Miracle-dz/UniFAR-FTUs huggingface dataset:
The Calliphora rpa mutant lacks the PDZ domain‐assembled INAD signalling complex

The visual transduction cascade of fly photoreceptors is a G protein‐coupled phospholipase C‐signalling pathway which is assembled into a supramolecular signalling complex by the PDZ (postsynaptic density protein‐95, discs large, Z0–1) domain protein INAD (inactivation no afterpotential D). The norpA‐encoded phospholipase Cβ, the light‐activated transient receptor potential (TRP) Ca2+ channel and an eye‐specific protein kinase C are bound to INAD and together form the core of the signalling complex. In the present study we show that the Calliphora rpa mutant, which has previously been hypothesized to represent an equivalent of Drosophila norpA mutants, has normal amounts of norpA mRNA but fails to express inaD mRNA. Electrophysiological recordings from the eyes of the rpa mutant reveal that the electroretinogram is reduced (about 12% of wild type) but not completely absent, and that it exhibits markedly prolonged deactivation kinetics. Furthermore, rpa mutants display a slow, light‐dependent degeneration of the photoreceptor cells. With respect to the INAD signalling complex, the rpa mutant is similar to the Drosophila inaD null mutant: not only INAD itself, but also the other core components of the INAD signalling complex, are reduced or absent in photoreceptor membranes of rpa flies. Residual TRP is localized throughout the plasma membrane of the photoreceptor cell, rather than being restricted to the microvillar photoreceptor membrane. [35S]methionine‐labelling of newly synthesized retinal proteins reveals that TRP is synthesized in the rpa mutant at wild‐type level, but is transported to or incorporated into the microvillar photoreceptor membrane at a much lower rate. We thus suggest, that the formation of the INAD signalling complex is required for specifically targeting its components to the photoreceptor membrane.
Axonal properties determine somatic firing in a model of in vitro CA1 hippocampal sharp wave/ripples and persistent gamma oscillations

Evidence has been presented that CA1 pyramidal cells, during spontaneous in vitro sharp wave/ripple (SPW‐R) complexes, generate somatic action potentials that originate in axons. ‘Participating’ (somatically firing) pyramidal cells fire (almost always) at most once during a particular SPW‐R whereas non‐participating cells virtually never fire during an SPW‐R. Somatic spikelets were small or absent, while ripple‐frequency EPSCs and IPSCs occurred during the SPW‐R in pyramidal neurons. These experimental findings could be replicated with a network model in which electrical coupling was present between small pyramidal cell axonal branches. Here, we explore this model in more depth. Factors that influence somatic participation include: (i) the diameter of axonal branches that contain coupling sites to other axons, because firing in larger branches injects more current into the main axon, increasing antidromic firing probability; (ii) axonal K+ currents and (iii) somatic hyperpolarization and shunting. We predict that portions of axons fire at high frequency during SPW‐R, while somata fire much less. In the model, somatic firing can occur by occasional generation of full action potentials in proximal axonal branches, which are excited by high‐frequency spikelets. When the network contains phasic synaptic inhibition, at the axonal gap junction site, gamma oscillations result, again with more frequent axonal firing than somatic firing. Combining the models, so as to generate gamma followed by sharp waves, leads to strong overlap between the population of cells firing during gamma and the population of cells firing during a subsequent sharp wave, as observed in vivo.
Human face recognition under occlusion using LBP and entropy weighted voting

In this paper a new block-based algorithm has been proposed to deal with facial occlusion when only one sample per person is available. A Local Binary Pattern (LBP) descriptor is applied on the image subblocks to extract distinctive texture features from those areas separately. Chi-Square is employed as histogram similarity metric in local classifiers corresponding to different image blocks. Finally, a weighted majority voting scheme is used for decision fusion. Local entropy is proposed to devote weights to classifiers results according to the block informative richness. This way, we can reduce the effect of blocks with appearance deformation on the final decision. Experimental results show the significantly high recognition accuracy of our method on the challenging AR face database compared to recent well-known approaches, without imposing computational complexity.
Real time analysis of the RNAI – RNAII – Rop complex by surface plasmon resonance : from a decaying surface to a standard kinetic analysis

