Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular interactions of fission yeast Skp1 and its role in the DNA damage checkpoint

Skp1 is a central component of the E3 ubiquitin ligase SCF (Skp1‐Cullin‐1‐F‐box). It forms an adapter bridge between Cullin‐1 and the substrate‐determining component, the F‐box protein. In order to establish the role of Skp1, a temperature sensitive (ts) screen was carried out using mutagenic PCR (polymerase chain reaction) and 9 independent ts mutants were isolated. Mapping the mutated residues on the 3‐D structure of human Skp1 suggested that the mutants would be compromised in binding to F‐box proteins but not Cullin‐1 (Pcu1). In order to assess the binding properties of ts Skp1, 12 F‐box proteins and Pcu1 were epitope‐tagged, and co‐immunoprecipitation performed. This systematic analysis showed that ts Skp1 retains binding to Pcu1. However, binding to three specific F‐box proteins, essential Pof1, Pof3 involved in maintaining genome integrity, and nonessential Pof10, was reduced. skp1ts cells exhibit a G2 cell cycle delay, which is attributable to activation of the DNA damage checkpoint. Intriguingly, contrary to pof3 mutants, in which this checkpoint is required for survival, checkpoint abrogation in skp1ts suppresses a G2 delay and furthermore almost rescues the ts phenotype. The activation mechanism of the DNA damage checkpoint therefore differs between pof3Δ and skp1ts, implicating a novel role for Skp1 in the checkpoint‐signalling cascade.
A poliovirus hybrid expressing a neutralization epitope from the major outer membrane protein of Chlamydia trachomatis is highly immunogenic

Trachoma and sexually transmitted diseases caused by Chlamydia trachomatis are major health problems worldwide. Epitopes on the major outer membrane protein (MOMP) of C. trachomatis have been identified as important targets for the development of vaccines. In order to examine the immunogenicity of a recombinant vector expressing a chlamydial epitope, a poliovirus hybrid was constructed in which part of neutralization antigenic site I of poliovirus type 1 Mahoney (PV1-M) was replaced by a sequence from variable domain I of the MOMP of C. trachomatis serovar A. The chlamydial sequence included the neutralization epitope VAGLEK. This hybrid was viable, grew very well compared with PV1-M, and expressed both poliovirus and chlamydial antigenic determinants. When inoculated into rabbits, this hybrid was highly immunogenic, inducing a strong response against both PV1-M and C. trachomatis serovar A. Antichlamydia titers were 10- to 100-fold higher than the titers induced by equimolar amounts of either purified MOMP or a synthetic peptide expressing the VAGLEK epitope. Furthermore, rabbit antisera raised against this hybrid neutralized chlamydial infectivity both in vitro, for hamster kidney cells, and passively in vivo, for conjunctival epithelia of cynomolgus monkeys. Because poliovirus infection induces a strong mucosal immune response in primates and humans, these results indicate that poliovirus-chlamydia hybrids could become powerful tools for the study of mucosal immunity to chlamydial infection and for the development of recombinant chlamydial vaccines.
Investigation of the effect of conservative interventions in thumb carpometacarpal osteoarthritis: systematic review and meta-analysis

Abstract Purpose: The purpose of this study was to conduct a current review of randomized controlled trials regarding the effect of conservative interventions on pain and function in people with thumb carpometacarpal (CMC) osteoarthritis (OA), perform a meta-analysis of the findings and summarize current knowledge. Method: Data were obtained from MEDLINE, CINAHL, Embase, PEDro and CENTRAL databases from their inception to May 2014. Reference lists of relevant literature reviews were also searched. All published randomized trials without restrictions to time of publication or language were considered for inclusion. Study subjects were symptomatic adults with thumb CMC OA. Two reviewers independently selected studies, conducted quality assessment and extracted results. Data were pooled in a meta-analysis, when possible, using a random-effects model. Quality of the body evidence was assessed using GRADE approach. Results: Sixteen RCTs involving 1145 participants met the inclusion criteria. Twelve were of high quality (PEDro score > 6). We found moderate quality evidence that manual therapy and therapeutic exercise combined with manual therapy improve pain in thumb CMC OA at short- and intermediate-term follow-up, and from low to moderate quality evidences that magneto therapy improves pain and function at short-term follow-up. Orthoses (splints) were found to improve function at long-term follow-up and pinch strength at short-term follow-up. Finally, we found from very low to low-quality evidence that other conservative interventions provide no significant improvement in pain and in function at short- and long-term follow-up. Conclusions: Some of the commonly performed conservative interventions performed in therapy have evidence to support their use to improve hand function and decrease hand pain. Additional research is required to determine the efficacy of other therapeutic interventions that are performed with patients with thumb CMC OA. Implications for Rehabilitation Manual therapy and exercise are an effective means of improving pain and function at short-term follow-up by patients with thumb CMC OA. Magneto therapy, manual therapy, manual therapy and exercise and Orthoses (splints) were found to have clinically significant results. Very few of the included studies showed a clinically significant effect size in favor of treatment.
Laboratory detection of antiphospholipid antibodies

