Miracle-dz/UniFAR-FTUs huggingface dataset:
Muscarinic and nicotinic acetylcholine receptor agonists: current scenario in Alzheimer's disease therapy

Alzheimer's disease (AD) has become the primary cause of dementia. It shows a progressive cognitive dysfunction with degenerating neurons. Acetylcholine receptors (AChRs) propagate the cognitive ability and it consists of two primary members namely muscarinic (mAChRs) and nicotinic receptors (nAChRs). Where mAChRs is G‐protein coupled receptor, (nAChRs) are ligand‐gated ion channels. The conventional therapeutic regimen for AD consists of three acetylcholinestearse inhibitors while a single NMDA receptor antagonist. Researchers around the globe are developing new and modifying the existing AChRs agonists to develop lead candidates with lower risk to benefit ratio where benefits clearly outweigh the adverse events.
Nonmuscle myosin IIA is involved in recruitment of apical junction components through activation of α-catenin

ABSTRACT MDCK dog kidney epithelial cells express two isoforms of nonmuscle myosin heavy chain II, IIA and IIB. Using the CRISPR/Cas9 system, we established cells in which the IIA gene was ablated. These cells were then transfected with a vector that expresses GFP–IIA chimeric molecule under the control of a tetracycline-responsible element. In the absence of Dox (doxycyclin), when GFP–IIA is expressed (GFP–IIA+), the cells exhibit epithelial cell morphology, but in the presence of Dox, when expression of GFP–IIA is repressed (GFP–IIA−), the cells lose epithelial morphology and strong cell–cell adhesion. Consistent with these observations, GFP–IIA− cells failed to assemble junction components such as E-cadherin, desmoplakin, and occludin at cell–cell contact sites. Therefore, IIA is required for assembly of junction complexes. MDCK cells with an ablation of the α-catenin gene also exhibited the same phenotype. However, when in GFP–IIA− cells expressed α-catenin lacking the inhibitory region or E-cadherin/α-catenin chimeras, the cells acquired the ability to establish the junction complex. These experiments reveal that IIA acts as an activator of α-catenin in junction assembly. Summary: The establishment and regulation of cell adhesion are fundamental to the development and maintenance of tissue organization in multicellular organisms. The role of nonmuscle myosin IIA is studied.
Putative Regulatory Factors Associated with Intramuscular Fat Content

Intramuscular fat (IMF) content is related to insulin resistance, which is an important prediction factor for disorders, such as cardiovascular disease, obesity and type 2 diabetes in human. At the same time, it is an economically important trait, which influences the sensorial and nutritional value of meat. The deposition of IMF is influenced by many factors such as sex, age, nutrition, and genetics. In this study Nellore steers (Bos taurus indicus subspecies) were used to better understand the molecular mechanisms involved in IMF content. This was accomplished by identifying differentially expressed genes (DEG), biological pathways and putative regulatory factors. Animals included in this study had extreme genomic estimated breeding value (GEBV) for IMF. RNA-seq analysis, gene set enrichment analysis (GSEA) and co-expression network methods, such as partial correlation coefficient with information theory (PCIT), regulatory impact factor (RIF) and phenotypic impact factor (PIF) were utilized to better understand intramuscular adipogenesis. A total of 16,101 genes were analyzed in both groups (high (H) and low (L) GEBV) and 77 DEG (FDR 10%) were identified between the two groups. Pathway Studio software identified 13 significantly over-represented pathways, functional classes and small molecule signaling pathways within the DEG list. PCIT analyses identified genes with a difference in the number of gene-gene correlations between H and L group and detected putative regulatory factors involved in IMF content. Candidate genes identified by PCIT include: ANKRD26, HOXC5 and PPAPDC2. RIF and PIF analyses identified several candidate genes: GLI2 and IGF2 (RIF1), MPC1 and UBL5 (RIF2) and a host of small RNAs, including miR-1281 (PIF). These findings contribute to a better understanding of the molecular mechanisms that underlie fat content and energy balance in muscle and provide important information for the production of healthier beef for human consumption.
Starch-based backwards SHG for in situ MEFISTO pulse characterization in multiphoton microscopy

