Establishment of THP-1 Monocytes with Compromised Mitochondrial Functions

The process of inflammation is important for both normal health and in a number of diseases, such as metabolic disorders, autoimmune diseases, and neurodegenerative diseases. Mitochondria are vital for the functioning of all cells. It had been implicated as a key player in inflammatory processes, especially through reactive oxygen species as signals of various immune responses. This study aimed to establish a THP-1 cell line with compromised mitochondrial functions, using antimycin A as a Complex III inhibitor, and to investigate the role of mitochondrial stress, as monitored by the expression of Hsp60, in inflammatory processes. High concentrations of antimycin A (100 and 200 μM) were cytotoxic to THP-1 monocytes that they were rapidly killed within 48 hours of exposure. Lower concentrations of antimycin A (5, 10, 25 and 50 μM) gave growth inhibition effects to THP-1 monocytes. Pyruvate and uridine were used with an intention of rescuing the THP-1 cell growth at lower antimycin A concentrations. The THP-1 monocytes treated with antimycin A with uridine and pyruvate showed more growth compared to the ones without uridine and pyruvate supplement. Yet this difference is insignificant statistically. The expressions of Hsp60 and TNF-α at the mRNA level was monitored using reverse transcriptase polymerase chain reaction. Hsp60 expression from THP-1 monocytes only showed some minor fluctuations in different antimycin A concentrations, regardless of uridine and iii pyruvate supplement, indicating the stress mitochondrial response was unobvious. On the other hand, TNF-α expression was dramatically down-regulated in THP-1 monocytes treated with antimycin A only compared to the untreated control and ones supplemented with uridine and pyruvate. These results suggest that antimycin A may have inhibition effect towards TNF-α expression, and uridine and pyruvate could also have other functions in THP-1 monocytes apart from redox rescue compounds. Yet the mitochondrial stress response shown by Hsp60 induction still remains to be further investigated

Mechanical ball shear, electromigration, and thermal cycling reliability testing on novel solder interconnects of highly integrated chips for advanced applications

In the near future, Ultra Large Scale Integrated Circuits (ULSI) with high integration has drawn the huge attention because of its potential applications in VR, AI, IoTs and automotive regions. Thermal budget and reliability concerns are two major issues that are urgently needed to be solved for these technologies. Since the increasing integration of ICs might lead to low yield concern, low fabrication temperature is expected to reduce the thermal impact on ICs properties. Besides, better reliability is also required to the electric devices for those to work under harsh outdoor environments. This study is tended to be focused on the novel solder bonds for the advanced ICs, including low temperature solder, Cu-core solder ball, and their response under various reliability tests. Three main reliability tests: (1) ball shear test, (2) electromigration test (EM) and (3) thermal cycling test (TCT), are conducted to evaluate the reliability of solder bonds. In this work, the novel Bi-40In solder alloy with improved mechanical property and the EM-resisted Cu-core solder ball are demonstrated. The re-designed low temperature solder joint reveals the superior ball shear strength than that of conventional eutectic Bi-33In joint. Additionally, the interconnects using Cu-core solder ball show the high resistance against EM under current stressing. Regarding TCT, the assemble joints with various grain structures are tested to realize the effects of Sn grain size on joint degradation and the possible ways for relieving the thermomechanical stress caused by TCT. The microstructure, elemental characteristics and grain structure are analyzed by FE-SEM, FE-EPMA and EBSD, respectively. The failure mechanisms for all reliability tests are addressed and discussed in details as well

Assessment of Changes in Knowledge and Stigmatization Following Tuberculosis Training Workshops in Taiwan

Background/PurposeThere is little understanding of the depth of knowledge of health workers involved in tuberculosis (TB) control programs, and even less is known about health workers attaching stigma to TB patients. This study surveyed health workers enrolled in TB training workshops prior to the execution of the directly observed treatment, short course (DOTS) program.MethodsAll participants attended the training course and completed structured questionnaires before (pre-test) and after training (post-test). The questionnaires were collected immediately following completion and the scores were analyzed.ResultsPair comparison of knowledge scores revealed that all participants made statistically significant improvements in level of TB knowledge, except those who had a history of TB (p = 0.331). Pair comparison of stigmatization scores revealed a reduction in stigmatization, with the DOTS workers attaching less stigma to TB patients. After training, caregivers, including women (p = 0.012), public health workers (p = 0.028), 40–49-year-old subjects (p = 0.035), those with an education of < 12 years (p = 0.024), those who had been a volunteer (p = 0.018), and those who had a history of TB and those who did not (p = 0.034, p = 0.036), were significantly less likely to stigmatize patients. TB knowledge was not found to be significantly correlated with stigmatization (pre-test, p = 0.298; post-test, p = 0.821).ConclusionTraining workshops in TB control were effective for promotion of knowledge and elimination of stigmatization in first-line caregivers. DOTS workers attached less stigma to TB patients than public health workers, and older workers who had been volunteers attached the least stigma

