Assembly and transport of a premessenger RNP particle

Salivary gland cells in the larvae of the dipteran Chironomus tentans offer unique possibilities to visualize the assembly and nucleocytoplasmic transport of a specific transcription product. Each nucleus harbors four giant polytene chromosomes, whose transcription sites are expanded, or puffed. On chromosome IV, there are two puffs of exceptional size, Balbiani ring (BR) 1 and BR 2. A BR gene is 35–40 kb, contains four short introns, and encodes a 1-MDa salivary polypeptide. The BR transcript is packed with proteins into a ribonucleoprotein (RNP) fibril that is folded into a compact ring-like structure. The completed RNP particle is released into the nucleoplasm and transported to the nuclear pore, where the RNP fibril is gradually unfolded and passes through the pore. On the cytoplasmic side, the exiting extended RNP fibril becomes engaged in protein synthesis and the ensuing polysome is anchored to the endoplasmic reticulum. Several of the BR particle proteins have been characterized, and their fate during the assembly and transport of the BR particle has been elucidated. The proteins studied are all added cotranscriptionally to the pre-mRNA molecule. The various proteins behave differently during RNA transport, and the flow pattern of each protein is related to the particular function of the protein. Because the cotranscriptional assembly of the pre-mRNP particle involves proteins functioning in the nucleus as well as proteins functioning in the cytoplasm, it is concluded that the fate of the mRNA molecule is determined to a considerable extent already at the gene level.

Heat-Shock-Induced Changes in Intracellular Ca2+ Level in Tobacco Seedlings in Relation to Thermotolerance1

Exposure of plants to elevated temperatures results in a complex set of changes in gene expression that induce thermotolerance and improve cellular survival to subsequent stress. Pretreatment of young tobacco (Nicotiana plumbaginifolia) seedlings with Ca2+ or ethylene glycol-bis(β-aminoethylether)-N,N,N′,N′-tetraacetic acid enhanced or diminished subsequent thermotolerance, respectively, compared with untreated seedlings, suggesting a possible involvement of cytosolic Ca2+ in heat-shock (HS) signal transduction. Using tobacco seedlings transformed with the Ca2+-sensitive, luminescent protein aequorin, we observed that HS temperatures induced prolonged but transient increases in cytoplasmic but not chloroplastic Ca2+. A single HS initiated a refractory period in which additional HS signals failed to increase cytosolic Ca2+. However, throughout this refractory period, seedlings responded to mechanical stimulation or cold shock with cytosolic Ca2+ increases similar to untreated controls. These observations suggest that there may be specific pools of cytosolic Ca2+ mobilized by heat treatments or that the refractory period results from a temporary block in HS perception or transduction. Use of inhibitors suggests that HS mobilizes cytosolic Ca2+ from both intracellular and extracellular sources.

Membrane lipid perturbation modifies the set point of the temperature of heat shock response in yeast.

Addition of a saturated fatty acid (SFA) induced a strong increase in heat shock (HS) mRNA transcription when cells were heat-shocked at 37 degrees C, whereas treatment with an unsaturated fatty acid (UFA) reduced or eliminated the level of HS gene transcription at 37 degrees C. Transcription of the delta 9-desaturase gene (Ole1) of Histoplasma capsulatum, whose gene product is responsible for the synthesis of UFA, is up-regulated in a temperature-sensitive strain. We show that when the L8-14C mutant of Saccharomyces cerevisiae, which has a disrupted Ole1 gene, is complemented with its own Ole1 coding region under control of its own promoter or Ole1 promoters of H. capsulatum, the level of HS gene transcription depends on the activity of the promoters. Fluorescence anisotropy of mitochondrial membranes of completed strains corresponded to the different activity of the Ole1 promoter used. We propose that the SFA/UFA ratio and perturbation of membrane lipoprotein complexes are involved in the perception of rapid temperature changes and under HS conditions disturbance of the preexisting membrane physical state causes transduction of a signal that induces transcription of HS genes.

