Deregulation of the transforming acidic coiled-coil protein 3 (TACC3), an important factor in the centrosome-microtubule system, has been linked to a variety of human cancer types. We have recently ...reported on the oncogenic potential of TACC3; however, the molecular mechanisms by which TACC3 mediates oncogenic function remain to be elucidated. In this study, we show that high levels of TACC3 lead to the accumulation of DNA double-strand breaks (DSBs) and disrupt the normal cellular response to DNA damage, at least in part, by negatively regulating the expression of ataxia telangiectasia mutated (ATM) and the subsequent DNA damage response (DDR) signaling cascade. Cells expressing high levels of TACC3 display defective checkpoints and DSB-mediated homologous recombination (HR) and non-homologous end joining (NHEJ) repair systems, leading to genomic instability. Importantly, high levels of TACC3 confer cellular sensitization to radiation and poly(ADP-ribose) polymerase (PARP) inhibition. Overall, our findings provide critical information regarding the mechanisms by which TACC3 contributes to genomic instability, potentially leading to cancer development, and suggest a novel prognostic, diagnostic and therapeutic strategy for the treatment of cancer types expressing high levels of TACC3.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Hetero-epitaxial thin films were obtained in PbTiO3/LaNiO3 thin films by using laser ablation for sequential deposition of each thin film. Structural variations were built to characterize the ...differences in local ferroelectric properties. For this study, 50 nm-thick-PTO thin films with (0 0 1) and (1 1 1) orientations were investigated. Piezoresponse force microscopy (PFM) was used to investigate the local ferroelectricity in the thin films. High piezoelectric responses were obtained in the thin films, with values of approximately 75 and 83 pm V−1 in the (0 0 1) and (1 1 1)-oriented thin films, respectively. It is notable that remarkable piezoelectric properties were obtained in the (1 1 1)-oriented thin films. The (1 1 1)-oriented thin films have the potential to be used as multi-bit memory because of the reduction of degradation in ferroelectricity and various directional piezoelectricity. We compared the functionalities of the (0 0 1)- and (1 1 1)-oriented thin films and obtained different performances in the thin films.
Aims: The objective of this study was to assess in vitro, whether heat‐killed (HK) lactic acid bacteria cells and fractionations of HK cells could suppress the viability of human cancer cells and ...inhibit the cytotoxicity associated with oxidative stress.
Methods and Results: Among the strains, the HK cells of Lactobacillus acidophilus 606 and Lactobacillus casei ATCC 393 exhibited the most profound inhibitory activity in all of the tested cell lines. HK cells of L. acidophilus 606 were determined to be less toxic to healthy human embryo fibroblasts (hEF cells) than were HK cells of L. casei ATCC 393. The soluble polysaccharides from L. acidophilus 606 evidenced the most effective anticancer activity, but inhibited hEF cell growth by only 20%. The soluble polysaccharides from L. acidophilus 606 were partly observed to induce apoptosis in the HT‐29 cells by DNA fragmentation and propidium iodine staining. Both the HK cells of L. acidophilus 606 and the soluble polysaccharide components of this strain also exhibited potent antioxidative activity.
Conclusions: Our findings suggest that the soluble polysaccharide fraction from L. acidophilus 606 may constitute a novel anticancer agent, which manifests a high degree of selectivity for human cancer cells and antioxidative agent in the food industry.
Significance and Impact of the Study: These soluble polysaccharide components from Lactobacillus may be applied to various foods, and used as adjuncts for cancer therapy and prevention.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Spin and charge are inseparable traits of an electron, but in one-dimensional solids, theory predicts their separation into collective modes--as independent excitation quanta (or particles) called ...spinons and holons. Experimentalists have long sought to verify this effect. Angle-resolved photoemission (ARPES) should provide the most direct evidence of spin-charge separation, as the single quasiparticle peak splits into a spinon-holon two-peak-like structure. Despite extensive ARPES experiments, the unambiguous observation of the two-peak structure has remained elusive. Here we report ARPES data from SrCuO2 , made possible by recent technological developments, that unequivocally show the spinon-holon two-peak structure and their distinct dispersions. The spinon and holon branches are found to have energy scales of approximately 0.43 and 1.3 eV, respectively, which are in quantitative agreement with the theoretical predictions. PUBLICATION ABSTRACT
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IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Objective The aim of this study was to evaluate alimentary satisfaction, gastrointestinal symptoms, and quality of life ≥10 years after esophagectomy with gastric pull-up. Methods Patients who had ...undergone esophagectomy with gastric pull-up before 2003 were interviewed regarding their alimentary function and completed the Gastrointestinal Quality of Life and RAND short-form, 36-item, questionnaires. Results We identified 67 long-term survivors after esophagectomy and gastric pull-up. Of these, 40 were located, and all agreed to participate. The median age was 75 years, and the median follow-up period was 12 years (interquartile range, 10-19). Most patients (88%) had no dysphagia, 90% were able to eat ≥3 meals/day, and 93% finished ≥50% of a typical meal. The mean alimentary comfort rating was 9 of 10. Dumping, diarrhea ≥3 times/day, or regurgitation occurred in 33% of patients. Six patients (15%) had aspiration episodes requiring hospitalization. The median weight loss after surgery was 26 lbs, and the current median body mass index was 25 kg/m2 . Only 2 patients were underweight (body mass index, <18.5 kg/m2 ). The median Gastrointestinal Quality of Life score was 2.9 of 4. The RAND scores were at the population mean in 1 category (physical function) and above the normal mean in the remaining 7 categories. Conclusions Long-term nutritional status, quality of life, and satisfaction with eating were excellent after esophagectomy with gastric pull-up. Gastrointestinal side effects were common, but serious complications such as aspiration were uncommon. Pessimism regarding the long-term ability to enjoy a meal and live with a good quality of life after esophagectomy is unwarranted.