Miracle-dz/UniFAR-FTUs huggingface dataset:
Hormonal signaling cascades required for phototaxis switch in wandering Leptinotarsa decemlineata larvae

Many animals exploit several niches sequentially during their life cycles, a fitness referred to as ontogenetic niche shift (ONS). To successfully accomplish ONS, transition between development stages is often coupled with changes in one or more primitive, instinctive behaviors. Yet, the underlining molecular mechanisms remain elusive. We show here that Leptinotarsa decemlineata larvae finish their ONS at the wandering stage by leaving the plant and pupating in soil. At middle wandering phase, larvae also switch their phototactic behavior, from photophilic at foraging period to photophobic. We find that enhancement of juvenile hormone (JH) signal delays the phototactic switch, and vise verse. Moreover, RNA interference (RNAi)-aided knockdown of LdPTTH (prothoracicotropic hormone gene) or LdTorso (PTTH receptor gene) impairs avoidance response to light, a phenotype nonrescuable by 20-hydroxyecdysone. Consequently, the RNAi beetles pupate at the soil surface or in shallow layer of soil, with most of them failing to construct pupation chambers. Furthermore, a combination of depletion of LdPTTH/LdTorso and disturbance of JH signal causes no additional effects on light avoidance response and pupation site. Finally, we establish that TrpA1 (transient receptor potential (TRP) cation channel) is necessary for light avoidance behavior, acting downstream of PTTH. We conclude that JH/PTTH cascade concomitantly regulates metamorphosis and the phototaxis switch, to drive ONS of the wandering beetles from plant into soil to start the immobile pupal stage. Author summary Many animals occupy distinct niches and utilize diverse resources at different development stages in order to meet stage-dependent requirements and overcome stage-specific limitations. This fitness is referred to as ontogenetic niche shift (ONS). During the preparation for ONS, animals often change one or more primitive, instinctive behaviors. Holometabolous insects, with four discrete developmental periods usually in different niches, are a suitable animal group to explore the molecular modes of these behavioral switches. Here we find that Leptinotarsa decemlineata larvae, an insect defoliator of potatoes, switch their phototactic behavior, from photophilic at feeding period to photophobic during the larval-pupal transition (wandering stage). This phototactic switch facilitates the wandering larvae to accomplish the ONS from potato plant to their pupation site below ground. We show that JH/PTTH cascade controls the phototaxis switch, through a step in photo transduction between the photoreceptor molecule and the transient receptor potential cation channel.
The integral function of the endocytic recycling compartment is regulated by RFFL-mediated ubiquitylation of Rab11 effectors

ABSTRACT Endocytic trafficking is regulated by ubiquitylation (also known as ubiquitination) of cargoes and endocytic machineries. The role of ubiquitylation in lysosomal delivery has been well documented, but its role in the recycling pathway is largely unknown. Here, we report that the ubiquitin (Ub) ligase RFFL regulates ubiquitylation of endocytic recycling regulators. An RFFL dominant-negative (DN) mutant induced clustering of endocytic recycling compartments (ERCs) and delayed endocytic cargo recycling without affecting lysosomal traffic. A BioID RFFL interactome analysis revealed that RFFL interacts with the Rab11 effectors EHD1, MICALL1 and class I Rab11-FIPs. The RFFL DN mutant strongly captured these Rab11 effectors and inhibited their ubiquitylation. The prolonged interaction of RFFL with Rab11 effectors was sufficient to induce the clustered ERC phenotype and to delay cargo recycling. RFFL directly ubiquitylates these Rab11 effectors in vitro, but RFFL knockout (KO) only reduced the ubiquitylation of Rab11-FIP1. RFFL KO had a minimal effect on the ubiquitylation of EHD1, MICALL1, and Rab11-FIP2, and failed to delay transferrin recycling. These results suggest that multiple Ub ligases including RFFL regulate the ubiquitylation of Rab11 effectors, determining the integral function of the ERC. Summary: The ubiquitin ligase RFFL regulates ubiquitylation of Rab11 effectors and the integral function of endocytic recycling compartments.
Enrichment sampling for a multi-site patient survey using electronic health records and census data

