Understanding the role of myoglobin content in Iberian pigs fattened in an extensive system through analysis of the transcriptome profile.
Meat color is the first perceived sensory feature and one of the most important quality traits. Myoglobin is the main pigment in meat, giving meat its characteristic cherry-red color, highly appreciated by the consumers. In the current study, we used the RNA-seq technique to characterize the longissimus dorsi muscle transcriptome in two groups of Iberian pigs with divergent breeding values for myoglobin content. As a result, we identified 57 differentially expressed genes and transcripts (DEGs). Moreover, we have validated the RNA-seq expression of a set of genes by quantitative PCR (qPCR). Functional analyses revealed an enrichment of DEGs in biological processes related to oxidation (HBA1), lipid metabolism (ECH1, PLA2G10, PLD2), inflammation (CHST1, CD209, PLA2G10), and immune system (CD209, MX2, LGALS3, LGALS9). The upstream analysis showed a total of five transcriptional regulatory factors and eight master regulators that could moderate the expression of some DEGs, highlighting SPI1 and MAPK1, since they regulate the expression of DEGs involved in immune defense and inflammatory processes. Iberian pigs with high myoglobin content also showed higher expression of the HBA1 gene and both molecules, myoglobin and hemoglobin, have been described as having a protective effect against oxidative and inflammatory processes. Therefore, the HBA1 gene is a very promising candidate gene to harbor polymorphisms underlying myoglobin content, whereby further studies should be carried out for its potential use in an Iberian pig selection program.


Laparoscopic ligature of the spermatic veins. A comparison between outpatient and hospitalised treatment.
The preferable operation for varicocele is ligation of all venous trunks of the spermatic vein above the internal orifice of the inguinal canal, traditionally performed by a retroperitoneal approach. An alternative method is laparoscopic ligature of the spermatic veins. To evaluate this procedure and to see if it can be done on an outpatient basis, 24 patients were operated upon laparoscopically. The patients were allocated to two series, one scheduled to be operated upon on an outpatient basis and one hospitalised. In 22 out of 24 patients the varicocele had disappeared completely at follow-up 1-3 months after the operation. Three of the patients operated upon late during the day in the outpatient group had to stay overnight. No complications occurred. The costs were more than 50% lower in the outpatient group. Laparoscopic ligature of the spermatic veins seems to be an attractive way to treat varicoceles, with good postoperative results and, if performed on an outpatient basis, with a substantial reduction of costs.


Stereospecific radiosynthesis of 3-fluoro amino acids: access to enantiomerically pure radioligands for positron emission tomography.
A variety of substituted non-racemic aziridine-2-carboxylates equivalent to amino acids were prepared and subjected to ring opening reaction by [18F/19F]fluoride. The regio and stereospecific ring opening depends on the substituents on the nitrogen as well as both the carbons of aziridines. The applicability of the methods to afford access to 3-[18F/19F]fluoro amino acids are illustrated.


Rapid Communication: High-resolution quantitative trait loci analysis identifies LTBP2 encoding latent transforming growth factor beta binding protein 2 associated with thoracic vertebrae number in a large F2 intercross between Landrace and Korean native pigs.
Number of vertebrae is associated with body size and meat productivity in pigs. The aim of this study was to identify QTL and associated positional candidate genes affecting the number of thoracic vertebrae (THO). A genomewide association study was conducted in a large resource population derived from an F intercross between Landrace and Korean native pigs using the Porcine SNP 60K BeadChip and the genomewide complex trait analysis (GCTA) program based on a linear mixed-effects model. A total of 38,385 SNP markers from 1,105 F progeny were analyzed for the THO trait after filtering for quality control. A total of 90 genomewide significant SNP markers ( < 1.30 × 10) on SSC 7 covering a 20-Mb region were identified for THO in this study. Several previous studies also mapped QTL for vertebral numbers in this region. The strongest association signals were detected at ASGA0035500 (-value = 4.46 × 10; 103,574,383 bp) and DIAS0000795 (-value = 4.46 × 10; 103,594,753 bp). The QTL region on SSC 7 for THO encompasses and , which are previously described candidate genes for vertebral number variation. To refine the QTL region, a haplotype-based linkage and linkage disequilibrium (LALD) analysis using the DualPHASE program was applied because subsequent conditional association and haplotype block analyses could not resolve the region that contains the 2 loci. The LALD analysis refined the critical region to a 533.9-kb region including ; was located outside the critical region. The gene encoding latent transforming growth factor beta binding protein 2 is involved in bone metabolisms. Based on these data, we propose as a positional candidate gene for THO in pigs. After further functional studies and verification of the association in other independent populations, these results could be useful for optimizing breeding programs that improve THO and other economically important traits in pigs.


Methotrexate for the Treatment of Graft-versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation.
Glucocorticoids have been the primary treatment of graft-versus-host disease (GVHD) over the past decade. Complete responses to steroid therapy are usually expected in almost one-third of aGVHD cases and partial response is anticipated in another one-third of patients. However, for those patients not responding to corticosteroid treatment, there is no standard second-line therapy for acute or chronic GVHD. Methotrexate (MTX) for treatment of steroid refractory GVHD has been evaluated in a number of studies. Results from peer-reviewed original articles were identified and the pooled data analyzed. Despite several limitations in data collection and analysis, weekly administration of methotrexate at a median dose of 7.5 mg/m(2) seems to be safe with minimal toxicities in the context of both aGVHD and cGVHD treatments. The observed overall response (OR) in patients with aGVHD to MTX treatment in the published studies was 69.9%, with complete response (CR) in 59.2% and PR in 10.6%. In cGVHD the OR was 77.6%, with CR reported in 49.6% and PR in 28% of patients. Predictors of better responses were lower grade GVHD, cutaneous involvement, and isolated organ involvement. MTX as a steroid sparing agent might reduce long-term complications and improve the quality of life of GVHD affected individuals.


Protein synthesis in brine shrimp embryos. Regulation of the formation of the ternary complex (Met-tRNAf X eIF-2 X GTP) by two purified protein factors and phosphorylation of Artemia eIF-2.
We have purified from the ribosomal wash of dormant and developing embryos of Artemia two proteins, Co-eIF-2(A) and Co-eIF-2(B). These factors are essential for ternary complex formation and binding of [35S]-Met-tRNAf to 40-S ribosomal subunits with 15-30 microgram eIF-2/ml of reaction mixture. On polyacrylamide gel electrophoresis in dodecylsulfate, Co-eIF-2(A) is composed of a single polypeptide of Mr 65 000, whereas Co-eIF-2(B) contains polypeptides of Mr 105000 and 112000. Co-eIF-2(A) is sensitive to 4.5 microM aurintricarboxylic acid but Co-eIF-2(B) requires approximately 15 microM aurintricarboxylic acid to give 50% inhibition of ternary complex formation. The stimulatory activity of both factors is abolished by pretreatment of the proteins with N-ethylmaleimide. Artemia eIF-2 rapidly bonds [3H]GDP or [3H]GTP and at 15 degrees C the initiation factor rapidly equilibrates bound nucleotides with free GDP or GTP. Both Co-eIF-2(A) and Co-eIF-2(B) have no effect on the exchange or the amount of nucleotide bound. The small subunit (Mr 43 000) of Artemia eIF-2 is phosphorylated in the presence of the rabbit reticulocyte heme-repressible kinase. Tryptic digestion of [32P]phosphorylated eIF-2 produces a single major phosphopeptide and several minor ones. Acid hydrolysis of these phosphopeptides, as well as of [32P]phosphorylated eIF-2, demonstrates that the radioactivity is predominantly associated with phosphoserine. Phosphorylated Artemia eIF-2 is active in ternary complex formation, in AUG-dependent binding of [35S]Met-tRNAf to 40-S ribosomal subunits and in cell-free protein synthesis. Both Co-eIF-2(A) and Co-eIF-2(B) stimulate ternary complex formation with phosphorylated eIF-2. A kinase that phosphorylates the small subunit of eIF-2 is present in the post-ribosomal supernatant as well as in the ribosomal wash of developing Artemia embryos.


Kaposi sarcoma in unusual locations.
Kaposi sarcoma (KS) is a multifocal, vascular lesion of low-grade malignant potential that presents most frequently in mucocutaneous sites. KS also commonly involves lymph nodes and visceral organs. This article deals with the manifestation of KS in unusual anatomic regions. Unusual locations of KS involvement include the musculoskeletal system, central and peripheral nervous system, larynx, eye, major salivary glands, endocrine organs, heart, thoracic duct, urinary system and breast. The development of KS within wounds and blood clots is also presented. KS in these atypical sites may prove difficult to diagnose, resulting in patient mismanagement. Theories to explain the rarity and development of KS in these unusual sites are discussed.


Clinical and microbiologic features of Shigella and enteroinvasive Escherichia coli infections detected by DNA hybridization.
To determine the clinical and microbiologic features of Shigella and enteroinvasive Escherichia coli (EIEC) infections, we investigated 410 children with diarrhea and 410 control children without diarrhea who were seen at Children's Hospital, Bangkok, Thailand, from January to June 1985. Shigella spp. were isolated from 96 (23%) and EIEC were isolated from 17 (4%) of 410 children with diarrhea and from 12 (3%) and 6 (1%) of 410 control children, respectively. The isolation rates of both pathogens increased with age and peaked in children 3 to 5 years old from whom Shigella spp. were isolated from 38% and EIEC were isolated from 9%. Shigella spp. were isolated from 52% and EIEC were isolated from 7% of 91 children with bloody diarrhea and from 15 and 3% of 319 children with nonbloody diarrhea. Fifteen (65%) of 23 EIEC were lactose positive, and all belonged to recognized EIEC serotypes. Among children with diarrhea, the stool blots of 76% of 17 children infected with EIEC, 45% of 96 children infected with Shigella spp., and 1% of 297 culture-negative children hybridized with the 17-kilobase EcoRI digestion fragment of pRM17, a recombinant plasmid containing DNA derived from the 140-megadalton Shigella flexneri plasmid. Although EIEC colonies can be reliably detected by DNA hybridization, detection by stool blot is less sensitive. Shigella spp. and EIEC are important causes of endemic diarrhea among children greater than 1 year old in Thailand.


Visual detection of DNA mutation using multicolor fluorescent coding.
A visual colorimetric method for detecting multiplex DNA mutations has been developed using multicolor fluorescent coding based on multistep FRET of cationic conjugated polymers. Expensive instruments and technical expertise are not required in this method. Also our visual system provides a quantitative detection by simply analyzing RGB values of images. Genomic DNAs extracted from 60 FFPE colon tissues can be sensitively determined by utilizing our visual assay with a high-throughput manner. Thus, it proves to be sensitive, reliable, cost-effective, simple, and high-throughput for mutation detection.