J. Mol. Rec RNA loop–loop complexes are motifs that regulate biological functions in both prokaryotic and eukaryotic organisms. In E. coli, RNAI, an antisense RNA encoded by the ColE1 plasmid, regulates the plasmid replication by recognizing through loop–loop interactions RNAII, the RNA primer that binds to the plasmidic DNA to initiate the replication. Rop, a plasmid-encoded homodimeric protein interacts with this transient RNAI–RNAII kissing complex. A surface plasmon resonance (SPR)-based biosensor was used to investigate this protein-nucleic acid ternary complex, at 5-C, in experimental conditions such as the protein binds either to the loop–loop complex while it dissociates or to a saturated stable RNAI–RNAII surface. The results show that RNAI hairpin dissociates from the RNAII surface 110 times slower in the presence of Rop than in its absence. Rop binds to RNAI–RNAII with an on-rate of 3.6T 10M s and an off-rate of 0.11 s, resulting in a binding equilibrium constant equal to 31nM. A Scatchard-plot analysis of the interaction monitored by SPR confirms a 1:1 complex of Rop and RNAI–RNAII as observed for non-natural Rop–loop–loop complexes. Copyright # 2008 John Wiley & Sons, Ltd.
The role of the sympathetic nervous system in the circulatory response of the rabbit to arterial hypoxia.

In the unanaesthetized rabbit two patterns of circulatory response to arterial hypoxia have recently been described (Korner, 1965a). Moderate reduction in arterial Po2 to 35-40 mm Hg was accompanied by immediate elevation of the cardiac output, maintenance of the arterial pressure, and an increase in heart rate after a few minutes' hypoxia. On the other hand, marked reduction in arterial Po2 to 25-30 mm Hg resulted in a transient fall in cardiac output, bradycardia and a rise in blood pressure. The latter type of response, but not the former, resulted from strong stimulation of the arterial chemoreceptors. On the efferent side, the part played by the sympathetic nervous system in these responses has not been defined. Reports regarding its role in the commonly observed elevation of cardiac output in other species have been confficting. In unanaesthetized dogs previous removal of the cardiac sympathetic nerves reduced the rise in cardiac output and heart rate during moderate arterial hypoxia (Nahas, Mather, Wargo & Adams, 1954), in contrast to earlier findings in anaesthetized animals (Harrison, Blalock, Pilcher & Wilson, 1927). However, in man, prolonged treatment with Rauwolfia alkaloids did not prevent a rise in cardiac output (Chidsey, Frye, Kahler & Braunwald, 1961). Even in animals in which the sympathetic outflow had been blocked by spinal anaesthesia an increase in cardiac output still occurred in different types of hypoxia (Penna, Soma & Aviado, 1962; Oberg & Guyton, 1963). The present experiments assess the role of the sympathetic nervous system in the different circulatory responses of the rabbit in hypoxia, by using a competitive autonomic ganglion-blocking agent and selective block of the alphaand beta-adrenergic systems (Ahlquist, 1948; 1958; Ariens, 1960). Stimulation of the alpha-system results in sympathetic constrictor responses, whilst activation of the beta-system produces chronotropic and inotropic effects on the heart and certain peripheral dilator
Reduced specificity of functional connectivity in the aging brain during task performance

The importance of studying connectivity in the aging brain is increasingly recognized. Recent studies have shown that connectivity within the default mode network is reduced with age and have demonstrated a clear relation of these changes with cognitive functioning. However, research on age‐related changes in other functional networks is sparse and mainly focused on prespecified functional networks. Using functional magnetic resonance imaging, we investigated age‐related changes in functional connectivity during a visual oddball task in a range of functional networks. It was found that compared with young participants, elderly showed a decrease in connectivity between areas belonging to the same functional network. This was found in the default mode network and the somatomotor network. Moreover, in all identified networks, elderly showed increased connectivity between areas within these networks and areas belonging to different functional networks. Decreased connectivity within functional networks was related to poorer cognitive functioning in elderly. The results were interpreted as a decrease in the specificity of functional networks in older participants. Hum Brain Mapp 35:319–330, 2014. © 2012 Wiley Periodicals, Inc.
A multicenter study of burnout, depression, and quality of life in minority and nonminority US medical students.

