Miracle-dz/UniFAR-FTUs huggingface dataset:
Crossing Languages in Text Retrieval via an Interlingua

We introduce an interlingua-based approach to cross-language information retrieval, in which queries, as well as documents, are mapped onto a language-independent concept layer on which retrieval operations are performed. This approach is contrasted with one which directly translates non-English queries (German and Portuguese, in our experiments) to English ones which, subsequently, are processed on English documents. We report on the empirical evaluation of both approaches on a large medical document collection (the Ohsumed corpus).
HY5, a positive regulator of light signaling, negatively controls the unfolded protein response in Arabidopsis

Significance In nature, plants are inevitably exposed to adverse conditions such as salinity, drought, and extreme temperatures. Recent reports suggest that environmental stresses critically affect the protein-folding capacity of endoplasmic reticula (ER), leading to ER stress. As the growth and development of plants significantly depend on light environment, the crosstalk between light signaling and ER stress response explained in current research can be a unique feature of plants. Our results suggest that light increases the ER stress sensitivity of plants and ELONGATED HYPOCOTYL 5, a positive regulator of light signaling, negatively regulates unfolded protein response gene expression in plant cells, which decreases the protein-folding capacity. The present study may form the basis for designing new strategies to increase stress tolerance of plants by tightly controlling light environment. Light influences essentially all aspects of plant growth and development. Integration of light signaling with different stress response results in improvement of plant survival rates in ever changing environmental conditions. Diverse environmental stresses affect the protein-folding capacity of the endoplasmic reticulum (ER), thus evoking ER stress in plants. Consequently, the unfolded protein response (UPR), in which a set of molecular chaperones is expressed, is initiated in the ER to alleviate this stress. Although its underlying molecular mechanism remains unknown, light is believed to be required for the ER stress response. In this study, we demonstrate that increasing light intensity elevates the ER stress sensitivity of plants. Moreover, mutation of the ELONGATED HYPOCOTYL 5 (HY5), a key component of light signaling, leads to tolerance to ER stress. This enhanced tolerance of hy5 plants can be attributed to higher expression of UPR genes. HY5 negatively regulates the UPR by competing with basic leucine zipper 28 (bZIP28) to bind to the G-box–like element present in the ER stress response element (ERSE). Furthermore, we found that HY5 undergoes 26S proteasome-mediated degradation under ER stress conditions. Conclusively, we propose a molecular mechanism of crosstalk between the UPR and light signaling, mediated by HY5, which positively mediates light signaling, but negatively regulates UPR gene expression.
Supramaximal CCK and CCh concentrations abolish VIP potentiation by inhibiting adenylyl cyclase activity.

Exocrine pancreatic secretion stimulated by vasoactive intestinal polypeptide (VIP), which acts through the adenylyl cyclase-cAMP pathway, is potentiated by stimulation with other secretagogues such as CCK and carbachol (CCh). However, the potentiating effect is abolished by the same secretagogues at supramaximal concentrations. In the present study, we examined the mechanisms by which supramaximal concentrations of CCK octapeptide (CCK-8) or CCh reduce the VIP-induced potentiation of amylase secretion from isolated rat pancreatic acini. VIP-stimulated amylase secretion was potentiated by submaximal stimulatory concentrations of CCK-8 and CCh but was reduced by the same reagents at higher concentrations. Supramaximal concentrations of CCK-8 or CCh also reduced forskolin-induced potentiation of amylase release but did not reduce that induced by 8-bromo-cAMP. Moreover, supramaximal concentrations of CCK-8 or CCh inhibited VIP-stimulated intracellular cAMP production as well as adenylyl cyclase activity. 12- O-tetradecanoylphorbol 13-acetate (TPA) also reduced the magnitude of the potentiation of amylase release caused by VIP plus CCK-8 or CCh, although TPA itself decreased neither VIP-stimulated adenylyl cyclase activity nor intracellular cAMP accumulation. These results indicate that supramaximal concentrations of CCK-8 and CCh reduce the potentiating effect of VIP and forskolin on amylase secretion by inhibiting the adenylyl cyclase activity. In addition, protein kinase C is suggested to be partly implicated in this inhibitory mechanism. The mechanisms that lead to such inhibition may be interlinked but distinct from each other.
RNA-binding specificity landscapes of designer pentatricopeptide repeat proteins elucidate principles of PPR–RNA interactions

