Miracle-dz/UniFAR-FTUs huggingface dataset:
Crystal Structure of a GH3 β-Glucosidase from the Thermophilic Fungus Chaetomium thermophilum

Beta-glucosidases (β-glucosidases) have attracted considerable attention in recent years for use in various biotechnological applications. They are also essential enzymes for lignocellulose degradation in biofuel production. However, cost-effective biomass conversion requires the use of highly efficient enzymes. Thus, the search for new enzymes as better alternatives of the currently available enzyme preparations is highly important. Thermophilic fungi are nowadays considered as a promising source of enzymes with improved stability. Here, the crystal structure of a family GH3 β-glucosidase from the thermophilic fungus Chaetomium thermophilum (CtBGL) was determined at a resolution of 2.99 Å. The structure showed the three-domain architecture found in other β-glucosidases with variations in loops and linker regions. The active site catalytic residues in CtBGL were identified as Asp287 (nucleophile) and Glu517 (acid/base). Structural comparison of CtBGL with Protein Data Bank (PDB)-deposited structures revealed variations among glycosylated Asn residues. The enzyme displayed moderate glycosylation compared to other GH3 family β-glucosidases with similar structure. A new glycosylation site at position Asn504 was identified in CtBGL. Moreover, comparison with respect to several thermostability parameters suggested that glycosylation and charged residues involved in electrostatic interactions may contribute to the stability of the enzyme at elevated temperatures. The reported CtBGL structure provides additional insights into the family GH3 enzymes and could offer new ideas for further improvements in β-glucosidases for more efficient use in biotechnological applications regarding cellulose degradation.
Utility of pre-chemotherapy echocardiographical assessment of cardiac abnormalities.

Background Echocardiography provides both morphological and functional information offering a potential advantage over nuclear medicine gated blood pool scans which only estimate ejection fraction. This additional information may be relevant to management of patients receiving potentially cardiotoxic cancer treatment. Patients and methods We retrospectively audited all prechemotherapy echocardiograms (ECHO) ordered by medical oncologists at our institution over a 36 months period. The primary objective was to determine the frequency of cardiac abnormality detection on the initial ECHO. We also looked at the frequency of clinically relevant cardiac abnormalities other than ejection fraction abnormalities including diastolic dysfunction, intracardiac shunts, moderate–severe valvular abnormalities, pulmonary hypertension, ventricular hypertrophy, pericardial effusion, wall motional abnormalities, ventricular dysfunction/dilatation, cardiac tumours and congenital anomalies. Results Baseline ECHOs were analysed in 217 consecutive patients. Female patients comprised 89% of population, and the majority had breast cancer (75.5%). The median age of the patients at the time of ECHO was 55 years (range, 16 to 87); 13.4% of patients had at least one clinically relevant abnormality on ECHO. Systolic and moderate diastolic dysfunctions were seen in 5% and 2.7%, respectively. Aortic stenosis was seen in five (2.3%) patients. Atrial septal defects were seen in two patients, moderate mitral regurgitations in two patients and left atrial tumour in one patient. A total of 7.4% of patients had abnormalities, which would not have been detected by gated blood pool scan (GBPS). The ECHO resulted in change in chemotherapy plan in 2.8% and referral to cardiology in 3.7%. Conclusions Our retrospective analysis suggests that prechemotherapy ECHO can provide more useful clinical information than the GBPS, which may impact on clinical management of cancer patients.
AttentivU: An EEG-Based Closed-Loop Biofeedback System for Real-Time Monitoring and Improvement of Engagement for Personalized Learning

