On the neural implausibility of the modular mind: Evidence for distributed construction dissolves boundaries between perception, cognition, and emotion.
Firestone & Scholl (F&S) rely on three problematic assumptions about the mind (modularity, reflexiveness, and context-insensitivity) to argue cognition does not fundamentally influence perception. We highlight evidence indicating that perception, cognition, and emotion are constructed through overlapping, distributed brain networks characterized by top-down activity and context-sensitivity. This evidence undermines F&S's ability to generalize from case studies to the nature of perception.


Metal-organic frameworks from zinc sulfite clusters, chains, and sheets: 4-connected, (3,4)-connected 3-D frameworks and 2-D arrays of catenane-like interlocking rings.
Even though open-framework solids have been made in a variety of compositions such as silicates, phosphates, germanates, borates, and phosphites, few are known that are based on trigonal-pyramidal sulfite anions. We report here the first synthetic and structural studies of metal-organic framework materials in the zinc sulfite composition. It is demonstrated here that Zn2+ and SO32- can form various neutral inorganic subunits that can be 0-D clusters, 1-D chains, or 2-D sheets. These inorganic subunits of different dimensionality can subsequently be connected into extended frameworks of higher dimensionality through bifunctional ligands. In (ZnSO3)2en, infinite corrugated ZnSO3 layers are pillared by ethylenediamine (en) molecules into a 3-D network that can be classified as a (3,4)-connected net based on tetrahedral Zn nodes and trigonal-pyramidal S nodes. In (ZnSO3)pip, infinite ZnSO3 chains are cross-linked with piperazine molecules into a 3-D framework that can be classified as 4-connected net based on tetrahedral Zn nodes only. In (ZnSO3)2(TMDPy)2, (ZnSO3)2 dimers are doubly bridged by trimethylenedipyridine molecules into an infinite chain with a string of circles. Each circle along the chain is interlocked with another circle from a chain in the perpendicular direction, creating a 2-D pattern with an infinite-square array of catenane-like units.


[Comparison of the effects of zopiclone and triazolam on the sleep of normal subjects].
Zopiclone 7.5 mg and triazolam 0.50 mg have been compared in a double-blind randomized cross-over sleep laboratory study. After a 6-day placebo, 12 healthy male volunteers aged 20-35 years received 2 active treatment sequences of 6 days separated by a 8-day placebo period and followed by a withdrawal period with placebo for 8 days. 22 polygraphic sleep recordings have been performed. The duration of nocturnal awakenings decreases at the beginning of treatment. Sleep onset latency is significantly decreased as well as the number of awakenings during sleep at the end of treatment. Both drugs improve the sleep efficiency index. Zopiclone increases total sleep time at the beginning and at the end of treatment. Triazolam increases this parameter at the end of the study only. Zopiclone, unlike triazolam increases the duration of deep NREM sleep-stages 3 and 4--at the beginning of treatment. No significant changes in sleep parameters were seen with zopiclone nor triazolam at the end of treatment. In sleep questionnaires, sleep onset latency is shorter under zopiclone than under triazolam and daytime drowsiness is less frequent with zopiclone.


Bradyrhizobium diazoefficiens USDA 110- Glycine max Interactome Provides Candidate Proteins Associated with Symbiosis.
Although the legume-rhizobium symbiosis is a most-important biological process, there is a limited knowledge about the protein interaction network between host and symbiont. Using interolog- and domain-based approaches, we constructed an interspecies protein interactome containing 5115 protein-protein interactions between 2291 Glycine max and 290 Bradyrhizobium diazoefficiens USDA 110 proteins. The interactome was further validated by the expression pattern analysis in nodules, gene ontology term semantic similarity, co-expression analysis, and luciferase complementation image assay. In the G. max-B. diazoefficiens interactome, bacterial proteins are mainly ion channel and transporters of carbohydrates and cations, while G. max proteins are mainly involved in the processes of metabolism, signal transduction, and transport. We also identified the top 10 highly interacting proteins (hubs) for each species. Kyoto Encyclopedia of Genes and Genomes pathway analysis for each hub showed that a pair of 14-3-3 proteins (SGF14g and SGF14k) and 5 heat shock proteins in G. max are possibly involved in symbiosis, and 10 hubs in B. diazoefficiens may be important symbiotic effectors. Subnetwork analysis showed that 18 symbiosis-related soluble N-ethylmaleimide sensitive factor attachment protein receptor proteins may play roles in regulating bacterial ion channels, and SGF14g and SGF14k possibly regulate the rhizobium dicarboxylate transport protein DctA. The predicted interactome provide a valuable basis for understanding the molecular mechanism of nodulation in soybean.


Central pathways controlling micturition and urinary continence.
The central control of micturition and urinary continence in cats and humans is organized in a similar manner. In cats, 4 areas in the brainstem and diencephalon are implicated in the control of micturition: (1) the pontine micturition center or Barrington area directly excites bladder motoneurons in the sacral cord during micturition; at the same time, it inhibits indirectly, via inhibitory gamma-aminobutyric acidergic and glycinergic interneurons in the medial sacral cord, the external urethral sphincter motoneurons; (2) the pontine continence center activates the external urethral sphincter motoneurons during continence; (3) the midbrain periaqueductal gray receives bladder filling information; and (4) the hypothalamus, in the beginning of micturition. According to positron emission tomography studies, in humans, the same supraspinal regions are active during micturition. Furthermore, the human cingulate and prefrontal cortices are activated during both micturition and continence, indicating that these areas are important for the onset of micturition, but not for the reflex itself. The primary motor cortex of the pelvic floor is important for voluntary pelvic floor contraction, but it is not involved in normal urinary continence.


Cold acclimation increases mitochondrial oxidative capacity without inducing mitochondrial uncoupling in goldfish white skeletal muscle.
Goldfish have been used for cold acclimation studies, which have focused on changes in glycolytic and oxidative enzymes or alterations in lipid composition in skeletal muscle. Here we examine the effects of cold acclimation on the functional properties of isolated mitochondria and permeabilized fibers from goldfish white skeletal muscle, focusing on understanding the types of changes that occur in the mitochondrial respiratory states. We observed that cold acclimation promoted a significant increase in the mitochondrial oxygen consumption rates. Western blot analysis showed that UCP3 was raised by ∼1.5-fold in cold-acclimated muscle mitochondria. Similarly, we also evidenced a rise in the adenine nucleotide translocase content in cold-acclimated muscle mitochondria compared to warm-acclimated mitochondria (0.96±0.05 vs 0.68±0.02 nmol carboxyatractyloside mg(-1) protein). This was followed by a 2-fold increment in the citrate synthase activity, which suggests a higher mitochondrial content in cold-acclimated goldfish. Even with higher levels of UCP3 and ANT, the effects of activator (palmitate) and inhibitors (carboxyatractyloside and GDP) on mitochondrial parameters were similar in both warm- and cold-acclimated goldfish. Thus, we propose that cold acclimation in goldfish promotes an increase in functional oxidative capacity, with higher mitochondrial content without changes in the mitochondrial uncoupling pathways.


Positive and Negative Cross-Talk between Lysophosphatidic Acid Receptor 1, Free Fatty Acid Receptor 4, and Epidermal Growth Factor Receptor in Human Prostate Cancer Cells.
Lysophosphatidic acid (LPA) is a lipid mediator that mediates cellular effects via G protein-coupled receptors (GPCRs). Epidermal growth factor (EGF) is a peptide that acts via a receptor tyrosine kinase. LPA and EGF both induce proliferation of prostate cancer cells and can transactivate each other's receptors. The LPA receptor LPA1 is particularly important for LPA response in human prostate cancer cells. Previous work in our laboratory has demonstrated that free fatty acid 4 (FFA4), a GPCR activated by ω-3 fatty acids, inhibits responses to both LPA and EGF in these cells. One potential mechanism for the inhibition involves negative interactions between FFA4 and LPA1, thereby suppressing responses to EGF that require LPA1 In the current study, we examined the role of LPA1 in mediating EGF and FFA4 agonist responses in two human prostate cancer cell lines, DU145 and PC-3. The results show that an LPA1-selective antagonist inhibits proliferation and migration to both LPA and EGF. Knockdown of LPA1 expression, using silencing RNA, blocks responses to LPA and significantly inhibits responses to EGF. The partial response to EGF that is observed after LPA1 knockdown is not inhibited by FFA4 agonists. Finally, the role of arrestin-3, a GPCR-binding protein that mediates many actions of activated GPCRs, was tested. Knockdown of arrestin-3 completely inhibits responses to both LPA and EGF in prostate cancer cells. Taken together, these results suggest that LPA1 plays a critical role in EGF responses and that FFA4 agonists inhibit proliferation by suppressing positive cross-talk between LPA1 and the EGF receptor.


Creating nanocavities of tunable sizes: hollow helices.
A general strategy for creating nanocavities with tunable sizes based on the folding of unnatural oligomers is presented. The backbones of these oligomers are rigidified by localized, three-center intramolecular hydrogen bonds, which lead to well-defined hollow helical conformations. Changing the curvature of the oligomer backbone leads to the adjustment of the interior cavity size. Helices with interior cavities of 10 A to >30 A across, the largest thus far formed by the folding of unnatural foldamers, are generated. Cavities of these sizes are usually seen at the tertiary and quaternary structural levels of proteins. The ability to tune molecular dimensions without altering the underlying topology is seen in few natural and unnatural foldamer systems.


Changes in intercellular coupling between pig oocytes and cumulus cells during maturation in vivo and in vitro.
Cumulus expansion and cumulus cell-oocyte coupling during in-vivo and in-vitro maturation of pig oocytes were studied by measuring [3H]uridine uptake. In vivo, cumulus expansion started before germinal vesicle breakdown (GVBD) (16 h versus 20 h after hCG) but no significant change occurred in the coupling index until 32 h after hCG. Intercellular coupling was decreasing at 32 h after hCG in oocytes at anaphase I and telophase I. Complete uncoupling was closely correlated with corona radiata expansion. In vitro, partial uncoupling was observed in oocyte-cumulus cell complexes from prepubertal and PMSG-stimulated gilts cultured for 16 and 32 h, respectively. The addition of FSH caused cumulus expansion, and the functional coupling between the cumulus cells and the oocyte was maintained up to at least 16 h of culture in complexes from prepubertal gilts. We conclude that, under our conditions, neither hormone-free nor FSH-supplemented medium ensured the same [3H]uridine uptake and uncoupling kinetics as during in-vivo maturation.