We report a simple methodology to provide complete pulse characterization at the sample plane of a two-photon excited fluorescence (TPEF) microscope. This is achieved by using backward propagating second-harmonic generation (SHG) from starch granules. Without any modification to the microscope, SHG-autocorrelation traces were obtained by using a single starch granule that was placed alongside the biological specimen being imaged. A spectrally resolved SHG autocorrelation was acquired by placing a spectrometer at the output port of the microscope. Complete in situ pulse information is then directly retrieved in an analytical way using the measurement of electric filed by interferometric spectral trace observation (MEFISTO) technique.
Estimation of the hydraulic conductivities of lupine roots by inverse modelling of high-resolution measurements of root water uptake.

BACKGROUND AND AIMS Radial and axial hydraulic conductivities are key parameters for proper understanding and modelling of root water uptake. Despite their importance, there is limited experimental information on how the radial and axial hydraulic conductivities vary along roots growing in soil. Here, a new approach was introduced to estimate inversely the profile of hydraulic conductivities along the roots of transpiring plants growing in soil. METHODS A three-dimensional model of root water uptake was used to reproduce the measured profile of root water uptake along roots of lupine plant grown in soil. The profile of fluxes was measured using a neutron radiography technique combined with injection of deuterated water as tracer. The aim was to estimate inversely the profiles of the radial and axial hydraulic conductivities along the roots. KEY RESULTS The profile of hydraulic conductivities along the taproot and the lateral roots of lupines was calculated using three flexible scenarios. For all scenarios, it was found that the radial hydraulic conductivity increases towards the root tips, while the axial conductivity decreases. Additionally, it was found that in soil with uniform water content: (1) lateral roots were the main location of root water uptake; (2) water uptake by laterals decreased towards the root tips due to the dissipation of water potential along the root; and (3) water uptake by the taproot was higher in the distal segments and was negligible in the proximal parts, which had a low radial conductivity. CONCLUSIONS The proposed approach allows the estimation of the root hydraulic properties of plants growing in soil. This information can be used in an advanced model of water uptake to predict the water uptake of different root types or different root architectures under varying soil conditions.
Defining the impact of sumoylation on substrate binding and catalysis by thymine DNA glycosylase

Abstract Thymine DNA glycosylase (TDG) excises thymine from mutagenic G·T mispairs generated by deamination of 5-methylcytosine (mC) and it removes two mC derivatives, 5−formylcytosine (fC) and 5−carboxylcytosine (caC), in a multistep pathway for DNA demethylation. TDG is modified by small ubiquitin-like modifier (SUMO) proteins, but the impact of sumoylation on TDG activity is poorly defined and the functions of TDG sumoylation remain unclear. We determined the effect of TDG sumoylation, by SUMO-1 or SUMO-2, on substrate binding and catalytic parameters. Single turnover experiments reveal that sumoylation dramatically impairs TDG base-excision activity, such that G·T activity is reduced by ≥45-fold and fC and caC are excised slowly, with a reaction half-life of ≥9 min (37°C). Fluorescence anisotropy studies reveal that unmodified TDG binds tightly to G·fC and G·caC substrates, with dissociation constants in the low nanomolar range. While sumoylation of TDG weakens substrate binding, the residual affinity is substantial and is comparable to that of biochemically-characterized readers of fC and caC. Our findings raise the possibility that sumoylation enables TDG to function, at least transiently, as reader of fC and caC. Notably, sumoylation could potentially facilitate TDG recruitment of other proteins, including transcription factors or epigenetic regulators, to these sites in DNA.
Supervised Disul fi ram ’ s Superior Effectiveness in Alcoholism Treatment : Ethical , Methodological , and Psychological Aspects

