Identification of Tumor Suppressive Genes Regulated by miR-31-5p and miR-31-3p in Head and Neck Squamous Cell Carcinoma

We identified the microRNA (miRNA) expression signature of head and neck squamous cell carcinoma (HNSCC) tissues by RNA sequencing, in which 168 miRNAs were significantly upregulated, including both strands of the miR-31 duplex (miR-31-5p and miR-31-3p). The aims of this study were to identify networks of tumor suppressor genes regulated by miR-31-5p and miR-31-3p in HNSCC cells. Our functional assays showed that inhibition of miR-31-5p and miR-31-3p attenuated cancer cell malignant phenotypes (cell proliferation, migration, and invasion), suggesting that they had oncogenic potential in HNSCC cells. Our in silico analysis revealed 146 genes regulated by miR-31 in HNSCC cells. Among these targets, the low expression of seven genes (miR-31-5p targets: CACNB2 and IL34; miR-31-3p targets: CGNL1, CNTN3, GAS7, HOPX, and PBX1) was closely associated with poor prognosis in HNSCC. According to multivariate Cox regression analyses, the expression levels of five of those genes (CACNB2: p = 0.0189; IL34: p = 0.0425; CGNL1: p = 0.0014; CNTN3: p = 0.0304; and GAS7: p = 0.0412) were independent prognostic factors in patients with HNSCC. Our miRNA signature and miRNA-based approach will provide new insights into the molecular pathogenesis of HNSCC.     

Stick-slip motion control based on cutter location data for an orthogonal-type robot

In this article, a new desktop orthogonal-type robot, which has the capacity of stick-slip motion control based on cutter location data, is presented for lapping small metallic molds with a curved surface. The robot consists of three single-axis devices with a high position resolution of 1 μm. A thin wooden stick tool with a ball-end shape is attached to the tip of the z-axis. In order to improve the lapping performance, a novel stick-slip motion control method is developed in the control system. The small stick-slip motion is orthogonally generated in the direction of the tool’s movement. The effectiveness of stick-slip motion control is examined through an actual lapping test of an LED lens cavity.     

Comparison of plasma lidocaine concentrations after injection of a fixed small volume in the stellate ganglion, the lumbar epidural space, or a single intercostal nerve

Carpal tunnel syndrome may be caused by repeated or sustained elevated carpal tunnel pressure. This study examined the relationship between carpal tunnel pressure, posture, and fingertip load. In 20 healthy individuals, carpal tunnel pressure was measured with a catheter inserted into the carpal tunnel of the dominant hand and connected to a pressure transducer. With the wrist in a pressure-neutral position, the subjects pressed on a force transducer with the index finger to levels of 0, 5, 10, and 15 N. They then pinched the transducer at the same levels of force. For both fingertip-loading postures, the carpal tunnel pressure increased with increasing fingertip load. Carpal tunnel pressures were significantly greater (p < 0.015) for the pinching task (14.2, 29.9, 41.9, and 49.7 mm Hg [1.89, 3.99, 5.59, and 6.63 kPa] for 0, 5, 10, and 15 N force levels, respectively) than for simple finger pressing (7.8, 14.1, 20.0, and 33.8 mm Hg [1.04, 1.88, 2.67, and 4.51 kPa]). This study indicates that although the external load on the finger remained constant between the two tasks, the internal loading, as measured by carpal tunnel pressure, experienced a near 2-fold increase by using a pinch grip. These findings should be given consideration in designing work tasks and tools because relatively low fingertip forces, especially in a pinch grip, elevate carpal tunnel pressures to levels that, if prolonged, may lead to the development or exacerbation of carpal tunnel syndrome.     