Abstract Pentatricopeptide repeat (PPR) proteins are helical-repeat proteins that offer a promising scaffold for the engineering of proteins to bind specified RNAs. PPR tracts bind RNA in a modular 1-repeat, 1-nucleotide fashion. An amino acid code specifying the bound nucleotide has been elucidated. However, this code does not fully explain the sequence specificity of native PPR proteins. Furthermore, it does not address nuances such as the contribution toward binding affinity of various repeat-nucleotide pairs or the impact of mismatches between a repeat and aligning nucleotide. We used an in vitro bind-n-seq approach to describe the population of sequences bound by four artificial PPR proteins built from consensus scaffolds. The specificity of these proteins can be accounted for by canonical code-based nucleotide recognition. The results show, however, that interactions near the 3′-end of binding sites make less contribution to binding affinity than do those near the 5′-end, that proteins with 11 and 14 repeats exhibit similar affinity for their intended targets but 14-repeats are more permissive for mismatches, and that purine-binding repeats are less tolerant of transversion mismatches than are pyrimidine-binding motifs. These findings have implications for mechanisms that establish PPR–RNA interactions and for optimizing PPR design to minimize off-target interactions.
Environmental Enrichment of Young Adult Rats (Rattus norvegicus) in Different Sensory Modalities Has Long-Lasting Effects on Their Ability to Learn via Specific Sensory Channels

Sensory modalities individuals use to obtain information from the environment differ among conspecifics. The relative contributions of genetic divergence and environmental plasticity to this variance remain yet unclear. Numerous studies have shown that specific sensory enrichments or impoverishments at the postnatal stage can shape neural development, with potential lifelong effects. For species capable of adjusting to novel environments, specific sensory stimulation at a later life stage could also induce specific long-lasting behavioral effects. To test this possibility, we enriched young adult Norway rats with either visual, auditory, or olfactory cues. Four to 8 months after the enrichment period we tested each rat for their learning ability in 3 two-choice discrimination tasks, involving either visual, auditory, or olfactory stimulus discrimination, in a full factorial design. No sensory modality was more relevant than others for the proposed task per se, but rats performed better when tested in the modality for which they had been enriched. This shows that specific environmental conditions encountered during early adulthood have specific long-lasting effects on the learning abilities of rats. Furthermore, we disentangled the relative contributions of genetic and environmental causes of the response. The reaction norms of learning abilities in relation to the stimulus modality did not differ between families, so interindividual divergence was mainly driven by environmental rather than genetic factors.
Landscape metrics as predictors of hydrologic connectivity between Coastal Plain forested wetlands and streams

Geographically isolated wetlands, those entirely surrounded by uplands, provide numerous landscape‐scale ecological functions, many of which are dependent on the degree to which they are hydrologically connected to nearby waters. There is a growing need for field‐validated, landscape‐scale approaches for classifying wetlands on the basis of their expected degree of hydrologic connectivity with stream networks. This study quantified seasonal variability in surface hydrologic connectivity (SHC) patterns between forested Delmarva bay wetland complexes and perennial/intermittent streams at 23 sites over a full‐water year (2014–2015). Field data were used to develop metrics to predict SHC using hypothesized landscape drivers of connectivity duration and timing. Connection duration was most strongly related to the number and area of wetlands within wetland complexes as well as the channel width of the temporary stream connecting the wetland complex to a perennial/intermittent stream. Timing of SHC onset was related to the topographic wetness index and drainage density within the catchment. Stepwise regression modelling found that landscape metrics could be used to predict SHC duration as a function of wetland complex catchment area, wetland area, wetland number, and soil available water storage (adj‐R2 = 0.74, p < .0001). Results may be applicable to assessments of forested depressional wetlands elsewhere in the U.S. Mid‐Atlantic and Southeastern Coastal Plain, where climate, landscapes, and hydrological inputs and losses are expected to be similar to the study area.
Comparison of Portable and Bench-Top Spectrometers for Mid-Infrared Diffuse Reflectance Measurements of Soils

