Miracle-dz/UniFAR-FTUs huggingface dataset:
Lobelia siphilitica Plants That Escape Herbivory in Time Also Have Reduced Latex Production

Flowering phenology is an important determinant of a plant’s reproductive success. Both assortative mating and niche construction can result in the evolution of correlations between phenology and other reproductive, functional, and life history traits. Correlations between phenology and herbivore defence traits are particularly likely because the timing of flowering can allow a plant to escape herbivory. To test whether herbivore escape and defence are correlated, we estimated phenotypic and genetic correlations between flowering phenology and latex production in greenhouse-grown Lobelia siphilitica L. (Lobeliaceae). Lobelia siphilitica plants that flower later escape herbivory by a specialist pre-dispersal seed predator, and thus should invest fewer resources in defence. Consistent with this prediction, we found that later flowering was phenotypically and genetically correlated with reduced latex production. To test whether herbivore escape and latex production were costly, we also measured four fitness correlates. Flowering phenology was negatively genetically correlated with three out of four fitness estimates, suggesting that herbivore escape can be costly. In contrast, we did not find evidence for costs of latex production. Generally, our results suggest that herbivore escape and defence traits will not evolve independently in L. siphilitica.
Estimation of Individual Growth Trajectories When Repeated Measures Are Missing

Individuals in a population vary in their growth due to hidden and observed factors such as age, genetics, environment, disease, and carryover effects from past environments. Because size affects fitness, growth trajectories scale up to affect population dynamics. However, it can be difficult to estimate growth in data from wild populations with missing observations and observation error. Previous work has shown that linear mixed models (LMMs) underestimate hidden individual heterogeneity when more than 25% of repeated measures are missing. Here we demonstrate a flexible and robust way to model growth trajectories. We show that state-space models (SSMs), fit using R package growmod, are far less biased than LMMs when fit to simulated data sets with missing repeated measures and observation error. This method is much faster than Markov chain Monte Carlo methods, allowing more models to be tested in a shorter time. For the scenarios we simulated, SSMs gave estimates with little bias when up to 87.5% of repeated measures were missing. We use this method to quantify growth of Soay sheep, using data from a long-term mark-recapture study, and demonstrate that growth decreased with age, population density, weather conditions, and when individuals are reproductive. The method improves our ability to quantify how growth varies among individuals in response to their attributes and the environments they experience, with particular relevance for wild populations.
A negative feedback regulation of MTORC1 activity by the lysosomal Ca2+ channel MCOLN1 (mucolipin 1) using a CALM (calmodulin)-dependent mechanism

ABSTRACT Macroautophagy/autophagy is an evolutionarily conserved pathway that is required for cellular homeostasis, growth and survival. The lysosome plays an essential role in autophagy regulation. For example, the activity of MTORC1, a master regulator of autophagy, is regulated by nutrients within the lysosome. Starvation inhibits MTORC1 causing autophagy induction. Given that MTORC1 is critical for protein synthesis and cellular homeostasis, a feedback regulatory mechanism must exist to restore MTORC1 during starvation. However, the molecular mechanism underlying this feedback regulation is unclear. In this study, we report that starvation activates the lysosomal Ca2+ release channel MCOLN1 (mucolipin 1) by relieving MTORC1's inhibition of the channel. Activated MCOLN1 in turn facilitates MTORC1 activity that requires CALM (calmodulin). Moreover, both MCOLN1 and CALM are necessary for MTORC1 reactivation during prolonged starvation. Our data suggest that lysosomal Ca2+ signaling is an essential component of the canonical MTORC1-dependent autophagy pathway and MCOLN1 provides a negative feedback regulation of MTORC1 to prevent excessive loss of MTORC1 function during starvation. The feedback regulation may be important for maintaining cellular homeostasis during starvation, as well as many other stressful or disease conditions.
PUF-8 facilitates homologous chromosome pairing by promoting proteasome activity during meiotic entry in C. elegans

