Miracle-dz/UniFAR-FTUs huggingface dataset:
A dialogue-like cell communication mechanism is conserved in filamentous ascomycete fungi and mediates interspecies interactions

Significance This study reveals that a dialogue-like communication mechanism, which mediates cell–cell fusion in filamentous fungi, is a conserved complex trait. It allows the communication and behavioral coordination of cells of distantly related species and mediates their mutual attraction and subsequent physical contact, although interspecies fusion does not occur. Through the activation of this signaling machinery, one species can reprogram the developmental program of the other fungus. These data promote our understanding of microbial communication, illustrate the mechanism of repurposing of existing building blocks in cellular evolution, revive the hypothesis of vegetative fusion as an avenue of horizontal gene transfer in fungi, and establish the idea of developmental reprogramming as a tool for controlling fungi.
Molecular profile of pure squamous cell carcinoma of the bladder identifies major roles for OSMR and YAP signalling

Pure squamous cell carcinoma (SCC) is the most common pure variant form of bladder cancer, found in 2–5% of cases. It often presents late and is unresponsive to cisplatin‐based chemotherapy. The molecular features of these tumours have not been elucidated in detail. We carried out whole‐exome sequencing (WES), copy number, and transcriptome analysis of bladder SCC. Muscle‐invasive bladder cancer (MIBC) samples with no evidence of squamous differentiation (non‐SD) were used for comparison. To assess commonality of features with urothelial carcinoma with SD, we examined data from SD samples in The Cancer Genome Atlas (TCGA) study of MIBC. TP53 was the most commonly mutated gene in SCC (64%) followed by FAT1 (45%). Copy number analysis revealed complex changes in SCC, many differing from those in samples with SD. Gain of 5p and 7p was the most common feature, and focal regions on 5p included OSMR and RICTOR. In addition to 9p deletions, we found some samples with focal gain of 9p24 containing CD274 (PD‐L1). Loss of 4q35 containing FAT1 was found in many samples such that all but one sample analysed by WES had FAT1 mutation or deletion. Expression features included upregulation of oncostatin M receptor (OSMR), metalloproteinases, metallothioneins, keratinisation genes, extracellular matrix components, inflammatory response genes, stem cell markers, and immune response modulators. Exploration of differentially expressed transcription factors identified BNC1 and TFAP2A, a gene repressed by PPARG, as the most upregulated factors. Known urothelial differentiation factors were downregulated along with 72 Kruppel‐associated (KRAB) domain‐containing zinc finger family protein (KZFP) genes. Novel therapies are urgently needed for these tumours. In addition to upregulated expression of EGFR, which has been suggested as a therapeutic target in basal/squamous bladder cancer, we identified expression signatures that indicate upregulated OSMR and YAP/TAZ signalling. Preclinical evaluation of the effects of inhibition of these pathways alone or in combination is merited.
Land management explains major trends in forest structure and composition over the last millennium in California’s Klamath Mountains

Significance We provide the first assessment of aboveground live tree biomass in a mixed conifer forest over the late Holocene. The biomass record, coupled with local Native oral history and fire scar records, shows that Native burning practices, along with a natural lightning-based fire regime, promoted long-term stability of the forest structure and composition for at least 1 millennium in a California forest. This record demonstrates that climate alone cannot account for observed forest conditions. Instead, forests were also shaped by a regime of frequent fire, including intentional ignitions by Native people. This work suggests a large-scale intervention could be required to achieve the historical conditions that supported forest resiliency and reflected Indigenous influence.
Restoring Honor by Slapping or Disowning the Daughter

The psychological processes underlying honor violence against kin are poorly understood. We assumed that honor violence against daughters who violate a gendered norm is designed to uphold family honor and nurture positive links to the community. Four studies with Indian men supported this formulation. As expected, endorsement of honor violence (i.e., slapping or disowning the daughter) increased insofar as perceived community awareness of the violation increased. Moreover, endorsement of honor violence was especially common among those whose identities were closely aligned (“fused”) with their community. Finally, a desire to restore threatened family honor, rather than a motivation to prevent future dishonor, motivates honor violence against daughters; conversely, a desire to prevent future dishonor motivates constructive activities such as advising. Ironically, a benign, culturally universal desire to maintain positive ties to the community can encourage community members to endorse violence toward transgressive kin.
Antifungal activity of [K3]temporin-SHa against medically relevant yeasts and moulds.