Mid-infrared (MIR) spectroscopy has received widespread interest as a method to complement traditional soil analysis. Recently available portable MIR spectrometers additionally offer potential for on-site applications, given sufficient spectral data quality. We therefore tested the performance of the Agilent 4300 Handheld FTIR (DRIFT spectra) in comparison to a Bruker Tensor 27 bench-top instrument in terms of (i) spectral quality and measurement noise quantified by wavelet analysis; (ii) accuracy of partial least squares (PLS) calibrations for soil organic carbon (SOC), total nitrogen (N), pH, clay and sand content with a repeated cross-validation analysis; and (iii) key spectral regions for these soil properties identified with a Monte Carlo spectral variable selection approach. Measurements and multivariate calibrations with the handheld device were as good as or slightly better than Bruker equipped with a DRIFT accessory, but not as accurate as with directional hemispherical reflectance (DHR) data collected with an integrating sphere. Variations in noise did not markedly affect the accuracy of multivariate PLS calibrations. Identified key spectral regions for PLS calibrations provided a good match between Agilent and Bruker DHR data, especially for SOC and N. Our findings suggest that portable FTIR instruments are a viable alternative for MIR measurements in the laboratory and offer great potential for on-site applications.
Roles of Three Cryptococcus neoformans and Cryptococcus gattii Efflux Pump-Coding Genes in Response to Drug Treatment

ABSTRACT Cryptococcus neoformans and Cryptococcus gattii species complexes are the etiologic agents of cryptococcosis. We have deciphered the roles of three ABC transporters, Afr1, Afr2, and Mdr1, in the representative strains of the two species, C. neoformans H99 and C. gattii R265. Deletion of AFR1 in H99 and R265 drastically reduced the levels of resistance to three xenobiotics and three triazoles, suggesting that Afr1 is the major drug efflux pump in both strains. Fluconazole susceptibility was not affected when AFR2 or MDR1 was deleted in both strains. However, when these genes were deleted in combination with AFR1, a minor additive effect in susceptibility toward several drugs was observed. Deletion of all three genes in both strains caused further increases in susceptibility toward fluconazole and itraconazole, suggesting that Afr2 and Mdr1 augment Afr1 function in pumping these triazoles. Intracellular accumulation of Nile Red significantly increased in afr1Δ mutants of both strains, but rhodamine 6G accumulation increased only in the mdr1Δ mutant of H99. Thus, the three efflux pumps play different roles in the two strains when exposed to different azoles and xenobiotics. AFR1 and AFR2 expression was upregulated in H99 and R265 when treated with fluconazole. However, MDR1 expression was upregulated only in R265 under the same conditions. We screened a library of transcription factor mutants and identified several mutants that manifested either altered fluconazole sensitivity or an increase in the frequency of fluconazole heteroresistance. Gene expression analysis suggests that the three efflux pumps are regulated independently by different transcription factors in response to fluconazole exposure.
Role of proNGF/p75 signaling in bladder dysfunction after spinal cord injury

Loss of bladder control is a challenging outcome facing patients with spinal cord injury (SCI). We report that systemic blocking of pro–nerve growth factor (proNGF) signaling through p75 with a CNS-penetrating small-molecule p75 inhibitor resulted in significant improvement in bladder function after SCI in rodents. The usual hyperreflexia was attenuated with normal bladder pressure, and automatic micturition was acquired weeks earlier than in the controls. The improvement was associated with increased excitatory input to the spinal cord, in particular onto the tyrosine hydroxylase–positive fibers in the dorsal commissure. The drug also had an effect on the bladder itself, as the urothelial hyperplasia and detrusor hypertrophy that accompany SCI were largely prevented. Urothelial cell loss that precedes hyperplasia was dependent on p75 in response to urinary proNGF that is detected after SCI in rodents and humans. Surprisingly, death of urothelial cells and the ensuing hyperplastic response were beneficial to functional recovery. Deleting p75 from the urothelium prevented urothelial death, but resulted in reduction in overall voiding efficiency after SCI. These results unveil a dual role of proNGF/p75 signaling in bladder function under pathological conditions with a CNS effect overriding the peripheral one.
Comparative efficacy and tolerability of pharmacological and somatic interventions in adult patients with treatment-resistant depression: a systematic review and network meta-analysis