Mechanistic insights into Lp(a)-induced IL-8 expression: a role for oxidized phospholipid modification of apo(a).
Elevated lipoprotein (a) [Lp(a)] levels are a causal risk factor for coronary heart disease. Accumulating evidence suggests that Lp(a) can stimulate cellular inflammatory responses through the kringle-containing apolipoprotein (a) [apo(a)] component. Here, we report that recombinant apo(a) containing 17 kringle (17K) IV domains elicits a dose-dependent increase in interleukin (IL)-8 mRNA and protein expression in THP-1 and U937 macrophages. This effect was blunted by mutation of the lysine binding site in apo(a) kringle IV type 10, which resulted in the loss of oxidized phospholipid (oxPL) on apo(a). Trypsin-digested 17K had the same stimulatory effect on IL-8 expression as intact apo(a), while enzymatic removal of oxPL from apo(a) significantly blunted this effect. Using siRNA to assess candidate receptors, we found that CD36 and TLR2 may play roles in apo(a)-mediated IL-8 stimulation. Downstream of these receptors, inhibitors of MAPKs, Jun N-terminal kinase and ERK1/2, abolished the effect of apo(a) on IL-8 gene expression. To assess the roles of downstream transcription factors, luciferase reporter gene experiments were conducted using an IL-8 promoter fragment. The apo(a)-induced expression of this reporter construct was eliminated by mutation of IL-8 promoter binding sites for either NF-κB or AP-1. Our results provide a mechanistic link between oxPL modification of apo(a) and stimulation of proinflammatory intracellular signaling pathways.


Thienoacene-fused pentalenes: syntheses, structures, physical properties and applications for organic field-effect transistors.
Three soluble and stable thienoacene-fused pentalene derivatives (1-3) with different π-conjugation lengths were synthesized. X-ray crystallographic analysis and density functional theory (DFT) calculations revealed their unique geometric and electronic structures due to the interaction between the aromatic thienoacene units and antiaromatic pentalene moiety. As a result, they all possess a small energy gap and show amphoteric redox behaviour. Time dependent (TD) DFT calculations were used to explain their unique electronic absorption spectra. These new compounds exhibited good thermal stability and ordered packing in solid state and thus their applications in organic field-effect transistors (OFETs) were also investigated. The highest field-effect hole mobility of 0.016, 0.036 and 0.001 cm(2) V(-1) s(-1) was achieved for solution-processed thin films of 1-3, respectively.


Enzyme-linked immunosorbent assay of bovine tuberculosis by crude mycobacterial protein 70.
MPB70 (mycobacterial protein of BCG 70) as T-cell stimulator has been tried with an intradermal skin test (IST) and enzyme-linked immunosorbent assay (ELISA) of bovine tuberculosis (BTB). In this study, crude mycobacterial protein 70 (CMP70) was prepared by anion exchange chromatography from the culture supernatant of Mycobacterium bovis AN5 and CMP70 ELISA was compared with purified protein derivative (PPD) ELISA. PPD and CMP70 ELISA have shown a positive reaction to the sera of M. bovis infected cattle and IST positive reactors. One of three IST negative cattle showed the nonspecific reaction in PPD ELISA, whereas all of the IST negative cattle (n=3) were did not show the nonspecific reaction in CMP70 ELISA. When each ELISA was applied to sixty-two IST positive cattle, ELISA positive reactors were eighty four per cent to CMP70 antigen and fifty-two per cent to PPD. CMP70 has been shown to be more specific and sensitive than PPD in ELISA.


Hydrological Conditions Affect the Interspecific Interaction between Two Emergent Wetland Species.
Hydrological conditions determine the distribution of plant species in wetlands, where conditions such as water depth and hydrological fluctuations are expected to affect the interspecific interactions among emergent wetland species. To test such effects, we conducted a greenhouse experiment with three treatment categories, interspecific interaction (mixed culture or monoculture), water depth (10 or 30 cm depth), and hydrological fluctuation (static or fluctuating water level), and two common emergent wetland plant species, Scirpus planiculumis Fr. (Cyperaceae) and Phragmites australis var. baiyangdiansis (Gramineae). An increase in the water depth significantly restrained the growth of both S. planiculumis and P. australis, while hydrological fluctuations did not obviously alter the growth of either species. In addition, both water depth and hydrological fluctuations significantly affected the interspecific interaction between these two wetland species. P. australis benefited from interspecific interaction under increasing water depth and hydrological fluctuations, and the RII values were clearly positive for plants grown at a water depth that fluctuated around 30 cm. The results may have some implications for understanding how S. planiculumis and P. australis, as well as wetland communities, respond to the natural variation or human modification of hydrological conditions.


[EFFECTIVENESS OF ANATOMIC FEMORAL COMPONENT PROSTHESIS FOR SEVERE DEVELOPMENTAL DYSPLASIA OF THE HIP IN TOTAL HIP ARTHROPLASTY].
To evaluate the effectiveness of anatomic femoral component prosthesis for severe development dysplasia of the hip (DDH) in total hip arthroplasty (THA). Between September 2009 and September 2013, 48 patients (51 hips) with severe DDH underwent THA with cementless anatomic femoral component prosthesis. There were 5 males (5 hips) and 43 females (46 hips) with an average age of 51 years (range, 28-67 years). The left hip was involved in 25 cases, the right hip in 20 cases, and bilateral hips in 3 cases. There were 39 cases (44 hips) of Crowe type III and 9 cases (7 hips) of Crowe type IV. The visual analogue scale (VAS) score was 5.72 +/- 1.84, and Harris score was 41.66 +/- 4.87 at preoperation. All patients had leg discrepancy with a length difference of (4.31 +/- 0.84) cm. The duration of surgery was 59-110 minutes (mean, 78.6 minutes), and the hospitalization days were 6-20 days (mean, 12.3 days). All patients obtained primary healing of incision without wound related complications of swelling, effusion, and infection. Two patients were found to have intramuscular venous thrombosis. All patients were followed up 10-54 months (mean, 29 months). Limp was observed at the early stage after operation in 9 patients and disappeared after 1 year, the other patients had normal gait. The VAS score 1.46?0.47, Harris score 88.66 +/- 3.48, and the leg length difference (1.15 +/- 0.33) cm at last follow-up all showed significant differences when compared with the preoperative values (P<0.05). No prosthesis loosening or subsidence, heterotopic ossification, dislocation, and infection occurred. Anatomic femoral component prosthesis for severe DDH in THA can relieve pain, and improve the hip joint function and limb discrepancy. Short-term effectiveness was satisfactory, but the long-term effectiveness should still be observed in future.


Quantitative trait loci affecting 4-nitroquinoline 1-oxide-induced tongue carcinogenesis in the rat.
The incidence of tongue carcinomas (TCs) induced by oral administration of 4-nitroquinoline 1-oxide in rats is strain dependent. The inbred Dark-Agouti (DA) strain showed a much higher susceptibility to large mass-forming infiltrative TCs than did the Wistar-Furth (WF) strain. Our previous study (M. Kitano et al, Jpn. J. Cancer Res., 87: 1097-1101, 1996) on crosses between these two strains postulated a dominant susceptibility gene in DA and a dominant resistance gene in WF rats. The present study mapped these loci by analyzing the backcrosses to each parent with simple sequence repeat polymorphisms. Five quantitative parameters were analyzed: (a) the number of TCs > 5 mm in diameter; (b) the total number of TCs per rat; (c) the diameter of the largest TCs (DTCmax values); (d) the number of non-TC cancers per rat; and (e) and the number of cancers of any site per rat. All of these parameters were closely correlated (P < 0.0001). DA rats had a semidominant gene (Stc1) favoring the development of 4-nitroquinoline 1-oxide-induced cancers on chromosome 19, closely linked to D19Mit9. Peak linkage was observed 4 cM distal from D19Mit9, with a logarithm of the odds (lod) score of 5.72 for the number of large TCs and 6.08 for the DTCmax. On the other hand, WF rats had a semidominant gene (Rtc1) mapped between D1Mit1 and D1Mit3, approximately 20 cM from D1Mit1, with a peak lod score of 3.30 for both the number of large TCs and the DTCmax. The main effect of Rtc1 seemed to be to reduce the size of the TCs. The action of these genes was dose dependent and cooperative. The final incidence of TC in DA, WF, F1, and backcross rats seemed to be explained by combinations of genotype at these two loci. Possible candidate genes for Stc1 and Rtc1 are discussed.


Nanoimaging of Low-Loss Plasmonic Waveguide Modes in a Graphene Nanoribbon.
Graphene nanoribbons are predicted to support low-loss and tunable plasmonic waveguide modes with an ultrasmall mode area. Experimental observation of the plasmonic waveguide modes in graphene nanoribbons, however, is challenging because conventional wet lithography has difficulty creating a clean graphene nanoribbon with a low edge roughness. Here, we use a dry lithography method to fabricate ultraclean and low-roughness graphene nanoribbons, which are then encapsulated in hexagonal boron nitride (hBN). We demonstrate low-loss plasmon propagation with a quality factor up to 35 in the ultraclean nanoribbon waveguide using cryogenic infrared nanoscopy. In addition, we observe both the fundamental and the higher-order plasmonic waveguide modes for the first time. All the plasmon waveguide modes can be tuned through electrostatic gating. The observed tunable plasmon waveguide modes in ultraclean graphene nanoribbons agree well with the finite-difference time-domain (FDTD) simulation results. They are promising for reconfigurable photonic circuits and devices at a subwavelength scale.


Pod1/Tcf21 is regulated by retinoic acid signaling and inhibits differentiation of epicardium-derived cells into smooth muscle in the developing heart.
Epicardium-derived cells (EPDCs) invade the myocardium and differentiate into fibroblasts and vascular smooth muscle (SM) cells, which support the coronary vessels. The transcription factor Pod1 (Tcf21) is expressed in subpopulations of the epicardium and EPDCs in chicken and mouse embryonic hearts, and the transcription factors WT1, NFATC1, and Tbx18 are expressed in overlapping and distinct subsets of Pod1-expressing cells. Expression of Pod1 and WT1, but not Tbx18 or NFATC1, is activated with all-trans-retinoic acid (RA) treatment of isolated chick EPDCs in culture. In intact chicken hearts, RA inhibition leads to decreased Pod1 expression while RA treatment inhibits SM differentiation. The requirements for Pod1 in differentiation of EPDCs in the developing heart were examined in mice lacking Pod1. Loss of Pod1 in mice leads to epicardial blistering, increased SM differentiation on the surface of the heart, and a paucity of interstitial fibroblasts, with neonatal lethality. Epicardial epithelial-to-mesenchymal transition (EMT) and endothelial differentiation of coronary vessels are relatively unaffected. On the surface of the myocardium, expression of multiple SM markers is increased in Pod1-deficient EPDCs, demonstrating premature SM differentiation. Increased SM differentiation also is observed in Pod1-deficient lung mesenchyme. Together, these data demonstrate a critical role for Pod1 in controlling mesenchymal progenitor cell differentiation into SM and fibroblast lineages during cardiac development.


