the Second Episode of Spontaneous Pneumothorax: Cost–Benefit Analysis
Authors: Divisi Duilio , Di Leonardo Gabriella , Crisci Roberto 
Published: May 2016

AbstractBackground
Video‐assisted thoracic surgery (VATS) was considered the gold standard approach in recurrent spontaneous pneumothorax, with unanimous consensus of opinions. The cost‐effectiveness analysis in the surgical treatment of recurrence of primary spontaneous pneumothorax (PSP) was carried out comparing VATS with muscle‐sparing axillary minithoracotomy (MSAM).MethodsBetween July 2006 and October 2012 we treated 56 patients with a second episode of PSP by VATS or open approach. Time of intervention, prolonged air leaks, duration of pleural drainage, length of hospitalization, and long‐term morbidity were evaluated, establishing the relationship between costs and quality‐adjusted life for each technique.ResultsThe assessment of pain and threshold of tenderness was more favorable in VATS in respect to MSAM during the 5 years of follow‐up (p = 0.004 and <0.001 at 1st year; p = 0.006 and <0.002 at 5th year). The minimally invasive method was less expensive than axillary minithoracotomy (2443.44 € vs. 3170.80 €). The quality‐adjusted life expectancy of VATS was better than that of MSAM (57.00 vs. 49.2 at 60 months) as well as the quality‐adjusted life year (0.03 at 1st year and 0.13 at 5th year). Incremental cost per life year gained of VATS versus MSAM was between 24,245.33 € (1st year) and 5776.31 € (5th year), making it advantageous at 3rd, 4th, and 5th years.ConclusionsVATS compared to MSAM in the treatment of a second episode of PSP ensured undoubted clinical advantages associated with significant cost savings.
Stratigraphy of the Upper Gondwana Formations around Sohagpur, Western Part of the Satpura Gondwana Basin, Central India
Authors: Sengupta Saradee , Sengupta Dhurjati Prasad , Bandyopadhyay Saswati 
Published: May 2016

Abstract:
The present work provides a detailed lithological map of the western part of the Satpura basin around Sohagpur and reports the presence of new archosauromorph fossil bones from that region. The study area is dominated by the Bagra Formation along with a narrow patch of the underlying upper part of the Denwa Formation. The lower Denwa and the underlying Pachmarhi formations are absent here. The presence of the Pachmarhi Formation, as a tongue shaped area, as mapped by Crookshank (1936) is discarded in this study on the basis of lithology and petrographic analyses, instead the presence of the Bagra Formation is suggested in this area. A comparison of the lithologies and the vertebrate faunas of the upper Gondwana formations between eastern and western part of the basin has been carried out for the first time. The comparison indicates that the Denwa Formation present in the western sector represents only the topmost part of the formation while the complete succession of Denwa is preserved in the eastern sector. The Bagra Formation in the western sector documents the presence of sheet-like sandstone bodies unlike the eastern part. The vertebrate fauna of the eastern part is dominated by temnospondyl amphibians while that of the western part is dominated by archosauromorph. The vertebrate fossils of upper part of Denwa Formation, found from similar lithologies in west and east though, have differences in the amount of transportation before their burial.
Holigarna (Anacardiaceae) from the Early Eocene of Western India and its Palaeogeographical and Palaeoclimatological Significance
Authors: Shukla Anumeha , Mehrotra Rakesh Chandra 
Published: May 2016

Abstract:
Thick lignite deposits on the western margin of India were preserved on account of thick vegetation which got buried underneath due to tectonic activities that occurred in northwestern part of India during the early Palaeogene. Study of the fossil flora preserved in these beds is important to deduce the palaeoclimate of the region. Therefore, a field work was undertaken to collect plant fossils from the Tarkeshwar lignite mine, Surat district, Gujarat (western India) which is still unexplored as far as the plant mega-remains are concerned. A fossil wood is systematically described from the Cambay Shale Formation of the mine considered to be of early Eocene in age. It shows close affinities with Holigarna (Anacardiaceae), particularly with H. beddomei and H. grahamii. This genus is evergreen in nature and grows in the Indo-Malayan region, while both the modern analogues of the fossil are endemic to semi-evergreen to evergreen forests of Western Ghats, south India, located at the equator. This not only confirms the palaeolatitudinal position of the Indian subcontinent at the equator during the early Palaeogene, but also indicates the presence of equatorial rain forest in the Indian subcontinent during the period. Based on the timetree, Sapindales started to diverge in the early Palaeocene (62– 57 Ma) as its oldest fossil is from the K-Pg boundary. Discovery of the present anacardiaceous fossil (belonging to Sapindales) from the early Eocene strengthens the above phylogenetic view.
Impact of Urbanization on Groundwater Quality in Vijayawada Urban Agglomeration, the New Capital Region of Andhra Pradesh, India – A Baseline Study
Authors: Rao P. N. , Prasad K. Maruthi , Madhusudhan B. J. , Krishna V. S. R. , Anand A. V. S. S. , Madhnure Pandith 
Published: May 2016

