Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification and characterization of VopT, a novel ADP‐ribosyltransferase effector protein secreted via the Vibrio parahaemolyticus type III secretion system 2

Vibrio parahaemolyticus strain RIMD2210633 has two sets of genes encoding two separate type III secretion systems (T3SSs), called T3SS1 and T3SS2. T3SS2 has a role in enterotoxicity and is present only in Kanagawa phenomenon‐positive strains, which are pathogenic to humans. Accordingly, T3SS2 is considered to be closely related to V. parahaemolyticus human pathogenicity. Despite this, the biological actions of T3SS2 and the identity of the effector protein(s) secreted by this system have not been well understood. Here we report that T3SS2 induces a cytotoxic effect in Caco‐2 and HCT‐8 cells. Moreover, it was revealed that VPA1327 (vopT), a gene encoded within the proximity of T3SS2, is partly responsible for this cytotoxic effect. The VopT shows approximately 45% and 44% identity with the ADP‐ribosyltransferase (ADPRT) domain of ExoT and ExoS, respectively, which are two T3SS‐secreted effectors of Pseudomonas aeruginosa. T3SS2 was found to be necessary not only for the secretion, but also for the translocation of the VopT into host cells. We also demonstrate that VopT ADP‐ribosylates Ras, a member of the low‐molecular‐weight G (LMWG) proteins both in vivo and in vitro. These results indicate that VopT is a novel ADPRT effector secreted via V. parahaemolyticus T3SS.
Activation of Smad2 but not Smad3 is required to mediate TGF-β signaling during axolotl limb regeneration

Axolotls are unique among vertebrates in their ability to regenerate tissues, such as limbs, tail and skin. The axolotl limb is the most studied regenerating structure. The process is well characterized morphologically; however, it is not well understood at the molecular level. We demonstrate that TGF-β1 is highly upregulated during regeneration and that TGF-β signaling is necessary for the regenerative process. We show that the basement membrane is not prematurely formed in animals treated with the TGF-β antagonist SB-431542. More importantly, Smad2 and Smad3 are differentially regulated post-translationally during the preparation phase of limb regeneration. Using specific antagonists for Smad2 and Smad3 we demonstrate that Smad2 is responsible for the action of TGF-β during regeneration, whereas Smad3 is not required. Smad2 target genes (Mmp2 and Mmp9) are inhibited in SB-431542-treated limbs, whereas non-canonical TGF-β targets (e.g. Mmp13) are unaffected. This is the first study to show that Smad2 and Smad3 are differentially regulated during regeneration and places Smad2 at the heart of TGF-β signaling supporting the regenerative process. Summary: TGFβ signaling has been implicated in scar formation after wounding. During axolotl limb regeneration, differential regulation of Smad effectors may explain why these animals do not scar.
Transcriptional repression by ApiAP2 factors is central to chronic toxoplasmosis

Bradyzoite differentiation is marked by major changes in gene expression resulting in a parasite that expresses a new repertoire of surface antigens hidden inside a modified parasitophorous vacuole called the tissue cyst. The factors that control this important life cycle transition are not well understood. Here we describe an important Toxoplasma transcriptional repressor mechanism controlling bradyzoite differentiation that operates exclusively in the tachyzoite stage. The ApiAP2 factor, AP2IV-4, is a nuclear factor dynamically expressed in late S phase through mitosis/cytokinesis of the tachyzoite cell cycle. Remarkably, deletion of the AP2IV-4 locus resulted in the increased expression of bradyzoite mRNAs in replicating tachyzoites, and in two different genetic lineages we confirmed the misexpression of tissue cyst wall components (e.g. BPK1, MCP4, CST1) and the bradyzoite surface antigen SRS9 in the tachyzoite stage. In the murine animal model, the loss of AP2IV-4 had profound biological consequences. Type II prugniaud strain parasites lacking AP2IV-4 were unable to form tissue cysts in brain tissue and the absence of this factor also recruited a potent immune response characterized by increases inflammatory monocytes, IFN-γ and higher numbers of both CD8+ and CD4+ T-cells. Altogether, these results indicate that suppression of bradyzoite antigens by AP2IV-4 during acute infection is required for Toxoplasma to establish a chronic infection in the immune-competent host. Author Summary The Toxoplasma biology that underlies the establishment of a chronic infection is developmental conversion of the acute tachyzoite stage into the latent bradyzoite-tissue cyst stage. Despite the important clinical consequences of this developmental pathway, the molecular basis of the switch mechanisms that control formation of the tissue cyst is still poorly understood. A fundamental feature of tissue cyst formation is the expression of bradyzoite-specific genes. Here we show the transcription factor AP2IV-4 directly silences bradyzoite mRNA and protein expression in the acute tachyzoite stage demonstrating that developmental control of tissue cyst formation is as much about when not to express bradyzoite genes as it is about when to activate them. Loosing the suppression of bradyzoite gene expression in the acute tachyzoite stage caused by deleting AP2IV-4 blocked the establishment of chronic disease in healthy animals through the pre-arming of the immune system suggesting a possible strategy for preventing chronic Toxoplasma infections.
Temporal causality between the exchange rate and the trade balance : the case of Brazil

