Miracle-dz/UniFAR-FTUs huggingface dataset:
Quercetin induces apoptosis and necroptosis in MCF-7 breast cancer cells.

OBJECTIVE This study investigated the quercetin (Que) effects on growth of MCF-7 human cancer breast cell line and its cellular death mechanism. BACKGROUND Quercetin has been found to be very efficacious against many different types of cancer cells. However, the study is not sufficiently powered to demonastrate anticancer mechanisms. METHODS MCF-7cells were treated by 50 µM/ ml of Que for 48 hours. MCF-7 cells were also pretreated with 10 Μm ZVAD (apoptosis inhibitor) or 3 mM Nec-1 (necroptosis inhibitor) for evaluation of cell death induced by apoptosis or necroptosis. RESULTS MTT and clonogenicity assays revealed that the Que induced a significant increase in cell viability and proliferation in presence of Nec-1 in comparison to the presence of ZVAD (p < 0.05). Que also increased apoptosis as revealed by DAPI staining and morphology evaluations. Following Que treatment Bcl-2 expression was significantly decreased while Bax expression was significantly increased. Que in presence of Nec-1 decreased expression of Bax gene, reduced apoptotic index, increased cell viability and proliferation of MCF-7 cells in comparison to absence of Nec-1. MCF-7 cells showed a significantly increased expression of RIPK1 and RIPK3 in response to Que plus ZVAD in comparison to absence of ZVAD. CONCLUSION Our results revealed that the high Que toxicity for breast cancer cells depends on multiple cell death pathways, which involve mainly necroptosis (Fig. 6, Ref. 21).
Unique Clinicopathologic Features Characterize ALK-Rearranged Lung Adenocarcinoma in the Western Population

Purpose: The anaplastic large cell kinase gene (ALK) is rearranged in ∼5% of lung adenocarcinomas within the Asian population. We evaluated the incidence and the characteristics of ALK-rearranged lung adenocarcinomas within the western population and the optimal diagnostic modality to detect ALK rearrangements in routine clinical practice. Experimental Design: We tested 358 lung adenocarcinomas from three institutions for ALK rearrangements by fluorescent in situ hybridization (FISH) and immunohistochemistry with and without tyramide amplification. The clinicopathologic characteristics of tumors with and without ALK rearrangements were compared. Results: We identified 20 (5.6%) lung adenocarcinomas with ALK rearrangements within our cohort of western patients. ALK rearrangement was associated with younger age (P = 0.0002), never smoking (P < 0.0001), advanced clinical stage (P = 0.0001), and a solid histology with signet-ring cells (P < 0.0001). ALK rearrangement was identified by FISH in 95% of cases and immunohistochemistry with and without tyramide amplification in 80% and 40% of cases, respectively, but neither FISH nor immunohistochemistry alone detected all cases with ALK rearrangement on initial screening. None of the ALK-rearranged tumors harbored coexisting EGFR mutations. Conclusions: Lung adenocarcinomas with ALK rearrangements are uncommon in the western population and represent a distinct entity of carcinomas with unique characteristics. For suspected cases, dual diagnostic testing, with FISH and immunohistochemistry, should be considered to accurately identify lung adenocarcinomas with ALK rearrangement. (Clin Cancer Res 2009;15(16):5216–23)
Endothelial Protective Monocyte Patrolling in Large Arteries Intensified by Western Diet and Atherosclerosis