Abstract:
Groundwater sampling was carried out in fast growing Vijayawada urban agglomeration in Andhra Pradesh state with a view to generate base line data and to assess groundwater quality, its variations vis-à-vis urbanization and hydrochemical characteristics. The groundwaters are found to be fresh to brackish, hard to very hard, often enriched with nitrate, phosphate, and faecal colliform indicating anthropogenic influence on groundwater on account of urbanization. Manganese and iron of geogenic origin are also found to be in high concentrations in some localities. The quality deterioration is more in shallow aquifers, as also in core urban and red soil covered areas. Spatial variations in groundwater quality are discernible, with high concentrations of SO4−,NO3− in core urban area suggesting the impact of urbanization. A wide range of chemical constituents indicate water rock interactions as influenced by anthropogenic activities controlling the urban aquifers. The order of abundance of cations is Na&gt;Mg&gt;Ca&gt;K, while the order of abundance of anions is Cl&gt;HCO3&gt;SO4&gt;NO3. The baseline study suggests the need to protect the groundwater resource through sound environmental protection measures for the welfare of the inhabitants in the city around which the new capital is proposed to be constructed for newly formed Andhra Pradesh state in India.
A Study on the Geochemistry of Groundwater Exhibiting Natural Attenuation of Phenols in the Alluvial Tracts of Oil Refinery Area of Bongaigaon District, Assam
Authors: Sankar K. Siva , Bhargav J. S. 
Published: May 2016

Abstract:
Hydrochemical and hydrogeological studies were carried out in the groundwater of Dhaligaon refinery area, Bongaigoan district, Assam. The study revealed that the area is underlain by alluvial deposits of thickness varying from 67 to 142 meters and the groundwater occurs in unconfined alluvial formations. Transmissivity values of the formations range from 2100 to 3800 m2/day. The effluents from the refinery are disposed off into a natural drain, “Tunia nala”, which contaminates the groundwater. The effluents contain constituents like phenol, nitrite, sulphide, iron etc, which subsequently seep into the dug well zone, but the phenol concentrations get naturally attenuated during the contaminant transport to the depths below. The probable reasons leading to natural attenuation of phenol as per in-situ hydrogeological and environmental conditions have been discussed.
Reservoir Characterization and Formation Evaluation of a “Royal Onshore Field”, Southern Niger Delta using Geophysical Well Log Data
Authors: Obiora Daniel N. , Gbenga David , Ogobiri Godwin 
Published: May 2016

Abstract:
The reservoir properties of three wells in Royal Field, Niger Delta basin was characterized using fundamental formula. The distributions and thicknesses of sand bodies were determined within each of the wells in the field using geophysical modeling software. The quantitative and qualitative analyses were done for the three exploration wells with the depth ranges of 4000-9700m for Royal well 1, 1000-8805m for Royal well 2, and 4000-8000m for Royal well 3. Each well has identified sand units. Royal well 1 and Royal well 2 have 5 sand units (A, B, C, D, E) each, with respective thicknesses 422m, 110m, 92m, 142m and 350m for well 1, and 82m, 65m, 214m, 362m, and 192m for well 2. Royal well 3 has 4 sand units (A, B, C, D), with respective thicknesses 135m, 80m, 269m and 229m. Petrophysical evaluations were made from well logs. The average porosity values obtained for Royal wells 1, 2, and 3 are 0.24, 0.18 and 0.22 respectively while the corresponding average permeability values are 2789mD, 1292mD, 1643mD. Porosity values obtained from porosity logs and density log (RHOB) using porosity formula are found to be within the range of 0.07-0.45, while their permeabilities range from 164 to 8453 milli Darcy. The water saturation obtained for each reservoir unit in combination with the resistivity index were used to prove the presence of hydrocarbon in these sands. Royal well 2 having its sand A, 80% hydrocarbon saturated and 82m thickness is the most prolific. The results clearly indicate that the application of this technique is very effective for the interpretation of reservoir properties.
SMR Geomechanics and Kinematic Analysis near Rasulpur, Fatehpur Sikri, Uttar Pradesh
Authors: Mondal M. E. A. , Siddique Tariq , Mondal Bulbul , Alam M. Masroor 
Published: May 2016

