Miracle-dz/UniFAR-FTUs huggingface dataset:
The Ca2+‐Regulated Photoprotein Obelin as a Tool for SELEX Monitoring and DNA Aptamer Affinity Evaluation

Bioluminescent solid‐phase analysis was proposed to monitor the selection process and to determine binding characteristics of the aptamer–target complexes during design and development of the specific aptamers. The assay involves Ca2+‐regulated photoprotein obelin as a simple, sensitive and fast reporter. Applicability and the prospects of the approach were exemplified by identification of DNA aptamers to cardiac troponin I, a highly specific early biomarker for acute myocardial infarction. Two structurally different aptamers specific to various epitopes of troponin I were obtained and then tested in a model bioluminescent assay.
Human vascular endothelial cells express epithelial growth factor in response to infection by Bartonella bacilliformis

Bartonella are Gram-negative bacterial pathogens that trigger pathological angiogenesis during infection of humans. Bartonella bacilliformis (Bb) is a neglected tropical agent endemic to South America, where it causes Carrión’s disease. Little is known about Bb’s virulence determinants or how the pathogen elicits hyperproliferation of the vasculature, culminating in Peruvian warts (verruga peruana) of the skin. In this study, we determined that active infection of human umbilical vein endothelial cells (HUVECs) by live Bb induced host cell secretion of epidermal growth factor (EGF) using ELISA. Killed bacteria or lysates of various Bb strains did not cause EGF production, suggesting that an active infection was necessary for the response. Bb also caused hyperproliferation of infected HUVECs, and the mitogenic response could be inhibited by the EGF-receptor (EGFR) inhibitor, AG1478. Bb strains engineered to overexpress recombinant GroEL, evoked greater EGF production and hyperproliferation of HUVECs compared to control strains. Conditioned (spent) media from cultured HUVECs that had been previously infected by Bb were found to be mitogenic for naïve HUVECs, and the response could be inhibited by EGFR blocking with AG1478. Bb cells and cell lysates stimulated HUVEC migration and capillary-like tube formation in transmigration and Matrigel assays, respectively. To our knowledge, this is the first demonstration of EGF production by Bb-infected endothelial cells; an association that could contribute to hyperproliferation of the vascular bed during bartonellosis.
Allopolyploid speciation accompanied by gene flow in a tree fern.

Hybridization in plants may result in hybrid speciation or introgression and, thus, is now widely understood to be an important mechanism of species diversity on an evolutionary time scale. Hybridization is particularly common in ferns, as is polyploidy, which often results from hybrid crosses. Nevertheless, hybrid speciation as an evolutionary process in fern lineages remains poorly understood. Here, we employ flow cytometry, phylogeny, genome-wide SNP datasets, and admixture and coalescent modeling to show that the scaly tree fern, Gymnosphaera metteniana is a naturally occurring allotetraploid species derived from hybridization between the diploids, G. denticulata and G. gigantea. Moreover, we detected ongoing gene flow between the hybrid species and its progenitors, and we found that G. gigantea and G. metteniana inhabit distinct niches, whereas climatic niches of G. denticulata and G. metteniana largely overlap. Taken together, these results suggest either some degree of intrinsic genetic isolation between the hybrid species and its parental progenitors or ecological isolation over short distances may be playing an important role in the evolution of reproductive barriers. Historical climate change may have facilitated the origin of G. metteniana, with the timing of hybridization coinciding with a period of intensification of the East Asian monsoon during the Pliocene and Pleistocene periods in southern China. Our study of allotetraploid G. metteniana represents the first genomic-level documentation of hybrid speciation in scaly tree ferns and, thus, provides a new perspective on evolution in the lineage.
Photoconducting Devices with Response in the Visible-Near-Infrared Region Based on Neutral Ni Complexes of Aryl-1,2-dithiolene Ligands.