Particle engineering for the production of respirable dry powder formulations

Hyaluronan (HA) plays an important role in lung pathophysiology. For this reason it has attracted great attention both as active ingredient and as excipient in treating lung diseases by direct pulmonary HA administration. The aim was the production of highly respirable and flowable HA powders either as a potential carrier for drug delivery or for being delivered directly by inhalation. Engineered sodium hyaluronate powders were produced by spray-drying technique. All the spray-dried powders were characterised in terms of particle size distribution, drug content, morphology and in vitro respirability. HA was successfully formulated with salbutamol sulphate in combination with leucine and highlighted remarkable aerodynamic performance (emitted dose equal to 83 % and FPF % equal to 97.1%). Moreover, HA colloidal solutions were designed and they were spray-dried. In order to improve particle aerodynamic characteristics, different types of excipients were investigated. In particular, stearylamine (5% w/w) allowed to obtain the best performance throughout the experimental set. Finally, in vitro biocompatibility was carried out by MTT assay and High Content Analysis for selected dry powder formulations and starting materials. The assays demonstrated the same outcome by confirming the HA biocompatibility and by producing the same rank of toxicity for the surfactants. The general conclusion of the project is that formulation containing HA and stearyl alcohol represents the best performing formulation.

Steric and mass-induced sea level variations in the Mediterranean Sea revisited

The total sea level variation (SLV) is the combination of steric and mass␣induced SLV, whose exact shares are key to understanding the oceanic response to climate system changes. Total SLV can be observed by radar altimetry satellites such as TOPEX/POSEIDON and Jason 1/2. The steric SLV can be computed through temperature and salinity profiles from in situ measurements or from ocean general circulation models (OGCM), which can assimilate the said observations. The mass-induced SLV can be estimated from its time-variable gravity (TVG) signals. We revisit this problem in the Mediterranean Sea estimating the observed, steric, and mass-induced SLV, for the latter we analyze the latest TVG data set from the GRACE (Gravity Recovery and Climate Experiment) satellite mission launched in 2002, which is 3.5 times longer than in previous studies, with the application of a two-stage anisotropic filter to reduce the noise in high-degree and -order spherical harmonic coefficients. We confirm that the intra-annual total SLV are only produced by water mass changes, a fact explained in the literature as a result of the wind field around the Gibraltar Strait. The steric SLV estimated from the residual of “altimetry minus GRACE” agrees in phase with that estimated from OGCMs and in situ measurements, although showing a higher amplitude. The net water fluxes through both the straits of Gibraltar and Sicily have also been estimated accordingly.

Level of involvement of clinical nurses in the evaluation of competence of nursing students

Objective. To determine the level of involvement of clinical nurses accredited by the Universitat Jaume I (Spain) as mentors of practice (Reference Nurses) in the evaluation of competence of nursing students. Methodolgy. Cross-sectional study, in which the “Clinical Practice Assessment Manual” (CPAM) reported by reference 41 nurses (n=55) were analyzed. Four quality criteria for completion were established: with information at least 80% of the required data, the presence of the signature and final grade in the right place. Verification of learning activities was also conducted. Data collection was performed concurrently reference for nurses and teachers of the subjects in the formative evaluations of clinical clerkship period in the matter “Nursing Care in Healthcare Processes “, from March to June 2013. Results. 63% of CPAM were completed correctly, without reaching the quality threshold established (80%). The absence of the signature is the main criteria of incorrect completion (21%). Nine learning activities do not meet the quality threshold set (80%) (p < 0.05). There are significant differences according to clinical units p < 0.05. From the 30 learning activities evaluated in the CPAM, it can be stated that nine of them do not reach the verification threshold established (80%), therefore it cannot be assumed that these activities had been completed by students and evaluated by the RefN throughout the clinical clerkship period. Conclusion. The level of involvement of Reference Nurse cannot be considered adequate, although strategies to encourage involvement through collaboration and training must be developed.

