Miracle-dz/UniFAR-FTUs huggingface dataset:
The histone deubiquitinase OTLD1 targets euchromatin to regulate plant growth

The Arabidopsis thaliana histone deubiquitinase OTLD1 represses the transcription of growth regulators and promotes plant growth. Targeting euchromatin to promote plant growth Posttranslational modifications of histones, such as ubiquitination, acetylation, and methylation, influence gene expression. Heterochromatin, the tightly packed form of chromatin associated with gene silencing, and euchromatin, the loosely packed chromatin of actively transcribed genes, are characterized by distinct types of histone modifications. Of the 50 deubiquitinases encoded by the Arabidopsis thaliana genome, only 2 are known to target histones, UBP26 and OTLD1. Keren and Citovsky found that OTLD1 promoted overall plant growth, likely by stimulating cell growth rather than proliferation. From a panel of genes that control plant growth, five were repressed by overexpression of OTLD1. OTLD1 associated with chromatin at the promoters of each of these genes and promoted epigenetic remodeling of the euchromatin-associated histone modifications, including loss of ubiquitination, acetylation, and methylation. Thus, OTLD1 promotes plant growth by stimulating the removal of euchromatic histone marks, thereby repressing the expression of genes that fine-tune growth. Histone monoubiquitination is associated with active chromatin and plays an important role in epigenetic regulation of gene expression in plants. Deubiquitinating enzymes remove the ubiquitin group from histones and thereby contribute to gene repression. The Arabidopsis thaliana genome encodes 50 deubiquitinases, yet only 2 of them—UBP26 and OTLD1, members of the USP/UBP (ubiquitin-specific protease and ubiquitin-binding protein) and OTU (ovarian tumor protease) deubiquitinase families—are known to target histones. Furthermore, UBP26 is the only plant histone deubiquitinase for which the functional role has been characterized in detail. We used gain- and loss-of-function alleles of OTLD1 to examine its role in the plant life cycle and showed that OTLD1 stimulates plant growth, increases cell size, and induces transcriptional repression of five major regulators of plant organ growth and development: GA20OX, WUS, OSR2, ARL, and ABI5. OTLD1 associated with chromatin at each of these target genes and promoted the removal of euchromatic histone acetylation, ubiquitination, and methylation marks. Thus, these data indicate that OTLD1 promotes the concerted epigenetic regulation of a set of genes that collectively limit plant growth.
Carbon Nano-Allotrope/Magnetic Nanoparticle Hybrid Nanomaterials as T2 Contrast Agents for Magnetic Resonance Imaging Applications

Magnetic resonance imaging (MRI) is the most powerful tool for deep penetration and high-quality 3D imaging of tissues with anatomical details. However, the sensitivity of the MRI technique is not as good as that of the radioactive or optical imaging methods. Carbon-based nanomaterials have attracted significant attention in biomaterial research in recent decades due to their unique physical properties, versatile functionalization chemistry, as well as excellent biological compatibility. Researchers have employed various carbon nano-allotropes to develop hybrid MRI contrast agents for improved sensitivity. This review summarizes the new research progresses in carbon-based hybrid MRI contrast agents, especially those reported in the past five years. The review will only focus on T2-weighted MRI agents and will be categorized by the different carbon allotrope types and magnetic components. Considering the strong trend in recent bio-nanotechnology research towards multifunctional diagnosis and therapy, carbon-based MRI contrast agents integrated with other imaging modalities or therapeutic functions are also covered.
From Breast Cancer to Antimicrobial: Combating Extremely Resistant Gram-Negative "Superbugs" Using Novel Combinations of Polymyxin B with Selective Estrogen Receptor Modulators.