The paper assesses the impact of intemational relative prices and domestic expenditure variables on Brazil' s foreign trade performance in the first half of the 1990s. It has been argued that the appreciation of the Real since 1994 has had a detrimental impact of the country's trade balance. However, using temporal precedence analysis, our results do not indicate that the trade balance is strongly affected by intemational rei ative prices, such as the exchange rate. Instead, domestic expenditure variables appear to be more powerful determinant of the country' s trade performance in recent years. Granger and error correction causality techniques are used to determine temporal precedence between the trade balance and the exchange rate in the period under examination. Our findings shed light on the debate over the sustainability of recent exchange rate-anchored macroeconomic stabilisation programmes, which is a topic that has encouraged a lot of debate among academics and practitioners.
Eliciting Causal Beliefs about Heart Attacks: A Comparison of Implicit and Explicit Methods

Objective To compare beliefs about the importance of different factors in causing heart attacks, elicited by explicit questionnaire ratings and an implicit vignette task. Method In two separate studies: (1) 107 adults (aged 40-60 years); and (2) 134 students completed two tasks: (a) a questionnaire in which they explicitly rated the importance of a number of causes of heart attacks; and (b) a vignette task in which they implicitly used risk factor information to estimate a hypothetical man’s likelihood of a heart attack. Results In both studies, family history was rated as a significantly less important cause than smoking or stress on the explicit questionnaire; in the implicit task, smoking and family history exerted a much greater influence on estimates of risk than did stress. Discussion The causal beliefs elicited by the two methods differ in important respects. The predictive validity of each measure, alone and in combination with other nonquestionnaire-based measures, needs to be determined.
Postrelease monitoring habitat selection by reintroduced burchell's zebra and blue wildebeest in southern Mozambique

Abstract Aim In Africa, reintroduction of wild animal species to conservation areas is a common practice, for the recovery or restoration of populations. Effective monitoring of reintroduced species requires understanding of basic ecological requirements such as habitat selection of these species in the new environment. Therefore, the present study investigated the habitat selection of zebra and wildebeest following their reintroduction into Maputo Special Reserve, south Mozambique, and we use binary logistic analyses to investigate the relative influence of biotic and abiotic factors in determining the habitat use. Location Maputo Special Reserve, south Mozambique. Methods We conducted the study from July 2016 to June 2017. The data were collected by direct observation, driving the vehicle along the reserve's roads that covered the vegetation communities where zebras and wildebeest are known to commonly occur. Habitat selection was calculated using selection indices (Manly's alpha), and binary logistic analyses were used to investigate the relative influence of biotic and abiotic factors in determining the habitat use. Results The arboreal savanna was the preferred habitat by both herbivore species. Habitat use of zebra appeared to be strongly determined by characteristics such as high grass cover, high grass greenness, and distance to water, while the habitat use by wildebeest, was strongly affected by grass height. Main conclusions Both zebra and wildebeest prefer arboreal savanna, forage selection likely drove preference of this habitat. Greater grass cover and greater percentage greenness of the grass both significantly increased the odds of zebra use of habitat, whereas the odds of use decreased with increases in distance to water, meaning an opportunity to ingest large amounts of grass biomass with higher quality, and this opportunity decreases with increasing in distance to water. Grass height was in the highest‐ranking model predicting habitat use by wildebeest, and during the dry season the use of habitat increased with increasing grass height, suggesting that selecting areas with tall grasses by wildebeest equated to choosing areas with higher grass quantity, as the food intake rate increases with grass height.
Splinting after Carpal Tunnel Surgical Treatment: Does It Really Matter?

