Demonstration of frequent occurrence of clonal T cells in the peripheral blood of patients with primary cutaneous T-cell lymphoma.
Clonal T cells have been demonstrated in skin lesions of all stages of cutaneous T-cell lymphomas (CTCLs). However, there are conflicting data regarding the CTCL stage at which dissemination of clonal cells into peripheral blood occurs. Although the multifocal occurrence of cutaneous CTCL lesions and T-cell recirculation suggest an early appearance of neoplastic cells in the blood, circulating clonal T cells have only been detected in advanced stages. We investigated their occurrence by a highly sensitive polymerase chain reaction (PCR) assay amplifying T-cell receptor gamma rearrangements and subsequent heteroduplex temperature gradient gel electrophoresis (HD-TGGE) of the amplification products. Circulating clonal T cells were found in 26 of 45 patients with mycosis fungoides (MF), six of seven with Sezary's syndrome (SS), 10 of 13 pleomorphic CTCLs, and three of four unclassified CTCLs. Corresponding skin specimens carried clonal T cells in 29 of 40 MF, three of four SS, 12 of 12 pleomorphic, and two of two unclassified CTCL patients. Except for the blood specimen of a psoriatic patient, all samples of 60 controls (psoriasis vulgaris, atopic dermatitis, and healthy volunteers) revealed polyclonal amplification products. In 30 of 32 CTCL patients carrying a clonal rearrangement in blood and skin, identity of both clones was indicated by HD-TGGE and confirmed by sequencing six of these cases. We found an unexpected high frequency of identical clonal T cells in peripheral blood and skin of CTCL patients, including early stages of MF. This supports the concept of an early systemic disease in CTCL and raises new questions concerning the pathogenesis.


Spatiotemporal Expression of Anticoagulation Factor Antistasin in Freshwater Leeches.
Antistasin, which was originally discovered in the salivary glands of the Mexican leech Haementeria officinalis, was newly isolated from Helobdella austinensis. To confirm the temporal expression of antistasin during embryogenesis, we carried out semi-quantitative RT-PCR. Hau-antistasin1 was uniquely expressed at stage 4 of the cleavage and was strongly expressed in the late stages of organogenesis, as were other antistasin members. In order to confirm the spatial expression of antistasin, we performed fluorescence in situ hybridization in the late stages of organogenesis. The expression of each antistasin in the proboscis showed a similar pattern and varied in expression in the body. In addition, the spatial expression of antistasin orthologs in different leeches showed the possibility of different function across leech species. Hau-antistasin1 was expressed in the same region as hedgehog, which is a known mediator of signal transduction pathway. Hau-antistasin1 is probably a downstream target of Hedgehog signaling, involved in segment polarity signal pathway.


Trichostatin A (TSA) sensitizes the human prostatic cancer cell line DU145 to death receptor ligands treatment.
The human prostatic carcinoma cell line DU145 has previously been found to be resistant to treatment with TNF-family ligands. However, TRAIL, TNF-alpha and anti-Fas antibodies (Ab) treatment in combination with the histone deacetylase inhibitor Trichostatin A (TSA) converted the phenotype of DU145 from resistant to sensitive. TSA induced 15% cell death but simultaneous treatment with TRAIL, TNF-alpha and anti-Fas Ab resulted in 55%, 70% and 40% cell death, respectively. Simultaneous treatment did not increase the level of TSA-induced histone acetylation, but induced the release of acetylated histones from chromatin into the cytosol. This release was caspase dependent since it was abrogated by Z-VAD-fmk. In addition, treatment with TSA induced caspase-9 activation and resulted in the release of cytochrome c and Smac/DIABLO from mitochondria. To further investigate the role of caspase-9 in TSA-mediated apoptosis we used two different approaches: (1) cells were pretreated with the caspase-9 inhibitor Z-LEHD-fmk, and (2) cells were transfected with a dominant-negative form of caspase-9. Both approaches gave similar results: cells became resistant to treatment with TSA. These data indicate that TSA mediates its effect via the mitochondrial pathway. This was confirmed by examining DU145 overexpressing Bcl-2. These transfectants were resistant to TSA treatment. Taken together, our data shows that only simultaneous treatment with TNF-family ligands and TSA in DU145 resulted in caspase activity sufficient to induce apoptosis. The combination of TSA and TNF-family ligands could potentially be the basis for the treatment of prostate cancer.


Insight into invertebrate defensin mechanism of action: oyster defensins inhibit peptidoglycan biosynthesis by binding to lipid II.
Three oyster defensin variants (Cg-Defh1, Cg-Defh2, and Cg-Defm) were produced as recombinant peptides and characterized in terms of activities and mechanism of action. In agreement with their spectrum of activity almost specifically directed against Gram-positive bacteria, oyster defensins were shown here to be specific inhibitors of a bacterial biosynthesis pathway rather than mere membrane-active agents. Indeed, at lethal concentrations, the three defensins did not compromise Staphylococcus aureus membrane integrity but inhibited the cell wall biosynthesis as indicated by the accumulation of the UDP-N-acetylmuramyl-pentapeptide cell wall precursor. In addition, a combination of antagonization assays, thin layer chromatography, and surface plasmon resonance measurements showed that oyster defensins bind almost irreversibly to the lipid II peptidoglycan precursor, thereby inhibiting the cell wall biosynthesis. To our knowledge, this is the first detailed analysis of the mechanism of action of antibacterial defensins produced by invertebrates. Interestingly, the three defensins, which were chosen as representative of the oyster defensin molecular diversity, bound differentially to lipid II. This correlated with their differential antibacterial activities. From our experimental data and the analysis of oyster defensin sequence diversity, we propose that oyster defensin activity results from selective forces that have conserved residues involved in lipid II binding and diversified residues at the surface of oyster defensins that could improve electrostatic interactions with the bacterial membranes.