SMEs and Level 2 BIM, the Way Forward

The UK construction industry comprises a very high proportion of SMEs that is companies employing up to 250. A Department for Business, Innovation and Skills research paper, found that SMEs had a 71.2% share of work in the construction industry. Micro and small firms (i.e. those employing up to 50) had a share of 46.7% of work (Ive and Murray 2013). The Government has high ambitions for UK construction. Having been found by successive government commissioned studies to be inefficient and highly fragmented, ambitious targets have been set for the industry to achieve 33% reduction in costs and 50% faster delivery by 2025. As a significant construction client, the Government has mandated the use of Level 2 BIM from 2016 on publicly funded projects over £5 million. The adoption of BIM plays a key role in the 2025 vision but a lack of clarity persists in the industry over BIM and significant barriers are perceived to its implementation, particularly amongst SMEs. However, industry wide transformation will be challenging without serious consideration of the capabilities of this large majority. Many larger firms, having implemented Level 2 BIM are now working towards Level 3 BIM while many of the smaller firms in the industry have not even heard of BIM. It would seem that fears of a ‘two tier’ industry are perhaps being realised. This paper builds on an earlier one (Mellon & Kouider 2014) and investigates, through field work, the level of Level 2 BIM implementation amongst SMEs compared to a large organisation. Challenges and innovative solutions identified through collected data are fully discussed and compared. It is suggested that where the SME perceives barriers towards adoption of the technologies which underpin BIM, they may consider collaborative methods of working as an interim step in order to work towards realising the efficiencies and benefits that these methods can yield. While the barriers to adoption of BIM are significant, it is suggested that they are not insurmountable for the SME and some recommendations for possible solutions are made.

Does Mandatory IFRS Adoption in the EU Level the International Playing Field Between Foreign and Domestic Analysts? ACES Working Papers, October 2011

International Financial Reporting Standards (IFRS) have been promoted as a global set of financial reporting standards that will help integrate global capital markets. We examine whether the mandatory European-wide adoption of IFRS in 2005 improved the forecast accuracy for foreign analysts relative to that of domestic analysts. We find that, on average, foreign analysts experience no incremental improvement in forecast accuracy relative to domestic analysts. However, we find that those foreign analysts who are familiar with IFRS do experience an incremental improvement in forecast accuracy relative to domestic analysts. We also find that this incremental improvement in forecast accuracy relative to domestic analysts is concentrated among firms domiciled in countries with both strong enforcement regimes and domestic accounting standards that differ significantly from IFRS. Our results highlight that both familiarity with IFRS and the quality of countries' enforcement environments play key roles in determining the extent to which IFRS adoption can reduce information asymmetry between foreign and domestic analysts.

Downscaled land surface temperatures obtained by a particle smoothing approach, with links to NetCDF files

This dataset contains continuous time series of land surface temperature (LST) at spatial resolution of 300m around the 12 experimental sites of the PAGE21 project (grant agreement number 282700, funded by the EC seventh Framework Program theme FP7-ENV-2011). This dataset was produced from hourly LST time series at 25km scale, retrieved from SSM/I data (André et al., 2015, doi:10.1016/j.rse.2015.01.028) and downscaled to 300m using a dynamic model and a particle smoothing approach. This methodology is based on two main assumptions. First, LST spatial variability is mostly explained by land cover and soil hydric state. Second, LST is unique for a land cover class within the low resolution pixel. Given these hypotheses, this variable can be estimated using a land cover map and a physically based land surface model constrained with observations using a data assimilation process. This methodology described in Mechri et al. (2014, doi:10.1002/2013JD020354) was applied to the ORCHIDEE land surface model (Krinner et al., 2005, doi:10.1029/2003GB002199) to estimate prior values of each land cover class provided by the ESA CCI-Land Cover product (Bontemps et al., 2013) at 300m resolution . The assimilation process (particle smoother) consists in simulating ensemble of LST time series for each land cover class and for a large number of parameter sets. For each parameter set, the resulting temperatures are aggregated considering the grid fraction of each land cover and compared to the coarse observations. Miniminizing the distance between the aggregated model solutions and the observations allow us to select the simulated LST and the corresponding parameter sets which fit the observations most closely. The retained parameter sets are then duplicated and randomly perturbed before simulating the next time window. At the end, the most likely LST of each land cover class are estimated and used to reconstruct LST maps at 300m resolution using ESA CCI-Land Cover. The resulting temperature maps on which ice pixels were masked, are provided at daily time step during the nine-year analysis period (2000-2009).

