Miracle-dz/UniFAR-FTUs huggingface dataset:
UBE2L6 is Involved in Cisplatin Resistance by Regulating the Transcription of ABCB6.

BACKGROUND Cisplatin is an important anticancer agent in cancer chemotherapy, but when resistant cells appear, treatment becomes difficult and prognosis is poor. OBJECTIVE In this study we investigated the gene expression profile in cisplatin sensitive and resistant cells, and identified the genes involved in cisplatin resistance. METHODS Comparison of gene expression profiles revealed that UBE2L6 mRNA is highly expressed in resistant cells. To elucidate whether UBE2L6 is involved in the acquisition of cisplatin resistance, UBE2L6-overexpressing cells established from cisplatin-sensitive cells and UBE2L6-silenced cells established from cisplatin-resistant cells were generated, and the sensitivity of cisplatin was examined. RESULTS The sensitivity of the UBE2L6- overexpressing cells did not change compared with the control cells, but the UBE2L6-silenced cells were sensitized to cisplatin. To elucidate the mechanism of UBE2L6 in cisplatin resistance, we compared the gene expression profiles of UBE2L6-silenced cells and control cells and found that the level of ABCB6 mRNA involved in cisplatin resistance was decreased. Moreover, ABCB6 promoter activity was partially suppressed in UBE2L6-silenced cells. CONCLUSION These results suggest that cisplatin-resistant cells have upregulated UBE2L6 expression and contribute to cisplatin resistance by regulating ABCB6 expression at the transcriptional level. UBE2L6 might be a molecular target that overcomes cisplatin resistance.
Autochthonous Cases of Mucosal Leishmaniasis in Northeastern Italy: Clinical Management and Novel Treatment Approaches

Mucosal leishmaniasis (ML) is a rare clinical variant of tegumentary leishmaniasis in Mediterranean Europe. Here we report on three autochthonous cases of head and neck ML in patients living in Northeastern Italy. Patients presented with non-specific, long-standing symptoms of upper respiratory tract involvement, mimicking other diseases. Parasitological diagnosis was reached by histopathology, immunohistochemistry and molecular biology on tissue specimens. Leishmania infantum was identified by molecular typing in all three cases. All patients reached a complete remission with protracted multivalent antileishmanial drugs; in one case, a novel approach of combined medical and endoscopic surgical treatment was carried out. High clinical suspicion led to a prompt diagnosis and deployment of a multivalent treatment. ML should be considered in the differential diagnosis of nasal, oral, and pharyngolaryngeal lesions in endemic areas. A prompt diagnosis is mandatory to establish a correct management; different antileishmanial medications as well as endoscopic surgical options may be required to reach a complete remission.
The binding process of BmKTX and BmKTX-D33H toward to Kv1.3 channel: a molecular dynamics simulation study

Abstract The potassium channel Kv1.3 is an important pharmacological target and the Kaliotoxin-type toxins (α-KTX-3 family) are its specific blockers. Here, we study the binding process of two kinds of Kaliotoxin-type toxins:BmKTX and its mutant (BmKTX-D33H) toward to Kv1.3 channel using MD simulation and umbrella sampling simulation, respectively. The calculated binding free energies are -27 kcal/mol and -34 kcal/mol for BmKTX and BmKTX-D33H, respectively, which are consistent with experimental results. The further analysis indicate that the characteristic of electrostatic potential of the α-KTX-3 have important effect on their binding modes with Kv1.3 channel; the residue 33 in BmKTX or BmKTX-D33H plays a key role in determine their binding orientations toward to Kv1.3 channel; when residue 33 (or 34) has negative electrostatic potential, the anti-parallel β-sheet domain of α-KTX-3 toxin peptide will keep away from the filter region of Kv1.3 channel, as BmKTX; when residue 33(or 34) has positive electrostatic potential, the anti-parallel β-sheet domain of α-KTX-3 toxin peptide will interact with the filter region of Kv1.3 channel, as BmKTX-D33H. Above all, electrostatic potential differences on toxin surfaces and correlations motions within the toxins will determine the toxin-potassium channel interaction model. In addition, the hydrogen bond interaction is the pivotal factor for the Kv1.3-Kaliotoxin association. Understanding the binding mechanism of toxin–potassium channel will facilitate the rational development of new toxin analogue. Communicated by Ramaswamy H. Sarma
Tonic GABAA Conductance Favors Spike-Timing-Dependent over Theta-Burst-Induced Long-Term Potentiation in the Hippocampus