RASA1 inhibits the progression of renal cell carcinoma by decreasing the expression of miR-223-3p and promoting the expression of FBXW7.
RAS p21 protein activator 1 (RASA1), also known as p120-RasGAP, is a RasGAP protein that functions as a signaling scaffold protein, regulating pivotal signal cascades. However, its biological mechanism in renal cell carcinoma (RCC) remains unknown. In the present study, RASA1, F-box/WD repeat-containing protein 7 (FBXW7), and miR-223-3p expression were assessed via quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot. Then, the targeted correlations of miR-223-3p with FBXW7 and RASA1 were verified via a dual-luciferase reporter gene assay. CCK-8, flow cytometry, and Transwell assays were implemented independently to explore the impact of RASA1 on cell proliferation, apoptosis, migration, and cell cycle progression. Finally, the influence of RASA1 on tumor formation in RCC was assessed in vivo through the analysis of tumor growth in nude mice. Results showed that FBXW7 and RASA1 expression were decreased in RCC tissues and cell lines, while miR-223-3p was expressed at a higher level. Additionally, FBXW7 and RASA1 inhibited cell proliferation but facilitated the population of RCC cells in the G0/G1 phase. Altogether, RASA1 may play a key role in the progression of RCC by decreasing miR-223-3p and subsequently increasing FBXW7 expression.


Single coronary artery with anomalous origin of the right coronary artery from the left anterior descending artery with a unique proximal course.
A 62-year-old man with hypertension and hypercholesterolemia was referred to our unit for evaluation of chest pain. A very rare variant of single coronary artery, in which the anomalous right coronary artery originated as a separate branch from the left anterior descending artery, was incidentally found on his coronary angiography. The anomalous right coronary artery in our case appears to be unique in that it courses intraseptally rather than rightwards proximally and has obstructive atherosclerotic lesions resulting in inferior ischemia. Moreover, the acute angle made by the anomalous right coronary artery to turn toward the atrioventricular groove may have reduced the flow velocity and contributed to the development of inferior ischemia.


Assay of advanced glycation endproducts (AGEs): surveying AGEs by chromatographic assay with derivatization by 6-aminoquinolyl-N-hydroxysuccinimidyl-carbamate and application to Nepsilon-carboxymethyl-lysine- and Nepsilon-(1-carboxyethyl)lysine-modified albumin.
Glycation of proteins leads to the formation of early glycation adducts (fructosamine derivatives) and advanced glycation endproducts (AGEs). Formation of AGEs has been linked to the development of cataract, diabetic complications, uraemia, Alzheimer's disease and other disorders. AGEs are a group of compounds of diverse molecular structure and biological function. To characterize AGE-modified proteins used in studies of structural and functional effects of glycation, an assay was developed that surveys the content of early and advanced glycation adducts in proteins. The assay procedure involved enzymic hydrolysis of protein substrate, derivatization of the hydrolysate with 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC) and HPLC of the resulting adducts with fluorimetric detection. Structural isomers of methylglyoxal-derived hydroimidazolone, glyoxal-derived hydroimidazolone, 3-deoxyglucosone-derived hydroimidazolone and N(delta)-(4-carboxy-4,6-dimethyl-5,6-dihydroxy-1,4,5,6-tetrahydropyrimidin-2-yl)-ornithine (THP) were determined for the first time. AGEs with intrinsic fluorescence (argpyrimidine, pentosidine) were assayed without derivatization. Limits of detection were 2-17 pmol and levels of recovery were 50-99%, depending on the analyte. The AQC assay resolved structural and epimeric isomers of methylglyoxal-derived hydroimidazolones and THP. Hydroimidazolones, THP and argpyrimidine were AGEs of short-to-intermediate stability under physiological conditions, with half-lives of 1-2 weeks. Their measurement provides further insight into the glycation process. The assay was applied to the characterization of human serum albumin minimally and highly modified by N(epsilon)-carboxymethyl-lysine and N(epsilon)-(1-carboxyethyl)-lysine.


Intubation Success through I-Gel® and Intubating Laryngeal Mask Airway® Using Flexible Silicone Tubes: A Randomised Noninferiority Trial.
Introduction. The study aims to test whether flexible silicone tubes (FST) improve performance and provide similar intubation success through I-Gel as compared to ILMA. Our trial is registered in CTRI and the registration number is "CTRI/2016/06/006997." Methods. One hundred and twenty ASA status I-II patients scheduled for elective surgical procedures needing tracheal intubation were randomised to endotracheal intubation using FST through either I-Gel or ILMA. In the ILMA group (n = 60), intubation was attempted through ILMA using FST and, in the I-Gel group (n = 60), FST was inserted through I-Gel airway. Results. Successful intubation was achieved in 36.67% (95% CI 24.48%-48.86%) on first attempt through I-Gel (n = 22/60) compared to 68.33% (95% CI 56.56%-80.1%) in ILMA (n = 41/60) (p = 0.001). The overall intubation success rate was also lower with I-Gel group [58.3% (95% CI 45.82%-70.78%); n = 35] compared to ILMA [90% (95% CI 82.41%-97.59%); n = 54] (p < 0.001). The number of attempts, ease of intubation, and time to intubation were longer with I-Gel compared to ILMA. There were no differences in the other secondary outcomes. Conclusion. The first pass success rate and overall success of FST through an I-Gel airway were inferior to those of ILMA.


A cloud-based car parking middleware for IoT-based smart cities: design and implementation.
This paper presents the generic concept of using cloud-based intelligent car parking services in smart cities as an important application of the Internet of Things (IoT) paradigm. This type of services will become an integral part of a generic IoT operational platform for smart cities due to its pure business-oriented features. A high-level view of the proposed middleware is outlined and the corresponding operational platform is illustrated. To demonstrate the provision of car parking services, based on the proposed middleware, a cloud-based intelligent car parking system for use within a university campus is described along with details of its design, implementation, and operation. A number of software solutions, including Kafka/Storm/Hbase clusters, OSGi web applications with distributed NoSQL, a rule engine, and mobile applications, are proposed to provide 'best' car parking service experience to mobile users, following the Always Best Connected and best Served (ABC&S) paradigm.


Assessment of the calcification of the nuchal ligament and osteophytes of the cervical spine in obstructive sleep apnoea subjects and snorers.
The previous reports suggest that obstructive sleep apnoea (OSA) is related to metabolic syndrome, mineral metabolism disorders and cardiovascular disease. In addition, a possible relationship between obesity and the calcification of ligaments has been implied. However, the potential link between OSA and the calcification of ligaments has not been directly studied. In this present study, to investigate the potential link between OSA and the calcification of ligaments, we examined the prevalence of the calcification of ligaments in OSA patients and the relationship between these findings and OSA severity. Eighty consecutive patients (60 males, 20 females) diagnosed as OSA or a heavy snorer based on full-night polyso-mnography were retrospectively recruited from May 2006 to July 2008. Each patient underwent cephalometric imaging examination before the arrangement of an oral appliance. One calibrated observer (YS) reviewed the cephalometric images for the presence of calcification of the nuchal ligament and osteophytes of the cervical spine. The prevalence of calcification of the nuchal ligament in OSA patients and snorers was 46.3% (males: 52%, females: 30%) There was a significant positive correlation between the severity of OSA (AHI) and the calcification of the nuchal ligament before and after adjusting for BMI. The prevalence of the calcification of the nuchal ligament in OSA subjects and snorers was higher than in previous studies with non-OSA subjects. In addition, it is suggested that the severity of OSA correlates with the presence of calcification of the nuchal ligament.


Fructofuranose 2-phosphate is the product of dephosphorylation of fructose 2,6-bisphosphate.
Using comparative ion-exchange chromatography on Dowex 1X4, the product of dephosphorylation of fructose 2,6-bisphosphate with purified yeast fructose-2,6-bisphosphate 6-phosphohydrolase, was shown to be identical to the furanose form of fructose 2-phosphate prepared by chemical synthesis according to Pontis and Fischer [Biochem. J. 89, 452-459 (1963)]. As expected for the furanose form of fructose 2-phosphate, the enzymatically formed product consumes 1 mol periodate/mol fructose 2-phosphate, whereas the chemically synthesized pyranose form consumes 2 mol periodate/mol. In addition, it is shown that the enzymatic product behaves identically to the furanose, not the pyranose, form of fructose 2-phosphate in hydrolysis of the ester bond at pH 4 and 37 degrees C, as described previously for the chemically synthesized compounds [Pontis and Fischer (1963) vide supra].


Frozen in time: a new method using cryo-scanning electron microscopy to visualize root-fungal interactions.
A new method of sample preparation for cryo-scanning electron microscopy was used to visualize internal infection of wheat (Triticum aestivum) roots by the pathogenic fungus Rhizoctonia solani AG-8. The new method retained fungal hyphae and root cells in situ in disintegrating root tissues, thus avoiding the distortions that can be introduced by conventional preparation by chemical fixation, dehydration and embedding. Infected roots frozen in liquid nitrogen were cryo-planed and etched (sublimed) at -80 degrees C for a critical length of time (up to 9 min) in the microscope column to reveal plant and fungal structures in three dimensions. Root and fungal structures were well preserved irrespective of infection severity. Root and hyphal cell walls were clearly seen and hyphal architecture within and between root cells was preserved. This rapid method permits three-dimensional in situ visualization of fungal invasion within roots and has broad application for examination of diseases caused by other necrotrophic fungi.


[The thalamus: a dynamic door to perception].
y dependent on the activity of our senses for our relationship with the outside world, we may consider the thalamus to be a key part of perception. DEVELOPMENT. Far from behaving as a simple relay station, the thalamic circuits represent the framework on which to build a truly dynamic biological filter which can select the messages to reach the cortex according to their relevance and the behavioural state of the person. Such filtering implies the participation of many neurotransmitters which represent as many different systems. Outstanding amongst these are the groups formed by acetylcholine and nitric oxide axons arising from the brainstem, and corticofugal fibers which are sent back from the cortex to the thalamus. CONCLUSIONS. In this paper we review the functional aspects of the thalamic control of information, particularly of the visual system, with reference to alterations derived from its malfunction.


Fruit fly (Diptera: Tephritidae) host status determination: critical conceptual, methodological, and regulatory considerations.
Although fruit fly host status determination/designation lies at the heart of strategic decisions on national and international trade of fruit and vegetables, all attempts thus far to define host plant status have been contentious and as a result long-standing disputes between commercial partners throughout the world have lingered over decades. Part of the problem is that too little effort has been devoted to understanding the underlying mechanisms involved in host plant use by fruit flies and that instead economic and political interests usually prevail. Here we review the most important evolutionary, biological, ecological, physiological, and behavioral aspects that drive host use by fruit flies, and then construct a flow diagram rooted in these fundamentals that outlines a series of steps and definitions to determine if a particular fruit or vegetable (and cultivars thereof) is a natural host, or a conditional (potential, artificial) host, or a nonhost. Along the way, we incorporate risk analysis considerations and propose that the underlying complexity determining host plant utilization by fruit flies requires a flexible systems approach capable of realistically dealing with fly/host/environment/geographic variability on a case-by-case basis.


