Miracle-dz/UniFAR-FTUs huggingface dataset:
TPX2 Inhibits Eg5 by Interactions with Both Motor and Microtubule*

Background: TPX2 is a mitotic microtubule-associated protein that regulates the kinesin, Eg5. Results: Full-length TPX2 is a more potent inhibitor of Eg5 velocity than truncated TPX2; differential regulation by TPX2 was not observed for monomeric Eg5. Conclusion: TPX2 inhibits Eg5 as a roadblock and by direct interaction with Eg5. Significance: TPX2 may contribute to the spatial and temporal regulation of the mitotic motor Eg5. The microtubule-associated protein, TPX2, regulates the activity of the mitotic kinesin, Eg5, but the mechanism of regulation is not established. Using total internal reflection fluorescence microscopy, we observed that Eg5, in extracts of mammalian cells expressing Eg5-EGFP, moved processively toward the microtubule plus-end at an average velocity of 14 nm/s. TPX2 bound to microtubules with an apparent dissociation constant of ∼200 nm, and microtubule binding was not dependent on the C-terminal tails of tubulin. Using single molecule assays, we found that full-length TPX2 dramatically reduced Eg5 velocity, whereas truncated TPX2, which lacks the domain that is required for the interaction with Eg5, was a less effective inhibitor at the same concentration. To determine the region(s) of Eg5 that is required for interaction with TPX2, we performed microtubule gliding assays. Dimeric, but not monomeric, Eg5 was differentially inhibited by full-length and truncated TPX2, demonstrating that dimerization or residues in the neck region are important for the interaction of TPX2 with Eg5. These results show that both microtubule binding and interaction with Eg5 contribute to motor inhibition by TPX2 and demonstrate the utility of mammalian cell extracts for biophysical assays.
Autologous HIV‐1 Neutralizing Antibodies: Emergence of Neutralization‐Resistant Escape Virus and Subsequent Development of Escape Virus Neutralizing Antibodies

The capacity of consecutive human sera to neutralize sequentially obtained autologous virus isolates was studied. HIV-I was isolated three times over a 48–164-week period from three individuals immediately after serocon-version and from two individuals in later stages of infection. Development of neutralizing antibodies to the primary virus isolates was detected 13–45 weeks after seroconversion. Emergence of escape virus with reduced sensitivity to neutralization by autologous sera was demonstrated. The patients subsequently developed neutralizing antibodies against the escape virus but after a delay. Titers of neutralizing antibodies against late virus isolates were generally low compared to initial neutralizing titers against primary virus isolates. The delay in appearance of neutralizing antibodies to the dominant viral strain at any time in the patient and the emergence of neutralization resistant escape virus may be part of the explanation of the apparent failure of the immune system to control HIV infection.
Effect of Capsular Injury on Acromioclavicular Joint Mechanics

Background: Traumatic disruption of the acromioclavicular joint capsule is associated with pain and instability after the injury and may lead to degenerative joint disease. The objective of this study was to quantify the effect of transection of the acromioclavicular joint capsule on the kinematics and the in situ forces in the coracoclavicular ligaments in response to external loading conditions. Methods: Eleven fresh-frozen human cadaveric shoulders were tested with use of a robotic/universal force-moment sensor testing system. The shoulders were subjected to three loading conditions (an anterior, posterior, and superior load of 70 N) in their intact state and after transection of the acromioclavicular joint capsule. Results: Transection of the capsule resulted in a significant (p < 0.05) increase in anterior translation (6.4 mm) and posterior translation (3.6 mm) but not in superior translation (1.6 mm). The effect of capsule transection on the forces in the coracoclavicular ligaments was also significant (p < 0.05) in response to anterior and posterior loading but not in response to superior loading. However, differences were found between the forces in the trapezoid and conoid ligaments. Under an anterior load, the mean in situ force (and standard deviation) in the trapezoid increased from 14 ± 14 N to 25 ± 19 N, while the mean force in the conoid increased from 15 ± 14 N to 49 ± 23 N, or 227%. In contrast, in response to a posterior load, the mean in situ force in the trapezoid increased from 23 ± 15 N to 38 ± 23 N, or 66% (p < 0.05), while the mean force in the conoid increased only 9%. Conclusions and Clinical Relevance: The large differences in the change of force in the conoid and trapezoid ligaments suggest that these ligaments should not be considered as one structure when surgical treatment is considered. Furthermore, transection of the capsule resulted in a shift of load to the coracoclavicular ligaments, which may render the intact coracoclavicular ligaments more likely to fail with anterior or posterior loading. The results of the present study also suggest that the intact coracoclavicular ligaments cannot compensate for the loss of capsular function during anterior-posterior loading as occurs in type-II acromioclavicular joint injuries.
Selection of Insensitive Acetylcholinesterase as a Resistance Mechanism in Aedes aegypti (Diptera: Culicidae) from Santiago de Cuba

