[Clinical efficacy of fluconazole, tinidazole and clindamycin vs fluconazole, tinidazole and azithromycin in the treatment of mixed cervical-vaginal infections, included those caused by Mycoplasma and Chlamydia trachomatis].
In the United States 19 million people acquire a sexually transmitted disease every year. Sexually transmitted diseases impact in gynecological terms because they may cause sterility, infertility and ectopic pregnancy. To compare the effectiveness of two combinations of three oral antimicrobial drugs in the treatment of mixed cervical-vaginal infections, included those caused by Mycoplasma and Chlamydia trachomatis. Aclinical, random, comparative, double-blind study included 50 patients assisting to infectology consult with diagnosis of mixed cervical-vaginal infection. Patients were divided into two groups: Group A (n = 25): fluconazole 37.5 mg, tinidazole 500 mg and azithromycin 250 mg; group B (n = 25): fluconazole 37.5 mg, tinidazole 500 mg and clindamycin 312.5 mg. Patients of both groups received two tablets twice p.o. for one day. Cultures were performed to corroborate the diagnosis and then to demonstrate effectiveness of the schemes studied. For the analysis of the data we used measures of central tendency, dispersion and inferential statistics for comparison of proportions by c2 and Fisher's exact tests with a significance level of p < 0.05. All patient got clinical cure; however, regarding the microbiologic eradication a positive case was identified in group A, requiring rescue treatment. The compliance in both groups was of 100%. In both groups, statistical analysis did not show significant differences. Three patients in group A had mild adverse effects. Patients mean age was 33.4 +/- 5.3 years. Both treatments showed similar effectiveness against mixed cervical-vaginal infections. Microbiological efficacy was of 96% and 100% in group A and B, respectively, besides, scheme of group B was better tolerated.


Mechanotransduction and Adrenergic Stimulation in Arrhythmogenic Cardiomyopathy: An Overview of in vitro and in vivo Models.
Arrhythmogenic Cardiomyopathy (AC) is a rare inherited heart disease, manifesting with progressive myocardium degeneration and dysfunction, and life-threatening arrhythmic events that lead to sudden cardiac death. Despite genetic determinants, most of AC patients admitted to hospital are athletes or very physically active people, implying the existence of other disease-causing factors. It is recognized that AC phenotypes are enhanced and triggered by strenuous physical activity, while excessive mechanical stretch and load, and repetitive adrenergic stimulation are mechanisms influencing disease penetrance. Different approaches have been undertaken to recapitulate and study both mechanotransduction and adrenergic signaling in AC, including the use of in vitro cellular and tissue models, and the development of in vivo models (particularly rodents but more recently also zebrafish). However, it remains challenging to reproduce mechanical load stimuli and physical activity in laboratory experimental settings. Thus, more work to drive the innovation of advanced AC models is needed to recapitulate these subtle physiological influences. Here, we review the state-of-the-art in this field both in clinical and laboratory-based modeling scenarios. Specific attention will be focused on highlighting gaps in the knowledge and how they may be resolved by utilizing novel research methodology.


A rational computational study of surface defect-mediated stabilization of low-dimensional Pt nanostructures on TiN(100).
Platinum is known as a catalyst with exceptional reactivity for many important reactions, e.g. the oxygen reduction reaction. To reduce the high cost of pure platinum catalysts, platinum on a carbon support is widely used in industrial fuel cell applications. However, these Pt/C systems suffer from poor stability. As a cost-efficient and more durable alternative, Pt single-atom catalysts on a TiN support have recently been suggested, and it has been shown that the single-atom catalysts are stable when anchored at a nitrogen vacancy site on the TiN surface in a nitrogen-lean environment. To further explore the perspective of Pt/TiN catalytic systems, we provide insights into the stability and morphology of Pt nanostructures at the TiN(100) surface, using a density-functional theory approach in combination with ab initio atomistic thermodynamics. Our results show that the formation of two-dimensional Pt nano-layers is preferred over the formation of three-dimensional Pt nano-clusters on the TiN substrate. Similar to the single-atom catalysts, nano-layers of Pt can be stabilized on the TiN(100) surface by surface nitrogen vacancies under nitrogen-lean conditions. By analyzing the electronic metal-support interaction (EMSI) between the Pt nano-layer and the TiN surface with surface defects, we demonstrate that a strong EMSI between the surrounding Ti and Pt atoms is important for stabilizing the catalyst nano-layer at the TiN surface, and that N vacancies lead to stronger Pt-Ti interaction. This work provides a rational computational platform for the design of new generation high-performance Pt-based fuel cells.


Off-flavor related volatiles in soymilk as affected by soybean variety, grinding, and heat-processing methods.
Off-flavor of soymilk is a barrier to the acceptance of consumers. The objectionable soy odor can be reduced through inhibition of their formation or through removal after being formed. In this study, soymilk was prepared by three grinding methods (ambient, cold, and hot grinding) from two varieties (yellow Prosoy and a black soybean) before undergoing three heating processes: stove cooking, one-phase UHT (ultrahigh temperature), and two-phase UHT process using a Microthermics direct injection processor, which was equipped with a vacuuming step to remove injected water and volatiles. Eight typical soy odor compounds, generated from lipid oxidation, were extracted by a solid-phase microextraction method and analyzed by gas chromatography. The results showed that hot grinding and cold grinding significantly reduced off-flavor as compared with ambient grinding, and hot grinding achieved the best result. The UHT methods, especially the two-phase UHT method, were effective to reduce soy odor. Different odor compounds showed distinct concentration patterns because of different formation mechanisms. The two varieties behaved differently in odor formation during the soymilk-making process. Most odor compounds could be reduced to below the detection limit through a combination of hot grinding and two-phase UHT processing. However, hot grinding gave lower solid and protein recoveries in soymilk.


Modular structure of glucocorticoid receptor domains is not equivalent to functional independence. Stability and activity of the steroid binding domain are controlled by sequences in separate domains.
A long-standing conundrum of glucocorticoid receptors has been why the steroid binding domain is active in hybrid proteins but not in isolation. For this reason, the precise boundaries of the steroid binding domain have not been defined. These questions have now been systematically examined with a variety of receptor deletion constructs. Plasmids encoding amino acids 537-673 and 537-795 of the rat receptor did not yield stable proteins, while the fusion of receptor or non-receptor sequences upstream of 537-673 afforded stable proteins that did not bind steroid. Wild type steroid binding affinity could be obtained, however, when proteins such as beta-galactosidase or dihydrofolate reductase were fused upstream of receptor amino acids 537-795. Studies of a series of dhfr/receptor constructs with deletions at the amino- and carboxyl-terminal ends of the receptor sequence localized the boundaries of the steroid binding domain to 550-795. The absence of steroid binding upon deletion of sequences in the carboxyl-terminal half of this domain was consistent with improperly folded receptor sequences. This conclusion was supported by analyses of the proteolysis and thermal stability of the mutant receptors. Thus, three independent regions appear to be required for the generation of the steroid binding form of receptors: 1) a protein sequence upstream of the steroid binding domain, which conveys stability to the steroid binding domain, 2) sequences of the carboxyl-terminal amino acids (674-795), which are required for the correct folding of the steroid binding domain, and 3) amino-terminal sequences (550-673), which may be sufficient for steroid binding after the entire steroid binding domain is properly folded. These results establish that the steroid binding domain of glucocorticoid receptors is not independently functional and illustrate the importance of both protein stability and protein folding when constructing mutant proteins.


Bacillus subtilis NrnB is expressed during sporulation and acts as a unique 3'-5' exonuclease.
All cells employ a combination of endo- and exoribonucleases to degrade long RNA polymers to fragments 2-5 nucleotides in length. These short RNA fragments are processed to monoribonucleotides by nanoRNases. Genetic depletion of nanoRNases has been shown to increase abundance of short RNAs. This deleteriously affects viability, virulence, and fitness, indicating that short RNAs are a metabolic burden. Previously, we provided evidence that NrnA is the housekeeping nanoRNase for Bacillus subtilis. Herein, we investigate the biological and biochemical functions of the evolutionarily related protein, B. subtilis NrnB (NrnBBs). These experiments show that NrnB is surprisingly different from NrnA. While NrnA acts at the 5' terminus of RNA substrates, NrnB acts at the 3' terminus. Additionally, NrnA is expressed constitutively under standard growth conditions, yet NrnB is selectively expressed during endospore formation. Furthermore, NrnA processes only short RNAs, while NrnB unexpectedly processes both short RNAs and longer RNAs. Indeed, inducible expression of NrnB can even complement the loss of the known global 3'-5' exoribonucleases, indicating that it acts as a general exonuclease. Together, these data demonstrate that NrnB proteins, which are widely found in Firmicutes, Epsilonproteobacteria and Archaea, are fundamentally different than NrnA proteins and may be used for specialized purposes.