Few antifungal agents are currently available for the treatment of fungal infections. Antimicrobial peptides (AMPs), which are natural molecules involved in the innate immune response of many organisms, represent a promising research method because of their broad killing activity. The aim of this study was to assess the activity of a frog AMP, [K3]temporin-SHa, against some species of yeasts and moulds, and to further explore its activity against Candida albicans. MIC determinations were performed according to EUCAST guidelines. Next, the activity of [K3]temporin-SHa against C. albicans was explored using time-killing curve experiments, membrane permeabilization assays, and electron microscopy. Finally, chequerboard assays were performed to evaluate the synergy between [K3]temporin-SHa and amphotericin B or fluconazole. [K3]temporin-SHa was found to be active in vitro against several yeasts with MIC between 5.5 and 45 µM. [K3]temporin-SHa displayed rapid fungicidal activity against C. albicans (inoculum was divided into two in less than an hour and no viable colonies were recovered after 5 h) with a mechanism that could be due to membrane permeabilization. [K3]temporin-SHa was synergistic with amphotericin B against C. albicans (FICI = 0.303). [K3]temporin-SHa could represent an additional tool to treat several Candida species and C. neoformans.
Characterizing tourniquet induced hemodynamics during total knee arthroplasty using diffuse optical spectroscopy

Tourniquet use creates a reduced blood surgical field during total knee arthroplasty (TKA), however, prolonged ischemia may cause postoperative tourniquet complications. To understand the effects of tourniquet‐induced ischemia, we performed a prospective observational study using quantitative broadband diffuse optical spectroscopy (DOS) to measure tissue hemodynamics and water and lipid concentrations before, during, and after tourniquet placement in subjects undergoing TKA. Data was collected for 6 months and, of the total subjects analyzed (n = 24), 22 were primary TKAs and 2 were revision TKA cases. We specifically investigated tourniquet‐induced hemodynamics based upon subject‐specific tissue composition and observed a significant relationship between the linear rate of deoxygenation after tourniquet inflation and water/lipid ratio (W/L, p < 0.0001) and baseline somatic tissue oxygen saturation, StO2 (p = 0.05). Subjects with a low W/L ratio exhibited a lower tissue metabolic rate of oxygen consumption, (tMRO2) (p = 0.008). Changes in deoxyhemoglobin [HbR] (p = 0.009) and lipid fraction (p = 0.001) were significantly different between high and low W/L subject groups during deoxygenation. No significant differences were observed for hemodynamics during reperfusion and total tourniquet time was neither significantly related to the hemodynamic hyperemic response (p = 0.73) nor the time to max StO2 after tourniquet release (p = 0.57). In conclusion, we demonstrate that DOS is capable of real‐time monitoring of tissue hemodynamics distal to the tourniquet during TKA, and that tissue composition should be considered. DOS may help surgeons stratify hemodynamics based upon tissue composition and eventually aid the preoperative risk assessment of vascular occlusions from tourniquet use during TKA.
Bidirectional substructure pseudo‐dynamic tests and analysis of a full‐scale two‐story buckling‐restrained braced frame