Rationale: Nonclassical mouse monocyte (CX3CR1high, Ly-6Clow) patrolling along the vessels of the microcirculation is critical for endothelial homeostasis and inflammation. Because of technical challenges, it is currently not established how patrolling occurs in large arteries. Objective: This study was undertaken to elucidate the molecular, migratory, and functional phenotypes of patrolling monocytes in the high shear and pulsatile environment of large arteries in healthy, hyperlipidemic, and atherosclerotic conditions. Methods and Results: Applying a new method for stable, long-term 2-photon intravital microscopy of unrestrained large arteries in live CX3CR1-GFP (green fluorescent protein) mice, we show that nonclassical monocytes patrol inside healthy carotid arteries at a velocity of 36 &mgr;m/min, 3× faster than in microvessels. The tracks are less straight but lead preferentially downstream. The number of patrolling monocytes is increased 9-fold by feeding wild-type mice a Western diet or by applying topical TLR7/8 (Toll-like receptor) agonists. A similar increase is seen in CX3CR1+/GFP/apoE−/− mice on chow diet, with a further 2- to 3-fold increase on Western diet (22-fold over healthy). In plaque conditions, monocytes are readily captured onto the endothelium from free flow. Stable patrolling is unaffected in CX3CR1-deficient mice and involves the contribution of LFA-1 (lymphocyte-associated antigen 1) and &agr;4 integrins. The endothelial damage in atherosclerotic carotid arteries was assessed by electron microscopy and correlates with the number of intraluminal patrollers. Abolishing patrolling monocytes in Nr4a1−/− apoE−/− mice leads to pronounced endothelial apoptosis. Conclusions: Arterial patrolling is a prominent new feature of nonclassical monocytes with unique molecular and kinetic properties. It is highly upregulated in hyperlipidemia and atherosclerosis in a CX3CR1-independent fashion and plays a potential role in endothelial protection.
Ecological consequences of interactions between ants and honeydew-producing insects

Interactions between ants and honeydew-producing hemipteran insects are abundant and widespread in arthropod food webs, yet their ecological consequences are very poorly known. Ant–hemipteran interactions have potentially broad ecological effects, because the presence of honeydew-producing hemipterans dramatically alters the abundance and predatory behaviour of ants on plants. We review several studies that investigate the consequences of ant–hemipteran interactions as ‘keystone interactions’ on arthropod communities and their host plants. Ant–hemipteran interactions have mostly negative effects on the local abundance and species richness of several guilds of herbivores and predators. In contrast, out of the 30 studies that document the effects of ant–hemipteran interactions on plants, the majority (73%) shows that plants actually benefit indirectly from these interactions. In these studies, increased predation or harassment of other, more damaging, herbivores by hemipteran-tending ants resulted in decreased plant damage and/or increased plant growth and reproduction. The ecological consequences of mutualistic interactions between honeydew-producing hemipterans and invasive ants relative to native ants have rarely been studied, but they may be of particular importance owing to the greater abundance, aggressiveness and extreme omnivory of invasive ants. We argue that ant–hemipteran interactions are largely overlooked and underappreciated interspecific interactions that have strong and pervasive effects on the communities in which they are embedded.
Oral Versus Initial Intravenous Therapy for Urinary Tract Infections in Young Febrile Children

Background. The standard recommendation for treatment of young, febrile children with urinary tract infection has been hospitalization for intravenous antimicrobials. The availability of potent, oral, third-generation cephalosporins as well as interest in cost containment and avoidance of nosocomial risks prompted evaluation of the safety and efficacy of outpatient therapy. Methods. In a multicenter, randomized clinical trial, we evaluated the efficacy of oral versus initial intravenous therapy in 306 children 1 to 24 months old with fever and urinary tract infection, in terms of short-term clinical outcomes (sterilization of the urine and defervescence) and long-term morbidity (incidence of reinfection and incidence and extent of renal scarring documented at 6 months by99mTc-dimercaptosuccinic acid renal scans). Children received either oral cefixime for 14 days (double dose on day 1) or initial intravenous cefotaxime for 3 days followed by oral cefixime for 11 days. Results. Treatment groups were comparable regarding demographic, clinical, and laboratory characteristics. Bacteremia was present in 3.4% of children treated orally and 5.3% of children treated intravenously. Of the short-term outcomes, 1) repeat urine cultures were sterile within 24 hours in all children, and 2) mean time to defervescence was 25 and 24 hours for children treated orally and intravenously, respectively. Of the long-term outcomes, 1) symptomatic reinfections occurred in 4.6% of children treated orally and 7.2% of children treated intravenously, 2) renal scarring at 6 months was noted in 9.8% children treated orally versus 7.2% of children treated intravenously, and 3) mean extent of scarring was ∼8% in both treatment groups. Mean costs were at least twofold higher for children treated intravenously ($3577 vs $1473) compared with those treated orally. Conclusions. Oral cefixime can be recommended as a safe and effective treatment for children with fever and urinary tract infection. Use of cefixime will result in substantial reductions of health care expenditures.
Combination therapies, effectiveness, and adherence in patients with HIV infection: clinical utility of a single tablet of emtricitabine, rilpivirine, and tenofovir