Ranibizumab and pegaptanib for the treatment of age-related macular degeneration: a systematic review and economic evaluation.
To assess the clinical effectiveness and cost-effectiveness of ranibizumab and pegaptanib for subfoveal choroidal neovascularisation (CNV) associated with wet age-related macular degeneration (AMD). Electronic databases were searched from inception to September 2006. Experts in the field were consulted and manufacturers' submissions were examined. The quality of included studies was assessed using standard methods and the clinical effectiveness data were synthesised through a narrative review with full tabulation of results. A model was developed to estimate the cost-effectiveness of ranibizumab and of pegaptanib (separately), compared with current practice or best supportive care, from the perspective of the NHS and Personal Social Services. Two time horizons were adopted for each model. The first adopted time horizons determined by the available trial data. The second analysis extrapolated effects of treatment beyond the clinical trials, adopting a time horizon of 10 years. The combined analysis of two randomised controlled trials (RCTs) of pegaptanib [0.3 mg (licensed dose), 1.0 mg and 3.0 mg] versus sham injection in patients with all lesion types was reported by three publications (the VISION study). Three published RCTs of ranibizumab were identified (MARINA, ANCHOR, FOCUS), and an additional unpublished RCT was provided by the manufacturer (PIER). Significantly more patients lost less than 15 letters of visual acuity at 12 months when taking pegaptanib (0.3 mg: 70% of patients; 1.0 mg: 71% of patients; 3.0 mg: 65% of patients) or ranibizumab (0.3 mg: 94.3-94.5%; 0.5 mg: 94.6-96.4%) than sham injection patients (55% versus pegaptanib and 62.2% versus ranibizumab) or, in the case of ranibizumab, photodynamic therapy (PDT) (64.3%). The proportion of patients gaining 15 letters or more (a clinically important outcome having a significant impact on quality of life) was statistically significantly greater in the pegaptanib group for doses of 0.3 and 1.0 mg but not for 3.0 mg, and for all ranibizumab groups compared to the sham injection groups or PDT. This was also statistically significant for patients receiving 0.5 mg ranibizumab plus PDT compared with PDT plus sham injection. Pegaptanib patients lost statistically significantly fewer letters after 12 months of treatment than the sham group [mean letters lost: 7.5 (0.3 mg), 6.5 (1.0 mg) or 10 (3.0 mg) vs 14.5 (sham)]. In the MARINA and ANCHOR trials, ranibizumab patients gained letters of visual acuity at 12 months whereas patients with sham injection or PDT lost about 10 letters (p<0.001) and in the PIER study, ranibizumab patients lost significantly fewer than the sham injection group. Significantly fewer patients receiving pegaptanib or ranibizumab deteriorated to legal blindness compared with the control groups. Adverse events were common for both pegaptanib andranibizumab but most were mild to moderate. Drug costs for 1 year of treatment were estimated as 4626 pounds for pegaptanib and 9134 pounds for ranibizumab. Non-drug costs accounted for an additional 2614 pounds for pegaptanib and 3120 pounds for ranibizumab. Further costs are associated with the management of injection-related adverse events, from 1200 pounds to 2100 pounds. For pegaptanib compared with usual care, the incremental cost-effectiveness ratio (ICER) ranged from 163,603 pounds for the 2-year model to 30,986 pounds for the 10-year model. Similarly, the ICERs for ranibizumab for patients with minimally classic and occult no classic lesions, compared with usual care, ranged from 152,464 pounds for the 2-year model to 25,098 pounds for the 10-year model. Patients with AMD of any lesion type benefit from treatment with pegaptanib or ranibizumab on measures of visual acuity when compared with sham injection and/or PDT. Patients who continued treatment with either drug appeared to maintain benefits after 2 years of follow-up. When comparing pegaptanib and ranibizumab, the evidence was less clear due to the lack of direct comparison through head-to-head trials and the lack of opportunity for indirect statistical comparison due to heterogeneity. The cost-effectiveness analysis showed that the two drugs offered additional benefit over the comparators of usual care and PDT but at increased cost. Future research should encompass trials to compare pegaptanib with ranibizumab and bevacizumab, and to investigate the role of verteporfin PDT in combination with these drugs. Studies are also needed to assess adverse events outside the proposed RCTs, to consider the optimal dosing regimes of these drugs and the benefits of re-treatment after initial treatment, and to review costing in more detail. Health state utilities and their relationship with visual acuity and contrast sensitivity, the relationship between duration of vision loss and the quality of life and functional impact of vision loss, behavioural studies of those genetically at risk are other topics requiring further research.


From droplets to nanowires: dynamics of vapor-liquid-solid growth.
Starting with a liquid eutectic droplet on a surface, we calculate its dynamical evolution into an epitaxial nanowire via the vapor-liquid-solid growth process. Our continuum approach incorporates kinetic effects and crystalline anisotropy in a natural way. Some realistic features appear automatically even for an isotropic solid, e.g., the tapered wire base. Crystal anisotropy leads to a richer variety of morphologies. For example, sixfold anisotropy leads to a wire shape having broken symmetry and an intriguing resemblance to the 110-oriented Si wires seen in Au-catalyzed growth on Si (111), while higher symmetry leads to a shape more like <111> Si wires.


Capecitabine-based treatment of a patient with a novel DPYD genotype and complete dihydropyrimidine dehydrogenase deficiency.
Fluoropyrimidines are frequently used anti-cancer drugs. It is known that patients with reduced activity of dihydropyrimidine dehydrogenase (DPD), the key metabolic enzyme in fluoropyrimidine inactivation, are at increased risk of developing severe fluoropyrimidine-related toxicity. Upfront screening for DPD deficiency and dose reduction in patients with partial DPD deficiency is recommended and improves patient safety. For patients with complete DPD deficiency, fluoropyrimidine-treatment has generally been discouraged. During routine pretreatment screening, we identified a 59-year-old patient with a sigmoid adenocarcinoma who proved to have a complete DPD deficiency. Genetic analyses showed that this complete absence of DPD activity was likely to be caused by a novel DPYD genotype, consisting of a combination of amplification of exons 17 and 18 of DPYD and heterozygosity for DPYD*2A. Despite absence of DPD activity, the patient was treated with capecitabine-based chemotherapy, but capecitabine dose was drastically reduced to 150 mg once every 5 days (0.8% of original dose). Pharmacokinetic analyses showed that the area under the concentration-time curve (AUC) and half-life of 5-fluorouracil were respectively tenfold and fourfold higher than control values of patients receiving capecitabine 850 mg/m2 . When extrapolating from the dosing schedule of once every 5 days to twice daily, the AUC of 5-fluorouracil was comparable to controls. Treatment was tolerated well for eight cycles by the patient without occurrence of capecitabine-related toxicity. This case report demonstrates that a more comprehensive genotyping and phenotyping approach, combined with pharmacokinetically-guided dose administration, enables save fluoropyrimidine-treatment with adequate drug exposure in completely DPD deficient patients.


Trading bits in the readout from a genetic network.
In the regulation of gene expression, information of relevance to the organism is represented by the concentrations of transcription factor molecules. To extract this information the cell must effectively "measure" these concentrations, but there are physical limits to the precision of these measurements. We use the gap gene network in the early fly embryo as an example of the tradeoff between the precision of concentration measurements and the transmission of relevant information. For thresholded measurements we find that lower thresholds are more important, and fine tuning is not required for near-optimal information transmission. We then consider general sensors, constrained only by a limit on their information capacity, and find that thresholded sensors can approach true information theoretic optima. The information theoretic approach allows us to identify the optimal sensor for the entire gap gene network and to argue that the physical limitations of sensing necessitate the observed multiplicity of enhancer elements, with sensitivities to combinations rather than single transcription factors.


Generation of a herpes simplex virus type 1 variant devoid of XbaI sites.
Using both selection enrichment and site-directed mutagenesis, a herpes simplex virus type 1 (HSV-1) strain 17 genome lacking all four XbaI sites has been generated. The site at 0.45 map units which lies within the gene coding for a polypeptide of 28,000 molecular weight was removed by selection enrichment, while the site at 0.29 map units which lies within the gene coding for glycoprotein H was removed by site-directed mutagenesis. The parental virus from which these two XbaI sites were deleted had previously had the sites at 0.07 and 0.63 map units removed through selection enrichment. The variant devoid of XbaI sites (X4) showed normal growth characteristics; its phenotype was normal apart from the absence of the thymidine kinase protein, which is believed to be unrelated to the loss of XbaI sites.


Interlinking journal and wiki publications through joint citation: Working examples from ZooKeys and Plazi on Species-ID.
Scholarly publishing and citation practices have developed largely in the absence of versioned documents. The digital age requires new practices to combine the old and the new. We describe how the original published source and a versioned wiki page based on it can be reconciled and combined into a single citation reference. We illustrate the citation mechanism by way of practical examples focusing on journal and wiki publishing of taxon treatments. Specifically, we discuss mechanisms for permanent cross-linking between the static original publication and the dynamic, versioned wiki, as well as for automated export of journal content to the wiki, to reduce the workload on authors, for combining the journal and the wiki citation and for integrating it with the attribution of wiki contributors.


Inter- and intralimb adaptations to a sensory perturbation during activation of the serotonin system after a low spinal cord transection in neonatal rats.
Activation of the serotonin system has been shown to induce locomotor activity following a spinal cord transection. This study examines how the isolated spinal cord adapts to a sensory perturbation during activation of the serotonergic system. Real-time and persistent effects of a perturbation were examined in intact and spinal transected newborn rats. Rats received a spinal surgery (sham or low thoracic transection) on postnatal day 1 and were tested 9 days later. At test, subjects were treated with the serotonergic receptor agonist quipazine (3.0 mg/kg) to induce stepping behavior. Half of the subjects experienced range of motion (ROM) restriction during stepping, while the other half did not. Differences in stepping behavior (interlimb coordination) and limb trajectories (intralimb coordination) were found to occur in both intact and spinal subjects. Adaptations were seen in the forelimbs and hindlimbs. Also, real-time and persistent effects of ROM restriction (following removal of the perturbation) were seen in ROM-restricted subjects. This study demonstrates the sensitivity of the isolated spinal cord to sensory feedback in conjunction with serotonin modulation.


Studies of hemorrhage on the optic disc.
The general medical and laboratory findings in 60 patients having a sector hemorrhage on the optic disc were compared with the findings in 102 patients with intraocular pressure elevation but without a disc hemorrhage. Of 22 parameters studied, systemic hypertension was the only abnormality which occurred significantly more frequently in the hemorrhage group. A study of the intraocular pressures suggests that hemorrhage may not be related to the level of intraocular pressure. Examinations of 50 patients with systemic hypertension and of 50 patients with cardiac abnormalities revealed no hemorrhage on the optic disc. These factors by themselves may not be responsible for the occurrence of hemorrhages.


[Effect of cAMP on the growth and development of luminescence in Photobacterium belozerskii].
The effect of cAMP on the parameters characterizing the development of luminescence in Photobacterium belozerskii is discussed. An addition of cAMP to the culture medium shortened the latent time of luminescence development by 3--6 hours. The intensity of bacterial luminescence increased with a varying rate. During luminescence enhancement the rate of luciferase synthesis increased by a factor of 10 to 10(3). The rate of luciferase synthesis and the maxiumum level of bacterial luminescence when cultivated in the glycerol medium containing arginine and proline increased under the influence of cAMP by 100 and 40 times, respectively. After an addition to cAMP into the glucose medium these parameters of luminescence development increased only when the medium contained arginine. After an addition of cAMP into the glycerol medium the rate of bacterial growth increased two-fold. Possible mechanisms regulating luminescence development and cAMP involvement in these processes are discussed.