Abstract A sample of Aedes aegypti (L.) (Diptera: Culicidae) from Santiago de Cuba, Cuba, with a high level of propoxur resistance compared with the reference susceptible Rockefeller strain (12.60× at the 50% lethal concentration [LC50] and 18.08 at the 90% lethal concentration [LC90]), with a 4.3% frequency of insensitive acetylcholinesterase (AChE) frequency, was subjected to propoxur selection for 13 successive generations to increase the frequency of this resistance mechanism in Ae. aegypti. High resistance to propoxur was developed during this selection (41.73-fold), and the frequency of insensitive AChE mechanism was increased 13.25-fold. Other mechanisms (overproduced esterases, glutathione transferases, or monooxygenases) were not detected in the propoxur-selected strain. The selection of an insensitive AChE resistance mechanism in Ae. aegypti has important implications and will be a valuable resource for genetic studies and molecular characterization of the ace gene mutation(s) associated with insecticide resistance in Ae. aegypti.
Isoform-specific Regulation of Akt Signaling by the Endosomal Protein WDFY2*

Recent work has led to the identification of novel endocytic compartments with functional roles in both protein trafficking and growth factor signal transduction. The phosphatidylinositol 3-phosphate binding, FYVE domain-containing protein WDFY2 is localized to a distinct subset of early endosomes, which are localized close to the plasma membrane. Here, we find that the serine/threonine kinase Akt interacts with these endosomes in an isoform-specific manner. Using quantitative fluorescence microscopy we demonstrate specific co-localization of WDFY2 with endogenous Akt2, but not Akt1. Moreover, depletion of WDFY2 leads to impaired phosphorylation of Akt in response to insulin due to isoform specific reduction of Akt2, but not Akt1, protein levels, and to a marked reduction in the insulin-stimulated phosphorylation of numerous Akt substrates. This is accompanied by an impairment in insulin-stimulated glucose transport and, after prolonged silencing, a reduction in the level of expression of adipogenic genes. We propose that WDFY2-enriched endosomes serve as a scaffold that enables specificity of insulin signaling through Akt2.
Nonlinear amplitude compression in magnetic resonance imaging: quantization noise reduction and data memory saving

Dynamic range improvement in magnetic resonance imaging (MRI) by nonlinear amplitude compression is proposed. Quantization noise reduction by a factor of 10 to 20 is confirmed by a numerical simulation, provided an appropriate nonlinear transform is chosen. The piecewise-linear transform is the best nonlinear transform studied so far. Implementing amplitude compression requires no additional hardware in a usual MRI system if the low spatial frequency lines of the magnetic resonance (MR) signal are selectively prescanned through an attenuator. The method will be particularly effective in 3-D imaging of large objects. MR angiography, and imaging of solids. <<ETX>>
‘Do not resuscitate’ decisions in continuing care psychiatric patients: what influences decisions?

AIMS AND METHOD We evaluated the various aspects of ‘do not resuscitate’ (DNR) decisions taken for psychiatric continuing care patients within NHS Ayrshire and Arran. Records were reviewed and nursing staff were asked their opinions about DNR orders in general and the way these were implemented on their wards. RESULTS There were 35 DNR orders among 88 continuing care patients in mental health wards for older adults. There were no DNR orders for the 25 continuing care patients in general adult psychiatry wards. Quality of life was the main issue when taking a DNR decision. Medical and nursing staff were involved in all decisions and the family in most. Patients were involved in only two cases. The documentation of the DNR order itself was satisfactory but documentation of the reasons behind the decision was inadequate. Patients with DNR status were perceived by ward staff to have more physical debilitation and more dependence on others. Local guidelines were being followed in most aspects, but these needed to be reviewed, as suggested within the resuscitation policy itself. CLINICAL IMPLICATIONS Decisions not to resuscitate may often be difficult to reach in psychiatric patients. Wards follow heterogeneous policies despite a resuscitation policy existing within the trust. Documentation needs to be improved and medical and nursing staff must reach a consensus regarding what constitutes quality of life and the appropriate time for a DNR decision.
Survival rates for horses undergoing stapled small intestinal anastomosis: 84 cases (1988-1997).