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The performance of LEDs with Ga-doped ZnO (Ga:ZnO) and Sn-doped In2O3 (ITO) current-spreading layers (CSLs) has been evaluated at high injection current densities. LEDs with electron ...beam-hydrothermally deposited Ga:ZnO transparent CSLs showed improved performance compared to electron beam deposited ITO at all current densities. External quantum efficiency and wall plug efficiency were both higher for blue emitting LEDs with ZnO. Luminous efficacy increased greatly for the ZnO-based CSL with a peak value of 113 lm/W compared to 82 lm/W for the ITO-based CSL, a 37% improvement.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Cytokeratin19 (KRT19) is widely used as a biomarker for the detection of disseminated tumors. Using an LC-MS/MS proteomics approach, we found that KRT19 was upregulated in HER2-overexpressing cells ...and tissues. KRT19 expression was induced by HER2-downstream ERK at the transcriptional level. Another HER2-downstream kinase, Akt, was found to phosphorylate KRT19 on Ser35 and induce membrane translocation of KRT19 and remodeling of KRT19 from filamentous to granulous form. KRT19 phosphorylated by Akt could bind HER2 on the plasma membrane and stabilized HER2 via inhibition of proteasome-mediated degradation of HER2. Silencing of KRT19 by shRNA resulted in increased ubiquitination and destabilization of HER2. Moreover, treatment of KRT19 antibody resulted in downregulation of HER2 and reduced cell viability. These data provide a new rationale for targeting HER2-positive breast cancers.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
In endothelial cells, two type I receptors of the transforming growth factor β (TGF-β) family, ALK1 and ALK5, coordinate to regulate embryonic angiogenesis in response to BMP9/10 and TGF-β. Whereas ...TGF-β binds to and activates ALK5, leading to Smad2/3 phosphorylation and inhibition of endothelial cell proliferation and migration, BMP9/10 and TGF-β also bind to ALK1, resulting in the activation of Smad1/5. SnoN is a negative regulator of ALK5 signaling through the binding and repression of Smad2/3. Here we uncover a positive role of SnoN in enhancing Smad1/5 activation in endothelial cells to promote angiogenesis. Upon ligand binding, SnoN directly bound to ALK1 on the plasma membrane and facilitated the interaction between ALK1 and Smad1/5, enhancing Smad1/5 phosphorylation. Disruption of this SnoN-Smad interaction impaired Smad1/5 activation and up-regulated Smad2/3 activity. This resulted in defective angiogenesis and arteriovenous malformations, leading to embryonic lethality at E12.5. Thus, SnoN is essential for TGF-β/BMP9-dependent biological processes by its ability to both positively and negatively modulate the activities of Smad-dependent pathways.
We examine the source of the longitudinal asymmetry in the ionospheric tidal structure by using the measurements of the plasma density and vertical plasma drift by the first Republic of China ...satellite. The consistent feature in plasma density and vertical plasma drift in all months is the development of the wave crests near 0°–10°E and 90°–100°E longitude. The appearance of the global wave‐4 or wave‐3 structure is determined by the morphology between 150°E and 300°E longitude. Two crests are pronounced in July–September, and only one crest appears during the December solstice in that longitude region. The crests of the wave‐4 structure between 150°E and 300°E longitude are much weaker than the crests near the longitudes of 0° and 90°E during July–September. The wave‐3 structure is pronounced in all months. The phase difference between the wave‐3 and wave‐4 structures is small near the longitudes of 0° and 90°E, and thus the superposition of the wave‐3 structure amplifies the wave‐4 crest intensity in those regions. The phase difference is large between 150°E and 300°E longitude, and thus the destructive superposition of the wave‐3 component weakens the wave‐4 crest in that region. The wave‐3 and wave‐4 structures are the permanent ionospheric features, and the significant portion of the longitudinal asymmetry is explained by the phase difference of the two structures.
Key Points
The vertical plasma drift induces the ionospheric longitudinal asymmetry
The asymmetry is explained by the wave‐4 and wave‐3 structure phase difference
Wave‐3 structure is the dominant structure in the ionosphere
Patients with Alzheimer's disease (AD) and AD related dementias (ADRD) often experience spatial disorientation that can lead to wandering behavior, characterized by aimless or purposeless movement. ...Wandering behavior has been associated with falls, caregiver burden, and nursing home placement. Despite the substantial clinical consequences of wandering, there is currently no standardized approach to objectively quantify wandering behavior. In this pilot feasibility study, we used a lightweight inertial sensor to examine mobility characteristics of a small group of 12 older adults with ADRD and mild cognitive impairment in their homes. Specifically, we evaluated their compliance with wearing a sensor for a minimum of 4 days. We also examined the ability of the sensor to measure turning frequency and direction changes, given that frequent turns and direction changes during walking have been observed in patients who wander. We found that all patients were able to wear the sensor yielding quantitative turn data including number of turns over time, mean turn duration, mean peak turn speed, and mean turn angle. We found that wanderers make more frequent, quicker turns compared to non-wanderers, which is consistent with pacing or lapping behavior. This study provides preliminary evidence that continuous monitoring in patients with dementia is feasible using a wearable sensor. More studies are needed to explore if objective measures of turning behaviors collected using inertial sensors can be used to identify wandering behavior.
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