The risk of needle stick accidents during surgical procedures: HIV-1 viral load in blood and bone marrow.
Health-care workers are at risk to acquire HIV through occupational exposure to blood of HIV-infected patients. The mean risk after a percutaneous exposure is approximately 0.3%. A large inoculum and a source patient with a high plasma viral load increases the transmission risk. To ensure the safety of the operating team, we try to reduce HIV viral load in plasma prior to high-risk interventions (cardiothoracic and orthopaedic surgery). However, in 15.7% of the exposures occurring in the operating room, the possible source material is bone marrow. To make more accurate exposure risk assessments, we measured HIV-1 RNA in both plasma and bone marrow of five HIV-infected patients undergoing surgery. We found that the plasma viral load was not different from the viral load in bone marrow.


Recurrent Microdeletions at Xq27.3-Xq28 and Male Infertility: A Study in the Czech Population.
Genetic causes of male infertility are hypothesized to involve multiple types of mutations, from single gene defects to complex chromosome rearrangements. Recently, several recurrent X-chromosome microdeletions (located in subtelomeric region of the long arm) were reported to be associated with male infertility in Spanish and Italian males. The aim of our study was to test their prevalence and infertility association in population of men from the Czech Republic. 107 males with pathological sperm evaluation resulting in nonobstructive infertility were compared to 131 males with normal fecundity. X-chromosome microdeletions were assessed by +/- PCR with three primer pairs for each region Xcnv64 (Xq27.3), Xcnv67 (Xq28) and Xcnv69 (Xq28). The latter microdeletion was further characterized by amplification across the deleted region, dividing the deletion into three types; A, B and C. We detected presence of isolated Xcnv64 deletion in 3 patients and 14 controls, and Xcnv69 in 3 patients and 6 controls (1 and 1 patient vs.4 and 1 control for types A and B respectively). There was one control with combined Xcnv64 and Xcnv69 type B deletions, and one patient with combination of Xcnv64 and Xcnv69 type C deletions. The frequency of the deletions was thus not higher in patient compared to control group, Xcnv64 was marginally associated with controls (adjusted Fisher´s exact test P = 0.043), Xcnv69 was not associated (P = 0.452). We excluded presence of more extensive rearrangements in two subjects with combined Xcnv64 and Xcnv69 deletions. There was no Xcnv67 deletion in our cohort. In conclusion, the two previously reported X-linked microdeletions (Xcnv64 and Xcnv69) do not seem to confer a significant risk to impaired spermatogenesis in the Czech population. The potential clinical role of the previously reported patient-specific Xcnv67 remains to be determined in a larger study population.


Functional and Structural Diversity of Insect Glutathione S-transferases in Xenobiotic Adaptation.
As a superfamily of multifunctional enzymes that is mainly associated with xenobiotic adaptation, glutathione S-transferases (GSTs) facilitate insects' survival under chemical stresses in their environment. GSTs confer xenobiotic adaptation through direct metabolism or sequestration of xenobiotics, and/or indirectly by providing protection against oxidative stress induced by xenobiotic exposure. In this article, a comprehensive overview of current understanding on the versatile functions of insect GSTs in detoxifying chemical compounds is presented. The diverse structures of different classes of insect GSTs, specifically the spatial localization and composition of their amino acid residues constituted in their active sites are also summarized. Recent availability of whole genome sequences of numerous insect species, accompanied by RNA interference, X-ray crystallography, enzyme kinetics and site-directed mutagenesis techniques have significantly enhanced our understanding of functional and structural diversity of insect GSTs.


Complete Technical Scheme for Automatic Biological Dose Estimation Platform.
To establish a complete technical solution for the automatic radiation biological dose estimation platform for biological dose estimation and classification of the wounded in large-scale radiation accidents, the "dose-effect curve by dicentric chromosome (DIC) automatic analysis" was established and its accuracy was verified. The effects of analyzed cell number and the special treatment of the culture on dose estimation by DIC automatic analysis were studied. Besides, sample processing capabilities of the special equipments were tested. The fitted "dose-effect curve by DIC automatic analysis" was presented as follows: Y = (0.01806 ± 0.00032) D 2 + (0.01279 ± 0.00084) D + (0.0004891 ± 0.0001358) (R 2 = 0.961). Three-gradient scanning method, culture refrigeration method, and interprofessional collaboration under extreme conditions were proposed to improve the detection speed, prolong the sample processing time window, and reduce the equipment investment. In addition, the optimized device allocation ratio for the automatic biological dose estimation laboratory was proposed to eliminate the efficiency bottleneck. The complete set of technical solutions for the high-throughput automatic biological dose estimation laboratory proposed in this study can meet the requirements of early classification and rapid biological dose assessment of the wounded during the large-scale nuclear radiation events, and it is worthy of further promotion.


The impact of different background noises on the Production Effect.
The presence of background noise has been previously shown to disrupt cognitive performance, especially memory. The amount of interference is derived from the acoustic characteristics of the noise; energetic vs. informational, steady-state vs. fluctuating. However, the literature is inconsistent concerning the effects of different types of noise on long-term memory free recall. In the present study, we tested the impact of different noises on recall of items that were learned under two conditions - silent or aloud reading, a Production Effect (PE) paradigm. As the PE represents enhanced memory for words read aloud relative to words read silently during study, we focused on the effect of noise on this robust memory phenomenon. The results showed that (a) steady-state energetic noise did not affect memory, with a recall advantage for aloud words (PE), comparable to a no-noise condition, (b) fluctuating-energetic noise and fluctuating-informational (eight-talkers babble) noise eliminated the PE, with similar recall for aloud and silent items. These results are discussed in light of their theoretical implications, stressing the role of attention in the PE. Ecological implications regarding studying in noisy environments are suggested.


Bone and suture regeneration in calvarial defects by e-PTFE-membranes and demineralized bone matrix and the impact on calvarial growth: an experimental study in the rat.
The aim of this study was to evaluate the effect of: guided tissue regeneration (GTR) alone, implantation of demineralized bone matrix (DBM) alone, and of the combined treatment on the healing of craniectomy defects involving the sagittal cranial suture, and to examine subsequent calvarial growth. Sixty four-week-old rats were used in the study. These animals were randomly assigned to five groups (A-E) of 12 animals. In four groups (A-D), a calvarial defect (5.0 mm) involving the sagittal suture was produced in each animal. Group A: The defect was left untreated. Group B: DBM was implanted into the defect. Group C: The cerebral and the galeal aspect of the defect was covered with an e-PTFE membrane. Group D: The defect was treated with the double membrane technique combined with implantation of DBM. Group E: The animals were sham-operated, no defect was created. In all groups, two gutta-percha points were placed to indicate the lateral borders of the parietal bones. Histological analysis 4 months following surgery showed that the untreated cranial defects (A) had healed with fibrous connective tissue in the midportion of the defect. The DBM grafted defects (B) healed either completely with bone containing DBM particles or partially with bone and connective tissue. The defects (D) treated with DBM combined with GTR healed completely with bone, while the defects (C) treated with membranes alone healed with bone but a suture-like tissue similar to the normal sagittal suture of the sham-operated controls (E) was always present in the midportion of the defect. Cephalometric radiography demonstrated that the membrane-treated (C) and the sham-operated animals (E) exhibited similar coronal growth of the cranial vault following treatment. Craniometric measurements on chemically defleshed specimens showed that sham-operated and membrane-treated animals presented significantly more biparietal width than the animals treated with DBM alone or DBM combined with GTR (P < 0.05). The results demonstrated that predictable osseous healing including the formation of a sagittal suture can be accomplished in craniectomy defects by GTR, and undisturbed cranial growth reestablished. The treatment of the defects with DBM alone or DBM combined with GTR resulted in craniosynostosis and reduced cranial growth.


Human immune interferon: induction in lymphoid cells by a calcium ionophore.
Human lymphocyte cultures produced interferon after treatment with the calcium ionophore A23187, but not after treatment with potassium ionophore nonactin. Interferon production was detectable between 3 and 6 h after ionophore treatment and reached the maximum level between 12 and 24 h. Ionophore-induced interferon appeared to be immune interferon on the basis of acid lability, lack of neutralization by antibody to leukocyte interferon, slow kinetics of activation of the antiviral state, and molecular characterization by isoelectrofocusing.


Speech intelligibility and subjective benefit in single-sided deaf adults after cochlear implantation.
Treatment with cochlear implants (CIs) in single-sided deaf individuals started less than a decade ago. CIs can successfully reduce incapacitating tinnitus on the deaf ear and allow, so some extent, the restoration of binaural hearing. Until now, systematic evaluations of subjective CI benefit in post-lingually single-sided deaf individuals and analyses of speech intelligibility outcome for the CI in isolation have been lacking. For the prospective part of this study, the Bern Benefit in Single-Sided Deafness Questionnaire (BBSS) was administered to 48 single-sided deaf CI users to evaluate the subjectively perceived CI benefit across different listening situations. In the retrospective part, speech intelligibility outcome with the CI up to 12 month post-activation was compared between 100 single-sided deaf CI users and 125 bilaterally implanted CI users (2nd implant). The positive median ratings in the BBSS differed significantly from zero for all items suggesting that most individuals with single-sided deafness rate their CI as beneficial across listening situations. The speech perception scores in quiet and noise improved significantly over time in both groups of CI users. Speech intelligibility with the CI in isolation was significantly better in bilaterally implanted CI users (2nd implant) compared to the scores obtained from single-sided deaf CI users. Our results indicate that CI users with single-sided deafness can reach open set speech understanding with their CI in isolation, encouraging the extension of the CI indication to individuals with normal hearing on the contralateral ear. Compared to the performance reached with bilateral CI users' second implant, speech reception threshold are lower, indicating an aural preference and dominance of the normal hearing ear. The results from the BBSS propose good satisfaction with the CI across several listening situations.


Statistical-mechanical studies of the alpha-beta transformation in keratin. IV. The Hill model.
The relationship between the two-dimensional Hill model and the David-Schor extension of the one-dimensional Zimm-Bragg model for the alpha right arrow over left arrow beta transformation in keratins is developed. On the basis of the assumptions of the David Schor model, it appears unlikely that the Hill model in its present form can give detailed agreement with the experimental tension-length isotherms.