ABSTRACT Pairing of homologous chromosomes is essential for genetic recombination during gametogenesis. In many organisms, chromosome ends are attached to cytoplasmic dynein, and dynein-driven chromosomal movements facilitate the pairing process. Factors that promote or control the cytoskeletal tethering of chromosomes are largely unknown. Here, we show that the conserved RNA-binding protein PUF-8 facilitates the tethering and pairing processes in the C. elegans germline by promoting proteasome activity. We have isolated a hypomorphic allele of pas-1, which encodes a proteasome core subunit, and find that the homologous chromosomes fail to pair in the puf-8; pas-1 double mutant due to failure of chromosome tethering. Our results reveal that the puf-8; pas-1 meiotic defects are caused by the loss of proteasome activity. The axis component HTP-3 accumulates prematurely in the double mutant, and reduction of its activity partially suppresses some of the puf-8; pas-1 meiotic defects, suggesting that HTP-3 might be an important target of the proteasome in promoting early meiotic events. In summary, our results reveal a role for the proteasome in chromosome tethering and identify PUF-8 as a regulator of proteasome activity during early meiosis. Summary: C. elegans mutants of the RNA-binding protein PUF-8 and the α1 proteasome subunit PAS-1 show meiotic defects and sterility that are due at least in part to increased activity of the axis component HTP-3 in premeiotic cells of the germline.
Cellular Interaction and Tumoral Penetration Properties of Cyclodextrin Nanoparticles on 3D Breast Tumor Model

Amphiphilic cyclodextrins are biocompatible oligosaccharides that can be used for drug delivery especially for the delivery of drugs with solubility problems thanks to their unique molecular structures. In this paper, Paclitaxel was used as a model anticancer drug to determine the inclusion complex properties of amphiphilic cyclodextrins with different surface charge. Paclitaxel-loaded cyclodextrin nanoparticles were characterized in terms of mean particle diameter, zeta potential, encapsulation efficacy, drug release profile and cell culture studies. It was determined that the nanoparticles prepared from the inclusion complex according to characterization studies have a longer release profile than the conventionally prepared nanoparticles. In order to mimic the tumor microenvironment, breast cancer cells and healthy fibroblast cells were used in 3-dimensional (3D) cell culture studies. It was determined that the activities of nanoparticles prepared by conventional methods behave differently in 2-dimensional (2D) and 3D cell cultures. In addition, it was observed that the nanoparticles prepared from the inclusion complex have a stronger anti-tumoral activity in the 3D multicellular tumor model than the drug solution. Furthermore, polycationic amphiphilic cyclodextrin nanoparticles can diffuse and penetrate through multilayer cells in a 3D tumor model, which is crucial for an eventual antitumor effect.
Encoding sensory and motor patterns as time-invariant trajectories in recurrent neural networks

Much of the information the brain processes and stores is temporal in nature—a spoken word or a handwritten signature, for example, is defined by how it unfolds in time. However, it remains unclear how neural circuits encode complex time-varying patterns. We show that by tuning the weights of a recurrent neural network (RNN), it can recognize and then transcribe spoken digits. The model elucidates how neural dynamics in cortical networks may resolve three fundamental challenges: first, encode multiple time-varying sensory and motor patterns as stable neural trajectories; second, generalize across relevant spatial features; third, identify the same stimuli played at different speeds—we show that this temporal invariance emerges because the recurrent dynamics generate neural trajectories with appropriately modulated angular velocities. Together our results generate testable predictions as to how recurrent networks may use different mechanisms to generalize across the relevant spatial and temporal features of complex time-varying stimuli.
Biocompatibility and mechanical behaviour of three-dimensional scaffolds for biomedical devices: process–structure–property paradigm

