Miracle-dz/UniFAR-FTUs huggingface dataset:
EGF receptor residues Leu679, Leu680 mediate selective sorting of ligand‐receptor complexes in early endosomal compartments

Dileucine‐based motifs have been shown to regulate endosomal sorting of a number of membrane proteins. Previously, we have shown that the dileucine motif Leu679, Leu680 in the juxtamembrane domain of the human epidermal growth factor receptor is involved in the endosome‐to‐lysosome transport of ligand‐receptor complexes. Substitution of alanine residues for Leu679, Leu680 led to a reduction in ligand‐induced receptor degradation without affecting internalization. In the current study, we have further characterized ligand‐dependent intracellular sorting of EGF receptors containing a L679A, L680A. Immunocytochemical studies reveal that although mutant receptors redistribute from the cell surface to transferrin receptor‐positive endocytic vesicles similar to wild‐type following ligand stimulation, their accumulation in Lamp‐1‐positive late endosomes/lysosomes is retarded compared to wild‐type. Kinetic analysis of 125I‐EGF trafficking shows that reduced accumulation of internalized mutant receptors in Lamp‐1–positive vesicles is due to rapid recycling of ligand‐receptor complexes from early endocytic compartments. In addition, the fraction of intracellular 125I‐EGF that is transported to late endocytic compartments in cells with mutant receptors is not as efficiently degraded as it is in cells with wild‐type receptors. Furthermore, wild‐type receptors in endocytic vesicles isolated by Percoll gradient fractionation are more resistant to in vitro digestion with proteinase K than mutant receptors. We propose that mutant receptors interact inefficiently with lysosomal sorting machinery, leading to their increased recycling. Our results are consistent with a model in which the Leu679, Leu680 signal facilitates sequestration of ligand‐receptor complexes into internal vesicles of multivesicular endosome‐to‐lysosome transport intermediates. J. Cell. Physiol. 185:47–60, 2000. © 2000 Wiley‐Liss, Inc.
Structural Studies on Molecular Interactions between Camel Peptidoglycan Recognition Protein, CPGRP-S, and Peptidoglycan Moieties N-Acetylglucosamine and N-Acetylmuramic Acid*

Background: PGRP-S is an innate immunity protein that protects hosts from invading microbes. Results: CPGRP-S forms linear polymers with alternating A-B and C-D contacts, and both GlcNAc and MurNAc bind at the same subsite. Conclusion: The mode of binding of camel PGRP-S is different from other PGRPs. Significance: The better antibacterial properties of camel PGRP-S can be exploited for therapeutic applications. Peptidoglycan (PGN) consists of repeating units of N-acetylglucosamine (GlcNAc) and N-acetylmuramic acid (MurNAc), which are cross-linked by short peptides. It is well known that PGN forms a major cell wall component of bacteria making it an important ligand for the recognition by peptidoglycan recognition proteins (PGRPs) of the host. The binding studies showed that PGN, GlcNAc, and MurNAc bind to camel PGRP-S (CPGRP-S) with affinities corresponding to dissociation constants of 1.3 × 10−9, 2.6 × 10−7, and 1.8 × 10−7 m, respectively. The crystal structure determinations of the complexes of CPGRP-S with GlcNAc and MurNAc showed that the structures consist of four crystallographically independent molecules, A, B, C, and D, in the asymmetric unit that exists as A-B and C-D units of two neighboring linear polymers. The structure determinations showed that compounds GlcNAc and MurNAc bound to CPGRP-S at the same subsite in molecule C. Both GlcNAc and MurNAc form several hydrogen bonds and extensive hydrophobic interactions with protein atoms, indicating the specific nature of their bindings. Flow cytometric studies showed that PGN enhanced the secretions of TNF-α and IL-6 from human peripheral blood mononuclear cells. The introduction of CPGRP-S to the PGN-challenged cultured peripheral blood mononuclear cells reduced the expressions of proinflammatory cytokines, TNF-α and IL-6. This showed that CPGRP-S inhibited PGN-induced production of proinflammatory cytokines and down-regulated macrophage-mediated inflammation, indicating its potential applications as an antibacterial agent.
EFFECT OF ORAL SENSORIMOTOR TREATMENT ON MEASURES OF GROWTH, EATING EFFICIENCY AND ASPIRATION IN THE DYSPHAGIC CHILD WITH CEREBRAL PALSY