Involvement of the thylakoidal NADH-plastoquinone-oxidoreductase complex in the early responses to ozone exposure of barley (Hordeum vulgare L.) seedlings.
A possible implication of the plastid NADH-plastoquinone-oxidoreductase (Ndh) complex in the response against ozone-mediated oxidative stress in barley (Hordeum vulgare L.) leaves was investigated. After a 4 h treatment, exposure of barley seedlings to moderate ozone concentrations produced leaf-age-dependent increases in lipid peroxidation, peroxidase, and Ndh complex activities in the thylakoid membranes. A significant amount and activity of the Ndh complex were detected in mature barley leaves, but not in young barley leaves. In fact, young barley leaves behaved like ndh-deficient leaves in most of the aspects studied. When plants were exposed to photo-oxidative light after ozone fumigation, the recovery of Fv/Fm was lower in young leaves than in mature leaves. Ozone treatment significantly decreased non-photochemical quenching (qN) in young leaves, but not in mature leaves. Mature leaves showed higher levels of the energy (DeltamuH+) dependent (qE) component of qN. Treatment with antimycin A, an inhibitor of cyclic electron flow, increased the decay of qN produced by ozone in young leaves, but not in mature ones. The reduction state of plastoquinone increased after ozone treatment in mature dark-adapted leaves and was strongly quenched by far red light. It is proposed that the function of the Ndh complex helps the maintenance of qN, probably through the poising of the redox steady-state level of the intersystem carriers and then by optimizing the rate of cyclic electron flow. This should constitute an age-dependent early response in barley leaves, by contributing to minimize photoinhibition in the presence of ozone and high light.


Efficient Photocatalytic Reduction of Hexavalent Chromium by BiVO4-Decorated MXene Photocatalysts and Their Charge Carrier Dynamics.
The synergistically MXene (Ti3C2Tx) co-catalyst-decorated BiVO4-based heterostructured photocatalysts have been synthesized by a hydrothermal approach with varied loading concentrations of MXene (Ti3C2Tx) to drive the hexavalent chromium reduction efficiently. The formation of the heterostructured photocatalyst was confirmed by the appearance of X-ray diffraction (XRD) peaks corresponding to the monoclinic BiVO4 phase and MXene (Ti3C2Tx) and also the antisymmetric (834 cm-1) and symmetric stretching (715 cm-1) of tetrahedral VO4 and D (1330 cm-1) and G (1570 cm-1) bands corresponding to MXene (Ti3C2Tx) in the Raman spectrum. The worm-like structures of BiVO4 nanocrystals grew onto the lamellar sheets of MXene (Ti3C2Tx), as shown by field emission scanning electron microscopy (FESEM), and has an increased surface area of 15.62 m2g-1 in the case of BVO-20-TC. X-ray photoelectron spectroscopy (XPS) analysis confirms the presence of V5+ and Ti3+states, and the uniform distribution of BiVO4 nanocrystals over lamellar sheets of MXene (Ti3C2Tx) is evident from energy-dispersive X-ray (EDX) analysis. The ultraviolet-diffuse reflectance spectroscopy (UV-DRS) spectra suggest a decrease in the band gap energy of BVO-20-TC to 2.335 eV, promoting a higher degree of visible light harvesting. Upon optimization, by varying the pH, the amount of the photocatalyst, and the concentration of Cr(IV), BVO-20-TC exhibits the highest photocatalytic efficiency (96.39%) while using a Cr(VI) concentration of 10 ppm at pH 2 and 15 mg of the photocatalyst, and the photoreduction of Cr(VI) to Cr(III) follows the pseudo-first-order reaction. The decrease in the PL intensity in BVO-20-TC reveals a faster transfer of electrons from MXene (Ti3C2Tx) to BiVO4. Further, the higher degree of band bending at the BiVO4/MXene (Ti3C2Tx) heterojunction, revealed from the Mott-Schottky analysis, facilitates efficient charge transfer and eventually faster and efficient photoreduction of Cr(VI) to Cr(III). The reusability and stability test undertaken for BVO-20-TC reveals that even after five cycles, the Cr (VI) photoreduction efficacy is retained. This work provides insights into photoreduction of Cr (VI) by using such heterostructures.


The SUPERFAMILY 1.75 database in 2014: a doubling of data.
We present updates to the SUPERFAMILY 1.75 (http://supfam.org) online resource and protein sequence collection. The hidden Markov model library that provides sequence homology to SCOP structural domains remains unchanged at version 1.75. In the last 4 years SUPERFAMILY has more than doubled its holding of curated complete proteomes over all cellular life, from 1400 proteomes reported previously in 2010 up to 3258 at present. Outside of the main sequence collection, SUPERFAMILY continues to provide domain annotation for sequences provided by other resources such as: UniProt, Ensembl, PDB, much of JGI Phytozome and selected subcollections of NCBI RefSeq. Despite this growth in data volume, SUPERFAMILY now provides users with an expanded and daily updated phylogenetic tree of life (sTOL). This tree is built with genomic-scale domain annotation data as before, but constantly updated when new species are introduced to the sequence library. Our Gene Ontology and other functional and phenotypic annotations previously reported have stood up to critical assessment by the function prediction community. We have now introduced these data in an integrated manner online at the level of an individual sequence, and--in the case of whole genomes--with enrichment analysis against a taxonomically defined background.


[A Case of Epithelioid Angiomyolipoma of the Kidney with Tumor Thrombus Extending into the Renal Vein : Case Report].
A 31-year-old man was referred to our hospital for macroscopic hematuria. An abdominal computed tomography (CT) scan showed a 36×30 mm enhancing left renal tumor with tumor thrombus extending into the left renal vein. Therefore,we diagnosed the tumor as a clinically classified cT3aN0M0 left renal cell carcinoma. Retroperitoneal laparoscopic radical left nephrectomy with renal vein thrombectomy was performed,with removal of the left kidney with the mass and tumor thrombus en bloc. The pathological diagnosis was epithelioid angiomyolipoma (EAML) of the left kidney. EAML is a rare tumor with malignant potential. In this case,although no signs of recurrence or metastasis have been observed for 9 months post-operation,we recommended a careful follow-up regimen.


"When you leave your country, this is what you're in for": experiences of structural, legal, and gender-based violence among asylum-seeking women at the Mexico-U.S. border.
Recent U.S. immigration policy has increasingly focused on asylum deterrence and has been used extensively to rapidly deport and deter asylum-seekers, leaving thousands of would-be asylum-seekers waiting indefinitely in Mexican border cities, a large and growing proportion of whom are pregnant and parenting women. In the border city of Tijuana, Mexico, these women are spending unprecedented durations waiting under unsafe humanitarian conditions to seek safety in the U.S, with rising concerns regarding increases in gender-based violence (GBV) among this population during the COVID-19 pandemic. Given existing gaps in evidence, we aimed to describe the lived experiences of GBV in the context of asylum deterrence policies among pregnant and parenting asylum-seeking women at the Mexico-U.S. border. Within the community-based Maternal and Infant Health for Refugee & Asylum-Seeking Women (MIHRA) study, we conducted semi-structured qualitative interviews with 30 asylum-seeking women in Tijuana, Mexico between June and December 2022. Eligible women had been pregnant or postpartum since March 2020, were 18-49 years old, and migrated for the purposes of seeking asylum in the U.S. Drawing on conceptualizations of structural and legal violence, we conducted a thematic analysis of participants' experiences of GBV in the context of asylum deterrence policies and COVID-19. Pregnant and parenting asylum-seeking women routinely faced multiple forms of GBV perpetuated by asylum deterrence policies at all stages of migration (pre-migration, in transit, and in Tijuana). Indefinite wait times to cross the border and inadequate/unsafe shelter exacerbated further vulnerability to GBV. Repeated exposure to GBV contributed to poor mental health among women who reported feelings of fear, isolation, despair, shame, and anxiety. The lack of supports and legal recourse related to GBV in Tijuana highlighted the impact of asylum deterrence policies on this ongoing humanitarian crisis. Asylum deterrence policies undermine the health and safety of pregnant and parenting asylum-seeking women at the Mexico-U.S. border. There is an urgent need to end U.S. asylum deterrence policies and to provide respectful, appropriate, and adequately resourced humanitarian supports to pregnant and parenting asylum-seeking women in border cities, to reduce women's risk of GBV and trauma.


Modulatory features of the novel spider toxin μ-TRTX-Df1a isolated from the venom of the spider Davus fasciatus.
Naturally occurring dysfunction of voltage-gated sodium (NaV ) channels results in complex disorders such as chronic pain, making these channels an attractive target for new therapies. In the pursuit of novel NaV modulators, we investigated spider venoms for new inhibitors of NaV channels. We used high-throughput screens to identify a NaV modulator in venom of the spider Davus fasciatus. Further characterization of this venom peptide was undertaken using fluorescent and electrophysiological assays, molecular modelling and a rodent pain model. We identified a potent NaV inhibitor named μ-TRTX-Df1a. This 34-residue peptide fully inhibited responses mediated by NaV 1.7 endogenously expressed in SH-SY5Y cells. Df1a also inhibited voltage-gated calcium (CaV 3) currents but had no activity against the voltage-gated potassium (KV 2) channel. The modelled structure of Df1a, which contains an inhibitor cystine knot motif, is reminiscent of the NaV channel toxin ProTx-I. Electrophysiology revealed that Df1a inhibits all NaV subtypes tested (hNaV 1.1-1.7). Df1a also slowed fast inactivation of NaV 1.1, NaV 1.3 and NaV 1.5 and modified the voltage-dependence of activation and inactivation of most of the NaV subtypes. Df1a preferentially binds to the domain II voltage-sensor and has additional interactions with the voltage sensors domains III and IV, which probably explains its modulatory features. Df1a was analgesic in vivo, reversing the spontaneous pain behaviours induced by the NaV activator OD1. μ-TRTX-Df1a shows potential as a new molecule for the development of drugs to treat pain disorders mediated by voltage-gated ion channels.


Diversity of Chromanol and Chromenol Structures and Functions: An Emerging Class of Anti-Inflammatory and Anti-Carcinogenic Agents.
Natural chromanols and chromenols comprise a family of molecules with enormous structural diversity and biological activities of pharmacological interest. A recently published systematic review described more than 230 structures that are derived from a chromanol ortpd chromenol core. For many of these compounds structure-activity relationships have been described with mostly anti-inflammatory as well as anti-carcinogenic activities. To extend the knowledge on the biological activity and the therapeutic potential of these promising class of natural compounds, we here present a report on selected chromanols and chromenols based on the availability of data on signaling pathways involved in inflammation, apoptosis, cell proliferation, and carcinogenesis. The chromanol and chromenol derivatives seem to bind or to interfere with several molecular targets and pathways, including 5-lipoxygenase, nuclear receptors, and the nuclear-factor "kappa-light-chain-enhancer" of activated B-cells (NFκB) pathway. Interestingly, available data suggest that the chromanols and chromenols are promiscuitively acting molecules that inhibit enzyme activities, bind to cellular receptors, and modulate mitochondrial function as well as gene expression. It is also noteworthy that the molecular modes of actions by which the chromanols and chromenols exert their effects strongly depend on the concentrations of the compounds. Thereby, low- and high-affinity molecular targets can be classified. This review summarizes the available knowledge on the biological activity of selected chromanols and chromenols which may represent interesting lead structures for the development of therapeutic anti-inflammatory and chemopreventive approaches.