Information about a person’s engagement and attention might be a valuable asset in many settings including work situations, driving, and learning environments. To this end, we propose the first prototype of a device called AttentivU—a system that uses a wearable system which consists of two main components. Component 1 is represented by an EEG headband used to measure the engagement of a person in real-time. Component 2 is a scarf, which provides subtle, haptic feedback (vibrations) in real-time when the drop in engagement is detected. We tested AttentivU in two separate studies with 48 adults. The participants were engaged in a learning scenario of either watching three video lectures on different subjects or participating in a set of three face-to-face lectures with a professor. There were three conditions administrated during both studies: (1) biofeedback, meaning the scarf (component 2 of the system) was vibrating each time the EEG headband detected a drop in engagement; (2) random feedback, where the vibrations did not correlate or depend on the engagement level detected by the system, and (3) no feedback, when no vibrations were administered. The results show that the biofeedback condition redirected the engagement of the participants to the task at hand and improved their performance on comprehension tests.
Brachypodium distachyon triphosphate tunnel metalloenzyme 3 is both a triphosphatase and an adenylyl cyclase upregulated by mechanical wounding

Proteins with a CyaB, thiamine triphosphatase domain (CYTH domain) may play a central role at the interface between nucleotide and polyphosphate metabolism. One of the plant CYTH domain‐containing proteins from Brachypodium distachyon, BdTTM3, is annotated in NCBI databases as an ‘adenylyl cyclase (AC)’ or a ‘triphosphate tunnel metalloenzyme’. The divergent nomenclature and the search for plant ACs induced us to experimentally confirm the enzymatic activity of BdTTM3. Based on in vitro analysis, we have shown that the recombinant form of BdTTM3 is a protein with high triphosphatase activity (binding both tripolyphosphate and ATP) and low AC activity. Furthermore, the analysis of BdTTM3 transcriptional activity indicates its involvement in the mechanism underlying responses to wounding stress in B. distachyon leaves.
Distribution of rods and cones in the red‐eared turtle retina (Trachemys scripta elegans)

We have identified the photoreceptors of Trachemys scripta elegans, an intensely studied species that is a model for color vision work. To recognize and count the different photoreceptor types, we labeled them with a combination of morphological and immunohistochemistry markers. The counts for the determination of the density of each photoreceptor type were made in wholemount retinas. The percentages found for each cone type were 29, 23, 21, 12, and 6%, respectively, for L (both types), double, M, S, and ultraviolet cones. The cones were found to be organized horizontally in a visual streak, a linear region with a higher density of photoreceptors that ends temporally in the periphery and more centrally in the nasal side. This region of high density of photoreceptors was not symmetrical along its extension; there was a region with conspicuous central density peaks in the temporal area, suggestive of an area centralis. We also observed a dorsoventral asymmetry in photoreceptor density, with greater density in the ventral region. This asymmetry was observed in cones and rods, but it was more pronounced in the rods. Our results corroborate and extend the findings of previous work in the literature describing the retinal photoreceptors of T. s. elegans and their spatial organization. The higher cone density within the visual streak reflects increased spatial resolution and its existence suggests the possibility of binocular vision. It is remarkable that within this region the entire potential for color vision is also present.
Physicochemical, Antioxidant activities, Textural and Sensory Properties of yoghurt fortified with different states and rates of pomegranate seeds (Punica granatum L.).

This study examines the effects of incorporating fresh, frozen, osmo-dehydrated, and dried pomegranate seeds, at different concentrations (5 %, 10 % and 20 %) on the physicochemical, antioxidant, textural and sensory properties of yoghurt. Antioxidant activity, pH, acidity, syneresis, and color of yoghurt were also evaluated during the storage (28 days) at 4 °C. The principal component analysis (PCA) was performed to assess the correlations between different yoghurt formulation and their sensory attributes. Data showed that the addition of pomegranate seeds reduced pH and modified the chromatics-coordinate (L*, a*, b*, C*, h°) and firmness of the yoghurt samples. In addition, acidity, °Brix, and syneresis increased compared to the control. Thanks to their high anthocyanin content, pomegranate seeds considerably improved the antioxidant activity essentially for yoghurt enriched with frozen seeds. In addition, the supplementation of 20 % of frozen seeds into yoghurt was the most appreciated by panelists and improved the sensory properties in comparison to other formulation. According to PCA, taste and appearance were the main criteria for the overall acceptability of yoghurt. After 28 days of storage, the reddish color was reinforced, however the antioxidant activity of yoghurts was reduced. Overall, it can be concluded that pomegranate seeds can be used as a natural ingredient to develop a novel yoghurt with high nutritional properties. This article is protected by copyright. All rights reserved.
Durvalumab for the treatment of non-small cell lung cancer

