Miracle-dz/UniFAR-FTUs huggingface dataset:
Silencing of glutaminase 1 resensitizes Taxol-resistant breast cancer cells to Taxol.

Taxol is a front‑line chemotherapeutic agent for the treatment of patients with multiple types of tumor. However, resistance to Taxol remains one of the principal causes of cancer‑associated mortality. Glutamine, which is metabolized via a glutaminase (GLS)‑dependent process, termed glutaminolysis, is important in cell growth and metabolism. The present study reported a novel mechanism underlying Taxol resistance in breast cancer cells. By investigating the glutamine metabolism of breast cancer cells in response to treatment with Taxol in vitro, it was observed that Taxol induced the uptake of glutamine and the expression of GLS1. Notably, Taxol‑resistant cancer cells exhibited upregulation in the metabolism of glutamine and expression of GLS1. In addition, overexpression of GLS1 rendered cancer cells resistant to Taxol, indicating that GLS1 may be the therapeutic target for overcoming Taxol resistance in clinical therapeutics. The results also demonstrated that knock‑down of GLS1 using small interfering RNA, resensitized the Taxol‑resistant breast cancer cells to Taxol.
High prevalence of cardiovascular diseases among other medically compromised conditions in dental patients: A retrospective study

Background: Over the last few decades, oral health care has become a greater priority as people live longer with serious medical conditions and disabilities. As a result, they require more comprehensive dental treatment. We are now, more than ever, at a turning point in history where dental care, or more broadly oral health care, is an integral part of medical care. Therefore, a need was felt to study the prevalence of medically compromised patients seeking dental treatments. Materials and Methods: The present study was a retrospective study conducted by reviewing the patient records starting from 1st January 2009 to 31st December 2010 for the presence of medically compromised conditions. Demographic data of the patients was also collected. Results: The prevalence of medically compromised conditions in dental patients of our hospital in the present study was 1.02%. The Cardiovascular diseases accounted to be the most prevalent condition (57.87%) followed by Endocrine disorders (35.73%). Conclusion: Even though the prevalence of medically compromised conditions in dental patients is not high, dentists should bear in mind that some of the patients may harbor such conditions, which are contraindicated for certain dental procedures or medication or require special attention when treating these patients.
Synergistic Effect of Thermal Energy on Bactericidal Action of Photolysis of H2O2 in Relation to Acceleration of Hydroxyl Radical Generation

ABSTRACT The purpose of the present study is to evaluate the effect of thermal energy on the yield of and the bactericidal action of hydroxyl radical generated by photolysis of H2O2. Different concentrations of H2O2 (250, 500, 750, and 1,000 mM) were irradiated with light-emitting diodes (LEDs) at a wavelength of 400 ± 20 nm at 25°C to generate hydroxyl radical. The 500 mM H2O2 was irradiated with the LEDs at different temperatures (25, 35, 45, and 55°C). Electron spin resonance spin trapping analysis showed that the yield of hydroxyl radicals increased with the temperature, as well as the concentration of H2O2. Streptococcus mutans and Enterococcus faecalis were used in the bactericidal assay. The LED-light irradiation of the bacterial suspensions in 500 mM H2O2 at 25°C could hardly kill the bacteria within 3 min, while the bactericidal effect was markedly enhanced with the temperature rise. For instance, a temperature increase to 55°C resulted in >99.999% reduction of viable counts of both bacterial species only within 1 min. The photolysis of 500 mM H2O2 at 55°C could reduce the viable counts of bacteria more efficiently than did the photolysis of 1,000 mM H2O2 at 25°C, although the yields of hydroxyl radical were almost the same under the both conditions. These findings suggest that the thermal energy accelerates the generation of hydroxyl radical by photolysis of H2O2, which in turn results in a synergistic bactericidal effect of hydroxyl radical and thermal energy.
A self-aligned CoSi2interconnection and contact technology for VLSI applications