Adherent cell thawing by infrared radiation.
Cryopreservation of adherent cells is crucial for commercial cell therapy technology, including effective distribution and storage. Fast thawing has been shown to increase cell recovery in vitrified samples. Previously, radiofrequency (RF) has been investigated as a heating source on large samples, either with or without magnetic particles. Also, laser heating with the aid of dye or nanoparticles has been utilized on sub-millimeter samples successfully. For slow freezing cryopreservation methods, the influence of rate of thawing on viability is less clear. Cryopreservation of surface adhered cells result in many cases in detachment from the surface. We illustrate how intense infrared radiation from a focused halogen illuminator accelerates thawing. We show that two epithelial cell lines, retinal pigment epithelium cells and heterogeneous human epithelial colorectal adenocarcinoma cells, can be effectively cryopreserved and recovered using a combination of slow freezing and fast thawing under infrared illumination. We were able to successfully thaw samples, of 2-4 mm thick, including the media, on the order of a second, providing a heating rate of thousands of Kelvin per minute. Under optimal conditions, we observed higher post-thawing cell viability rates and higher cell adhesion with infrared thawing than with water bath thawing. We suggest that bulk warming with infrared radiation has an advantage over surface warming of surface-attached cells, as it alleviates cell stress during the process of thawing. These findings will pave the way for novel approaches to treating substrate-adhered cells and 3D scaffolds with cells and organoids. This technology may serve as a crucial component in lab-on-chip systems for medical testing and therapeutic use.


Solvent-free MALDI-MS for the analysis of a membrane protein via the mini ball mill approach: case study of bacteriorhodopsin.
A mini ball mill (MBM) solvent-free matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) method allows for the analysis of bacteriorhodopsin (BR), an integral membrane protein that previously presented special analytical problems. For well-defined signals in the molecular ion region of the analytes, a desalting procedure of the MBM sample directly on the MALDI target plate was used to reduce adduction by sodium and other cations that are normally attendant with hydrophobic peptides and proteins as a result of the sample preparation procedure. Mass analysis of the intact hydrophobic protein and the few hydrophobic and hydrophilic tryptic peptides available in the digest is demonstrated with this robust new approach. MS and MS/MS spectra of BR tryptic peptides and intact protein were generally superior to the traditional solvent-based method using the desalted "dry" MALDI preparation procedure. The solvent-free method expands the range of peptides that can be effectively analyzed by MALDI-MS to those that are hydrophobic and solubility-limited.


Response of uptake and translocation of phenanthrene to nitrogen form in lettuce and wheat seedlings.
Polycyclic aromatic hydrocarbons (PAHs) are widespread chemicals that are potentially carcinogenic and toxic to human due to dietary intake of food crops contaminated by PAHs. To date, the mechanisms underlying root uptake and acropetal translocation of PAHs in crops are poorly understood. Here we describe uptake and translocation of phenanthrene (a model PAH) in relation to nitrogen form and concentration in wheat and lettuce seedlings. At concentrations of 0-15 mM, phenanthrene uptake by roots is enhanced with an increase in ammonium and inhibited with an increment of nitrate. Phenanthrene concentration in shoots is much lower than in roots, suggesting that the direction of phenanthrene transport is acropetal. Ammonium reduces both phenanthrene accumulation and bioconcentration factor in shoots, as well as translocation factor, but nitrate elevates them. Phenanthrene uptake increases nutrient solution pH in the treatments with either nitrate or ammonium. Thus, it is concluded that the root uptake and acropetal translocation of phenanthrene in crops are associated with nitrogen form. Our results provide both a novel insight into the mechanism on PAH transport in higher plants and a promising agronomic strategy to minimize PAH contamination in crops or to improve phytoremediation of PAH-contaminated soils or water via nitrogen management.


Natural anti-immunoglobulin autoantibodies: irrelevant by-products or immunoregulatory molecules?
Anti-immunoglobulin autoantibodies (anti-Ig auto-Abs), particularly IgM-anti-IgG (classical rheumatoid factor), have been studied mainly in the context of rheumatoid arthritis. In this article we focus on other members of the anti-Ig family, including the natural IgG-anti-F(ab')2 auto-Ab, and look for clinical and experimental findings supporting a role of these antibodies in the regulation of the immune response. We discuss the evidence for suppression of auto- and alloreactive B cells by IgG-anti-F(ab')2 auto-Ab and the role of this Ab in the pathogenesis of certain diseases, such as autoimmune hemolytic anemia. The structure of the antibody's antigen-binding site was clarified by isolating the VL and VH gene segments from the cDNA of B cells. Sequence analyses revealed germline gene identity of VL chains and 88% homology with the closest germline gene of VH chains. Finally, we discuss hypothetical models concerning the immunoregulatory role of natural anti-Ig auto-Abs.


Effect of maternal smoking during pregnancy on gestational weight gain and birthweight: A stratified analysis by pregestational weight status.
In Japan, low birthweight (LBW) of infants is a major public health concern. Gestational weight gain (GWG) may be associated with LBW of infants. On the other hand, maternal smoking during pregnancy is a well-known factor associated with infant birthweight. Thus, this study aimed to examine the effect of maternal smoking during pregnancy on GWG and birthweight stratified by pregestational weight status. A retrospective cohort study was designed, which included three hospitals of Yamanashi Prefecture, Japan. The study included babies born between 2013 and 2014 from mothers having singleton pregnancies. The outcomes analyzed were GWG (difference between maternal weight measured at prenatal check-up just before delivery and pregestational weight based on information from clinical records) and birthweight of infants stratified by pregestational maternal body mass index (BMI). This study included 1150 singleton babies and their mothers. After excluding individuals with incomplete data, the final number of analyzed participants was 1078. The mean maternal age at delivery was 31.3 ± 5.1 years. The mean pregestational BMI was 21.3 ± 3.4 kg/m2. The mean GWG was 10.0 ± 4.1 kg. After adjusting for confounding factors, maternal smoking during pregnancy was positively associated with GWG in all categories (underweight: p<0.0001; normal weight: p<0.0001; overweight: p=0.01). Maternal smoking during pregnancy was also significantly associated with lower birthweight in underweight and normal-weight mothers (underweight: p=0.04, normal-weight: p=0.03). Maternal smoking status is significantly associated with higher GWG and lower birthweight. Based on the Developmental Origins of Health and Disease (DOHaD) hypothesis, the growth of infants born from smoking mothers needs close observation.


The case for genome-wide association studies of bone acquisition in paediatric and adolescent populations.
Peak bone mass, the maximum amount of bone accrued at the end of the growth period, is an important predictor of future risk of osteoporosis and fracture. Hence, the contribution of genetic factors influencing bone accrual is of considerable interest to the osteoporosis research community. In this article, we review evidence that genetic factors play an important role in bone growth, describe the genetic loci implicated so far and briefly discuss lessons learned from the application of genome-wide association studies. Moreover, we attempt to make the case for genetic investigations of bone mineral density in paediatric and young adult populations, describing their potential to increase our knowledge of the process of bone metabolism throughout the life course, and in turn, identify novel targets for the pharmacological treatment of osteoporosis.


Trends of Dengue Disease Epidemiology.
Dengue disease is an emerging mosquito-borne viral infection transmitted between humans by Aedes spp. that are distributed mainly in the tropical and subtropical region along with chikungunya and zika diseases. The distribution of dengue disease is influenced by local variation, such as geography, rainfall, temperature, and rapid urbanization or migration. The epidemy of mosquito-borne infection significantly led to increased number of cases and hyperendemicity which induce a more severe form of dengue accompanied by cocirculation of chikungunya and zika. The rapid global spreading of dengue disease created public health burdens that are presently unfulfilled by the absence of specific therapy, simple diagnosis tool for the early phase, and effective and efficient vector control system. This review highlights the current situation of dengue distribution, epidemiology, and new strategies for early dengue diagnosis and risk prediction of severity that can be used to improve oversight and alleviate the heavy burden of the disease.


[Prevention of an IgE response to bovine beta-lactoglobulin by gene immunization in mice].
The therapeutic routes for the treatment of allergy have as their objective to prevent or diminish the specific IgE responsible for the appearance of the allergic reaction. This allergic reaction survives in the genetically predisposed subject and results in a dis-equilibrium of the "Th1-Th2 balance" by increasing the Th2 response. This Th2 response induces the production of IgE against environmental antigens, which from that time on become allergens. In this context, use of gene immunisation seems to be very interesting. The immunisation consists of the injection of an expression vector of bacterial origin, containing the cDNA of a protein of interest. Different studies have shown that the injection of such a plasmid into mice initiates a specific immune response of Th1 (IgG2a) type, stopping all further response of the Th2 (IgG1 and IgE) type. This "non-allergic" response is due to the intrinsic properties of the bacterial ADN, notably the presence of sequences of immunostimulants, the adjuvant of the Th1 response. We have sought to show such a preventative effect in the case of a food protein, bovine beta-lactoglobulin (BLG), a major allergen of cow's milk. Firstly, we made a expression plasmid that contained the cDNA of BLG. Intramuscular administration of this plasmid to mice allowed expression of the BLG in the native form at the site of the injection. The primary response induced by this type of immunisation is characterised by a mixed IgG1/IgG2a response and an absence of anti-BLG IgE. In addition, pre-immunisation of the mice with a plasmid that contained the cDNA of BLG prevented all further sensitisation with the protein administered by the intra-peritoneal route in the presence of alum, an adjuvant of the Th2 response. It appeared further that the preventative effect is dependent on the latent time between gene and protein immunisation. Prevention of the anti-BLG IgE response seems to result in an active inhibition by the cytokines such as interferon-gamma and interleukin 10, rather than a reduction in the production of type Th2 cytokines. Use of efficacious non-pathogenic vectors, that may be administered by the digestive route, could envisage a specific protection in the case of severe food allergies.


Comparative histology of pulmonary neuroendocrine cell system in mammalian lungs.
It is increasingly recognized that neuroepithelial endocrine cells and organoid clusters of these cells termed neuroepithelial bodies are widely distributed in the respiratory tract of vertebrates. This review focuses on the neuroepithelial endocrine system in the airway epithelium of mammals according to observations made in a wide range of species, as it appears in light and electron microscopy by means of various visualization techniques under normal and experimental conditions. Because there are similarities but also marked differences between species, wherever possible studies in human airways are emphasized. Conventional histochemical and ultrastructural studies including microspectrofluorimetry have demonstrated the amine-handling properties and the presence of neurosecretory granules in neuroendocrine cells of the epithelium of all mammals studies so far. The neuroepithelial bodies are innervated by morphological afferent- and efferentlike synaptic specializations. These, together with the presence of reciprocal synapses, emphasize that these cells may be involved in dual functions of chemoreception and secretion. Light and electron microscopic immunohistochemistry has demonstrated that neuroepithelial endocrine cells may contain various biogenic agents, suggesting that the neuroendocrine system is highly heterogeneous. Neural elements may interact in a complex manner, and the activation of certain neural pathways may control the release of biogenic substances to influence physiological airway functions. They may be particularly relevant in pulmonary diseases. Consequently, the function of this system is complex and it is highly probable that many of its aspects are still not elucidated.


