Miracle-dz/UniFAR-FTUs huggingface dataset:
Calcium Imaging of GPCR Activation Using Arrays of Reverse Transfected HEK293 Cells in a Microfluidic System

Reverse-transfected cell arrays in microfluidic systems have great potential to perform large-scale parallel screening of G protein-coupled receptor (GPCR) activation. Here, we report the preparation of a novel platform using reverse transfection of HEK293 cells, imaging by stereo-fluorescence microscopy in a flowcell format, real-time monitoring of cytosolic calcium ion fluctuations using the fluorescent protein Cameleon and analysis of GPCR responses to sequential sample exposures. To determine the relationship between DNA concentration and gene expression, we analyzed cell arrays made with variable concentrations of plasmid DNA encoding fluorescent proteins and the Neurokinin 1 (NK1) receptor. We observed pronounced effects on gene expression of both the specific and total DNA concentration. Reverse transfected spots with NK1 plasmid DNA at 1% of total DNA still resulted in detectable NK1 activation when exposed to its ligand. By varying the GPCR DNA concentration in reverse transfection, the sensitivity and robustness of the receptor response for sequential sample exposures was optimized. An injection series is shown for an array containing the NK1 receptor, bitter receptor TAS2R8 and controls. Both receptors were exposed 14 times to alternating samples of two ligands. Specific responses remained reproducible. This platform introduces new opportunities for high throughput screening of GPCR libraries.
Depression in Women with Breast Cancer: A Systematic Review of Cross-Sectional Studies in Iran

Objective: Breast cancer is one of the most common cancers in women and has more severe mental and emotional effects than other types. Depression as a mental disorder affects people’s mental well-being, physical symptoms, occupational performance, and finally quality of life. The aim of this study was to determine depression levels in Iranian women with breast cancer. Methods: A systematic review study was conducted in 2017. English and Persian databases (PubMed, SCOPUS, Web of Science, Google Scholar, SID, Magiran) were searched with key words such as Depression Or Depressive Disorders AND Women AND Breast Cancer OR Tumor OR Neoplasm OR Malignancy AND Iran. Inclusion criteria allowed for cross-sectional studies conducted in Iran (published in English or Persian language journals), studies that had key words in their keywords or their titles and standard instruments for measuring depression in patients. Of the 160 publications found, eight were selected after reviewing the title, abstract and full article. Results: Age of women with breast cancer in selected studies ranged from 43.8 (SD = 47.1) to 55.9 (SD = 14.6) years. Duration of cancer in most studies was about 1-2 years. In most studies, mild levels of depression for women with breast cancer were present. However, in one study it was stated that 69.4% of participants had serious levels of depression. Conclusions: There is increase in the risk of depression in women with breast cancer. Therefore, it seems necessary to plan preventive and therapeutic measures in order to improve the mental health and quality of life of the affected patients.
Timescales of Intrinsic BOLD Signal Dynamics and Functional Connectivity in Pharmacologic and Neuropathologic States of Unconsciousness