Total V9 rDNA information organized at the metabarcode level (Database W4)

The present data set provides a tab separated text file compressed in a zip archive. The file includes metadata for each TaraOceans V9 rDNA metabarcode including the following fields: md5sum = unique identifier; lineage = taxonomic path associated to the metabarcode; pid = % identity to the closest reference barcode from V9_PR2; sequence = nucleotide sequence of the metabarcode; refs = identity of the best hit reference sequence(s); TARA_xxx = number of occurrences of this barcode in each of the 334 samples; totab = total abundance of the barcode ; cid = identifier of the OTU to which the barcode belongs; and taxogroup = high-taxonomic level assignation of this barcode. The file also includes three categories of functional annotations: (1) Chloroplast: yes, presence of permanent chloroplast; no, absence of permanent chloroplast ; NA, undetermined. (2) Symbiont (small partner): parasite, the species is a parasite; commensal, the species is a commensal; mutualist, the species is a mutualist symbiont, most often a microalgal taxon involved in photosymbiosis; no the species is not involved in a symbiosis as small partner; NA, undetermined. (3) Symbiont (host): photo, the host species relies on a mutualistic microalgal photosymbiont to survive (obligatory photosymbiosis); photo_falc, same as photo, but facultative relationship; photo_klep, the host species maintains chloroplasts from microalgal prey(s) to survive; photo_klep_falc, same as photo_klep, but facultative; Nfix, the host species must interact with a mutualistic symbiont providing N2 fixation to survive; Nfix_falc, same as Nfix, but facultative; no, the species is not involved in any mutualistic symbioses; NA, undetermined. For example, the collodarian/Brandtodinium symbiosis is annotated: Chloroplast, "no"; Symbiont (small), "no"; Symbiont (host), "photo", for the collodarian host; and: Chloroplast, "yes"; Symbiont (small), "mutualist"; Symbiont (host), "no", for the dinoflagellate microalgal endosymbiont.chloroplast = "yes", "no" or "NA"; symbiont.small = "parasite", "commensal", "mutualist", "no" or "NA"; symbiont.host = "photo", "photo_falc", "photo_klep", "Nfix", no or NA; benef = "Nfix", "no" or "NA"; trophism = Metazoa , heterotroph , NA , photosymbiosis , phototroph according to the previous fields.

Disentangling the impact of seroconversion age and set-point viral load on ART-free HIV survival

Thesis (Master's)--University of Washington, 2016-06

Exploration of the cell-cycle genes found within the RIKEN FANTOM2 data set

The cell cycle is one of the most fundamental processes within a cell. Phase-dependent expression and cell-cycle checkpoints require a high level of control. A large number of genes with varying functions and modes of action are responsible for this biology. In a targeted exploration of the FANTOM2-Variable Protein Set, a number of mouse homologs to known cell-cycle regulators as well as novel members of cell-cycle families were identified. Focusing on two prototype cell-cycle families, the cyclins and the NIMA-related kinases (NEKs), we believe we have identified all of the mouse members of these families, 24 cyclins and 10 NEKs, and mapped them to ENSEMBL transcripts. To attempt to globally identify all potential cell cycle-related genes within mouse, the MGI (Mouse Genome Database) assignments for the RIKEN Representative Set (RPS) and the results from two homology-based queries were merged. We identified 1415 genes with possible cell-cycle roles, and 1758 potential paralogs. We comment on the genes identified in this screen and evaluate the merits of each approach.