Twenty‐seven children (mean age 5.1 years) with cerebral palsy and moderate eating impairment were studied to determine frequency of aspiration and the effect of 10 and 20 weeks of oral sensorimotor therapy on eating efficiency and measures of growth (weight, skinfold thickness). The eating efficiency of the children did not change markedly in response to oral sensorimotor therapy. Children maintained their centile rank in weight‐for‐age and skinfold‐for‐age measurements. However, there was no catch‐up growth. The findings suggest that eating efficiency is not a good estimator of treatment outcome, but rather a diagnostic indicator of the severity of eating impairment. Monitoring of these children's growth is essential in order to provide nutritional rehabilitation as soon as their eating skills can no longer keep up with growth demands.
[Epidemiologic aspect of lyme borreliosis among the inhabitants of Podlasie Province].

UNLABELLED The aim of this study was to evaluate Lyme borreliosis morbidity among the inhabitants of Podlasie Province in the years of 1996-2000. MATERIAL AND METHODS The new cases of Lyme borreliosis reported in the years of 1996-2000 in Podlasie Province were analyzed. The analysis included the data from Mz-56 and Mz-57 forms and the information from epidemiologic investigations sent to Regional Sanitary and Epidemiologic Station in Bialystok. In 1996-2000, screening examinations were carried out in the same group of 358 forestry workers including 44 (12.29%) females and 314 (87.71%) males aged from 21 to 64 (x = 41.2) years. Immunoenzymatic test of ELISA Borrelia recombinant IgM and IgG by Biomedica firm (Austria) were used to detect B. burgdorferi antibodies. RESULTS In 1996-2000, 4933 of borreliosis cases were registered in Poland including 1377 (27.91%) in Podlasie Province. The morbidity rate in Podlasie province ranged from 15.05% in 1996 year to 21.29% in 2000 year of the whole country morbidity. At the same time, the incidence rate in Podlasie Province ranged from 9.09 in 1996 to 32.2 in 2000 year and was 6.72-fold higher than the incidence rate in the whole country. In Eastern and Central region of the province, 80.54% of cases were registered whereas, 14.09% by the Lakeside of Augustów and Suwalki only 5.37% in the western region of the province. It was proved that the morbidity increased in proportion to the age of patients (41.39% of patients were at the age of 30-49) and it decreased only above the age of 60. Thus, Lyme borreliosis affects mainly people at working age. The increase in B. burgdorferi antibody detectability was noticed in the population of forestry workers; it was detected in 38.55% in 1995 and in 2000 in 43.56% of the examined. Interestingly, 81 people infected with B.b in 1995-2000 included 74 men and only 7 women, supporting the statement that B.b infection affects mainly working professionals and the risk increases with the practice. CONCLUSIONS Our studies indicate that Lyme borreliosis is a serious health problem among the inhabitants of Podlasie Province which is an endemic area for Ixodes ricinus ticks infected with B. burgdorferi spirochete.
Cost per care of the first year of direct antiviral agents in the Liguria Region: a multicenter analysis

Aims Despite the remarkable efficacy shown in clinical practice, concerns have been raised about the costs associated with direct antiviral agent (DAA) therapy. This article presents the real-life costs for DAA treatment sustained by the Italian National Health Service in the Liguria Region (Northern Italy). Methods A retrospective analysis of the cost per care sustained for DAA treatment, relating to the period from January 1 to December 31, 2015 in five centers in Liguria was performed. All patients undergoing DAA-based treatments for hepatitis C virus (HCV) infection were enrolled. On-treatment costs included: HCV treatment, laboratory test, outpatient services, attended visits, drugs used for the management of adverse events (erythropoietin, albumin or red blood cell packs) and inpatient service admissions. Results In total, 327 patients were enrolled. No difference in terms of sustained virologic response (SVR) rate among different treatments was reported. The majority (85.0%) of patients did not report any side effects and only 15 (4.6%) required hospital admission. Forty-two patients (12.8%) required high-cost drugs for the management of adverse events. The overall cost sustained was €14,744,433. DAA±ribavirin (RBV) accounted for the wide majority of this cost (98.9%; €14,585,123). Genotype (GT) 1, the most commonly treated GT, was associated with an average cost of €43,445 per patient. Detailed analysis of the costs for GT 1 showed the treatment based on ritonavir boosted paritaprevir/ombitasvir + dasabuvir±RBV with an average cost of €24,978 (RBV+) and €25,448 (RBV−) per patient was the most cost-effective. The average cost per SVR was €48,184. Once again, the ritonavir boosted paritaprevir/ombitasvir + dasabuvir regimen was associated with the lowest cost/SVR (€25,448/SVR [GT 1b] and similar results for other GTs). Conclusion Antiviral regimen is the major contributor to costs in the treatment of HCV infection. Appropriate regimen selection could result in a major cost saving, which can be reinvested to allow more patients to be treated.
Are Adolescent Boys with Klinefelter Syndrome Androgen Deficient? A Longitudinal Study of Finnish 47,XXY Boys