Abstract Objective: Major depressive disorder (MDD) affects about 10–15% of the general population in a lifetime. A considerable number of patients fail to achieve full symptom remission despite adequate treatment and are considered treatment resistant (TRD). The current study compared the relative efficacy and tolerability of pharmacological and somatic TRD interventions by means of a Bayesian network meta-analysis. Research design and methods: An electronic literature search of MEDLINE, MEDLINE In-Process, EMBASE, PsycInfo, EconLit and Cochrane Library databases for trials published between September 2003 and September 2014 was conducted. Key outcomes extracted were disease severity change from baseline, response and remission rates at various timepoints and discontinuation due to adverse events. Results: Of the 3876 abstracts identified, 31 publications/randomised controlled trials (RCTs) were included in the analysis; 19 RCTs investigating 13 pharmacological interventions and 12 RCTs investigating electroconvulsive therapy (ECT) and repetitive transcranial magnetic stimulation (rTMS). The evidence synthesis investigating efficacy outcomes of TRD treatments demonstrated superior efficacy for ketamine compared to pharmacological and somatic interventions at 2 weeks after treatment initiation. At 4, 6 and 8 weeks, quetiapine augmentation (800 mg/day) and risperidone augmentation were found to be the first and second best treatments, respectively. Networks were small for response rate and remission rate outcomes at most timepoints. The most tolerable treatment was lamotrigine augmentation showing a comparable profile to placebo/sham. Conclusions: This analysis revealed scarcity of long-term data on sustained remission that would allow a comparative long-term efficacy assessment. Key limitations of the analysis can be considered the search timeframe and the use of mapping formula for the depression scores.
Sex and Age Effects of Functional Connectivity in Early Adulthood

Abstract Functional connectivity (FC) in resting-state functional magnetic resonance imaging (rs-fMRI) is widely used to find coactivating regions in the human brain. Despite its widespread use, the effects of sex and age on resting FC are not well characterized, especially during early adulthood. Here we apply regression and graph theoretical analyses to explore the effects of sex and age on FC between the 116 AAL atlas parcellations (a total of 6670 FC measures). rs-fMRI data of 494 healthy subjects (203 males and 291 females; age range: 22–36 years) from the Human Connectome Project were analyzed. We report the following findings. (1) Males exhibited greater FC than females in 1352 FC measures (1025 survived Bonferroni correction; \documentclass{aastex}\usepackage{amsbsy}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{bm}\usepackage{mathrsfs}\usepackage{pifont}\usepackage{stmaryrd}\usepackage{textcomp}\usepackage{portland, xspace}\usepackage{amsmath, amsxtra}\pagestyle{empty}\DeclareMathSizes{10}{9}{7}{6}\begin{document} $$p < 7.49{ \rm{E}} - 6$$ \end{document}). In 641 FC measures, females exhibited greater FC than males but none survived Bonferroni correction. Significant FC differences were mainly present in frontal, parietal, and temporal lobes. Although the average FC values for males and females were significantly different, FC values of males and females exhibited large overlap. (2) Age effects were present only in 29 FC measures and all significant age effects showed higher FC in younger subjects. Age and sex differences of FC remained significant after controlling for cognitive measures. (3) Although sex \documentclass{aastex}\usepackage{amsbsy}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{bm}\usepackage{mathrsfs}\usepackage{pifont}\usepackage{stmaryrd}\usepackage{textcomp}\usepackage{portland, xspace}\usepackage{amsmath, amsxtra}\pagestyle{empty}\DeclareMathSizes{10}{9}{7}{6}\begin{document} $$\times$$ \end{document} age interaction did not survive multiple comparison correction, FC in females exhibited a faster cross-sectional decline with age. (4) Male brains were more locally clustered in all lobes but the cerebellum; female brains had a higher clustering coefficient at the whole-brain level. Our results indicate that although both male and female brains show small-world network characteristics, male brains were more segregated and female brains were more integrated. Findings of this study further our understanding of FC in early adulthood and provide evidence to support that age and sex should be controlled for in FC studies of young adults.
The Triplet State of 6‐thio‐2′‐deoxyguanosine: Intrinsic Properties and Reactivity Toward Molecular Oxygen