A recent addition to the anti-human immunodeficiency virus armamentarium of drugs is rilpivirine, which is a potent non-nucleoside reverse transcriptase inhibitor. This review focuses on the clinical utility of rilpivirine in terms of efficacy and virologic suppression, drug resistance, drug-drug interactions, and safety. The rilpivirine-tenofovir-emtricitabine combination is a safe and effective regimen for use in most patients who are ready to start first-line anti-human immunodeficiency virus therapy. Although drug resistance can be a problem in patients who initiate therapy on rilpivirine-based regimens with viral loads > 100,000 copies of viral RNA/mL, this problem can be alleviated by first starting therapy with efavirenz-tenofovir-emtricitabine for several months to suppress viral load to <50 copies/mL before switching to rilpivirine-based therapy. E138K is the most important mutation associated with resistance against rilpivirine and its development must be avoided whenever possible, because this mutation confers broad cross-resistance against all approved members of the non-nucleoside reverse transcriptase inhibitor family of drugs.
Transoral CO2 Laser Microsurgery Outcomes for Early Glottic Carcinomas T1-T2

Abstract Introduction Transoral laser microsurgery (TLM) has won territory in larynx oncology, establishing itself as an effective option in treatment of glottic, supraglottic, and hypopharynx tumors. Its advantages include limited resections, a reduction in number of tracheostomies, and the use of nasogastric tubes. Moreover, its oncological benefits are similar to those from open surgery in patients with early or advanced stages, when correctly selected. Objective The objective of this study is to review oncologic outcomes obtained with the treatment of a series of glottic tumors, treated by TLM. Methods Retrospective analysis of patients previously untreated, diagnosed with squamous cell carcinoma of the glottis (T1a, T1b, T2) in a tertiary university hospital. Endpoints for analysis were local control, overall and disease-specific survival, and larynx preservation rate. Results The study group included 58 patients that met the inclusion criteria: 57 (98.3%) men and 1 (1.7%) woman. Mean age was 65.5 ± 10.7 years (Min: 46/Max: 88). The tumor stages of the patients included were 30 T1a, 11 (19%) T1b, and 17 (29.3%) T2. Three-year overall survival rate was 89.7% (Fig. 1), and three-year disease-specific survival rate was 96.5%, three-year local control rate was 98.3%, and three-year organ preservation rate was 98.3%. Conclusion TLM is a safe and effective option in the treatment of glottis carcinomas, associated with less morbidity and a high percentage of local control, overall survival, specific survival, and organ preservation.
The Interplay Between Monocytes/Macrophages and CD4+ T Cell Subsets in Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by inflammation of the synovial lining (synovitis). The inflammation in the RA joint is associated with and driven by immune cell infiltration, synovial hyperproliferation, and excessive production of proinflammatory mediators, such as tumor necrosis factor α (TNFα), interferon γ (IFNγ), interleukin (IL)-1β, IL-6, and IL-17, eventually resulting in damage to the cartilage and underlying bone. The RA joint harbors a wide range of immune cell types, including monocytes, macrophages, and CD4+ T cells (both proinflammatory and regulatory). The interplay between CD14+ myeloid cells and CD4+ T cells can significantly influence CD4+ T cell function, and conversely, effector vs. regulatory CD4+ T cell subsets can exert profound effects on monocyte/macrophage function. In this review, we will discuss how the interplay between CD4+ T cells and monocytes/macrophages may contribute to the immunopathology of RA.
Interactions between Exposure to Environmental Polycyclic Aromatic Hydrocarbons and DNA Repair Gene Polymorphisms on Bulky DNA Adducts in Human Sperm

