Miracle-dz/UniFAR-FTUs huggingface dataset:
RAB-5 and RAB-10 cooperate to regulate neuropeptide release in Caenorhabditis elegans

Neurons secrete neuropeptides from dense core vesicles (DCVs) to modulate neuronal activity. Little is known about how neurons manage to differentially regulate the release of synaptic vesicles (SVs) and DCVs. To analyze this, we screened all Caenorhabditis elegans Rab GTPases and Tre2/Bub2/Cdc16 (TBC) domain containing GTPase-activating proteins (GAPs) for defects in DCV release from C. elegans motoneurons. rab-5 and rab-10 mutants show severe defects in DCV secretion, whereas SV exocytosis is unaffected. We identified TBC-2 and TBC-4 as putative GAPs for RAB-5 and RAB-10, respectively. Multiple Rabs and RabGAPs are typically organized in cascades that confer directionality to membrane-trafficking processes. We show here that the formation of release-competent DCVs requires a reciprocal exclusion cascade coupling RAB-5 and RAB-10, in which each of the two Rabs recruits the other’s GAP molecule. This contributes to a separation of RAB-5 and RAB-10 domains at the Golgi–endosomal interface, which is lost when either of the two GAPs is inactivated. Taken together, our data suggest that RAB-5 and RAB-10 cooperate to locally exclude each other at an essential stage during DCV sorting.
Appropriate Use of Information on Family History of Disease in Recruitment for Linkage Analysis Studies

When conducting genetic studies for complex traits, large samples are commonly required to detect any of the number of genes with relatively low effect thought to underly such traits. This is because, in contrast to monogenic diseases, complex traits typically result from a number of different genetic pathways (genetic heterogeneity) and any sample is likely to contain a considerable fraction of sporadic cases (phenocopies). Such samples are time‐consuming and costly to recruit and analyse. Methods which might be used to decrease sample size include attempting to select families, with the aim of reducing genetic heterogeneity or phenocopy rate within the sample. Selecting cases with positive family history of disease should reduce the phenocopy rate, and this strategy has been employed in linkage studies of complex disease, although evaluations of such a strategy have been equivocal.
Rab GTPases Are Recruited to Chlamydial Inclusions in Both a Species-Dependent and Species-Independent Manner

ABSTRACT Chlamydiae are obligate intracellular bacteria that replicate within an inclusion that is trafficked to the peri-Golgi region where it fuses with exocytic vesicles. The host and chlamydial proteins that regulate the trafficking of the inclusion have not been identified. Since Rab GTPases are key regulators of membrane trafficking, we examined the intracellular localization of several green fluorescent protein (GFP)-tagged Rab GTPases in chlamydia-infected HeLa cells. GFP-Rab4 and GFP-Rab11, which function in receptor recycling, and GFP-Rab1, which functions in endoplasmic reticulum (ER)-to-Golgi trafficking, are recruited to Chlamydia trachomatis, Chlamydia muridarum, and Chlamydia pneumoniae inclusions, whereas GFP-Rab5, GFP-Rab7, and GFP-Rab9, markers of early and late endosomes, are not. In contrast, GFP-Rab6, which functions in Golgi-to-ER and endosome-to-Golgi trafficking, is associated with C. trachomatis inclusions but not with C. pneumoniae or C. muridarum inclusions, while the opposite was observed for the Golgi-localized GFP-Rab10. Colocalization studies between transferrin and GFP-Rab11 demonstrate that a portion of GFP-Rab11 that localizes to inclusions does not colocalize with transferrin, which suggests that GFP-Rab11's association with the inclusion is not mediated solely through Rab11's association with transferrin-containing recycling endosomes. Finally, GFP-Rab GTPases remain associated with the inclusion even after disassembly of microtubules, which disperses recycling endosomes and the Golgi apparatus within the cytoplasm, suggesting a specific interaction with the inclusion membrane. Consistent with this, GFP-Rab11 colocalizes with C. trachomatis IncG at the inclusion membrane. Therefore, chlamydiae recruit key regulators of membrane trafficking to the inclusion, which may function to regulate the trafficking or fusogenic properties of the inclusion.
Floral Transmission of Erwinia tracheiphila by Cucumber Beetles in a Wild Cucurbita pepo