Objective We describe a stratified sampling design that combines electronic health records (EHRs) and United States Census (USC) data to construct the sampling frame and an algorithm to enrich the sample with individuals belonging to rarer strata. Materials and Methods This design was developed for a multi-site survey that sought to examine patient concerns about and barriers to participating in research studies, especially among under-studied populations (eg, minorities, low educational attainment). We defined sampling strata by cross-tabulating several socio-demographic variables obtained from EHR and augmented with census-block-level USC data. We oversampled rarer and historically underrepresented subpopulations. Results The sampling strategy, which included USC-supplemented EHR data, led to a far more diverse sample than would have been expected under random sampling (eg, 3-, 8-, 7-, and 12-fold increase in African Americans, Asians, Hispanics and those with less than a high school degree, respectively). We observed that our EHR data tended to misclassify minority races more often than majority races, and that non-majority races, Latino ethnicity, younger adult age, lower education, and urban/suburban living were each associated with lower response rates to the mailed surveys. Discussion We observed substantial enrichment from rarer subpopulations. The magnitude of the enrichment depends on the accuracy of the variables that define the sampling strata and the overall response rate. Conclusion EHR and USC data may be used to define sampling strata that in turn may be used to enrich the final study sample. This design may be of particular interest for studies of rarer and understudied populations.
Phytotoxic and Genotoxic Effects of Copper Nanoparticles in Coriander (Coriandrum sativum—Apiaceae)

Engineered metal nanoparticles have been widely used in several applications that may lead to increased exposure to the environment. In this study, we assessed the phytotoxic effect of various concentrations of copper nanoparticles CuNP, (200, 400 and 800 mg/L) on coriander (Coriandrum sativum) plants grown hydroponically. C. sativum plants treated with CuNP demonstrated decreased biomass and root length in comparison to control untreated plants. Additionally, decreased levels of photosynthetic pigments (chlorophyll a and b) were also seen in C. sativum plants treated with CuNP, as well as damage to the C. sativum root plasma membrane as demonstrated by Evan’s blue dye and increased electrolyte leakage. Moreover, our results exhibited increased levels of H2O2 and MDA on C. Sativum plants treated with CuNP. X-Ray Fluorescence (XRF) analysis confirmed that C. sativum treated with CuNP accumulated the latter in plant root tissues. Random amplified polymorphic DNA (RAPD) analysis confirmed the genotoxic effect of CuNP, which altered the C. sativum genome. This was shown by the different banding pattern of RAPD. Overall, our results exhibited that CuNP is toxic to C. sativum plants.
Experimental Applications of in situ Liver Perfusion Machinery for the Study of Liver Disease

The liver is involved in a wide range of activities in vertebrates and some other animals, including metabolism, protein synthesis, detoxification, and the immune system. Until now, various methods have been devised to study liver diseases; however, each method has its own limitations. In situ liver perfusion machinery, originally developed in rats, has been successfully adapted to mice, enabling the study of liver diseases. Here we describe the protocol, which is a simple but widely applicable method for investigating the liver diseases. The liver is perfused in situ by cannulation of the portal vein and suprahepatic inferior vena cava (IVC), with antegrade closed circuit circulation completed by clamping the infrahepatic IVC. In situ liver perfusion can be utilized to evaluate immune cell migration and function, hemodynamics and related cellular reactions in each type of hepatic cells, and the metabolism of toxic or other compounds by changing the composition of the circulating media. In situ liver perfusion method maintains liver function and cell viability for up to 2 h. This study also describes an optional protocol using density-gradient centrifugation for the separation of different types of hepatic cells, allowing the determination of changes in each cell type. In summary, this method of in situ liver perfusion will be useful for studying liver diseases as a complement to other established methods.
Down-regulation of microRNA-34a-5p promotes trophoblast cell migration and invasion via targetting Smad4