Computer identification of musical instruments using pattern recognition with cepstral coefficients as features.
Cepstral coefficients based on a constant Q transform have been calculated for 28 short (1-2 s) oboe sounds and 52 short saxophone sounds. These were used as features in a pattern analysis to determine for each of these sounds comprising the test set whether it belongs to the oboe or to the sax class. The training set consisted of longer sounds of 1 min or more for each of the instruments. A k-means algorithm was used to calculate clusters for the training data, and Gaussian probability density functions were formed from the mean and variance of each of the clusters. Each member of the test set was then analyzed to determine the probability that it belonged to each of the two classes; and a Bayes decision rule was invoked to assign it to one of the classes. Results have been extremely good and are compared to a human perception experiment identifying a subset of these same sounds.


Colostrum and milk pasteurization improve health status and decrease mortality in neonatal calves receiving appropriate colostrum ingestion.
The objective of the study was to evaluate if on-farm heat treatment of colostrum and bulk tank milk can improve calf health status and morbidity and mortality rates during the first 21d of life in neonatal Holstein calves receiving appropriate colostrum ingestion. A total of 587 calves were randomly assigned to 2 groups of males and females over 18mo. The nonpasteurized group (n=287, 143 males and 144 females) was fed frozen (-20°C) colostrum (6-8L during the first 12h of life) that was previously reheated up to 40°C. They were also fed refrigerated (4°C) raw milk from the bulk tank that was also reheated up to 40°C (1.8L every 12h). The pasteurized group (n=300, 150 males and 150 females) was also fed colostrum and milk, but both were pasteurized before freezing. Blood samples were drawn from all calves to obtain serum at 2 to 5d of life. Serum total protein (g/dL) was determined using a commercially available refractometer. Colostrum and milk underwent routine bacteriological analysis to determine total plate counts (cfu/mL) and total coliform counts (cfu/mL). All the calves underwent clinical examination every 24h during the first 21d of life. Every day, calves were clinically diagnosed either as being healthy or suffering from respiratory disease, neonatal calf diarrhea, or suffering other diseases. On-farm heat treatment for colostrum and milk reduced total plate counts and total coliform counts between 1 and 2 log10. Pasteurization of colostrum and milk significantly decreased the morbidity and mortality (5.2 and 2.8%) in comparison with calves receiving nonpasteurized colostrum and milk (15.0 and 6.5%), respectively, during the first 21d of life, even in animals receiving appropriate colostrum ingestion.


A collection of annotated and harmonized human breast cancer transcriptome datasets, including immunologic classification.
The increased application of high-throughput approaches in translational research has expanded the number of publicly available data repositories. Gathering additional valuable information contained in the datasets represents a crucial opportunity in the biomedical field. To facilitate and stimulate utilization of these datasets, we have recently developed an interactive data browsing and visualization web application, the Gene Expression Browser (GXB). In this note, we describe a curated compendium of 13 public datasets on human breast cancer, representing a total of 2142 transcriptome profiles. We classified the samples according to different immune based classification systems and integrated this information into the datasets. Annotated and harmonized datasets were uploaded to GXB. Study samples were categorized in different groups based on their immunologic tumor response profiles, intrinsic molecular subtypes and multiple clinical parameters. Ranked gene lists were generated based on relevant group comparisons. In this data note, we demonstrate the utility of GXB to evaluate the expression of a gene of interest, find differential gene expression between groups and investigate potential associations between variables with a specific focus on immunologic classification in breast cancer. This interactive resource is publicly available online at: http://breastcancer.gxbsidra.org/dm3/geneBrowser/list.


Disruption of the utrophin-actin interaction by monoclonal antibodies and prediction of an actin-binding surface of utrophin.
Monoclonal antibody (mAb) binding sites in the N-terminal actin-binding domain of utrophin have been identified using phage-displayed peptide libraries, and the mAbs have been used to probe functional regions of utrophin involved in actin binding. mAbs were characterized for their ability to interact with the utrophin actin-binding domain and to affect actin binding to utrophin in sedimentation assays. One of these antibodies was able to inhibit utrophin-F-actin binding and was shown to recognize a predicted helical region at residues 13-22 of utrophin, close to a previously predicted actin-binding site. Two other mAbs which did not affect actin binding recognized predicted loops in the second calponin homology domain of the utrophin actin-binding domain. Using the known three-dimensional structure of the homologous actin-binding domain of fimbrin, these results have enabled us to determine the likely orientation of the utrophin actin-binding domain with respect to the actin filament.