Abstract:
Slope stability of mine slopes is often associated with safety and economics during excavation. Sandstone is excavated from Rasulpur area of Fatehpur Sikri in Uttar Pradesh for the purpose of crushed, decorative and dimension stones. In the present paper an attempt has been made to characterize the rock slope faces into different stability classes. Characterization is based on geological and geotechnical parameters recorded on the outcrop during field investigation and supplemented by geomechanical properties by the laboratory test for strength of the rock intact. SMR Geomechanics classification is used to identify the stability class and remedial measures are also suggested to reduce any possible hazard. Kinematic analysis of slope was also investigated to determine the probability of any possible structurally controlled failure. On the basis of SMR Geomechanics calculations slope under investigation lies under good stability class i.e. 2a and 2b. Installation of nets during excavation can be done and for better safety spot and systematic rock bolting can be done. Kinematic study reveals that toppling failures may occur, special care must be given to the joint set which can trigger toppling failure.
Mifepristone increases mRNA translation rate, triggers the unfolded protein response, increases autophagic flux, and kills ovarian cancer cells in combination with proteasome or lysosome inhibitors
Authors: Zhang Lei , Hapon Maria B. , Goyeneche Alicia A. , Srinivasan Rekha , Gamarra-Luques Carlos D. , Callegari Eduardo A. , Drappeau Donis D. , Terpstra Erin J. , Pan Bo , Knapp Jennifer R. , Chien Jeremy , Wang Xuejun , Eyster Kathleen M. , Telleria Carlos M. 
Published: May 2016

The synthetic steroid mifepristone blocks the growth of ovarian cancer cells, yet the mechanism driving such effect is not entirely understood. Unbiased genomic and proteomic screenings using ovarian cancer cell lines of different genetic backgrounds and sensitivities to platinum led to the identification of two key genes upregulated by mifepristone and involved in the unfolded protein response (UPR): the master chaperone of the endoplasmic reticulum (ER), glucose regulated protein (GRP) of 78 kDa, and the CCAAT/enhancer binding protein homologous transcription factor (CHOP). GRP78 and CHOP were upregulated by mifepristone in ovarian cancer cells regardless of p53 status and platinum sensitivity. Further studies revealed that the three UPR‐associated pathways, PERK, IRE1α, and ATF6, were activated by mifepristone. Also, the synthetic steroid acutely increased mRNA translation rate, which, if prevented, abrogated the splicing of XBP1 mRNA, a non‐translatable readout of IRE1α activation. Moreover, mifepristone increased LC3‐II levels due to increased autophagic flux. When the autophagic–lysosomal pathway was inhibited with chloroquine, mifepristone was lethal to the cells. Lastly, doses of proteasome inhibitors that are inadequate to block the activity of the proteasomes, caused cell death when combined with mifepristone; this phenotype was accompanied by accumulation of poly‐ubiquitinated proteins denoting proteasome inhibition. The stimulation by mifepristone of ER stress and autophagic flux offers a therapeutic opportunity for utilizing this compound to sensitize ovarian cancer cells to proteasome or lysosome inhibitors.
Short-term velocity variations and sliding sensitivity of a slowly surging glacier
Authors: Flowers Gwenn E. , Jarosch Alexander H. , Belliveau Patrick T. A. P. , Fuhrman Lucas A. 
Published: May 2016

ABSTRACTWe use daily surface velocities measured over several weeks in 2007 and 2008 on a slowly surging glacier in Yukon, Canada, to examine the ordinary melt-season dynamics in the context of the ongoing surge. Horizontal velocities within and just below the ~1.5 km-long zone of fastest flow, where the surge is occurring, are often correlated during intervals of low melt. This correlation breaks down during melt events, with the lower reaches of the fast-flow zone responding first. Velocity variability in this lower reach is most highly correlated with melt; velocities above and below appear to respond at least as strongly to the velocity variations of this reach as to local melt. GPS height records are suggestive of ice/bed separation occurring in the fast-flow zone but not below it, pointing to a hydrological cause for the short-term flow variability in the surging region. Independent velocity measurements over 6 years show a maximum July flow anomaly coincident with the location most responsive to melt. Results from a simple model of dashpots and frictional elements lend support to the hypothesis that this zone partly drives the dynamics of the ice above and below it. We speculate that the slow surge may enhance glacier sensitivity to melt-season processes, including short-term summer sliding events.
Pediatrician preferences, local resources, and economic factors influence referral to a subspecialty access clinic
Authors: Di Guglielmo Matthew D. , Greenspan Jay S. , Abatemarco Diane J. 
Published: May 2016