We elucidate here process–structure–property relationships in implantable biomaterials processed by rapid prototyping approaches that are based on the principle of additive manufacturing. The conventional methods of fabrication of biomedical devices including freeze casting and sintering are limited because of difficulties in adaptation at the host site and mismatch in micro/macrostructure, mechanical and physical properties with the host tissue. Moreover, additive manufacturing has the advantage of fabricating patient-specific designs, which can be obtained from the computed tomography scan of the defect site. The discussion here comprises two parts – the first part briefly describes the evolution and underlying reasons that have led to 3D printing of scaffolds for tissue regeneration. The second part focuses on biocompatibility and mechanical properties of 3D scaffolds, fabricated by different approaches. The article concludes with a discussion on functionally graded scaffolds and vascularisation of 3D porous scaffolds that are envisaged to meet the requirements of the biomedical industry. In general, the mechanical properties of 3D printed scaffolds are governed by pore architecture, pore volume and percentage porosity. To ensure long-term endurance and the ability to withstand abrupt impact, it is important that the fabricated materials have a good combination of strength and energy absorption capability. While scaffolds with high interconnected porosity are preferred for tissue regeneration, such structures lack adequate mechanical strength and energy absorption capability. These mutually opposing requirements of high porosity and mechanical strength in conjunction with high energy absorption have hindered the application of 3D scaffolds as biomedical devices. In this regard, functionally graded 3D structures with high strength and energy absorption are potentially attractive for biomedical devices.
Attrition during a randomized controlled trial of reduced nicotine content cigarettes as a proxy for understanding acceptability of nicotine product standards

AIMS To determine (1) if nicotine content affects study attrition-a potential behavioral measure of acceptability-in a trial that required compliance with three levels of reduced nicotine content (RNC) cigarettes, and (2) if attrition is associated with subjective and behavioral responses to RNC cigarettes. DESIGN Secondary analysis of a 35-day, parallel-design, open-label, randomized controlled trial. After a 5-day baseline period, participants were randomized to smoke for three 10-day periods: their preferred brand (control group) or RNC cigarettes with three nicotine levels in a within-subject stepdown (one group: high-moderate-low) or non-stepdown (five groups: high-low-moderate, low-moderate-high, low-high-moderate, moderate-low-high, moderate-high-low) fashion. SETTING A single site in Philadelphia, PA, USA. PARTICIPANTS A total of 246 non-treatment-seeking daily smokers [mean age = 39.52, cigarettes per day (CPD) = 20.95, 68.3% white] were recruited from October 2007 to June 2013. MEASUREMENTS The primary outcome was attrition. Key predictors were nicotine content transition and study period. Exploratory predictors were taste and strength subjective ratings, total puff volume and carbon monoxide (CO) boost. Covariates included: age, gender, race, education and nicotine dependence. FINDINGS Overall attrition was 31.3% (n = 77): 24.1% of the control and 25.0% of the stepdown RNC cigarette groups dropped out versus 44.6% of non-stepdown groups (P = 0.006). Compared with controls, attrition odds were 4.5 and 4.7 times greater among smokers transitioning from preferred and the highest RNC cigarettes to the lowest RNC cigarettes, respectively (P = 0.001 and 0.003). Providing more favorable initial taste ratings of study cigarettes decreased attrition odds by 2% (P = 0.012). CONCLUSIONS The majority of participants completed a 35-day trial of varying levels of reduced nicotine content cigarettes. Participant dropout was greater for cigarettes with lower nicotine content and less in smokers reporting more favorable subjective ratings of the cigarettes.
Placental-mediated increased cytokine response to lipopolysaccharides: a potential mechanism for enhanced inflammation susceptibility of the preterm fetus