Synaptic plasticity is triggered by different patterns of network activity. Here, we investigated how LTP in CA3-CA1 synapses induced by different stimulation patterns is affected by tonic GABAA conductances in rat hippocampal slices. Spike-timing-dependent LTP was induced by pairing Schaffer collateral stimulation with antidromic stimulation of CA1 pyramidal neurons. Theta-burst-induced LTP was induced by theta-burst stimulation of Schaffer collaterals. We mimicked increased tonic GABAA conductance by bath application of 30 μm GABA. Surprisingly, tonic GABAA conductance selectively suppressed theta-burst-induced LTP but not spike-timing-dependent LTP. We combined whole-cell patch-clamp electrophysiology, two-photon Ca2+ imaging, glutamate uncaging, and mathematical modeling to dissect the mechanisms underlying these differential effects of tonic GABAA conductance. We found that Ca2+ transients during pairing of an action potential with an EPSP were less sensitive to tonic GABAA conductance-induced shunting inhibition than Ca2+ transients induced by EPSP burst. Our results may explain how different forms of memory are affected by increasing tonic GABAA conductances under physiological or pathologic conditions, as well as under the influence of substances that target extrasynaptic GABAA receptors (e.g., neurosteroids, sedatives, antiepileptic drugs, and alcohol). SIGNIFICANCE STATEMENT Brain activity is associated with neuronal firing and synaptic signaling among neurons. Synaptic plasticity represents a mechanism for learning and memory. However, some neurotransmitters that escape the synaptic cleft or are released by astrocytes can target extrasynaptic receptors. Extrasynaptic GABAA receptors mediate tonic conductances that reduce the excitability of neurons by shunting. This results in the decreased ability for neurons to fire action potentials, but when action potentials are successfully triggered, tonic conductances are unable to reduce them significantly. As such, tonic GABAA conductances have minimal effects on spike-timing-dependent synaptic plasticity while strongly attenuating the plasticity evoked by EPSP bursts. Our findings shed light on how changes in tonic conductances can selectively affect different forms of learning and memory.
Influence of Experimental Parameters of a Continuous Flow Process on the Properties of Very Small Iron Oxide Nanoparticles (VSION) Designed for T1-Weighted Magnetic Resonance Imaging (MRI)

This study reports the development of a continuous flow process enabling the synthesis of very small iron oxide nanoparticles (VSION) intended for T1-weighted magnetic resonance imaging (MRI). The influence of parameters, such as the concentration/nature of surfactants, temperature, pressure and the residence time on the thermal decomposition of iron(III) acetylacetonate in organic media was evaluated. As observed by transmission electron microscopy (TEM), the diameter of the resulting nanoparticle remains constant when modifying the residence time. However, significant differences were observed in the magnetic and relaxometric studies. This continuous flow experimental setup allowed the production of VSION with high flow rates (up to 2 mL·min−1), demonstrating the efficacy of such process compared to conventional batch procedure for the scale-up production of VSION.
Improving the Recognition Accuracy of Memristive Neural Networks via Homogenized Analog Type Conductance Quantization

Conductance quantization (QC) phenomena occurring in metal oxide based memristors demonstrate great potential for high-density data storage through multilevel switching, and analog synaptic weight update for effective training of the artificial neural networks. Continuous, linear and symmetrical modulation of the device conductance is a critical issue in QC behavior of memristors. In this contribution, we employ the scanning probe microscope (SPM) assisted electrode engineering strategy to control the ion migration process to construct single conductive filaments in Pt/HfOx/Pt devices. Upon deliberate tuning and evolution of the filament, 32 half integer quantized conductance states in the 16 G0 to 0.5 G0 range with enhanced distribution uniformity was achieved. Simulation results revealed that the numbers of the available QC states and fluctuation of the conductance at each state play an important role in determining the overall performance of the neural networks. The 32-state QC behavior of the hafnium oxide device shows improved recognition accuracy approaching 90% for handwritten digits, based on analog type operation of the multilayer perception (MLP) neural network.
APETx-Like Peptides from the Sea Anemone Heteractis crispa, Diverse in Their Effect on ASIC1a and ASIC3 Ion Channels