HOST EFFECTS ON FERTILITY AND REPRODUCTIVE SUCCESS OF DENDROCTONUS PONDEROSAE HOPKINS (COLEOPTERA: SCOLYTIDAE).
Mountain pine beetles from lodgepole and limber pine in western Canada were crossbred. We compared data about reproductive success and fecundity of parents as well as development, mortality, and fertility of their progeny to determine whether there was reproductive isolation among beetle populations in these hosts. Three factors, directly or indirectly related to the host, influenced reproductive performance of parents (reproductive success, egg gallery length, fecundity, and number of eggs laid per centimeter of gallery) as well as the mortality, dry weight, and fat content of the progeny: (1) the host species in which progeny were reared, (2) the host species in which the female parent was reared, and (3) whether both parents originated from the same or different host species. Limber pine appears to be a better host for Dendroctonus ponderosae reproduction and survival than lodgepole pine. Nonetheless, beetles reared from lodgepole and limber pine can reproduce in either host and will mate with each other. Progeny of all crosses were fertile. Thus, there is no apparent barrier to prevent beetles from the two host species from interbreeding in the field.


A Traumatic Dislocation of the Atlas from the Axis in a Patient with Atlantooccipital Assimilation.
Atlantooccipital assimilation is defined as the complete or partial fusion of the caudal portion of the occiput with the cranial portion of the atlas. We report an extremely rare case of a traumatic dislocation of the atlas from the axis (C1 from C2), which lead to internal decapitation in a patient with atlantooccipital assimilation. This report reviews the background of atlantooccipital assimilations and their clinical relevance.


Poly(ADP-ribose) polymerase-1 causes mitochondrial damage and neuron death mediated by Bnip3.
Excessive pathophysiological activity of the nuclear enzyme poly(ADP-ribose) polymerase-1 (PARP1) causes neuron death in brain hypoxia/ischemia by inducing mitochondrial permeability transition and nuclear translocation of apoptosis-inducing factor (AIF). Bcl-2/adenovirus E1B 19 kDa-interacting protein (Bnip3) is a prodeath BH3-only Bcl-2 protein family member that is induced in hypoxia, and has effects on mitochondrial permeability and neuronal survival similar to those caused by PARP1 activation. We hypothesized that Bnip3 is a critical mediator of PARP1-induced mitochondrial dysfunction and neuron death. Hypoxic death of mouse cortical neuron cultures was mitigated by deletion of either PARP1 or Bnip3, indicating that both factors are involved. Direct normoxic PARP1 activation by a DNA alkylating agent enhanced Bnip3 expression, and caused Bnip3-dependent mitochondrial membrane permeability, AIF translocation, and neuron death. Hypoxia produced PARP1-dependent depletion of nicotinamide adenine dinucleotide (NAD(+)) and inhibition of the NAD(+)-dependent class III histone deactelyase (HDAC) sirtuin-1 (SIRT1). This, in turn, led to hyperacetylation and nuclear localization of the forkhead box (Fox) protein FoxO3a, followed by enhanced association of FoxO3a with the Bnip3 upstream promoter region, increased levels of Bnip3 transcript, and elevated mitochondrial Bnip3 immunoreactivity. Finally, FoxO3a silencing using a lentiviral short hairpin RNA approach significantly reduced hypoxic Bnip3 expression, mitochondrial damage, and neuron death. Together, these data illustrate a direct PARP1-mediated hypoxic signaling pathway involving NAD(+) depletion, SIRT1 inhibition, FoxO3a-driven Bnip3 generation, and mitochondrial AIF release.


Prevalence of sudden speechlessness in critical care units.
Sudden speechlessness (SS) is commonly experienced by patients admitted to critical care units. Although literature findings document challenges associated with periods of SS, the prevalence is unknown. The purpose of this study is to determine the prevalence and characteristics of adult SS patients in four critical care units at a university-affiliated tertiary care hospital. Data are collected on 9 randomly selected days over a 4-month period. The daily prevalence of SS ranges from 16% to 24% in each unit. Characteristic data collected includes patient age, gender, medical diagnosis related to SS episode, type of speechlessness, days since SS began, and communication strategies in use. Respiratory intubation related to various clinical diagnoses is the main cause for SS. Use of multiple specific strategies to convey needs during SS periods are identified. Follow-up studies to further define the prevalence of SS in settings beyond the critical care environment are recommended.


Reinvestigation of the total Li(+)/H(+) ion exchange on the garnet-type Li5La3Nb2O12.
Li(+)/H(+) exchange was performed on Li5La3Nb2O12 using CH3COOH. After X-ray powder diffraction experiments to check the quality of Li5-xHxLa3Nb2O12, the chemical formulation was determined by thermogravimetric analysis coupled with mass spectrometry and flame photometry. The results showed unambiguously that the Li(+)/H(+) exchange was not total and that some CH3COOH remained in the sample. Raman experiments revealed in addition that the organic contribution on the spectrum was due either to metal acetate or to ionic bond to the crystal.


Surface passivation of gallium nitride by ultrathin RF-magnetron sputtered Al2O3 gate.
An ultrathin RF-magnetron sputtered Al2O3 gate on GaN subjected to postdeposition annealing at 800 °C in O2 ambient was systematically investigated. A cross-sectional energy-filtered transmission electron microscopy revealed formation of crystalline Al2O3 gate, which was supported by X-ray diffraction analysis. Various current conduction mechanisms contributing to leakage current of the investigated sample were discussed and correlated with metal-oxide-semiconductor characteristics of this sample.


The open-field behaviour of mice infected with Trichinella pseudospiralis.
The behaviour of mice exposed to graded doses of Trichinella pseudospiralis larvae was monitored in an open-field situation. Ambulatory activity declined briefly during the acute phase of the infection (day 11) but regained pre-infection levels 1 week later. Animals receiving heavy doses of T. pseudospiralis exhibited a mild increase in the level of ambulatory activity during the chronic phase of the infection. The infections did not affect the level of exploratory activity. The effects of the T. pseudospiralis infections on the behaviour of the mouse host were much less pronounced than those induced by T. spiralis. It is suggested that these differences may be associated with the small size of T. pseudospiralis and the lack of capsule formation.


Effectiveness of nebulized hypertonic saline and epinephrine in hospitalized infants with bronchiolitis.
The objective of the study is to verify effects of nebulized 3% saline hypertonic solution (HS) in comparison to normal saline (NS) in addition to epinephrine in hospitalized children with bronchiolitis. Infants were randomly assigned either to receive every 6 hours nebulized NS (group I) or 3% HS (group II) in addition to epinephrine (1.5 mg) and to conventional treatment. The main endpoints of this study were the length of stay (LOS) in hospital and the clinical response score (CSS). Patients presented a significant decrease in CSS from the first through the third day of treatment, present in the first group but even more evident in the second group (p=0.0001). Comparison between group I and II data shows significant decrease in CSS in the 3% HS-treated patients both at the second (p<0.005) and at the third day of treatment (p<0.005). Infants in the NS control group had a mean LOS of 5.6±1.6 days, whereas children treated with 3% HS were discharged with a LOS of 4.9±1.3 days, reaching a significant decrease in stay (p<0.05). In hospitalized patients bronchiolitis nebulized 3% HS and epinephrine significantly decreased symptoms and LOS as compared to 0.9% NS and epinephrine.


Microglia extracellular vesicles: focus on molecular composition and biological function.
Extracellular vesicles (EVs) are a heterogeneous family of cell-derived lipid bounded vesicles comprising exosomes and microvesicles. They are potentially produced by all types of cells and are used as a cell-to-cell communication method that allows protein, lipid, and genetic material exchange. Microglia cells produce a large number of EVs both in resting and activated conditions, in the latter case changing their production and related biological effects. Several actions of microglia in the central nervous system are ascribed to EVs, but the molecular mechanisms by which each effect occurs are still largely unknown. Conflicting functions have been ascribed to microglia-derived EVs starting from the neuronal support and ending with the propagation of inflammation and neurodegeneration, confirming the crucial role of these organelles in tuning brain homeostasis. Despite the increasing number of studies reported on microglia-EVs, there is also a lot of fragmentation in the knowledge on the mechanism at the basis of their production and modification of their cargo. In this review, a collection of literature data about the surface and cargo proteins and lipids as well as the miRNA content of EVs produced by microglial cells has been reported. A special highlight was given to the works in which the EV molecular composition is linked to a precise biological function.


Use of aripiprazole for delirium in the elderly: a short review.
The effects and tolerability of antipsychotics in delirium treatment remain controversial. Compared to other antipsychotics, aripiprazole differs in pharmacological activity because it exerts its effect as a dopamine D2 partial agonist. The guidelines of the American Psychiatric Association rank aripiprazole highly among antipsychotics with regard to safety, and this drug is likely to be useful for delirium treatment. Here, we reviewed the efficacy and safety of aripiprazole for delirium. The results of our literature review on the efficacy and safety of delirium treatments suggest that aripiprazole is an effective treatment option for delirium in the elderly. Aripiprazole is as effective as other antipsychotics in improving delirium symptoms, and it is safer because it is less likely to cause extrapyramidal symptoms, excessive sedation, and weight gain. However, these findings are based on only a few clinical studies of elderly patients with delirium. Therefore, further investigations are necessary.


Pattern of distribution of blood group antigens on human epidermal cells during maturation.
The distribution in human epidermis of A, B, and H blood group antigens and of a precursor carbohydrate chain, N-acetyl-lactosamine, was examined using immunofluorescence staining techniques. The material included tissue from 10 blood group A, 4 blood group B, and 9 blood group O persons. Murine monoclonal antibodies were used to identify H antigen (type 2 chain) and N-acetyl-lactosamine. Human antisera were used to identify A and B antigens. In all groups N-acetyl-lactosamine and H antigen were found on the cell membranes of the spinous cell layer. N-acetyl-lactosamine was present mainly on the lower spinous cells whereas H antigen was seen predominantly on upper spinous cells or on the granular cells. Epithelia from blood group A or B persons demonstrated A or B antigens, respectively, but only if the tissue sections were trypsinized before staining. In such cases A or B antigens were found on the cell membranes in the granular cell layer.