Variation of a benthic heterotrophic bacteria community with different respiratory metabolisms in Coyuca de Benítez coastal lagoon (Guerrero, Mexico).
The fluctuations of the number, biomass and composition of the heterotrophic community were studied daily for two days, according to depth, pH, Eh, O2 and organic carbon concentration within a zone of the canal between the Coyuca de Benitez lagoon (Guerrero, Mexico) and the coastal waters. At the three moments of the day studied (6 am, 2 pm and 10 pm), the oxygen concentrations in the overlying water and in the superficial sediment layer were near air-saturation in the diurnal samplings (582 microM at 6 am and 665 microM at 2 pm), and sub-satured during the night (158 microM). In the sediments, the models of vertical distribution of Eh and organic carbon distributions were very irregular due to the bio-perturbation of the benthic, meio- and macrofauna, whose activity allows the superficial organic carbon to migrate towards sediment deeper layers. Vertical distribution of the different viable bacteria populations seems to be related to the hydrodynamic patterns of the communicating canal and sediments heterogeneity. In the sediment column, the heterotrophic bacteria total number varied from 6.8 to 20.3 x 108 cells cm(-3). The highest heterotrophic bacterial biomass values were encountered during the diurnal samplings (39.2 microgC.l(-1) at 6 am and 34.4 microgC.(l(-1) at 2 pm) and the lowest during the night (9.7 microgC.l(-1). The fluctuations of viable heterotrophic bacteria populations with different respiratory metabolisms (aerobic, microaerophilic and anaerobic) can be explained by the existence of suboxic microniches that appear when particles of sediment are resuspended due to the water circulation and the benthic infauna excavating activity, that allows the supernatant water oxygen to penetrate through its galleries towards deeper sediment zones. The statistical analysis (Multiple lineal regression model r2 > or = 0.5) showed that the on the whole, the hydrological parameters are not influence over the bacterial number and bacterial biomass distribution (r2 < or = 0.5), Nevertheless, the variations of the heterotrophic bacteria community observed in the two days sampling, seem to be governed (with F-values of 0.6 to 0.9) by the irregular flows of bio-available organic material and the sediment porosity.


Two-electron HCl to H2 photocycle promoted by Ni(II) polypyridyl halide complexes.
Photochemical HX splitting requires the management of two protons and the execution of multielectron photoreactions. Herein, we report a photoinduced two-electron reduction of a polypyridyl Ni(II) chloride complex that provides a route to H2 evolution from HCl. The excited states of Ni complexes are too short to participate directly in HX activation, and hence, the excited state of a photoredox mediator is exploited for the activation of HX at the Ni(II) center. Nanosecond transient absorption (TA) spectroscopy has revealed that the excited state of the polypyridine results in a photoreduced radical that is capable of mediating HX activation by producing a Ni(I) center by halogen-atom abstraction. Disproportionation of the photogenerated Ni(I) intermediate affords Ni(II) and Ni(0) complexes. The Ni(0) center is capable of reacting with HX to produce H2 and the polypyridyl Ni(II) dichloride, closing the photocycle for H2 generation from HCl.


Peptides containing glutamine repeats as substrates for transglutaminase-catalyzed cross-linking: relevance to diseases of the nervous system.
Many proteins contain reiterated glutamine residues, but polyglutamine of excessive length may result in human disease by conferring new properties on the protein containing it. One established property of a glutamine residue, depending on the nature of the flanking residues, is its ability to act as an amine acceptor in a transglutaminase-catalyzed reaction and to make a glutamyl-lysine cross-link with a neighboring polypeptide. To learn whether glutamine repeats can act as amine acceptors, we have made peptides with variable lengths of polyglutamine flanked by the adjacent amino acid residues in the proteins associated with spinocerebellar ataxia type 1 (SCA1), Machado-Joseph disease (SCA3), or dentato-rubral pallidoluysian atrophy (DRPLA) or those residues adjacent to the preferred cross-linking site of involucrin, or solely by arginine residues. The polyglutamine was found to confer excellent substrate properties on any soluble peptide; under optimal conditions, virtually all the glutamine residues acted as amine acceptors in the reaction with glycine ethyl-ester, and lengthening the sequence of polyglutamine increased the reactivity of each glutamine residue. In the presence of transglutaminase, peptides containing polyglutamine formed insoluble aggregates with the proteins of brain extracts and these aggregates contained glutamyl-lysine cross-links. Repeated glutamine residues exposed on the surface of a neuronal protein should form cross-linked aggregates in the presence of any transglutaminase activated by the presence of Ca2+.


Biliary reconstruction in right lobe living-donor liver transplantation: Comparison of different techniques in 321 recipients.
To assess the incidence of biliary complications after right lobe living-donor liver transplantation (LDLT) in patients undergoing duct-to-duct choledochocholedochostomy or Roux-en-Y choledochojejunostomy reconstruction. Biliary tract complications remain one of the most serious morbidities following liver transplantation. No large series has yet been carried out to compare the 2 techniques in LDLT. This study undertook a retrospective assessment of the relation between the method of biliary reconstruction used and the complications reported. Between February 1998 and June 2004, 321 patients received right lobe LDLT. Biliary reconstruction was achieved with Roux-en-Y choledochojejunostomy in 121 patients, duct-to-duct choledochocholedochostomy in 192 patients, and combined Roux-en-Y and duct-to-duct choledochocholedochostomy in 8 patients. The number of graft bile duct and anastomosis, mode of anastomosis, use of stent tube, and management of biliary complications were analyzed. The overall incidence of biliary complications was 24.0%. Univariate analysis revealed that hepatic artery complications, cytomegalovirus infections, and blood type incompatibility were significant risk factors for biliary complications. The respective incidence of biliary leakage and stricture were 12.4% and 8.3% for Roux-en-Y, and 4.7% and 26.6% for duct-to-duct reconstruction. Duct-to-duct choledochocholedochostomy showed a significantly lower incidence of leakage and a higher incidence of stricture; however, 74.5% of the stricture was managed with endoscopic treatment. The authors found an increase in the biliary stricture rate in the duct-to-duct choledochocholedochostomy group. Because of greater physiologic bilioenteric continuity, less incidence of leakage, and easy endoscopic access, duct-to-duct reconstruction represents a feasible technique in right lobe LDLT.