Higher-level language deficits resulting from left primary cerebellar lesions

Background: Contemporary neuropsychological studies suggest that cerebellar lesions may impact upon higher-level cognitive functioning via mechanisms of crossed cerebello-cerebral diaschisis. Accordingly, right cerebellar lesions have been previously associated with linguistic impairments such as reduced word fluency and agrammatic output. Recently, however, neuroimaging investigations have also identified ipsilateral cerebral hypoperfusion as a consequence of cerebellar lesions, implicating a potential role for the left cerebellum in the mediation of language processes. Aims: The purpose of this research was to investigate the effects of left cerebellar lesions of vascular origin, on general as well as high-level language skills. Methods & Procedures: Linguistic profiles were compiled for five individuals with left primary cerebellar lesions utilising a comprehensive language test battery. Individual scores relevant to each subtest were compared to a group of non-neurologically impaired controls. The criterion for anomalous performance was established as greater than or equal to 1.5 SD below the mean of the control group. Outcomes & Results: The findings of this research suggest that higher-level language deficits may result from left primary cerebellar lesions. All participants demonstrated deficits on measures of word fluency, sentence construction within a set context, producing word definitions, and producing multiple definitions for the same word. Deficits were also noted for several participants on measures of understanding figurative language, forming word associations, identifying and correcting semantic absurdities, and producing synonyms and antonyms. Conclusions: The results presented challenge the notion of a lateralised linguistic cerebellum, supporting a potential role for the left as well as right cerebellar hemispheres in the regulation of language processes, presumably via cerebellar-basal ganglia/thalamo-cortical pathways.

Adverse Health Effects of Chronic Exposure to Low-Level Cadmium in Foodstuffs and Cigarette Smoke

Cadmium is a cumulative nephrotoxicant that is absorbed into the body from dietary sources and cigarette smoking. The levels of Cd in organs such as liver and kidney cortex increase with age because of the lack of an active biochemical process for its elimination coupled with renal reabsorption. Recent research has provided evidence linking Cd-related kidney dysfunction and decreases in bone mineral density in nonoccupationally exposed populations who showed no signs of nutritional deficiency. This challenges the previous view that the concurrent kidney and bone damage seen in Japanese itai-itai disease patients was the result of Cd toxicity in combination with nutritional deficiencies, notably, of zinc and calcium. Further, such Cd-linked bone and kidney toxicities were observed in people whose dietary Cd intakes were well within the provisional tolerable weekly intake (PTWI) set by the Joint Food and Agriculture Organization/World Health Organization Expert Committee on Food Additives of 1 mug/kg body weight/day or 70 mug/day. This evidence points to the much-needed revision of the current PTWI for Cd. Also, evidence for the carcinogenic risk of chronic Cd exposure is accumulating and Cd effects on reproductive outcomes have begun to emerge.

Phobic anxiety in 11 nations: part II. Hofstede's dimensions of national cultures predict national-level variations

Hofstede's dimensions of national cultures termed Masculinity-Femininity (MAS) and Uncertainty Avoidance (UAI) (Hofstede, 2001) are proposed to be of relevance for understanding national-level differences in self-assessed fears. The potential predictive role of national MAS was based on the classical work of Fodor (Fodor, 1974). Following Fodor, it was predicted that masculine (or tough) societies in which clearer differentiations are made between gender roles (high MAS) would report higher national levels of fears than feminine (or soft/modest) societies in which such differentiations are made to a clearly lesser extent (low MAS). In addition, it was anticipated that nervous-stressful-emotionally-expressive nations (high UAI) would report higher national levels of fears than calm-happy and low-emotional countries (low UAI), and that countries high on both MAS and UAI would report the highest national levels of fears. A data set comprising 11 countries (N > 5000) served as the basis for analyses. As anticipated, (a) high MAS predicted higher national levels of Agoraphobic fears and of Bodily Injury-Illness-Death fears; (b) higher scores on both UAI and MAS predicted higher national scores on Bodily Injury-Illness-Death fears, fears of Sexual and Aggressive Scenes, and Harmless Animals fears; (c) higher UAI predicted higher national levels of Harmless Animals, Bodily Injury-Illness-Death, and Agoraphobic fears. (C) 2003 Elsevier Ltd. All rights reserved.