'Antiphospholipid' (aPL) antibodies are a heterogenous group of autoantibodies that are now considered to be directed mainly to plasma proteins or protein-phospholipid complexes 1. Standardisation of assays for anticardiolipin (aCL) antibodies and lupus anti coagulants (LA) have been fraught with difficulty despite numerous attempts to perform this by International Standardisation Workshops and Committees.
Differentiation and identification of Enterococcus durans, E. hirae and E. villorum

Aims: To compare different tests in the identification of Enterococcus durans, E. hirae and E. villorum strains. These bacteria belong to the E. faecium species group and are phylogenetically closely related, as evidenced by 16S rRNA sequence homologies of over 98·8%.
Path switching in content centric and named data networks

ICN communication is inherently multipath and potentially multi-destination. Content Centric and Named Data Networks at present do not offer a mechanism to direct traffic onto a specific path in multipath or a specific destination in a multi-destination environment, because the forwarding plane multiplexes packets across nexthops dynamically. This makes it challenging to provide practical multipath traceroute and ping applications, or implement multipath-aware congestion control, traffic engineering or SDN solutions. The symmetry of forward and reverse paths in Content Centric and Named Data Networks allows one to compute an end-to-end path label in a Data message on the reverse path and subsequently use this label to forward an Interest message through a specific nexthop. ICN Path Switching is a method of high-speed Interest forwarding in Content Centric and Named Data networks based on exact matching of a nexthop label retrieved from the Interest's path label against a nexthop ID in the ICN Forwarder's Adjacency database. ICN Path Switching maintains all major characteristics of CCN / NDN architectures, such as multicasting, caching, flow balance, etc. Simulations demonstrate that path labels are consistent with ICN control plane routing state in the presence of route updates. Analysis of ICN Path Switching with regards to Multiprotocol Label Switching (MPLS) and Segment Routing architectures suggests that it offers similar advantages at lower complexity with the potential to simplify network operations.
Technology-Assisted Rehabilitation of Writing Skills in Parkinson's Disease: Visual Cueing versus Intelligent Feedback

Recent research showed that visual cueing can have both beneficial and detrimental effects on handwriting of patients with Parkinson's disease (PD) and healthy controls depending on the circumstances. Hence, using other sensory modalities to deliver cueing or feedback may be a valuable alternative. Therefore, the current study compared the effects of short-term training with either continuous visual cues or intermittent intelligent verbal feedback. Ten PD patients and nine healthy controls were randomly assigned to one of these training modes. To assess transfer of learning, writing performance was assessed in the absence of cueing and feedback on both trained and untrained writing sequences. The feedback pen and a touch-sensitive writing tablet were used for testing. Both training types resulted in improved writing amplitudes for the trained and untrained sequences. In conclusion, these results suggest that the feedback pen is a valuable tool to implement writing training in a tailor-made fashion for people with PD. Future studies should include larger sample sizes and different subgroups of PD for long-term training with the feedback pen.
Evidence for an asthma risk locus on chromosome Xp: a replication linkage study