OBJECTIVE To determine the well-being of minority medical students in a multicenter sample of US medical students. PARTICIPANTS AND METHODS All 1098 medical students at 3 medical schools in Minnesota were surveyed in April 2004. Validated instruments were used to assess burnout, depression, and quality of life (QOL). Students were also asked about the prevalence of significant personal life events in the previous 12 months and strategies used to cope with stress. RESULTS Although symptoms of depression and overall burnout were similar among minority and nonminority students, minority students were more likely to have a low sense of personal accomplishment (P=.02) and lower QOL In a number of domains (all P< or =.05). These differences persisted on multivariate analysis that controlled for demographic characteristics and recent life events. Minority students were also more likely to have a child (P=.01), originate from outside Minnesota (P<.001), and experience a major personal Illness in the last 12 months (P=.03). CONCLUSION As a group, the minority medical students in this survey had a lower sense of personal accomplishment and QOL than nonminority students. Additional studies are needed to provide insight regarding the causes of these inequities and the unique challenges faced by minority medical students. Efforts to improve minority students' well-being, QOL, and learning experience may help prevent attrition among minority medical students and promote diversification in the physician workforce.
Immediate loading in the maxilla using flapless surgery, implants placed in predetermined positions, and prefabricated provisional restorations: a retrospective 3-year clinical study.

BACKGROUND Immediate loading of dental implants shortens the treatment time and makes it possible to give the patient an esthetic appearance during the whole treatment period. PURPOSE The aim of the present study was to evaluate an immediate-loading treatment protocol, which included flapless surgery, implants placed in predetermined positions and connected to prefabricated provisional restorations, and the 3-year clinical results. MATERIALS AND METHODS A total of 97 Brånemark System Mk IV implants (Nobel Biocare AB, Gothenburg, Sweden) with a machined surface were inserted in the maxillas of 46 patients. A presurgical three-dimensional model of the patients' soft tissue and underlying alveolar bone anatomy was created, which allowed the clinician to place the implants in predetermined positions and connect them to prefabricated provisional restorations. A surgical template with drilling guides corresponding to each implant was used. The apical part of the master guide was equipped with a circular "mucotome," which punched out a 5 mm hole in the mucosa to eliminate the need for flap elevation. The patients received 25 fixed partial prostheses and 27 single-tooth restorations. Bone quality and quantity were assessed. Radiographic examinations were performed on the day of surgery/loading and at the 1-, 2-, and 3-year follow-up visits. RESULTS All implant sites showed intact buccal and lingual bone walls during surgery, confirming the accuracy of the bone-mapping procedure. The prefabricated temporary restorations fitted, meaning that the implants were positioned clinically in the same way as on the cast. Nine implants in eight patients failed during the first 8 weeks of loading. This resulted in a cumulative survival rate of 91% after 3 years of prosthetic load. The survival rate of splinted implants was 94%. The number of failed implants was significantly higher in cases of single-tooth replacements and placement in soft bone sites and smokers. The failed implants were successfully replaced according to a two-stage protocol. All patients finally received the expected restoration. The marginal bone resorption was on average 1.0 mm during the first year of loading, 0.4 mm during the second year, and 0.1 mm during the third year. CONCLUSIONS The study confirmed the feasibility of an immediate-loading treatment protocol in the maxilla, which included flapless surgery, implants and abutments placed in predetermined positions, and prefabricated provisional restorations. All failures occurred within the first 2 months of loading. The unchanged survival rate and the low average bone loss found during the following 34-month study period indicate a good long-term prognosis for the performed immediate-loading treatment.
Noonan's Syndrome and Autoimmune Diseases