ABSTRACT Introduction: The prognosis of patients with advanced non-small cell lung cancer (NSCLC) remains poor, with a 5-year overall survival rate of around 15%. Immune checkpoint inhibitors, such as programmed cell death protein 1 and programmed death-ligand 1 (PD-L1) inhibitors, have opened a new era in the management of NSCLC. Three checkpoint inhibitors (nivolumab, pembrolizumab, and atezolizumab) are currently approved by the US Food and Drug Administration (FDA) for advanced NSCLC. Durvalumab, an anti-PD-L1 antibody, is under investigation in several trials. Areas covered: This article reviews the pharmacological properties, clinical efficacy, and safety of durvalumab as monotherapy and in combination with other drugs for the treatment of locally advanced and advanced NSCLC. Expert opinion: Durvalumab as monotherapy or in combination with tremelimumab was effective with well-tolerated safety profiles for advanced NSCLC in several phase I or II studies. The PACIFIC study assessed the effectiveness of durvalumab as maintenance therapy following definitive chemoradiotherapy for unresectable stage III NSCLC, and met its primary endpoints of progression-free survival and overall survival. These results led to FDA approval for this NSCLC population. It will be exciting to follow ongoing phase III studies assessing how durvalumab fits into the rapidly evolving therapeutic landscape for advanced NSCLC.
A New Approach of Mathematical Analysis of Structure of Graphene as a Potential Material for Composites

The new analysis of a simplified plane model of single-layered graphene is presented in this work as a potential material for reinforcement in ultralight and durable composites. However, owing to the clear literature discrepancies regarding the mechanical properties of graphene, it is extremely difficult to conduct any numerical analysis to design parts of machines and devices made of composites. Therefore, it is necessary to first systemize the analytical and finite element method (FEM) calculations, which will synergize mathematical models, used in the analysis of mechanical properties of graphene sheets, with the very nature of the chemical bond. For this reason, the considered model is a hexagonal mesh simulating the bonds between carbon atoms in graphene. The determination of mechanical properties of graphene was solved using the superposition method and finite element method. The calculation of the graphene tension was performed for two main directions of the graphene arrangement: armchair and zigzag. The computed results were verified and referred to articles and papers in the accessible literature. It was stated that in unloaded flake of graphene, the equilibrium of forces exists; however, owing to changes of inter-atom distance, the inner forces occur, which are responsible for the appearance of strains.
Bioprofiling TS/A Murine Mammary Cancer for a Functional Precision Experimental Model

The TS/A cell line was established in 1983 from a spontaneous mammary tumor arisen in an inbred BALB/c female mouse. Its features (heterogeneity, low immunogenicity and metastatic ability) rendered the TS/A cell line suitable as a preclinical model for studies on tumor–host interactions and for gene therapy approaches. The integrated biological profile of TS/A resulting from the review of the literature could be a path towards the description of a precision experimental model of mammary cancer.
Preparation and Deep Characterization of Composite/Hybrid Multi-Scale and Multi-Domain Polymeric Microparticles