Background: Cerebral palsy is a nonprogressive motor impairment syndrome that has no effective cure. The etiology of most cases of cerebral palsy remains unknown; however, recent epidemiologic data have demonstrated an association between fetal neurologic injury and infection/inflammation. Maternal infection/inflammation may be associated with the induction of placental cytokines that could result in increased fetal proinflammatory cytokine exposure, and development of neonatal neurologic injury. Therefore, we sought to explore the mechanism by which maternal infection may produce a placental inflammatory response. We specifically examined rat placental cytokine production and activation of the Toll-like receptor 4 (TLR4) pathway in response to lipopolysaccharide exposure at preterm and near-term gestational ages. Methods: Preterm (e16) or near-term (e20) placental explants from pregnant rats were treated with 0, 1, or 10 μg/mL lipopolysaccharide. Explant integrity was assessed by lactate dehydrogenase assay. Interleukin-6 and tumor necrosis alpha levels were determined using enzyme-linked immunosorbent assay kits. TLR4 and phosphorylated nuclear factor kappa light chain enhancer of activated B cells (NFκB) protein expression levels were determined by Western blot analysis. Results: At both e16 and e20, lactate dehydrogenase levels were unchanged by treatment with lipopolysaccharide. After exposure to lipopolysaccharide, the release of interleukin-6 and tumor necrosis alpha from e16 placental explants increased by 4-fold and 8–9-fold, respectively (P < 0.05 versus vehicle). Conversely, interleukin-6 release from e20 explants was not significantly different compared with vehicle, and tumor necrosis alpha release was only 2-fold higher (P < 0.05 versus vehicle) following exposure to lipopolysaccharide. Phosphorylated NFκB protein expression was significantly increased in the nuclear fraction from placental explants exposed to lipopolysaccharide at both e16 and e20, although TLR4 protein expression was unaffected. Conclusion: Lipopolysaccharide induces higher interleukin-6 and tumor necrosis alpha expression at e16 versus e20, suggesting that preterm placentas may have a greater placental cytokine response to lipopolysaccharide infection. Furthermore, increased phosphorylated NFκB indicates that placental cytokine induction may occur by activation of the TLR4 pathway.
Vancomycin Prophylaxis for Prevention of Clostridium difficile Infection Recurrence in Renal Transplant Patients

Background: Incidence of primary and recurrent Clostridium difficile infection (CDI) is higher in solid-organ transplant recipients than in the average hospitalized patient. Strategies for preventing recurrent CDI are limited. Prophylaxis with oral vancomycin (VPPx) for preventing recurrent CDI may be beneficial, but there is limited evidence supporting its use. Objective: To examine the impact of VPPx (125 mg twice daily) for the prevention of recurrent CDI in renal transplant recipients (RTX) receiving high-risk broad spectrum antibiotics (BSAs). Methods: Adult RTX with history of CDI, hospitalized with receipt of BSAs during a unit-specific CDI outbreak period—January 1, 2012, to December 31, 2015—were divided into 2 matched cohorts: patients who received VPPx concomitantly with BSAs and patients who did not. The primary objective was incidence of CDI recurrence, defined as CDI occurring ≤30 days after receipt of BSAs but ≥48 hours after beginning VPPx. Univariate analysis was performed. Results: Baseline characteristics were similar; however, the VPPx group had more severe primary CDI and were receiving BSAs for more severe infections. There were no cases of CDI recurrence in the VPPx group (0% [0/12] vs 8% [2/24], P = 0.54). Conclusion: Although sufficient power was not obtained to detect statistically significant differences between the intervention and control groups, a 0% incidence of recurrent CDI while receiving VPPx in this high-risk patient population is compelling because it pertains to the avoidance of CDI-related morbidity and mortality in transplant recipients. Future prospective studies are needed to better evaluate the impact of this preventive strategy.
Effect of epigallocatechin-3-gallate, major ingredient of green tea, on the pharmacokinetics of rosuvastatin in healthy volunteers