Expression of hBUB1 in acute myeloid leukemia.
hBUB1 gene is a component of the mitotic checkpoint that monitors proper assembly of the mitotic spindles and the alteration of the hBUB1 gene has been found to be associated with chromosomal instability in some tumor cell lines. We analyzed the coding region of the hBUB1 gene for mutations and its expression in 92 acute myeloid leukemia (AML) specimens and five hematopoietic cell lines. We also used Southern hybridization to analyze the genomic DNA of those cases, which had aberrant transcription to confirm the lesion. A thymine/cytosine polymorphism at 8 bp upstream of the 5' splice acceptor site of exon 10 was observed in Raji cell line and two AML specimens without a resultant change in the expression of hBUB1. Reduced expression and aberrant transcription of the hBUB1 gene, which may affect the control of mitotic checkpoint, were detected in AML specimens by reverse transcription-polymerase chain reaction (RT-PCR) analysis. Our study suggests that the mutation of the hBUB1 gene is a rare event in AML, and further studies are necessary to clarify its role in leukemia.


Transient hydrodynamic finite-size effects in simulations under periodic boundary conditions.
We use lattice-Boltzmann and analytical calculations to investigate transient hydrodynamic finite-size effects induced by the use of periodic boundary conditions. These effects are inevitable in simulations at the molecular, mesoscopic, or continuum levels of description. We analyze the transient response to a local perturbation in the fluid and obtain the local velocity correlation function via linear response theory. This approach is validated by comparing the finite-size effects on the steady-state velocity with the known results for the diffusion coefficient. We next investigate the full time dependence of the local velocity autocorrelation function. We find at long times a crossover between the expected t^{-3/2} hydrodynamic tail and an oscillatory exponential decay, and study the scaling with the system size of the crossover time, exponential rate and amplitude, and oscillation frequency. We interpret these results from the analytic solution of the compressible Navier-Stokes equation for the slowest modes, which are set by the system size. The present work not only provides a comprehensive analysis of hydrodynamic finite-size effects in bulk fluids, which arise regardless of the level of description and simulation algorithm, but also establishes the lattice-Boltzmann method as a suitable tool to investigate such effects in general.


Enhancing existing approaches to peripheral T-cell lymphoma.
The National Comprehensive Cancer Network (NCCN) practice guidelines for peripheral T-cell lymphoma (PTCL) accentuate the lack of standard treatment options for this disease. Outcomes with conventional therapies, many of which are borrowed from B-cell lymphoma, are poor. Strategies to enhance existing approaches include creating a new platform for first-line therapy and adding novel agents, such as denileukin diftitox, to existing chemotherapy platforms. Furthermore, to improve outcomes, patients must reach transplant through effective first-line therapies. Additionally, treatment should be individualized based on histopathologic subtype, as all PTCL patients will not respond to the same treatment regimen.


Molecular identification and phylogenetic characterisation of Thelohanellus kitauei - short communication.
Thelohanellus kitauei was isolated from the koi Cyprinus carpio haematopterus, and the 18S rRNA gene of T. kitauei was amplified by optimised nested-PCR. The PCR product was sequenced and compared with other 18S rRNA genes of Thelohanellus species to investigate the relationships between their host specificities and infection sites. Based on the 18S rRNA sequences, T. kitauei is most closely related to T. hovorkai (which can infect the intestine). Phylogenetic analysis revealed that T. kitauei was clustered with other Thelohanellus spp. infecting Cyprininae. The present study suggests that the infection site and the host specificity (subfamily level) are reflected in the genetic relationships among Thelohanellus species.


Cervical cancer screening and psychosocial barriers perceived by patients. A systematic review.
This study aimed at integrating research discussing the role of perceived psychosocial barriers in cervical cancer screening (CCS) uptake. In particular, we analyzed the evidence for the associations between CCS uptake and perceived psychosocial barriers and frequency of psychosocial barriers identified by women. A systematic search of peer-reviewed papers published until 2011 in 8 databases yielded 48 original studies, analyzing data obtained from 155 954 women. The majority of studies (k = 43) applied correlational design, while 5 had experimental design. Experimental research indicated a positive effect of 75% of psychosocial interventions targeting barriers. The interventions resulted in a significant increase of CCS uptake. Overall 100% of correlational studies indicated that perceiving lower levels of barriers significantly predicted higher CCS uptake. 53 psychosocial barriers were listed in at least 2 original correlational studies: 9.5% of barriers were related to CCS facilities/environment, 67.9% dealt with personal characteristics of the patient, and 22.6% addressed social factors. As many as 35.9% of perceived barriers referred to negative emotions related to CCS examination procedures and collecting CCS results, whereas 25.7% of barriers referred to prior contacts with health professionals. Leaflets or discussion on psychosocial barriers between patients and health professionals involved in CCS might increase CCS uptake and thus reduce cervical cancer mortality rates. Communication skills training for health professionals conducting CCS might focus on the most frequently reported barriers, referring to emotions related to CCS examination and collecting CCS results.


Skin Wound following Irradiation Aggravates Radiation-Induced Brain Injury in a Mouse Model.
Radiation injury- and radiation combined with skin injury-induced inflammatory responses in the mouse brain were evaluated in this study. Female B6D2F1/J mice were subjected to a sham, a skin wound (SW), 9.5 Gy 60Co total-body gamma irradiation (RI), or 9.5 Gy RI combined with a skin puncture wound (RCI). Survival, body weight, and wound healing were tracked for 30 days, and mouse brain samples were collected on day 30 after SW, RI, RCI, and the sham control. Our results showed that RCI caused more severe animal death and body weight loss compared with RI, and skin wound healing was significantly delayed by RCI compared to SW. RCI and RI increased the chemokines Eotaxin, IP-10, MIG, 6Ckine/Exodus2, MCP-5, and TIMP-1 in the brain compared to SW and the sham control mice, and the Western blot results showed that IP-10 and p21 were significantly upregulated in brain cells post-RI or -RCI. RI and RCI activated both astrocytes and endothelial cells in the mouse brain, subsequently inducing blood-brain barrier (BBB) leakage, as shown by the increased ICAM1 and GFAP proteins in the brain and GFAP in the serum. The Doublecortin (DCX) protein, the "gold standard" for measuring neurogenesis, was significantly downregulated by RI and RCI compared with the sham group. Furthermore, RI and RCI decreased the expression of the neural stem cell marker E-cadherin, the intermediate progenitor marker MASH1, the immature neuron cell marker NeuroD1, and the mature neuron cell marker NeuN, indicating neural cell damage in all development stages after RI and RCI. Immunohistochemistry (IHC) staining further confirmed the significant loss of neural cells in RCI. Our data demonstrated that RI and RCI induced brain injury through inflammatory pathways, and RCI exacerbated neural cell damage more than RI.


Distribution and cloning of eukaryotic mRNAs by means of differential display: refinements and optimization.
Differential display has been developed as a tool to detect and characterize altered gene expression in eukaryotic cells. The basic principle is to systematically amplify messenger RNAs and then distribute their 3' termini on a denaturing polyacrylamide gel. Here we provide methodological details and examine in depth the specificity, sensitivity and reproducibility of the method. We show that the number of anchored oligo-dT primers can be reduced from twelve to four that are degenerate at the penultimate base from the 3' end. We also demonstrate that using optimized conditions described here, multiple RNA samples from related cells can be displayed simultaneously. Therefore process-specific rather than cell-specific genes could be more accurately identified. These results enable further streamlining of the technique and make it readily applicable to a broad spectrum of biological systems.


Effect of silane compounds on bonding to fused quartz of tri-n-butylborane initiated resin.
This study aimed to investigate how different compositions of experimental silane-based primers in a methyl methacrylate solution containing 3-(trimethoxysilyl)propyl methacrylate (3-TMSPMA) or 3-(4-methacryloyloxyphenyl)propyl trimethoxysilane (3-MPPTS) might act as silicon dioxide bonding agents. With or without post-silanization heat treatment, primer-treated quartz discs were bonded using the MMA-TBB resin and their bond strengths were evaluated. The disks were primed with one of the following materials: 1 mol% 3-TMSPMA, 2 mol% 3-TMSPMA, 1 mol% 3-MPPTS, and 2 mol% 3-MPPTS. Shear bond strength was determined both before and after thermocycling. Statistical analyses were performed with non-parametric procedure (Kruskal-Wallis, Mann-Whitney U, and Steel-Dwass tests). Both primers were effective with heat treatment to enhance bonding between quartz and the MMA-TBB, and the bonding durability of the 1 and 2 mol% 3-MPPTS (16.8 and 24.9 MPa) with heat groups was significantly higher than in the 1 and 2 mol% 3-TMSPMA (5.4 and 9.8 MPa) with heat groups.


Smoking cessation among persons in recovery.
The literature on smoking cessation for those in recovery from other drug use is reviewed. Reasons for engaging in this work, arguments against treatment of smoking along with another drug, characteristics of drug users who smoke, and treatment content implications are reviewed. Outcomes of 24 studies are presented. It is concluded that the future of research and practice in this arena should include facilitating smoking cessation among those early in recovery.


[Treatment of choanal atresia].
17 unilateral and 6 bilateral choanal atresias in children were observed in the ENT-Dept. of the University Hospital Erlangen during 1975-1982. Bilateral choanal atresia requires immediate trepanation by using the CO2 or Argon laser technique. The surgical procedure in unilateral choanal atresia is postponed until the age of 4 years. Transnasal microsurgical approach is preferred in these cases because it involves minimal damage to the developing structures. The satisfying results are reported.


