Miracle-dz/UniFAR-FTUs huggingface dataset:
Gβγ Signaling Promotes Breast Cancer Cell Migration and Invasion

Signaling through G protein-coupled receptors (GPCRs) promotes breast cancer metastasis. G proteins convey GPCR signals by dissociating into Gα and Gβγ subunits. The aim of the present study was to determine whether blockade of Gβγ signaling suppresses breast cancer cell migration and invasion, which are critical components of metastasis. Conditioned media (CM) of NIH-3T3 fibroblasts are widely used as chemoattractants in in vitro cancer metastasis studies. Expression of a Gβγ scavenger peptide attenuated NIH-3T3 CM-induced migration and invasion of both metastatic breast cancer MDA-MB-231 and MDA-MB-436 cells by 40 to 50% without effects on cell viability. Migration and invasion of cells in response to NIH-3T3 CM were also blocked by 8-(4,5,6-trihydroxy-3-oxo-3H-xanthen-9-yl)-1-naph-thalene-carboxylic acid) (M119K), a Gβγ inhibitor, with maximum inhibition exceeding 80% and half-maximal inhibitory concentration (IC50) values of 1 to 2 μM. M119K also attenuated Rac-dependent formation of lamellipodia, a key structure required for metastasis. Constitutively active Rac1 rescued Gβγ blockade-mediated inhibition of breast cancer cell migration, whereas dominant negative Rac1 inhibited cell migration similar to Gβγ blockade. Furthermore, M119K suppressed Gi protein-coupled CXC chemokine receptor 4 (CXCR4)-dependent MDA-MB-231 cell migration by 80% with an IC50 value of 1 μM, whereas tyrosine kinase receptor-dependent cell migration was significantly less inhibited. However, CXCR4-dependent inhibition of adenylyl cyclase, a Giα-mediated response in MDA-MB-231 cells, was not blocked by M119K but was blocked by pertussis toxin, which selectively inactivates Giα. This report is the first to directly demonstrate the role of Gβγ in cancer cell migration and invasion and suggests that targeting Gβγ signaling pathways may provide a novel strategy for suppressing breast cancer metastasis.
Meningococcal lipopolysaccharide (LPS)-derived oligosaccharide-protein conjugates evoke outer membrane protein- but not LPS-specific bactericidal antibodies in mice: influence of adjuvants

Meningococcal lipopolysaccharide (LPS)-derived oligosaccharides (OS) were coupled to tetanus toxoid (TT) and purified P1.7,16 outer membrane proteins (OMP). The immunogenicities of the conjugates with and without the addition of the adjuvant Quil A or the nonionic block polymer L121 were studied in mice. Immunotype L2 and L3,7,9 OS-TT conjugates induced immunoglobulin G (IgG) responses that were strongly augmented by Quil A and L121. These adjuvants not only enhanced the amount of IgG evoked but also shifted the IgG subclass distribution from mainly IgG1 toward the complement-activating subclasses IgG2a and IgG2b. The antibodies induced were directed against the OS part of meningococcal LPS. They were not bactericidal for group B meningococci. Both the L3,7,9 OS-P1.7,16 OMP conjugate and purified P1.7,16 OMP evoked a strong IgG response against the P1.7,16 OMP but not against the L3,7,9 LPS. These anti-OMP IgG responses were comparable to the IgG OMP-specific responses induced by the H44/76 or HIII-5 outer membrane vesicles but still did not lyse group B meningococcal strains. The IgG response evoked with OS-OMP or purified OMP consisted mainly of the IgG1 subclass, whereas the H44/76 or HIII-5 outer membrane vesicles induced high amounts of bactericidal IgG2a and IgG2b antibodies next to the IgG1 antibodies. The addition of the adjuvant Quil A or L121 to OS-OMP or OMP resulted in the induction of high levels of bactericidal anti-P1.7,16-specific OMP antibodies, as reflected by the presence of substantial amounts of IgG2a and IgG2b antibodies. These results indicate that (i) mouse anti-LPS antibodies evoked by LPS-derived OS-protein conjugates are not bactericidal for group B meningococci, (ii) extensive purification of P1.7,16 OMP can lead to the loss of the intrinsic adjuvant properties of outer membrane vesicle preparations, and (iii) the addition of suitable adjuvants restores the ability of these purified P1.7,16 OMP to induce bactericidal antibodies.
Cemented total knee arthroplasty for gonarthrosis in patients 55 years old or younger.