ABSTRACT Cucumber beetles, Acalymma vittatum (F.) and Diabrotica undecipunctata howardi (Barber), are specialist herbivores of cucurbits and the vector of Erwinia tracheiphila (E.F. Smith) Holland, the causative agent of wilt disease. Cucumber beetles transmit E. tracheiphila when infected frass falls onto leaf wounds at the site of beetle feeding. We show that E. tracheiphila also can be transmitted via the floral nectaries of Cucurbita pepo ssp. texana L. Andres (Texas gourd). Under field conditions, we found that beetles aggregate in flowers in the late morning, that these beetles chew the anther filaments that cover the nectaries in male flowers thereby exposing the nectary, and that beetle frass accumulates on the nectary. We use real-time polymerase chain reaction to show that most of the flowers produced during the late summer possess beetle frass containing E. tracheiphila. Greenhouse experiments, in which cultures of E. tracheiphila are deposited onto floral nectaries, show that Texas gourds can contract wilt disease through the floral nectaries. Finally, we use green fluorescent protein-transformed E. tracheiphila to document the movement of E. tracheiphila through the nectary into the xylem of the pedicel before the abscission of the flower. Together, these data show that E. tracheiphila can be transmitted through infected frass that falls on or near the floral nectaries. We hypothesize that the concentration of frass from many beetles in the flowers increases both exposure to and the concentration of E. tracheiphila and plays a major role in the dynamics of wilt disease in both wild populations and cultivated squash fields.
FPGA Implementation of the Power Electronic Converter Model for Real-Time Simulation of Electromagnetic Transients

This paper presents an enhanced implementation methodology for the associated discrete circuit model of a power-electronic converter in a field-programmable gate array-based real-time power systems simulator. The simulator is intended for the testing and performance evaluation of digital control/protection platforms based on the hardware-in-the-loop concept. The salient features of the proposed implementation are: 1) It eliminates the need for corrective measures to reduce error due to the lack of synchronization between the simulation time-grid and output signals of the control/protection platform; 2) it provides scalability, that is, it maintains calculation time, within each simulation time step, nearly fixed irrespective of the system size; and 3) it enables the use of a small simulation timestep, for example, a couple of hundreds of nanoseconds for the overall system, in contrast to the microseconds range time-steps used in the existing simulators. Thus, it is also able to provide a wide frequency bandwidth for the simulation results. This paper also reports the implementation results and their verifications corresponding to real-time simulation of two converter units based on less than 60-ns calculation time within each simulation time step. The scalability property is also verified based on real-time simulation of six converter units.
Game Theory for Multi-Access Edge Computing: Survey, Use Cases, and Future Trends

Game theory (GT) has been used with significant success to formulate, and either design or optimize, the operation of many representative communications and networking scenarios. The games in these scenarios involve, as usual, diverse players with conflicting goals. This paper primarily surveys the literature that has applied theoretical games to wireless networks, emphasizing use cases of upcoming multiaccess edge computing (MEC). MEC is relatively new and offers cloud services at the network periphery, aiming to reduce service latency backhaul load, and enhance relevant operational aspects such as quality of experience or security. Our presentation of GT is focused on the major challenges imposed by MEC services over the wireless resources. The survey is divided into classical and evolutionary games. Then, our discussion proceeds to more specific aspects which have a considerable impact on the game’s usefulness, namely, rational versus evolving strategies, cooperation among players, available game information, the way the game is played (single turn, repeated), the game’s model evaluation, and how the model results can be applied for both optimizing resource-constrained resources and balancing diverse tradeoffs in real edge networking scenarios. Finally, we reflect on lessons learned, highlighting future trends and research directions for applying theoretical model games in upcoming MEC services, considering both network design issues and usage scenarios.
Simultaneous estimation of stereo correspondence and camera geometry from marker tracks