Body composition of children with myelomeningocele, determined by 40K, urinary creatinine and anthropometric measures.
The purpose of this study was to develop a method to prevent obesity in myelomeningocele (MM) children by determining the effects of growth, calories and physical activity on body composition and to apply this data to clinical practice, specifically, to correlate lean body mass (LBM) with calorie needs and to correlate body fatness with anthropometry measures. The body compositions of 14 children (four males and ten females) with MM were estimated from potassium content (40K), urinary creatinine and anthropometry measurements at the beginning and end of a six-month period. Three subjects who did not have MM were also evaluated as controls. Dietary and physical activity and dietary-goals estimates were taken from records kept by the patients after initial discussion of physical activity and dietary goals with the families. The study showed potassium content (40K), or LBM, in children with MM to be approximately 50% of the potassium content (40K) of children without MM. The percentage of LBM correlated with physical activity, but not with the location of neurological lesion. Lean body mass and creatinine excretion also were significantly correlated, indicating that creatinine excretion is a good measure of lean body tissue in these children. Thorax and abdominal skinfolds, as well as total circumferential measurements (waist being highest), showed significant correlations with the percent of body fat. The caloric intake requirement to maintain the growth of a child with MM was found to be approximately 50% of the recommended daily allowance (RDA) for a child without MM of the same age. Changes in LBM were observed in children with MM who increased physical activity over a six-month interval and were greater than in those who reduced calories alone, however not significantly, presumably due to the short duration of the study. To prevent obesity, physical activity should begin in infancy; this will increase LBM and thereby calorie needs. Skinfolds and circumferences (abdominal and thorax skinfolds and waist circumference) which significantly correlated with body fat should be used clinically. Calorie needs according to LBM should be reduced to 50% of the RDA or approximately nine cal/cm height for maintenance or seven cal/cm height for weight loss in MM children after age six (possibly at three to four years of age if nonambulatory).


Safety effects of wider edge lines on rural, two-lane highways.
Although it is generally expected that wider lines will have a positive effect on vehicle safety, there have not been any convincing evidence based on the crash data analysis, partly because of the lack of relevant data. In this paper, the safety effect of wider edge lines was examined by analyzing crash frequency data for road segments with and without wider edge lines. The data from three states, Kansas, Michigan, and Illinois, have been analyzed. Because of different nature of data from each state, a different statistical analysis approach was employed for each state: an empirical Bayes, before-after analysis of Kansas data, an interrupted time series design and generalized linear segmented regression analysis of Michigan data, and a cross sectional analysis of Illinois data. Although it is well-known that causation is hard to establish based on observational studies, the results from three extensive statistical analyses all point to the same findings. The consistent findings lend support to the positive safety effects of wider edge lines installed on rural, two-lane highways.


Long-range transport in an assembly of ZnO quantum dots: the effects of quantum confinement, Coulomb repulsion and structural disorder.
We have studied the storage and long-range transport of electrons in a porous assembly of weakly coupled ZnO quantum dots permeated with an aqueous and a propylene carbonate electrolyte solution. The number of electrons per ZnO quantum dot is controlled by the electrochemical potential of the assembly; the charge of the electrons is compensated by ions present in the pores. We show with optical and electrical measurements that the injected electrons occupy the S, P, and D type conduction electron levels of the quantum dots; electron storage in surface states is not important. With this method of three-dimensional charge compensation, up to ten electrons per quantum-dot can be stored if the assembly is permeated with an aqueous electrolyte. The screening of the electron charge is less effective in the case of an assembly permeated with a propylene carbonate electrolyte solution. Long-range electron transport is studied with a transistor set-up. In the case of ZnO assemblies permeated with an aqueous electrolyte, two quantum regimes are observed corresponding to multiple tunnelling between the S orbitals (at a low occupation) and P orbitals (at a higher occupation). In a ZnO quantum-dot assembly permeated with a propylene carbonate electrolyte solution, there is a strong overlap between these two regimes.


The morphological features of Aegyptianella bacterifera: an intraerythrocytic rickettsia of frogs from Corsica.
Study of ultrathin sections and freeze-fracture replicas of erythrocytes containing Aegyptianella bacterifera (Rickettsiales; Anaplasmataceae) revealed that the organisms develop within a membrane bound vacuole in the erythrocyte cytoplasm. The organisms divide by binary fission to produce about 12 rickettsiae in a mature inclusion. The organisms have gram-negative cell envelopes. The distribution of intramembranous particles within the outer and plasma membranes of A. bacterifera is similar to that of other rickettsiae and gram-negative bacteria such as Escherichia coli. The definition of the genus Aegyptianella should be broadened to include rickettsiae measuring up to 5 microns in length prior to division which develop within membrane bound inclusions in erythrocytes of their hosts.


Doubly N-Methylated Porphyrinoids.
Chirality-induced aromatic π-electronic macrocycles, porphyrin and corroles, were synthesized through doubly inner N-methylation through multistep and one-pot reactions, respectively. The exact structures of doubly N-methylated porphyrin and corroles were revealed by single-crystal synchrotron X-ray analysis, exhibiting two N-methyl groups located on neighboring pyrrole rings in up/down conformations. These doubly inner N-substitutions of the π-electronic macrocycles induced distorted geometries, resulting in chiroptical properties after optical resolutions.


Outer-Sphere Control of Catalysis on Surfaces: A Comparative Study of Ti(IV) Single-Sites Grafted on Amorphous versus Crystalline Silicates for Alkene Epoxidation.
The effect of outer-sphere environment on alkene epoxidation catalysis using an organic hydroperoxide oxidant is demonstrated for calix[4]arene-TiIV single-sites grafted on amorphous vs crystalline delaminated zeotype (UCB-4) silicates as supports. A chelating calix[4]arene macrocyclic ligand helps enforce a constant TiIV inner-sphere, as characterized by UV-visible and X-ray absorption spectroscopies, thus enabling the rigorous comparison of outer-sphere environments across different siliceous supports. These outer-sphere environments are characterized by solid-state 1H NMR spectroscopy to comprise proximally organized silanols confined within 12 membered-ring cups in crystalline UCB-4, and are responsible for up to 5-fold enhancements in rates of epoxidation by TiIV centers.


Comparison of static and dynamic sensory product characterizations based on check-all-that-apply questions with consumers.
The aim of the present work was to compare static and dynamic sensory product characterizations based on check-all-that-apply (CATA) questions with consumers. Three studies involving a total of 310 consumers were carried out. In each study, a between-subjects experimental design was used to compare static sensory characterizations obtained using CATA questions with dynamic characterizations over a relatively short time period using temporal CATA (TCATA). Three different product categories were evaluated (orange juice, strawberry yogurt, and vanilla milk desserts) using 6-11 sensory terms. TCATA data were analysed as CATA considering fixed time periods throughout the evaluation. CATA and TCATA were compared in terms of frequency of use of the terms, sample discrimination, and sample and term configurations. Asking consumers to continuously select the attributes that applied to describe a product and to deselect those that no longer applied during the evaluation period did not substantially modify the average citation proportion of terms or the maximum citation proportion for individual terms for liquid and semi-solid products with a relatively fast oral preparatory phase. Although both methodologies provided similar information, additional insights on how similarities and differences among samples evolved during consumption were obtained with TCATA in the case of products that experience large temporal changes or attributes with strong time-dependency. CATA provided similar information as TCATA for sensory attributes that did not change substantially during the evaluation period. Results from the present work suggest that static and dynamic product sensory characterizations using CATA questions with consumers provide complementary information about consumer experiences with food products.


AtHaspin phosphorylates histone H3 at threonine 3 during mitosis and contributes to embryonic patterning in Arabidopsis.
Post-translational histone modifications regulate many aspects of chromosome activity. Threonine 3 of histone H3 is highly conserved, but the significance of its phosphorylation is unclear, and the identity of the corresponding kinase in plants is unknown. Therefore, we characterized the candidate kinase in Arabidopsis thaliana, called AtHaspin. Recombinant AtHaspin in vitro phosphorylates histone H3 at threonine 3. Reduction of H3 threonine 3 phosphorylation level and reduced chromatin condensation in interphase nuclei by AtHaspin RNAi supports the proposition that this kinase is involved in histone H3 phosphorylation in vivo in mitotic cells. In addition, we provide a developmental function for a Haspin kinase. At the whole plant level, altered expression of the kinase induced pleiotropic phenotypes with defects in floral organs and vascular tissue. It reduced fertility and modified adventitious shoot apical meristems that then gave rise to plants with multi-rosettes and multi-shoots. Haspin mutant embryos frequently showed alteration in division plane orientation that could be traced back to the earliest divisions of embryo development, thus Haspin contributes to embryonic patterning.


An SPRI beads-based DNA purification strategy for flexibility and cost-effectiveness.
Current solid-phase reversible immobilization (SPRI) beads technology is widely used in molecular biology due to its convenience for DNA manipulation. However, the high performance commercial SPRI beads have no price advantage over our method. Furthermore, the use of commercially available SPRI beads standards does not provide the flexibility required for a number of specific nucleic acid handling scenarios. We report an efficient DNA purification strategy by combining home-made beads-suspension buffer with SPRI beads. The method tests the critical concentrations of polyethylene glycol (PEG) 8000 and beads to maximise recovery. And the composition of the SPRI beads DNA purification system (SDPS) was determined at 20% PEG 8000, 2 M NaCl and 16.3 mM MgCl2, and 1.25 mg/ml beads (1/8th original concentration). Then, we tested the DNA recovery of the SDPS, and the result showed that it was comparable to the control (AMPure XP beads). In the study, we have also developed an adjustment SPRI beads DNA purification system (ASDPS), the volume of ASDPS per reaction is 0.6× reaction volume (beads/samples). The performance of ASDPS is similar to SDPS and the control. But the cost of our methods is only about 1/24th of the control. To further assess its performance, we prepare the DNA-seq libraries to evaluate the yield, library quality, capture efficiency and consistency. We have compared all these results with the performance of the control and confirmed its efficiency. We have proposed an alternative DNA purification approach with great flexibility, allowing researchers to manipulate DNA in different conditions. And ultimately, its application will benefit molecular biology research in the future.


Transforming Impossible into Possible (TIP) for SUD recovery: A promising practice innovation to combat the opioid crisis.
The purpose of this study is to examine the psychological self-sufficiency (PSS) process among low-income individuals participating in the Transforming Impossible into Possible (TIP) program and explore the implications of TIP as a SUD recovery intervention. A sample of 622 individuals from 9 local job training programs in a large Midwestern city was used to examine the group differences in substance abuse barrier and employment hope as they relates to economic self-sufficiency (ESS). Individuals in the TIP program (n = 315) had statistically significant path coefficients between substance abuse barriers, employment hope and ESS while the non-TIP counterpart (n = 307) showed a significant path only between employment hope and ESS. Also, the time difference score in substance abuse barrier and ESS was greater for the TIP group compared to the non-TIP comparison group. Results provide implications for social work practice among persons with SUDs. While the traditional employment programs focused only on the interview and job skills, TIP allowed participants to discover their resources to address the inner obstacles that have been holding them back. TIP could serve as a promising model to treat SUDs and support the recovery process.