Novel therapeutic approaches are urgently needed to combat nosocomial infections caused by extremely drug-resistant (XDR) "superbugs. " This study aimed to investigate the synergistic antibacterial activity of polymyxin B in combination with selective estrogen receptor modulators (SERMs) against problematic Gram-negative pathogens. In vitro synergistic antibacterial activity of polymyxin B and the SERMs tamoxifen, raloxifene, and toremifene was assessed using the microdilution checkerboard and static time-kill assays against a panel of Gram-negative isolates. Polymyxin B and the SERMs were ineffective when used as monotherapy against polymyxin-resistant minimum inhibitory concentration ([MIC] ≥8 mg/L) Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii. However, when used in combination, clinically relevant concentrations of polymyxin B and SERMs displayed synergistic killing against the polymyxin-resistant P. aeruginosa, K. pneumoniae, and A. baumannii isolates as demonstrated by a ≥2-3 log10 decrease in bacterial count (CFU/ml) after 24 hours. The combination of polymyxin B with toremifene demonstrated very potent antibacterial activity against P. aeruginosa biofilms in an artificial sputum media assay. Moreover, polymyxin B combined with toremifene synergistically induced cytosolic green fluorescence protein release, cytoplasmic membrane depolarization, permeabilizing activity in a nitrocefin assay, and an increase of cellular reactive oxygen species from P. aeruginosa cells. In addition, scanning and transmission electron micrographs showed that polymyxin B in combination with toremifene causes distinctive damage to the outer membrane of P. aeruginosa cells, compared with treatments with each compound per se. In conclusion, the combination of polymyxin B and SERMs illustrated a synergistic activity against XDR Gram-negative pathogens, including highly polymyxin-resistant P. aeruginosa isolates, and represents a novel combination therapy strategy for the treatment of infections because of problematic XDR Gram-negative pathogens.
Functional consequences of sarcopenia and dynapenia in the elderly

Purpose of reviewThe economic burden due to the sequela of sarcopenia (muscle wasting in the elderly) are staggering and rank similarly to the costs associated with osteoporotic fractures. In this article, we discuss the societal burden and determinants of the loss of physical function with advancing age, the physiologic mechanisms underlying dynapenia (muscle weakness in the elderly), and provide perspectives on related critical issues to be addressed. Recent findingsRecent epidemiological findings from longitudinal aging studies suggest that dynapenia is highly associated with both mortality and physical disability even when adjusting for sarcopenia indicating that sarcopenia may be secondary to the effects of dynapenia. These findings are consistent with the physiologic underpinnings of muscle strength, as recent evidence demonstrates that alterations in muscle quantity, contractile quality and neural activation all collectively contribute to dynapenia. SummaryAlthough muscle mass is essential for regulation of whole body metabolic balance, overall neuromuscular function seems to be a critical factor for maintaining muscle strength and physical independence in the elderly. The relative contribution of physiologic factors contributing to muscle weakness are not fully understood and further research is needed to better elucidate these mechanisms between muscle groups and across populations.
Nanolipid Gel of an Antimycotic Drug for Treating Vulvovaginal Candidiasis—Development and Evaluation

This paper focuses on the development and evaluation of mucoadhesive vaginal gel of fluconazole using nanolipid carriers to enhance tissue deposition in treating vulvovaginal candidiasis. Treatment of vulvovaginal candidiasis includes antimycotic agents prescribed for 1 to 7 days or longer, in relapse either orally or topically. The delivery of fluconazole as nanolipid carriers in vaginal gel can be proposed as suitable alternative to the existing conventional formulations to improve the patient acceptability, compliance and localized drug action. The nanolipid carriers of fluconazole were prepared by phase inversion temperature technique and incorporated into Carbopol 974P as gelling polymer. GRAS excipients selected and optimized were Precirol ATO 5, oleic acid and Kolliphor RH 40 to produce nanolipid dispersions. Stable nanolipid dispersions were developed using sodium dodecyl sulfate as the charge inducer. The optimized nanolipid dispersion of fluconazole had particle size, polydispersity index and zeta potential value of 158.33 ± 2.55 nm, 0.278 ± 0.003 and − 27.33 ± 0.40 mV, respectively and the average entrapment of fluconazole in the lipid carriers was found to be 67.24 ± 0.87%. The optimized vaginal gel had satisfactory mucoadhesive strength and rheological properties to facilitate vaginal application. The fluconazole release from the gel was sustained showing 30.69 ± 1.02% drug deposition in the porcine vaginal mucosa at the end of 8 h with improved antifungal activity against Candida albicans during well diffusion studies. The optimized gel was non-irritant to the vaginal mucosa of female Wistar rats with no signs of erythema or edema.
The Role of Microstructure in Toughness Behaviour of Microalloyed Steels