Testosterone (T)-substitution therapy is widely used in adult patients with Klinefelter syndrome (KS) to prevent symptoms and sequels of androgen deficiency, but it is currently unknown if adolescent boys with KS benefit from early T therapy. To evaluate the optimal age to start T substitution, we searched for signs of androgen deficiency in pubertal boys with KS. 14 nonmosaic 47,XXY boys, aged 10–13.9 y, were followed up for 4–37 mo with staging of puberty and frequent reproductive hormone measurements. Furthermore, indices reflecting androgen action (serum SHBG, leptin, and prostate-specific antigen (PSA) levels) were studied. Both onset and progression of puberty according to Tanner stages were normal in boys with KS. Consistently, serum T concentrations increased as expected and remained normal throughout follow-up. Changes in the indices of androgen action (decreases in serum SHBG and leptin, and increase in serum PSA concentrations) occurred normally, except that average leptin levels were higher in the boys with KS (KS boys 11.8 ± 7.0 μg/L; controls 7.6 ± 4.7 μg/L; p = 0.033). Despite normal T concentrations, the KS boys displayed from the age of 13 y elevated serum FSH and LH levels, and exaggerated gonadotropin responses to gonadotropin-releasing hormone. These data do not demonstrate an unequivocal androgen deficiency in adolescent boys with KS that would necessitate androgen supplementation therapy during early puberty.
Quality and Antioxidant Properties of Fresh-cut Apple Wedges from 10 Cultivars During Modified Atmosphere Packaging Storage

Antioxidant activity and quality parameters of skin-on apple wedges from 10 cultivars were examined during chill storage and over two growing seasons. Storage of fresh-cut apple wedges had a significant impact on quality parameter indices such as browning index (p < 0.001) and texture firmness (p < 0.001). Headspace gas analysis indicated that the degree of browning negatively correlated to oxygen (-0.69) and positively (0.70) correlated to carbon dioxide levels. Antioxidant capacity as assessed by three in vitro methods (DPPH, FRAP and ORAC) decreased significantly for 9 of the 10 cultivars after 5 days of storage at 3 ± 1 °C (p < 0.001). These indices increased in case of Shampion apples over the same storage period for all three assays. With regard to antioxidant capacity and quality parameters, the cultivars Gloster, Alwa, Idared and Jonica were the best performing overall and could therefore be recommended as a core ingredient in fresh-cut fruit products.
Disclosing the Role of IT Suppliers as Digital Innovation Enablers for SMEs: A Strategy Analysis of the European IT Sales Channel

As Information Technologies (IT) play a growingly strategic role in several industries, Small and Medium Enterprises (SMEs) adopt IT solutions to trigger Digital Innovation supporting their processes and improving their products and services. SMEs' scarce resources and inadequate IT competencies forces them to demand support from IT suppliers in the IT adoption and Digital Innovation journey, however, little attention was paid to the business models and strategies of IT suppliers in the academic and professional literature, and SMEs find it difficult to assess and select IT suppliers that best responds to their needs and aims. This study's goal is to provide a detailed picture of the IT Sales Channel and its players in the European market. A classification framework is proposed and eleven different business models are identified. The study leverages multiple case studies relying on semi-standardized interviews with Chief Executive Officers and Marketing Managers of leading European IT suppliers.
Gilles de la tourette syndrome: Clinical and family study of 50 cases

Fifty patients with Tourette syndrome were evaluated; data included family history, clinical characteristics, response to haloperidol, and side effects during haloperidol therapy. Sixteen patients had a family history of Tourette syndrome, and another 16 had a family history of tics. Twenty‐four families had more than 2 members with Tourette syndrome or tics. There was no preponderance of families with a Jewish, Eastern European background in this sample. Thirty‐four patients had obsessive‐compulsive behavior. Among the 50 patients there was a high frequency of sleep disturbance, learning disability, self‐destructive behavior, inappropriate sexual activity, and antisocial behavior. Family history was significantly related to the occurrence of sleep distrubance, obsessivecompulsive behavior, haloperidol response, and the frequency of side effects caused by haloperidol. The precise mode of genetic transmission in familial Tourette syndrome remains to be determined.
Integrated pest management of “Golden Delicious” apples