A new species of cascade frog (Amphibia: Ranidae) in the Amolops monticola group from China.
A new species, Amolops wenshanensis sp. nov., is described from Guangxi and Yunnan Provinces, China. The new species is a member of the A. monticola group, and is distinguished from its congeners using morphological and molecular data. The new species is diagnosed by having glandular dorsolateral folds; smooth skin; side of head dark with a light-colored upper lip stripe extending to axilla; green dorsal coloration in life; immaculate venter; indistinct transverse bands on dorsal surfaces of limbs; tympanum distinct; pineal body absent; all fingertips expanded with circummarginal grooves; two oblique vomerine teeth; vocal sac and white nuptial pad present in males; supratympanic fold absent; outer metatarsal tubercle absent; glandular gold-white flank spot absent; and skin on venter not translucent. A molecular phylogenetic analysis is performed using the mitochondrial (mt) NADH dehydrogenase subunit 2 (ND2) gene and parts of flanking tRNA genes for nine of the 15 members of the A. monticola group with available homologous sequences. The new species is sister to a clade containing A. cucae and A. compotrix, two species known from adjacent parts of Vietnam and Laos. The new species differs from its congeners by having an uncorrected p-distance of > 6.7% in the mt DNA fragment examined. At present, the new species is known from small, montane streams near Wenshan, Yunnan Province, and Jingxi, Guangxi Province, China.


[Detection of the expression of alpha3-integrin on hantavirus permissive cells].
To express and purify human alpha3-integrin to serve as the antigen to prepare its antibody and to separate the Vero cell clones without expression of alpha3-integrin. The human alpha3-integrin gene was amplified by using RT-PCR, then subcloned into a pQE30 expression vector and expressed in E. coli. The gene expression was confirmed by Western blot assay. Rabbit was inoculated with purified antigen to stimulate the antibody generation. The target Vero cells were separated by negative selection using antibody plus complement mediated cytolysis. The separated cell clones were confirmed by immunofluorescence and Western blot assay. The alpha3- integrin gene was cloned and expressed effetively, Western blot assay revealed that the expressed protein held good immune reactivity. High titer antibody was generated. However the expression of alpha3-integrin was not detected on Vero, VeroE6, Hep-2, 2BS and 293 cells. The results of the study suggested that hantavirus has other receptors on Vero cells beside alpha 3-integrin.


[Application of chromosome microarray analysis for patients with skeletal anomalies and a normal karyotype].
To analyze patients with skeletal anomalies (SA) but a normal karyotype using chromosome microarray analysis (CMA). From June 2012 to May 2015, 43 children found to have skeletal anomalies with or without other abnormalities were subjected to karyotyping analysis. For those with a normal karyotype, DNA was extracted and hybridized with Affymetrix CytoScan 750 kb arrays following the manufacturer's protocol. The results were analyzed with CHAS v2.0 software. Two patients (4.65%) were detected with an abnormal karyotype. The remaining 41 patients with a normal karyotype were classified into 3 groups: isolated SA (n=17), SA with mental retardation (n=6), and SA with other structural anomalies (n=18). Clinically significant copy number variations (CNVs) were found in 21.95% (9/41) of the cases, which included 17.65% (3/17) with isolated SA, 33.33% (2/6) with SA and mental retardation, and 22.22% (4/18) of SA with other structural deformities. Whole-genome CMA can detect clinically significant CNVs which may not be found by conventional karyotyping analysis and increase the detection rate by approximately 21.95%. It may be recommended for patients with SA but a normal karyotype.


Primary multilocular cystic undifferentiated (embryonal) sarcoma of the liver in childhood resembling hydatid cyst of the liver.
Undifferentiated (embryonal) sarcoma (UES) is a very rare primary malignant tumour of the liver; typically presenting in later childhood. This tumour usually appears on CT and ultrasound as a predominantly solid mass with or without cystic areas. We report a case of primary UES which had a multilocular cystic appearance resembling a hydatid cyst on imaging.


Efficient dye-sensitized solar cells with catalytic multiwall carbon nanotube counter electrodes.
We report the successful application of multiwall carbon nanotubes (CNTs) as electrocatalysts for triiodide reduction in a dye-sensitized solar cell (DSSC). Defect-rich edge planes of bamboolike-structure multiwall CNTs facilitate the electron-transfer kinetics at the counter electrode-electrolyte interface, resulting in low charge-transfer resistance and an improved fill factor. In combination with a dye-sensitized TiO2 photoanode and an organic liquid electrolyte, a multiwall CNT counter-electrode DSSC shows 7.7% energy conversion efficiency under 1 sun illumination (100 mW/cm(2), air mass 1.5 G). The short-term stability test at moderate conditions confirms the robustness of CNT counter-electrode DSSCs.


Identification of A and B forms of monoamine oxidase in the iris-ciliary body, superior cervical ganglion, and pineal gland of albino rabbits.
The properties of monoamine oxidase activity in homogenates of the iris-ciliary body, superior cervical ganglion, and pineal gland of albino rabbits have been studied. Inhibition curves using specific inhibitors support the concept of A and B enzyme forms, with the following ratios of A/B activity: iris-ciliary body, 40/60; superior cervical ganglion, 90/10; pineal gland, 13/87. Experiments on enzymes from animals with superior cervical ganglionectomy indicate that both A and B forms in the iris-ciliary body have a predominantly extraneuronal location. No significant differences in activity were observed between iris-ciliary body preparations from normal and denervated animals with substrates specific for A or B forms, or with substrates deaminated by both A and B forms. With tryptamine as substrate the iris enzyme can be inhibited by a variety of common monoamine oxidase inhibitors. Topical application of the inhibitor pargyline lowers intraocular pressure in the normal rabbit eye but not in the sympathetically denervated eye. This observation and in vitro data suggest that the mechanism of action of pargyline is through the adrenergic system and not dependent upon intrinsic activity.


Integration of auxin and brassinosteroid pathways by Auxin Response Factor 2.
Plant form is shaped by a complex network of intrinsic and extrinsic signals. Light-directed growth of seedlings (photomorphogenesis) depends on the coordination of several hormone signals, including brassinosteroids (BRs) and auxin. Although the close relationship between BRs and auxin has been widely reported, the molecular mechanism for combinatorial control of shared target genes has remained elusive. Here we demonstrate that BRs synergistically increase seedling sensitivity to auxin and show that combined treatment with both hormones can increase the magnitude and duration of gene expression. Moreover, we describe a direct connection between the BR-regulated BIN2 kinase and ARF2, a member of the Auxin Response Factor family of transcriptional regulators. Phosphorylation by BIN2 results in loss of ARF2 DNA binding and repression activities. arf2 mutants are less sensitive to changes in endogenous BR levels, whereas a large proportion of genes affected in an arf2 background are returned to near wild-type levels by altering BR biosynthesis. Together, these data suggest a model where BIN2 increases expression of auxin-induced genes by directly inactivating repressor ARFs, leading to synergistic increases in transcription.


The Angiotensin-Converting Enzyme Inhibitor Lisinopril Mitigates Memory and Motor Deficits in a Drosophila Model of Alzheimer's Disease.
The use of angiotensin-converting enzyme inhibitors (ACEis) has been reported to reduce symptoms of cognitive decline in patients with Alzheimer's disease (AD). Yet, the protective role of ACEis against AD symptoms is still controversial. Here, we aimed at determining whether oral treatment with the ACEi lisinopril has beneficial effects on cognitive and physical functions in a Drosophila melanogaster model of AD that overexpresses the human amyloid precursor protein and the human β-site APP-cleaving enzyme in neurons. We found a significant impairment in learning and memory as well as in climbing ability in young AD flies compared to control flies. After evaluation of the kynurenine pathway of tryptophan metabolism, we also found that AD flies displayed a >30-fold increase in the levels of the neurotoxic 3-hydroxykynurenine (3-HK) in their heads. Furthermore, compared to control flies, AD flies had significantly higher levels of the reactive oxygen species (ROS) hydrogen peroxide in their muscle-enriched thoraces. Lisinopril significantly improved deficits in learning and memory and climbing ability in AD flies. The positive impact of lisinopril on physical function might be, in part, explained by a significant reduction in ROS levels in the thoraces of the lisinopril-fed AD flies. However, lisinopril did not affect the levels of 3-HK. In conclusion, our findings provide novel and relevant insights into the therapeutic potential of ACEis in a preclinical AD model.


Myeloma-related disorders in cats commonly present as extramedullary neoplasms in contrast to myeloma in human patients: 24 cases with clinical follow-up.
Myeloma-related disorders (MRD) are rare neoplasms of plasma cells. Published case reports describe a diversity of clinical presentations with confusing terminology and diagnostic criteria as a consequence of the assumption that MRD in cats are analogous to those in dogs or humans. The aim of the study was to describe clinical, clinicopathologic and imaging findings, response to treatment, survival and possible associations with other diseases or vaccination in a large case series. A priori hypotheses were that cats with MRD commonly present with extramedullary involvement and uncommonly have radiographic bone lesions, in contrast to human patients. Twenty-four cats with MRD confirmed by cytology or histopathology and immunohistochemistry. A multicenter retrospective study was performed. Two types of clinical presentation were observed. The first group (n = 17) had neoplasia involving abdominal organs, bone marrow, or both. All developed systemic clinical signs and paraproteinemia. Five of 7 cats that received chemotherapy improved clinically or had decreased serum globulin concentration (median survival, 12.3 months; range, 8.5-22 months). The second group comprised 7 cats with skin masses, 2 of which were paraproteinemic and developed rapidly worsening systemic signs. In cats without systemic signs, excision of the skin masses appeared to be associated with prolonged survival (up to 2.4 years). Cats with MRD commonly presented with extramedullary involvement (67%), versus humans with MRD (5%) (P < .001), and uncommonly presented with radiographic bone lesions (8%) versus humans with MRD (80%) (P < .001). Radiographic bone lesions are uncommon in cats with MRD and extramedullary presentation is common, relative to human myeloma.


Increase in intracellular calcium ion in smooth muscle cells induced by low-density lipoprotein.
It was investigated whether low-density lipoprotein (LDL) had effects on intracellular Ca2+ concentration in the smooth muscle cell (SMC). LDL promoted SMC proliferation and increased intracellular Ca2+ by a two-phase pattern, an initial peak and a following plateau. Each phase was suppressed by treatment with ryanodine or extracellular Ca(2+)-free buffer. This increase in intracellular Ca2+ was also suppressed by anti-LDL receptor antibody. Moreover, inositol triphosphate (IP3) was elevated with short-term LDL treatment. Since SMC proliferation is the most important event in atherosclerosis and LDL is one of the main risk factors, it was concluded that LDL might trigger SMC proliferation by increasing IP3 and intracellular Ca2+ through LDL receptor.