OBJECTIVE To determine whether location and type of small intestinal anastomosis and other variables were associated with short- and long-term survival rates in horses undergoing stapled small intestinal anastomosis. DESIGN Retrospective study. ANIMALS 84 horses that underwent small intestinal anastomosis. PROCEDURE Medical records from 1988 to 1997 were examined for horses that underwent stapled small intestinal anastomosis. Horses were allotted into 4 groups: jejunojejunostomy (n = 27), jejunoileostomy (11), jejunoileocecostomy with small intestinal resection (20), and jejunoileocecostomy without small intestinal resection (26). Survival rates and other variables were determined. RESULTS Horses that underwent jejunoileocecostomy without resection had a significantly higher survival rate at all intervals than did horses in the other 3 groups. At 180 and 365 days after surgery, horses that underwent jejunojejunostomy had a significantly lower survival rate than those that underwent jejunoileocecostomy with intestinal resection. Horses that underwent jejunoileocecostomy with intestinal resection had a significantly higher survival rate at 1 year, compared with the combined jejunojejunostomy and jejunoileostomy groups. Preoperative heart rate was inversely associated with survival rate. Overall survival rates at discharge and 1 year were 81 and 56%, respectively. For horses that underwent small intestinal resection, survival rates at discharge and 1 year were 65 and 47%, respectively. CONCLUSIONS AND CLINICAL RELEVANCE Horses that underwent anastomosis of the small intestine to the cecum without resection had the highest survival rate, compared with horses that required intestinal resection. In some instances, resection and anastomosis involving the cecum had better prognosis than resections involving 2 segments of the small intestine.
A survey of dairy farmers' practices and attitudes towards some aspects of arable-land management in the Darling Downs and South Burnett regions of Queensland

The Darling Downs and Southern Inland Burnett are important geographical subregions of the Queensland dairy industry. The system of dairy farming in these subregions is unique in Australia in that it is based on grazed annual forage crops rather than pastures. When these soils were first cultivated up to 110 years ago they were inherently fertile. However, erosion and fertility decline has reduced their productive capacity and there is a need for the adoption of farming practices that are less exploitative. In February 1997, a survey was conducted to determine dairy farmers' practices and attitudes toward management strategies that were being recommended to grain farmers in the subtropical cereal belt for sustaining the soil resource base. These strategies included greater use of ley pastures, opportunistic double-cropping, zero-till planting and higher fertiliser inputs. We found that dairy farmers were generally familiar with and understanding of the potential benefits of these approaches to their farming enterprises. However, farmers raised a number of issues that need consideration in the transfer of these practices to dairy forage production. These included concerns that an increased emphasis on pastures would result in lower and less-reliable forage production; that double-cropping is practiced more out of necessity than in the belief it is a better way to farm; that zero tillage may not be suitable on clay soils that have been trampled by cattle and that farmers rely primarily on their own observations of crop performance to determine fertiliser use. These findings have particular implications for research and extension activities conducted with dairy farmers and are also relevant to work conducted with other cropping enterprises that incorporate grazing animals in their farming program.
Tumor origin of endothelial cells in human neuroblastoma.