Background: Splinting of the wrist after carpal tunnel release (CTR) has been practiced by many surgeons especially in North America. The main reason wasto prevent possible adverse events of bowstringing of flexor tendons and the median nerve, pillar pain, entrapment of the median nerve in scar tissue and wound dehiscence. Studies on the effect of splinting after standard CTR had dismal results. The duration of splinting in standard CTR has been either too long (for 2-4 weeks) or too short (48 hours only). Objective: The aim of our study was to compare the effects of post-operative splinting for duration of one week with no splinting. Patients and Methods: All 20 of our patients underwent a standardized open CTR. Post operatively, they were randomized into a splinted (n=10) and a non-splinted (n=10) group. The splint was kept for 2 weeks. Patients were reviewed at regular intervals of one week, two weeks and three months. At each follow up, these patients were clinically assessed for outcome of the Boston questionnaire. Results: All patients presented with significant improvement in the post-operative evaluation within each group. However, there was no significant difference between the two groups for any of the outcome measurements at sequential and at final follow-up. Conclusion: We concluded that wrist splinting in the immediate post-operative period has no advantage when compared with the non-splinting wrist after a standard open carpal tunnel release.
Effect of low isoflurane concentrations on the ventilation-perfusion distribution in injured canine lungs.

BACKGROUND Rapid recovery and weaning from ventilatory support and cardiovascular stability are suggested advantages of isoflurane inhalation, in concentrations ranging from 0.1 to 0.6 vol%, for long-term sedation in mechanical ventilated patients. This study was designed to determine whether isoflurane in low concentrations impairs pulmonary gas exchange by increasing ventilation and perfusion (V(A)/Q) mismatch during lung injury. METHODS Fourteen anesthetized dogs received in random order 0, 0.25, or 0.5 vol% end-tidal isoflurane before and after induction of lung injury with oleic acid. Gas exchange was assessed by blood gas analysis and by estimating the V(A)/Q distributions using the multiple inert gas elimination technique. RESULTS Administration of oleic acid produced a lung injury with severe V(A)/Q mismatch and 38 +/- 4% intrapulmonary shunting of blood. During lung injury, isoflurane accounted for a dose-related increase in blood flow to shunt units from 38 +/- 4 to 42 +/- 3 (0.25 vol%) and 48 +/- 4% (0.5 vol%) (P < 0.05), dispersion pulmonary blood flow distribution from 0.94 +/- 0.07 to 1.01 +/- 0.09 (0.25 vol%) and 1.11 +/- 0.11% (0.5 vol%) (P < 0.05), and a decrease in perfusion of normal V(A)/Q units from 58 +/- 5 to 55 +/- 4 (0.25 vol%) and 50 +/- 4% (0.5 vol%) (P < 0.05) (mean +/- SE). Isoflurane decreased arterial oxygen partial pressure from 72 +/- 4 to 62 +/- 4 mmHg (0.25 vol%) and 56 +/- 4 mmHg (0.5 vol%) (P < 0.05) and oxygen delivery from 573 +/- 21 to 529 +/- 19 ml. kg. min (0.25 vol%) and 505 +/- 22 ml. kg. min (0.5 vol%) (P < 0.05). Gas exchange, perfusion of shunt and normal V(A)/Q units, and pulmonary blood flow distribution was similar in absence of lung injury with and without isoflurane. Isoflurane 0.5 vol% lowered cardiac output during all conditions (P < 0.05). CONCLUSIONS Inhalation of low concentrations of isoflurane contributed to increased V(A)/Q mismatch and decreased systemic blood flow and oxygen delivery in mechanically ventilated animals with injured lungs.
How to Evaluate Gonadal Function in the Cryptorchid Boy. Lessons from New Testicular Markers

