Abstract Klebsiella pneumoniae , Klebsiella variicola and Klebsiella quasipneumoniae are difficult to differentiate phenotypically, leading to misinterpretation of their infection prevalence. We ...propose a multiplex PCR for blaSHV, LEN and OKP and their flanking gene ( deo R). Since this scheme focuses only on chromosomal genes, it will be feasible for Klebsiella identification in the clinical routine.
The rate and pathway of ferrihydrite (Fh) transformation at oxic conditions to more stable products is controlled largely by temperature, pH, and the presence of other ions in the system such as ...nitrate (NO3 –), sulfate (SO4 2–), and arsenate (AsO4 3–). Although the mechanism of Fh transformation and oxyanion complexation have been separately studied, the effect of surface complex type and strength on the rate and pathway remains only partly understood. We have developed a kinetic model that describes the effects of surface complex type and strength on Fh transformation to goethite (Gt) and hematite (Hm). Two sets of oxyanion-adsorbed Fh samples were prepared, nonbuffered and buffered, aged at 70 ± 1.5 °C, and then characterized using synchrotron X-ray scattering methods and wet chemical analysis. Kinetic modeling showed a significant decrease in the rate of Fh transformation for oxyanion surface complexes dominated by strong inner-sphere (SO4 2– and AsO4 3–) versus weak outer-sphere (NO3 –) bonding and the control. The results also showed that the Fh transformation pathway is influenced by the type of surface complex such that with increasing strength of bonding, a smaller fraction of Gt forms compared with Hm. These findings are important for understanding and predicting the role of Fh in controlling the transport and fate of metal and metalloid oxyanions in natural and applied systems.
A novel, integrated, in vitro gastrointestinal (GI) system is presented to study oral bioavailability parameters of small molecules. Three compartments were combined into one hyphenated, flow-through ...set-up. In the first compartment, a compound was exposed dynamically to enzymatic digestion in three consecutive microreactors, mimicking the processes of the mouth, stomach, and intestine. The resulting solution (chyme) continued to the second compartment, a flow-through barrier model of the intestinal epithelium allowing absorption of the compound and metabolites thereof. The composition of the effluents from the barrier model were analysed either offline by electrospray-ionisation-mass spectrometry (ESI-MS), or online in the final compartment using chip-based ESI-MS. Two model drugs, omeprazole and verapamil, were used to test the integrated model. Omeprazole was shown to be broken down upon treatment with gastric acid, but reached the cell barrier unharmed when introduced to the system in a manner emulating an enteric-coated formulation. In contrast, verapamil was unaffected by digestion. Finally, a reduced uptake of verapamil was observed when verapamil was introduced to the system dissolved in apple juice, a simple food matrix. It is envisaged that this integrated, compartmentalised GI system has potential for enabling future research in the fields of pharmacology, toxicology, and nutrition.
Forensic hair evidence can be used to obtain retrospective timelines of drug use by analysis of hair segments. However, this is a laborious and time-consuming process, and mass spectrometric (MS) ...imaging techniques, which show great potential for single-hair targeted analysis, are less useful due to differences in hair growth rate between individual hairs. As an alternative, a fast untargeted analysis method was developed that uses direct analysis in real time–high-resolution mass spectrometry (DART-HRMS) to longitudinally scan intact locks of hair without extensive sample preparation or segmentation. The hair scan method was validated for cocaine against an accredited liquid chromatography/tandem mass spectrometry (LC/MS/MS) method. The detection limit for cocaine in hair was found to comply with the cutoff value of 0.5 ng/mg recommended by the Society of Hair Testing; that is, the DART hair scan method is amenable to forensic cases. Under DART conditions, no significant thermal degradation of cocaine occurred. The standard DART spot size of 5.1 ± 1.1 mm could be improved to 3.3 ± 1.0 mm, corresponding to approximately 10 days of hair growth, by using a high spatial resolution exit cone. By use of data-dependent product ion scans, multiple drugs of abuse could be detected in a single drug user hair scan with confirmation of identity by both exact mass and MS/HRMS fragmentation patterns. Furthermore, full-scan high-resolution data were retrospectively interrogated versus a list of more than 100 compounds and revealed additional hits and temporal profiles in good correlation with reported drug use.
Recent studies in simple model organisms have shown that centromere pairing is important for ensuring high-fidelity meiotic chromosome segregation. However, this process and the mechanisms regulating ...it in higher eukaryotes are unknown. Here we present the first detailed study of meiotic centromere pairing in mouse spermatogenesis and link it with key events of the G2/metaphase I transition. In mouse we observed no evidence of the persistent coupling of centromeres that has been observed in several model organisms. We do however find that telomeres associate in non-homologous pairs or small groups in B type spermatogonia and pre-leptotene spermatocytes, and this association is disrupted by deletion of the synaptonemal complex component SYCP3. Intriguingly, we found that, in mid prophase, chromosome synapsis is not initiated at centromeres, and centromeric regions are the last to pair in the zygotene-pachytene transition. In late prophase, we first identified the proteins that reside at paired centromeres. We found that components of the central and lateral element and transverse filaments of the synaptonemal complex are retained at paired centromeres after disassembly of the synaptonemal complex along diplotene chromosome arms. The absence of SYCP1 prevents centromere pairing in knockout mouse spermatocytes. The localization dynamics of SYCP1 and SYCP3 suggest that they play different roles in promoting homologous centromere pairing. SYCP1 remains only at paired centromeres coincident with the time at which some kinetochore proteins begin loading at centromeres, consistent with a role in assembly of meiosis-specific kinetochores. After removal of SYCP1 from centromeres, SYCP3 then accumulates at paired centromeres where it may promote bi-orientation of homologous centromeres. We propose that, in addition to their roles as synaptonemal complex components, SYCP1 and SYCP3 act at the centromeres to promote the establishment and/or maintenance of centromere pairing and, by doing so, improve the segregation fidelity of mammalian meiotic chromosomes.