A two‐story buckling‐restrained brace (BRB) frame was tested under bidirectional in‐plane and out‐of‐plane loading to evaluate the BRB stability and gusset plate design. The test comprised pseudo‐dynamic loadings using the 1999 Chi‐Chi earthquake scaled to the 50%, 10%, and 2% probability of exceedance in 50 years and a cyclic regime of increasing amplitudes of up to 3.0% story drift ratio (SDR). The specimen had a unique configuration where the beams were connected to the columns through shear tabs welded to the column flanges and bolted to the beam webs. Stable hysteretic behavior with only minor cracking at the gusset‐to‐column welds was observed under the pseudo‐dynamic tests, with maximum in‐plane and out‐of‐plane SDRs of 2.24% and 1.47% respectively. Stable behavior continued into the cyclic test where fracture of the gusset‐to‐column welds occurred in the first cycle to simultaneous bidirectional SDR of 3.0%. The observed BRB stability is consistent with a methodology developed for BRB frames under simultaneous in‐plane and out‐of‐plane drifts. The specimen behavior was studied using a finite element model. It was shown that gusset plates are subjected to a combination of BRB force and frame action demands, with the latter increasing the gusset‐to‐beam and gusset‐to‐column interface demands by an average of 69% and 83% respectively. Consistent with the test results, failure at the gusset‐to‐column interfaces is computed when frame action demands are included, thus confirming that not considering frame action demands may results in unconservative gusset plate designs. Copyright © 2016 John Wiley & Sons, Ltd.
MRI in the Diagnosis of Endometriosis and Related Diseases

Endometriosis, a common chronic inflammatory disease in female of reproductive age, is closely related to patient symptoms and fertility. Because of its high contrast resolution and objectivity, MRI can contribute to the early and accurate diagnosis of ovarian endometriotic cysts and deeply infiltrating endometriosis without the need for any invasive procedure or radiation exposure. The ovaries, which are the most frequent site of endometriosis, can be afflicted by multiple related conditions and diseases. For the diagnosis of deeply infiltrating endometriosis and secondary adhesions among pelvic organs, fibrosis around the ectopic endometrial gland is usually found as a T2 hypointense lesion. This review summarizes the MRI findings obtained for ovarian endometriotic cysts and their physiologically and pathologically related conditions. This article also includes the key imaging findings of deeply infiltrating endometriosis.
Genome-wide landscape of ApiAP2 transcription factors reveals a heterochromatin-associated regulatory network during Plasmodium falciparum blood-stage development

Abstract Heterochromatin-associated gene silencing controls multiple physiological processes in malaria parasites, however, little is known concerning the regulatory network and cis-acting sequences involved in the organization of heterochromatin and how they modulate heterochromatic gene expression. Based on systematic profiling of genome-wide occupancy of eighteen Apicomplexan AP2 transcription factors by ChIP-seq analysis, we identify and characterize eight heterochromatin-associated factors (PfAP2-HFs), which exhibit preferential enrichment within heterochromatic regions but with differential coverage profiles. Although these ApiAP2s target euchromatic gene loci via specific DNA motifs, they are likely integral components of heterochromatin independent of DNA motif recognition. Systematic knockout screenings of ApiAP2 factors coupled with RNA-seq transcriptomic profiling revealed three activators and three repressors of heterochromatic gene expression including four PfAP2-HFs. Notably, expression of virulence genes is either completely silenced or significantly reduced upon the depletion of PfAP2-HC. Integrated multi-omics analyses reveal autoregulation and feed-forward loops to be common features of the ApiAP2 regulatory network, in addition to the occurrence of dynamic interplay between local chromatin structure and ApiAP2s in transcriptional control. Collectively, this study provides a valuable resource describing the genome-wide landscape of the ApiAP2 family and insights into functional divergence and cooperation within this family during the blood-stage development of malaria parasites.
Central femoral tunnel placement can reduce stress and strain around bone tunnels and graft more than anteromedial femoral tunnel in anterior cruciate ligament reconstruction