Role of autophagy-related proteins ATG8f and ATG8h in the maintenance of autophagic activity in Arabidopsis roots under phosphate starvation

Nutrient starvation-induced autophagy is a conserved process in eukaryotes. Plants defective in autophagy show hypersensitivity to carbon and nitrogen limitation. However, the role of autophagy in plant phosphate (Pi) starvation response is relatively less explored. Among the core autophagy-related (ATG) genes, ATG8 encodes a ubiquitin-like protein involved in autophagosome formation and selective cargo recruitment. The Arabidopsis thaliana ATG8 genes, AtATG8f and AtATG8h, are notably induced in roots under low Pi. In this study, we show that such upregulation correlates with their promoter activities and can be suppressed in the phosphate response 1 (phr1) mutant. Yeast one-hybrid analysis failed to attest the binding of the AtPHR1 transcription factor to the promoter regions of AtATG8f and AtATG8h. Dual luciferase reporter assays in Arabidopsis mesophyll protoplasts also indicated that AtPHR1 could not transactivate the expression of both genes. Loss of AtATG8f and AtATG8h leads to decreased root microsomal-enriched ATG8 but increased ATG8 lipidation. Moreover, atg8f/atg8h mutants exhibit reduced autophagic flux estimated by the vacuolar degradation of ATG8 in the Pi-limited root but maintain normal cellular Pi homeostasis with reduced number of lateral roots. While the expression patterns of AtATG8f and AtATG8h overlap in the root stele, AtATG8f is more strongly expressed in the root apex and root hair and remarkably at sites where lateral root primordia develop. We hypothesize that Pi starvation-induction of AtATG8f and AtATG8h may not directly contribute to Pi recycling but rely on a second wave of transcriptional activation triggered by PHR1 that fine-tunes cell type-specific autophagic activity

Long-term results of intensity-modulated radiotherapy concomitant with chemotherapy for hypopharyngeal carcinoma aimed at laryngeal preservation

<p>Abstract</p> <p>Background</p> <p>The objective of this retrospective study is to investigate laryngeal preservation and long-term treatment results in hypopharyngeal carcinoma treated with intensity-modulated radiotherapy (IMRT) combined with chemotherapy.</p> <p>Methods</p> <p>Twenty-seven patients with hypopharyngeal carcinoma (stage II-IV) were enrolled and underwent concurrent chemoradiotherapy. The chemotherapy regimens were monthly cisplatin and 5-fluorouracil for six patients and weekly cisplatin for 19 patients. All patients were treated with IMRT with simultaneous integrated boost technique. Acute and late toxicities were recorded based on CTCAE 3.0 (Common Terminology Criteria for Adverse Events).</p> <p>Results</p> <p>The median follow-up time for survivors was 53.0 months (range 36-82 months). The initial complete response rate was 85.2%, with a laryngeal preservation rate of 63.0%. The 5-year functional laryngeal, local-regional control, disease-free and overall survival rates were 59.7%, 63.3%, 51.0% and 34.8%, respectively. The most common greater than or equal to grade 3 acute and late effects were dysphagia (63.0%, 17 of 27 patients) and laryngeal stricture (18.5%, 5 of 27 patients), respectively. Patients belonging to the high risk group showed significantly higher risk of tracheostomy compared to the low risk group (p = 0.014).</p> <p>Conclusions</p> <p>After long-term follow-up, our results confirmed that patients with hypopharyngeal carcinoma treated with IMRT concurrent with platinum-based chemotherapy attain high functional laryngeal and local-regional control survival rates. However, the late effect of laryngeal stricture remains a problem, particularly for high risk group patients.</p