Controller design of desktop-size NC machine tool with multi-application function

In this paper, a desktop-size NC machine tool is first presented to have multi-application function, such as 3D-machining modes with and without handling a machining force, and profiling-control modes with and without using stick-slip motion. The NC machine tool consists of three single-axis devices with a high resolution of 1???m in position. A ball end mill called router bit or a thin wood-stick tool can be attached to the tip of the z-axis. The proposed machine tool realizes compliant motion required for the profiling control along a desired trajectory. The profiling-control mode can be applied to the lapping process of a metallic LED lens cavity. Next, a control strategy with fine stick-slip motion is further added to the profiling-control system to improve the lapping performance. The fine stick-slip motion is generated orthogonally to the direction of the tool movement. Generally, the stick-slip motion is an undesirable phenomenon to be eliminated in precision machineries. However, the proposed machine tool employs the fine stick-slip motion to partly regulate slight finishing energy. The effectiveness of the machine tool is demonstrated through an actual machining test of a wood material and a lapping test of a metallic LED lens cavity.     

Structural basis for binding of the plasmid ColIb-P9 antisense Inc RNA to its target RNA with the 5'-rUUGGCG-3' motif in the loop sequence

The sequence 5'-rUUGGCG-3' is conserved within the loop regions of antisense RNAs or their targets involved in replication of various prokaryotic plasmids. In IncIalpha plasmid ColIb-P9, the partially base paired 21-nucleotide loop of a stem-loop called structure I within RepZ mRNA contains this hexanucleotide sequence, and comprises the target site for the antisense Inc RNA. In this report, we find that the base pairing interaction at the 5'-rGGC-3' sequence in the hexanucleotide motif is important for interaction between Inc RNA and structure I. In addition, the 21-base loop domain of structure I is folded tighter than predicted, with the hexanucleotide sequence at the top. The second U residue in the sequence is favored for Inc RNA binding in a base-specific manner. On the other hand, the upper domain of the Inc RNA stem-loop is loosely structured, and maintaining the loop sequence single-stranded is important for the intermolecular interaction. Based on these results, we propose that a structural feature in the loop I domain, conferred probably by the conserved 5'-rUUGGCG-3' sequence, favors binding to a complementary, single-stranded RNA. This model also explains how the RepZ mRNA pseudoknot, described in the accompanying paper (Asano, K., and Mizobuchi, K. (1998) J. Biol. Chem. 273, 11815-11825) is formed specifically with structure I. A possible conformation adopted by the 5'-rUUGGCG-3' loop sequence is discussed.     

Pure red cell aplasia and myasthenia gravis with thymoma: a case report and review of the literature

In women, osteoporosis with fractures can happen between 50 years, the age of the menopause, and 80 years. Over these three decades, the condition of bone metabolism is not the same. The years after menopause present with high bone turnover. During these years, the administration of antiresorptive drugs is promising: Estrogens (plus progestagens), calcitonins, bisphosphonates. About 10 years after the menopause bone turnover slows down to low turnover. Now the administration of bone-formation stimulating agents is to be preferred: fluorides in the first line, perhaps anabolics in single cases. The prominent fracture of women older than 75 years is the hip fracture (type II osteoporosis). Bone turnover mostly is accelerated again, now due to secondary hyperparathyroidism as a consequence of long-lasting calcium and vitamin D deficiency. For treatment, calcium plus vitamin D is recommended. The exact diagnosis of the metabolic status of the skeleton is a prerequisite for the choice of the optimal therapeutic principle.     

Comparative study of activity of cerium oxide at thermal reduction temperatures of 1300–1550 °C for solar thermochemical two-step water-splitting cycle

Thermochemical two-step water-splitting using CeO₂ (cerium oxide) particles was studied to examine oxygen and hydrogen productivity and repeatability at thermal reduction (T-R) temperatures of 1300–1550 °C and water decomposition (W-D) temperatures of 400–1000 °C for the production of hydrogen from water using concentrated solar radiation as the energy source. The temperature dependency of oxygen and hydrogen productivity and the cyclic repeatability of CeO₂ are reported in this paper. The characteristic features of CeO₂ particles in the thermochemical two-step water-splitting cycle are compared with the well-known highly active reactive mediums of zirconia-supported Ni-ferrites (NiFe₂O₄/m-ZrO₂ and NiFe₂O₄/c-YSZ) and unsupported NiFe₂O₄.     