In recent years, therapeutic peptides have gained a lot interest as demonstrated by the 60 peptides approved as drugs in major markets and 150+ peptides currently in clinical trials. However, while ...small molecule docking is routinely used in rational drug design efforts, docking peptides has proven challenging partly because docking scoring functions, developed and calibrated for small molecules, perform poorly for these molecules. Here, we present random forest classifiers trained to discriminate correctly docked peptides. We show that, for a testing set of 47 protein–peptide complexes, structurally dissimilar from the training set and previously used to benchmark AutoDock Vina’s ability to dock short peptides, these random forest classifiers improve docking power from ∼25% for AutoDock scoring functions to an average of ∼70%. These results pave the way for peptide-docking success rates comparable to those of small molecule docking. To develop these classifiers, we compiled the ProptPep37_2021 data set, a curated, high-quality set of 322 crystallographic protein–peptides complexes annotated with structural similarity information. The data set also provides a collection of high-quality putative poses with a range of deviations from the crystallographic pose, providing correct and incorrect poses (i.e., decoys) of the peptide for each entry. The ProptPep37_2021 data set as well as the classifiers presented here are freely available.
Exogenous visual orienting by reward Failing, Michel F; Theeuwes, Jan
Journal of vision,
2014-Jan-01, 2014-01-01, 20140101, Volume:
14, Issue:
5
Journal Article
Peer reviewed
Open access
Classic spatial cueing experiments have demonstrated that salient cues have the ability to summon attention as evidenced by performance benefits when the cue validly indicates the target location and ...costs when the cue is invalid. Here we show that nonsalient cues that are associated with reward also have the ability to capture attention. We demonstrate performance costs and benefits in attentional orienting towards a nonsalient cue that acquired value through reward learning. The present study provides direct evidence that stimuli associated with reward have the ability to exogenously capture spatial attention independent of task-set, goals and salience.
Pulse oximetry-derived oxygen saturation is typically >97% in normoxia and hyperoxia, limiting its clinical use. The new Oxygen Reserve Index (ORi), a relative indicator of the partial pressure of ...oxygen dissolved in arterial blood (PaO2) in the range of 100-200 mm Hg, may allow additional monitoring of oxygen status.
In this prospective validation intervention study, 20 healthy volunteers were breathing standardized oxygen concentrations ranging from mild hypoxia (fraction of inspired oxygen = 0.14) to hyperoxia (fraction of inspired oxygen = 1.0) via a tight-fitting face mask. ORi was measured noninvasively by multiwavelength pulse co-oximetry using 2 finger sensors. These ORi values (unitless scale, 0.00-1.00) were compared with measured PaO2 values. Repeated-measurements correlation analysis was performed to assess the ORi/PaO2 relationship. ORi trending ability was assessed using a 4-quadrant plot. The area under the receiver operating characteristics curve was calculated to assess the prediction of hypoxia (low-ranged PaO2, <100 mm Hg).
Within the ORi-sensitive range, a strong positive correlation was found between ORi and PaO2 for both sensors (R = 0.78 and 0.83; P < .0001). ORi trending of PaO2 was good within this range (concordance rate = 94%). The prediction of PaO2 <100 mm Hg was also good, with an area under the receiver operating characteristics curve of 0.91 and 99% sensitivity and 82% specificity.
In this prospective volunteer validation study, a strong and positive correlation between PaO2 and ORi was found, together with a good trending ability. Based on these data, the future use of ORi as a continuous noninvasive monitoring tool for assessing oxygenation status in patients receiving supplemental oxygen might be supported.
•Mn enhanced the aqueous corrosion resistance of Al when alloyed in solid solution.•A thinner passive layer with closer to stoichiometry composition was formed on Al-Mn.•Selective surface dissolution ...of Mn increased free volume at metal/oxide interface.•Simulation showed barrier characteristics of oxide increased with free volume in Al.
The effects of manganese on the aqueous corrosion of aluminum-manganese alloys were investigated by experiments and atomistic simulations. Electrochemical measurements, x-ray photoelectron spectroscopy, and atom probe tomography analysis indicate that manganese addition enhanced the corrosion resistance of aluminum without participating in the surface oxidation. The selective dissolution of manganese was believed to increase the free volume at the metal/oxide interface to facilitate the formation of a denser, thinner oxide layer with closer to stoichiometry composition. Atomistic simulations showed that the oxide layer compactness increased, and defect density decreased with increasing free volume content in Al, resulting in enhanced barrier characteristics.
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