Cyclopia: an epidemiologic study in a large dataset from the International Clearinghouse of Birth Defects Surveillance and Research.
Cyclopia is characterized by the presence of a single eye, with varying degrees of doubling of the intrinsic ocular structures, located in the middle of the face. It is the severest facial expression of the holoprosencephaly (HPE) spectrum. This study describes the prevalence, associated malformations, and maternal characteristics among cases with cyclopia. Data originated in 20 Clearinghouse (ICBDSR) affiliated birth defect surveillance systems, reported according to a single pre-established protocol. A total of 257 infants with cyclopia were identified. Overall prevalence was 1 in 100,000 births (95%CI: 0.89-1.14), with only one program being out of range. Across sites, there was no correlation between cyclopia prevalence and number of births (r = 0.08; P = 0.75) or proportion of elective termination of pregnancy (r = -0.01; P = 0.97). The higher prevalence of cyclopia among older mothers (older than 34) was not statistically significant. The majority of cases were liveborn (122/200; 61%) and females predominated (male/total: 42%). A substantial proportion of cyclopias (31%) were caused by chromosomal anomalies, mainly trisomy 13. Another 31% of the cases of cyclopias were associated with defects not typically related to HPE, with more hydrocephalus, heterotaxia defects, neural tube defects, and preaxial reduction defects than the chromosomal group, suggesting the presence of ciliopathies or other unrecognized syndromes. Cyclopia is a very rare defect without much variability in prevalence by geographic location. The heterogeneous etiology with a high prevalence of chromosomal abnormalities, and female predominance in HPE, were confirmed, but no effect of increased maternal age or association with twinning was observed.


Haplotype diversity in 11 candidate genes across four populations.
Analysis of haplotypes based on multiple single-nucleotide polymorphisms (SNP) is becoming common for both candidate gene and fine-mapping studies. Before embarking on studies of haplotypes from genetically distinct populations, however, it is important to consider variation both in linkage disequilibrium (LD) and in haplotype frequencies within and across populations, as both vary. Such diversity will influence the choice of "tagging" SNPs for candidate gene or whole-genome association studies because some markers will not be polymorphic in all samples and some haplotypes will be poorly represented or completely absent. Here we analyze 11 genes, originally chosen as candidate genes for oral clefts, where multiple markers were genotyped on individuals from four populations. Estimated haplotype frequencies, measures of pairwise LD, and genetic diversity were computed for 135 European-Americans, 57 Chinese-Singaporeans, 45 Malay-Singaporeans, and 46 Indian-Singaporeans. Patterns of pairwise LD were compared across these four populations and haplotype frequencies were used to assess genetic variation. Although these populations are fairly similar in allele frequencies and overall patterns of LD, both haplotype frequencies and genetic diversity varied significantly across populations. Such haplotype diversity has implications for designing studies of association involving samples from genetically distinct populations.


Foretelling the Phenotype of a Genomic Sequence.
Estimating phenotypic features (physical and biochemical traits) in a biological organism from their genomic sequence alone and/or environmental conditions has major applications in anthropological paleontology and criminal forensics, for example. To what extent do genomic sequences generally and causally determine phenotypic features of organisms, environmental conditions aside? We present results of two studies, one in blackfly (Insecta:Diptera:Simuliidae) larvae in two species (Simulium ignescens and S. tunja) with four phenotypic features, including the area and spot pattern of the cephalic apotome (in the form of a latin cross on the dorsal side of the head), the postgenal cleft (area under the head on the ventral side) and general body color in larva specimens; the second in strains of Arabidopsis thaliana. They establish that a substantial component of these phenotypic features (over 75 percent) are at least logically inferable, if not causally determined, by genomic fragments alone, despite the fact that these phenotypic features are not 100 percent determined entirely by genetic traits. These results suggest that it is possible to infer the genetic contribution in the determination of specific phenotypic features of a biological organism, without recourse to the causal chain of metabolomics and proteomic events leading to them from genomic sequences.


Malignancies in systemic lupus erythematosus: an update.
Patients with systemic lupus erythematosus (SLE) have altered incidences of certain malignancies as compared with the general population. This review summarizes the recent literature on risk of malignancy in SLE and proposed mechanisms for these altered susceptibilities. Recent studies have confirmed previous data showing an increased risk of hematological, lung, thyroid, liver, cervical and vulvovaginal cancers, while demonstrating a decreased risk of breast and prostate cancer. Lymphomagenesis in SLE has been linked to increased activity of multiple inflammatory cytokines as well as possible viral causes. The decreased rates of hormone-sensitive cancers, such as breast and prostate is speculated to be related to the presence of lupus autoantibodies and downregulation of certain proteins in SLE. This knowledge has been utilized to investigate new therapeutic modalities for these malignancies. Recent data confirm previously reported altered malignancy rates in SLE. There has been some elucidation of mechanisms underlying cancer development in SLE, although additional work is yet to be done.


Efficacy and Safety Extrapolation Analyses for Atomoxetine in Young Children with Attention-Deficit/Hyperactivity Disorder.
This extrapolation analysis qualitatively compared the efficacy and safety profile of atomoxetine from Lilly clinical trial data in 6-7-year-old patients with attention-deficit/hyperactivity disorder (ADHD) with that of published literature in 4-5-year-old patients with ADHD (two open-label [4-5-year-old patients] and one placebo-controlled study [5-year-old patients]). The main efficacy analyses included placebo-controlled Lilly data and the placebo-controlled external study (5-year-old patients) data. The primary efficacy variables used in these studies were the ADHD Rating Scale-IV Parent Version, Investigator Administered (ADHD-RS-IV-Parent:Inv) total score, or the Swanson, Nolan and Pelham (SNAP-IV) scale score. Safety analyses included treatment-emergent adverse events (TEAEs) and vital signs. Descriptive statistics (means, percentages) are presented. Acute atomoxetine treatment improved core ADHD symptoms in both 6-7-year-old patients (n=565) and 5-year-old patients (n=37) (treatment effect: -10.16 and -7.42). In an analysis of placebo-controlled groups, the mean duration of exposure to atomoxetine was ∼ 7 weeks for 6-7-year-old patients and 9 weeks for 5-year-old patients. Decreased appetite was the most common TEAE in atomoxetine-treated patients. The TEAEs observed at a higher rate in 5-year-old versus 6-7-year-old patients were irritability (36.8% vs. 3.6%) and other mood-related events (6.9% each vs. <3.0%). Blood pressure and pulse increased in both 4-5-year-old patients and 6-7-year-old patients, whereas a weight increase was seen only in the 6-7-year-old patients. Although limited by the small sample size of the external studies, these analyses suggest that in 5-year-old patients with ADHD, atomoxetine may improve ADHD symptoms, but possibly to a lesser extent than in older children, with some adverse events occurring at a higher rate in 5-year-old patients.


Optical pump-rejection filter based on silicon sub-wavelength engineered photonic structures.
The high index contrast of the silicon-on-insulator (SOI) platform allows the realization of ultra-compact photonic circuits. However, this high contrast hinders the implementation of narrow-band Bragg filters. These typically require corrugation widths of a few nanometers or double-etch geometries, hampering device fabrication. Here we report, for the first time, to the best of our knowledge, on the realization of SOI Bragg filters based on sub-wavelength index engineering in a differential corrugation width configuration. The proposed double periodicity structure allows narrow-band rejection with a single etch step and relaxed width constraints. Based on this concept, we experimentally demonstrate a single-etch, 220 nm thick, Si Bragg filter featuring a corrugation width of 150 nm, a rejection bandwidth of 1.1 nm, and an extinction ratio exceeding 40 dB. This represents a 10-fold width increase, compared to conventional single-periodicity, single-etch counterparts with similar bandwidths.


Impact of nosocomial infections in trauma: does age make a difference?
The effect of age and infection on outcome after trauma is unknown. We evaluated the incidence and impact that nosocomial infection (NI) and age have on morbidity and mortality. Several risk factors were identified and analyzed for correlation with infection. Prospective data were collected on patients admitted for > or = 3 days over a 2-year period. Each patient was followed by an infectious disease specialist throughout their hospitalization. Centers for Disease Control and Prevention guidelines were used to diagnose infection. Of the 3,254 patients admitted, 88% were < 65 and 12% were > or = 65 years of age. Injury Severity Score was not significantly different (older vs. younger). Five hundred one (17.4%) of the younger patients developed an NI with a significantly higher hospital length of stay (LOS), intensive care unit (ICU) LOS, and mortality compared with the noninfected group. One hundred forty-seven (39%) of the older group developed an NI and also had significant increases in hospital LOS, ICU LOS, and mortality. Older infected patients had the highest hospital LOS, ICU LOS, and mortality. The greatest relative risk of mortality was demonstrated with the combination of increased age and NI. Once infected, however, younger patients with penetrating trauma had a greater relative risk of mortality in the group-specific comparison. Many risk factors were associated with infection. Only chronic obstructive pulmonary disease in elderly trauma patients was a significant independent risk factor for infection. NI significantly increases hospital LOS, ICU LOS, and mortality after injury. Age increases risk of infection matched for injury severity, with a significantly higher hospital LOS, ICU LOS, and mortality. Once infected, however, younger patients with penetrating trauma have the greatest risk of mortality. Chronic obstructive pulmonary disease in elderly trauma patients was found to be an independent predictor of infection.


[Stages in the development of neuroses in the dog and effects of preparations with antidepressive and tranquilizing properties].
In modelling of neuroses, successive stages of development of this pathology were observed in dogs. The first stage is characterized by circular disturbances of conditioned activity, vegetative shifts of compensatory character and intensification of individual characteristics of behaviour. At the second stage, parallel with sharp disturbances of conditioned reflexes and with vegetative dystonia, a distortion of emotional reactions was observed in dogs. It is essential that resumption of neurotization episodes in experiments on dogs with the second stage of disease promoted a development of depressive-like states. Diazepam corrected the behavioural and vegetative shifts at the first stage of neurosis. Non-typical antidepressants eliminated the manifestation of symptoms complex of the disease, especially at prolonged treatment.


Sponsorship of national and regional professional paediatrics associations by companies that make breast-milk substitutes: evidence from a review of official websites.
Professional paediatrics associations play an important role in promoting the highest standard of care for women and children. Education and guidelines must be made in the best interests of patients. Given the importance of breastfeeding for the health, development and survival of infants, children and mothers, paediatric associations have a particular responsibility to avoid conflicts of interest with companies that manufacture breast-milk substitutes (BMSs). The objective of this study was to investigate the extent to which national and regional paediatric associations are sponsored by BMS companies. Data were collected on national paediatric associations based on online searches of websites and Facebook pages. Sites were examined for evidence of financial sponsorship by the BMS industry, including funding of journals, newsletters or other publications, conferences and events, scholarships, fellowship, grants and awards. Payment for services, such as exhibitor space at conferences or events and paid advertisements in publications, was also noted. Overall, 68 (60%) of the 114 paediatric associations with a website or Facebook account documented receiving financial support from BMS companies. Sponsorship, particularly of conferences or other events, was the most common type of financial support. The prevalence of conference sponsorship is highest in Europe and the Americas, where about half of the associations have BMS company-sponsored conferences. Thirty-one associations (27%) indicated that they received funding from BMS companies as payment for advertisements or exhibitor space. Only 18 associations (16%) have conflict of interest policies, guidelines, or criteria posted online. Despite the well-documented importance of breastfeeding and the widespread recognition that commercial influences can shape the behaviours of healthcare professionals, national and regional paediatric associations commonly accept funding from companies that manufacture and distribute BMS. Paediatric associations should function without the influence of commercial interests.