The results of 68 cemented total knee arthroplasties (TKAs) in 50 patients with gonarthrosis who were 55 years old or younger at the time of surgery were reviewed. These patients were operated on between 1979 and 1987 and were followed for an average of 6.2 years. The average age of the patients was 50 years. Patients were evaluated by the Hospital for Special Surgery knee score. The average preoperative score was 53, and the average follow-up score was 90. Overall, 55 TKAs were rated as excellent and 13 as good. Using the knee rating score advocated by the Knee Society, the average postoperative score was 92 for pain and 84 for function. There were four successful reoperations for patellar component loosening, all in metal-backed patellae. The femoral and tibial components in these patients were intact, and at the follow-up period, two knees were rated as excellent and two as good. Detailed roentgenographic evaluation demonstrated that 20% of tibial components had radiolucencies in at least one zone on the anteroposterior roentgenogram and in 11% on the lateral roentgenogram. Femoral radiolucencies occurred in only 2% of knees. Patellar radiolucencies in one or more zones occurred in 20% of knees that had not had patellar revision. No complete or progressive radiolucencies at the bone-cement interface were noted for any component, and no components were considered to be roentgenographically loose. Cemented TKAs can achieve excellent long-term results in patients younger than 55 years old with gonarthrosis of the knee. These results compare with those obtained in published reports on older age groups. (ABSTRACT TRUNCATED AT 250 WORDS)
Nek2A destruction marks APC/C activation at the prophase‐to‐prometaphase transition by spindle‐checkpoint‐restricted Cdc20

Nek2 isoform A (Nek2A) is a presumed substrate of the anaphase‐promoting complex/cyclosome containing Cdc20 (APC/CCdc20). Nek2A, like cyclin A, is degraded in mitosis while the spindle checkpoint is active. Cyclin A prevents spindle checkpoint proteins from binding to Cdc20 and is recruited to the APC/C in prometaphase. We found that Nek2A and cyclin A avoid being stabilized by the spindle checkpoint in different ways. First, enhancing mitotic checkpoint complex (MCC) formation by nocodazole treatment inhibited the degradation of geminin and cyclin A, whereas Nek2A disappeared at a normal rate. Second, depleting Cdc20 effectively stabilized cyclin A but not Nek2A. Nevertheless, Nek2A destruction crucially depended on Cdc20 binding to the APC/C. Third, in contrast to cyclin A, Nek2A was recruited to the APC/C before the start of mitosis. Interestingly, the spindle checkpoint very effectively stabilized an APC/C‐binding mutant of Nek2A, which required the Nek2A KEN box. Apparently, in cells, the spindle checkpoint primarily prevents Cdc20 from binding destruction motifs. Nek2A disappearance marks the prophase‐to‐prometaphase transition, when Cdc20, regardless of the spindle checkpoint, activates the APC/C. However, Mad2 depletion accelerated Nek2A destruction, showing that spindle checkpoint release further increases APC/CCdc20 catalytic activity.
Factors Affecting Health-Promoting Behaviors of University Students in Jordan

Objectives: To determine health promoting behaviors of university students in Jordan and factors influencing them. Design and Methods: A cross-sectional descriptive design was used to recruit convenience sample (n = 525) of university students receiving education from two governmental and one private universities in Jordan. Data were collected between September 2013 and January 2014 by using Health Promoting Lifestyle Profile II. Pender Model provided conceptual framework to guide the study. Results: The mean score of Health Promoting Lifestyle Profile of the student was at (127.87 ± 19.91). Significant differences were found between Health Promoting Lifestyle Profile mean score and the mean score of its subscales and student’s age, gender, employment status, family income, university type, and faculty type. Conclusions: These findings suggest that interventions are needed to enhance the practice of health promoting behaviours. These interventions should focus on demographic variations among university students.
MIST1 and PTF1 Collaborate in Feed-Forward Regulatory Loops That Maintain the Pancreatic Acinar Phenotype in Adult Mice