Polymeric microparticles were produced following a three-step procedure involving (i) the production of an aqueous nanoemulsion of tri and monofunctional acrylate-based monomers droplets by an elongational-flow microemulsifier, (ii) the production of a nanosuspension upon the continuous-flow UV-initiated miniemulsion polymerization of the above nanoemulsion and (iii) the production of core-shell polymeric microparticles by means of a microfluidic capillaries-based double droplets generator; the core phase was composed of the above nanosuspension admixed with a water-soluble monomer and gold salt, the shell phase comprised a trifunctional monomer, diethylene glycol and a silver salt; both phases were photopolymerized on-the-fly upon droplet formation. Resulting microparticles were extensively analyzed by energy dispersive X-rays spectrometry and scanning electron microscopy to reveal the core-shell morphology, the presence of silver nanoparticles in the shell, organic nanoparticles in the core but failed to reveal the presence of the gold nanoparticles in the core presumably due to their too small size (c.a. 2.5 nm). Nevertheless, the reddish appearance of the as such prepared polymer microparticles emphasized that this three-step procedure allowed the easy elaboration of composite/hybrid multi-scale and multi-domain polymeric microparticles.
The Causal Relationship of Circulating Triglycerides and Glycated Hemoglobin: A Mendelian Randomization Study.

CONTEXT The association between circulating triglycerides (TG) and glycated hemoglobin A1c (HbA1c), a biomarker for type 2 diabetes, has been widely addressed, but the causal direction of the relationship is still ambiguous. OBJECTIVE To confirm the causal relationship between TG and HbA1c by bidirectional and two-step Mendelian Randomization (MR) approaches. METHODS We carried out a bidirectional MR approach using the summarized results from the public database to examine any potential causal effects between serum TG and HbA1c in 16,000 individuals of the Taiwan Biobank cohort. We used the MR estimate and the MR inverse variance-weighted method to reveal that relationship between TG and HbA1c. To further determine whether the DNA methylation at specific sequences mediating the causal pathway between TG and HbA1c, using two-step MR approach. RESULTS We identified a single-unit increase in TG measured via log transformation of mg/dl data was associated with a significant increase of 10 units of HbA1c (95% CI = 1.05-18.95, P = 0.029). In contrast, the genetic determinants of HbA1c do not contribute to the amount of circulating TG, (beta = 1.75, 95% CI = -11.50-14.90). Sensitivity analyses, included the weighted-median approach and MR-egger regression supports, were performed to confirm no pleiotropic effect exist among these instrumental variables. Furthermore, we identified the genetic variant, rs1823200, is associated with both methylation of the CpG site adjacent to CADPS gene and HbA1c level. CONCLUSION Our study suggests that higher circulating TG can affect on genomic methylation status, ultimately causing elevated level of circulating HbA1c.
Mixing it up: the biological significance of hybrid skeletal muscle fibers

ABSTRACT Skeletal muscle fibers are classified according to the myosin heavy chain (MHC) isoforms and other myofibrillar proteins expressed within these cells. In addition to ‘pure’ fibers expressing single MHC isoforms, many fibers are ‘hybrids’ that co-express two or more different isoforms of MHC or other myofibrillar proteins. Although hybrid fibers have been recognized by muscle biologists for more than three decades, uncertainty persists about their prevalence in normal muscles, their role in fiber-type transitions, and what they might tell us about fiber-type regulation at the cellular and molecular levels. This Review summarizes current knowledge on the relative abundance of hybrid fibers in a variety of muscles from different species. Data from more than 150 muscles from 39 species demonstrate that hybrid fibers are common, frequently representing 25% or more of the fibers in normal muscles. Hybrid fibers appear to have two main roles: (1) they function as intermediates during the fiber-type transitions associated with skeletal muscle development, adaptation to exercise and aging; and (2) they provide a functional continuum of fiber phenotypes, as they possess physiological properties that are intermediate to those of pure fiber types. One aspect of hybrid fibers that is not widely recognized is that fiber-type asymmetries – such as dramatic differences in the MHC composition along the length of single fibers – appear to be a common aspect of many fibers. The final section of this Review examines the possible role of differential activities of nuclei in different myonuclear domains in establishing fiber-type asymmetries. Summary: Hybrid muscle fibers co-expressing multiple myosin heavy chain isoforms are common components of skeletal muscles. This Review examines the prevalence of these fibers and the conditions under which they occur.
A 2004 PRIMER ON THE MEDICAL MANAGEMENT OF DIABETES