Disulfiram (DSF) causes the ALDH-mediated deterrence of alcohol consumption. We review recent meta-analyses showing the superior effectiveness of supervised disulfiram (SD) in alcoholism treatment compared with oral naltrexone or acamprosate (ACP). The success of SD is also consistent with the almost complete absence of alcoholism in Japanese homozygotes for ‘inefficient’ ALDH. However, SD is an underused treatment and some clinicians have ethical objections to DSF. We examine these objections and argue that they are based on a misunderstanding of how DSF works. In particular, we argue that SD is not as is often claimed a variety of aversion therapy but aids cognitive, behavioural, educational and psychosocial interventions. It has some unique features that need to be better understood if it is to be properly compared with other treatments and effectively employed to help alcoholic patients, especially those who have not responded to other evidence-based interventions.
Asian Dust Storm Elevates Children’s Respiratory Health Risks: A Spatiotemporal Analysis of Children’s Clinic Visits across Taipei (Taiwan)

Concerns have been raised about the adverse impact of Asian dust storms (ADS) on human health; however, few studies have examined the effect of these events on children’s health. Using databases from the Taiwan National Health Insurance and Taiwan Environmental Protection Agency, this study investigates the documented daily visits of children to respiratory clinics during and after ADS that occurred from 1997 to 2007 among 12 districts across Taipei City by applying a Bayesian structural additive regressive model controlled for spatial and temporal patterns. This study finds that the significantly impact of elevated children’s respiratory clinic visits happened after ADS. Five of the seven lagged days had increasing percentages of relative rate, which was consecutively elevated from a 2-day to a 5-day lag by 0.63%∼2.19% for preschool children (i.e., 0∼6 years of age) and 0.72%∼3.17% for school children (i.e., 7∼14 years of age). The spatial pattern of clinic visits indicated that geographical heterogeneity was possibly associated with the clinic’s location and accessibility. Moreover, day-of-week effects were elevated on Monday, Friday, and Saturday. We concluded that ADS may significantly increase the risks of respiratory diseases consecutively in the week after exposure, especially in school children.
A Systematic Review of 10 Years of Augmented Reality Usability Studies: 2005 to 2014

Augmented Reality (AR) interfaces have been studied extensively over the last few decades, with a growing number of user-based experiments. In this paper, we systematically review 10 years of the most influential AR user studies, from 2005 to 2014. A total of 291 papers with 369 individual user studies have been reviewed and classified based on their application areas. The primary contribution of the review is to present the broad landscape of user-based AR research, and to provide a high-level view of how that landscape has changed. We summarize the high-level contributions from each category of papers, and present examples of the most influential user studies. We also identify areas where there have been few user studies, and opportunities for future research. Among other things, we find that there is a growing trend toward handheld AR user studies, and that most studies are conducted in laboratory settings and do not involve pilot testing. This research will be useful for AR researchers who want to follow best practices in designing their own AR user studies.
Evaluation of Virtual Measurements of Scanned Dental Impressions

Plaster models are tools of fundamental relevance for diagnose and orthodontic treatment planning [1-3]. Dental models are employed for evaluation of sagital, vertical and transversal dimensions and also for crowding or spacing measurements. However, plaster models present some disadvantages, such as huge space for storage, risk of loss or breakage and possibility of mold proliferation over long term [2].
Influence of reaction temperature on yields of bio-oil from fast pyrolysis of sugarcane residues

This paper reports a study on production of pyrolysis oil from sugarcane residues, namely sugarcane bagasse (SB), sugarcane leaves (SL) and sugarcane tops (ST). This research investigated the effects of reaction temperature on pyrolysis products of these residues. Pyrolysis oil samples were characterized. Their elemental composition, density, pH value, viscosity and heating values as well as water, solids, ash contents were determined. It was found that the optimal reaction temperatures for pyrolysis of SB, SL and ST were 499°C, 403°C and 402°C, which gave maximal oil yields of 64.6, 53.4, and 52.2 wt. % on a dry biomass basis, respectively.
Peroxisome proliferator-activated receptor γ mediates porcine placental angiogenesis through hypoxia inducible factor-, vascular endothelial growth factor- and angiopoietin-mediated signaling