Environmental events are processed on multiple timescales via hierarchical organization of temporal receptive windows (TRWs) in the brain. The dependence of neural timescales and TRWs on altered states of consciousness is unclear. States of reduced consciousness are marked by a shift toward slowing of neural dynamics (<1 Hz) in EEG/ECoG signals. We hypothesize that such prolongation of intrinsic timescales are also seen in blood-oxygen-level-dependent (BOLD) signals. To test this hypothesis, we measured the timescales of intrinsic BOLD signals using mean frequency (MF) and temporal autocorrelation (AC) in healthy volunteers (n = 23; male/female 14/9) during graded sedation with propofol. We further examined the relationship between the intrinsic timescales (local/voxel level) and its regional connectivity (across neighboring voxels; regional homogeneity, ReHo), global (whole-brain level) functional connectivity (GFC), and topographical similarity (Topo). Additional results were obtained from patients undergoing deep general anesthesia (n = 12; male/female: 5/7) and in patients with disorders of consciousness (DOC) (n = 21; male/female: 14/7). We found that MF, AC, and ReHo increased, whereas GFC and Topo decreased, during propofol sedation. The local alterations occur before changes of distant connectivity. Conversely, all of these parameters decreased in deep anesthesia and in patients with DOC. We conclude that propofol synchronizes local neuronal interactions and prolongs the timescales of intrinsic BOLD signals. These effects may impede communication among distant brain regions. Furthermore, the intrinsic timescales exhibit distinct dynamic signatures in sedation, deep anesthesia, and DOC. These results improve our understanding of the neural mechanisms of unconsciousness in pharmacologic and neuropathologic states. SIGNIFICANCE STATEMENT Information processing in the brain occurs through a hierarchy of temporal receptive windows (TRWs) in multiple timescales. Anesthetic drugs induce a reversible suppression of consciousness and thus offer a unique opportunity to investigate the state dependence of neural timescales. Here, we demonstrate for the first time that sedation with propofol is accompanied by the prolongation of the timescales of intrinsic BOLD signals presumably reflecting enlarged TRWs. We show that this is accomplished by an increase of local and regional signal synchronization, effects that may disrupt information exchange among distant brain regions. Furthermore, we show that the timescales of intrinsic BOLD signals exhibit distinct dynamic signatures in sedation, deep anesthesia, and disorders of consciousness.
Measuring the representational space of music with fMRI: a case study with Sting

ABSTRACT Functional brain imaging has revealed much about the neuroanatomical substrates of higher cognition, including music, language, learning, and memory. The technique lends itself to studying of groups of individuals. In contrast, the nature of expert performance is typically studied through the examination of exceptional individuals using behavioral case studies and retrospective biography. Here, we combined fMRI and the study of an individual who is a world-class expert musician and composer in order to better understand the neural underpinnings of his music perception and cognition, in particular, his mental representations for music. We used state of the art multivoxel pattern analysis (MVPA) and representational dissimilarity analysis (RDA) in a fixed set of brain regions to test three exploratory hypotheses with the musician Sting: (1) Composing would recruit neutral structures that are both unique and distinguishable from other creative acts, such as composing prose or visual art; (2) listening and imagining music would recruit similar neural regions, indicating that musical memory shares anatomical substrates with music listening; (3) the MVPA and RDA results would help us to map the representational space for music, revealing which musical pieces and genres are perceived to be similar in the musician’s mental models for music. Our hypotheses were confirmed. The act of composing, and even of imagining elements of the composed piece separately, such as melody and rhythm, activated a similar cluster of brain regions, and were distinct from prose and visual art. Listened and imagined music showed high similarity, and in addition, notable similarity/dissimilarity patterns emerged among the various pieces used as stimuli: Muzak and Top 100/Pop songs were far from all other musical styles in Mahalanobis distance (Euclidean representational space), whereas jazz, R&B, tango and rock were comparatively close. Closer inspection revealed principaled explanations for the similarity clusters found, based on key, tempo, motif, and orchestration.
Glucose Metabolism Abnormalities in Cushing Syndrome: From Molecular Basis to Clinical Management

An impaired glucose metabolism, which often leads to the onset of diabetes mellitus (DM), is a common complication of chronic exposure to exogenous and endogenous glucocorticoid (GC) excess and plays an important part in contributing to morbidity and mortality in patients with Cushing syndrome (CS). This article reviews the pathogenesis, epidemiology, diagnosis, and management of changes in glucose metabolism associated with hypercortisolism, addressing both the pathophysiological aspects and the clinical and therapeutic implications. Chronic hypercortisolism may have pleiotropic effects on all major peripheral tissues governing glucose homeostasis. Adding further complexity, both genomic and nongenomic mechanisms are directly induced by GCs in a context-specific and cell-/organ-dependent manner. In this paper, the discussion focuses on established and potential pathologic molecular mechanisms that are induced by chronically excessive circulating levels of GCs and affect glucose homeostasis in various tissues. The management of patients with CS and DM includes treating their hyperglycemia and correcting their GC excess. The effects on glycemic control of various medical therapies for CS are reviewed in this paper. The association between DM and subclinical CS and the role of screening for CS in diabetic patients are also discussed.
A review: effect of conductive polymers on the conductivities of electrospun mats