Cardiac deformation may be measured by following radiopaque markers in 3-D with two X-ray cameras simultaneously. The 3-D positions of the markers can be reconstructed when (1) the camera geometry, and (2) the stereo correspondence are known. When observing large numbers (10-100) of identically shaped markers in an uncalibrated X-ray stereo camera set-up, both (1) and (2) are unknown. In the present study we developed a method to estimate (1) and (2) simultaneously from the sets of marker tracks obtained in the two views. In a computer simulation of 48 markers attached to a moving heart, 30% of the tracks were considered as missing, so only 24 stereo track pairs remained. On the average the method identified 23 pairs, 0.5% of which were false. Accurate estimates were obtained for the angles defining the camera geometry (RMS error 0.02/spl deg/ to 1/spl deg/).
Identification of four new members of the internalin multigene family of Listeria monocytogenes EGD

Listeria monocytogenes is a bacterial pathogen that is able to invade nonphagocytic cells. Two surface proteins, internalin, the inlA gene product, and InlB, play important roles in the entry into cultured mammalian cells. These proteins also have extensive sequence similarities. Previously, Southern hybridization predicted the existence of an internalin multigene family. Recently, InlC, a secreted protein of 30 kDa homologous to InlA and InlB, was identified. In this work, we identified and characterized four new members of the internalin multigene family, inlC2, inlD, inlE, and inlF which encode proteins of 548, 567, 499, and 821 amino acids respectively. inlC2, inlD, and inlE are contiguous on the chromosome of L. monocytogenes EGD, whereas inlF is located in a different chromosomal region. These four inl gene products display the principal features of internalin, namely, a signal sequence, two regions of repeats (or LRR and B repeats), and a putative cell wall anchor sequence containing the sorting motif LPXTG. The four inl genes were maximally expressed albeit at a low level during early exponential growth in bacterial medium at 37 degrees C. The role of these inl genes in L. monocytogenes invasion was assessed by constructing isogenic chromosomal deletion mutants and testing them for entry into various nonphagocytic cells. Unexpectedly, the inlC2, inlD, inlE, and inlF null mutants were not affected for entry into any of the cell lines tested, raising the possibility that these genes are needed for an aspect of pathogenicity other than invasion. The identity of such an aspect remains to be determined.
Validation of MET estimates and step measurement using the ActivPAL physical activity logger

Abstract The purpose of this study was to determine the validity of the metabolic equivalent (MET) equation and step rate function of the ActivPAL™ physical activity logger in a group of females. Using a standard treadmill protocol, 62 females aged 15–25 years walked on a treadmill at speeds between 3.2 and 7.0 km · h−1 while wearing an ActivPAL. Oxygen consumption was measured using expired gas analysis at each speed and METs for each speed were estimated based on each participant's own resting metabolic rate. A sub-set of 18 participants also wore an Actigraph. Results showed that the in-built equation in the ActivPAL significantly underestimated (P < 0.001) METs under treadmill conditions at higher intensities. The ActivPAL equation is based on step rate yet the relationship between counts and measured METs (r = 0.76; P < 0.001) is stronger than that between steps and measured METs (r = 0.59; P < 0.001). Both the ActivPAL and Actigraph step functions showed no significant difference (P > 0.05) to video recorded step rate except at the slowest walking speed where the Actigraph significantly underestimated steps (P < 0.05). The development of a new equation based on the counts–METs relationship that includes a variety of speeds and activities would be useful. The ActivPAL step function performs better than the Actigraph at the slowest walking speed under treadmill conditions.
In-group as part of the self: In-group favoritism is mediated by medial prefrontal cortex activation

Abstract Our identity consists of knowledge about our individual attributes (personal identity) as well as knowledge about our shared attributes derived from our membership in certain social groups (social identity). As individuals seek to achieve a positive self-image, they aim at comparing favorably with other individuals or their in-group comparing favorably with referent out-groups. Imaging data suggest a network centered on the medial prefrontal cortex (MPFC) to instantiate functions that are integral to the self, conceived as the personal self. Given that the social self is constituted by the same mechanisms as the personal self, we expect MPFC activation also for situations in which the social self is addressed, for instance when situations permit evaluative intergroup comparisons. Accordingly, participants worked on a modified version of the minimal group paradigm in the present functional magnetic resonance imaging experiment. Imaging data revealed activation within a network centered on the dorsal MPFC specifically for social identity processes. Furthermore, this activation showed correlation with the displayed in-group bias. The present findings show that social and personal identity processes draw on the same cerebral correlates and hence it is concluded that a network centered on the MPFC subserves functions integral to the self.
Continuous nebulized albuterol attenuates acute lung injury in an ovine model of combined burn and smoke inhalation*