Background Nucleotide excision repair (NER) and base excision repair (BER) are the primary mechanisms for repair of bulky adducts caused by chemical agents, such as PAHs. It is expected that polymorphisms in NER or BER genes may modulate individual susceptibility to PAHs exposure. Here, we evaluate the effects of PAHs exposure and polymorphisms in NER and BER pathway, alone or combined, on polycyclic aromatic hydrocarbon-DNA (PAH–DNA) adducts in human sperm. Methodology/Principal Findings Sperm PAH-DNA adducts were measured by immunofluorescent assay using flow cytometry in a sample of 465 infertile adults. Polymorphisms of XPA, XPD, ERCC1, XPF, and XRCC1 were determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) techniques. The PAHs exposure was detected as urinary 1-hydroxypyrene (1-OHP) levels. In multivariate models adjusted for potential confounders, we observed that XRCC1 5′pUTR -T/C, Arg194Trp, Arg399Gln polymorphisms were associated with increased sperm adduct levels. Furthermore, the stratified analysis indicated that adverse effects of XRCC1 Arg194Trp, Arg399Gln polymorphisms on PAH-DNA adducts were detected only in the high PAHs exposure group. Conclusions/Significance These findings provided the first evidence that polymorphisms of XRCC1 may modify sperm PAH-DNA adduct levels and may be useful biomarkers to identify individuals susceptible to DNA damage resulting from PAHs exposure.
Understanding the Impact of ErbB Activating Events and Signal Transduction on Antigen Processing and Presentation: MHC Expression as a Model

Advances in molecular pathology have changed the landscape of oncology. The ability to interrogate tissue samples for oncogene amplification, driver mutations, and other molecular alterations provides clinicians with an enormous level of detail about their patient’s cancer. In some cases, this information informs treatment decisions, especially those related to targeted anti-cancer therapies. However, in terms of immune-based therapies, it is less clear how to use such information. Likewise, despite studies demonstrating the pivotal role of neoantigens in predicting responsiveness to immune checkpoint blockade, it is not known if the expression of neoantigens impacts the response to targeted therapies despite a growing recognition of their diverse effects on immunity. To realize the promise of ‘personalized medicine’, it will be important to develop a more integrated understanding of the relationships between oncogenic events and processes governing anti-tumor immunity. One area of investigation to explore such relationships centers on defining how ErbB/HER activation and signal transduction influences antigen processing and presentation.
High Prevalence of Fluoroquinolone-Resistant Group B Streptococci among Clinical Isolates in China and Predominance of Sequence Type 19 with Serotype III

ABSTRACT A total of 146 group B streptococcus isolates from 8 cities across China belonged to four serotypes. Serotype Ia was more common in children. A high prevalence of resistance was observed for levofloxacin (37.7%), erythromycin (71.2%), clindamycin, (53.4%), and tetracycline (81.5%). The levofloxacin and clindamycin resistances among the 4 serotypes differed significantly. Eighty percent of fluoroquinolone-resistant isolates belonged to the sequence type 19 (ST19)/serotype III clone, with GyrA-ParC-ParE triple substitutions. This clone carried the erm(B), mef(E), and tet(M) genes.
Assessing retino-geniculo-cortical connectivities in Alzheimer's Disease with a neural mass model

Longitudinal studies have shown that increase of mean frequency within the theta band may be considered as an early symptom of progression into Alzheimer's Disease (AD). Also, slowing of mean frequency within the alpha band has long since been known to be a def nitive marker in AD. This work is aimed at developing a better understanding of alterations in neuronal connectivity underlying Electroencephalogram (EEG) changes in AD. Specif cally, connectivity changes in the dorso-lateral geniculo-cortical pathway are studied using a neural mass computational model. Connectivity parameters in the model are informed by the most recent experimental data on mammalian Lateral Geniculate Nucleus (dorsal). A slowing of the mean power spectra of the model output is observed with increase in both excitatory and inhibitory parameters in the intra-thalamic and thalamocortical pathways and a decrease of sensory pathway synaptic connectivity. The biological plausibility of the results suggest potential of further model extension in AD research.
HUBBLE SPACE TELESCOPE IMAGES AND KPNO SPECTROSCOPY OF THE BINARY BLACK HOLE CANDIDATE SDSS J153636.22+044127.0