The effects of conductive polymers on conductivities and morphologies of electrospun fabrics are analyzed. The factors that affect the conductivities and morphologies are discussed. Some applications of these conductive nanofibers are reported. The introduction of conductive polymers into nanofiber mats has the potential to provide sufficient conductivity for many applications. An improved conductivity can be achieved by maximizing the content of conjugated polymers. The selection of conductive and carrier polymers, solvents, doping agents, oxidizing agents and ratios of them are also important to obtain sufficient properties. Carbon fiber, carbon black and carbon nanotubes are not covered in this review.
Delineating the GRIN1 phenotypic spectrum

Objective: To determine the phenotypic spectrum caused by mutations in GRIN1 encoding the NMDA receptor subunit GluN1 and to investigate their underlying functional pathophysiology. Methods: We collected molecular and clinical data from several diagnostic and research cohorts. Functional consequences of GRIN1 mutations were investigated in Xenopus laevis oocytes. Results: We identified heterozygous de novo GRIN1 mutations in 14 individuals and reviewed the phenotypes of all 9 previously reported patients. These 23 individuals presented with a distinct phenotype of profound developmental delay, severe intellectual disability with absent speech, muscular hypotonia, hyperkinetic movement disorder, oculogyric crises, cortical blindness, generalized cerebral atrophy, and epilepsy. Mutations cluster within transmembrane segments and result in loss of channel function of varying severity with a dominant-negative effect. In addition, we describe 2 homozygous GRIN1 mutations (1 missense, 1 truncation), each segregating with severe neurodevelopmental phenotypes in consanguineous families. Conclusions: De novo GRIN1 mutations are associated with severe intellectual disability with cortical visual impairment as well as oculomotor and movement disorders being discriminating phenotypic features. Loss of NMDA receptor function appears to be the underlying disease mechanism. The identification of both heterozygous and homozygous mutations blurs the borders of dominant and recessive inheritance of GRIN1-associated disorders.
Specifying and Analyzing Virtual Network Services Using Queuing Petri Nets

For optimal placement and orchestration of network services, it is crucial that their structure and semantics are specified clearly and comprehensively and are available to an orchestrator. Existing specification approaches are either ambiguous or miss important aspects regarding the behavior of virtual network functions (VNFs) forming a service. We propose to formally and unambiguously specify the behavior of these functions and services using Queuing Petri Nets (QPNs). QPNs are an established method that allows to express queuing, synchronization, stochastically distributed processing delays, and changing traffic volume and characteristics at each VNF. With QPNs, multiple VNFs can be connected to complete network services in any structure, even specifying bidirectional network services containing loops.We propose a tool-based workflow that supports the specification of network services and the automatic generation of corresponding simulation code to enable an in-depth analysis of their behavior and performance. In a case study, we show how developers can benefit from analysis insights, e.g., to anticipate the impact of different service configurations. We also discuss how management and orchestration systems can benefit from our clear and comprehensive specification approach and its extensive analysis possibilities, leading to better placement of VNFs and improved Quality of Service.
Muscle Atrophy Induced by Mechanical Unloading: Mechanisms and Potential Countermeasures

Prolonged periods of skeletal muscle inactivity or mechanical unloading (bed rest, hindlimb unloading, immobilization, spaceflight and reduced step) can result in a significant loss of musculoskeletal mass, size and strength which ultimately lead to muscle atrophy. With advancement in understanding of the molecular and cellular mechanisms involved in disuse skeletal muscle atrophy, several different signaling pathways have been studied to understand their regulatory role in this process. However, substantial gaps exist in our understanding of the regulatory mechanisms involved, as well as their functional significance. This review aims to update the current state of knowledge and the underlying cellular mechanisms related to skeletal muscle loss during a variety of unloading conditions, both in humans and animals. Recent advancements in understanding of cellular and molecular mechanisms, including IGF1-Akt-mTOR, MuRF1/MAFbx, FOXO, and potential triggers of disuse atrophy, such as calcium overload and ROS overproduction, as well as their role in skeletal muscle protein adaptation to disuse is emphasized. We have also elaborated potential therapeutic countermeasures that have shown promising results in preventing and restoring disuse-induced muscle loss. Finally, identified are the key challenges in this field as well as some future prospectives.
PM Origin or Exposure Duration? Health Hazards from PM-Bound Mercury and PM-Bound PAHs among Students and Lecturers