Andreev peaks and massive magnons in cuprate superconductor-normal-superconductor junctions
The projected SO(5) theory [pSO(5)] is used to resolve the puzzle of two distinct energy gaps in high T(c) superconductor-normal-superconductor junctions. Counter to the conventional theory of multiple Andreev reflections (MAR), the differential resistance peaks are associated with the antiferromagnetic resonance observed in neutron scattering, and not with Cooper pair breaking. The pSO(5) and MAR theories differ by the expected tunneling charges at the peaks. We propose that shot noise experiments could discriminate against the conventional interpretation.


[Surgery for cancer of proximal regions of the rectum].
The results of treatment of 1652 patients, operated for proximal cancer recti, were presented. Resectability had constituted (84.0 +/- 0.9)%. In (95.7 +/- 0.5)% patients a primarily-restoration operations were accomplished. In (76.0 +/- 1.1)% patients the standard operations were performed, in (8.9 +/- 0.8)%--the extended operations, in (11.5 +/- 0.9)%--combined and in (5.5 +/- 0.6)%--simultant. All the patients after the simultant operations performance had survived. Eligibility of application of the operation methods, technical manipulations and devices, elaborated in the clinic, for the treatment of this group of patients was proved.


Malignant histiocytosis: A light- and electron-microscopic and histochemical study.
The light- and electron-microscopic features and histochemical characterization of three consecutive cases of malignant histiocytosis (MH) are reported. Each case demonstrated involvement of lymph nodes and bone marrow. In the lymph node, the characteristic destructive sinusoidal pattern of involvement by cytologically malignant cells was present. Phagocytosis by malignant cells was rare and most readily appreciated in the imprint preparations. The major problem in differential diagnosis related to defining the histiocytic nature of the malignant cells. This question was resolved by the demonstration of diffuse cytoplasmic staining with the nonspecific esterase and acid phosphatase reactions as well as the ultrastructural demonstration of histiocytes. Although benign, reactive histiocytes were positive, malignant histiocytes did not stain for lysozyme by an immunoperoxidase technique. In contrast to the uniform appearance of these cases, many reports of MH in the past have consisted of heterogeneous cases with variable histologic appearances from a proliferation of predominantly mature histiocytes with marked phagocytosis to cytologically malignant cells with little apparent functional activity. This variation in histologic appearance is due in part to inclusion of cases of reactive histiocytic proliferations, including the recently described virus-associated hemophagocytic syndrome.


HRegNet: A Hierarchical Network for Efficient and Accurate Outdoor LiDAR Point Cloud Registration.
Point cloud registration is a fundamental problem in 3D computer vision. Outdoor LiDAR point clouds are typically large-scale and complexly distributed, which makes the registration challenging. In this paper, we propose an efficient hierarchical network named HRegNet for large-scale outdoor LiDAR point cloud registration. Instead of using all points in the point clouds, HRegNet performs registration on hierarchically extracted keypoints and descriptors. The overall framework combines the reliable features in deeper layer and the precise position information in shallower layers to achieve robust and precise registration. We present a correspondence network to generate correct and accurate keypoints correspondences. Moreover, bilateral consensus and neighborhood consensus are introduced for keypoints matching, and novel similarity features are designed to incorporate them into the correspondence network, which significantly improves the registration performance. In addition, we design a consistency propagation strategy to effectively incorporate spatial consistency into the registration pipeline. The whole network is also highly efficient since only a small number of keypoints are used for registration. Extensive experiments are conducted on three large-scale outdoor LiDAR point cloud datasets to demonstrate the high accuracy and efficiency of the proposed HRegNet. The source code of the proposed HRegNet is available at https://github.com/ispc-lab/HRegNet2.


Semi-rational evolution of the 3-(3-hydroxyalkanoyloxy)alkanoate (HAA) synthase RhlA to improve rhamnolipid production in Pseudomonas aeruginosa and Burkholderia glumae.
The 3-(3-hydroxyalkanoyloxy)alkanoate (HAA) synthase RhlA is an essential enzyme involved in the biosynthesis of HAAs in Pseudomonas and Burkholderia species. RhlA modulates the aliphatic chain length in rhamnolipids, conferring distinct physicochemical properties to these biosurfactants exhibiting promising industrial and pharmaceutical value. A detailed molecular understanding of substrate specificity and catalytic performance in RhlA could offer protein engineering tools to develop designer variants involved in the synthesis of novel rhamnolipid mixtures for tailored eco-friendly products. However, current directed evolution progress remains limited due to the absence of high-throughput screening methodologies and lack of an experimentally resolved RhlA structure. In the present work, we used comparative modeling and chimeric-based approaches to perform a comprehensive semi-rational mutagenesis of RhlA from Pseudomonas aeruginosa. Our extensive RhlA mutational variants and chimeric hybrids between the Pseudomonas and Burkholderia homologs illustrate selective modulation of rhamnolipid alkyl chain length in both Pseudomonas aeruginosa and Burkholderia glumae. Our results also demonstrate the implication of a putative cap-domain motif that covers the catalytic site of the enzyme and provides substrate specificity to RhlA. This semi-rational mutant-based survey reveals promising 'hot-spots' for the modulation of RL congener patterns and potential control of enzyme activity, in addition to uncovering residue positions that modulate substrate selectivity between the Pseudomonas and Burkholderia functional homologs. DATABASE: Model data are available in the PMDB database under the accession number PM0081867.


[Virulence factors of Salmonella: from molecular genetics to diagnostic applications].
Salmonella serotype Typhimurium is a facultative intracellular pathogen that causes a systemic infection in naturally, or experimentally, infected mice. After oral contamination, Typhimurium colonizes the ileal mucosa and Peyer's patches and invades draining mesenteric lymph nodes. From these primary sites of infection, bacteria dissiminate to the reticuloendothelial system and proliferate rapidly in spleen and liver. Several virulence factors are encoded by chromosomal genes. The ability of Typhimurium to adhere to and invade epithelial cells has been associated with flagella, pili of type I and mannose-resistant haemagglutinating activity. By comparing the virulence of isogenic strains, it appeared that these traits played a marginal role and were not essential for full virulence expression. It is now clear that other surface structures are important for the invasiness capacity of Typhimurium. To multiply in the reticuloendothelial system, a complete lipopolysaccharide is necessary for the bacteria in resisting serum bactericidal activity and producing tissue damage. Salmonella have evolved a specialized iron-binding ligand, termed enterobactin, to acquire iron necessary for their multiplication. Enterobactin competes with the host iron-binding proteins (transferrin or lactoferrin) to secure the iron required by the bacteria. Though the presence of an enterotoxin in Salmonella is still controversial, there is now substantial evidence to support this concept. Recently, a gene encoding an enterotoxin has been cloned from Typhimurium and expressed in E. coli. Typhimurium strains harbour a 90 kilobases (kb) plasmid which is essential for virulence. This plasmid encodes virulence factors required for replication of Salmonella in liver and spleen. It was postulated that the plasmid allowed Typhimurium to multiply in Kupffer cells and in splenic macrophages. The virulence-associated region of the plasmid restored full virulence to plasmidless strains. Transposon insertion mutagenesis demonstrated the existence of two DNA sequences, designated Vir A and Vir B, which are essential for virulence expression. The Vir A region has been sequenced; it encodes four polypeptides with apparent molecular mass of 27,000, 28,000, 33,000 and 70,000. The Vir B region encodes two polypeptides of 38,000 and 43,000. In an attempt to identify bacterial components contributing to invasion of HeLa cells by Salmonella serovar Typhi, we cloned a 30 kb DNA sequence necessary for entry of bacteria into epithelial cells. However, this sequence is not sufficient for conferring an invasive phenotype to E. coli strains. From this DNA fragment, a short segment of 487 bp was subcloned, sequenced and used as probe to detect Salmonella.(ABSTRACT TRUNCATED AT 400 WORDS)


Clinicoradiologic correlation in adult patients diagnosed with novel influenza A (H1N1).
Influenza A(H1N1) infection affected Indian population in 2009. Patients needed ICU admission and monitoring. To describe and correlate clinical and radiographic features of Influenza A(H1N1) infection in patients hospitalised in Intensive care unit. Retrospective study of records of 100 RT-PCR confirmed patients with Influenza A(H1N1) infection from August 2009 to March 2010 was done. Each patient underwent an evaluation to determine clinical and radiographic features. Mean age of the patients was 33.43 years (+/- 12.152) with maximum patients between 18-40 years, with 53% males and 43% females. Cough (96%), Fever (95%), breathlessness (83%), throat pain (34%), crepitations (69%), Tachypnoea (59%)were the prominent symptoms and signs. 61% (n = 63) had comorbid condition like pregnancy (n = 13,20.63%), Diabetes Mellitus (DM) (n = 12,19.05%), HT (n = 11,17.60%), Obesity (n = 10, 15.87%) and Rheumatic Valvular Heart Disease (RVHD) (n = 6,09.52%). Chest X ray was abnormal in 91% patients and normal in 09% pts. Bilateral findings were seen in 61.53% cases. Most common zones affected were lower zones (77.46%), then middle zones (71.42%), followed by upper zones (42.7%). Most common patterns were consolidation (64.83%), reticulonodular (24.17%) and nodular (10.98%). 27.47% had two, 21.97% had four, 19.78% had three,12.08% had six, 7.69% had five and 10.98% had single zone involvement. Fever, cough and tachypnoea were present in all 100% pts with nodular pattern while crepitations were observed in 79.66% cases of consolidation. Patchy consolidation was seen in comorbidities like pregnancy (n = 10) and obesity (n = 06), while reticulonodular pattern was observed in hypertensive patients (n = 06). Maximum number of deaths were between 21 and 30 years of age (60.71%). Total number of deaths were 28 with 60.71% (n = 17) deaths between 21 and 30 years of age. Deaths were more in presence of comorbidities like Pregnancy (n = 5, 17.85%), Hypertension (n = 4,14.28%), Diabetes (n = 3 10.21%) and RVHD (n = 3,10.71%), in presence of RLZ involvement (92.85%), RMZ (89.28%), LMZ (85.21%) and RUZ involvement (71.42%), with consolidation pattern (57.14%) followed by reticulonodular pattern (21.42%) and in presence of six zone involvement (36.37%) followed by four zone (35%) and then by three(33%) and two (32%) zone involvement. Mean duration of hospital stay was 9.1 days. 23% patients stayed for less than 5 days, 41% stayed between 9 and 14 days while only 7% required to stay for more than 15 days. 37% pts showed normal Xray at the time of discharge or death. 38% patients showed persistence of radiological lesion at discharge or death. Young to middle age patients were commonly affected. Common comorbidities were Pregnancy, Diabetes, Hypertension, and Obesity and patients had fever, cough, breathlessness, tachypnoea, crepitations as common clinical features. Radiologically it was multizonal, bilateral disease with predominant lower zone involvement and common patterns were consolidation followed by reticulonodular and nodular. Patchy consolidation was more common in pregnancy and obesity while reticulonodular pattern was more in hypertensive patients. Fever, cough and tachypnoea were present in all 100% pts with nodular pattern. Crepitations were common in pts with consolidation. Clinical recovery preceded radiological recovery. Young to middle aged individuals died more. Deaths were more in presence of comorbidities like Pregnancy, HT, DM and RVHD, also with RLZ, RMZ, LMZ involvement and with consolidation pattern and with six zone involvement.