Metal bis(1,2-dithiolene) complexes belonging to the class [Ni(Ar-edt)2]x- [Ar-edt2- = arylethylene-1,2-dithiolate; Ar = phenyl, (1x-), 2-naphthyl (2x-); x = 0 and 1] were fully characterized by NMR, UV-visible-near-infrared (UV-vis-NIR), diffuse reflectance, and FT-IR spectroscopy, as well as cyclic voltammetry and single-crystal X-ray diffraction analysis. These complexes have emerged as new photoconducting materials that allowed for the development of a prototype of photodetectors with response in the vis-NIR region. The photodetecting devices showed in some cases quantum efficiencies orders of magnitude higher than those of previously reported 1,2-dithiolene systems.
Regional variations in geographic access to inpatient hospices and Place of death: A Population-based study in England, UK

Background There is much variation in hospice use with respect to geographic factors such as area-based deprivation, location of patient’s residence and proximity to services location. However, little is known about how the association between geographic access to inpatient hospice and hospice deaths varies by patients’ region of settlement. Study aim To examine regional differences in the association between geographic access to inpatient hospice and hospice deaths. Methods A regional population-based observational study in England, UK. Records of patients aged ≥ 25 years (n = 123088) who died from non-accidental causes in 2014, were extracted from the Office for National Statistics (ONS) death registry. Our cohort comprised of patients who died at home and in inpatient hospice. Decedents were allocated to each of the nine government office regions of England (London, East Midlands, West Midlands, East, Yorkshire and The Humber, South West, South East, North West and North East) through record linkage with their postcode of usual residence. We defined geographic access as a measure of drive times from patients’ residential location to the nearest inpatient hospice. A modified Poisson regression estimated the association between geographic access to hospice, comparing hospice deaths (1) versus home deaths (0). We developed nine regional specific models and adjusted for regional differences in patient’s clinical & socio-demographic characteristics. The strength of the association was estimated with adjusted Proportional Ratios (aPRs). Findings The percentage of deaths varied across regions (home: 86.7% in the North East to 73.0% in the South East; hospice: 13.3% in the North East to 27.0% in the South East). We found wide differences in geographic access to inpatient hospices across regions. Median drive times to hospice varied from 4.6 minutes in London to 25.9 minutes in the North East. We found a dose-response association in the East: (aPRs: 0.22–0.78); East Midlands: (aPRs: 0.33–0.63); North East (aPRs: 0.19–0.87); North West (aPRs: 0.69–0.88); South West (aPRs: 0.56–0.89) and West Midlands (aPRs: 0.28–0.92) indicating that decedents who lived further away from hospices locations (≥ 10 minutes) were less likely to die in a hospice. Conclusion The clear dose-response associations in six regions underscore the importance of regional specific initiatives to improve and optimise access to hospices. Commissioners and policymakers need to do more to ensure that home death is not due to limited geographic access to inpatient hospice care.
Covert sleep-related biological processes are revealed by probabilistic analysis in Drosophila

Significance Reduced sleep duration and disrupted sleep quality are correlated with adverse mental and physical health outcomes. Better tools for measuring the internal drives for sleep and wake in model organisms would facilitate understanding the role of sleep quality in health. We defined two conditional probabilities, P(Wake) and P(Doze), that can be calculated from recordings of Drosophila activity without disturbing the animal. We demonstrated that P(Wake) is a measure of sleep depth and that P(Doze) is a measure of sleep pressure. In parallel, we developed an automatic classifier for state-based analysis of Drosophila behavior. These analysis tools will improve our understanding of the pharmacology and neuronal regulation of behavioral drives in the Drosophila brain. Sleep pressure and sleep depth are key regulators of wake and sleep. Current methods of measuring these parameters in Drosophila melanogaster have low temporal resolution and/or require disrupting sleep. Here we report analysis tools for high-resolution, noninvasive measurement of sleep pressure and depth from movement data. Probability of initiating activity, P(Wake), measures sleep depth while probability of ceasing activity, P(Doze), measures sleep pressure. In vivo and computational analyses show that P(Wake) and P(Doze) are largely independent and control the amount of total sleep. We also develop a Hidden Markov Model that allows visualization of distinct sleep/wake substates. These hidden states have a predictable relationship with P(Doze) and P(Wake), suggesting that the methods capture the same behaviors. Importantly, we demonstrate that both the Doze/Wake probabilities and the sleep/wake substates are tied to specific biological processes. These metrics provide greater mechanistic insight into behavior than measuring the amount of sleep alone.
In situ photosynthetic performance of Laminaria digitata (Phaeophyceae) during spring tides in Northern Brittany