Impact of Oncogenic Targets by Tumor-Suppressive miR-139-5p and miR-139-3p Regulation in Head and Neck Squamous Cell Carcinoma

We newly generated an RNA-sequencing-based microRNA (miRNA) expression signature of head and neck squamous cell carcinoma (HNSCC). Analysis of the signature revealed that both strands of some miRNAs, including miR-139-5p (the guide strand) and miR-139-3p (the passenger strand) of miR-139, were downregulated in HNSCC tissues. Analysis of The Cancer Genome Atlas confirmed the low expression levels of miR-139 in HNSCC. Ectopic expression of these miRNAs attenuated the characteristics of cancer cell aggressiveness (e.g., cell proliferation, migration, and invasion). Our in silico analyses revealed a total of 28 putative targets regulated by pre-miR-139 (miR-139-5p and miR-139-3p) in HNSCC cells. Of these, the GNA12 (guanine nucleotide-binding protein subunit alpha-12) and OLR1 (oxidized low-density lipoprotein receptor 1) expression levels were identified as independent factors that predicted patient survival according to multivariate Cox regression analyses (p = 0.0018 and p = 0.0104, respectively). Direct regulation of GNA12 and OLR1 by miR-139-3p in HNSCC cells was confirmed through luciferase reporter assays. Moreover, overexpression of GNA12 and OLR1 was detected in clinical specimens of HNSCC through immunostaining. The involvement of miR-139-3p (the passenger strand) in the oncogenesis of HNSCC is a new concept in cancer biology. Our miRNA-based strategy will increase knowledge on the molecular pathogenesis of HNSCC.     

A survey of perfluorooctane sulfonate and related perfluorinated organic compounds in water,fish, birds,and humans from Japan

Occurrence of perfluorooctane sulfonate (PFOS) in the tissues of humans and wildlife is well documented. In this study, concentrations and distribution of PFOS, perfluorohexane sulfonate (PFHS), and perfluorobutane sulfonate (PFBS) were determined in samples of surface water, fish and bird blood and livers, and human blood collected in Japan. Notable concentrations of PFOS were found in surface water and fish from Tokyo Bay. PFOS was found in all of the 78 samples of fish blood and liver analyzed. Based on the concentrations of PFOS in water and in fish livers, bioconcentration factors were calculated to range from 274 to 41 600. Concentrations of PFOS in the blood of Japanese human volunteers ranged from 2.4 to 14 ng/mL. PFHS was detected in 33% of the fishes analyzed, at concentrations severalfold less than those of PFOS.     

Activities of maturation-promoting factor (MPF) and mitogen-activated protein kinase (MAPK) are not required for the global histone deacetylation observed after germinal vesicle breakdown (GVBD) in porcine oocytes

The acetylation of nuclear core histone has been suggested to work as an epigenetic mark for transmitting gene expression patterns to daughter cells. Global histone deacetylations, presumably involved in the reprogramming of the gene expression, have been observed after germinal vesicle breakdown (GVBD) in a cell cycle-dependent manner during meiotic maturation of mouse and porcine oocytes, although the regulation mechanism of histone deacetylation has not been studied well. In the present study, we examined the involvement of a crucial cell-cycle-regulator, maturation-promoting factor (MPF), and a meiosis-related kinase, mitogen-activated protein kinase (MAPK), in the global histone deacetylation during porcine oocyte maturation. In order to know whether the activities of MPF and MAPK were required, or the breakdown of GV membrane was sufficient, for the global histone deacetylation observed after GVBD, we artificially destroyed the GV membrane of the porcine immature oocytes. The artificial GV destruction (AGVD) induced histone deacetylation without the activation of MPF and MAPK. This deacetylation after AGVD was not affected by an MPF inhibitor, roscovitine, or an inhibitor of protein synthesis, cycloheximide, but was completely prevented by an inhibitor of histone deactylases (HDACs), trichostatine A. HDAC1 was present in the GV of the immature oocytes and localized on chromosomes after GVBD and AGVD. These results suggest that the MPF and MAPK activities were dispensable and the breakdown of the GV membrane was sufficient for the global histone deacetylation, which was catalyzed by HDAC activity.