Background: Asthma is a complex genetic disorder characterized by chronic inflammation in the airways. Identification of genetic risk factors for asthma has been complicated due to genetic heterogeneity and influence from environmental risk factors. Despite the fact that multiple genetic linkage studies have been carried out the results are still conflicting and call for replication experiments. A Danish genome‐wide scan has prior reported evidence for candidate regions for asthma susceptibility genes on chromosomes 1p, 5q, 6p, 12q and Xp. Linkage to chromosome 12q was later confirmed in the same replication sample as used in the present study. The aim of the study was to replicate linkage to candidate regions for asthma in an independent Danish sample.
Physiological Roles of Three Na+/H+ Antiporters in the Halophilic Bacterium Vibrio parahaemolyticus

Vibrio parahaemolyticus mutants lacking three Na+/H+ antiporters (NhaA, NhaB, NhaD) were constructed. The AnhaA strains showed significantly higher sensitivity to LiCl regarding their growth compared to the parental strain. The AnhaA and AnhaB strains exhibited higher sensitivities to LiCl. The mutant XACabd lacking all of the three antiporters could not grow in the presence of 500 mM LiCl at pH 7.0, or 50 mM at pH 8.5. The XACabd mutant was also sensitive to 1.0 M NaCl at pH 8.5. These results suggest that Na+/H+ antiporters, especially NhaA, are responsible for resistance to LiCl and to high concentrations of NaCl. Reduced Na+/H+ and Li+/H+ antiport activities were observed with everted membrane vesicles of AnhaB strains. However, Li+/H+ antiport activities of AnhaB strains were two times higher than those of AnhaA strains when cells were cultured at pH 8.5. It seems that expression of nhaA and nhaB is dependent on medium pH to some extent. In addition, HQNO (2‐heptyl‐4‐hydroxyquinoline N‐oxide), which is a potent inhibitor of the respiratory Na+ pump, inhibited growth of XACabd, but not of the wild type strain. Moreover, survival rate of XACabd under hypoosmotic stress was lower than that of wild type strain. It is likely that the Na+/H+ antiporters are involved in osmoregulation under hypoosmotic stress. Based on these findings, we propose that the Na+/H+ antiporters cooperate with the respiratory Na+ pump in ionic homeostasis in V. parahaemolyticus
Electroluminescence From Two Junction Punch Through Structures in Silicon Nanowires

Hot carrier electroluminescence in two junction devices under punch through conditions manufactured in silicon on insulator nanowires are investigated. Of interest is the spectral content of the light emission, as well as the external power efficiency and the light extraction efficiency. An order of magnitude improvement in external power efficiency was achieved relative to a bulk silicon p-n junction in avalanche.
Endocan Is a Novel Chondroitin Sulfate/Dermatan Sulfate Proteoglycan That Promotes Hepatocyte Growth Factor/Scatter Factor Mitogenic Activity*

Proteoglycans that modulate the activities of growth factors, chemokines, and coagulation factors regulate in turn the vascular endothelium with respect to processes such as inflammation, hemostasis, and angiogenesis. Endothelial cell-specific molecule-1 is mainly expressed by endothelial cells and regulated by pro-inflammatory cytokines (Lassalle, P., Molet, S., Janin, A., Heyden, J. V., Tavernier, J., Fiers, W., Devos, R., and Tonnel, A. B. (1996) J. Biol. Chem. 271, 20458–20464). We demonstrate that this molecule is secreted as a soluble dermatan sulfate (DS) proteoglycan. This proteoglycan represents the major form either secreted by cell lines or circulating in the human bloodstream. Because this proteoglycan is specifically secreted by endothelial cells, we propose to name it endocan. The glycosaminoglycan component of endocan consists of a single DS chain covalently attached to serine 137. Endocan dose-dependently increased the hepatocyte growth factor/scatter factor (HGF/SF)-mediated proliferation of human embryonic kidney cells, whereas the nonglycanated form of endocan did not. Moreover, DS chains purified from endocan mimicked the endocan-mediated increase of cell proliferation in the presence of HGF/SF. Overall, our results demonstrate that endocan is a novel soluble dermatan sulfate proteoglycan produced by endothelial cells. Endocan regulates HGF/SF-mediated mitogenic activity and may support the function of HGF/SF not only in embryogenesis and tissue repair after injury but also in tumor progression.
Retinoic acid induced heparin‐binding protein expression and localization during gastrulation, neurulation, and organogenesis