Adenovirus serotype 3 and 7 infection with acute respiratory failure in children in Taiwan, 2010-2011.
Increased incidence of adenovirus infection in children was noticed since September 2010 in Taiwan and severe cases requiring intensive care were noted later. We did this study to find the clinical characteristics and risk factors associated with severe adenovirus infection. We collected cases of severe adenovirus infection between November 2010 and June 2011 to analyze their clinical characteristics in two medical centers in northern Taiwan. Severe adenovirus infection was defined as laboratory-confirmed adenovirus cases with required intensive care. Hexon gene sequencing was performed for molecular genotyping. 45 patients were included, 22 cases (49%) were infected with serotype 7, 19 (42%) with serotype 3, and 4 with serotype 2. The median age (range) was 2.75 years (0.08-15.43 years); 87% were below 5 years. Male to female ratio was 1.65 (28 to 17). Of these patients, 56% had underlying neurological diseases, 50% experienced fever higher than 40°C and 69% suffered fever longer than one week. The clinical diagnosis included pneumonia in 40 (89%) patients, bronchopneumonia in 5 (11%), and encephalitis in 7 (16%). At least 22 patients had pleural effusion. They had complications of respiratory failure (53%), acute respiratory distress syndrome (24%), hypotension (40%), and 6 (13%) patients needed extracorporeal membranous oxygenation. Ten (22%) patients died, all with underlying major systemic diseases and 7 (70%) infected with serotype 7. Adenovirus serotype 7 and 3 can cause severe disease-even death-in children, especially those with underlying neurological diseases. Patients infected with adenovirus serotype 7 tended to have a higher case-fatality rate.


Acute inflammatory injury in the lung precipitated by oxidant stress induces fibroblasts to synthesize and release transforming growth factor-alpha.
Although transforming growth factor-alpha (TGF-alpha) is widely distributed in transformed cells and in some normal cells and much is known about its structure and metabolism, there is little information about its physiological actions. TGF-alpha is not thought to be synthesized by nontransformed fibroblasts, but it is thought to be a mitogen for these and epithelial cells (Derynck, R. (1986) J. Cell. Biochem. 32, 293-304). We report here that fibroblasts obtained from hamsters with oxidant-induced lung injury release TGF-alpha at levels comparable with those reported for transformed cells. In conditioned media, one isoform of 18 kDa was recognized by a monoclonal antibody to mature TGF-alpha; five isoforms ranging from 18 to 42 kDa were recognized in cell lysates. Conditioned media from these fibroblasts stimulated tyrosine phosphorylation of the epidermal growth factor (EGF)/TGF-alpha receptor, competed with radioactive EGF for binding sites on A431 cells, and were mitogenic for mesenchymal and epithelial cells. This mitogenic activity could be almost completely blocked by anti-TGF-alpha. Conditioned media from normal lung fibroblasts exhibited none of these activities. Using normal lung fibroblasts, we found that TGF-alpha synthesis could be induced in vitro with 25 nmol/ml EGF, suggesting that the induction in vivo may have been due, in part, to a stimulation by EGF (or TGF-alpha) released by other cell types such as alveolar macrophages recruited to the injury site. TGF-alpha is, in general, a mitogen for epithelial cells (Derynck, 1986); more specific to acute injury in the lung, it may affect the proliferation (Ryan, R. M., Mineo-Kuhn, M. M., Kromer, C. M., and Finkelstein, J. N. (1994) Am. J. Physiol. 266, L17-L23) and metabolic activities (Whitsett, J. A., Weaver, T. E., Lieberman, M. A., Clark, J. G., and Daugherty, C. (1987) J. Biol. Chem. 262, 7908-7913) of alveolar epithelial type II cells. This is, we believe, the first report of a fibroblast-derived TGF-alpha induced with oxidant injury. If this response was ubiquitously manifested in other tissues, then fibroblast-derived TGF-alpha might be an important determinant of the epithelial and mesenchymal hyperplasia commonly observed in tissue repair.


Quaternary 2D Transition Metal Dichalcogenides (TMDs) with Tunable Bandgap.
Alloying/doping in 2D material is important due to wide range bandgap tunability. Increasing the number of components would increase the degree of freedom which can provide more flexibility in tuning the bandgap and also reduces the growth temperature. Here, synthesis of quaternary alloys Mox W1-x S2y Se2(1-y) is reported using chemical vapor deposition. The composition of alloys is tuned by changing the growth temperatures. As a result, the bandgap can be tuned which varies from 1.61 to 1.85 eV. The detailed theoretical calculation supports the experimental observation and shows a possibility of wide tunability of bandgap.


Intracavitary liposome-mediated p53 gene transfer into glioblastoma with endogenous wild-type p53 in vivo results in tumor suppression and long-term survival.
A cavitary glioblastoma model was created by injection of RT-2 cells, which express endogenous wild type p53, into the peritoneal cavity of nude mice. This model developed multiple layers of tumor cells invading the peritoneal surface and was used to mimic the postoperative surgical cavity remaining after glioblastoma (GBM) excision in patients. Rhodamine labeled DMRIE/DOPE + DNA complexes were found to penetrate at least 20 tumor cell layers. Injection of p53 gene/liposome complexes into the intraperitoneal cavity after the tumor was established resulted in massive tumor necrosis. Prominent staining of human p53 protein using the DO-1 antibody was found in tumor cells near the necrotic lesions. Tumor explants expressed human p53 protein and showed a 54% growth reduction in an in vitro growth assay. Further, DMRIE/DOPE mediated p53 gene transfection significantly increased the mean survival time of tumor bearing mice compared to vector control. These results demonstrate the efficiency of using exogenous wild type p53 to suppress glioblastoma cell with endogenous wild type p53 in vivo through liposome mediated transfection method.


Acceptance, caries reduction and reported adverse effects of fluoride prophylaxis in Norway.
Water fluoridation has not been introduced in Norway, although 99% of the population receive water with suboptimal fluoride levels. Alternative methods of fluoride prophylaxis have gained wide acceptance in this country. While less than 1% of the children received fluoride tablet in 1971, sales data in 1976 indicated a daily supply of fluoride tablets to 50% of the 0-5-year-olds and to 20% of the 6-11-year-olds. Most schoolchildren have joined mass prophylactic programs with regular with regular applications of fluoride solutions. Furthermore, fluoride-containing dentifrices have become available and are increasingly used. The increased use of fluoride has been paralleled by a marked reduction in caries and restorative need. During the past 5 years, a reduction of about 45% in the number of fillings inserted in 6-17-year-old children has been noted. In some areas, a 70% reduction has been recorded. The ratio between expenses for prophylaxis and savings in cost of treatment is favorable. The Norwegian Adverse Drug Reaction Committe received 34 case reports of adverse effects ascribed to fluoride prophylaxis, from 1970 to 1977. None of the 25 follow-up studies performed, suggested fluoride to have been responsible for the reported symptoms. In Norway, the benefits of fluoride prophylaxis are becoming increasingly evident.


Ontogeny of Nk-1+ natural killer cells. I. Promotion of Nk-1+ cells in fetal, baby, and old mice.
Using anti-Nk-1.1 serum, the alloantiserum specific for murine natural killer (NK) cells, we followed the ontogenetic development of Nk-1+ cells in fetal thymus, liver, and spleen. A transient population of Nk-1+ cells in fetal thymus was observed on day 14 but not on day 16 of gestation. On day 16 of gestation, Nk-1+ cells were detected only in liver and spleen. The proportion of Nk-1+ cells in spleen remained high (20 to 30%) at birth and persisted until 2 to 3 wk old. The Nk-1+ cells in "baby" (1 to 2 wk old) spleen bound to YAC cells but failed to lyse them in 51Cr-release assay. Upon induction with interferon (IF), the proportion of Nk-1+ cells increased, but the lytic activity remained low, suggesting that the "baby" NK-1+ cells are immature in lytic function. In old mice (12 to 14 mo), Nk-1+ cells were also detectable, even though NK activities were lower compared with those of the young adult (6 to 8 wk old) mice. The Nk-1+ cells of old mice were readily induced by IF to exhibit activities, and the induced NK cells were Nk-1+. We have thus established Nk-1.1 antigen as an early hemopoietic differentiation antigen. Splenic Nk-1- cells could be induce by IF to become NK-1+ cells, which could be inactive or active in NK assays, dependent on the age of the mice.


Methods to Measure Water Permeability.
Water permeability is a key feature of the cell plasma membranes and it has seminal importance for a number of cell functions such as cell volume regulation, cell proliferation, cell migration, and angiogenesis to name a few. The transport of water occurs mainly through plasma membrane water channels , the aquaporins, who have very important function in physiological and pathophysiological states. Due to the above the experimental assessment of the water permeability of cells and tissues is necessary. The development of new methodologies of measuring water permeability is a vibrant scientific field that constantly develops during the past three decades along with the advances in imaging mainly. In this chapter we describe and critically assess several methods that have been developed for the measurement of water permeability both in living cells as well as in tissues with a focus in the first category.


Investigation of Potential Drug Targets for Cholesterol Regulation to Treat Alzheimer's Disease.
Despite extensive research and seven approved drugs, the complex interplay of genes, proteins, and pathways in Alzheimer's disease remains a challenge. This implies the intricacies of the mechanism for Alzheimer's disease, which involves the interaction of hundreds of genes, proteins, and pathways. While the major hallmarks of Alzheimer's disease are the accumulation of amyloid plaques and tau protein tangles, excessive accumulation of cholesterol is reportedly correlated with Alzheimer's disease patients. In this work, protein-protein interaction analysis was conducted based upon the genes from a clinical database to identify the top protein targets with most data-indicated involvement in Alzheimer's disease, which include ABCA1, CYP46A1, BACE1, TREM2, GSK3B, and SREBP2. The reactions and pathways associated with these genes were thoroughly studied for their roles in regulating brain cholesterol biosynthesis, amyloid beta accumulation, and tau protein tangle formation. Existing clinical trials for each protein target were also investigated. The research indicated that the inhibition of SREBP2, BACE1, or GSK3B is beneficial to reduce cholesterol and amyloid beta accumulation, while the activation of ABCA1, CYP46A1, or TREM2 has similar effects. In this study, Sterol Regulatory Element-Binding Protein 2 (SREBP2) emerged as the primary protein target. SREBP2 serves a pivotal role in maintaining cholesterol balance, acting as a transcription factor that controls the expression of several enzymes pivotal for cholesterol biosynthesis. Novel studies suggest that SREBP2 performs a multifaceted role in Alzheimer's disease. The hyperactivity of SREBP2 may lead to heightened cholesterol biosynthesis, which suggested association with the pathogenesis of Alzheimer's disease. Lowering SREBP2 levels in an Alzheimer's disease mouse model results in reduced production of amyloid-beta, a major contributor to Alzheimer's disease progression. Moreover, its thoroughly analyzed crystal structure allows for computer-aided screening of potential inhibitors; SREBP2 is thus selected as a prospective drug target. While more protein targets can be added onto the list in the future, this work provides an overview of key proteins involved in the regulation of brain cholesterol biosynthesis that may be further investigated for Alzheimer's disease intervention.