Cobalt silicide is investigated in view of possible application in a self-aligned technology. Extremely smooth, highly conductive CoSi2films are obtained using rapid thermal processing for silicide formation starting from deposited cobalt layers (on Si). The phase formation is studied by XRD and RBS. No lateral silicide formation is observed at contact edges. The influence of Si consumption and dopant behavior on diode performance is studied. Shallow arsenic (0.15 µm deep) and boron (0.3 µm deep) junctions are successfully silicided. Very low contact resistances are obtained between the silicide and n+ and p+ regions. MOS transistors were fabricated with CoSi2on the source, drain, and gate. An increase in current driving capability is noticed while no degradation of other electrical parameters due to the silicide processing steps is observed. At some critical points, comparison is made with the TiSi2process.
Linear Demasking Techniques Are Unreliable for Estimating the Circadian Phase of Ambulatory Temperature Data

Clinical investigators often use ambulatory temperature monitoring to assess the endogenous phase and amplitude of an individual's circadian pacemaker for diagnostic and research purposes. However, an individual's daily schedule includes changes in levels of activity, in posture, and in sleep-wake state, all of which are known to have masking or evoked effects on core body temperature (CBT) data. To compensate for or to correct these masking effects, many investigators have developed “demasking” techniques to extract the underlying circadian phase and amplitude data. However, the validity of these methods is uncertain. Therefore, the authors tested a variety of analytic methods on two different ambulatory data sets from two different studies in which the endogenous circadian pacemaker was not synchronized to the sleep-wake schedule. In both studies, circadian phase estimates calculated from CBT collected when each subject was ambulatory (i.e., free to perform usual daily activities) were compared to those calculated during the same study when the same subject's activities were controlled. In the first study, 24 sighted young and older subjects living on a 28-h scheduled “day” protocol were studied for approximately 21 to 25 cycles of 28-h each. In the second study, a blind man whose endogenous circadian rhythms were not synchronized to the 24-h day despite his maintenance of a regular 24-h sleep-wake schedule was studied for more than 80 consecutive 24-h days. During both studies, the relative phase of the endogenous (circadian) and evoked (scheduled activity-rest) components of the ambulatory temperature data changed progressively and relatively slowly, enabling analysis of the CBT rhythm at nearly all phase relationships between the two components. The analyses of the ambulatory temperature data demonstrate that the masking of the CBT rhythm evoked by changes in activity levels, posture, or sleep-wake state associated with the evoked schedule of activity and rest can significantly obscure the endogenous circadian component of the signal, the object of study. In addition, the masking effect of these evoked responses on temperature depends on the circadian phase at which they occur. These nonlinear interactions between circadian phase and sleep-wake schedule render ambulatory temperature data unreliable for the assessment of endogenous circadian phase. Even when proposed algebraic demasking techniques are used in an attempt to reveal the endogenous temperature rhythm, the phase estimates remain severely compromised.
Comparison of effects of margarite extract and recombinant human superoxide dismutase on paraquat-induced superoxide anion radicals in rat lung.

The effects of medicinal margarite extract and recombinant human superoxide dismutase (r-h SOD) on acute paraquat intoxication were examined in the rat lung. Forty-eight Sprague-Dawley rats under pentobarbital anesthesia were randomly assigned to one of four groups receiving i.v. injection of physiological saline (control), i.v. injection of 70 mg/kg paraquat, or i.v. injection of either 50 mg/kg of margarite extract or 50,000 unit/kg of r-h SOD 10 minutes before and 1 and 2 hours after an equivalent paraquat administration. Examination of lung superoxide anion radicals (O2-.), lipid peroxides, and histopathological changes showed that paraquat significantly increased superoxide anion radicals (383% of control) reacted with CLA-phenyl. Both margarite extract and r-h SOD decreased superoxide anion radicals to 119% and 83% of control, respectively. Margarite extract, rather than r-h SOD, significantly alleviated the paraquat-induced infiltration of polymorphonuclear leukocytes and macrophages into the alveolar walls. There were no significant inter-group differences in lipid peroxides in the lung. Component analysis showed that margarite extract was rich in L- and D-arginine. The scavenging mechanism of margarite extract may be related to L-arginine but needs to be further verified in the future study.
Increased apoptosis during papilloma development in mice susceptible to tumor progression