Thiopurine prodrugs are currently among the leading treatment options for leukemia, immunosuppression, and arthritis. Patients undergoing long‐term thiopurine treatment are at a higher risk of developing sunlight‐induced skin cancers than the general population. This side effect originates from the cellular metabolization of thiopurine prodrugs to form 6‐thio‐2′‐deoxyguanosine, which can absorb UVA radiation, populating its reactive triplet state and leading to oxidatively generated damage. However, the photo‐oxidation mechanism is not fully understood. In this contribution, the oxidation potential and the adiabatic triplet energy of 6‐thio‐2′‐deoxyguanosine are estimated computationally, whereas the intrinsic rate of triple‐state decay and the rate constant for triplet quenching by molecular oxygen are determined using time‐resolved spectroscopic techniques. A singlet oxygen quantum yield of 0.24 ± 0.02 is measured in aqueous solution (0.29 ± 0.02 in acetonitrile). Its magnitude correlates with the relatively low percentage of triplet‐O2 collision events that generate singlet oxygen (SΔ = 37%). This behavior is rationalized as being due to the exergonic driving force for electron transfer between the triplet state of 6‐thio‐2′‐deoxyguanosine and molecular oxygen (ΔGET = −69.7 kJ mol−1), resulting in the formation of a charge‐transfer complex that favors nonradiative decay to the ground state over triplet energy transfer.
Notch/Her12 signalling modulates, motile/immotile cilia ratio downstream of Foxj1a in zebrafish left-right organizer

Foxj1a is necessary and sufficient to specify motile cilia. Using transcriptional studies and slow-scan two-photon live imaging capable of identifying the number of motile and immotile cilia, we now established that the final number of motile cilia depends on Notch signalling (NS). We found that despite all left-right organizer (LRO) cells express foxj1a and the ciliary axonemes of these cells have dynein arms, some cilia remain immotile. We identified that this decision is taken early in development in the Kupffer’s Vesicle (KV) precursors the readout being her12 transcription. We demonstrate that overexpression of either her12 or Notch intracellular domain (NICD) increases the number of immotile cilia at the expense of motile cilia, and leads to an accumulation of immotile cilia at the anterior half of the KV. This disrupts the normal fluid flow intensity and pattern, with consequent impact on dand5 expression pattern and left-right (L-R) axis establishment.
A comparative modeling study on non-climatic and climatic risk assessment on Asian Tiger Mosquito (Aedes albopictus)

Aedes albopictus, the Asian Tiger Mosquito, vector of Chikungunya, Dengue Fever and Zika viruses, has proven its hardy adaptability in expansion from its natural Asian, forest edge, tree hole habitat on the back of international trade transportation, re-establishing in temperate urban surrounds, in a range of water receptacles and semi-enclosures of organic matter. Conventional aerial spray mosquito vector controls focus on wetland and stagnant water expanses, proven to miss the protected hollows and crevices favoured by Ae. albopictus. New control or eradication strategies are thus essential, particular in light of potential expansions in the southeastern and eastern USA. Successful regional vector control strategies require risk level analysis. Should strategies prioritize regions with non-climatic or climatic suitability parameters for Ae. albopictus? Our study used current Ae. albopictus distribution data to develop two independent models: (i) regions with suitable non-climatic factors, and (ii) regions with suitable climate for Ae. albopictus in southeastern USA. Non-climatic model processing used Evidential Belief Function (EBF), together with six geographical conditioning factors (raster data layers), to establish the probability index. Validation of the analysis results was estimated with area under the curve (AUC) using Ae. albopictus presence data. Climatic modeling was based on two General Circulation Models (GCMs), Miroc3.2 and CSIRO-MK30 running the RCP 8.5 scenario in MaxEnt software. EBF non-climatic model results achieved a 0.70 prediction rate and 0.73 success rate, confirming suitability of the study site regions for Ae. albopictus establishment. The climatic model results showed the best-fit model comprised Coldest Quarter Mean Temp, Precipitation of Wettest Quarter and Driest Quarter Precipitation factors with mean AUC value of 0.86. Both GCMs showed that the whole study site is highly suitable and will remain suitable climatically, according to the prediction for 2055, for Ae. albopictus expansion.