Peroxisome proliferator-activated receptor (PPAR) γ has been reported to be implicated in placentation in mice. Previous studies have demonstrated that PPARγ is also expressed in porcine placenta, primarily localized in vascular endothelial cells (VECs). The present study aimed to investigate the roles of PPARγ during porcine placental angiogenesis and examine the molecular mechanisms involved in its actions. VECs were incubated with the PPARγ agonist rosiglitazone and the antagonist T0070907, and their angiogenic potential was evaluated using cellular impedance, wound healing and tube formation assays. Reverse transcription-quantitative polymerase chain reaction was used to assess the mRNA expression levels of angiogenic factors, including hypoxia-inducible factors (HIFs), vascular endothelial growth factor (VEGF) isoforms, VEGF receptors (VEGFRs) and angiopoietins (Angs). The results demonstrated that the adhesive, proliferative and migratory capabilities of VECs were potentiated by rosiglitazone and suppressed by T0070907. Notably, tube formation was invariably promoted during PPARγ activation and blockade. The mRNA expression levels of HIF1α, HIF2α, VEGFR2, VEGF188 and Ang-1 were revealed to be upregulated following treatment of VECs with rosiglitazone, whereas they were downregulated following treatment with T0070907. However, the mRNA expression levels of placental growth factor and VEGF120 were consistently downregulated following PPARγ activation and blockade, whereas VEGF164 mRNA levels remained unaltered. The results of the present study suggested that PPARγ may mediate porcine placental angiogenesis, by interfering with HIF-, VEGF- and angiopoietin-mediated signaling pathways.
Unstable and stable regimes of polariton condensation

Modulational instabilities play a key role in a wide range of nonlinear optical phenomena, leading e.g. to the formation of spatial and temporal solitons, rogue waves and chaotic dynamics. Here we experimentally demonstrate the existence of a modulational instability in condensates of cavity polaritons, arising from the strong coupling of cavity photons with quantum well excitons. For this purpose we investigate the spatiotemporal coherence properties of polariton condensates in GaAs-based microcavities under continuous-wave pumping. The chaotic behavior of the instability results in a strongly reduced spatial and temporal coherence and a significantly inhomogeneous density. Additionally we show how the instability can be tamed by introducing a periodic potential so that condensation occurs into negative mass states, leading to largely improved coherence and homogeneity. These results pave the way to the exploration of long-range order in dissipative quantum fluids of light within a controlled platform.
Overlap at the molecular and immunohistochemical levels between angioimmunoblastic T-cell lymphoma and a subgroup of peripheral T-cell lymphomas without specific morphological features

The overlap of morphology and immunophenotype between angioimmunoblastic T-cell lymphoma (AITL) and other nodal peripheral T-cell lymphomas (n-PTCLs) is a matter of current interest whose clinical relevance and pathogenic background have not been fully established. We studied a series of 98 n-PTCL samples (comprising 57 AITL and 41 PTCL-NOS) with five TFH antibodies (CD10, BCL-6, PD-1, CXCL13, ICOS), looked for mutations in five of the genes most frequently mutated in AITL (TET2, DNMT3A, IDH2, RHOA and PLCG1) using the Next-Generation-Sequencing Ion Torrent platform, and measured the correlations of these characteristics with morphology and clinical features. The percentage of mutations in the RHOA and TET2 genes was similar (23.5% of cases). PLCG1 was mutated in 14.3%, IDH2 in 11.2% and DNMT3A in 7.1% of cases, respectively. In the complete series, mutations in RHOA gene were associated with the presence of mutations in IDH2, TET2 and DNMT3A (p < 0.001, p = 0.043, and p = 0.029, respectively). Fourteen cases featured RHOA mutations without TET2 mutations. A close relationship was found between the presence of these mutations and a TFH-phenotype in AITL and PTCL-NOS patients. Interestingly, BCL-6 expression was the only TFH marker differentially expressed between AITL and PTCL-NOS cases. There were many fewer mutated cases than there were cases with a TFH phenotype. Overall, these data suggest alternative ways by which neoplastic T-cells overexpress these proteins. On the other hand, no clinical or survival differences were found between any of the recognized subgroups of patients with respect to their immunohistochemistry or mutational profile.
The Scalp Time-Varying Networks of N170: Reference, Latency, and Information Flow