The peak frequency of motor-related gamma oscillations is modulated by response competition.
Movement execution generally occurs in an environment with numerous distractors, and requires the selection of a motor plan from multiple possible alternatives. However, the impact of such distractors on cortical motor function during movement remains largely unknown. Previous studies have identified two movement-related oscillatory responses that are critical to motor planning and execution, and these responses include the peri-movement beta event-related desynchronization (ERD) and the movement-related gamma synchronization (MRGS). In the current study, we investigate how visual distractors cuing alternative movements modulate the beta ERD and MRGS responses. To this end, we recorded magnetoencephalography (MEG) during an arrow-based version of the Eriksen flanker task in 42 healthy adults. All MEG data were transformed in to the time-frequency domain and the beta ERD and MRGS responses were imaged using a beamformer. Virtual sensors (voxel time series) were then extracted from the peak voxels of each response for the congruent and incongruent flanker conditions separately, and these data were examined for conditional differences during the movement. Our results indicated that participants exhibited the classic "flanker effect," as they responded significantly slower during incongruent relative to congruent trials. Our most important MEG finding was a significant increase in the peak frequency of the MRGS in the incongruent compared to the congruent condition, with no conditional effect on response amplitude. In addition, we found significantly stronger peri-movement beta ERD responses in the ipsilateral motor cortex during incongruent compared to congruent trials, but no conditional effect on frequency. These data are the first to show that the peak frequency of the MRGS response is linked to the task parameters, and varies from trial to trial in individual participants. More globally, these data suggest that beta and gamma oscillations are modulated by visual distractors causing response competition.


miR-138 suppressed the progression of osteoarthritis mainly through targeting p65.
MicroRNAs are reported to play key roles in regulating the main risk factors for osteoarthritis (OA) chondrogenesis. In the current study, we focused on miR-138, which has never been explored in OA. The expression of miR-138 and p65 was explored in the cartilage tissues of OA patients and compared with those of normal controls. We then explored the effects of miR-138 on NF-κB signaling activation in both human OA chondrocytes and chondrogenic SW1353 cells in the presence of 10 nM TNFα. The protein levels of p65, COX-2 and IL6 were determined using Western blot analysis. To validate the target gene of miR-138, a dual luciferase reporter assay was performed. The level of miR-138 was markedly reduced in the OA cartilage tissues compared with those of normal controls. Real-time PCR analysis demonstrated that the level of miR-138 decreased after TNFα treatment for 3, 6, and 12 h in the normal chondrocytes and OA chondrocytes. Furthermore, overexpression of miR-138 suppressed the protein levels of p65, COX-2 and IL6 in human OA chondrocytes and chondrogenic SW1353 cells. A dual luciferase reporter assay demonstrated that miR-138 significantly suppressed the relative luciferase activity of pmirGLO-p65-3'UTR. More importantly, treatment with TNFα significantly enhanced the protein levels of p65, COX-2 and IL6. However, overexpression of miR-138 could partially abolish such effects. We demonstrated that reduced miR-138 expression enhanced the destruction of the cartilage tissues among OA patients, mainly through targeting p65.


[Contributions from the critical leisure field to the health promotion].
The studies about leisure for health promotion still tend to choose the active body occupation in the free-time (leisure activities), revealing the influence of the functionalist way of thinking, which trying to reduce the links between society and health-disease process, undoubtedly do not keep with the purpose of population health promotion. Focusing on this idea, and keeping in mind the premise that in the Brazilian physical training there are different opinions since the earliest 80s which try to achieve the purpose to avoid the ideas of the functionalist way of thinking. However, those opinions are almost unknown both in the Brazilian public health system and the collective health system, once the bibliography revision about leisure activities development was made in the country, looking for ideas taken in common knowledge for health promotion presuppositions, this report has the aim to show critical and alternatives concepts of leisure in the way it is linked to healthy as a real social change, using a political-pedagogical proposal called lazerania. In general, this is an emancipatory concept of leisure, which comes from the sport phenomenon as a problem and provides the feeling, thinking and behavior of the population, trying to build a society based on solidarity and consumer participation.


Neutral temperature range in incubators: performance of equipment in current use and new developments.
Low-birth-weight neonates should be nursed at thermoneutrality inside incubators. Thermoneutrality control is essential to enhance body growth and to reduce neonatal illnesses and mortality. Guidelines have been published to provide the thermoneutral range, but the recommendations did not always take into account all ambient and physiological parameters influencing thermoneutrality. In most marketed incubators, the heat supply is controlled through convective air flow (closed incubators) or through radiant power density (radiant warmer beds). The heating unit (on/off cycling or adjustable proportional control) is activated by an error signal calculated from the difference between a controlled temperature and a reference value preset by the clinician. The controlled variable can be either the incubator air or the skin temperature of the anterior abdominal region of the neonate. The neonate's size, thermal properties of the mattress and of incubator walls, air temperature and humidity, air velocity, incubator wall temperatures all influence the heat exchanges between the neonate and the surroundings, and, consequently, modify the obtention of thermoneutrality. Moreover, studies of the physiological mechanisms by which the neonate regulates body heat storage suggest that metabolic rate, behavior, vigilance level, nursing care, and heater control processes should also be taken into account. Little attention has been paid to these factors, and incubator performances are often disappointing. This article reviews the different factors that modify thermoneutral condition. An attempt is made to suggest new ways to design equipment incorporating these factors in algorithms controlling heater processes in order to reach the optimal thermal environment in which the neonate should be nursed.