This study assessed inhalation exposure to particulate matter (PM1)-bound mercury (Hgp) and PM1-bound polycyclic aromatic hydrocarbons (PAHs) among university students. For this purpose, simultaneous indoor (I) and outdoor (O) measurements were taken from two Polish technical universities (in Gliwice and Warsaw) located in distinct areas with respect to ambient concentrations and major sources of PM. The indoor geometric mean concentrations of Hgp were found to be 1.46 pg·m−3 and 6.38 pg·m−3 in Warsaw and Gliwice, while the corresponding outdoor concentrations were slightly lower at 1.38 pg·m−3 and 3.03 pg·m−3, respectively. A distinct pattern was found with respect to PAH concentrations with estimated I/O values of 22.2 ng·m−3/22.5 ng·m−3 in Gliwice and 10.9 ng·m−3/11.12 ng·m−3 in Warsaw. Hazard quotients (HQs) as a result of exposure to Hgp for students aged 21 ranged from 3.47 × 10−5 (Warsaw) to 1.3 × 10−4 (Gliwice) in terms of reasonable maximum exposure (RME). The non-cancer human health risk value related to Hgp exposure was thus found to be below the acceptable risk level value of 1.0 given by the US EPA. Daily exposure values for lecture hall occupants, adjusted to the benzo(a)pyrene (BaP) toxicity equivalent (BaPeq), were 2.9 and 1.02 ng·m−3 for the Gliwice and Warsaw students, respectively. The incremental lifetime cancer risk (ILCR) values with respect to exposure to PM1-bound PAHs during the students’ time of study were 5.49 × 10−8 (Warsaw) and 1.43 × 10−7 (Gliwice). Thus, students’ exposure to indoor PAHs does not lead to increased risk of lung cancer.
The Diamond Fields of Southern Africa

THIS book is a greatly enlarged edition, in English, of Dr. Wagner's “Die Diamantfü hrenden Gesteine Sudafrikas,” which was published five years ago. The author states in his preface his aim to be that the book should “contain all that is worth knowing” concerning the subject of which it treats. If he has not altogether realised his ambition—and it is only necessary to glance at the list of 255 titles of works in his bibliography to realise the impossibility of doing so in a book of fewer than 350 pages—we may admit that he has certainly produced a work containing all that it is most important for prospectors, diggers, mining engineers, and investors, to whom the work is specially addressed, to know. Geologists also will find in it a good résumé of the work done in connection with the rocks containing the diamonds.The Diamond Fields of Southern Africa.By Dr. P. A. Wagner. Pp. xxv + 347 + xxxvi plates. (Johannesburg: The Transvaal Leader; London: The Technical Book-Shop, 1914.) Price 27s. 6d. net.
Biochemical Mechanism of Rhododendrol-Induced Leukoderma

RS-4-(4-hydroxyphenyl)-2-butanol (rhododendrol (RD))—a skin-whitening ingredient—was reported to induce leukoderma in some consumers. We have examined the biochemical basis of the RD-induced leukoderma by elucidating the metabolic fate of RD in the course of tyrosinase-catalyzed oxidation. We found that the oxidation of racemic RD by mushroom tyrosinase rapidly produces RD-quinone, which gives rise to secondary quinone products. Subsequently, we confirmed that human tyrosinase is able to oxidize both enantiomers of RD. We then showed that B16 cells exposed to RD produce high levels of RD-pheomelanin and protein-SH adducts of RD-quinone. Our recent studies showed that RD-eumelanin—an oxidation product of RD—exhibits a potent pro-oxidant activity that is enhanced by ultraviolet-A radiation. In this review, we summarize our biochemical findings on the tyrosinase-dependent metabolism of RD and related studies by other research groups. The results suggest two major mechanisms of cytotoxicity to melanocytes. One is the cytotoxicity of RD-quinone through binding with sulfhydryl proteins that leads to the inactivation of sulfhydryl enzymes and protein denaturation that leads to endoplasmic reticulum stress. The other mechanism is the pro-oxidant activity of RD-derived melanins that leads to oxidative stress resulting from the depletion of antioxidants and the generation of reactive oxygen radicals.
XIAP Limits Autophagic Degradation of Sox2 and Is A Therapeutic Target in Nasopharyngeal Carcinoma Stem Cells