Exceptional time response, stability and selectivity in doubly-activated phenyl selenium-based glutathione-selective platform.
A phenyl-selenium-substituted coumarin probe was synthesized for the purpose of achieving highly selective and extremely rapid detection of glutathione (GSH) over cysteine (Cys)/homocysteine (Hcy) without background fluorescence. The fluorescence intensity of the probe with GSH shows a ∼100-fold fluorescent enhancement compared with the signal generated for other closely related amino acids, including Cys and Hcy. Importantly, the substitution reaction with the sulfhydryl group of GSH at the 4-position of the probe, which is doubly-activated by two carbonyl groups, occurs extremely fast, showing subsecond maximum fluorescence intensity attainment; equilibrium was reached within 100 ms (UV-vis). The probe selectivity for GSH was confirmed in Hep3B cells by confocal microscopy imaging.


A high-concentrate diet provokes inflammation, endoplasmic reticulum stress, and apoptosis in mammary tissue of dairy cows through the upregulation of STIM1/ORAI1.
High-concentrate feeding can induce subacute ruminal acidosis, which leads to mammary tissue injury in dairy cows. Therefore, the purpose of this research was to evaluate the effect of high-concentrate feeding on STIM1 (stromal interaction molecule 1)/ORAI1 (Orai calcium release-activated calcium modulator 1)-mediated inflammation, endoplasmic reticulum stress (ERS), and apoptosis in the mammary tissue of dairy cows. A total of 12 healthy mid-lactating Holstein cows of similar weight were randomly allotted into the following 2 groups: a high-concentrate (HC) group (concentrate:forage = 6:4) and a low-concentrate (LC) group (concentrate:forage = 4:6). The trial lasted for 3 wk. After the feeding experiment, rumen fluid, lacteal vein blood, and mammary tissue samples were collected. The results showed that the HC diet significantly increased blood lipopolysaccharide levels, decreased ruminal pH, and upregulated the concentrations of Ca2+ and proinflammatory cytokines, including TNF-α, IL-1β, and IL-6, and the enzyme activities of caspase-3, caspase-9, PKC, and IKK. The upregulation of STIM1, ORAI1, PKCα, IKKβ, phosphorylated-IκBα, phosphorylated-p65, TNF-α, and IL-1α proteins in the HC group indicated activation of the STIM1/ORAI1-mediated inflammatory signaling pathway compared with that in the LC group. The HC diet also induced ERS by increasing the mRNA and protein abundances of GRP78, CHOP, PERK, ATF6, and IRE1α in the mammary tissue. Compared with the LC group, the mRNA expression levels and protein abundances of caspase-3, cleaved caspase-3, caspase-9, and BAX were markedly increased in the HC group. However, the mRNA and protein expression levels of Bcl-2 were significantly decreased in the HC group. Therefore, this study demonstrated that the HC diet can activate the store-operated calcium entry channel by upregulating the expression of STIM1 and ORAI1 and induce inflammation, ERS, and apoptosis in the mammary tissue of dairy cows.


Wide Variation in Absolute Cardiovascular Risk Assessment in Aboriginal and Torres Strait Islander People with Type 2 Diabetes.
Absolute cardiovascular risk assessment (CVRA) is based on the combined effects of multiple risk factors and can identify asymptomatic individuals at high risk of cardiovascular disease (CVD). Aboriginal and Torres Strait Islander people, the Indigenous people of Australia, are disproportionately affected by CVD and diabetes. Our study aimed to investigate variations in the use of absolute CVRA in patients with diabetes at Indigenous community healthcare centers and to identify patient and health center characteristics that may contribute to this variation. Audits of clinical records of 1,728 patients with a known diagnosis of diabetes across 121 health centers in four Australian States/Territories [Northern Territory (NT), South Australia, Western Australia, and Queensland] over the period 2012-2014 were conducted as part of a large-scale continuous quality improvement program. Multilevel regression modeling was used to quantify variation in recording of CVRA attributable to health center and patient characteristics. The proportion of eligible patients with documented CVRA was 33% (n = 574/1,728). The majority (95%) of assessments were conducted in the NT. Multilevel regression analysis showed health center characteristics accounted for 70% of the variation in assessments in the NT. Government-operated health centers had 18.8 times the odds (95% CI 7.7-46.2) of recording CVRA delivery compared with other health centers. Health centers in the NT delivered the majority of absolute CVRA to Indigenous patients with diabetes in our study. Health systems factors that may have facilitated provision of CVRA in the NT include decision support tools and a reporting process for CVRA delivery. Implementation of similar systems in other jurisdictions may help improve CVRA delivery. Early identification and treatment of high risk individuals through wider use of CVRA may help reduce the burden of CVD in Indigenous Australians with diabetes.


Osmotic shrinkage of giant egg-lecithin vesicles.
Osmotic shrinkage of giant egg-lecithin vesicles was observed by phase-contrast microscopy. The vesicles remained or became spherical when shrinking. Small and thick-walled vesicles formed visible fingers attached to the sphere. The water permeability of the single bilayer was found to be 41 micrometers/s. A variety of observations indicate that osmosis induces a parallel lipid flow between the monolayers of the bilayer, leading to a strong positive spontaneous curvature. They also suggest the formation of mostly submicroscopic daughter vesicles. The estimated coupling constant, 2 . 10(-6) mol/mol, is large enough to be biologically significant.


Three-dimensional porous silicon-MWNT heterostructure with superior lithium storage performance.
A novel three-dimensional porous Si-MWNT heterostructure was designed to meet the demand of high-capacity and long-life lithium storage. This material presented a stable capacity above 1000 mAh g(-1) for nearly 200 cycles, which benefited from its highly porous structure combined with robust MWNT connections that accommodated the host volume change and improved the electric conductivity.


Reduced Radiation Dose with Model-based Iterative Reconstruction versus Standard Dose with Adaptive Statistical Iterative Reconstruction in Abdominal CT for Diagnosis of Acute Renal Colic.
To evaluate the accuracy of reduced-dose abdominal computed tomographic (CT) imaging by using a new generation model-based iterative reconstruction (MBIR) to diagnose acute renal colic compared with a standard-dose abdominal CT with 50% adaptive statistical iterative reconstruction (ASIR). This institutional review board-approved prospective study included 118 patients with symptoms of acute renal colic who underwent the following two successive CT examinations: standard-dose ASIR 50% and reduced-dose MBIR. Two radiologists independently reviewed both CT examinations for presence or absence of renal calculi, differential diagnoses, and associated abnormalities. The imaging findings, radiation dose estimates, and image quality of the two CT reconstruction methods were compared. Concordance was evaluated by κ coefficient, and descriptive statistics and t test were used for statistical analysis. Intraobserver correlation was 100% for the diagnosis of renal calculi (κ = 1). Renal calculus (τ = 98.7%; κ = 0.97) and obstructive upper urinary tract disease (τ = 98.16%; κ = 0.95) were detected, and differential or alternative diagnosis was performed (τ = 98.87% κ = 0.95). MBIR allowed a dose reduction of 84% versus standard-dose ASIR 50% (mean volume CT dose index, 1.7 mGy ± 0.8 [standard deviation] vs 10.9 mGy ± 4.6; mean size-specific dose estimate, 2.2 mGy ± 0.7 vs 13.7 mGy ± 3.9; P < .001) without a conspicuous deterioration in image quality (reduced-dose MBIR vs ASIR 50% mean scores, 3.83 ± 0.49 vs 3.92 ± 0.27, respectively; P = .32) or increase in noise (reduced-dose MBIR vs ASIR 50% mean, respectively, 18.36 HU ± 2.53 vs 17.40 HU ± 3.42). Its main drawback remains the long time required for reconstruction (mean, 40 minutes). A reduced-dose protocol with MBIR allowed a dose reduction of 84% without increasing noise and without an conspicuous deterioration in image quality in patients suspected of having renal colic.


Improving "color rendering" of LED lighting for the growth of lettuce.
Light plays a vital role on the growth and development of plant. On the base of white light with high color rendering to the benefit of human survival and life, we proposed to improve "color rendering" of LED lighting for accelerating the growth of lettuce. Seven spectral LED lights were adopted to irradiate the lettuces under 150 μmol·m-2·s-1 for a 16 hd-1 photoperiod. The leaf area and number profiles, plant biomass, and photosynthetic rate under the as-prepared LED light treatments were investigated. We let the absorption spectrum of fresh leaf be the emission spectrum of ideal light and then evaluate the "color rendering" of as-prepared LED lights by the Pearson product-moment correlation coefficient and CIE chromaticity coordinates. Under the irradiation of red-yellow-blue light with high correlation coefficient of 0.587, the dry weights and leaf growth rate are 2-3 times as high as the sharp red-blue light. The optimized LED light for lettuce growth can be presumed to be limited to the angle (about 75°) between the vectors passed through the ideal light in the CIE chromaticity coordinates. These findings open up a new idea to assess and find the optimized LED light for plant growth.