The micromechanisms involved in cleavage propagation in the brittle and ductile-brittle behaviour of microalloyed steels are analysed. The cleavage process is divided into three different steps which must take place dynamically in order to succeed: nucleation of a microcrack in a microstructural feature, propagation of the microcrack across the particle-matrix boundary and finally, propagation across the matrix surmounting high angle boundaries. The microstructural parameters involved in the three steps are considered, together with their effective surface energy values. Depending on testing temperature, the microstructural feature controlling cleavage fracture changes. In relation to the ductile-brittle transition, the main parameter is the volume fraction of coarse microstructural units surrounded by high angle boundaries.
Automatic detection of small bowel tumors in endoscopic capsule images by ROI selection based on discarded lightness information

This paper addresses the problem of automatic detection of tumoral frames in endoscopic capsule videos by using features directly extracted from the color space. We show that tumor can be appropriately discriminated from normal tissue by using only color information histogram measures from the Lab color space and that light saturated regions are usually classified as tumoral regions when color based discriminative procedures are used. These regions are correctly classified if lightening is discarded becoming the tissue classifier based only on the color differences a and b of the Lab color space. While current state of the art systems for small bowel tumor detection usually rely on the processing of the whole frame regarding features extraction this paper proposes the use of fully automatic segmentation in order to select regions likely to contain tumoral tissue. Classification is performed by using Support Vector Machine (SVM) and Multilayer Perceptron (MLP) by using features from color channels a and b of the Lab color space. The proposed algorithm outperforms in more than 5% a series of other algorithms based on features obtained from the higher frequency components selected from Wavelets and Curvelets transforms while saving important computational resources. In a matter of fact the proposed algorithm is more than 25 times faster than algorithms requiring wavelet/curvelet and co-occurrence computations.
Density Functional Study of Electronic and Optical Properties of Ternary Mixed Chalcogenides Topological Insulators

This paper presented a theoretical study of structural, electronic, and optical properties of the ternary mixed chalcogenides Topological Insulators with a formula M2X2Y (M = Bi, X = Te and Y= Se, S) using density functional theory (DFT) within the local density approximation (LDA). From the calculation, we have evaluated the bulk modulus and its corresponding pressure derivatives of these compounds. The linear photon-energy dependent of dielectric functions, some optical properties such as reflectivity, refraction index, conductivity function, and energy-loss spectra, have also been obtained and analyzed within the electronic band structures and density of states of these compounds.
Temporal coding of reward-guided choice in the posterior parietal cortex

Significance A central question in systems neuroscience is how cognitive functions can arise from the interplay of many different brain areas. For example the cognitive act of forming a decision requires a concerted computation involving sensory, mnemonic, and executive information residing in neural circuits that have different anatomical locations, that operate on different temporal scales, and that extend over different spatial dimensions. We find that in a central cortical hub—the posterior parietal cortex—firing rate information about upcoming decisions is pulsed according to intrinsic temporal structure in the beta- and gamma-frequency ranges. The brain may use temporal structure at several time scales to support distributed computations that underlie reward-guided decisions. Making a decision involves computations across distributed cortical and subcortical networks. How such distributed processing is performed remains unclear. We test how the encoding of choice in a key decision-making node, the posterior parietal cortex (PPC), depends on the temporal structure of the surrounding population activity. We recorded spiking and local field potential (LFP) activity in the PPC while two rhesus macaques performed a decision-making task. We quantified the mutual information that neurons carried about an upcoming choice and its dependence on LFP activity. The spiking of PPC neurons was correlated with LFP phases at three distinct time scales in the theta, beta, and gamma frequency bands. Importantly, activity at these time scales encoded upcoming decisions differently. Choice information contained in neural firing varied with the phase of beta and gamma activity. For gamma activity, maximum choice information occurred at the same phase as the maximum spike count. However, for beta activity, choice information and spike count were greatest at different phases. In contrast, theta activity did not modulate the encoding properties of PPC units directly but was correlated with beta and gamma activity through cross-frequency coupling. We propose that the relative timing of local spiking and choice information reveals temporal reference frames for computations in either local or large-scale decision networks. Differences between the timing of task information and activity patterns may be a general signature of distributed processing across large-scale networks.
Weight and Veterans’ Environments Study (WAVES) I and II: Rationale, Methods, and Cohort Characteristics