PURPOSE Malignant cells are genetically unstable and prone to develop chemotherapy resistance, whereas tumor vasculature is usually of host origin and genetically stable. Tumor endothelial microvessels attract interest as therapeutic targets, but their genetic instability would curtail such approach. Here, we have investigated the tumor origin of endothelial microvessels in human neuroblastoma (NB). MATERIALS AND METHODS Paraffin-embedded tissue sections from 10 MYCN-amplified tumors (six stage 4, three stage 3, and one stage 1) were studied. Endothelial cells (ECs) were detected by immunofluorescent staining for CD31 or CD105, and MYCN amplification was detected using fluorescence in situ hybridization (FISH). In xenografts of the HTLA-230 human NB cell line, human ECs were detected by CD31 staining, mouse ECs were detected by CD34 staining, and MYCN amplification and murine DNA were detected using FISH. RESULTS MYCN-amplified ECs formed approximately 70% of tumor endothelial microvessels in two stage 4 tumors and 20% in one stage 3 tumor. Similar results were obtained after EC labeling with CD31 or CD105. Staining for alpha-smooth muscle actin in combination with MYCN FISH demonstrated that tumor-derived ECs were coated with pericytes. These vessels were functional because they contained RBCs. Approximately 70% of endothelial vessels from HTLA-230 xenografts stained for human CD31, but not murine CD34, and displayed MYCN amplification, thus proving their tumor origin. CONCLUSION NB-associated endothelial microvessels can originate from tumor cells, and this finding challenges the tenet that tumor vasculature is genetically stable. The possibility that NB-derived ECs are chemotherapy resistant warrants further investigation.
Prevention of collagen crosslinking increases form-deprivation myopia in tree shrew.

To examine whether collagen crosslinking is important for the regulation of refractive development, tree shrews were treated with agents that block collagen crosslinking [beta-aminoproprionitrile (beta-APN), or D-penicillamine (DPA)] and underwent monocular deprivation (MD) of form vision by eyelid closure to induce myopia. MD began on the first day of visual exposure and continued for 75 days. After 15-20 days of visual exposure, daily intraperitoneal injections of beta-APN (beta-APN MD animals, n = 5) or DPA (DPA MD animals, n = 5) were administered for 17-21 days. beta-APN open animals (n = 5) received the same injection schedule, but both eyes remained open. Saline MD animals (n = 5) received i.p. saline and MD. At 75 days of visual exposure, the MD eyes of beta-APN treated tree shrews were highly myopic (-23.6 +/- 3.3 D) in comparison to their open control eyes. This was markedly greater than the difference in saline MD animals (-11.0 +/- 0.8 D). DPA MD animals showed a relative myopia of -14.3 +/- 2.2 D. The structural correlate of the myopia, elongation of the vitreous chamber in the deprived eyes relative to the control eyes, was significantly greater in the beta-APN MD animals 0.53 +/- 0.03 mm, which was not significantly different from the saline MD group. Thinning of the posterior sclera, but not the cornea, was observed in the deprived eyes of beta-APN treated tree shrews, along with a tessellated appearance to the fundus. The eyes of the beta-APN open animals showed no significant differences from normal. Beta-APN MD and DPA MD treated chickens did not develop greater myopia or vitreous chamber elongation than standard MD chickens. The selective effect of the lathyritic agents on the deprived eyes in tree shrew suggests that collagen crosslinking interacts, in the mammalian sclera, with a retinally-derived signal to regulate the elongation of the eye in myopia.
Crossing beef x beef and beef x Brown Swiss: pregnancy rate, calf survival, weaning age and rate.

October pregnancy rate, calf survival to weaning, weaning age, weaning rate and actual kg of calf weaned/cow exposed were determined in a 4-yr study involving 880 matings of Angus (A), Hereford (H) and Charolais (C) sires to A, H, C and Brown Swiss (BS) dams. Cows were mated in single-sire herds for 45 or 60 d under pasture conditions; heifers were bred to produce their first calf at 3 yr of age. Pregnancy rate of lactating dams was 9.4% higher (P less than .01) than for non-lactating dams. Pregnancy rates for straightbred matings were 87.5%, 80.6% and 75.4%, respectively, for A, H and C groups (P less than .05). No differences (P greater than .10) due to sire breed were found for any of the traits studied except for calf age at weaning. Calves from C sires were younger (P less than .01) at weaning than calves from H and A sires. Breed-of-dam differences (P less than .05 to P less than .01) were found for all traits studied except calf survival rate. All BS dams produced crossbred calves and had lower pregnancy and weaning rates (both P less than .01), calves were younger at weaning (P less than .05), had lower kg of calf weaned/cow exposed (P less than .05) than for beef-breed dams producing crossbred calves. Crossbred calves from BS dams were 4.9, 11.0 and 3.4 d younger (P less than .05 to P less than .01) at weaning, respectively, than crossbred calves from H, A and C dams. (ABSTRACT TRUNCATED AT 250 WORDS)
Crystal Structure of the Ribosome at 5.5 Å Resolution