Objective:Albuterol, due to its bronchodilatory and anti-inflammatory effects, is given via continuous nebulization in children with severe asthma. Combined burn and smoke inhalation injury frequently results in acute lung injury due to a combination of airway obstruction and inflammation. We hypothesized that albuterol administered via continuous nebulization would mitigate acute lung injury after smoke inhalation injury and burn. Design:Randomized prospective animal model. Subjects:Twenty adult female sheep (mean weight, 33.1 ± 0.9 kg). Interventions:Adult ewes were subjected to a 40% body surface area third-degree flame burn and smoke inhalation injury after tracheostomy. Sheep were allocated to a) sham group, b) saline continuous nebulization group, c) 20 mg of albuterol continuous nebulization group, or d) 40 mg of albuterol continuous nebulization group (n = 5 animals per group). All groups received intravenous lactated Ringer’s solution at 4 mL · kg−1 · %burn−1 · 24 hrs−1 for resuscitation and were equally mechanically ventilated throughout the 48-hr study period. Pulmonary and cardiac function, lung lymph flow, bronchial obstruction score, and wet/dry lung weights were recorded. Results:Compared with saline and control groups, the albuterol groups had lower pause and peak inspiratory pressures, decreased pulmonary transvascular fluid flux, a significantly higher Pao2/Fio2 ratio, and decreased shunt fraction at 48 hrs postinjury. The wet-to-dry lung weight ratio and bronchial obstruction scores were lower for sheep receiving albuterol. Conclusions:Continuous nebulization of albuterol improves pulmonary function via improved airway clearance and decreased fluid flux in a combined burn/smoke inhalation injury model.
Platelet-activating factor acetylhydrolase is increased in lung lavage fluid from patients with acute respiratory distress syndrome

ObjectivePlatelet-activating factor (PAF) is a proinflammatory phospholipid that may contribute to inflammation in the acute respiratory distress syndrome (ARDS). PAF acetylhydrolase (PAF-AH) degrades PAF and regulates its biological activity. We characterized PAF-AH in bronchoalveolar lavage fluid from ARDS patients (n = 33, 22 survivors), patients at risk for ARDS (n = 6), and healthy controls (n = 6). DesignBronchoalveolar lavage was performed during acute (<96 hrs from onset), plateau (6 to 12 days), and late (≥14 days) phases of ARDS. PatientsIntubated patients with ARDS or a risk factor for ARDS. Measurements and Main ResultsIn ARDS, total bronchoalveolar lavage PAF-AH activity was markedly increased in the acute phase (87 ± 89 mU/mL, n = 33) and then decreased in the plateau (23 ± 14 mU/mL, n = 10) and late phases (19 ± 14 mU/mL, n = 7) (p = .003). Total bronchoalveolar lavage PAF-AH activity during the acute phase of ARDS was also increased as compared with patients at risk for ARDS (16 ± 13 mU/mL, n = 6) and healthy controls (3 ± 3 mU/mL, n = 6) (p < .001). In contrast, plasma PAF-AH activities were the same in controls (3215 ± 858 mU/mL, n = 6), in patients at risk for ARDS (3606 ± 1607 mU/mL, n = 6), and during the acute phase of ARDS (3098 ± 2395 mU/mL, n = 33) (p = .18). PAF-AH mRNA was present in alveolar macrophages in the acute phase of ARDS (five of six) and in at-risk patients (two of three) but not in healthy controls. ConclusionsPAF-AH activity is increased in bronchoalveolar lavage fluid from patients with ARDS. Likely sources include leakage of plasma PAF-AH into alveoli or release of PAF-AH from injured cells; however, the presence of PAF-AH mRNA in alveolar macrophages suggests that PAF-AH may be actively synthesized in the lungs of patients with ARDS. PAF-AH activity in the lungs of ARDS patients may regulate inflammation caused by PAF and related oxidized phospholipids generated in the inflammatory response.
AIR ACCESS LIBERALISATION, MARKETING PROMOTION AND TOURISM TRADE