Monitoring of plant protection product (PPP) residues in “Golden Delicious” apples was performed in 2011–2013, where 216 active substances were analysed with three analytical methods. Integrated pest management (IPM) production and improved IPM production were compared. Results were in favour of improved IPM production. Some active compounds determined in IPM production (boscalid, pyraclostrobin, thiacloprid and thiametoxam) were not found in improved IPM production. Besides that, in 2011 and 2012, captan residues were lower in improved IPM production. Risk assessment was also performed. Chronic exposure of consumers was low in general, but showed no major differences for IPM and improved IPM production for active substances determined in both types of production. Analytical results were compared with the European Union report of 2010 where 1.3% of apple samples exceeded maximum residue levels (MRLs), while MRL exceedances were not observed in this survey.
Motor-unit categorization based on contractile and histochemical properties: a glycogen depletion analysis of normal and reinnervated rat tibialis anterior muscle.

1. Isolated and glycogen-depleted motor units (MUs) have been studied in normal and reinnervated tibialis anterior (TA) muscles of the rat to examine 1) the correspondence between physiological and histochemical classifications, 2) the extent to which unit properties cluster according to type, 3) the relation between unit force and fatigability, and 4) the extent to which reinnervated MUs recover their former properties. 2. MUs were isolated by ventral root dissection and stimulation in reinnervated and normal TA muscles, 3.5-8 mo after common peroneal (CP) nerve section and resuture and in age-matched control rats, respectively. The units were characterized physiologically for classification into four types: slow twitch (S), fast twitch, fatigue resistant (FR), fast twitch fatigue intermediate (FI), and fast twitch fatigue sensitive (FF). Four muscle fiber types were identified histochemically with the use of a modification of the techniques of Brooke and Kaiser, and Guth and Samaha to delineate fiber subtypes on the basis of the pH sensitivity of myofibrillar adenosine triphosphatase (ATPase). 3. Neither the time-to-peak twitch force development nor the profile of unfused tetanus ("sag test") was unambiguous in separating fast from slow MUs. However, all units with a time to peak greater than 22 ms were fatigue resistant, and this time was chosen to delineate fast from slow. The fast unit population was further subdivided on the basis of their fatigability. There is normally a small proportion of S units (6% S) that increased to 20% after reinnervation. Although the fast population was subdivided, there was a continuous distribution of fatigue indexes in normal and reinnervated muscles with the highest number of fast units falling into the FI category. The proportions of fast units were 28% FR, 45% FI, and 21% FF in normal muscles and 29% FR, 38% FI, and 13% FF in reinnervated muscles. 4. In normal muscles, delineation of fast and slow fibers and subdivision of fast fiber types on the basis of acid and alkali stability of myofibrillar ATPase provided a histochemical classification that showed 78% correspondence with physiological classification of the same identified units. In reinnervated muscles the correspondence between physiological and histochemical classifications was reduced to 72%. 5. The normal correlation between MU fatigability and isometric force in TA muscles was not seen in reinnervated muscles that contained more FR MUs. Mean fatigue index from normal units was significantly less at 0.55 +/- 0.03 (mean +/- SE) compared with 0.68 +/- 0.03 from reinnervated units. (ABSTRACT TRUNCATED AT 400 WORDS)
Identification and characterization of ANKK1: A novel kinase gene closely linked to DRD2 on chromosome band 11q23.1

The dopamine D2 receptor has been extensively studied in relation to alcoholism, substance abuse, and nicotine dependence. The most frequently examined polymorphism linked to this gene is the Taq1A restriction fragment length polymorphism (RFLP) (dbSNP rs1800497; g.32806C>T in GenBank AF050737.1), which has been associated with a reduction in D2 receptor density, although this is not universally accepted. The Taq1A RFLP lies 10 kB downstream of DRD2 and may therefore fall within a different coding region than the DRD2 gene or within a regulatory region. Within this downstream region, we have identified a novel kinase gene, named ankyrin repeat and kinase domain containing 1 (ANKK1), which contains a single serine/threonine kinase domain and is expressed at low levels in placenta and whole spinal cord RNA. This gene is a member of an extensive family of proteins involved in signal transduction pathways. The DRD2 Taq1A RFLP is a single nucleotide polymorphism (SNP) that causes an amino acid substitution within the 11th ankyrin repeat of ANKK1 (p.Glu713Lys), which, while unlikely to affect structural integrity, may affect substrate‐binding specificity. If this is the case, then changes in ANKK1 activity may provide an alternative explanation for previously described associations between the DRD2 Taq1A RFLP and neuropsychiatric disorders such as addiction. Hum Mutat 23:540‐545, 2004. © 2004 Wiley‐Liss, Inc.
Heteromorphism of “Homomorphic” Sex Chromosomes in Two Anole Species (Squamata, Dactyloidae) Revealed by Synaptonemal Complex Analysis