Breast cancer survival and hormone replacement therapy: a cohort analysis.
Controversy exists regarding the safety of hormone replacement therapy (HRT) after a diagnosis of breast cancer. The objective of this study is to perform a matched cohort analysis to evaluate the impact of HRT on mortality in breast cancer survivors. Patients with breast cancer who received HRT after diagnosis of breast cancer were identified. Control subjects were identified from the regional cancer registry. Matching criteria included age at diagnosis, stage of breast cancer, and year of diagnosis. Controls were selected only if they were alive at the time of initiation of HRT of the matched case. Only subjects not included in a previously reported matched analysis were selected. One hundred twenty-five cases were matched with 362 controls. Ninety-eight percent (123/125) of the cases received systemic estrogen; 90/125 (72%) also received a progestational agent. The median interval between diagnosis of breast cancer and initiation of HRT was 46 months (range 0-401 months). The median duration of HRT was 22 months (range 1-357 months). The risk of death was lower among the HRT survivors; odds ratio 0.28 (95% confidence interval 0.11-0.71). This analysis does not suggest that HRT after the treatment of breast cancer is associated with an adverse outcome.


Quantification of gravity-induced skin strain across the breast surface.
Quantification of the magnitude of skin strain in different regions of the breast may help to estimate possible gravity-induced damage whilst also being able to inform the selection of incision locations during breast surgery. The aim of this study was to quantify static skin strain over the breast surface and to estimate the risk of skin damage caused by gravitational loading. Fourteen participants had 21 markers applied to their torso and left breast. The non-gravity breast position was estimated as the mid-point of the breast positions in water and soybean oil (higher and lower density than breast respectively). The static gravity-loaded breast position was also measured. Skin strain was calculated as the percentage extension between adjacent breast markers in the gravity and non-gravity loaded conditions. Gravity induced breast deformation caused peak strains ranging from 14 to 75% across participants, with potentially damaging skin strain (>60%) in one participant and skin strains above 30% (skin resistance zone) in a further four participants. These peak strain values all occurred in the longitudinal direction in the upper region of the breast skin. In the latitudinal direction, smaller-breasted participants experienced greater strain on the outer (lateral) breast regions and less strain on the inner (medial) breast regions, a trend which was reversed in the larger breasted participants (above size 34D). To reduce tension on surgical incisions it is suggested that preference should be given to medial latitudinal locations for smaller breasted women and lateral latitudinal locations for larger breasted women.


Reflex changes in hindlimb and renal vascular resistance in response to distention of the isolated pulmonary arteries of the dog.
We describe a preparation that uses a constant flow, right heart bypass for perfusion of an isolated pouch of the main pulmonary arteries at controlled pressures, and show that increments in pressure in the pulmonary arterial pouch are accompanied by increases in systemic vascular resistance and in hindlimb vascular resistance. These changes are demonstrated over the whole range of 5-120 cm H2O pressure in the pulmonary arterial pouch. In contrast there are no significant changes in renal vascular resistance or heart rate. We find that changing the temperature of the perfusate in the pulmonary arterial pouch from 37 degrees C to 30 degress C is associated with a decrease in systemic vascular resistance. Furthermore, the effects of raising the pulmonary arterial pouch pressure and of cooling are abolished by cervical vagotomy. These findings suggest that there is a tonic reflex vasoconstrictor tone generated by the activity of receptors lying in or close to the walls of the pulmonary artery. These findings also suggest that the differential effects on systemic vascular resistance and renal resistance may provide one mechanism by which changes in blood volume may lead to appropriate changes in renal solute excretion.


Current-induced dynamics of skyrmion strings.
Dynamics of string-like objects is an important issue in a broad range of physical systems, including vortex lines in superconductors, viscoelastic polymers, and superstrings in elementary particle physics. In noncentrosymmetric magnets, string forms of magnetic skyrmions are present as topological spin objects, and their current-induced dynamics has recently attracted intense interest. We show in the chiral magnet MnSi that the current-induced deformation dynamics of skyrmion strings results in transport response associated with the real-space Berry phase. Prominent nonlinear Hall signals emerge above the threshold current only in the skyrmion phase. We clarify the mechanism for these nonlinear Hall signals by adopting spin density wave picture to describe the moving skyrmion lattice; deformation of skyrmion strings occurs in an asymmetric manner due to the Dzyaloshinskii-Moriya interaction, which leads to the nonreciprocal nonlinear Hall response originating from an emergent electromagnetic field. This finding reveals the dynamical nature of string-like objects and consequent transport outcomes in noncentrosymmetric systems.