The present study investigated the effects of anteromedial (AM) and central femoral footprint placement on stress and strain distribution around the femoral and tibial tunnel and graft following anterior cruciate ligament reconstruction (ACLR). A three‐dimensional (3D) reconstructed knee model was validated and used for simulating ACLR by finite element analysis. A combined loading during normal human walking was applied to the knee models using different anatomic femoral tunnel placement at 20° knee flexion. The results of von Mises stress and principal strain at the entrances of the femoral and tibial tunnel and ACL graft was determined. The peak von Mises stress and the maximum principal strain in the AM footprint group were 8.78 MPa and 8850.89 μ‐strain at the entrance of femoral tunnel, and 5.29 MPa and 5553.27 μ‐strain at the entrance of tibial tunnel. The results in the AM footprint group were higher than that in the central footprint group. The peak von Mises stress around the ACL graft following AM footprint ACLR was 28.63 MPa, higher than that following the central footprint ACLR. The AM footprint ACLR generated more significant peak von Mises stress and maximum principal strain around the entrances of femoral and tibial tunnel and the graft than the central footprint. The present results are of clinical relevance as they can provide a better understanding of tunnel enlargement and graft failure.
The nucleoporin Gle1 activates DEAD-box protein 5 (Dbp5) by promoting ATP binding and accelerating rate limiting phosphate release

Abstract The DEAD-box protein Dbp5 is essential for RNA export, which involves regulation by the nucleoporins Gle1 and Nup159 at the cytoplasmic face of the nuclear pore complex (NPC). Mechanistic understanding of how these nucleoporins regulate RNA export requires analyses of the intrinsic and activated Dbp5 ATPase cycle. Here, kinetic and equilibrium analyses of the Saccharomyces cerevisiae Gle1-activated Dbp5 ATPase cycle are presented, indicating that Gle1 and ATP, but not ADP-Pi or ADP, binding to Dbp5 are thermodynamically coupled. As a result, Gle1 binds Dbp5-ATP > 100-fold more tightly than Dbp5 in other nucleotide states and Gle1 equilibrium binding of ATP to Dbp5 increases >150-fold via slowed ATP dissociation. Second, Gle1 accelerated Dbp5 ATPase activity by increasing the rate-limiting Pi release rate constant ∼20-fold, which remains rate limiting. These data show that Gle1 activates Dbp5 by modulating ATP binding and Pi release. These Gle1 activities are expected to facilitate ATPase cycling, ensuring a pool of ATP bound Dbp5 at NPCs to engage RNA during export. This work provides a mechanism of Gle1-activation of Dbp5 and a framework to understand the joint roles of Gle1, Nup159, and other nucleoporins in regulating Dbp5 to mediate RNA export and other Dbp5 functions in gene expression.
Influence different polishing systems on roughness and colour stability of chairside CAD/CAM blocks with laminate veneer thickness

Objective: The aim of this study was to evaluate the effect of different polishing systems on the colour stability of different laminate veneer blocks for chair-side CAD-CAM after ultraviolet (UV) ageing. Methods: About 240 sample (13 × 13 × 0.7) were prepared from four different CAD-CAM blocks IPS e.max CAD (IP), IPS Empress CAD (IE), Mark II (M) and Lava Ultimate (LU)) with A1 shade. Each group was divided into five subgroups (n = 12) according to the control (C) and four different polishing system: Sof-Lex (S), Edenta (E), Identoflex (I) and Zircon Brite (Z). Surface roughnesses (Ra) were measured by a profilometer before and after polishing. The baseline colour values were recorded according to the CIELab system. The colour coordinates (L*, a* and b*) of the samples were measured before and after UV ageing, and colour differences (ΔE00) were calculated by using the CIEDE2000 colour difference formula. A two-way ANOVA and Tukey test methods were used to analyse the data (α = 0.05). Results: A significant interaction was observed between CAD-CAM blocks and polishing system (p < 0.001). The higher Ra and colour difference was calculated in LU in the Z group after polished and the lower Ra and colour difference was calculated in the IP in the S group after polished. For the IP group, the glazing procedure showed higher Ra and ΔE values with Z group than polished S system, whereas there is no statistical differences. Conclusion: It is concluded that polishing with the Sof-Lex system improves significantly smoothness and colour stability. However, there is no success in using the Zircon Brite polishing system.
Validation of the Thai Version of the Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale

Objective This study aims to validate the Thai translation of the Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS). Methods The English version was translated into Thai and then back-translated into English. The translated version underwent 2 rounds of cognitive pretesting to assess the ease of comprehension, ease of use and comfort with the scale. Then, it underwent large clinimetric testing. Results The Thai version was validated in 354 PD patients. The comparative fit index (CFI) for all four parts of the Thai version of the MDS-UPDRS was 0.93 or greater. Exploratory factor analysis identified isolated item differences in factor structure between the Thai and English versions. Conclusion The overall factor structure of the Thai version was consistent with that of the English version based on the high CFIs (all CFI ≥ 0.90). Hence, it can be designated the official Thai version of the MDS-UPDRS.
Migraine‐Associated Mutation in the Na,K‐ATPase Leads to Disturbances in Cardiac Metabolism and Reduced Cardiac Function

Background Mutations in ATP1A2 gene encoding the Na,K‐ATPase α2 isoform are associated with familial hemiplegic migraine type 2. Migraine with aura is a known risk factor for heart disease. The Na,K‐ATPase is important for cardiac function, but its role for heart disease remains unknown. We hypothesized that ATP1A2 is a susceptibility gene for heart disease and aimed to assess the underlying disease mechanism. Methods and Results Mice heterozygous for the familial hemiplegic migraine type 2–associated G301R mutation in the Atp1a2 gene (α2 +/G301R mice) and matching wild‐type controls were compared. Reduced expression of the Na,K‐ATPase α2 isoform and increased expression of the α1 isoform were observed in hearts from α2 +/G301R mice (Western blot). Left ventricular dilation and reduced ejection fraction were shown in hearts from 8‐month‐old α2 +/G301R mice (cardiac magnetic resonance imaging), and this was associated with reduced nocturnal blood pressure (radiotelemetry). Cardiac function and blood pressure of 3‐month‐old α2 +/G301R mice were similar to wild‐type mice. Amplified Na,K‐ATPase–dependent Src kinase/Ras/Erk1/2 (p44/42 mitogen‐activated protein kinase) signaling was observed in hearts from 8‐month‐old α2 +/G301R mice, and this was associated with mitochondrial uncoupling (respirometry), increased oxidative stress (malondialdehyde measurements), and a heart failure–associated metabolic shift (hyperpolarized magnetic resonance). Mitochondrial membrane potential (5,5´,6,6´‐tetrachloro‐1,1´,3,3´‐tetraethylbenzimidazolocarbocyanine iodide dye assay) and mitochondrial ultrastructure (transmission electron microscopy) were similar between the groups. Proteomics of heart tissue further suggested amplified Src/Ras/Erk1/2 signaling and increased oxidative stress and provided the molecular basis for systolic dysfunction in 8‐month‐old α2 +/G301R mice. Conclusions Our findings suggest that ATP1A2 mutation leads to disturbed cardiac metabolism and reduced cardiac function mediated via Na,K‐ATPase–dependent reactive oxygen species signaling through the Src/Ras/Erk1/2 pathway.
eQTL mapping using allele-specific count data is computationally feasible, powerful, and provides individual-specific estimates of genetic effects

Using information from allele-specific gene expression (ASE) can improve the power to map gene expression quantitative trait loci (eQTLs). However, such practice has been limited, partly due to computational challenges and lack of clarification on the size of power gain or new findings besides improved power. We have developed geoP, a computationally efficient method to estimate permutation p-values, which makes it computationally feasible to perform eQTL mapping with ASE counts for large cohorts. We have applied geoP to map eQTLs in 28 human tissues using the data from the Genotype-Tissue Expression (GTEx) project. We demonstrate that using ASE data not only substantially improve the power to detect eQTLs, but also allow us to quantify individual-specific genetic effects, which can be used to study the variation of eQTL effect sizes with respect to other covariates. We also compared two popular methods for eQTL mapping with ASE: TReCASE and RASQUAL. TReCASE is ten times or more faster than RASQUAL and it provides more robust type I error control.