Currently, five peptide modulators of acid-sensing ion channels (ASICs) attributed to structural class 1b of sea anemone toxins have been described. The APETx2 toxin is the first and most potent ASIC3 inhibitor, so its homologs from sea anemones are known as the APETx-like peptides. We have discovered that two APETx-like peptides from the sea anemone Heteractis crispa, Hcr 1b-3 and Hcr 1b-4, demonstrate different effects on rASIC1a and rASIC3 currents. While Hcr 1b-3 inhibits both investigated ASIC subtypes with IC50 4.95 ± 0.19 μM for rASIC1a and 17 ± 5.8 μM for rASIC3, Hcr 1b-4 has been found to be the first potentiator of ASIC3, simultaneously inhibiting rASIC1a at similar concentrations: EC50 1.53 ± 0.07 μM and IC50 1.25 ± 0.04 μM. The closest homologs, APETx2, Hcr 1b-1, and Hcr 1b-2, previously demonstrated the ability to inhibit hASIC3 with IC50 63 nM, 5.5, and 15.9 μM, respectively, while Hcr 1b-2 also inhibited rASIC1a with IC50 4.8 ± 0.3 μM. Computer modeling allowed us to describe the peculiarities of Hcr 1b-2 and Hcr 1b-4 interfaces with the rASIC1a channel and the stabilization of the expanded acidic pocket resulting from peptides binding which traps the rASIC1a channel in the closed state.
Preliminary Investigation of Effect of Neem-Derived Pesticides on Plasmopara halstedii Pathotype 704 in Sunflower under In Vitro and In Vivo Conditions

Two neem-derived pesticides were examined under in vitro and in vivo conditions to test their efficacy in controlling Plasmopara halstedii pathotype 704, a causal agent of downy mildew in sunflower. All the tested concentrations of neem leaf extract and the highest concentration of commercial neem product significantly reduced the sporangial germination under in vitro conditions. In in vivo experiment, 3-days old pre-treated seedlings with both concentrations of neem leaf extract and the highest concentration of commercial product showed a significant reduction in the infection indicating possible systemic effect of neem. When the seedlings were treated following the infection with P. halstedii (i.e., post-treatment), only the highest concentrations of neem leaf extract and the commercial product showed a significant reduction in the infection indicating curative effect of neem. Possibilities for the control of P. halstedii with neem-derived pesticides are discussed.
A fluorescence method to visualize the nuclear boundary by the lipophilic dye DiI

ABSTRACT Here, we describe a procedure to fluorescently contrast the nuclear boundary using the lipophilic carbocyanine dye DiI in cultured human cells. Our procedure is simple and is applicable to detect nuclear boundary defects, which may be relevant to studies on nuclear envelope dynamics, micronuclei formation and cancer biology. Abbreviations DiI: 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate; DiO: 3,3ʹ-dioctadecyloxacarbocyanine perchlorate; NE: nuclear envelope; RanBP2: Ran-binding protein 2/Nucleoporin 358
Sleep Quality and Mental Disorder Symptoms among Canadian Public Safety Personnel

Poor sleep quality is associated with numerous mental health concerns and poorer overall physical health. Sleep disturbances are commonly reported by public safety personnel (PSP) and may contribute to the risk of developing mental disorders or exacerbate mental disorder symptoms. The current investigation was designed to provide estimates of sleep disturbances among PSP and explore the relationship between sleep quality and mental health status. PSP completed screening measures for sleep quality and diverse mental disorders through an online survey. Respondents (5813) were grouped into six categories: communications officials, correctional workers, firefighters, paramedics, police officers, and Royal Canadian Mounted Police (RCMP). Many PSP in each category reported symptoms consistent with clinical insomnia (49–60%). Rates of sleep disturbances differed among PSP categories (p < 0.001, ω = 0.08). Sleep quality was correlated with screening measures for post-traumatic stress disorder (PTSD), depression, anxiety, social anxiety disorder, panic disorder, and alcohol use disorder for all PSP categories (r = 0.18–0.70, p < 0.001). PSP who screened positive for insomnia were 3.43–6.96 times more likely to screen positive for a mental disorder. All PSP reported varying degrees of sleep quality, with the lowest disturbances found among firefighters and municipal/provincial police. Sleep appears to be a potentially important factor for PSP mental health.
Pre-pregnancy body mass index and time to pregnancy among couples pregnant within a year: A China cohort study