Towards disease-modifying treatment of Alzheimer's disease: drugs targeting beta-amyloid.
Pathological, genetic, biochemical and pharmacological studies support the hypothesis that brain accumulation of oligomeric species of beta-amyloid (Abeta) peptides may cause Alzheimer's disease (AD). Drugs currently used for the treatment of AD produce limited clinical benefits and do not treat the underlying causes of the disease. In the last 10 years, new therapeutic approaches targeting Abeta have been discovered and developed with the hope of modifying the natural history of the disease. Several active and passive immunotherapy approaches are under investigation in clinical trials with the aim of accelerating Abeta clearance from the brain of the AD patients. The most advanced of these immunological approaches is bapineuzumab, composed of humanized anti-Abeta monoclonal antibodies, that is being tested in two large late-stage trials. Compounds that interfere with proteases regulating Abeta formation from amyloid precursor protein (APP) are also actively pursued. Unfortunately, the most biologically attractive of these proteases, beta-secretase, that regulates the first step of the amyloidogenic APP metabolism, was found to be particularly problematic to block and only one compound (CTS21166) has reached clinical testing so far. Conversely, several inhibitors of gamma-secretase, the protease that regulates the last metabolic step generating Abeta, have been identified, the most advanced being LY-450139 (semagacestat), presently in Phase III clinical development. Compounds that stimulate alpha-secretase, the enzyme responsible for the non-amyloidogenic metabolism of APP, are also being developed one of them, EHT-0202, has recently started a Phase II study. Furthermore, brain penetrant inhibitors of Abeta aggregation have been identified and one of such compounds, PBT-2, has produced encouraging neuropsychological results in a recently completed Phase II study. With all these anti-Abeta approaches in clinical testing, we will know in few years if the Abeta hypothesis of AD is correct.


A multi-component integrated approach for the elimination of schistosomiasis in the People's Republic of China: design and baseline results of a 4-year cluster-randomised intervention trial.
Despite major successes in its control over the past 50years, schistosomiasis japonica continues to be a public health problem in the People's Republic of China (P.R. China). Historically, the major endemic foci occur in the lakes and marshlands along the Yangtze River, areas where transmission interruption has proven difficult. The current endemic situation may alter due to the closure of the Three Gorges Dam. Considerable environmental and ecological changes are anticipated that may result in new habitats for the oncomelanid intermediate snail host of Schistosoma japonicum (Sj), thereby increasing the risk of transmission. The current national control program for P.R. China involves a multi-component integrated strategy but, despite targeting multiple transmission pathways, certain challenges remain. As the Chinese government pushes towards elimination, there is a requirement for additional tools, such as vaccination, for long-term prevention. Whereas the zoonotic nature of schistosomiasis japonica adds to the complexity of control, it provides a unique opportunity to develop a transmission blocking vaccine targeting bovines to assist in the prevention of human infection and disease. Mathematical modelling has shown that control options targeting the various transmission pathways of schistosomiasis japonica and incorporating bovine vaccination, mass human chemotherapy and mollusciciding could lead to its elimination from P.R. China. Here we present the study design and baseline results of a four-year cluster randomised intervention trial we are undertaking around the schistosomiasis-endemic Dongting Lake in Hunan Province aimed at determining the impact on schistosome transmission of the multi-component integrated control strategy, including bovine vaccination using a heterologous "prime-boost" delivery platform based on the previously tested SjCTPI vaccine.


Incisional hernia repair in Sweden 2002.
Incisional hernia is a common problem after abdominal surgery. The complication and recurrence rates following the different repair techniques are a matter of great concern. Our aim was to study the results of incisional hernia repair in Sweden. A questionnaire was sent to all surgical departments in Sweden requesting data concerning incisional hernia repair performed during the year 2002. Eight hundred and sixty-nine incisional hernia repairs were reported from 40 hospitals. Specialist surgeons performed the repair in 782 (83.8%) patients. The incisional hernia was a recurrence in 148 (17.0%) patients. Thirty-three per cent of the hernias were subsequent to transverse, subcostal or muscle-splitting incisions or laparoscopic procedures. Suture repair was performed in 349 (40.2%) hernias. Onlay mesh repair was more common than a sublay technique. The rate of wound infection was 9.6% after suture repair and 8.1% after mesh repair. The recurrence rate was 29.1% with suture repair, 19.3% with onlay mesh repair, and 7.3% with sublay mesh repair. This survey revealed that there is room for improvement regarding the incisional hernia surgery in Sweden. Suture repair, with its unacceptable results, is common and mesh techniques employed may not be optimal. This study has led to the instigation of a national incisional hernia register.


VirB, a key transcriptional regulator of virulence plasmid genes in Shigella flexneri, forms DNA-binding site dependent foci in the bacterial cytoplasm.
VirB is a key regulator of genes located on the large virulence plasmid (pINV) in the bacterial pathogen Shigella flexneri VirB is unusual; it is not related to other transcriptional regulators, instead, it belongs to a family of proteins that primarily function in plasmid and chromosome partitioning; exemplified by ParB. Despite this, VirB does not function to segregate DNA, but rather counters transcriptional silencing mediated by the nucleoid structuring protein, H-NS. Since ParB localizes subcellularly as discrete foci in the bacterial cytoplasm, we chose to investigate the subcellular localization of VirB to gain novel insight into how VirB functions as a transcriptional anti-silencer. To do this, a GFP-VirB fusion that retains the regulatory activity of VirB and yet, does not undergo significant protein degradation in S. flexneri, was used. Surprisingly, discrete fluorescent foci were observed in live wild-type S. flexneri cells and an isogenic virB mutant using fluorescence microscopy. In contrast, foci were rarely observed (<10%) in pINV-cured cells or in cells expressing a GFP-VirB fusion carrying amino acid substitutions in the VirB DNA binding domain. Finally, the 25 bp VirB-binding site was demonstrated to be sufficient and necessary for GFP-VirB focus formation using a set of small surrogate plasmids. Combined, these data demonstrate that the VirB:DNA interactions required for the transcriptional anti-silencing activity of VirB on pINV are a prerequisite for the subcellular localization of VirB in the bacterial cytoplasm. The significance of these findings, in light of the anti-silencing activity of VirB, is discussed.ImportanceThis study reveals the subcellular localization of VirB, a key transcriptional regulator of virulence genes found on the large virulence plasmid (pINV) in Shigella. Fluorescent signals generated by an active GFP-VirB fusion form 2, 3, or 4 discrete foci in the bacterial cytoplasm, predominantly at the quarter cell position. These signals are completely dependent upon VirB interacting with its DNA binding site found either on the virulence plasmid or an engineered surrogate. Our findings: 1) provide novel insight into VirB:pINV interactions, 2) suggest that VirB may have utility as a DNA marker, and 3) raise questions about how and why this anti-silencing protein that controls virulence gene expression on pINV of Shigella spp. forms discrete foci/hubs within the bacterial cytoplasm.


Optimized diagnosis of acute dengue fever in Swedish travelers by a combination of reverse transcription-PCR and immunoglobulin M detection.
The dengue viruses (genus Flavivirus, family Flaviviridae) are mosquito borne and cause 100 million cases of dengue fever each year in most tropical and subtropical areas of the world. Increased global travel has been accompanied by an increased import not only of dengue but also of severe fevers of unknown origin to Sweden. Fifty-seven Swedish travelers to dengue epidemic areas, with clinical and serologically diagnosed dengue fever, were included in this study. To find fast and reliable methods to diagnose dengue in the early phase of the disease, patient acute-phase sera were investigated for the presence of dengue-specific immunoglobulin M (IgM) antibodies by enzyme-linked immunosorbent assay (ELISA) and also for dengue serotype (DEN-1 to DEN-4)-specific RNA by different PCR assays. The results showed that 15/20 (75%) of the samples collected 5 days or later post onset of disease, but only 5/37 (14%) of the samples collected on days 0 to 4, contained dengue-specific IgM. Of the samples collected on days 0 to 4 post onset, dengue RNAs of subtypes 1, 2, and 3 were detected by multiplex and/or by TaqMan PCR in 29/37 (78%); of these PCR-positive samples, 93% (27/29) were found IgM negative. By a combination of IgM ELISA and PCR assays, 84% (48/57) of the acute-phase samples were found to be positive. Our results demonstrated that detection of dengue viral RNA by reverse transcription-PCR and Taq-Man PCR is an excellent tool for the early diagnoses of dengue fever and that the IgM assay is a reliable complement for samples collected from day 5 post onset.


Survival of airborne Pasteurella tularensis at different atmospheric temperatures.
The aerosol survival, recovery, and death rate of Pasteurella tularensis SCHU S5 disseminated in particle sizes of 1 to 5 mum were significantly affected by air temperature. The highest aerosol recovery of viable P. tularensis was observed within -7 and 3 C; the recovery decreased significantly below and above this temperature range. The death rate of airborne P. tularensis was not significantly influenced by an increase in temperature from -40 to 24 C. However, a progressive increase in atmospheric temperature from 24 to 35 C resulted in increased death rates; thus, a linear relationship appeared to be present between the temperature and death rates. At 49 C, the recoveries of viable airborne P. tularensis were significantly lower and the death rates were higher than at the other temperatures.


Efficient blind spectral unmixing of fluorescently labeled samples using multi-layer non-negative matrix factorization.
The ample variety of labeling dyes and staining methods available in fluorescence microscopy has enabled biologists to advance in the understanding of living organisms at cellular and molecular level. When two or more fluorescent dyes are used in the same preparation, or one dye is used in the presence of autofluorescence, the separation of the fluorescent emissions can become problematic. Various approaches have been recently proposed to solve this problem. Among them, blind non-negative matrix factorization is gaining interest since it requires little assumptions about the spectra and concentration of the fluorochromes. In this paper, we propose a novel algorithm for blind spectral separation that addresses some of the shortcomings of existing solutions: namely, their dependency on the initialization and their slow convergence. We apply this new algorithm to two relevant problems in fluorescence microscopy: autofluorescence elimination and spectral unmixing of multi-labeled samples. Our results show that our new algorithm performs well when compared with the state-of-the-art approaches for a much faster implementation.