Programmed cell death (apoptosis) is known to occur not only during normal development and tissue remodeling but also during neoplasia. Despite the suggested role of apoptosis in preventing the proliferation of malignant cells, a positive correlation between tumor progression and the presence of apoptotic cells has been found in different types of cancer, including epithelial tumors. In normal mouse skin, the role of apoptosis is not completely understood, and it has been suggested that terminal differentiation may be a special case of apoptosis. In the work reported here, we counted apoptotic cells in mouse skin tumors generated with a two‐stage chemical carcinogenesis protocol. We analyzed papillomas from outbred SENCAR mice at different times during promotion, and to better determine the correlation between apoptosis and tumor progression, we compared papillomas generated from two inbred strains derived from the SENCAR stock that differ in their susceptibility to tumor progression. Our results showed that in mouse skin chemical carcinogenesis, the number of apoptotic cells was greater in papillomas that may have been in the process of progressing to squamous cell carcinomas. This conclusion is also supported by the fact that papillomas from SENCAR P/Bt. mice, a tumor progression–susceptible strain derived from outbred SENCAR mice, had more apoptotic cells than papillomas from progression‐resistant SSIN mice. Mol. Carcinog. 20:137–142, 1997. © 1997 Wiley‐Liss, Inc.
Avian Host and Mosquito (Diptera: Culicidae) Vector Competence Determine the Efficiency of West Nile and St. Louis Encephalitis Virus Transmission

Abstract The ability of the invading NY99 strain of West Nile virus (WNV) to elicit an elevated viremia response in California passerine birds was critical for the effective infection of Culex mosquitoes. Of the bird species tested, Western scrub jays, Aphelocoma coerulescens, produced the highest viremia response, followed by house finches, Carpodacus mexicanus, and house sparrows, Passer domesticus. Most likely, few mourning, Zenaidura macroura, or common ground, Columbina passerine, doves and no California quail, Callipepla californica, or chickens would infect blood-feeding Culex mosquitoes. All Western scrub jays and most house finches succumbed to infection. All avian hosts produced a lower viremia response and survived after infection with an endemic strain of St. Louis encephalitis virus. Culex species varied in their susceptibility to infection with both viruses, with Culex stigmatosoma Dyar generally most susceptible, followed by Culex tarsalis Coquillett, and then Culex p. quinquefasciatus Say. Populations within Culex species varied markedly in their susceptibility, perhaps contributing to the focality of WNV amplification. Transmitting female Cx. tarsalis expectorated from six to 3,777 plaque-forming units (PFU) of WNV during transmission trials, thereby exposing avian hosts to a wide range of infectious doses. Highly susceptible house finches and moderately susceptible mourning doves were infected by subcutaneous inoculation with decreasing concentrations of WNV ranging from 15,800 to <0.3 PFU. All birds became infected and produced comparable peak viremias on days 2–3 postinoculation; however, the rise in viremia titer and onset of the acute phase of infection occurred earliest in birds inoculated with the highest doses. WNV virulence in birds seemed critical in establishing elevated viremias necessary to efficiently infect blood feeding Culex mosquitoes.
Transcription Factors NRF2 and NF-κB Are Coordinated Effectors of the Rho Family, GTP-binding Protein RAC1 during Inflammation*

Background: RAC1 is a small G-protein of the Rho family that activates the transcription factor NF-κB to elicit an inflammatory response. Results: We have found that RAC1 also induces the NRF2/ARE pathway, which in term blocks RAC1-dependent NF-κB activation. Conclusion: RAC1 modulates inflammation by coordinating the activity of pro-inflammatory NF-κB and anti-oxidant NRF2 transcription factors. Significance: Therapeutic intervention on RAC1 could help modulate pro- and anti-inflammatory processes. The small GTPase protein RAC1 participates in innate immunity by activating a complex program that includes cytoskeleton remodeling, chemotaxis, activation of NADPH oxidase, and modulation of gene expression. However, its role in regulating the transcriptional signatures that in term control the cellular inflammatory profiles are not well defined. Here we investigated the functional and mechanistic connection between RAC1 and the transcription factor NRF2 (nuclear factor erythroid 2-related factor 2), master regulator of the anti-oxidant response. Lipopolysaccharide and constitutively active RAC1Q61L mutant induced the anti-oxidant enzyme heme-oxygenase-1 (HO-1) through activation of NRF2. The use of KEAP1-insensitive NRF2 mutants indicated that RAC1 regulation of NRF2 is KEAP1-independent. Interestingly, NRF2 overexpression inhibited, whereas a dominant-negative mutant of NRF2 exacerbated RAC1-dependent activation of nuclear factor-κB (NF-κB), suggesting that NRF2 has an antagonistic effect on the NF-κB pathway. Moreover, we found that RAC1 acts through NF-κB to induce NRF2 because either expression of a dominant negative mutant of IκBα that leads to NF-κB degradation or the use of p65-NF-κB-deficient cells demonstrated lower NRF2 protein levels and basally impaired NRF2 signature compared with control cells. In contrast, NRF2-deficient cells showed increased p65-NF-κB protein levels, although the mRNA levels remain unchanged, indicating post-translational alterations. Our results demonstrate a new mechanism of modulation of RAC1 inflammatory pathway through a cross-talk between NF-κB and NRF2.
Salvage surgery of cervical recurrences after neck dissection or radiotherapy