ASTEROID LIGHTCURVE ANALYSIS AT CS3-PALMER DIVIDE STATION: 2018 JULY-SEPTEMBER.
Lightcurves for 12 main-belt asteroids were obtained at the Center for Solar System Studies-Palmer Divide Station (CS3-PDS) from 2018 July-September. Analysis of a larger amplitude lightcurve in 2018 for 5175 Ables lead to new analysis and results for earlier apparitions. The Hungaria asteroid (37378) 2001 VU76 is possibly a super-fast rotator with a period and size that put it just above the so-called "spin barrier."


[The Role of Novel Agents in the Treatment of Soft Tissue Sarcoma].
Soft tissue sarcomas are rare disease and the development of efficacious drug is urgently needed. The challenge is continuing, and recently 2 drugs, trabectedin and eribulin, were approved in Japan. Both drugs were investigated in patients with liposarcoma or leiomyosarcoma in randomized phase III trials as compared to dacarbazine. Eribulin was superior in terms of overall survival and trabectedin was superior in terms of progression-free survival compared to dacarbazine. This article reviews the efficacy and safety of both drugs.


The Impact of Body Mass Index Upon the Efficacy of Adalimumab in Hidradenitis Suppurativa.
Elevated BMI in Hidradenitis Suppurativa is associated with decreased response to Adalimumab therapy. BMI is proposed to segregate distinct disease subtypes. It remains unresolved whether a threshold BMI exists above which increased dosages may provide clinical benefit. Individual patient data from 578 PIONEER Phase 3 participants were analyzed. Descriptive, multivariable regression analysis and receiver operating characteristic (ROC) curves were calculated to assess the relationship between BMI and clinical outcome measures using R v3.5.3. Participants in the overweight and obese BMI category had reduced odds (58 and 67%, respectively) of achieving HiSCR [OR = 0.42 (95%CI -0.19, 0.91) p = 0.03], [OR = 0.33 (95%CI 0.16, 0.67) p = 0.002] compared to participants with BMI < 25. Reduction in AN count and IHS4 score was not significantly associated. ROC analysis did not reveal any cut off value predictive of treatment outcome. No correlation between BMI and baseline disease activity or covariate interactions were identified. These findings suggest BMI is a significant covariate in the setting of lower baseline disease activity, supporting the concept of disease heterogeneity and differential therapeutic response to Adalimumab.


SUMO-activating SAE1 transcription is positively regulated by Myc.
Myc protein plays a fundamental role in regulation of cell cycle, proliferation, differentiation and apoptosis by modulating the expression of a large number of targets. Here we report the transactivation ability of the human Myc protein to activate the SUMO-activating enzyme SAE1 transcription. We found that Myc activates SAE1 transcription via direct binding to canonical E-Boxes sequences located close to the SAE1 transcription start site. A recent report has highlighted the crucial role of the SAE gene expression in Myc mediated oncogenesis. Our study adds new insight in this context since we show here that Myc directly activates SAE1 transcription, suggesting that Myc oncogenic activity which depends on SAE1 is ensured by Myc itself through direct binding and transcriptional activation of SAE1 expression.


Squishy nanotraps: hybrid cellulose nanocrystal-zirconium metallogels for controlled trapping of biomacromolecules.
A brick-and-mortar-like ultrasoft nanocomposite metallogel is formed by crosslinking cellulose nanocrystals (CNC) with ammonium zirconium carbonate (AZC) to trap and reconfigure dextran, a model biomacromolecule. The bricks (CNC) reinforce the metallogel, compete with dextran in reacting with AZC, and decouple long-time dextran dynamics from network formation, while the mortar (AZC) imparts bimodality to the dextran diffusion.


Primary disseminated leptomeningeal oligodendroglioma with 1p deletion. Case report.
The authors report the case of a 2-year-old boy with a primary, diffuse leptomeningeal oligodendroglioma in which the deletion of chromosome arm lp was identified by performing a fluorescence in situ hybridization (FISH) analysis. This previously healthy child initially presented with malaise, anorexia, nausea, vomiting, and macrocephaly. Imaging studies confirmed the presence of hydrocephalus, and a ventriculoperitoneal shunt was placed. The postoperative course was complicated by emesis, continued weight loss, and numerous seizurelike episodes. A contrast-enhanced magnetic resonance imaging study performed approximately 10 weeks postoperatively showed diffuse leptomeningeal thickening and enhancement without evidence of an intraparenchymal mass lesion. A right frontal lobe brain biopsy revealed a hypercellular proliferation of small oligodendroglioma-like cells, which occupied the leptomeninges diffusely and spared the underlying cortical gray matter. The tumor cells displayed prominent perinuclear clearing and had evenly spaced, uniformly round nuclei. Occasional mitotic figures were observed. Background vessels were thin and delicate, and there was no evidence of necrosis. The tumor cells showed strong immunoreactivity for S100 protein; the results of immunohistochemical staining were negative for glial fibrillary acidic protein, vimentin, epithelial membrane antigen, NeuN, and synaptophysin. The deletion of lp was demonstrated by FISH analysis; lq, 19p, and 19q were intact. This appears to be the first reported case of a primary diffuse leptomeningeal oligodendroglioma in which a lp deletion was identified.


Seroimmunity following vaccination in infants by an inactivated poliovirus vaccine prepared on Vero cells.
An inactivated poliovirus vaccine prepared from cultures of Vero cells has been tested on 61 infants from two to 11 months of age (mean age, 4.3 months) for tolerance and serologic potency. Three doses of vaccine were given one month apart at the same time that diphtheria-tetanus-pertussis vaccine was injected at another body site. Poliovirus-neutralizing antibody titers were measured before the first and third injections and one month after each. The titer was considered positive when the dilution was greater than or equal to 1:4. The tolerance has been good. Thirty-one infants were assessable for serologic efficacy; all had significant serologic responses after two injections of polio vaccine, regardless of the titer of maternally transmitted antibodies before the immunizations. The third injection did not significantly increase the antibody titer observed after the first two doses.


An Extract of Glycyrrhiza glabra (GutGard) Alleviates Symptoms of Functional Dyspepsia: A Randomized, Double-Blind, Placebo-Controlled Study.
A randomized, double-blind, placebo-controlled study was conducted to evaluate the efficacy of GutGard, an extract of Glycyrrhiza glabra, in patients with functional dyspepsia. The primary outcome variables of the study were the change in the severity symptoms and the global assessment of efficacy. The quality of life was evaluated as a secondary outcome measure. The patients received either placebo or GutGard (75 mg twice daily) for 30 days. Efficacy was evaluated in terms of change in the severity of symptoms (as measured by 7-point Likert scale), the global assessment of efficacy, and the assessment of quality of life using the short-form Nepean Dyspepsia Index. In comparison with placebo, GutGard showed a significant decrease (P ≤ .05) in total symptom scores on day 15 and day 30, respectively. Similarly, GutGard showed marked improvement in the global assessment of efficacy in comparison to the placebo. The GutGard group also showed a significant decrease (P ≤ .05) in the Nepean dyspepsia index on day 15 and 30, respectively, when compared to placebo. GutGard was generally found to be safe and well-tolerated by all patients. GutGard has shown significant efficacy in the management of functional dyspepsia.


Determination of Bortezomib in API Samples Using HPLC: Assessment of Enantiomeric and Diastereomeric Impurities.
A new, normal phase high performance liquid chromatography (NP-HPLC) method was developed for separation of Bortezomib (BZB) enantiomers and quantitative determination of (1S,2R)-enantiomer of BZB in active pharmaceutical ingredient (API) samples. The developed method was validated based on International Conference on Harmonisation (ICH) guidelines and it was proved to be accurate, precise and robust. The obtained resolution (RS) between the enantiomers was more than 2. The calibration curve for (1S,2R)-enantiomer was found to be linear in the concentration range of 0.24-5.36 mg/L with regression coefficient (R2) of 0.9998. Additionally, the limit of detection (LOD) and limit of quantification (LOQ) were 0.052 and 0.16 mg/L, respectively. Also, in this study, a precise, sensitive and robust gradient reversed-phase HPLC (RP-HPLC) method was developed and validated for determination of BZB in API samples. The detector response was linear over the concentration range of 0.26-1110.5 mg/L. The values of R2, LOD and LOQ were 0.9999, 0.084 and 0.25 mg/L, respectively. For both NP-HPLC and RP-HPLC methods, all of the RSD (%) values obtained in the precision study were <1.0%. System suitability parameters in terms of tailing factor (TF), number of theoretical plates (N) and RS were TF < 2.0, N > 2,000 and RS > 2.0. The performance of two common integration methods of valley to valley and drop perpendicular for drawing the baseline between two adjacent peaks were investigated for the determination of diastereomeric impurity (Imp-D) in the BZB-API samples. The results showed that the valley to valley method outperform the drop perpendicular method for calculation of Imp-D peak areas. Therefore, valley to valley method was chosen for peak integration.


Environmental enrichment improves cognition in aged Alzheimer's transgenic mice despite stable beta-amyloid deposition.
Environmental enrichment (EE) has been shown to improve cognitive performance and brain indices of cognition in normal mice and rats. Because the therapeutic potential of intensive, long-term EE to benefit patients with Alzheimer's disease (AD) has yet to be explored, the present study evaluated the effect of long-term EE on cognition in an animal model of AD, the APPsw transgenic mouse. Beginning at 16 months of age, APPsw mice were put into EE or standard housing for 4 months and then tested in four cognitive-based tasks (Morris maze, circular platform, platform recognition, and radial arm water maze) between 20 and 22 months of age. Our results indicate that long-term EE of aged APPsw mice results in global, overall improvement in cognitive function across these tasks without decreasing brain beta-amyloid (A beta) deposition. The results suggest that long-term EE/cognitive stimulation could provide cognitive stabilization or improvement to AD patients through mechanisms independent of A beta deposition and clearance.


Patient access to reimbursed biological disease-modifying antirheumatic drugs in the European region.
Background & Objectives: Biological disease-modifying antirheumatic drugs (bDMARDs) for the treatment of rheumatoid arthritis (RA) are not always accessible to all patients in accordance with international guidelines, partly owing to their high direct costs against a background of restricted healthcare budgets. This study compares the size of RA patient populations with access to reimbursed bDMARDs across 37 European countries, Russia, and Turkey, according to their treatment eligibility defined by European League Against Rheumatism (EULAR) recommendations and national reimbursement criteria. Methods: The size of the RA patient population eligible for bDMARD treatment was estimated in a population model using published RA epidemiological data and clinical criteria defined by 2013 EULAR recommendations along with national reimbursement criteria defined in a survey of the 39 countries in November 2015. Results: According to EULAR recommendations, 32% of the total RA population in the European region is eligible for bDMARD treatment. However, only an average 59% of this EULAR-eligible population remains eligible after applying national reimbursement criteria (from 86% in 'high access' to 13% in 'low-access' countries). Conclusion: Access to reimbursed bDMARDs remains unequal in the European region. As biosimilars of bDMARDs are introduced, changes in reimbursement criteria may increase access to bDMARDs and reduce this inequality.