Noonan's syndrome (NS) is a relatively common disease with an estimated incidence between 1/1,000 and 1/2,500 live births. NS is characterised by dysmorphic facies, short stature, chest deformity, ear abnormalities, cryptorchidism, ocular abnormalities, cubitus valgus, webbed neck, cutaneous and hair abnormalities, cardiovascular anomalies and delayed psychomotor development. The diagnosis rests solely on clinical criteria. Children with NS have a large number of potential health problems of which it is essential to be aware. Reports of autoimmune thyroiditis have been published. The aim of the present investigation was to study the prevalence of markers of autoimmune diseases, such as thyroglobulin antibodies (Tg-Ab) and antibodies to thyroid peroxidase (TPO-Ab) as well as IgA-antiendomysium antibodies (EMA) and IgA-antigliadin antibodies (AGA) in children with NS. As part of a Swedish multicenter trial to promote growth in patients with NS, Tg-Ab, TPOAb, AGA and EMA were measured in serum samples from 30 children, 16 girls and 14 boys, with NS, age range 3-20 years (mean age 12 years). All patients were diagnosed by one experienced clinician (O.W.) and evaluated according to the scoring system by Dunca et al. The control group comprised 386 schoolchildren, 199 girls and 187 boys, aged 11-13 years (mean 12 years). Tg-Ab were detected in 20% (6/30) and TPOAb in 10% ( 5 / 3 0 ) of the patients, as compared to 14% (54/386) and 6% (22/386) of the controls
The Effectiveness of Resisted Movement Training on Sprinting and Jumping Performance

Hrysomallis, C. The effectiveness of resisted movement training on sprinting and jumping performance. J Strength Cond Res 26(1): 299–306, 2012—Resisted movement training is that in which the sports movement is performed with added resistance. To date, the effectiveness on enhancing sprint speed or vertical jump height had not been reviewed. The objectives of this review were to collate information on resisted training studies for sprinting and vertical jumping, ascertain whether resisted movement training was superior to normal unresisted movement training, and identify areas for future research. The review was based on peer-reviewed journal articles identified from electronic literature searches using MEDLINE and SPORTDiscus data bases from 1970 to 2010. Resisted sprint training was found to increase sprint speed but, in most cases, was no more effective than normal sprint training. There was some evidence that resisted sprint training was superior in increasing speed in the initial acceleration phase of sprinting. Resisted jump training in the form of weighted jump squats was shown to increase vertical jump height, but it was no more effective than plyometric depth jump training. Direct comparisons between resisted jump training and unresisted normal jump training were limited, but loaded eccentric countermovement jump squat training with unloaded concentric phase and eccentric landing was shown to generate superior results for elite jumpers. More prospective studies on resisted sprint training are required along with monitoring both kinematic and kinetic adaptations to fully determine any underlying mechanisms for any improvements in sprint speed. Based on the available data, the benefits and superiority of resisted sprint training have not been fully established. As for resisted jump training, although there are some promising findings, these results need to be duplicated by other researchers before resisted jump training can be claimed to be more effective than other forms of jump training.
Lipid Mediator Informatics and Proteomics in Inflammation-Resolution

Lipid mediator informatics is an emerging area denoted to the identification of bioactive lipid mediators (LMs) and their biosynthetic profiles and pathways. LM informatics and proteomics applied to inflammation, systems tissues research provides a powerful means of uncovering key biomarkers for novel processes in health and disease. By incorporating them with system biology analysis, we review here our initial steps toward elucidating relationships among a range of bimolecular classes and provide an appreciation of their roles and activities in the pathophysiology of disease. LM informatics employing liquid chromatography-ultraviolet-tandem mass spectrometry (LC-UV-MS/MS), gas chromatography-mass spectrometry (GC-MS), computer-based automated systems equipped with databases and novel searching algorithms, and enzyme-linked immunosorbent assay (ELISA) to evaluate and profile temporal and spatial production of mediators combined with proteomics at defined points during experimental inflammation and its resolution enable us to identify novel mediators in resolution. The automated system including databases and searching algorithms is crucial for prompt and accurate analysis of these lipid mediators biosynthesized from precursor polyunsaturated fatty acids such as eicosanoids, resolvins, and neuroprotectins, which play key roles in human physiology and many prevalent diseases, especially those related to inflammation. This review presents detailed protocols used in our lab for LM informatics and proteomics using LC-UV-MS/MS, GC-MS, ELISA, novel databases and searching algorithms, and 2-dimensional gel electrophoresis and LC-nanospray-MS/MS peptide mapping.
In Vitro Antiviral Activity and Single-Dose Pharmacokinetics in Humans of a Novel, Orally Bioavailable Inhibitor of Human Rhinovirus 3C Protease