The ability of Laminaria digitata (Hudson) J.V. Lamouroux to cope with rapid and drastic changes in light was studied in the field by measuring photosystem II fluorescence, net oxygen roduction and pigment content. Experiments were conducted during two spring tides of late spring in Northern Brittany where low spring tides occur around noon. Daily patterns of the photosynthetic performance of Laminaria digitata were observed in relation to changes in incident under- water light. Photoinhibitory light exposure induced a sharp decrease of the optimal quantum yield (Fv/Fm), a decline of the net oxygen production in the first of the two spring tides investigated and a concomitant increase in the de-epoxidation ratio of the Violaxanthin pool. Photoinhibition persisted at a lower extent at the end of the day and complete recovery was achieved during the night. The implications of the photoinhibition of photosynthesis of Laminaria digitata are discussed in relation to the natural ambient conditions experienced in the field.
Phosphatidylcholine Containing Long Chain Omega-3 Fatty Acids: a Treatment Adjunct for Patients with Anorexia Nervosa?

BACKGROUND Anorexia nervosa (AN) is a serious mental disorder with a high mortality rate and often a chronic course. In contrast to many other common mental disorders, there is no drug therapy approved for AN. METHODS We performed a narrative literature review to consider whether a choline-containing molecule, such as phosphatidylcholine (PC), with an omega (ω)-3 long chain polyunsaturated fatty acid (LCPUFA) could be a potential future medicinal treatment for AN. RESULTS Choline and LCPUFAs have individually shown benefit for mental health. Case series and pilot studies suggest ω-3 LCPUFAs may be effective in eating disorders. However, pharmacodynamic and pharmacokinetic considerations suggest a greater benefit from the combination of both components. CONCLUSION The combination of a choline-containing molecule with an ω-3 LCPUFA may be clinically effective and well tolerated. This idea is supported by the current literature on the role of inflammation, the microbiome, the gut-brain-axis, hormonal, neurotransmitter and intracellular signalling, and on the structure and fluidity of nerve cells membranes in patients with AN.
Aminoacyl-tRNA synthetases

The aminoacyl-tRNA synthetases are an essential and universally distributed family of enzymes that plays a critical role in protein synthesis, pairing tRNAs with their cognate amino acids for decoding mRNAs according to the genetic code. Synthetases help to ensure accurate translation of the genetic code by using both highly accurate cognate substrate recognition and stringent proofreading of noncognate products. While alterations in the quality control mechanisms of synthetases are generally detrimental to cellular viability, recent studies suggest that in some instances such changes facilitate adaption to stress conditions. Beyond their central role in translation, synthetases are also emerging as key players in an increasing number of other cellular processes, with far-reaching consequences in health and disease. The biochemical versatility of the synthetases has also proven pivotal in efforts to expand the genetic code, further emphasizing the wide-ranging roles of the aminoacyl-tRNA synthetase family in synthetic and natural biology.
Slc35a1 deficiency causes thrombocytopenia due to impaired megakaryocytopoiesis and excessive platelet clearance in the liver.