Abstract Trophoblastic dysfunction, such as insufficient migration and invasion, is well-known to be correlated with preeclampsia (PE). Recently, microRNAs (miRNAs) have been implicated in diverse biological processes and human diseases, including PE. However, the expression and functions of miRNAs in the progression of PE, especially in the regulation of trophoblast cell migration and invasion remain largely unclear. Here, we compared the miRNAs expression profiles of PE patients with healthy controls using microarray assay and chose a significant increased miRNA-miR-34a-5p for further investigation. Overexpression of miR-34a-5p dramatically reduced migration and invasion in trophoblast HTR-8/SVneo cells, whereas enhanced by its inhibitor. Luciferase activity assay showed that miR-34a-5p directly target Smad family member 4 (Smad4), which is associated with cancer cell invasiveness and metastasis. We also found that Smad4 was down-regulated in PE patients, and an inverse relationship between Smad4 and miR-34a-5p expression levels was observed in placental tissues from PE patients. Further study showed that knockdown of Smad4 effectively attenuated the promoting effects of miR-34a-5p inhibition on the migration and invasion of HTR-8/SVneo cells. Taken together, these findings suggest that inhibition of miR-34a-5p improves invasion and migration of trophoblast cells by directly targetting Smad4, which indicated the potential of miR-34a-5p as a therapeutic target against PE.
Electrospinning of Cyclodextrin Functional Nanofibers for Drug Delivery Applications

Electrospun nanofibers have sparked tremendous attention in drug delivery since they can offer high specific surface area, tailored release of drugs, controlled surface chemistry for preferred protein adsorption, and tunable porosity. Several functional motifs were incorporated into electrospun nanofibers to greatly expand their drug loading capacity or to provide the sustained release of the embedded drug molecules. In this regard, cyclodextrins (CyD) are considered as ideal drug carrier molecules as they are natural, edible, and biocompatible compounds with a truncated cone-shape with a relatively hydrophobic cavity interior for complexation with hydrophobic drugs and a hydrophilic exterior to increase the water-solubility of drugs. Further, the formation of CyD-drug inclusion complexes can protect drug molecules from physiological degradation, or elimination and thus increases the stability and bioavailability of drugs, of which the release takes place with time, accompanied by fiber degradation. In this review, we summarize studies related to CyD-functional electrospun nanofibers for drug delivery applications. The review begins with an introductory description of electrospinning; the structure, properties, and toxicology of CyD; and CyD-drug complexation. Thereafter, the release of various drug molecules from CyD-functional electrospun nanofibers is provided in subsequent sections. The review concludes with a summary and outlook on material strategies.
The Space-Time Congruency Effect: A Meta-Analysis

Several reaction time (RT) studies report faster responses when responses to temporal information are arranged in a spatially congruent manner than when this arrangement is incongruent. The resulting space-time congruency effect is commonly attributed to a culturally salient localization of temporal information along a mental timeline (e.g., a mental timeline that runs from left to right). The present study aims to provide a compilation of the published RT studies on this time-space association in order to estimate the size of its effect and the extent of potential publication bias in this field of research. In this meta-analysis, three types of task are distinguished due to hitherto existing empirical findings. These findings suggest that the extent to which time is made relevant to the experimental task has a systematic impact on whether or not the mental timeline is activated. The results of this meta-analysis corroborate these considerations: First, experiments that make time a task-relevant dimension have a mean effect size of d = 0.46. Second, in experiments in which time is task irrelevant, the effect size does not significantly deviate from zero. Third, temporal priming studies have a surprisingly high mean effect size of d = 0.47, which, however, should be adjusted to d = 0.36 due to publication bias.
A Handy Flexible Micro-Thermocouple Using Low-Melting-Point Metal Alloys