Retinoic acid induced heparin‐binding protein (RIHB) is a highly basic, soluble polypeptide of the chick embryonic extracellular matrix. We have examined the expression and localization of RIHB during very early embryogenesis by in situ hybridization and immunohistochemistry. RIHB mRNA is very weakly detectable above background in the blastodiscs of unincubated eggs. The expression increases greatly over the first 24 hours of incubation, and is observed throughout the blastodisc in all three of the germ layers following gastrulation. As neurulation occurs, the expression becomes more restricted to certain areas, notably the ectoderm, the neural folds, and especially the notochord. After the neural tube has formed the expression in the tube itself decreases dramatically, whereas the expression in the head ectoderm and the notochord persists. After 72 hours of incubation expression remains relatively high throughout most of the embryo, with higher levels of expression in regions undergoing organogenesis and lower levels in organs which have already differentiated. RIHB protein is also weakly detectable in unincubated eggs as patches of immunoreactive material between the blastodisc and the vitelline. After 6 hours of incubation small regions of basement membrane are immunoreactive. RIHB is detected in this matrix, apparently before even fibronectin. The amount of RIHB protein increases dramatically over the first 24 hours of incubation. It is found in basement membrane separating the epiblast from the hypoblast, then later in that separating the ectoderm from the mesoderm. It is also detected surrounding individual cells, especially of the ectodermal layer. During neurulation RIHB is observed in the basement membrane surrounding the neural fold and the notochord, and in the lamina separating the ectodermal, mesodermal, and endodermal layers. Later in development, RIHB is detected in the basement membrane under the epidermis, throughout the developing limbs, and in the lamina of various developing organs, such as the eye, the pulmonary bud, the intestine, and the mesonephros. These results demonstrate that RIHB is highly expressed during the early embryonic period, by all three germ layers, and is an important and very early component of the embryonic extracellular matrix. Its very broad expression and localization argue for a more general role in development than its demonstrated weak neurotrophic activity. © 1994 Wiley‐Liss, Inc.
Application of a Fluorogenic PCR Assay for Typing and Subtyping of Influenza Viruses in Respiratory Samples

ABSTRACT A fluorogenic PCR-based method (TaqMan-PCR) was developed for typing and subtyping of influenza virus genomes in clinical specimens. The TaqMan-PCR employs a probe technology that exploits the endogenous 5′–3′ nuclease activity of the Taq DNA polymerase to allow direct detection of the amplicon by release of a fluorescent reporter during the PCR. Therefore, post-PCR analysis is avoided since hybridization with the fluorogenic probe and quantification of the amplified product is performed simultaneously during PCR cycling. The specificity of the method was evaluated on 86 influenza A (25 H1N1 and 61 H3N2) and 49 influenza B virus reference strains and isolates. The sensitivity of the technique was found to be at the level of 0.1 50% tissue culture infective dose. This TaqMan-PCR was applied prospectively to surveillance work by community-based sampling in Germany during the last two influenza seasons. Seven hundred five throat swabs were analyzed during the winter of 1997–1998. A total of 195 of 705 samples (28%) were positive by PCR. Influenza viruses could be isolated from 125 specimens (18%). During the 1998–1999 season, 1,840 respiratory samples were received. Influenza viruses were isolated from 281 specimens (15%) out of 525 throat swabs (29%) which were positive for influenza A or B virus by TaqMan-PCR. Further differentiation of influenza A virus-positive swabs revealed an intensive circulation of the subtype H3N2 during both seasons, 1997–1998 and 1998–1999. The TaqMan-PCR was much more sensitive than culture and revealed an excellent correlation for typing and subtyping of influenza viruses when samples were positive by both methods.
Results of a national asthma campaign survey of primary care in Scotland.