We present Hubble Space Telescope WFPC2/PC images and KPNO 4 m long-slit spectroscopy of the QSO SDSS J153636.22+044127.0, which we advanced as a candidate binary supermassive black hole. The images reveal a close companion coincident with the radio source identified by Wrobel & Laor. It appears to be consistent with a Mg ∼ −21.4 elliptical galaxy, if it is at the QSO redshift. The spectroscopy, however, shows no spatial offset between the red or blue Balmer lines. The companion is thus not the source of either the red or blue broad-line systems; SDSS J153636.22+044127.0 is highly unlikely to be a chance superposition of objects or an ejected black hole. Over the ΔT = 0.75 yr difference between the rest-frame epoch of the present and SDSS spectroscopy, we find no velocity shift to within 40 km s−1, nor any amplitude change in either broad-line system. The lack of a shift can be admitted under the binary hypothesis, if the implied radial velocity is a larger component of the full orbital velocity than was assumed in our earlier work. A strong test of the binary hypothesis requires yet longer temporal baselines. The lack of amplitude variations is unusual for the alternative explanation of this object as a “double-peaked” emitter; we further argue that SDSS J153636.22+044127.0 has unique spectral features that have no obvious analogue with other members of this class.
Thermal tolerance of crustacean larvae (zoea I) in two different populations of the kelp crab Taliepus dentatus (Milne-Edwards)

SUMMARY Studies of thermal tolerance in marine ectotherms are key in understanding climate effects on ecosystems; however, tolerance of their larval stages has rarely been analyzed. Larval stages are expected to be particularly sensitive. Thermal stress may affect their potential for dispersal and zoogeographical distribution. A mismatch between oxygen demand and the limited capacity of oxygen supply to tissues has been hypothesized to be the first mechanism restricting survival at thermal extremes. Therefore, thermal tolerance of stage zoea I larvae was examined in two populations of the Chilean kelp crab Taliepus dentatus, which are separated by latitude and the thermal regime. We measured temperature-dependent activity, oxygen consumption, cardiac performance, body mass and the carbon (C) and nitrogen (N) composition in order to: (1) examine thermal effects from organismal to cellular levels, and (2) compare the thermal tolerance of larvae from two environmental temperature regimes. We found that larval performance is affected at thermal extremes indicated by decreases in activity, mainly in maxilliped beat rates, followed by decreases in oxygen consumption rates. Cardiac stroke volume was almost temperature-independent. Through changes in heart rate, cardiac output supported oxygen demand within the thermal window whereas at low and high temperature extremes heart rate declined. The comparison between southern and central populations suggests the adaptation of southern larvae to a colder temperature regime, with higher cardiac outputs due to increased cardiac stroke volumes, larger body sizes but similar body composition as indicated by similar C:N ratios. This limited but clear differentiation of thermal windows between populations allows the species to widen its biogeographical range.
The concentration of ionized magnesium in barnacle muscle fibres.

1. The total Mg in isolated fibres of Balanus aquila was 10‐5 m‐mole/kg wet wt. 2. The intracellular free Mg was measured by a null point method using Eriochrome Blue as an indicator of free Mg, and internal dialysis with solutions of varying ionized Mg concentrations. The results indicated a free Mg of 6 mM or 4‐2 m‐mole/kg wet wt. in the intracellular water immediately surrounding the dialysis capillary. 3. The ATP concentration was estimated to be 4‐9 m‐mole/kg wet wt. 4. A tentative partitioning of Mg among various intracellular constitutents based on present data combined with published work by others is (m‐mole/kg wet wt): free, 4‐2; MgATP, 4‐2; myofibrillar bound, 1; residual (presumably bound to arginine phosphate and phosphate) ca. 1.
Analysis, modeling and generation of self-similar VBR video traffic

We present a detailed statistical analysis of a 2-hour long empirical sample of VBR video. The sample was obtained by applying a simple intraframe video compression code to an action movie. The main findings of our analysis are (1) the tail behavior of the marginal bandwidth distribution can be accurately described using “heavy-tailed” distributions (e.g., Pareto); (2) the autocorrelation of the VBR video sequence decays hyperbolically (equivalent to long-range dependence) and can be modeled using self-similar processes. We combine our findings in a new (non-Markovian) source model for VBR video and present an algorithm for generating synthetic traffic. Trace-driven simulations show that statistical multiplexing results in significant bandwidth efficiency even when long-range dependence is present. Simulations of our source model show long-range dependence and heavy-tailed marginals to be important components which are not accounted for in currently used VBR video traffic models.