Physical activity increases the resistin concentration in hemodialyzed patients without metabolic syndrome.
Resistin (RES) concentration increases in end-stage renal disease patients. However, there have been no studies defining the role of physical activity in RES concentrations in hemodialyzed (HD) patients. This study was aimed to determine metabolic and inflammatory effects, including RES, of 4-week supervised rehabilitation program in HD patients, with or without metabolic syndrome (MS). The study was completed by 28 patients aged 56.9±13.3 years ( x ¯ ± SD ) who were HD for 50.6±73.4 months, and 30 controls aged 61.5±8.3 years with normal renal function. Both the groups were divided into two subgroups with respect to MS. Individualized supervised rehabilitation program based on physiotherapy, including exercises, was provided to each subject for 4 weeks. Baseline and post-intervention complete blood count, glycated hemoglobin (HbA1c) and levels of serum RES, leptin, adiponectin, cystatin C, erythropoietin, high sensitivity C-reactive protein (hs-CRP), tumor necrosis factor alpha (TNF-α), interleukin-6, transforming growth factor- β1, plasminogen activator inhibitor-1 homocysteine, insulin, albumin, parathyroid hormone (PTH), and phosphorus were measured. Compared to controls, HD patients showed higher baseline leucocytes count and higher serum concentrations of RES, leptin, cystatin C, hs-CRP, TNF-α, homocysteine, phosphorus, PTH while hemoglobin, glucose, and albumin concentrations. A positive correlation between serum albumin and RES concentrations was observed in HD patients. Post-intervention RES increase was observed in HD patients without MS (post-intervention 34.22±8.89 vs baseline 30.16±11.04 ng/mL; P=0.046) while no change was observed in patients with MS and in the control group. MS modifies a RES response to the rehabilitation program in HD patients.


Probing voltage drop variations in graphene with photoelectron spectroscopy.
We use X-ray photoelectron spectroscopy (XPS) for characterization of voltage drop variations of large area single-layer graphene on quartz substrates, by application of a voltage bias across two gold electrodes deposited on top. By monitoring the spatial variation of the kinetic energies of emitted C1s photoelectrons, we extract voltage variations in the graphene layer in a chemically specific format. The potential drop is uniform across the entire layer in the pristine sample but is not uniform in the oxidized one, due to cracks and/or morphological defects created during the oxidation process. This new way of data gathering reintroduces XPS as a major analytical tool for extracting electrical as well as chemical information about surface and/or nanostructured materials.


[Management of recurrent lower lip carcinomas].
In this study patients who had locoregional recurrence of lower lip carcinomas after therapies such as surgery, electrocoagulation, cryotherapy or traditional local therapies are discussed. The records of 16 cases (1 female, 15 males; mean age 58 years; range 30 to 83 years) with recurrent lower lip carcinoma admitted between March 2002 and September 2007 to Dr. Abdurrahman Yurtarslan Oncology Training and Research Hospital, Ear, Nose and Throat Department were retrospectively reviewed. Fourteen patients had been treated in other institutions, while two had been treated in our center. Four of the patients had recurrence in the lip, four patients had recurrence only in the neck, and the remaining eight patients had both lip and neck recurrence. Ten patients received modified radical or radical neck dissection because of their palpable lymphadenopathies, three patients received supraomohyoid neck dissection due to non palpable lymphadenopathies, and the remaining three patients did not have neck dissection because of co-morbid diseases. Seven patients (43%) died in the first postoperative year because of lower lip carcinomas and three patients died because of other reasons. Six patients survived for the first two years without any evidence of disease. Patient survival will be affected by the applied treatment. For patients with primary lower lip cancers, otolaryngologists experienced in oncology must plan surgery rather than local treatments. In case of locoregional recurrence, immediate treatment should be planned.


Measurement of contact-line dissipation in a nanometer-thin soap film.
We report a direct measurement of the friction coefficient ξ(c) of two fluctuating contact lines formed on a fiber surface when a long glass fiber intersects the two water-air interfaces of a thin soap film. The glass fiber of diameter d in the range of 0.4-4 μm and length 100-300 μm is glued onto the front end of a rectangular cantilever used for atomic force microscopy. As a sensitive mechanical resonator, the hanging fiber probe can accurately measure a minute change of its viscous damping caused by the soap film. By measuring the broadening of the resonant peak of the hanging fiber probe with varying viscosity η of the soap film and different surface treatments of the glass fiber, we confirm that the contact line dissipation obeys a universal scaling law, ξ(c)=απdη, where the coefficient α=1.1±0.3 is insensitive to the change of liquid-solid contact angle. The experimental result is in good agreement with the numerical result based on the phase field model under the generalized Navier boundary conditions.


pH dependence of the acetylcholine receptor channel: a species variation.
The effects of pH changes on the miniature endplate current (mepc) and on endplate current fluctuations (acetylcholine [ACh] noise) were examined at the neuromuscular junction in vitro in two species of frogs. In Rana pipiens the relationship between the decay time constant of the mepc (tau') and pH had a symmetrical bell shape; the value of tau' being largest at pH 7 and decreasing at more acid or more alkaline pH. In acid pH the mepc amplitude (A) decreased relative to its value at pH 7, and in alkaline pH A increased. In Rana ridibunda a narrower and asymmetric bell-shaped dependence of tau' on pH, having a maximum of pH 5.5, was found. The mepc amplitude was again reduced in acid pH but had a peak at pH 5.5. Also, its value at pH 9 was larger than at pH 7. These results were obtained with a number of different buffers and were not found to be sensitive to the nature of the buffer chosen. By performing ACh-noise analysis we found that in Rana pipiens at acid pH (5.5-5.0), the single channel conductance (gamma) and the single channel open time (tau) were significantly reduced relative to their value at pH 7. However, in Rana ridibunda at acid pH (5.4) gamma was unchanged and tau was markedly increased relative to their values at pH 7. The results can be explained quantitatively by electrostatic interaction between two fixed and titratable ionic groups and a mobile charge in the receptor molecule. The model fits the data for groups having pKs approximately 4.8 and approximately 9.8 for Rana pipiens and approximately 4.6 and approximately 6.3 for Rana ridibunda. The groups can be tentatively identified as amino acid residues; glutamic or aspartic and lysine or tyrosine for Rana pipiens; glutamic or aspartic and histidine for Rana ridibunda. The difference in the fitted values of the other model parameters for these two species can be attributed to differences in the spatial configuration of the charged groups.


Mapping T and B lymphocyte epitopes of bovine herpesvirus-1 glycoprotein B.
Glycoprotein B (gB) is a major envelope protein of bovine herpesvirus-1 (BHV-1). As a subunit vaccine, the extracellular domain of recombinant gB induces neutralizing antibody and T cell responses that engender protection against virus challenge. Here, lymphocytes from animals of different parentage were analysed for T cell proliferation to the gB extracellular domain for immune recognition. Four truncated overlapping gB gene segments encoding 742 amino acids were expressed from a baculovirus vector to identify antigenic regions. One immunodominant region (amino acids 254-532) was recognized by T cells from immune individuals of different parentage. Serial synthetic peptides spanning this region localized the T cell (amino acids 319-340 and 415-436) and B cell (amino acids 331-352, 475-496 and 487-508) epitopes. Elucidation of gB epitopes indicates the diverse and distinctive recognition by T cells and antibodies of this envelope glycoprotein by cattle, the natural host of BHV-1.


RENEB Inter-Laboratory Comparison 2021: Inter-Assay Comparison of Eight Dosimetry Assays.
Tools for radiation exposure reconstruction are required to support the medical management of radiation victims in radiological or nuclear incidents. Different biological and physical dosimetry assays can be used for various exposure scenarios to estimate the dose of ionizing radiation a person has absorbed. Regular validation of the techniques through inter-laboratory comparisons (ILC) is essential to guarantee high quality results. In the current RENEB inter-laboratory comparison, the performance quality of established cytogenetic assays [dicentric chromosome assay (DCA), cytokinesis-block micronucleus assay (CBMN), stable chromosomal translocation assay (FISH) and premature chromosome condensation assay (PCC)] was tested in comparison to molecular biological assays [gamma-H2AX foci (gH2AX), gene expression (GE)] and physical dosimetry-based assays [electron paramagnetic resonance (EPR), optically or thermally stimulated luminescence (LUM)]. Three blinded coded samples (e.g., blood, enamel or mobiles) were exposed to 0, 1.2 or 3.5 Gy X-ray reference doses (240 kVp, 1 Gy/min). These doses roughly correspond to clinically relevant groups of unexposed to low exposed (0-1 Gy), moderately exposed (1-2 Gy, no severe acute health effects expected) and highly exposed individuals (>2 Gy, requiring early intensive medical care). In the frame of the current RENEB inter-laboratory comparison, samples were sent to 86 specialized teams in 46 organizations from 27 nations for dose estimation and identification of three clinically relevant groups. The time for sending early crude reports and more precise reports was documented for each laboratory and assay where possible. The quality of dose estimates was analyzed with three different levels of granularity, 1. by calculating the frequency of correctly reported clinically relevant dose categories, 2. by determining the number of dose estimates within the uncertainty intervals recommended for triage dosimetry (±0.5 Gy or ±1.0 Gy for doses <2.5 Gy or >2.5 Gy), and 3. by calculating the absolute difference (AD) of estimated doses relative to the reference doses. In total, 554 dose estimates were submitted within the 6-week period given before the exercise was closed. For samples processed with the highest priority, earliest dose estimates/categories were reported within 5-10 h of receipt for GE, gH2AX, LUM, EPR, 2-3 days for DCA, CBMN and within 6-7 days for the FISH assay. For the unirradiated control sample, the categorization in the correct clinically relevant group (0-1 Gy) as well as the allocation to the triage uncertainty interval was, with the exception of a few outliers, successfully performed for all assays. For the 3.5 Gy sample the percentage of correct classifications to the clinically relevant group (≥2 Gy) was between 89-100% for all assays, with the exception of gH2AX. For the 1.2 Gy sample, an exact allocation to the clinically relevant group was more difficult and 0-50% or 0-48% of the estimates were wrongly classified into the lowest or highest dose categories, respectively. For the irradiated samples, the correct allocation to the triage uncertainty intervals varied considerably between assays for the 1.2 Gy (29-76%) and 3.5 Gy (17-100%) samples. While a systematic shift towards higher doses was observed for the cytogenetic-based assays, extreme outliers exceeding the reference doses 2-6 fold were observed for EPR, FISH and GE assays. These outliers were related to a particular material examined (tooth enamel for EPR assay, reported as kerma in enamel, but when converted into the proper quantity, i.e. to kerma in air, expected dose estimates could be recalculated in most cases), the level of experience of the teams (FISH) and methodological uncertainties (GE). This was the first RENEB ILC where everything, from blood sampling to irradiation and shipment of the samples, was organized and realized at the same institution, for several biological and physical retrospective dosimetry assays. Almost all assays appeared comparably applicable for the identification of unexposed and highly exposed individuals and the allocation of medical relevant groups, with the latter requiring medical support for the acute radiation scenario simulated in this exercise. However, extreme outliers or a systematic shift of dose estimates have been observed for some assays. Possible reasons will be discussed in the assay specific papers of this special issue. In summary, this ILC clearly demonstrates the need to conduct regular exercises to identify research needs, but also to identify technical problems and to optimize the design of future ILCs.