Sialic acid is a common terminal residue of glycans on proteins and acidic sphingolipids such as gangliosides with important biological functions. The sialylation process is controlled by more than 20 different sialyltransferases, many of which exhibit overlapping functions. Thus, it is difficult to determine the overall biological function of sialylation by targeted deletion of individual sialyltransferase. To address this question, we established a mouse line with the Slc35a1 gene flanked by loxP sites. Slc35a1 encodes the CMP-sialic acid transporter that transports CMP-sialic acid from cytoplasm into the Golgi apparatus for sialylation. Here we report our study regarding the role of sialylation on megakaryocytes and platelets using a mouse line with significantly reduced sialylation in megakaryocytes and platelets (Plt Slc35a1-/-). The major phenotype of Plt Slc35a1-/- mice was thrombocytopenia. The number of bone marrow megakaryocytes in Plt Slc35a1-/- mice was reduced, and megakaryocyte maturation was also impaired. In addition, an increased number of desialylated platelets was cleared by Kupffer cells in the liver of Plt Slc35a1-/- mice. This study provides new insights into the role of sialylation in platelet homeostasis and the mechanisms of thrombocytopenia in diseases associated with platelet desialylation, such as immune thrombocytopenic purpura and a rare congenital disorder of glycosylation (CDG), SLC35A1-CDG, which is caused by SLC35A1 mutations.
Class enumeration false positive in skew-t family of continuous growth mixture models

Growth Mixture Modeling (GMM) has gained great popularity in the last decades as a methodology for longitudinal data analysis. The usual assumption of normally distributed repeated measures has been shown as problematic in real-life data applications. Namely, performing normal GMM on data that is even slightly skewed can lead to an over selection of the number of latent classes. In order to ameliorate this unwanted result, GMM based on the skew t family of continuous distributions has been proposed. This family of distributions includes the normal, skew normal, t, and skew t. This simulation study aims to determine the efficiency of selecting the “true” number of latent groups in GMM based on the skew t family of continuous distributions, using fit indices and likelihood ratio tests. Results show that the skew t GMM was the only model considered that showed fit indices and LRT false positive rates under the 0.05 cutoff value across sample sizes and for normal, and skewed and kurtic data. Simulation results are corroborated by a real educational data application example. These findings favor the development of practical guides of the benefits and risks of using the GMM based on this family of distributions.
Local structural plasticity of the Staphylococcus aureus evasion protein EapH1 enables engagement with multiple neutrophil serine proteases

Members of the EAP family of Staphylococcus aureus immune evasion proteins potently inhibit the neutrophil serine proteases (NSPs) neutrophil elastase, cathepsin-G, and proteinase-3. Previously, we determined a 1.8 Å resolution crystal structure of the EAP family member EapH1 bound to neutrophil elastase. This structure revealed that EapH1 blocks access to the enzyme's active site by forming a noncovalent complex with this host protease. To determine how EapH1 inhibits other NSPs, we studied here the effects of EapH1 on cathepsin-G. We found that EapH1 inhibits cathepsin-G with a Ki of 9.8 ± 4.7 nm. Although this Ki value is ∼466-fold weaker than the Ki for EapH1 inhibition of neutrophil elastase, the time dependence of inhibition was maintained. To define the physical basis for EapH1's inhibition of cathepsin-G, we crystallized EapH1 bound to this protease, solved the structure at 1.6 Å resolution, and refined the model to Rwork and Rfree values of 17.4% and 20.9%, respectively. This structure revealed a protease-binding mode for EapH1 with cathepsin-G that was globally similar to that seen in the previously determined EapH1–neutrophil elastase structure. The nature of the intermolecular interactions formed by EapH1 with cathepsin-G differed considerably from that with neutrophil elastase, however, with far greater contributions from the inhibitor backbone in the cathepsin-G–bound form. Together, these results reveal that EapH1's ability to form high-affinity interactions with multiple NSP targets is due to its remarkable level of local structural plasticity.
Nail hyperpigmentation in ACTH-secreting pituitary adenoma (Cushing’s disease) and its resolution after successful trans-sphenoidal excision

Hyperpigmentation is a known physical examination finding in conditions where adrencorticotrophic hormone (ACTH) is excessive. This is because ACTH shares the same affinity with α-melanocyte-stimulating hormone (MSH) for the melanocortin-1 receptor (MC1R). MC1R is considered the most important
An Overview of Piperazine Scaffold as Promising Nucleus for Different Therapeutic Targets.