Using the scalp time-varying network method, the present study is the first to investigate the temporal influence of the reference on N170, a negative event-related potential component (ERP) appeared about 170 ms that is elicited by facial recognition, in the network levels. Two kinds of scalp electroencephalogram (EEG) references, namely, AR (average of all recording channels) and reference electrode standardization technique (REST), were comparatively investigated via the time-varying processing of N170. Results showed that the latency and amplitude of N170 were significantly different between REST and AR, with the former being earlier and smaller. In particular, the information flow from right temporal-parietal P8 to left P7 in the time-varying network was earlier in REST than that in AR, and this phenomenon was reproduced by simulation, in which the performance of REST was closer to the true case at source level. These findings indicate that reference plays a crucial role in ERP data interpretation, and importantly, the newly developed approximate zero-reference REST would be a superior choice for precise evaluation of the scalp spatio-temporal changes relating to various cognitive events.
Nitrous oxide emission reduction in temperate biochar-amended soils

Biochar, a pyrolysis product of organic residues, is an amendment for agricultural soils to improve soil fertility, sequester CO 2 and reduce greenhouse gas (GHG) emissions. In highly weathered tropical soils laboratory incubations of soil-biochar mixtures revealed substantial reductions for nitrous oxide (N 2 O) and carbon dioxide (CO 2 ). In contrast, evidence is scarce for temperate soils. In a three-factorial laboratory incubation experiment two different temperate agricultural soils were amended with green waste and coffee grounds biochar. N 2 O and CO 2 emissions were measured at the beginning and end of a three month incubation. The experiments were conducted under three different conditions (no additional nutrients, glucose addition, and nitrate and glucose addition) representing different field conditions. We found mean N 2 O emission reductions of 60 % compared to soils without addition of biochar. The reduction depended on biochar type and soil type as well as on the age of the samples. CO 2 emissions were slightly reduced, too. NO 3 – but not NH 4 + concentrations were significantly reduced shortly after biochar incorporation. Despite the highly significant suppression of N 2 O emissions biochar effects should not be transferred one-to-one to field conditions but need to be tested accordingly.
Analysis of Mitochondrial Function and Localisation during Human Embryonic Stem Cell Differentiation In Vitro

Human embryonic stem cell (hESC) derivatives show promise as viable cell therapy options for multiple disorders in different tissues. Recent advances in stem cell biology have lead to the reliable production and detailed molecular characterisation of a range of cell-types. However, the role of mitochondria during differentiation has yet to be fully elucidated. Mitochondria mediate a cells response to altered energy requirements (e.g. cardiomyocyte contraction) and, as such, the mitochondrial phenotype is likely to change during the dynamic process of hESC differentiation. We demonstrate that manipulating mitochondrial biogenesis alters mesendoderm commitment. To investigate mitochondrial localisation during early lineage specification of hESCs we developed a mitochondrial reporter line, KMEL2, in which sequences encoding the green fluorescent protein (GFP) are targeted to the mitochondria. Differentiation of KMEL2 lines into the three germ layers showed that the mitochondria in these differentiated progeny are GFP positive. Therefore, KMEL2 hESCs facilitate the study of mitochondria in a range of cell types and, importantly, permit real-time analysis of mitochondria via the GFP tag.