Effect of antioxidant therapy on the sperm DNA integrity improvement; a longitudinal cohort study.
The effect of antioxidant therapy on sperm DNA fragmentation index (DFI) and achieving natural pregnancy were under debate. Very few studies have showed the rate of pregnancy rate after the antioxidant therapy due to ethical and technical limitations. The aim of this cohort study was to determine the improvement rate of sperm DFI and natural pregnancy rate after the antioxidant therapy in infertile men. 1645 infertile men were subjected for this study from May 2015 to December 2017. The Spermogram and sperm DFI were assessed using World Health Organization (WHO) 2010-based protocols and sperm chromatin structure assay (SCSA), respectively, in sperm samples before and after antioxidant therapy. The total sperm DFI improvement rate was 38.9% in the total population. Sperm DFI improvement had close correlation with total motility (r= 0.731, p= 0.001) and progressive motility improvement (r= 0.885, p= 0.001); 16.8% of individuals who completed antioxidant therapy for nine months achieved natural pregnancy. The results of the current study suggested that SCSA along with spermogram might be a suitable option for the evaluation of fertility potential. In addition, antioxidant therapy may be useful for men with high levels of sperm DFI. However, the rate of pregnancy was still low and other treatment protocols such as assisted reproductive technology may be necessary.


A conserved functional role of pectic polymers in stomatal guard cells from a range of plant species.
Guard cell walls combine exceptional strength and flexibility in order to accommodate the turgor pressure-driven changes in size and shape that underlie the opening and closing of stomatal pores. To investigate the molecular basis of these exceptional qualities, we have used a combination of compositional and functional analyses in three different plant species. We show that comparisons of FTIR spectra from stomatal guard cells and those of other epidermal cells indicate a number of clear differences in cell-wall composition. The most obvious characteristics are that stomatal guard cells are enriched in phenolic esters of pectins. This enrichment is apparent in guard cells from Vicia faba (possessing a type I cell wall) and Commelina communis and Zea mays (having a type II wall). We further show that these common defining elements of guard cell walls have conserved functional roles. As previously reported in C. communis, we show that enzymatic modification of the pectin network in guard cell walls in both V. faba and Z. mays has profound effects on stomatal function. In all three species, incubation of epidermal strips with a combination of pectin methyl esterase and endopolygalacturonase (EPG) caused an increase in stomatal aperture on opening. This effect was not seen when strips were incubated with EPG alone indicating that the methyl-esterified fraction of homogalacturonan is key to this effect. In contrast, arabinanase treatment, and incubation with feruloyl esterase both impeded stomatal opening. It therefore appears that pectins and phenolic esters have a conserved functional role in guard cell walls even in grass species with type II walls, which characteristically are composed of low levels of pectins.


[Work capacity of skeletal muscles and energetics of muscular work during adaptation to cold].
After the cold adaptation muscle contraction and the working capacity decreased. However, the muscles of the adapted to cold rats are able to save the initial power for a longer time. The muscular work of adapted to cold rats involves a greater expenditure of energy as compared with the control rats. Changes of the working capacity of skeletal muscles in control rats after noradrenalin administration are similar to those occurring in adapted to cold rats.


Immunogenic and protective properties of GP5 and M structural proteins of porcine reproductive and respiratory syndrome virus expressed from replicating but nondisseminating adenovectors.
Porcine reproductive and respiratory syndrome virus (PRRSV) is responsible for significant economic losses in the porcine industry. Currently available commercial vaccines do not allow optimal and safe protection. In this study, replicating but nondisseminating adenovectors (rAdV) were used for the first time in pigs for vaccinal purposes. They were expressing the PRRSV matrix M protein in fusion with either the envelope GP5 wild-type protein (M-GP5) which carries the major neutralizing antibody (NAb)-inducing epitope or a mutant form of GP5 (M-GP5m) developed to theoretically increase the NAb immune response. Three groups of fourteen piglets were immunized both intramuscularly and intranasally at 3-week intervals with rAdV expressing the green fluorescent protein (GFP, used as a negative control), M-GP5 or M-GP5m. Two additional groups of pigs were primed with M-GP5m-expressing rAdV followed by a boost with bacterially-expressed recombinant wild-type GP5 or were immunized twice with a PRRSV inactivated commercial vaccine. The results show that the rAdV expressing the fusion proteins of interest induced systemic and mucosal PRRSV GP5-specific antibody response as determined in an ELISA. Moreover the prime with M-GP5m-expressing rAdV and boost with recombinant GP5 showed the highest antibody response against GP5. Following PRRSV experimental challenge, pigs immunized twice with rAdV expressing either M-GP5 or M-GP5m developed partial protection as shown by a decrease in viremia overtime. The lowest viremia levels and/or percentages of macroscopic lung lesions were obtained in pigs immunized twice with either the rAdV expressing M-GP5m or the PRRSV inactivated commercial vaccine.


Differences among brain tumor stem cell types and fetal neural stem cells in focal regions of histone modifications and DNA methylation, broad regions of modifications, and bivalent promoters.
Aberrational epigenetic marks are believed to play a major role in establishing the abnormal features of cancer cells. Rational use and development of drugs aimed at epigenetic processes requires an understanding of the range, extent, and roles of epigenetic reprogramming in cancer cells. Using ChIP-chip and MeDIP-chip approaches, we localized well-established and prevalent epigenetic marks (H3K27me3, H3K4me3, H3K9me3, DNA methylation) on a genome scale in several lines of putative glioma stem cells (brain tumor stem cells, BTSCs) and, for comparison, normal human fetal neural stem cells (fNSCs). We determined a substantial "core" set of promoters possessing each mark in every surveyed BTSC cell type, which largely overlapped the corresponding fNSC sets. However, there was substantial diversity among cell types in mark localization. We observed large differences among cell types in total number of H3K9me3+ positive promoters and peaks and in broad modifications (defined as >50 kb peak length) for H3K27me3 and, to a lesser extent, H3K9me3. We verified that a change in a broad modification affected gene expression of CACNG7. We detected large numbers of bivalent promoters, but most bivalent promoters did not display direct overlap of contrasting epigenetic marks, but rather occupied nearby regions of the proximal promoter. There were significant differences in the sets of promoters bearing bivalent marks in the different cell types and few consistent differences between fNSCs and BTSCs. Overall, our "core set" data establishes sets of potential therapeutic targets, but the diversity in sets of sites and broad modifications among cell types underscores the need to carefully consider BTSC subtype variation in epigenetic therapy. Our results point toward substantial differences among cell types in the activity of the production/maintenance systems for H3K9me3 and for broad regions of modification (H3K27me3 or H3K9me3). Finally, the unexpected diversity in bivalent promoter sets among these multipotent cells indicates that bivalent promoters may play complex roles in the overall biology of these cells. These results provide key information for forming the basis for future rational drug therapy aimed at epigenetic processes in these cells.


CycD1, a putative G1 cyclin from Antirrhinum majus, accelerates the cell cycle in cultured tobacco BY-2 cells by enhancing both G1/S entry and progression through S and G2 phases.
A putative G1 cyclin gene, Antma;CycD1;1 (CycD1), from Antirrhinum majus is known to be expressed throughout the cell cycle in the meristem and other actively proliferating cells. To test its role in cell cycle progression, we examined the effect of CycD1 expression in the tobacco (Nicotiana tabacum) cell suspension culture BY-2. Green fluorescent protein:CycD1 is located in the nucleus throughout interphase. Using epitope-tagged CycD1, we show that it interacts in vivo with CDKA, a cyclin dependent protein kinase that acts at both the G1/S and the G2/M boundaries. We examined the effect of induced expression at different stages of the cell cycle. Expression in G0 cells accelerated entry into both S-phase and mitosis, whereas expression during S-phase accelerated entry into mitosis. Consistent with acceleration of both transitions, the CycD1-associated cyclin dependent kinase can phosphorylate both histone H1 and Rb proteins. The expression of cyclinD1 led to the early activation of total CDK activity, consistent with accelerated cell cycle progression. Continuous expression of CycD1 led to moderate increases in growth rate. Therefore, in contrast with animal D cyclins, CycD1 can promote both G0/G1/S and S/G2/M progression. This indicates that D cyclin function may have diverged between plants and animals.


JAL (RH48) blood group antigen: serologic observations.
JAL (RH48) is a low-prevalence antigen in the Rh blood group system and anti-JAL has caused hemolytic disease of the newborn. JAL is associated with either a haplotype carrying depressed C and e antigens or one carrying depressed c and e antigens. Blood samples from JAL+ people were tested, published serologic findings were confirmed, serologic studies were extended to include expression of other Rh antigens, and the antibody specificities produced by three sensitized JAL+ probands are reported. Red blood cell (RBC) samples from 17 (12 probands) JAL+ persons were tested by hemagglutination using standard methods. RBCs from both the Caucasian JAL+ probands had the (C)(e) haplotype and weakened C, e, hr(B), and hr(S) antigens. JAL+ samples from black persons had the (c)(e) haplotype and expressed weakened c, e, f, V, VS, hr(B), and hr(S) antigens. Plasma from three sensitized c+e+ JAL+ probands contained alloanti-c, alloanti-e, or alloantibody of apparent anti-Rh17 specificity. This study shows that this alloanti-Rh17-like antibody recognizes the high-prevalence antigen antithetical to JAL that has been named CEST. The presence of the JAL antigen has a quantitative (weakening) effect on the expression of C, e, hr(B), and hr(S) antigens in Caucasian persons and of c, e, f, V, VS, hr(B), and hr(S) antigens in people of black African ancestry. A qualitative effect also was demonstrated by the presence of alloanti-c or alloanti-e in the plasma of two transfused c+e+ patients and by an antibody (anti-CEST) that recognizes the high-prevalence antigen antithetical to JAL.