Purpose: To present the rationale, methods, and cohort characteristics for 2 complementary “big data” studies of residential environment contributions to body weight, metabolic risk, and weight management program participation and effectiveness. Design: Retrospective cohort. Setting: Continental United States. Participants: A total of 3 261 115 veterans who received Department of Veterans Affairs (VA) health care in 2009 to 2014, including 169 910 weight management program participants and a propensity score–derived comparison group. Intervention: The VA MOVE! weight management program, an evidence-based lifestyle intervention. Measures: Body mass index, metabolic risk measures, and MOVE! participation; residential environmental attributes (eg, food outlet availability and walkability); and MOVE! program characteristics. Analysis: Descriptive statistics presented on cohort characteristics and environments where they live. Results: Forty-four percent of men and 42.8% of women were obese, whereas 4.9% of men and 9.9% of women engaged in MOVE! About half of the cohort had at least 1 supermarket within 1 mile of their home, whereas they averaged close to 4 convenience stores (3.6 for men, 3.9 for women) and 8 fast-food restaurants (7.9 for men, 8.2 for women). Forty-one percent of men and 38.6% of women did not have a park, and 35.5% of men and 31.3% of women did not have a commercial fitness facility within 1 mile. Conclusion: Drawing on a large nationwide cohort residing in diverse environments, these studies are poised to significantly inform policy and weight management program design.
Biomechanical Forces Promote Immune Regulatory Function of Bone Marrow Mesenchymal Stromal Cells

Mesenchymal stromal cells (MSCs) are believed to mobilize from the bone marrow in response to inflammation and injury, yet the effects of egress into the vasculature on MSC function are largely unknown. Here we show that wall shear stress (WSS) typical of fluid frictional forces present on the vascular lumen stimulates antioxidant and anti‐inflammatory mediators, as well as chemokines capable of immune cell recruitment. WSS specifically promotes signaling through NFκB‐COX2‐prostaglandin E2 (PGE2) to suppress tumor necrosis factor‐α (TNF‐α) production by activated immune cells. Ex vivo conditioning of MSCs by WSS improved therapeutic efficacy in a rat model of traumatic brain injury, as evidenced by decreased apoptotic and M1‐type activated microglia in the hippocampus. These results demonstrate that force provides critical cues to MSCs residing at the vascular interface which influence immunomodulatory and paracrine activity, and suggest the potential therapeutic use of force for MSC functional enhancement. Stem Cells 2017;35:1259–1272
Corneal Collagen Cross-Linking for Keratoconus: Systematic Review

Purpose To evaluate the efficacy of collagen cross-linking (CXL) one year after treatment for keratoconus compared to no treatment by summarizing randomized controlled trials (RCTs) using a systematic review. Methods Trials meeting the selection criteria were quality appraised, and the data were extracted by two independent authors. The outcome parameters included maximum keratometry (Kmax), corneal thickness at the thinnest point, best spectacle-corrected visual acuity (BSCVA), uncorrected visual acuity (UCVA), spherical equivalent (SE) refraction, and cylindrical refraction one year after CXL. We compared the changes in the above parameters with the control group. Results We identified five RCTs involving 289 eyes that met the eligibility criteria for this systematic review. The changes in BSCVA from baseline to one year exhibited a significant difference between the two groups. There was no statistically significant difference between the two groups for changes in corneal thickness and cylindrical refraction. We did not conduct a meta-analysis in Kmax, UCVA, and SE refraction because their I2 values were greater than 50%. Conclusions According to the systematic review, CXL may be effective in halting the progression of keratoconus for one year under certain conditions, although evidence is limited due to the significant heterogeneity and paucity of RCTs.
Joint Causal Inference from Observational and Experimental Datasets