A series of 113 patients operated on in the period 1980–1989 for a neck recurrence from a head and neck cancer was studied. All patients had no other evidence of disease. The male/female ratio was 93/20, and the median age was 58 years (range 28–87). Previous treatment consisted of surgery (SG) ± radiotherapy (RT) in 81 patients (SG group) and only RT in 32 (RT group): 59 cases presented a relapse in the treated neck and 54 in the contralateral side. All but one contralateral recurrences were in the SG group. Ten patients were lost to followup. The observed 5‐year survival rate of the whole series was 29.2% (95% confidence interval, 0%–38%). Considering patients with ipsilateral recurrences, the 5‐year disease‐free survival rate was 38.7% (95% c.i., 28.7%–48.7%) and 27% (95% c.i., 18%–36%) for the SG and the AT group, respectively. The 5‐year disease‐free survival rate after SG for contralateral recurrences was 38.8% (95% c.i., 23.8%–53.8%). Dimension and mobility of the neck nodes were the only demonstrable prognostic factors.
DNA Recombination-Initiation Plays a Role in the Extremely Biased Inheritance of Yeast [rho−] Mitochondrial DNA That Contains the Replication Origin ori5

ABSTRACT Hypersuppressiveness, as observed in Saccharomyces cerevisiae, is an extremely biased inheritance of a small mitochondrial DNA (mtDNA) fragment that contains a replication origin (HS [rho−] mtDNA). Our previous studies showed that concatemers (linear head-to-tail multimers) are obligatory intermediates for mtDNA partitioning and are primarily formed by rolling-circle replication mediated by Mhr1, a protein required for homologous mtDNA recombination. In this study, we found that Mhr1 is required for the hypersuppressiveness of HS [ori5] [rho−] mtDNA harboring ori5, one of the replication origins of normal ([rho+]) mtDNA. In addition, we detected an Ntg1-stimulated double-strand break at the ori5 locus. Purified Ntg1, a base excision repair enzyme, introduced a double-stranded break by itself into HS [ori5] [rho−] mtDNA at ori5 isolated from yeast cells. Both hypersuppressiveness and concatemer formation of HS [ori5] [rho−] mtDNA are simultaneously suppressed by the ntg1 null mutation. These results support a model in which, like homologous recombination, rolling-circle HS [ori5] [rho−] mtDNA replication is initiated by double-stranded breakage in ori5, followed by Mhr1-mediated homologous pairing of the processed nascent DNA ends with circular mtDNA. The hypersuppressiveness of HS [ori5] [rho−] mtDNA depends on a replication advantage furnished by the higher density of ori5 sequences and on a segregation advantage furnished by the higher genome copy number on transmitted concatemers.
Cutting Edge: Mouse Pellino-2 Modulates IL-1 and Lipopolysaccharide Signaling1