Options for the medical management of diabetes have increased substantially in recent years. Numerous large clinical trials conducted over the last 2 decades have clearly established that good blood glucose control slows or prevents the progression of diabetic microvascular complications including retinopathy. But while there are now more tools to help control blood glucose, it is still not easy for patients to meet their glycemic targets. Effective diabetes management requires dedicated self-care on the part of the patient and the expert assistance of skilled healthcare professionals. Effective use of self-monitoring of blood glucose levels and hemoglobin A1c can help to assess the progress of glycemic control, but both these modalities are underutilized. A number of new approaches are currently in development for diabetes management, including new agents to manage weight and blood glucose, and new technologies to continuously monitor glucose and administer insulin. These innovations will ultimately make it easier for patients to attain their glycemic targets and reduce the progression of diabetes-related complications. (Adv Stud Ophthalmol. 2005;2(1):20-25)
Features of Media Multitasking in School-Age Children

The paper addresses the phenomenon of media multitasking that is being widely spread among children and adolescents in the context of digital socialization. The previous research has revealed its strong connection with cognitive control, executive functions, and academic performance, yet the specificity and efficacy of media multitasking performance, especially among children while they carry out usual activities, remains insufficiently studied. A quasi-experimental study, including digital tasks of various types on a computer and smartphone, the dots task for executive functions, and a socio-psychological questionnaire, was conducted with the participants of three age groups: 7–10, 11–13, and 14–16 years old (N = 154). The results indicate that media multitasking is connected not with sex, but age; the older the participants are, the more likely they tend to work in a multitasking mode. Furthermore, preference for multitasking has been found to be positively related to higher user activity. Although the total task performance rate is insignificantly lower in the multitasking group as compared to the non-multitasking one, a significant negative effect of media multitasking on total performance time was revealed. The results of the study that indicate a strong connection of media multitasking with the intensity of Internet usage, cognitive functions, and performance time, suggest its considerable role in social and cognitive functioning of children and adolescents.
Molecular signaling of G‐protein‐coupled receptor in chronic heart failure and associated complications

The well‐known condition of heart failure is a clinical syndrome that results when the myocardium's ability to pump enough blood to meet the body's metabolic needs is impaired. Most of the cardiac activity is maintained by adrenoceptors, are categorized into two main α and β and three distinct subtypes of β receptor: β1‐, β2‐, and β3‐adrenoceptors. The β adrenoreceptor is the main regulatory macro proteins, predominantly available on heart and responsible for down regulatory cardiac signaling. Moreover, the pathological involvement of Angiotensin‐converting enzyme 1 (ACE1)/angiotensin II (Ang II)/angiotensin II type 1 (AT1) axis and beneficial ACE2/Ang (1‐7)/Mas receptor axis also shows protective role via Gi βγ, during heart failure these receptors get desensitized or internalized due to increase in the activity of G‐protein‐coupled receptor kinase 2 (GRK2) and GRK5, responsible for phosphorylation of G‐protein‐mediated down regulatory signaling. Here, we investigate the various clinical and preclinical data that exhibit the molecular mechanism of upset level of GRK change the cardiac activity during failing heart.
Calculation of specific absorption rate (SAR) in human brain neurons using complex permittivity

Abstract The effect of the external electromagnetic radiation on the human brain has been investigated by the numerical calculation of the frequency-dependent complex permittivity. Using the Hodgkin–Huxley neuron model, an analytical method for the calculation of the electromagnetic power absorption in the brain neurons is proposed based on the complex permittivity of neuron membranes. The effect of the human head is considered through the calculation of forward and backward travelling electromagnetic waves. The modified time-dependent Hodgkin–Huxley equations have been used to obtain the reflectivity and transmissivity of the external stimulus at the membrane of the cell. The amount of absorbed energy by the human head is presented in the form of the electromagnetic absorption rate.