Evidence for triclosan-induced activation of human and rodent xenobiotic nuclear receptors.
The bacteriostat triclosan (2,4,4'-trichloro-2'-hydroxydiphenylether) (TCS) decreases rat serum thyroxine via putative nuclear receptor (NR) interaction(s) and subsequent transcriptional up-regulation of hepatic catabolism and clearance. However, due to the evolutionary divergence of the constitutive androstane and pregnane-X receptors (CAR, PXR), TCS-mediated downstream effects may be species-dependent. To test the hypothesis that TCS activates xenobiotic NRs across species, cell-based NR reporter assays were employed to assess potential activation of rat, mouse, and human PXR, and rat, mouse, and three splice variants of human CAR. TCS activated hPXR, acted as an inverse agonist of hCAR1, and as a weak agonist of hCAR3. TCS failed to activate rPXR in full-length receptor reporter assays, and instead acted as a modest inverse agonist of rCAR. Consistent with the rat data, TCS also failed to activate mPXR and was a modest inverse agonist of mCAR. These data suggest that TCS may interact with multiple NRs, including hPXR, hCAR1, hCAR3, and rCAR in order to potentially affect hepatic catabolism. Overall these data support the conclusion that TCS may interact with NRs to regulate hepatic catabolism and downstream thyroid hormone homeostasis in both rat and human models, though perhaps by divergent mechanisms.


Altering DNA-Programmable Colloidal Crystallization Paths by Modulating Particle Repulsion.
Colloidal crystal engineering with DNA can be used to realize precise control over nanoparticle (NP) arrangement. Here, we investigate a case of DNA-based assembly where the properties of DNA as a polyelectrolyte brush are employed to alter a hybridization-driven NP crystallization pathway. Using the coassembly of DNA-conjugated proteins and spherical gold nanoparticles (AuNPs) as a model system, we explore how steric repulsion between noncomplementary, neighboring NPs due to overlapping DNA shells can influence their ligand-directed behavior. Specifically, our experimental data coupled with coarse-grained molecular dynamics (MD) simulations reveal that, by changing factors related to NP repulsion, two structurally distinct outcomes can be achieved. When steric repulsion between DNA-AuNPs is significantly greater than that between DNA-proteins, a lower packing density crystal lattice is favored over the structure that is predicted by design rules based on DNA hybridization considerations alone. This is enabled by the large difference in DNA density on AuNPs versus proteins and can be tuned by modulating the flexibility, and thus conformational entropy, of the DNA on the constituent particles. At intermediate ligand flexibility, the crystallization pathways are energetically similar, and the structural outcome can be adjusted using the density of DNA duplexes on DNA-AuNPs and by screening the Coulomb potential between them. Such lattices are shown to undergo dynamic reorganization upon changing the salt concentration. These data help elucidate the structural considerations necessary for understanding repulsive forces in DNA-mediated assembly and lay the groundwork for using them to increase architectural diversity in engineering colloidal crystals.


ASSESSMENT OF CEREBRAL PERFUSION IN PATIENTS WITH HEMODYNAMIC ISCHEMIC STROKE UNDERGOING RECONSTRUCTIVE BRACHIOCEPHALIC ARTERY INTERVENTIONS.
The paper deals with the assessment of cerebral perfusion in patients in the acute period of acute cerebrovascular accident before and after revascularization surgery. It gives a clinical example of using contrast-free perfusion magnetic resonance imaging (MRI) in a patient with hemodynamic ischemic stroke. The use of this technique made it possible to determine indications for early carotid endarterectomy for the contralateral internal carotid artery and to evaluate positive postoperative changes in cerebral perfusion and the patient's neurological status. The authors analyzed the current literature on this problem with a particular emphasis on the possibilities of using dynamic susceptibility contrast-enhanced and arterial spin-labeling contrast-free perfusion MRI in this category of patients. Carotid endarterectomy in the acute period of acute cerebrovascular accident can improve cerebral hemodynamics and the patient's neurological status and prevent recurrent cerebral circulatory disorders. Indications for this surgery should be determined by taking into consideration the results of perfusion MRI techniques (single-photon computed tomography contrastenhanced and contrast-free perfusion MRI).


Risk of Human Immunodeficiency Virus Acquisition Among High-Risk Heterosexuals With Nonviral Sexually Transmitted Infections: A Systematic Review and Meta-Analysis.
Nonviral sexually transmitted infections (STIs) increase risk of sexually acquired human immunodeficiency virus (HIV) infection. Updated risk estimates carefully scrutinizing temporality bias of studies are needed. We conducted a systematic review (PROSPERO CRD42018084299) of peer-reviewed studies evaluating variation in risk of HIV infection among high-risk heterosexuals diagnosed with any of: Chlamydia trachomatis, Mycoplasma genitalium, Neisseria gonorrhoeae, Treponema pallidum, and/or Trichomonas vaginalis. We searched PubMed, Web of Science, and Embase databases through December 2017 and included studies where STIs and HIV were assessed using laboratory tests or medical examinations and where STI was diagnosed before HIV. After dual screening, data extraction, and risk of bias assessment, we meta-analytically pooled risk ratios (RRs). We found 32 eligible studies reporting k = 97 effect size estimates of HIV acquisition risk due to infection with one of the abovementioned STIs. Most data were based on women engaged in sex work or other high-risk occupations in developing countries. Many studies did not measure or adjust for known confounders, including drug injection and condom use, and most were at medium or high risk of bias because of the potential for undetected HIV infection to have occurred before STI infection. Human immunodeficiency virus acquisition risk increased among women infected with any pathogen; the effect was greatest for women infected with Mycoplasma genitalium (RR, 3.10; 95% confidence interval [CI], 1.63-5.92; k = 2) and gonorrhea (RR, 2.81; 95% CI, 2.25-3.50; k = 16) but also statistically significant for women infected with syphilis (RR, 1.67; 95% CI, 1.23-2.27; k = 17), trichomonas (RR, 1.54; 95% CI, 1.31-1.82; k = 17), and chlamydia (RR, 1.49; 95% CI, 1.08-2.04; k = 14). For men, data were space except for syphilis (RR, 1.77; 95% CI, 1.22-2.58; k = 5). Nonviral STI increases risk of heterosexual HIV acquisition, although uncertainty remains because of risk of bias in primary studies.