Piperazine scaffolds are a group of heterocyclic atoms having pharmacological values and shows significant results in pharmaceutical chemistry. Piperazine has the flexible core structure for the design and synthesis of new bioactive compounds. These flexible heterogenous compounds exhibit various biological roles, primarily anticancer, antioxidant, cognition enhancers, antimicrobial, antibacterial, antiviral, antifungal, anti-inflammatory, anti-HIV-1 inhibitors, antidiabetic, antimalarial, antidepressant, antianxiety and anticonvulsant activities etc. In the past few years, researchers focused on the therapeutic profile of piperazine synthons for different biological targets. The present review highlights the development in designing and pharmacological activities of nitrogen-containing piperazine moiety as a therapeutic agent. The extensive popularity of piperazine as a drug of abuse and their vast heterogeneity research efforts over the last years motivated the new investigators to further explore this area.
The implementation of a structured specialized consultation for psoriasis management

ABSTRACT Objectives: Psoriasis is a chronic skin disease requiring a multidimensional approach, given its varying appearance, presence of comorbidities and complex treatment regimens. Psoriasis care is however often performed fragmented and, in case of flares, reactive with little integrated information on and for the patient. Literature suggests a multileveled approach of psoriasis, but the effects of its implementation have not yet been validated. The aim of this study is to analyze the impact of a multileveled psoriasis consultation format, named PsoPlus, which has been implemented since 2012 in the Department of Dermatology at Ghent University Hospital in Belgium. Methods: The patient population was divided into two groups: one following the regular consultation and one following the PsoPlus format. Demographic data, clinical outcome and treatment approach of psoriasis patients were compared. Results: Patients who opted for the specialized PsoPlus consultation were younger and had longer disease duration. Decision parameters such as disease severity and quality of life were reported more often in the PsoPlus group. In the latter, a higher rate of patients were started on systemic therapy compared to the regular consultation group, and reporting on adverse events was done more frequently. Conclusion: The implementation of a specialized consultation with comprehensive guidance facilitates documentation on disease-relevant parameters such as disease severity and quality of life. This format can be seen as a guidance for capturing data in a structured manner, with evidence showing that it significantly impacts treatment decision, treating not only psoriasis but the patient as a whole. Graphical abstract
The molecular mechanism of the aberrant expression of the B-cell specific PAX5 gene in t(8;21) AML

B-cell specific gene PAX5 (Busslinger, 2004) is aberrantly expressed in t(8;21) AML (Tiacci et al., 2004) and is potentially involved in blocking myeloid differentiation. To understand the mechanism of PAX5 deregulation in t(8;21) AML we examined the expression, chromatin structure, histone modifications and RNA Polymerase II recruitment at PAX5 in t(8;21) AML, in non-t(8;21) myeloid precursors and in a pre-B-cell-line. Our studies show that in non t(8;21) myeloid precursors, the PAX5 gene is poised for transcription but is repressed by polycomb complexes. This polycomb repression is alleviated in t(8;21) cells leading to PAX5 expression. t(8;21) AML model Kasumi-1 carries an activating C-KIT mutation that leads to constitutive activation of different downstream signalling pathways (Larizza et al., 2005). Some of these signalling pathways have been shown to regulate association of polycomb complexes with chromatin (Voncken et al., 2005). Our study shows that small molecule mediated inhibition of constitutively activated JNK, MEK and P38 signalling in Kasumi-1 cells lead to a down regulation of PAX5 expression, decrease in elongating RNA Polymerase II and H327ac with concomitant increase in H3K27me3 at PAX5. This suggests that deregulated MAPkinase signalling in t(8;21) AML leads to the dissociation of polycomb complexes from PAX5 causing its activation. It also suggests a novel role of tyrosine kinase mutations in lineage specification and differentiation block in t(8;21) AML.