The objective of the present study is two-fold. Firstly, to assess the impact of air access liberalization on tourism demand for Mauritius and secondly to analyse the dual impact of the interplay between air access liberalization and marketing promotion efforts on tourism demand. Using an Autoregressive Distributed Lag model, the results suggest that air access liberalisation is an important ingredient, albeit to a lesser extent as compared to other classical explanatory variables, of tourism demand. The results also highlight the fact that Mauritius is perceived as a luxurious destination and tourists are also deemed to be price sensitive. Moreover our dynamic approach interestingly confirms the presence of repeat tourism in the island. Finally, the findings also uncover the positive impact of the interplay between air access liberalization and marketing promotion efforts on fostering tourism demand.
Physical and Functional Interactions between Pathogen-Induced Arabidopsis WRKY18, WRKY40, and WRKY60 Transcription Factors[W]

Limited information is available about the roles of specific WRKY transcription factors in plant defense. We report physical and functional interactions between structurally related and pathogen-induced WRKY18, WRKY40, and WRKY60 transcription factors in Arabidopsis thaliana. The three WRKY proteins formed both homocomplexes and heterocomplexes and DNA binding activities were significantly shifted depending on which WRKY proteins were present in these complexes. Single WRKY mutants exhibited no or small alterations in response to the hemibiotrophic bacterial pathogen Pseudomonas syringae and the necrotrophic fungal pathogen Botrytis cinerea. However, wrky18 wrky40 and wrky18 wrky60 double mutants and the wrky18 wrky40 wrky60 triple mutant were substantially more resistant to P. syringae but more susceptible to B. cinerea than wild-type plants. Thus, the three WRKY proteins have partially redundant roles in plant responses to the two distinct types of pathogens, with WRKY18 playing a more important role than the other two. The contrasting responses of these WRKY mutants to the two pathogens correlated with opposite effects on pathogen-induced expression of salicylic acid–regulated PATHOGENESIS-RELATED1 and jasmonic acid–regulated PDF1.2. While constitutive expression of WRKY18 enhanced resistance to P. syringae, its coexpression with WRKY40 or WRKY60 made plants more susceptible to both P. syringae and B. cinerea. These results indicate that the three WRKY proteins interact both physically and functionally in a complex pattern of overlapping, antagonistic, and distinct roles in plant responses to different types of microbial pathogens.
Antimutator variants of DNA polymerases

Evolution balances DNA replication speed and accuracy to optimize replicative fitness and genetic stability. There is no selective pressure to improve DNA replication fidelity beyond the background mutation rate from other sources, such as DNA damage. However, DNA polymerases remain amenable to amino acid substitutions that lower intrinsic error rates. Here, we review these ‘antimutagenic’ changes in DNA polymerases and discuss what they reveal about mechanisms of replication fidelity. Pioneering studies with bacteriophage T4 DNA polymerase (T4 Pol) established the paradigm that antimutator amino acid substitutions reduce replication errors by increasing proofreading efficiency at the expense of polymerase processivity. The discoveries of antimutator substitutions in proofreading-deficient ‘mutator’ derivatives of bacterial Pols I and III and yeast Pol δ suggest there must be additional antimutagenic mechanisms. Remarkably, many of the affected amino acid positions from Pol I, Pol III, and Pol δ are similar to the original T4 Pol substitutions. The locations of antimutator substitutions within DNA polymerase structures suggest that they may increase nucleotide selectivity and/or promote dissociation of primer termini from polymerases poised for misincorporation, leading to expulsion of incorrect nucleotides. If misincorporation occurs, enhanced primer dissociation from polymerase domains may improve proofreading in cis by an intrinsic exonuclease or in trans by alternate cellular proofreading activities. Together, these studies reveal that natural selection can readily restore replication error rates to sustainable levels following an adaptive mutator phenotype.