Giant left atrial thrombus 17 years after orthotopic heart transplantation.
We present the case of a 66-year-old woman who underwent orthotopic heart transplantation 17 years earlier for dilated cardiomyopathy. After 7 years allograft coronary vasculopathy developed requiring coronary artery angioplasty. In year 15 postoperatively she experienced congestive heart failure and she became symptomatic requiring diuretics and digoxin treatment. In year 16 postoperatively a routine coronary computed tomography (CT) angiography study revealed a giant thrombus in the left atrium. The patient had had no thromboembolic-related symptoms. Anticoagulation therapy was introduced and the patient has not presented any thromboembolic-related complication. As the symptoms of cardiac insufficiency worsened we decided to evaluate the patient for re-transplantation.


Disciform macular degeneration in young adults.
We describe cases of haemorrhagic disciform macular detachment occurring in young adults in association with multifocal disease at the level of the retinal pigment epithelium (RPE). The cause of the original focal lesions is unknown. Our cases demonstrate a variable and unpredictable clinical course in which the disciform response may develop rapidly.


Neural stem cell- and Schwann cell-loaded biodegradable polymer scaffolds support axonal regeneration in the transected spinal cord.
Biodegradable polymer scaffolds provide an excellent approach to quantifying critical factors necessary for restoration of function after a transection spinal cord injury. Neural stem cells (NSCs) and Schwann cells (SCs) support axonal regeneration. This study examines the compatibility of NSCs and SCs with the poly-lactic-co-glycolic acid polymer scaffold and quantitatively assesses their potential to promote regeneration after a spinal cord transection injury in rats. NSCs were cultured as neurospheres and characterized by immunostaining for nestin (NSCs), glial fibrillary acidic protein (GFAP) (astrocytes), betaIII-tubulin (immature neurons), oligodendrocyte-4 (immature oligodendrocytes), and myelin oligodendrocyte (mature oligodendrocytes), while SCs were characterized by immunostaining for S-100. Rats with transection injuries received scaffold implants containing NSCs (n=17), SCs (n=17), and no cells (control) (n=8). The degree of axonal regeneration was determined by counting neurofilament-stained axons through the scaffold channels 1 month after transplantation. Serial sectioning through the scaffold channels in NSC- and SC-treated groups revealed the presence of nestin, neurofilament, S-100, and betaIII tubulin-positive cells. GFAP-positive cells were only seen at the spinal cord-scaffold border. There were significantly more axons in the NSC- and SC- treated groups compared to the control group. In conclusion, biodegradable scaffolds with aligned columns seeded with NSCs or SCs facilitate regeneration across the transected spinal cord. Further, these multichannel biodegradable polymer scaffolds effectively serve as platforms for quantitative analysis of axonal regeneration.


Osteonecrosis of the Femoral Head as a Potential Pitfall in 18 F-PSMA-1007 PET.
PSMA-targeted PET agents are mainly involved for prostate cancer; however, unspecific bone uptakes can be challenging for the clinician. We report the case of a 71-year-old man with history of recurrent prostate cancer initially treated by surgery and radiation therapy. 18 F-PSMA 1007 PET/CT was performed. Beside hyperfixing lymph nodes, focal uptake was found in right femoral head with shell subchondral hypofixation and no morphologic correlate on CT. MRI found bilateral osteonecrosis of the femoral head. This case emphasizes that osteonecrosis of the femoral head can mimic a metastasis uptake, even with normal CT, without however the fixation being constant.


Rule-based ranking schemes for antiretroviral trials.
Endpoints are a continuing source of controversy in clinical trials of antiretroviral (specifically, anti-HIV) treatments. The most visible disagreement is about the respective roles of morbidity and mortality as endpoints, and laboratory measurements as endpoints. Laboratory measurements have been intensely examined as possible surrogates for clinical outcomes, but the definition of the usual clinical outcome-first occurrence or recurrence of an AIDS-defining condition or death-has received little critical scrutiny. First disease progression has serious weakness as an endpoint, and one should consider alternatives. In this paper, we suggest using rule-based schemes to rank patients' post-randomization histories and then using the ranks as an outcome measure, an extension of the work by Follmann et al. on heart disease. We evaluated six rule-based ranking schemes for antiretroviral trials by applying them to 60 participants in CPCRA 002 and comparing the results to subjective rankings given by five experts. The expert's rankings were in good agreement with each other, and the six rule-based schemes were clearly differentiated by their degree of agreement with the expert's rankings. The ranking scheme most in accord with the experts ranked patients first by seriousness of their most serious AIDS-defining disease, second by the timing of that disease, and the third by the total number of AIDS-defining diseases they experienced. Finally, we used this rule-based rankings to re-analyse CPCRA 002.


Reliability and validity of the Florida Sexual History Questionnaire.
The Florida Sexual History Questionnaire (FSHQ) is a brief 20-item questionnaire designed to assess male sexual dysfunction. The validity and reliability of the scale were examined in 33 diabetic impotent males and 58 nondiabetic, age-equivalent nonimpotent males. The FSHQ was found to have high internal consistency and split-half reliability and significantly discriminated between nonimpotent and impotent subjects. Among diabetic impotent subjects, some of the test items were correlated significantly with physiological measures of sexual functioning. However, the FSHQ failed to discriminate between diabetics diagnosed as having organic or psychogenic impotence. This latter finding is discussed within the context of recent suggestions that it may not be possible to draw a clear dichotomy between organic and psychogenic impotence.