ABSTRACT Much remains unknown regarding the regulatory networks formed by transcription factors in mature, differentiated mammalian cells in vivo, despite many studies of individual DNA-binding transcription factors. We report a constellation of feed-forward loops formed by the pancreatic transcription factors MIST1 and PTF1 that govern the differentiated phenotype of the adult pancreatic acinar cell. PTF1 is an atypical basic helix-loop-helix transcription factor complex of pancreatic acinar cells and is critical to acinar cell fate specification and differentiation. MIST1, also a basic helix-loop-helix transcription factor, enhances the formation and maintenance of the specialized phenotype of professional secretory cells. The MIST1 and PTF1 collaboration controls a wide range of specialized cellular processes, including secretory protein synthesis and processing, exocytosis, and homeostasis of the endoplasmic reticulum. PTF1 drives Mist1 transcription, and MIST1 and PTF1 bind and drive the transcription of over 100 downstream acinar genes. PTF1 binds two canonical bipartite sites within a 0.7-kb transcriptional enhancer upstream of Mist1 that are essential for the activity of the enhancer in vivo. MIST1 and PTF1 coregulate target genes synergistically or additively, depending on the target transcriptional enhancer. The frequent close binding proximity of PTF1 and MIST1 in pancreatic acinar cell chromatin implies extensive collaboration although the collaboration is not dependent on a stable physical interaction.
Etiopathogenesis of Inflammatory Bowel Disease: The Importance of the Pediatric Perspective

Inflammatory bowel disease (IBD) is now recognized as a common chronic disease affecting children and adolescents. This article will review recent advances made in the fields of genetics, epidemiology, gut ecology, and immunology regarding the etiopathogenesis of IBD, with particular emphasis on the contributions made by pediatric studies. Areas where further study of the pediatric age group would be beneficial will be highlighted.
Isolation and Fusion of Protoplasts from Mesophyll Cells of Dendrobium Pompadour

Protoplasts were isolated from Dendrobium Pompadour leaves grown in vitro. Yields of 3x10 5 - 2.5x10 6 mesophyll protoplasts per gram fresh weight were obtained depending on factors such as digesting enzyme, osmoticum concentration, and leaf size. Small leaves (2.5-3 cm in length and 0.3 g in weight) were digested with 5 ml of enzyme solution containing 1% Cellulase Onozuka R-10, 1% Macerozyme R- 10, 0.5% Driselase, and 0.4 M mannitol. The mixture of leaves and enzyme solution was incubated at 30 C for 3 h on a gyr otary shaker with an agitation speed of 80 rpm. Purification of protoplasts on a sucrose gradient yielded very clean protoplasts that are free of raphide crystals. The fusion of protoplasts was carried out using 40% polyethylene glycol. Video microscopic studies revealed that fusion occurred when osmotic gradient was lowered.
Real‐time Inferior Vena Caval Ultrasonography: Normal and Abnormal Findings and Its Use in Assessing Right‐heart Function

We studied the inferior vena cava (IVC) as an index of right-heart function in 111 patients. A two-dimensional echocardiographic sector was used to visualize the IVC, and its M-mode cursor was used to generate a time-motion record of the IVC size and pulsation. Normal subjects had a small presystolic A wave (less than 125% of the end-diastolic IVC dimension), a small systolic V wave (less than 140% of the enddiastolic IVC dimension), and a 50% inspiratory decrease in IVC dimension. The A wave was absent in patients with atrial fibrillation. When normalized for body surface area, mean end-diastolic IVC dimension correlated with mean right atrial pressure (r = 0.72, p < 0.001). An A wave > 125% of end-diastolic IVC dimension was recorded in 71% of patients with sinus rhythm and an elevated right ventricular end-diastolic pressure of 10 mm Hg or greater, but in no patient with right ventricular end-diastolic pressure of less than 10 mm Hg (p < 0.001). A V wave 140% of end-diastolic IVC dimension was recorded in 75% of patients with severe tricuspid insufficiency, but in no patient with mild or no tricuspid insufficiency (p < 0.001). The inspiratory decrease in IVC dimension correlated with radionuclide right ventricular ejection fraction (r = 0.75, p < 0.001); no respiratory variation in end-diastolic IVC dimension occurred in patients with significant right ventricular dysfunction (right ventricular ejection fraction less than 25%) or in patients with constrictive pericarditis.
Rickettsial septicemia in farmed Atlantic and chinook salmon in British Columbia: Clinical presentation and experimental transmission.