Role of vaptans in the management of hydroelectrolytic imbalance in liver cirrhosis.
Ascites and hyponatremia are the most common complications in patients with liver cirrhosis and develop as a consequence of a severe impairment of liver function and portal hypertension. Increasing evidences support the central role of renal function alterations in the pathogenesis of hydroelectrolytic imbalances in cirrhotic patients, thus implying a dense cross-talk between liver and kidney in the systemic and splanchnic vascular homeostasis in such subjects. Since Arginin Vasopressin (AVP) hyperincretion occurs at late stage of cirrhosis and plays an important role in the development of refractory ascites, dilutional hyponatremia and finally hepato-renal syndrome, selective antagonists of AVP receptors V2 (vaptans) have been recently introduced in the therapeutic algorithm of advanced cirrhotic patients. Despite the promising results of earlier phase-two studies, randomized controlled trials failed to find significant results in terms of efficacy of such drugs both in refractory ascites and hyponatremia. Moreover, concerns on their safety profile arise, due to the number of potentially severe side effects of vaptans in the clinical setting, such as hypernatremia, dehydration, renal impairment, and osmotic demyelination syndrome. More robust data from randomized controlled trials are needed in order to confirm the potential role of vaptans in the management of advanced cirrhotic patients.


Low level of ochratoxin A affects genome-wide expression in kidney of pig.
Ochratoxin A (OTA) is a mycotoxin produced by fungus belonging to Aspergillus and Penicillium genra. The aim of the present paper was to investigate if a low concentration OTA has toxic effect in pigs. Twelve piglets were fed with a control or an OTA (0.05 mg/kg feed) contaminated diet. After 30 days, animals were slaughtered and samples of blood and kidney were used for further analyses. The mycotoxin analyses showed a significant higher (6.25 times) concentration of OTA in the kidney of OTA intoxicated piglets than in control ones. While OTA has no effect on the urea and creatinine concentration, the microarray analysis of the effect of OTA on genome wide expression in the kidney of intoxicated piglets, revealed that approximately 105 different transcripts were significantly altered. As shown by the microarray results, 0.05 mg/kg of OTA can principally interfere with: i) canonical pathways (CD28 Signaling in T Helper Cells, Role of NFAT in Regulation of the Immune Response, Relaxin Signaling, IL-1 Signaling) ii) molecular and cellular function (cellular movement cellular function and maintenance, cellular growth and proliferation cellular assembly and organization, cell death and survival) etc. However, alteration of renal and urological system development and function and renal necrosis predicted through Ingenuity Pathway Analysis (IPA) were not supported by clinical pathological data. In conclusion, OTA toxicity was found even at low concentration of toxin, correlated with the activation of immune response pathways, oxidative stress response and early carcinogenic events. This effect need to be further investigated and analyzed in the context of human health.


Reperfusion injury of the rat bladder is worse than ischemia.
Previous studies have demonstrated that in vivo and in vitro ischemia of the bladder results in decreased contractile responses. However, to our knowledge the effect of reperfusion following ischemia of the bladder is not known. Adult male rats were subjected to bilateral bladder ischemia and varying periods of reperfusion. In vivo ischemia was created for 4 hours by reversibly clamping the 2 vesical arteries for 4 hours. Reperfusion was produced by removing the clamps and allowing the animals to recover for 1 day, 1 week or 1 month after surgery. Following recovery bladders strips were studied using field stimulation (FS), carbachol and KCl. The maximal contractile response and rate of response generated were recorded digitally and analyzed. The maximal responses to FS, carbachol and adenosine triphosphate (ATP) were not decreased by 4-hour ischemia alone, whereas the response to KCl was decreased significantly. The contractile responses to FS and KCl were significantly decreased after 1 day and 1 week of reperfusion. Responses after 1 month of reperfusion were increased significantly compared with responses after 1 week of reperfusion. The responses to ATP were not affected by ischemia or reperfusion. The contractile response to KCl was significantly more sensitive to ischemia than the responses to carbachol, ATP or FS, whereas the contractile response to FS was significantly more sensitive to reperfusion than the other forms of stimulation. This study demonstrates clearly that injury by reperfusion following ischemia is more detrimental than the effects of ischemia alone and FS contraction is the most sensitive form of stimulation to reperfusion damage. This study also demonstrates the ability of the bladder to recover from ischemic and reperfusion injuries.


Detection of low-contrast objects: experimental comparison of single- and multi-detector row CT with a phantom.
To compare single-detector row computed tomography (CT) and multi-detector row CT by using an experimental phantom containing a contrast-detail modulus for detection of low-contrast structures to optimize acquisition protocols. The parameters milliampere seconds, reconstructed section thickness, and elementary collimation for multi-detector CT were varied for two pitches with single- and multi-detector CT. For objective assessment of image quality, contrast-to-noise ratio (CNR) was calculated for an 8-HU low-contrast 15-mm-diameter object. Subjective assessment of image quality was performed by means of visual detection of low-contrast objects of various sizes by four independent observers. For each acquisition protocol, the effective doses required to obtain the CNR thresholds allowing 100% detection of 5-, 7-, and 9-mm-diameter objects were compared at single- and multi-detector CT at comparable section sensitivity profile with analysis of variance. Significant correlation was found between CNR measurements and subjective object detection (r = 0.95, P <.05). CNRs of 1.0, 0.8, and 0.6 were required to detect 100% of the 5-, 7-, and 9-mm-diameter objects, respectively. For reconstructed section thickness of 5-10 mm, comparable x-ray doses were required with single- and multi-detector CT to detect objects. For reconstructed sections thinner than 5 mm, single- and multi-detector CT allowed detection of only the 7- and 9-mm-thick objects, but a higher x-ray dose was required for multi- than for single-detector CT (P <.05). Multi-detector CT is less effective than single-detector CT in detection of small low-contrast objects if sections thinner than 5 mm are used. Results for single- and multi-detector CT were similar for sections 5 mm or thicker.


The correlation between pancreatic dysfunction markers and selected indices of periodontitis.
Periodontitis is a major risk factor of systemic diseases with inflammatory etiology. Numerous studies have established the connection between periodontal condition and diabetes, but there are no reports in the literature on the relationship between periodontitis and other pancreas conditions. The activity of pancreatic enzymes is an important parameter of pancreatic damage, and is also a diagnostic marker of acute and chronic pancreatitis, and the bleeding index determines the periodontitis activity. To date, the periodontal status in both of the above-mentioned conditions has not been examined. The objective of the study was to provide a clinical evaluation of oral cavity hygiene and the condition of periodontal tissues in patients diagnosed with pancreatic adenocarcinoma or chronic pancreatitis and in the control group, and to assess the correlation between the activity of periodontitis and the concentration of glycated hemoglobin HbA1c, lipase activity and pancreatic amylase in serum from the examined groups. The serum activity levels of amylase, lipase and HbA1c concentration were correlated with periodontitis activity markers in patients diagnosed with chronic pancreatitis (n = 41), pancreatic cancer (n = 29) and in the control group (n = 50). In the group with chronic pancreatitis, we have found a positive association between the bleeding on probing (BOP) and the amylase activity (r = 0.64) as well as the lipase (r = 0.62; p < 0.05). The patients diagnosed with pancreatic cancer evinced a higher value of the inflammatory response index, namely 1.51, than the other studied groups (H = 24.94; p = 0.01). Patients diagnosed with chronic pancreatitis evinced the highest periodontitis activity indices: BOP: 62.53% (H = 61.31; p = 0.01) and probing depth (PD): 4.14 ±0.89 mm (H = 22.43; p < 0.0001). The study showed that periodontitis in patients with pancreatic cancer is independent of the state of oral hygiene. In the group of patients with chronic pancreatitis, the observed positive correlation between the bleeding index and the enzyme activity suggests interaction between the examined diseases.


c-Myc/Max heterodimers bind cooperatively to the E-box sequences located in the first intron of the rat ornithine decarboxylase (ODC) gene.
The oncoprotein c-Myc plays an important role in cell proliferation, transformation, inhibition of differentiation and apoptosis. These functions most likely result from the transcription factor activity of c-Myc. As a heterodimer with Max, the c-Myc protein binds to the E-box sequence (CACGTG), which is also recognized by USF dimers. In order to test differences in target gene recognition of c-Myc/Max, Max and USF dimers, we compared the DNA binding characteristics of these proteins in vitro using vaccinia viruses expressing full-length c-Myc and Max proteins. As expected, purified c-Myc/max binds specifically to a consensus E-box. The optimal conditions for DNA binding by either c-Myc/Max, Max or USF dimers differ with respect to ionic strength and Mg2+ ion concentration. Most interestingly, the c-Myc/Max complex binds with a high affinity to its natural target, the rat ODC gene, which contains two adjacent, consensus E-boxes. High affinity binding results from teh ability of c-Myc/Max dimers to bind cooperatively to these E-boxes. We propose that differential cooperative binding by E-box binding transcription factors could contribute to target gene specificity.


A Discrete, Boron-Containing Triangular Triradical.
A neutral boron-containing triangular triradical based on a triptycene derivative has been designed and synthesized. Its structure, bonding and physical property have been studied by EPR spectroscopy, SQUID magnetometry and single crystal X-ray diffraction, as well as theoretical calculations. The triradical has a series of isosceles triangle conformations in the solution due to the Jahn-Teller distortion, leading to the splitting of the two low-lying doublet states. This factor together with negligible spin-orbit coupling (SOC) of composing light atoms quenches the spin frustration. The work represents a rare example of a neutral through-space triangular triradical.


Inhibition of eukaryotic tRNA transcription by potential Z-DNA sequences.
The effect of d(CA/TG)n DNA segments on tRNA transcription has been examined. Alternating purine-pyrimidine tracts were cloned at a long distance from, adjacent to, or within the coding sequence of a tRNAPro gene from Caenorhabditis elegans and shown to be able to assume the A-DNA conformation in vitro in physiological salt concentrations. The transcriptional level of these constructs was compared to that of normal tDNAPro by micro-injection into Xenopus laevis oocytes. Our results show a strong inhibitory effect by potential Z-DNA sequences only when these are placed in the flanking regions of the gene or when they are located between the elements (Box A and Box B) of the split promoter. Transcription was studied in parallel with supercoiled and linear DNA molecules carrying a d(CA/TG) stretch 124-bp long in front of the tRNAPro gene. The results show the same level of inhibition of Po/III transcription regardless of the topological status of the injected DNA.