Rationale: Nasopharyngeal carcinoma (NPC) is the most frequent head and neck tumor in South China. The presence of cancer stem cells (CSCs) in NPC contributes to tumor maintenance and therapeutic resistance, while the ability of CSCs to escape from the apoptosis pathway may render them the resistant property to the therapies. Inhibitor of apoptosis proteins family proteins (IAPs), which are overexpressed in nasopharyngeal carcinoma stem cells, may play an important role in maintaining nasopharyngeal cancer stem cell properties. Here, we develop a novel CSC-targeting strategy to treat NPC through inhibiting IAPs. Methods: Human NPC S-18 and S-26 cell lines were used as the model system in vitro and in vivo. Fluorescence activated cell sorting (FACS) assay was used to detect nasopharyngeal SP cells and CD44+ cells. The characteristics of CSCs were defined by sphere suspension culture, colony formation assay and cell migration. The role of XIAP on the regulation of Sox2 protein stability and ERK1-mediated phosphorylation of Sox2 signaling pathway were analyzed using immunoblotting, immunoprecipitation, immunofluorescence, phosphorylation mass spectrometry, siRNA silencing and plasmid overexpression. The correlation between XIAP and Sox2 in NPC biopsies and their role in prognosis was performed by immunohistochemistry. APG-1387 or chemotherapies-induced cell death and apoptosis in S-18 and S-26 were determined by WST, immunoblotting and flow cytometry assay. Results: IAPs, especially X chromosome-linked IAP (XIAP), were elevated in CSCs of NPC, and these proteins were critically involved in the maintenance of CSCs properties by enhancing the stability of Sox2. Mechanistically, ERK1 kinase promoted autophagic degradation of Sox2 via phosphorylation of Sox2 at Ser251 and further SUMOylation of Sox2 at Lys245 in non-CSCs. However, XIAP blocked autophagic degradation of Sox2 by inhibiting ERK1 activation in CSCs. Additionally, XIAP was positively correlated with Sox2 expression in NPC tissues, which were associated with NPC progression. Finally, we discovered that a novel antagonist of IAPs, APG-1387, exerted antitumor effect on CSCs. Also, the combination of APG-1387 with CDDP /5-FU has a synergistic effect on NPC. Conclusion: Our study highlights the importance of IAPs in the maintenance of CSCs in NPC. Thus, XIAP is a promising therapeutic target in CSCs and suggests that NPC patients may benefit from a combination treatment of APG-1387 with conventional chemotherapy.
Self-Propagating Combustion Synthesis, Luminescent Properties and Photocatalytic Activities of Pure Ca12Al14O33: Tb3+(Sm3+)

The dual-functional Ca12Al14O33: Tb3+ and Ca12Al14O33: Sm3+ materials were prepared by the Self-Propagating Combustion Synthesis (SPCS) technology. The structure, morphology and light absorption property were investigated by XRD, FT-IR, UV-Vis DRS and SEM etc. The doping of Tb3+ and Sm3+ ions had not changed cubic structure of Ca12Al14O33 but leaded to the slight lattice dilatation and the red-shifts of absorption peaks/edges. The excitation and emission spectra indicated that Ca12Al14O33: Tb3+ and Ca12Al14O33: Sm3+ are superior green and red luminescent materials, respectively, and it displayed the distinctly refined structure characteristics which had importantly reference value for the energy level investigation of Tb3+ and Sm3+ ions. Meanwhile, Ca12Al14O33: Tb3+ and Ca12Al14O33: Sm3+ also exhibited the improved photocatalytic degradation for removing dye MB compared with bare Ca12Al14O33.