We describe the crystal structure of the complete Thermus thermophilus 70S ribosome containing bound messenger RNA and transfer RNAs (tRNAs) at 5.5 angstrom resolution. All of the 16S, 23S, and 5S ribosomal RNA (rRNA) chains, the A-, P-, and E-site tRNAs, and most of the ribosomal proteins can be fitted to the electron density map. The core of the interface between the 30S small subunit and the 50S large subunit, where the tRNA substrates are bound, is dominated by RNA, with proteins located mainly at the periphery, consistent with ribosomal function being based on rRNA. In each of the three tRNA binding sites, the ribosome contacts all of the major elements of tRNA, providing an explanation for the conservation of tRNA structure. The tRNAs are closely juxtaposed with the intersubunit bridges, in a way that suggests coupling of the 20 to 50 angstrom movements associated with tRNA translocation with intersubunit movement.
Childhood Traumatic Grief: A Multi-Site Empirical Examination of the Construct and its Correlates

This study evaluated the construct of childhood traumatic grief (CTG) and its correlates through a multi-site assessment of 132 bereaved children and adolescents. Youth completed a new measure of the characteristics, attributions, and reactions to exposure to death (CARED), as well as measures of CTG, posttraumatic stress disorder (PTSD), depression, and anger. CTG was distinct from but highly correlated with PTSD, depression, and, to a lesser degree, anger. In contrast to a recent study of complicated grief, CTG severity was significantly associated with the degree to which the death was viewed as traumatic. CTG was also associated with caregivers' emotional reaction at the time of the death and caregivers' current sadness. Clinical implications and recommendations for future research are discussed.
Lenalidomide plus Rituximab as Initial Treatment for Mantle-Cell Lymphoma.

BACKGROUND Mantle-cell lymphoma is generally incurable. Initial treatment is not standardized but usually includes cytotoxic chemotherapy. Lenalidomide, an immunomodulatory compound, and rituximab, an anti-CD20 antibody, are active in patients with recurrent mantle-cell lymphoma. We evaluated lenalidomide plus rituximab as a first-line therapy. METHODS We conducted a single-group, multicenter, phase 2 study with induction and maintenance phases. During the induction phase, lenalidomide was administered at a dose of 20 mg daily on days 1 through 21 of every 28-day cycle for 12 cycles; the dose was escalated to 25 mg daily after the first cycle if no dose-limiting adverse events occurred during the first cycle and was reduced to 15 mg daily during the maintenance phase. Rituximab was administered once weekly for the first 4 weeks and then once every other cycle until disease progression. The primary end point was the overall response rate. Secondary end points included outcomes related to safety, survival, and quality of life. RESULTS A total of 38 participants were enrolled at four centers from July 2011 through April 2014. The median age was 65 years. On the basis of the Mantle Cell Lymphoma International Prognostic Index scores, the proportions of participants with low-risk, intermediate-risk, and high-risk disease at baseline were similar (34%, 34%, and 32%, respectively). The most common grade 3 or 4 adverse events were neutropenia (in 50% of the patients), rash (in 29%), thrombocytopenia (in 13%), an inflammatory syndrome ("tumor flare") (in 11%), anemia (in 11%), serum sickness (in 8%), and fatigue (in 8%). At the median follow-up of 30 months (through February 2015), the overall response rate among the participants who could be evaluated was 92% (95% confidence interval [CI], 78 to 98), and the complete response rate was 64% (95% CI, 46 to 79); median progression-free survival had not been reached. The 2-year progression-free survival was estimated to be 85% (95% CI, 67 to 94), and the 2-year overall survival 97% (95% CI, 79 to 99). A response to treatment was associated with improvement in quality of life. CONCLUSIONS Combination biologic therapy consisting of lenalidomide plus rituximab was active as initial therapy for mantle-cell lymphoma. (Funded by Celgene and Weill Cornell Medical College; ClinicalTrials.gov number, NCT01472562.).