A handy, flexible micro-thermocouple using low-melting-point metal alloys is proposed in this paper. The thermocouple has the advantages of simple fabrication and convenient integration. Bismuth/gallium-based mixed alloys are used as thermocouple materials. To precisely inject the metal alloys to the location of the sensing area, a micro-polydimethylsiloxane post is designed within the sensing area to prevent outflow of the metal alloy to another thermocouple pole during the metal-alloy injection. Experimental results showed that the Seebeck coefficient of this thermocouple reached −10.54 μV/K, which was much higher than the previously reported 0.1 μV/K. The thermocouple was also be bent at 90° more than 200 times without any damage when the mass ratio of the bismuth-based alloy was <60% in the metal-alloy mixture. This technology mitigated the difficulty of depositing traditional thin–film thermocouples on soft substrates. Therefore, the thermocouple demonstrated its potential for use in microfluidic chips, which are usually flexible devices.
Reproducibility and accuracy of late gadolinium enhancement cardiac magnetic resonance measurements for the detection of left atrial fibrosis in patients undergoing atrial fibrillation ablation procedures.

Aims Late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) may define left atrial (LA) anatomy and structural remodelling, and facilitate atrial fibrillation (AF) ablation. We aimed to assess the intra- and inter-observer reproducibility and agreement of LGE-CMR parameters with direct application to AF ablation techniques. Methods and results One experienced and one non-experienced observer performed complete LGE-CMR data analysis twice, on different days, in 40 randomly selected LGE-CMR examinations [20 performed before ablation (pre-ablation) and 20 performed 3 months after ablation (post-ablation)]. Four additional observers (two experienced and two non-experienced) performed complete LGE-CMR data analysis in a subgroup of 30 patients (15 pre-ablation and 15 post-ablation). All LGE-CMR were performed in sinus rhythm. Intra- and inter-observer reproducibility of LA volume, LA area, and sphericity index (SI) was high: coefficient of variation <10% and intraclass correlation coefficient >0.71. Geometric congruency of repeated reconstruction of LA shape was high: maximal error <5 mm for intra-observer and <8 mm for inter-observer. The precision of scar location increased with extent of scar, and was high (Dice coefficient >0.75) when the scar area was >5 cm2 for a single observer and >15 cm2 for multiple observers. Non-experienced observers performed equally well to experienced observers. Conclusion Late gadolinium enhancement cardiac magnetic resonance measurements of LA area, volume, and SI were reproducible, and geometric congruency of LA shape was high. Location of scar was precise for scar areas >5 cm2 for single observers and >15 cm2 for multiple observers, regardless of the observers' experience. These results may serve as a reference for future studies on the role for substrate-based AF ablation procedures.
S29434, a Quinone Reductase 2 Inhibitor: Main Biochemical and Cellular Characterization

Quinone reductase 2 (QR2, E.C. 1.10.5.1) is an enzyme with a feature that has attracted attention for several decades: in standard conditions, instead of recognizing NAD(P)H as an electron donor, it recognizes putative metabolites of NADH, such as N-methyl- and N-ribosyl-dihydronicotinamide. QR2 has been particularly associated with reactive oxygen species and memory, strongly suggesting a link among QR2 (as a possible key element in pro-oxidation), autophagy, and neurodegeneration. In molecular and cellular pharmacology, understanding physiopathological associations can be difficult because of a lack of specific and powerful tools. Here, we present a thorough description of the potent, nanomolar inhibitor [2-(2-methoxy-5H-1,4b,9-triaza(indeno[2,1-a]inden-10-yl)ethyl]-2-furamide (S29434 or NMDPEF; IC50 = 5–16 nM) of QR2 at different organizational levels. We provide full detailed syntheses, describe its cocrystallization with and behavior at QR2 on a millisecond timeline, show that it penetrates cell membranes and inhibits QR2-mediated reactive oxygen species (ROS) production within the 100 nM range, and describe its actions in several in vivo models and lack of actions in various ROS-producing systems. The inhibitor is fairly stable in vivo, penetrates cells, specifically inhibits QR2, and shows activities that suggest a key role for this enzyme in different pathologic conditions, including neurodegenerative diseases.
Dynamic cerebral autoregulation is attenuated in young fit women