Bone banks and allografts in community practice.
The increasing volume of orthopaedic reconstructive procedures requiring replacement of bone stock justifies the initiation of programs of bone banking in community hospitals. Provided that strict criteria are followed to assure rigorous screening of donor bone and the reliable preservation of bone graft material, community banking is safe and cost-effective. Banked allograft bone can be used successfully in a wide variety of orthopaedic procedures performed in community hospitals. In general, the best uses are filling bone cavities, buttressing, and augmenting the quantity of autograft bone. In revision reconstructive surgery of the hip, bank bone is used to replace bone stock in protrusio, acetabular dysplasia, and proximal femoral deficiency. The best and most common indication for the use of bank bone in tumor surgery is after curettage or excision of benign lesions. Allografts may be used to reconstruct bony defects after excision of malignant tumors and in the surgical treatment of metastatic disease. These instances require larger bone bank facilities than those commonly available in a community hospital setting. Medicolegal considerations related to bone banking and the use of allografts in community practice include the regulatory requirements outlined in the UAGA, questions concerning negligence liability, and theories of strict product liability. Overall, good medical practice and obtaining informed consents will minimize legal risks related to bone banking and transplantation in a community setting.


Formation of polyphenyl chains through hierarchical reactions: Ullmann coupling followed by cross-dehydrogenative coupling.
From an interplay of UHV-STM imaging and DFT calculations, we have illustrated on-surface formation of polyphenyl chains through a hierarchical reaction pathway involving two different kinds of reactions (Ullmann coupling and cross-dehydrogenative coupling), which will provide a deeper understanding of on-surface chemical reactions and an alternative and efficient strategy to fabricate desired surface molecular nanostructures.


Protective effect of the PAF antagonist BN 52021 in an experimental renal warm ischemia model.
Platelet activating factor is involved in warm ischemic damage. We studied the effect of the PAF receptor antagonist BN 52021 in an experimental model of 60 min of renal warm ischemia in which the left kidney was flushed with Euro-Collins solution and a right nephrectomy was performed. Eighty Wistar rats were divided into a sham-operated group, two control groups, and four study groups, according to the dosage and route of BN 52021 administration. BN 52021 was used in the flush solution at concentrations of 0.1 and 0.5 mg/ml, or intravenously prior to ischemia at 5 and 10 mg/kg body weight. Creatinine clearance per 100 g body weight, fractional sodium excretion, and conventional histology were studied. Rats that received BN 52021 intravenously showed a significantly higher creatinine clearance than controls. Intravenous BN 52021 produced a higher acceleration of renal function recovery at 10 mg/kg than at 5 mg/kg body weight. Conventional histology was better in animals that received BN 52021 at 10 mg/kg body weight than in controls. Addition of BN 52021 to Euro-Collins flushing solution showed no protective effect. We conclude that intravenous BN 52021 shows a renal protective effect against warm ischemia.


Role of interleukin-6 in uncoupling of bone in vivo in a human squamous carcinoma coproducing parathyroid hormone-related peptide and interleukin-6.
OCC tumor has been established from a human squamous carcinoma associated with humoral hypercalcemia of malignancy (HHM) and shown to overproduce parathyroid hormone-related peptide (PTHrP) and cause aggressive hypercalcemia when implanted into nude rats. In the present study, we have demonstrated by reverse transcription-polymerase chain reaction and Northern blot analysis that OCC tumor also overexpressed interleukin 6 (IL-6) mRNA and that tumor-bearing animals exhibited a marked increase in plasma IL-6 as well as PTHrP concentrations. When a monoclonal antibody against human IL-6 was injected to block the activities of tumor-derived IL-6, bone loss in tumor-bearing animals was significantly prevented. Quantitative bone histomorphometric analysis revealed that treatment with anti-IL-6 antibody caused a substantial decrease in both osteoclast number and eroded surface (as parameters of bone resorption) and also a significant increase in the mineral apposition rate, but little effect on the osteoblastic surface. These results provide in vivo evidence suggesting that in tumors coproducing IL-6 and PTHrP, IL-6 is involved not only in the acceleration of osteoclastic bone resorption but also, at least in part, in the suppression of osteoblastic functions in HHM syndrome.


EVOLUTION AND COADAPTATION OF THERMOREGULATORY BEHAVIOR AND WING PIGMENTATION PATTERN IN PIERID BUTTERFLIES.
This paper addresses the question of how the relationship between morphological structure and functional performance differs in related groups of organisms. I describe the relationship between a suite of phenotypic characters (behavioral posture and the pattern of wing pigmentation) and one function of these characters (thermoregulatory performance) for two groups of butterflies in the family Pieridae, focusing on how behavior and wing pattern interact to affect specific aspects of thermoregulation. Using both natural and experimentally created variation in wing-melanization patterns, I develop and test a series of predictions about the relations among thermoregulatory posture, melanization pattern, body temperature, and flight activity. Results show that increased melanization in different wing regions has positive, negative, or neutral effects in increasing body temperature of Pieris butterflies. The angle of the wings used during basking alters the relative importance of different modes of heat transfer and thereby determines the contribution of different dorsal wing regions to thermoregulation. Experimentally increased dorsal melanization can either increase or decrease the onset of flight activity and can directly alter thermoregulatory posture. For Pieris, dorsal melanization affects basking and flight, while ventral melanization primarily affects overheating. These results are used to generate a functional map relating melanization pattern to thermoregulatory performance in Pieris. Reflectance-basking posture, white background color, and melanization pattern represent coadapted characters in Pieris that interact to determine thermoregulatory performance. The differences in thermoregulatory posture and background color between pierid butterflies in the subfamilies Pierinae and Coliadinae have led to a reorganization and partial reversal of the thermoregulatory effects of melanization pattern. I suggest that this change in the physical mechanism of thermoregulatory adaption in pierids has qualitatively altered the nature of selection on wing-melanization pattern.


Antigen capsid-display on human adenovirus 35 via pIX fusion is a potent vaccine platform.
Durable protection against complex pathogens is likely to require immunity that comprises both humoral and cellular responses. While heterologous prime-boost regimens based on recombinant, replication-incompetent Adenoviral vectors (AdV) and adjuvanted protein have been able to induce high levels of concomitant humoral and cellular responses, complex manufacturing and handling in the field may limit their success. To combine the benefits of genetic and protein-based vaccination within one vaccine construct and to facilitate their use, we generated Human Adenovirus 35 (HAdV35) vectors genetically encoding a model antigen based on the Plasmodium falciparum (P. falciparum) circumsporozoite (CS) protein and displaying a truncated version of the same antigen (CSshort) via protein IX on the capsid, with or without a flexible glycine-linker and/or a 45Å-spacer. The four tested pIX-antigen display variants were efficiently incorporated and presented on the HAdV35 capsid irrespective of whether a transgene was encoded or not. Transgene-expression and producibility of the display-/expression vectors were not impeded by the pIX-display. In mice, the pIX-modified vectors induced strong humoral antigen-specific immunity that increased with the inclusion of the linker-/spacer molecules, exceeded the responses induced by the genetic, transgene-expressing HAdV35 vector, and surpassed recombinant protein in potency. In addition, the pIX- display/expression vectors elicited high antigen-specific cellular immune responses that matched those of the genetic HAdV35 vector expressing CS. pIX-modified display-/expression HAdV vectors may therefore be a valuable technology for the development of vaccines against complex pathogens, especially in resource-limited settings.


Determining the effects of sperm activation in anuran cloaca on motility and DNA integrity in Epidalea calamita (Bufonidae).
The effect of time inside the animal's cloaca on sperm quality after hormone-induced spermiation is unknown. However, this knowledge is critical for the development of assisted reproductive biotechnologies in amphibians. Out-of-season spermatozoa were collected from Epidalea calamita for 4h after injection of 10IU g-1 human chorionic gonadotrophin either hourly (Group I (n =10); four samples per male) or every 2h (Group II (n =9); two samples per male). Sperm samples were assessed for motility and DNA integrity using the sperm chromatin dispersion (SCD) test and the sperm chromatin structure assay (SCSA). The collection strategy affected total motility (mean (±s.e.m.) 84.4±9.9% vs 73.6±16.7% in Group I and II respectively; P =0.014) and the sperm motility index (67.6±17.7% vs 57.6±16.3% in Group I and II respectively; P =0.034). There was a significant effect of the male in Group II, but not in Group I. In Group I, the quality of the first samples collected was lower than that of samples collected thereafter (P ≤ 0.032). No significant correlations were found between the results of the SCD test and SCSA, showing that these techniques provide different information in this species. In conclusion, collecting spermatozoa every hour resulted in better sperm quality and may be more efficient. However, the between-male differences were considerable and collection of spermatozoa at just 1h after hormone treatment produced lower-quality spermatozoa.


Quantitative determination of thermally derived off-flavor compounds in milk using solid-phase microextraction and gas chromatography.
Many volatile compounds generated during the thermal processing of milk have been associated with cooked, stale, and sulfurous notes in milk and are considered as off-flavor by most consumers. A headspace solid-phase microextraction (HS-SPME)/gas chromatographic technique for the quantitative analysis of thermally derived off-flavor compounds was developed in this study. The extraction temperature, time, and sample amount were optimized using a randomized 2(3) central composite rotatable design with 2 central replicates and 2 replicates in each factorial point along with response surface methodology. Calibration curves were constructed in milk using the standard addition technique, and then used to quantify 20 off-flavor compounds in raw, pasteurized, and UHT milk samples with various fat contents. The concentrations of these volatiles in raw and pasteurized milk samples were not significantly different. However, dimethyl sulfide, 2-hexanone, 2-heptanone, 2-nonanone, 2-undecanone, 2-methylpropanal, 3-methylbutanal, heptanal, and decanal were found at higher concentrations in UHT milk as compared with raw and pasteurized milk samples. In addition, the concentration of methyl ketones was greater in UHT milk with higher fat content. The calculated odor activity values suggested that 2,3-butanedione, 2-heptanone, 2-nonanone, 2-methylpropanal, 3-methylbutanal, nonanal, decanal, and dimethyl sulfide could be important contributors to the off-flavor of UHT milk. The HS-SPME technique developed in this study is accurate and relatively simple, and can be used for the quantification of thermally derived off-flavor compounds in milk.