Modeling human postural sway using an intermittent control and hemodynamic perturbations.
Ground reaction force during human quiet stance is modulated synchronously with the cardiac cycle through hemodynamics [1]. This almost periodic hemodynamic force induces a small disturbance torque to the ankle joint, which is considered as a source of endogenous perturbation that induces postural sway. Here we consider postural sway dynamics of an inverted pendulum model with an intermittent control strategy, in comparison with the traditional continuous-time feedback controller. We examine whether each control model can exhibit human-like postural sway, characterized by its power law behavior at the low frequency band 0.1-0.7Hz, when it is weakly perturbed by periodic and/or random forcing mimicking the hemodynamic perturbation. We show that the continuous control model with typical feedback gain parameters hardly exhibits the human-like sway pattern, in contrast with the intermittent control model. Further analyses suggest that deterministic, including chaotic, slow oscillations that characterize the intermittent control strategy, together with the small hemodynamic perturbation, could be a possible mechanism for generating the postural sway.


Higher plasma interleukin-18 levels associated with poor quality of sleep in peritoneal dialysis patients.
Sleep disorders are prevalent in patients with end-stage renal disease. Increasing evidence suggests that cytokines are involved in the regulation of sleep and wakefulness. The purpose of this study was to examine the relationship between quality of sleep and plasma interleukin-18 levels in peritoneal dialysis patients. Plasma interleukin-18 levels were determined by the enzyme-linked immunosorbent assay (ELISA) methodology in 57 peritoneal dialysis patients. Quality of sleep was measured using the Pittsburgh Sleep Quality Index. Demographic and routine laboratory data were recorded. In our cohort, the poor sleepers had higher plasma interleukin-18 levels (559.16 +/- 261.22 pg/ml vs 397.49 +/- 191.81 pg/ml, P = 0.01). The plasma interleukin-18 level was positively correlated with the Pittsburgh Sleep Quality Index score (r = 0.286, P = 0.031), that is, there was a positive association between higher plasma interleukin-18 levels and poorer quality of sleep. This study demonstrates that interleukin-18 may be involved in sleep disorders in end-stage renal disease patients. Higher plasma interleukin-18 levels are associated with poorer quality of sleep in peritoneal dialysis patients. Whether a cause-and-effect relationship exists between interleukin-18 and quality of sleep deserves further study.


Bent DNA functions as a replication enhancer in Saccharomyces cerevisiae.
Previous studies have demonstrated that bent DNA is a conserved property of Saccharomyces cerevisiae autonomously replicating sequences (ARSs). Here we showed that bending elements are contained within ARS subdomains identified by others as replication enhancers. To provide a direct test for the function of this unusual structure, we analyzed the ARS activity of plasmids that contained synthetic bent DNA substituted for the natural bending element in yeast ARS1. The results demonstrated that deletion of the natural bending locus impaired ARS activity which was restored to a near wild-type level with synthetic bent DNA. Since the only obvious common features of the natural and synthetic bending elements are the sequence patterns that give rise to DNA bending, the results suggest that the bent structure per se is crucial for ARS function.


Combination of Prostate Cancer Antigen 3 and Prostate-Specific Antigen Improves Diagnostic Accuracy in Men at Risk of Prostate Cancer.
- Prostate cancer antigen 3 (PCA3) is a noncoding RNA that is highly overexpressed in prostate cancer (PCa) tissue and excreted in urine in patients with PCa. - To assess the clinical utility of urinary PCA3 in men at risk of PCa. - We retrospectively reviewed a cohort of 271 men (median age, 63 years) with elevated prostate-specific antigen (PSA), and/or strong family history, and/or abnormal digital rectal examination findings. Diagnostic sensitivity, specificity, positive and negative predictive values (PPV, NPV), positive and negative likelihood ratios (LR+, LR-), and diagnostic odds ratio (DOR), and area under the receiver-operating characteristic curves (AUC) were evaluated. - PCA3 score was a significant predictor of prostate biopsy outcome ( P < .001). A PCA3 score of 30 was the optimal cutoff for our study cohort, with a diagnostic sensitivity of 72.7%, specificity of 67.5%, PPV of 47.1%, NPV of 86.2%, LR+ of 2.24, LR- of 0.40, and DOR of 5.55. At this cutoff score, the PCA3 assay could avoid 57.4% of unnecessary invasive biopsies in the overall study cohort and 70.3% in the subgroup with PSA level in the "gray zone" (4-10 ng/mL). A logistic regression algorithm combining PCA3 with PSA increased the AUC from 0.571 for PSA-only to 0.729 ( P < .001). The logistic combined marker gained the ability to discriminate low-grade from high-grade cancers. - Our data suggest that PCA3 improves the diagnostic sensitivity and specificity of PSA and that the combination of PCA3 with PSA gives better overall performance in identification of PCa than serum PSA alone in the high-risk population.


Separation of peptides and oligonucleotides using a monolithic polymer layer and pressurized planar electrophoresis and electrochromatography.
The rapid separation of mixtures of six peptides using porous polymer monolithic layers in electrophoresis and pressurized planar electrochromatography modes has been achieved. The separations in the former mode were performed on a generic hydrophobic poly(butyl methacrylate-co-ethylene dimethacrylate) layer with no ionizable functionalities and required 2 min. This layer also enabled the separation of three oligonucleotides. The separation in the pressurized planar electrochromatographic mode was carried out using a negatively charged layer prepared via cografting of 2-acrylamido-2-methyl-1-propanesulfonic acid and 2-hydroxyethyl methacrylate on top of the generic hydrophobic monolith and was completed in 1 min.


Mucoepidermoid carcinoma of the thyroid gland arising from a papillary epithelial neoplasm.
We report a case of mucoepidermoid carcinoma of the thyroid gland. The simultaneous association of papillary and mucoepidermoid carcinoma in a Hashimoto's thyroiditis makes the present observation unusual. Surgery was limited due to local extension of the neoplasm. The patient consequently underwent external radiotherapy followed by radiometabolic therapy. The patient survived 11 months after diagnosis. As far as the histogenesis of the neoplasm is concerned, we believe that mucoepidermoid areas correspond to squamous and mucinous metaplasia of a preexisting papillary carcinoma. Transition areas between elements morphologically characteristic of both neoplasms were observed. Histochemical and immunohistochemical studies confirmed the diagnosis of a carcinoma with multiple aspects showing a focal positive reaction for thyroglobulin or keratin antisera. Therefore, this demonstrates different functional activities of the neoplastic cells. There is still debate about adjuvant therapies, the results of which appear for the moment very poor.


Effects of the 5-HT2 receptor antagonist, ritanserin on hyperthermia and depletion of 5-HT in frontal cortex induced by a 5-HT releasing drug, p-chloroamphetamine (PCA) in mice.
Effects of the 5-HT2 receptor antagonist, ritanserin on hyperthermia and depletion of 5-HT induced by the 5-HT-releasing drug, p-chloroamphetamine (PCA) were investigated. Ritanserin significantly suppressed PCA-induced hyperthermia in mice. PCA elicited decreases in 5-HT levels in the mouse frontal cortex. 5-HT reduction elicited by PCA was also attenuated by pretreatment with ritanserin. Since hyperthermia facilitates neurotoxicity induced by amphetamine analogue, ritanserin may inhibit PCA-induced 5-HT neurotoxicity by inhibiting hyperthermia.


Temperature dependence of the colloidal agglomeration inhibition: computer simulation study.
There exist experimental evidences that the structure and extension of colloidal aggregates in suspensions change dramatically with temperature. This results in an associated change in the suspension rheology. Experimental studies of the inhibitor applications to control the particle clustering have revealed some unexpected tendencies. Namely, the heating of colloidal suspensions has provoked either extension or reduction of the colloidal aggregates. To elucidate the origin of this behavior, we investigate the influence of temperature on the stabilizing effect of the inhibitor, applying an associative two-component fluid model. Our results of the canonical Monte Carlo simulations indicate that the anomalous effect of the temperature may not be necessarily explained by the temperature dependent changes in the inhibitor tail conformation, as has been suggested recently by Won et al. [Langmuir 21, 924 (2005)]. We show that the competition between colloid-colloid and colloid-inhibitor associations, which, in turn, depends on the temperature and the relative concentrations, may be one of the main reasons for the unexpected temperature dependence of inhibitor efficacy.


[Diagnosis and treatment of congenital bronchopulmonary malformations. A review of 32 cases].
Analysis of our experience and propositions on the diagnosis and treatment of congenital bronchopulmonary malformations (BPM). Retrospective study of BPM diagnosed between 1997 and 2001. Analysis of clinical spectrum, diagnosis tools, treatment, and clinical outcome. Thirty-two cases of BPM have been investigated (11 cystic adenomatoid malformations, 7 pulmonary sequestrations, 7 bronchogenic cysts, 4 congenital lobar emphysema, and 3 complex emphysematous malformations). Nineteen patients had a prenatal diagnosis. For 9 others, symptoms occurred before 4 years of age. Evaluation included a CT-scan in all patients (BPM involution in one). Surgical treatment was performed in 30 patients (lobectomy in 18), with a mean age of 7 months for asymptomatic patients. During the follow-up (mean: 3 years), respiratory symptoms were reported in 10 cases, 3 of them were related to the BPM. Improvement in prenatal ultrasound diagnosis modified the management strategy. Considering the risk of pulmonary complications, surgical treatment is required during the first months of life. For congenital lobar emphysema, and some pulmonary sequestrations or small cystic adenomatoid malformations (<3 cm), conservative attitude may be preferred. BPM justify a multidisciplinary management.


A Unique Presentation of the Glenoid, Coracoid, and Proximal Humerus Fractures.
Fractures of the proximal humerus are common injuries with a bimodal age distribution. They usually present in younger patients after high-energy trauma and in elderly patients after lower-energy trauma. Fractures of the proximal humerus are rarely associated with concomitant fractures of the glenoid, and this is a complex injury pattern that indicates the presence of significant instability. Such injuries are usually treated surgically. Even more rarely, patients may present with proximal humerus fractures and fractures of the coracoid process. A male patient presented to our emergency department (ED) after a fall off the loading platform of his heavy goods vehicle (HGV), resulting in a right shoulder injury. During his initial assessment in ED, a computerised tomography (CT) scan demonstrated the presence of a comminuted proximal humerus fracture, a comminuted anterior glenoid wall fracture, and a coracoid process displaced fracture. Surgical fixation of all three fractures was undertaken in the same sitting. This is the first case described in the literature with a combination of the above injuries and serves as a reminder that as trauma complexity and incidence continue to increase, we should maintain a high index of diagnostic suspicion when dealing with such patients. Furthermore, we present our treatment approach for this case and the rationale behind it.