We introduce Joint Causal Inference (JCI), a powerful formulation of causal discovery from multiple datasets that allows to jointly learn both the causal structure and targets of interventions from statistical independences in pooled data. Compared with existing constraint-based approaches for causal discovery from multiple data sets, JCI offers several advantages: it allows for several different types of interventions in a unified fashion, it can learn intervention targets, it systematically pools data across different datasets which improves the statistical power of independence tests, and most importantly, it improves on the accuracy and identifiability of the predicted causal relations. A technical complication that arises in JCI is the occurrence of faithfulness violations due to deterministic relations. We propose a simple but effective strategy for dealing with this type of faithfulness violations. We implement it in ACID, a determinism-tolerant extension of Ancestral Causal Inference (ACI) (Magliacane et al., 2016), a recently proposed logic-based causal discovery method that improves reliability of the output by exploiting redundant information in the data. We illustrate the benefits of JCI with ACID with an evaluation on a simulated dataset.
Metallicity and Alpha-Element Abundance Measurement in Red Giant Stars from Medium-Resolution Spectra

We present a technique that applies spectral synthesis to medium-resolution spectroscopy (MRS; R ∼ 6000) in the red (6300 Å < λ < 9100 Å) to measure [Fe/H] and [α/Fe] of individual red giant stars over a wide metallicity range. We apply our technique to 264 red giant stars in seven Galactic globular clusters and demonstrate that it reproduces the metallicities and α-enhancements derived from high-resolution spectroscopy (HRS). The MRS technique excludes the three Ca II triplet lines and instead relies on a plethora of weaker lines. Unlike empirical metallicity estimators, such as the equivalent width of the Ca II triplet, the synthetic method presented here is applicable over an arbitrarily wide metallicity range and is independent of assumptions about the α-enhancement. Estimates of cluster mean [Fe/H] from different HRS studies show typical scatter of ~0.1 dex but can be larger than 0.2 dex for metal-rich clusters. The scatter in HRS abundance estimates among individual stars in a given cluster is also comparable to 0.1 dex. By comparison, the scatter among MRS [Fe/H] estimates of individual stars in a given cluster is ~0.1 dex for most clusters but 0.17 dex for the most metal-rich cluster, M71 (⟨ [ Fe/H ] ⟩ = − 0.8). A star-by-star comparison of HRS versus MRS [α/Fe] estimates indicates that the precision in [ α/Fe ]MRS is 0.05 dex. The errors in [ Fe/H ]MRS and [ α/Fe ]MRS increase beyond 0.25 dex only below signal-to-noise ratios of 20 Å−1, which is typical for existing MRS of the red giant stars in Leo I, one of the most distant Milky Way satellites (250 kpc).
Adoption of ICU Telemedicine in the United States

Objective:ICU telemedicine is a novel approach for providing critical care services from a distance. We sought to study the extent of use and patterns of adoption of this technology in U.S. ICUs. Design:Retrospective study combining a systematic listing of ICU telemedicine installations with hospital characteristic data from the Centers for Medicare and Medicaid Services. We examined adoption over time and compared hospital characteristics between facilities that have adopted ICU telemedicine and those that have not. Setting:U.S. ICUs. Setting:U.S. hospitals from 2002 to 2010. Interventions:None. Measurements and Main Results:The number of hospitals using ICU telemedicine increased from 16 (0.4% of total) to 213 (4.6% of total) between 2003 and 2010. The number of ICU beds covered by telemedicine increased from 598 (0.9% of total) to 5,799 (7.9% of total). The average annual rate of ICU bed coverage growth was 101% per year in the first four study years but slowed to 8.1% per year over the last four study years (p < 0.001 for difference in linear trend). Compared with non-adopting hospitals, hospitals adopting ICU telemedicine were more likely to be large (percentage with > 400 beds: 11.1% vs 3.7%, p < 0.001), teaching (percentage with resident coverage: 31.4% vs 21.9%, p = 0.003), and urban (percentage located in metropolitan statistical areas with more than 1 million residents: 45.3% vs 30.1%, p < 0.001). Conclusions:ICU telemedicine adoption was initially rapid but recently slowed. Efforts are needed to uncover the barriers to future growth, particularly regarding the optimal strategy for using this technology most effectively and efficiently.