Iguanians (Pleurodonta) are one of the reptile lineages that, like birds and mammals, have sex chromosomes of ancient origin. In most iguanians these are microchromosomes, making a distinction between the X and Y as well as between homeologous sex chromosomes in other species difficult. Meiotic chromosome analysis may be used to elucidate their differentiation, because meiotic prophase chromosomes are longer and less condensed than metaphase chromosomes, and the homologues are paired with each other, revealing minor heteromorphisms. Using electron and fluorescent microscopy of surface spread synaptonemal complexes (SCs) and immunolocalization of the proteins of the SC (SYCP3), the centromere, and recombination nodules (MLH1), we examined sex chromosome synapsis and recombination in 2 species of anoles (Dactyloidae), Anolis carolinensis and Deiroptyx coelestinus, in which the sex chromosomes represent the ancestral condition of iguanians. We detected clear differences in size between the anole X and Y microchromosomes and found an interspecies difference in the localization of the pseudoautosomal region. Our results show that the apparent homomorphy of certain reptile sex chromosome systems can hide a cryptic differentiation, which potentially may influence the evolution of sexual dimorphism and speciation.
The Effects of Nigella Sativa Seed Extract on Bone Healing in an Experimental Model

AbstractThe purpose of this study was to histologically evaluate the effects on bone healing of nigella sativa seed extract applied on calvarial defects in an ovariectomized rat model. The study included 32 female rats weighing 280 to 310 g with an average age of 3 months. A defect was created with a trephine burr on each rat calvarium. The rats were divided into 2 groups (control and study) of 8 animals each. All the defects were grafted with a gelatin sponge mixed with normal saline. In the study group, nigella sativa seed extract was applied systemically using an oro-gastric tube. Half of the animals in each group were sacrificed after 2 weeks, and the others after 4 weeks. In the control groups, the defects were not completely filled with regenerated bone. Osteoblast cells were observed more in the study groups. A higher rate of osteoclasts was determined in the control groups. In addition, the nigella sativa group had a statistically greater amount of bone formation than the others group at both 2 weeks and 4 weeks (P <0.05). The systemic application of nigella sativa seed extract demonstrated incredibly positive effects on enhanced bone healing in this experimental osteoporotic model.
[Prognostic factors associated with resectable pulmonary metastases from colorectal cancer].

OBJECTIVE To analyze prognostic factors associated with survival in a group of patients who underwent resection of pulmonary metastases from colorectal cancer. PATIENTS AND METHODS A retrospective review was performed for 55 consecutive patients who had undergone resection of pulmonary metastases from colorectal adenocarcinoma between January 1993 and June 2004. Univariate and multivariate analyses were performed to assess the effect of the recorded variables on overall survival. RESULTS Median overall survival was 32.9 months and the probability of survival at 1, 3, and 5 years was 79%, 44%, and 22%, respectively. Survival was lower in patients in whom the largest metastasis was at least 4 cm (8.6 vs 34.5 months, P=.0085) and in patients with elevated levels of carcinoembryonic antigen (24.5 vs 41.4 months, P=.05). Significantly longer survival was observed in patients who received adjuvant chemotherapy after surgery (49.8 vs 30.9 months, P=.0058). Preoperative positron emission tomography (PET) and the absence of previous or synchronous liver metastases were associated with a nonsignificant trend toward increased survival. In the multivariate analysis, only size of the largest pulmonary metastasis influenced overall survival (P=.036). CONCLUSIONS The preoperative variables that best predicted survival in our patients were size of the largest pulmonary metastasis and the level of carcinoembryonic antigen. Prospective studies are needed to determine the usefulness of PET for tumor staging prior to resection of pulmonary metastases.