Young women exhibit higher prevalence of orthostatic hypotension with presyncopal symptoms compared to men. These symptoms could be influenced by an attenuated ability of the cerebrovasculature to respond to rapid blood pressure (BP) changes [dynamic cerebral autoregulation (dCA)]. The influence of sex on dCA remains unclear. dCA in 11 fit women (25 ± 2 years) and 11 age‐matched men (24 ± 1 years) was compared using a multimodal approach including a sit‐to‐stand (STS) and forced BP oscillations (repeated squat‐stand performed at 0.05 and 0.10 Hz). Prevalence of initial orthostatic hypotension (IOH; decrease in systolic ≥ 40 mmHg and/or diastolic BP ≥ 20 mmHg) during the first 15 sec of STS was determined as a functional outcome. In women, the decrease in mean middle cerebral artery blood velocity (MCAvmean) following the STS was greater (−20 ± 8 vs. −11 ± 7 cm sec−1; P = 0.018) and the onset of the regulatory change (time lapse between the beginning of the STS and the increase in the conductance index (MCAvmean/mean arterial pressure) was delayed (P = 0.007). Transfer function analysis gain during 0.05 Hz squat‐stand was ~48% higher in women (6.4 ± 1.3 vs. 3.8 ± 2.3 cm sec−1 mmHg−1; P = 0.017). Prevalence of IOH was comparable between groups (women: 4/9 vs. men: 5/9, P = 0.637). These results indicate the cerebrovasculature of fit women has an attenuated ability to react to rapid changes in BP in the face of preserved orthostasis, which could be related to higher resting cerebral blood flow allowing women to better face transient hypotension.
Ovulatory status of overweight women without Polycystic Ovary Syndrome

Objective: Obesity is one of the extra hypothalamic-pituitary-ovarian axis factors that can influence ovulation. The isolated impact of obesity on ovulation without other comorbidities needs to be further studied. Our goal is to evaluate the association between the anovulation in the ultrasonographic monitoring of the ovulation cycle and the body mass increase of infertile patients without polycystic ovaries of a university service. Methods: Case-control study performed at the Human Reproduction Laboratory of the University Hospital. We evaluated 1,356 ultrasound monitoring reports of ovulation between January 2011 and December 2015. We named case those patients who ovulated on the monitored cycle. After applying the exclusion criteria, we consolidated a total of 110 cases and 118 controls. The exposure variables were normal BMI or patients classified with a BMI above normal. Data analysis was performed using SPSS 22.0. Differences in proportions were assessed by X2 test Pearson, Fisher and Wilcoxon test. The value of p<0.05 was considered statistically significant. Results: The groups were comparable in age, age at menarche, number of pregnancies, deliveries, cesarean sections and abortions, number of antral follicles, FSH, prolactin and TSH values. Among the anovulatory patients, 57 (51.82%) were overweight, while among ovulatory patients, 44 (37.29%) were in this same BMI category. The odds ratio was 1.8655, with a significant p value (p<0.05). Conclusion: There was an association between anovulation and increase in the Body Mass Index, with an increased risk of anovulation in patients with BMI above normal.
Deep Learning and Handcrafted Method Fusion: Higher Diagnostic Accuracy for Melanoma Dermoscopy Images

This paper presents an approach that combines conventional image processing with deep learning by fusing the features from the individual techniques. We hypothesize that the two techniques, with different error profiles, are synergistic. The conventional image processing arm uses three handcrafted biologically inspired image processing modules and one clinical information module. The image processing modules detect lesion features comparable to clinical dermoscopy information—atypical pigment network, color distribution, and blood vessels. The clinical module includes information submitted to the pathologist—patient age, gender, lesion location, size, and patient history. The deep learning arm utilizes knowledge transfer via a ResNet-50 network that is repurposed to predict the probability of melanoma classification. The classification scores of each individual module from both processing arms are then ensembled utilizing logistic regression to predict an overall melanoma probability. Using cross-validated results of melanoma classification measured by area under the receiver operator characteristic curve (AUC), classification accuracy of 0.94 was obtained for the fusion technique. In comparison, the ResNet-50 deep learning based classifier alone yields an AUC of 0.87 and conventional image processing based classifier yields an AUC of 0.90. Further study of fusion of conventional image processing techniques and deep learning is warranted.