In normal clinical practice, testicular evaluation in boys has relied on palpation and testosterone determination after hCG stimulation, which reflects the activity of interstitial Leydig cells. However, the most active compartment of the testis before puberty is the seminiferous tubule compartment, in which Sertoli cells proliferate and secrete anti-Müllerian hormone (AMH) and inhibin B. The recent development of commercially available assays for these two peptides has provided the pediatrician with excellent tools to assess the existence of functional testicular tissue in boys with no need for hCG stimulation. Serum AMH determination is also useful to assess testicular tissue mass and function in patients with intersex disorders. The determination of testosterone, its precursors and dihydrotestosterone, after hCG stimulation, should be reserved for situations in which Leydig cell function needs to be specifically assessed.
Sandwich structured electrostatic/electrets parallel-plate power generator for low acceleration and low frequency vibration energy harvesting

This paper reports an improved design, fabrication method, testing and analysis of electrostatic/electrets parallel-plate power generator driven by sinusoidal vibration sources having low acceleration (<;0.05 g) and low frequency vibration (<;50Hz). An electrostatic/electrets power generator is designed with sandwich structure containing two capacitive systems. Apart from the virtue of harvesting small vibration energy source, it also generates higher power output than conventional two-layer parallel-plate structure by reducing damping effect caused by inherent electrostatic force Fe. A localized corona charging method, using charging mask, for ion implantation into electrets has significantly reduced the fast charge decaying problem in micro scale patterned electrets plates and simplified the charging procedure.
Missing females: a disaggregated analysis.

The problem of sex ratio imbalance in India needs a disaggregated analysis. The absence of such analysis masks the seriousness of the problem among certain groups and in certain areas. This paper presents data on female/male ratio for scheduled castes scheduled tribes and the rest of the population. While further disaggregation among various subgroups is necessary the data presented here help to identify some major problem areas. (EXCERPT)
Truncated tree codes for streaming data: Infinite-memory reliability using finite memory

We present a finite-memory code construction for streaming data systems. In our model a sequence of independent and identically distributed messages arrives at the transmitter according to a deterministic arrival process. Each message must be estimated by the decoder after a fixed delay. Prior work on this model relied on the use of semi-infinite tree-codes with growing encoder and decoder memory. We show that the same reliability that was attained in those constructions, which was based on an error-exponent analysis, can also be obtained by a finite-memory construction. In our construction both encoder and decoder have finite memory, although the instantaneous constraint length of the code (and of the decoding process) is time-varying in a periodic manner. The closer to capacity one wants to operate, the greater the memory our construction requires to match the infinite-memory results. For a given rate and delay it is straightforward to solve for the memory required to attain the same reliability as the earlier strategies.
PTC124 is an orally bioavailable compound that promotes suppression of the human CFTR-G542X nonsense allele in a CF mouse model

Nonsense mutations inactivate gene function and are the underlying cause of a large percentage of the individual cases of many genetic disorders. PTC124 is an orally bioavailable compound that promotes readthrough of premature translation termination codons, suggesting that it may have the potential to treat genetic diseases caused by nonsense mutations. Using a mouse model for cystic fibrosis (CF), we show that s.c. injection or oral administration of PTC124 to Cftr−/− mice expressing a human CFTR-G542X transgene suppressed the G542X nonsense mutation and restored a significant amount of human (h)CFTR protein and function. Translational readthrough of the premature stop codon was demonstrated in this mouse model in two ways. First, immunofluorescence staining showed that PTC124 treatment resulted in the appearance of hCFTR protein at the apical surface of intestinal glands in Cftr−/− hCFTR-G542X mice. In addition, functional assays demonstrated that PTC124 treatment restored 24–29% of the average cAMP-stimulated transepithelial chloride currents observed in wild-type mice. These results indicate that PTC124 can effectively suppress the hCFTR-G542X nonsense mutation in vivo. In light of its oral bioavailability, safety toxicology profile in animal studies, and efficacy with other nonsense alleles, PTC124 has the potential to be an important therapeutic agent for the treatment of inherited diseases caused by nonsense mutations.
Sensitive detection of BCR-ABL1 mutations in patients with chronic myeloid leukemia after imatinib resistance is predictive of outcome during subsequent therapy.