Background Extreme pre-pregnancy body mass index (BMI) values have been associated with reduced fecundability and prolonged time to pregnancy in previous studies. However, the effect in fertile couples is unclear. Objectives This study aimed to evaluate the association between pre-pregnancy BMI and fecundability, measured as time to pregnancy (TTP), among couples that achieved pregnancy within 1 year. Methods This was a retrospective cohort study of 50,927 couples wishing to conceive, enrolled in the National Free Preconception Health Examination Project (NFPHEP) in Chongqing, China, during 2012–2016. Participants’ weight and height were measured by NFPHEP-trained preconception guidance physicians. TTP measured in months was used to determine subfecundity (TTP >6 months). The strength of association between BMI and TTP/subfecundity was measured with fecundability odds ratios (FOR)/odds ratios (OR) and their corresponding 95% confidence intervals (CI), calculated with Cox and logistic regression analysis. We used restricted cubic spline regression (RCS) to test the observed FOR trends. Results Compared to women with normal BMI, women with pre-pregnancy overweight/obesity had longer TTP (FOR = 0.96, 95% CI: 0.94–0.99) and increased risk of subfecundity (OR = 1.08, 95% CI: 1.00–1.17). There was no association between TTP and male BMI. RCS trends varied when data were stratified by male pre-pregnancy BMI, with the greatest change detected in pre-pregnancy underweight men. Conclusions Pre-pregnancy overweight/obesity was associated with longer TTP and subfecundity among women who became pregnant within 1 year; this effect was likely mediated by their partners’ pre-pregnancy BMI. These findings indicate that BMI could affect fecundability, independently of affecting the risk of sterility. Advice on weight management and maintaining healthy weight should be included in couples’ preconception guidance.
More than sugar in the milk: human milk oligosaccharides as essential bioactive molecules in breast milk and current insight in beneficial effects

Abstract Human milk is the gold standard for newborn infants. Breast milk not only provides nutrients, it also contains bioactive components that guide the development of the infant’s intestinal immune system, which can have a lifelong effect. The bioactive molecules in breast milk regulate microbiota development, immune maturation and gut barrier function. Human milk oligosaccharides (hMOs) are the most abundant bioactive molecules in human milk and have multiple beneficial functions such as support of growth of beneficial bacteria, anti-pathogenic effects, immune modulating effects, and stimulation of intestine barrier functions. Here we critically review the current insight into the benefits of bioactive molecules in mother milk that contribute to neonatal development and focus on current knowledge of hMO-functions on microbiota and the gastrointestinal immune barrier. hMOs produced via genetically engineered microorganisms are now applied in infant formulas to mimic the nutritional composition of breast milk as closely as possible, and their prospects and scientific challenges are discussed in depth.
Sleeve for Knee Angle Monitoring: An IMU-POF Sensor Fusion System

The knee flexion-extension angle is an important variable to be monitored in various clinical scenarios, for example, during physical rehabilitation assessment. The purpose of this work is to develop and validate a sensor fusion system based on a knee sleeve for monitoring of physical therapy. The system consists of merging data from two inertial measurement units (IMUs) and an intensity-variation based Polymer Optical Fiber (POF) curvature sensor using a quaternion-based Multiplicative Extended Kalman Filter (MEKF). The proposed data fusion method is magnetometer-free and deals with sensors’ uncertainties through reliability intervals defined during gait. Walking trials were performed by twelve healthy participants using our knee sleeve system and results were validated against a gold standard motion capture system. Additionally, a comparison with other three knee angle estimation methods, which are exclusively based on IMUs, was carried out. The proposed system presented better performance (mean RMSE <inline-formula><tex-math notation="LaTeX">$< $</tex-math></inline-formula> 3.3<inline-formula><tex-math notation="LaTeX">$^\circ$</tex-math></inline-formula>, LFM coefficients, <inline-formula><tex-math notation="LaTeX">$a_1$</tex-math></inline-formula> = 0.99 <inline-formula><tex-math notation="LaTeX">$\pm$</tex-math></inline-formula> 0.04, <inline-formula><tex-math notation="LaTeX">$a_0$</tex-math></inline-formula> = 0.70 <inline-formula><tex-math notation="LaTeX">$\pm$</tex-math></inline-formula> 2.29, <inline-formula><tex-math notation="LaTeX">$R^2$</tex-math></inline-formula> = 0.98 <inline-formula><tex-math notation="LaTeX">$\pm$</tex-math></inline-formula> 0.01 and <inline-formula><tex-math notation="LaTeX">$\rho _C$</tex-math></inline-formula> <inline-formula><tex-math notation="LaTeX">$>$</tex-math></inline-formula> 0.99) when compared to the other evaluated methods. Experimental results demonstrate the usability and feasibility of our system to estimate knee motion with high accuracy, repeatability, and reproducibility. This wearable system may be suitable for motion assessment in rehabilitation labs in future studies.
Tolcapone, a potent aggregation inhibitor for the treatment of familial leptomeningeal amyloidosis