BackgroundPediatric patients seek timely access to subspecialty care within a complex delivery system while facing barriers: distance, economics, and clinician shortages.AimWe examined stakeholder perceptions about solutions to the access challenge. We engaged over 300 referring primary care pediatricians in the evaluation of Access Clinics at an academic children’s hospital.MethodsUsing an anonymous online survey, we asked pediatricians about their and their patients’ experiences and analyzed factors that may influence referrals.FindingsReferring pediatricians reported satisfaction; they provided feedback about their patients’ experiences, physician communication, and referral influences. Distance from the Access Clinic does not correlate with differences in referral volume; living in areas with higher child populations and higher median income is associated with more referrals. Referring pediatricians have strong opinions about referrals, are attuned to patient experiences, and desire bi-directional communication. Multiple factors influence referral to and acceptance of Access Clinics, but external influences have less impact than expected.
An allosteric role for receptor activity-modifying proteins in defining GPCR pharmacology
Authors: J Gingell Joseph , Simms John , Barwell James , Poyner David R , Watkins Harriet A , Pioszak Augen A , Sexton Patrick M , Hay Debbie L 
Published: May 2016

AbstractG protein-coupled receptors are allosteric proteins that control transmission of external signals to regulate cellular response. Although agonist binding promotes canonical G protein signalling transmitted through conformational changes, G protein-coupled receptors also interact with other proteins. These include other G protein-coupled receptors, other receptors and channels, regulatory proteins and receptor-modifying proteins, notably receptor activity-modifying proteins (RAMPs). RAMPs have at least 11 G protein-coupled receptor partners, including many class B G protein-coupled receptors. Prototypic is the calcitonin receptor, with altered ligand specificity when co-expressed with RAMPs. To gain molecular insight into the consequences of this protein–protein interaction, we combined molecular modelling with mutagenesis of the calcitonin receptor extracellular domain, assessed in ligand binding and functional assays. Although some calcitonin receptor residues are universally important for peptide interactions (calcitonin, amylin and calcitonin gene-related peptide) in calcitonin receptor alone or with receptor activity-modifying protein, others have RAMP-dependent effects, whereby mutations decreased amylin/calcitonin gene-related peptide potency substantially only when RAMP was present. Remarkably, the key residues were completely conserved between calcitonin receptor and AMY receptors, and between subtypes of AMY receptor that have different ligand preferences. Mutations at the interface between calcitonin receptor and RAMP affected ligand pharmacology in a RAMP-dependent manner, suggesting that RAMP may allosterically influence the calcitonin receptor conformation. Supporting this, molecular dynamics simulations suggested that the calcitonin receptor extracellular N-terminal domain is more flexible in the presence of receptor activity-modifying protein 1. Thus, RAMPs may act in an allosteric manner to generate a spectrum of unique calcitonin receptor conformational states, explaining the pharmacological preferences of calcitonin receptor-RAMP complexes. This provides novel insight into our understanding of G protein-coupled receptor-protein interaction that is likely broadly applicable for this receptor class.
Contribution of ammonia oxidation to chemoautotrophy in Antarctic coastal waters
Authors: Tolar Bradley B , Ross Meredith J , Wallsgrove Natalie J , Liu Qian , Aluwihare Lihini I , Popp Brian N , Hollibaugh James T 
Published: May 2016

Abstract
There are few measurements of nitrification in polar regions, yet geochemical evidence suggests that it is significant, and chemoautotrophy supported by nitrification has been suggested as an important contribution to prokaryotic production during the polar winter. This study reports seasonal ammonia oxidation (AO) rates, gene and transcript abundance in continental shelf waters west of the Antarctic Peninsula, where Thaumarchaeota strongly dominate populations of ammonia-oxidizing organisms. Higher AO rates were observed in the late winter surface mixed layer compared with the same water mass sampled during summer (mean±s.e.: 62±16 versus 13±2.8 nm per day, t-test P&lt;0.0005). AO rates in the circumpolar deep water did not differ between seasons (21±5.7 versus 24±6.6 nm per day; P=0.83), despite 5- to 20-fold greater Thaumarchaeota abundance during summer. AO rates correlated with concentrations of Archaea ammonia monooxygenase (amoA) genes during summer, but not with concentrations of Archaea amoA transcripts, or with ratios of Archaea amoA transcripts per gene, or with concentrations of Betaproteobacterial amoA genes or transcripts. The AO rates we report (&lt;0.1–220 nm per day) are ~10-fold greater than reported previously for Antarctic waters and suggest that inclusion of Antarctic coastal waters in global estimates of oceanic nitrification could increase global rate estimates by ~9%. Chemoautotrophic carbon fixation supported by AO was 3–6% of annualized phytoplankton primary production and production of Thaumarchaeota biomass supported by AO could account for ~9% of the bacterioplankton production measured in winter. Growth rates of thaumarchaeote populations inferred from AO rates averaged 0.3 per day and ranged from 0.01 to 2.1 per day.