Previous in vitro studies have demonstrated the inhibitory effect of green tea on drug transporters. Because rosuvastatin, a lipid-lowering drug widely used for the prevention of cardiovascular events, is a substrate for many drug transporters, there is a possibility that there is interaction between green tea and rosuvastatin. The aim of this study was to investigate the effect of green tea on the pharmacokinetics of rosuvastatin in healthy volunteers. An open-label, three-treatment, fixed-sequence study was conducted. On Day 1, 20 mg of rosuvastatin was given to all subjects. After a 3-day washout period, the subjects received 20 mg of rosuvastatin plus 300 mg of epigallocatechin-3-gallate (EGCG), a major ingredient of green tea (Day 4). After a 10-day pretreatment of EGCG up to Day 14, they received rosuvastatin (20 mg) plus EGCG (300 mg) once again (Day 15). Blood samples for the pharmacokinetic assessments were collected up to 8 hours after each dose of rosuvastatin. A total of 13 healthy volunteers were enrolled. Compared with the administration of rosuvastatin alone, the concomitant use at Day 4 significantly reduced the area under the concentration–time curve from time 0 to the last measurable time (AUClast) by 19% (geometric mean ratio 0.81, 90% confidence interval [CI] 0.67–0.97) and the peak plasma concentration (Cmax) by 15% (geometric mean ratio 0.85, 90% CI 0.70–1.04). AUClast or Cmax of rosuvastatin on Day 15 was not significantly different from that on Day 1. This study demonstrated that co-administration of EGCG reduces the systemic exposure of rosuvastatin by 19%, and pretreatment of EGCG can eliminate that effect of co-administration of EGCG.
Seasonal Variation in Population Dynamics of Helminth Parasites in Clarias batrachus from Natural wetlands of Sylhet, Bangladesh

A year round field investigations were conducted with the aim to examine the seasonal variation in population dynamics of helminth parasites in Clarias batrachus from different natural aquatic habitat of north-eastern region of Bangladesh, Sylhet. This article summarizes the percentage of prevalence, mean intensity, abundance and index of infestation of helminth parasites in the C. batrachus during different months and seasons of the year in accordance with temperature, humidity and rainfall. The investigation period were categorized into four seasons i.e. pre-monsoon (February-April), monsoon (May-July), post-monsoon (August- October) and winter (November- January). A total 180 C. batrachus host individuals were examined and among them 139 (67.87%) specimens were found to be infested with 2205 individuals of parasites of three different groups namely trematode, cestode and nematode. Almost (100%) prevalence of helminth infestation were recorded from both male and female C. batrachus during the winter (Nov-Jan), followed by (Feb-April) pre-monsoon (66.67-86.67%) and (Aug-Sep) post-monsoon (66.67-80.00%) while lowest (53.33-60.00%) in monsoon or rainy season (May-July). Lower range of environmental temperature (21.0525.050C), associated with moderate humidity (62.00-64.00%) and scarcity of rainfall increases the intensity of helminthes parasitic infestation in C. batrachus . In consistent to this, with the gradual increasing in ambient temperature (28.01- 30.010C) and humidity (75.00-89.00%) associated with moderate rainfall (33.40-790.90 mm) declining the intensity of helminthes infestation in C. batrachus of the study area. International Journal of Natural Sciences (2015), 5(2) 86-89
Skin Friction Measurements Using Elastic Films

A new technology for distributed measurements of skin friction and pressure has been developed. The active element for this sensor is a thin film made of an elastomer with known thickness and shear modulus. The film deforms under load but does not compress or yield. The measurement is accomplished by determining the normal and tangential deformations of the film surface, and then converting these deformations into pressure and skin friction using a finite element model. This technology is currently under development for measurements of skin friction and pressure in wind tunnels, water tunnels, and for contact forces. In this article, we report the results from several experiments that demonstrate the operation of the sensor in both low speed and high speed wind tunnels. Validation of the skin friction measurements is demonstrated using a full developed channel flow and a high Reynolds number boundary layer. In the channel flow, measurements of skin friction using the sensor are compared to experimental and theoretical standards and agreement is better than 5% full scale. Measurements of skin friction are also conducted in a water tunnel with a high Reynolds number boundary layer. Here the results are compared to experimental skin friction measurements conducted using a drag balance and LDV measurements of velocity at the wall. The sensor again compares to the experimental measurements to better than 5% full scale. Finally, a qualitative demonstration is of unsteady flow on a cylinder in cross flow is presented demonstrating the potential for an unsteady skin friction sensor.