ABSTRACT (E)-(S)-4-((S)-2-{3-[(5-methyl-isoxazole-3-carbonyl)-amino]-2-oxo-2H-pyridin-1-yl}-pent-4-ynoylamino)-5-((S)-2-oxo-pyrrolidin-3-yl)-pent-2-enoic acid ethyl ester (Compound 1) is a novel, irreversible inhibitor of human rhinovirus (HRV) 3C protease {inactivation rate constant (Kobs/[I]) of 223,000 M−1s−1}. In cell-based assays, Compound 1 was active against all HRV serotypes (35 of 35), HRV clinical isolates (5 of 5), and related picornaviruses (8 of 8) tested with mean 50% effective concentration (EC50) values of 50 nM (range, 14 to 122 nM), 77 nM (range, 72 to 89 nM), and 75 nM (range, 7 to 249 nM), respectively. Compound 1 inhibited HRV 3C-mediated polyprotein processing in infected cells in a concentration-dependent manner, providing direct confirmation that the cell-based antiviral activity is due to inhibition of 3C protease. In vitro and in vivo nonclinical safety studies showed Compound 1 to be without adverse effects at maximum achievable doses. Single oral doses of Compound 1 up to 2,000 mg in healthy volunteers were found to be safe and well tolerated in a phase I-ascending, single-dose study. Compound 1 estimated free observed maximum concentration in plasma (Cmax) for 500-, 1,000-, and 2,000-mg doses were higher than the protein binding-corrected EC50 required to inhibit 80% of the HRV serotypes tested. Treatment of HRV 52-infected cells with one to five 2-h pulses of 150 nM Compound 1 (corresponding to the Cmax at the 500-mg dose) was sufficient to effect a significant reduction in viral replication. These experiments highlight Compound 1 as a potent, orally bioavailable, irreversible inhibitor of HRV 3C protease and provide data that suggest that Cmax rather than the Cmin might be the key variable predicting clinical efficacy.
Apoptosis in different compartments of antrum and corpus mucosa in chronic Helicobacter pylori gastritis. An 18-year follow-up study.

BACKGROUND The association of apoptosis was analysed in three different compartments (foveolar cells--FC, proliferating zone--PZ and glandular part--GP) of antrum and corpus mucosa specimens with development of atrophy and the extent of apoptosis as depending on grade of chronic inflammation, activity of gastritis and Helicobacter pylori colonization at two time points of an 18-year follow-up in an adult population from Saaremaa, Estonia, with a high prevalence of H. pylori infection were compared. METHODS A total of 68 persons (31 men, 37 women; median age, 39 years in 1979) from a primary sample of 304 subjects, endoscoped in 1979 and reinvestigated by endoscopy and biopsy in 1997, were included in the study. The state of the gastric mucosa and the presence of H. pylori in the antrum and corpus mucosa were assessed in accordance with the Sydney system. The dynamics of apoptotic index (AI) between two time points in 1979 and 1997 was evaluated in antrum biopsies of 49 persons and in corpus biopsies of 64 persons. Apoptosis was measured using terminal deoxyuridine nucleotide nick end labelling (TUNEL) histochemistry. RESULTS The antrum as well as the corpus of 2/68 persons were H. pylori negative at both time points. Atrophy developed in 9/68 persons in the antrum and in 23/68 in the corpus. In PZ and GP of the corpus mucosa as well as in GP of the antrum mucosa, AI decreased significantly during 18 years compared with initial values (P < 0.05), which was not associated with development of atrophy. In all compartments of the antrum and corpus mucosa, studied at the initial and end points of observation, AI did not reveal a difference in persons with and without development of atrophy (P > 0.05). In the samples of 1979 the highest independent effect on the value of AI in the FC compartment for the antrum was exerted by grade of activity of gastritis (P = 0.01) and in GP by degree of chronic inflammation (P = 0.03), while in the samples of 1997 the highest effect was exerted by grade of H. pylori colonization (P = 0.02 and 0.03 in FC and GP, respectively). For the corpus mucosa AI was most strongly affected also by grade of activity of gastritis in FC compartment (P = 0.02) and by degree of chronic inflammation in PZ (P = 0.04), but not by grade of H. pylori colonization. CONCLUSION AI was not associated with development of atrophy, but was largely dependent on grade of activity of gastritis and degree of chronic inflammation; in the antrum mucosa AI depended also on grade of H. pylori colonization.