Pellino is a Drosophila protein originally isolated in a two-hybrid screen for proteins interacting with the serine/threonine kinase, pelle. Although mammalian homologs have been identified in mouse and man, the function of pellino is as yet unknown. In this study, the cloning, expression pattern, and a preliminary characterization of mouse pellino-2 is described. These studies reveal that mouse pellino-2 is expressed during embryogenesis and in a tissue-restricted manner in the adult. IL-1 induces the association of mouse pellino-2 with the mouse pelle-like kinase/IL-1R-associated kinase protein, a mammalian homolog of pelle. Ectopic pellino-2 expression did not result in NF-κB activation. However, ectopic expression of a mouse pellino-2 antisense construct inhibited IL-1 or LPS-induced activation of NF-κB-dependent IL-8 promoter activity. Our data reveal that mouse pellino-2 is a tissue-restricted component of a signaling pathway that couples the mouse pelle-like kinase/IL-1R-associated kinase protein to IL-1- or LPS-dependent signaling.
Ten reasons why we should NOT use severity scores as entry criteria for clinical trials or in our treatment decisions*

Objective:Severity scores such as Acute Physiology and Chronic Health Evaluation II have been advocated as entry criteria for clinical trials and in clinical decision-making. We present ten reasons why we believe this approach is not appropriate and may even be detrimental. Data Sources:Available relevant literature from authors' personal databases and personal knowledge of past and future clinical trial development. Data Synthesis:Severity scores were not designed for use in individual patients or for therapeutic decision-making for specific interventions. Difficulties with the time window needed to calculate these scores and the need to administer therapies early further limit their use in this context. The complex nature of the scores makes it difficult to use them at the bedside and there is considerable interobserver variability in score calculation. Inclusion of chronic health and age points in severity scores may prevent younger, previously healthy patients, with similar acute physiological dysfunction and therefore total lower severity scores, from trial inclusion or from receiving therapies that may be beneficial. Conclusions:We believe severity of illness scores are poor surrogates for risk stratification and should not be used as a criterion for patient enrollment into clinical trials or as the basis for individual treatment decisions.
Are Fluctuating Asymmetry Studies Adequately Sampled? Implications of a New Model for Size Distribution

Previous work on fluctuating asymmetry (FA) has highlighted its controversial relationship with environmental stress and genetic architecture. While size‐based measures of FA have been assumed to have half‐normal distributions within populations, studies of model developmental mechanisms have suggested other plausible distributions for FA. We investigated the distribution of FA in large empirical data sets of wing shape and wing size asymmetry from three species of insects (cotton aphid Aphis gossipyii Glover, honeybee Apis mellifera, and long‐legged fly Chrysosoma crinitus). Regardless of measurement method, FA was best described by a double Pareto–lognormal (DPLN) distribution or one of its limiting functional forms. To investigate convergence of mean sample FA to the population mean at various sample sizes, we sampled repeatedly under a DPLN distribution using parameter values that best fitted our data. Sample variances are much larger, and hence, convergence is slowed considerably with univariate or multivariate size‐based measures of FA in contrast to a multivariate shape‐based measure of FA. We suggest that much of the past work on FA may be undersampled, and we recommend using multivariate shape‐based approaches or collecting larger data sets in future studies. We also discuss the implications of the DPLN distribution for understanding the developmental mechanisms underlying FA.
Tunneling Nanotubes and Gap Junctions–Their Role in Long-Range Intercellular Communication during Development, Health, and Disease Conditions

Cell-to-cell communication is essential for the organization, coordination, and development of cellular networks and multi-cellular systems. Intercellular communication is mediated by soluble factors (including growth factors, neurotransmitters, and cytokines/chemokines), gap junctions, exosomes and recently described tunneling nanotubes (TNTs). It is unknown whether a combination of these communication mechanisms such as TNTs and gap junctions may be important, but further research is required. TNTs are long cytoplasmic bridges that enable long-range, directed communication between connected cells. The proposed functions of TNTs are diverse and not well understood but have been shown to include the cell-to-cell transfer of vesicles, organelles, electrical stimuli and small molecules. However, the exact role of TNTs and gap junctions for intercellular communication and their impact on disease is still uncertain and thus, the subject of much debate. The combined data from numerous laboratories indicate that some TNT mediate a long-range gap junctional communication to coordinate metabolism and signaling, in relation to infectious, genetic, metabolic, cancer, and age-related diseases. This review aims to describe the current knowledge, challenges and future perspectives to characterize and explore this new intercellular communication system and to design TNT-based therapeutic strategies.