Etiological agents of septicemia most frequently diagnosed in netpen-reared salmon in British Columbia include Aeromonas salmonicida (furuncu-losis) in Atlantic salmon (Salmo salar), Vibrio anguil-larum (vibriosis) in chinook salmon (Oncorhynchus tshawytscha), and Renibacterium salmoninarum (bac-terial kidney disease) in both species. In November 1991, a rickettsia-like organism, similar to an agent described in farmed salmonids in Chile, was suspected as the agent responsible for an outbreak of septicemia resulting in mortality at a growout site located in the coastal waters of Vancouver Island (1). This paper presents the clinical and laboratory findings during investigation of this disease outbreak. In addition, this paper will present brief comments on an experimental transmission study to determine the pathogenicity of the agent.
Visual Comparison of an Artificial Pupil Contact Lens to Monovision

Purpose. To assess and compare the effects of contact-lens based artificial pupil design and monovision correction on visual performance. Methods. In a cross-over study design, 22 presbyopic patients (age range 50 to 64 years) were evaluated using artificial pupil contact lens on the non-dominant eye and monovision. After 1 month, binocular distance visual acuity (BDVA), binocular near visual acuity (BNVA), defocus curve, binocular distance contrast sensitivity, binocular near contrast sensitivity, and stereoacuity were measured, under photopic conditions (85 cd/m2), in each patient after contact lens fitting. Moreover, BDVA and binocular distance contrast sensitivity were examined under mesopic conditions (5 cd/m2). Results. Average artificial pupil contact lens and monovision BDVA were 0.02 ± 0.04 and 0.00 ± 0.09 logMAR for photopic conditions, and 0.16 ± 0.06 and 0.13 ± 0.12 logMAR for binocular near visual acuity under mesopic conditions, respectively. No statistically significant differences were found between the two types of lenses at distance for both lighting levels (p > 0.05), but there were, however, significant differences at intermediate distances and near vision (p < 0.05). Binocular distance contrast sensitivity revealed statistically significant differences between artificial pupil contact lens and monovision for 1.5 cycles per degree (cpd) under photopic conditions, and 12 and 18 cpd under mesopic conditions (p < 0.05), respectively. Statistically significant differences for all spatial frequencies except for 1.5 cpd were found at near vision (p < 0.05). The mean values of stereoacuity obtained for artificial pupil contact lens (221 ± 32 sec arc) were slightly worse than for monovision correction (210 ± 49 sec arc), and statistically significant differences were not found (p = 0.23). Conclusions. Monovision performed better than an artificial pupil contact lens of the same material for near visual acuity and near contrast sensitivity. Only, the artificial pupil contact lens provides better intermediate visual acuity.
Clinical Holistic Medicine: Social Problems Disguised as Illness

Many of the diseases seen in the clinic are actually symptoms of social problems. It is often easier for the physician to treat the symptoms than to be a coach and help the patient to assume responsibility in order to improve quality of life, social situation, and relations. If the physician ignores the signs of the disease as a symptom of social problems, and treats the patient with pharmaceuticals, he can give the patient the best justification in the world not to do anything about the situation. It is very important that the physician is not tricked by the games the socially troubled patient, more or less unconsciously, is playing. A firm and wise attitude that confronts the patient with his or her lack of responsibility for solving social problems seems to be a constructive way out. The physician can give holding and support, but the responsibility must remain with the patient. Often it is better for the patient that the physician abstains from giving drugs that can remedy the symptoms and takes the role of a coach instead. Suffering is not necessarily bad, suffering is actually highly motivating and often the most efficient source of learning. Coaching can help the patient canalize his motivation into highly constructive considerations and behavior. A holistic approach thus gives the patient learning and helps him rehabilitate his social reality. Concerning children with recurrent or chronic pain, we have observed an overuse of painkillers, where we believe part is of a psychosomatic nature due to poor thriving in the family. Here the physician has an important job helping the parents to develop as persons, teaching them the basic holding of awareness, respect, care, acknowledgment and acceptance of their child. Most of the chronic pain and discomfort with children can be improved if the physician understands how to use the holistic medical toolbox.
Spaceborne lidar observations of the ice‐nucleating potential of dust, polluted dust, and smoke aerosols in mixed‐phase clouds