Hereditary transthyretin amyloidosis (ATTR) is a disease characterized by the extracellular deposition of transthyretin (TTR) amyloid fibrils. Highly destabilizing TTR mutations cause leptomeningeal amyloidosis, a rare, but fatal, disorder in which TTR aggregates in the brain. The disease remains intractable, since liver transplantation, the reference therapy for systemic ATTR, does not stop mutant TTR production in the brain. In addition, despite current pharmacological strategies have shown to be effective against in vivo TTR aggregation by stabilizing the tetramer native structure and precluding its dissociation, they display low brain permeability. Recently, we have repurposed tolcapone as a molecule to treat systemic ATTR. Crystal structures and biophysical analysis converge to demonstrate that tolcapone binds with high affinity and specificity to three unstable leptomeningeal TTR variants, stabilizing them and, consequently, inhibiting their aggregation. Because tolcapone is an FDA‐approved drug that crosses the blood–brain barrier, our results suggest that it can translate into a first disease‐modifying therapy for leptomeningeal amyloidosis.
Paternity Assignment in White Guinea Yam (Dioscorea Rotundata) Half-Sib Progenies from Polycross Mating Design Using SNP Markers

White Guinea yam is mostly a dioecious outcrossing crop with male and female flowers produced on distinct plants. Fertile parents produce high fruit set in an open pollination polycross block, which is a cost-effective and convenient way of generating variability in yam breeding. However, the pollen parent of progeny from polycross mating is usually unknown. This study aimed to determine paternity in white Guinea yam half-sib progenies from polycross mating design. A total of 394 half-sib progenies from random open pollination involving nine female and three male parents was genotyped with 6602 SNP markers from DArTSeq platform to recover full pedigree. A higher proportion of expected heterozygosity, allelic richness, and evenness were observed in the half-sib progenies. A complete pedigree was established for all progenies from two families (TDr1685 and TDr1688) with 100% accuracy, while in the remaining families, paternity was assigned successfully only for 56 to 98% of the progenies. Our results indicated unequal paternal contribution under natural open pollination in yam, suggesting unequal pollen migrations or gene flow among the crossing parents. A total of 3.8% of progenies lacking paternal identity due to foreign pollen contamination outside the polycross block was observed. This study established the efficient determination of parental reconstruction and allelic contributions in the white Guinea yam half-sib progenies generated from open pollination polycross using SNP markers. Findings are useful for parental reconstruction, accurate dissection of the genetic effects, and selection in white Guinea yam breeding program utilizing polycross mating design.
Placensin is a glucogenic hormone secreted by human placenta

FBN1 encodes asprosin, a glucogenic hormone, following furin cleavage of the C‐terminus of profibrillin 1. Based on evolutionary conservation between FBN1 and FBN2, together with conserved furin cleavage sites, we identified a peptide hormone placensin encoded by FBN2 based on its high expression in trophoblasts of human placenta. In primary and immortalized murine hepatocytes, placensin stimulates cAMP production, protein kinase A (PKA) activity, and glucose secretion, accompanied by increased expression of gluconeogenesis enzymes. In situ perfusion of liver and in vivo injection with placensin also stimulate glucose secretion. Placensin is secreted by immortalized human trophoblastic HTR‐8/SVneo cells, whereas placensin treatment stimulates cAMP‐PKA signaling in these cells, accompanied by increases in MMP9 transcripts and activities, thereby promoting cell invasion. In pregnant women, levels of serum placensin increase in a stage‐dependent manner. During third trimester, serum placensin levels of patients with gestational diabetes mellitus are increased to a bigger extent compared to healthy pregnant women. Thus, placensin represents a placenta‐derived hormone, capable of stimulating glucose secretion and trophoblast invasion.