7-Hy­droxy­indan-1-one

In the title compound, C9H8O2, an intra­molecular O—H⋯O hydrogen bond generates an S(6) ring. The dihedral angle between the mean plane of the S(6) ring and the benzene ring is 1.89 (2)°. In the crystal, inversion-related mol­ecules are linked by pairs of O—H⋯O hydrogen bonds, forming a cyclic dimers with R 2 2(12) graph-set motif. Weak inter­molecular C—H⋯Ocarbon­yl and C—H⋯Ohy­droxy hydrogen bonds link the dimers into chains along [010], generating two C(6) motifs that overlap three C atoms, forming R 2 2(8) ring motifs

Trypsin-induced proteome alteration during cell subculture in mammalian cells

<p>Abstract</p> <p>Background</p> <p>It is essential to subculture the cells once cultured cells reach confluence. For this, trypsin is frequently applied to dissociate adhesive cells from the substratum. However, due to the proteolytic activity of trypsin, cell surface proteins are often cleaved, which leads to dysregulation of the cell functions.</p> <p>Methods</p> <p>In this study, a triplicate 2D-DIGE strategy has been performed to monitor trypsin-induced proteome alterations. The differentially expressed spots were identified by MALDI-TOF MS and validated by immunoblotting.</p> <p>Results</p> <p>36 proteins are found to be differentially expressed in cells treated with trypsin, and proteins that are known to regulate cell metabolism, growth regulation, mitochondrial electron transportation and cell adhesion are down-regulated and proteins that regulate cell apoptosis are up-regulated after trypsin treatment. Further study shows that bcl-2 is down-regulated, p53 and p21 are both up-regulated after trypsinization.</p> <p>Conclusions</p> <p>In summary, this is the first report that uses the proteomic approach to thoroughly study trypsin-induced cell physiological changes and provides researchers in carrying out their experimental design.</p

Late initiation of renal replacement therapy is associated with worse outcomes in acute kidney injury after major abdominal surgery

Introduction Abdominal surgery is probably associated with more likelihood to cause acute kidney injury (AKI). The aim of this study was to evaluate whether early or late start of renal replacement therapy (RRT) defined by simplified RIFLE (sRIFLE) classification in AKI patients after major abdominal surgery will affect outcome. Methods A multicenter prospective observational study based on the NSARF ( National Taiwan University Surgical ICU Associated Renal Failure) Study Group database. 98 patients (41 female, mean age 66.4 +/- 13.9 years) who underwent acute RRT according to local indications for post-major abdominal surgery AKI between 1 January, 2002 and 31 December, 2005 were enrolled The demographic data, comorbid diseases, types of surgery and RRT, as well as the indications for RRT were documented. The patients were divided into early dialysis (sRIFLE-0 or Risk) and late dialysis (LD, sRIFLE -Injury or Failure) groups. Then we measured and recorded patients' outcome including in-hospital mortality and RRT wean-off until 30 June, 2006. Results The in-hospital mortality was compared as endpoint. Fifty-seven patients (58.2%) died during hospitalization. LD (hazard ratio (HR) 1.846; P = 0.027), old age (HR 2.090; P = 0.010), cardiac failure (HR 4.620; P < 0.001), pre-RRT SOFA score (HR 1.152; P < 0.001) were independent indicators for in-hospital mortality. Conclusions The findings of this study support earlier initiation of acute RRT, and also underscore the importance of predicting prognoses of major abdominal surgical patients with AKI by using RIFLE classification

Comment on "Periodic Phase Synchronization in Coupled Chaotic Oscillators"

2 pages.-- PACS numbers: 05.45.Xt, 05.45.Pq.-- Final full-text version of the paper available at: http://dx.doi.org/10.1103/PhysRevE.73.038201.Kye et al. [Phys. Rev. E 68, 025201(R) (2003)] have recently claimed that, before the onset of Chaotic Phase Synchronization in coupled phase coherent oscillators, there exists a temporally coherent state called Periodic Phase Synchronization (PPS). Here we give evidence that some of their numerical calculations are flawed, while we provide theoretical arguments that indicate that PPS is not to be expected generically in this type of systems.This work was supported by MEC (Spain) and FEDER under Grant Nos. BFM2001-0341-C02-02, FIS2004-00953 (CONOCE2), and FIS2004-05073-C04-03.http://dx.doi.org/10.1103/PhysRevE.73.03820