PURPOSE BCR-ABL1 mutation analysis is recommended to facilitate selection of appropriate therapy for patients with chronic myeloid leukemia after treatment with imatinib has failed, since some frequently occurring mutations confer clinical resistance to nilotinib and/or dasatinib. However, mutations could be present below the detection limit of conventional direct sequencing. We developed a sensitive, multiplexed mass spectrometry assay (detection limit, 0.05% to 0.5%) to determine the impact of low-level mutations after imatinib treatment has failed. PATIENTS AND METHODS Mutation status was assessed in 220 patients treated with nilotinib or dasatinib after they experienced resistance to imatinib. RESULTS Mutations were detected by sequencing in 128 patients before commencing nilotinib or dasatinib therapy (switchover). In 64 patients, 132 additional low-level mutations were detected by mass spectrometry alone (50 of 132 mutations were resistant to nilotinib and/or dasatinib). When patients received the inhibitor for which the mutation confers resistance, 84% of the low-level resistant mutations rapidly became dominant clones detectable by sequencing, including 11 of 12 T315I mutations. Subsequent complete cytogenetic response rates were lower for patients with resistant mutations at switchover detected by sequencing (0%) or mass spectrometry alone (16%) compared with patients with other mutations or no mutations (41% and 49%, respectively; P < .001). Failure-free survival among the 100 patients with chronic phase chronic myeloid leukemia when resistant mutations were detected at switchover by sequencing or mass spectrometry alone was 0% and 0% compared with 51% and 45% for patients with other mutations or no mutations (P = .003). CONCLUSION Detection of low-level mutations after imatinib resistance offers critical information to guide subsequent therapy selection. If an inappropriate kinase inhibitor is selected, there is a high risk of treatment failure with clonal expansion of the resistant mutant.
Insights to Systematic Risk and Diversification Across a Joint Probability Distribution

This paper analyses and develops insights to systematic risk and diversification when random, imperfectly dependent, losses are aggregated. Systematic risk and diversification are shown to vary across layers of component losses according to local dependence and volatility structures. Systematic risk is high and diversification is weak overall if high risk layers are heavily dependent on the aggregate loss. This result explains weak diversification observed in financial markets despite weak to moderate correlations overall. A coherent risk setup is assumed in this paper, where risks are measured using distortion and allocated using the Euler principle.
Monitoring Surface Chemical Changes in the Bacterial Cell Wall

Gram-negative bacteria can alter the composition of the lipopolysaccharide (LPS) layer of the outer membrane as a response to different growth conditions and external stimuli. These alterations can, for example, promote attachment to surfaces and biofilm formation. The changes occur in the outermost layer of the cell and may consequently influence interactions between bacterial cells and surrounding host tissue, as well as other surfaces. Microscopic analyses, fractionation of bacterial cells, or other traditional microbiological assays have previously been used to study these alterations. These methods can, however, be time consuming and do not always give detailed chemical information about the bacterial cell surface. We here present an analytical method that provides chemical information on the outermost portion of bacterial cells with respect to protein, peptidoglycan, lipid, and polysaccharide content. The method involves cryo-x-ray photoelectron spectroscopy analyses of the outermost portion (within ∼10 nm of the surface) of intact bacterial cells followed by a multivariate curve resolution analysis of carbon spectra. It can be used as a tool for characterizing and monitoring variations in the chemical composition of bacterial cell walls or of isolated outer membrane vesicles, variations that result from e.g. mutations or external stimuli. The method enabled us to predict accurately the alterations in polysaccharide content and surface chemistries of a set of well characterized Escherichia coli LPS mutants. The described approach may moreover be applied to monitor surface chemical composition of other biological samples.
International ICT Spillover

Recent developments in information and communication technology (ICT) have affected all economic activities across the world. Although there is ample evidence for the direct impact of ICT on productivity, the spillover effect of ICT has so far not been sufficiently investigated, especially in the international context. This chapter discusses ICT and its spillover effects on labor productivity using an empirical growth model and panel data for 69 countries over the period 1992-2006. The results show that ICT and its spillover have positive impacts on productivity worldwide, but the effects are much stronger in developed countries than those in the less developed countries.