Previous laboratory studies and in situ measurements have shown that dust particles possess the ability to nucleate ice crystals, and smoke particles to some extent as well. Even with coatings of pollutants such as sulphate and nitrate on the surface of dust particles, it has been shown that polluted dust particles are still able to nucleate ice in the immersion, deposition, condensation, and contact freezing modes, albeit less efficiently than unpolluted dust. The ability of these aerosols to act as ice nuclei in the Earth's atmosphere has important implications for the Earth's radiative budget and hence global climate change. Here we determine the relationship between cloud thermodynamic phase and dust, polluted dust, and smoke aerosols individually by analyzing their vertical profiles over a ∼5 year period obtained by NASA's spaceborne lidar, Cloud‐Aerosol Lidar with Orthogonal Polarization. We found that when comparing the effects of temperature and aerosols, temperature appears to have the dominant influence on supercooled liquid cloud fraction. Nonetheless, we found that aerosols still appear to exert a strong influence on supercooled liquid cloud fraction as suggested by the existence of negative temporal and spatial correlations between supercooled liquid cloud fraction and frequencies of dust aerosols from around the world, at the −10°C, −15°C, −20°C, and −25°C isotherms. Although smoke aerosol frequencies were also found to be negatively correlated with supercooled liquid cloud fraction, their correlations are weaker in comparison to those between dust frequencies and supercooled liquid cloud fraction. For the first time, we show this based on observations from space, which lends support to previous studies that dust and potentially smoke aerosols can globally alter supercooled liquid cloud fraction. Our results suggest that the ice‐nucleating ability of these aerosols may have an indirect climatic impact that goes beyond the regional scale, by influencing cloud thermodynamic phase globally.
Doxorubicin alters the mitochondrial dynamics machinery and mitophagy in the liver of treated animals

Doxorubicin (Dox) is an effective chemotherapeutic agent, but known to cause cardiac and hepatic toxicity. Mechanisms of toxicity have not been clearly identified, but shown to involve oxidative stress and mitochondrial dysfunction. However, antioxidant supplementation has only shown modest protection from Dox‐induced toxicity in clinical trials. Therefore, further research is required to discern alternative mechanisms that may also play an important role in Dox‐induced toxicity. Thus, we aimed to investigate the role of mitochondrial fusion and fission in Dox‐induced hepatic toxicity, which has not yet been investigated. Six‐week‐old male F344 rats were injected IP with 20 mg/kg of Dox or saline. Once administered, both groups of animals were fasted with no food or water until sacrifice 24 h later. Dox decreased content of primary regulators of mitochondrial fusion (OPA1, MFN1, and MFN2) with no effect on regulators of fission (DRP1 and FIS1), thus shifting the balance favoring mitochondrial fission. Moreover, it was determined that mitochondrial fission was likely not coupled to cell proliferation or cytochrome c release leading to the activation of mitochondrial‐mediated apoptotic signaling. Rather, mitochondrial fission may be coupled to mitophagy and may be an adaptive response to protect against Dox‐induced hepatic toxicity. This is the first study to report the role of altered mitochondrial dynamics and mitophagy machinery in Dox‐induced hepatic injury.
Predicting suicide attempts by time-varying frequency of nonsuicidal self-injury among Chinese community adolescents.

OBJECTIVE This study predicted suicide attempts (SA) by time-varying frequency of nonsuicidal self-injury (NSSI) beyond the contributions of their shared risk factors and examined gender differences in this association. This study also tested for a moderating effect of NSSI in the relationship between suicide ideation (SI) and SA. METHOD A large number of Chinese adolescents participated in this study (the exact number of participants varied from 3,623 to 6,911 in different analyses). They completed questionnaires assessing NSSI, SA, SI, borderline personality disorder features, depressive symptoms, and self-criticism 3 times at 6-month intervals. Generalized estimating equations were used to test the hypotheses. RESULTS In females, but not in males, NSSI was significantly associated with future SA after controlling for the effects of shared risk factors. With the same frequency of SI, the frequency of NSSI also enhanced the risk for future SA. CONCLUSIONS This study established a longitudinal association between NSSI and SA, which could not be fully accounted for by their shared risk factors, in Chinese female community adolescents. Moreover, female adolescents who frequently engage in NSSI may gain the capability for attempting suicide.