OBJECTIVE To identify within primary care in Scotland how far procedures for asthma review and patient education match guideline recommendations. DESIGN AND SETTING Telephone survey of a one in four stratified random sample of all 1058 general practices in Scotland. PARTICIPANTS Practice nurses, general practitioners. MAIN OUTCOME MEASURES Number of practices matching guideline recommendations for asthma review, targeting of care, use of structured asthma records, provision of management plans, education, and regular audit. RESULTS Of 276 general practices contacted 91% (251) completed the questionnaire; 93% (228) ran an asthma review service; 74% (166) employed a specially trained asthma nurse; 39% (106) had a policy for providing action plans; 63% (155) had carried out an asthma audit in the previous 3 years; 76% (218) used a structured tool in consultations, 46% with use of computer technology, 34% used only a manual stamp. Sixty-six per cent (173) had searched for patients overusing beta2 agonists; 32% (79) had searched for patients on medication treatment step 3 and above. Single- or two-partner practices were less likely to follow guideline recommendations but neither rurality nor deprivation was related to guideline compliance. CONCLUSIONS Three-quarters of Scottish general practices have trained asthma nurses and offer patients asthma review, but only a minority have proactive care procedures for targeting patients or a policy for providing patients with action plans. Practice systems are underused for identifying 'at-risk' patients. There is a need for proactive procedures and provision of self-management materials to patients. Access to trained asthma nurses needs to be improved.
In Vitro Osteogenic Differentiation of Adipose Stem Cells After Lentiviral Transduction With Green Fluorescent Protein

Background: Adipose-derived stem cells (ASCs) have the potential to differentiate into osteogenic cells that can be seeded into scaffolds for tissue engineering for use in craniofacial bone defects. Green fluorescent protein (GFP) has been widely used as a lineage marker for mammalian cells. The use of fluorescent proteins enables cells to be tracked during manipulation such as osteogenic differentiation within three-dimensional scaffolds. The purpose of this study was to examine whether ASCs introduced with GFP-encoding lentivirus vector exhibit adequate GFP fluorescence and whether the expression of GFP interfered with osteogenic differentiation of ASCs in both monolayer and three-dimensional scaffolds in vitro. Methods: Primary ASCs were harvested from the inguinal fat pad of Sprague Dawley rats. Isolated ASCs were cultured and infected with a lentiviral vector encoding GFP and plated into both monolayers and three-dimensional scaffolds in vitro. The cells were then placed in osteogenic medium. Osteogenic differentiation of the GFP-ASCs was assessed using alizarin red S, alkaline phosphate staining, and immunohistochemistry staining of osteocalcin with quantification of alizarin red S and osteocalcin staining. Results: The efficacy of infection of ASCs with a lentiviral vector encoding GFP was high. Cell-cultured GFP-ASCs remained fluorescent over the 8 weeks of the study period. The GFP-ASCs were successfully induced into osteogenic cells both in monolayers and three-dimensional scaffolds. Whereas the quanitification of alizarin red S revealed no difference between osteoinduced ASCs with or without GFP, the quantification of osteocalcin revealed increased staining in the GFP group. Conclusions: Transduction of isolated ASCs using a lentiviral vector encoding GFP is an effective method for tracing osteoinduced ASCs in vitro. Quantification data showed no decrease in staining of the osteoinduced ASCs.
Neurotrophic Keratopathy: Therapeutic Approach Using a Novel Matrix Regenerating Agent.

PURPOSE To evaluate the efficacy and tolerance of a new matrix-regenerating agent (RGTA), Cacicol®, a polymer that mimics heparan sulfates bound to extracellular matrix proteins, avoiding its proteolysis, to treat neurotrophic keratopathy (NK). METHODS Uncontrolled prospective clinical study performed between January 2014 and May 2016. Twenty-five patients (25 eyes) with corneal neurotrophic ulcers, nonresponsive to at least 2 weeks of conservative therapy, were treated with Cacicol, instilled once/twice a week. During follow-up, slit-lamp examination, anterior segment photography, fluorescein-dye testing, and best-corrected visual acuity were analyzed. Ulcer evolution was evaluated using image analysis software (ImageJ®) and healing defined as decrease of the corneal ulcer area. An independent observer measured ulcer area. RESULTS All patients had complete corneal healing within an average of 4.13 ± 2.32 weeks. Mean ulcer area decreased significantly (P = 0.001) from 16.51% ± 18.56% (1st day) to 8.68% ± 11.25% at the 7th day and to 4.73% ± 10.75% at the 14th day. Compared with day 1, mean ulcer area decreased 60.24% after 7 days (P = 0.001), 54.92% after 14 days (P = 0.059), and 83.00% after 21 days (P = 0.003). Two cases of recurrence (8.0%) were registered. No systemic or local side effects were noticed. CONCLUSIONS The new regenerating agent, Cacicol, represents an effective and safe therapy to treat NK.