How Supervisor-Subordinate Guanxi Influence Employee Innovative Behavior: A Moderated Mediation Model.
In the practice of inspiring employees' innovative behavior (IB), managers often pay attention to the role of policies, capitals, incentive measures, equipment and other factors, while ignoring the role of the relationship between leaders and employees. Based on social exchange theory and conservation of resources theory, this paper is to examine the mediating role of job satisfaction (JS) and organizational commitment (OC) in the relationship between supervisor-subordinate guanxi (SSG) and employee IB, and the moderating role of psychological safety (PS) in the series mediation model between SSG and employee IB. Cross-sectional data came from 207 employees of Chinese scientific and technological enterprises. The participants completed the SSG scale, JS scale, OC scale, IB scale, and PS scale. SPSS PROCESS macro was used to test the research hypothesis. SSG was positively associated with employee IB. SSG can not only influence IB through JS or OC (SSG→JS→IB; SSG→OC→IB) but also influence IB through JS and OC (SSG→JS→OC→IB). PS moderated the joint mediating effects between SSG and IB (SSG→JS→OC→IB). To stimulate employees' IB within an enterprise can pay attention to the relationship between leaders and employees, improve employee JS, and strengthen employee OC. The lower the PS, the stronger the joint mediation effects between SSG and employee IB. Therefore, leaders should also pay attention to employees with high PS to avoid the counterproductive effect of cultivating SSG.


Effect of CuO on the efficiency of sulfur capture of Ca-based compounds during coal combustion.
The efficiency of sulfur capture of CaO, Ca(OH)2 and CaCO3 as well as the effect of CuO on them were studied. Results showed that the efficiency of sulfur capture of Ca(OH)2 is the highest among these three compounds. When CuO was used with each of CaO, Ca(OH)2 and CaCO3 at the same time, the efficiency of all of them would rise, and that of Ca(OH)2 raise most. The efficiency of sulfur capture of Ca(OH)2 with CuO is 14.4% higher than that without CuO.


Information transfer in multienzyme complexes--1. Thermodynamics of conformational constraints and memory effects in the bienzyme glyceraldehyde-3-phosphate-dehydrogenase-phosphoribulokinase complex of Chlamydomonas reinhardtii chloroplasts.
Oxidized phosphoribulokinase is almost inactive in its isolated state but becomes active when associated with glyceraldehyde-3-phosphate dehydrogenase. There is therefore an information transfer that takes place between these two enzymes. However, when the complex dissociates, free oxidized phosphoribulokinase is even more active than when it is associated with glyceraldehyde-3-phosphate dehydrogenase. This means that glyceraldehyde-3-phosphate dehydrogenase exerts an imprinting effect upon phosphoribulokinase which persists for a while after the parting of the two proteins. Various methods derived from statistical thermodynamics can be used to estimate the fraction of energy transferred from glyceraldehyde-3-phosphate dehydrogenase to phosphoribulokinase and which alters the kinetic parameters of the latter enzyme. In the complex, the decrease of the free energy associated with the binding of ribulose 5-phosphate is larger than that of ATP. This implies that the mutual association of the two enzymes facilitates the binding of the former substrate but is without effect on that of the latter. The main effect exerted by the association of the two enzymes is to decrease by about 10 kJ/mol the height of the energy barrier of the catalytic process. Phosphoribulokinase keeps an imprinting effect exerted by glyceraldehyde-3-phosphate dehydrogenase after the parting of the two enzymes. Part of the energy transferred from one protein to the other is used to decrease slightly the apparent binding free energy of the two substrates of phosphoribulokinase by about 1.5 kJ/mol. Whereas the previous association of the two enzymes does not significantly alter substrate binding to phosphoribulokinase, it greatly affects catalysis and decreases by about 16 kJ/mol the height of the energy barrier pertaining to this step. Therefore, within multienzyme complexes, information and energy can be transferred between proteins. Statistical thermodynamics offers the possibility of estimating how this energy is used to alter the various kinetic parameters of the reaction.


Triiodothyronine autoantibodies in Graves' disease: their changes after antithyroid therapy and relationship with the thyroglobulin antibodies.
Sera of 63 patients with Graves' disease, and 49 control subjects were assayed for T3 autoantibodies by a sensitive radioimmunoassay after being stripped of the endogenous thyroid hormone. T3 autoantibodies were demonstrated in 27% of patients with Graves' disease. After antithyroid treatment, T3 autoantibodies in 75% of the patients with positive antibody before therapy changed to negative titre during a follow-up period of 1 to 12 months. Also, a significant decrease of T3 autoantibodies was observed at 1 month after therapy in all patients who received antithyroid treatment. A further study of T3 autoantibodies and anti-thyroglobulin antibodies showed that the latter were demonstrated in 100% of patients with positive T3 autoantibodies and that T3 autoantibodies existed in about one third of patients with positive anti-thyroglobulin antibodies. The results suggested that T3 autoantibodies could be a subpopulation of the heterogenous anti-thyroglobulin antibodies. Although the fall of T3 autoantibodies in some patients was correlated to that of anti-thyroglobulin antibodies, the overall correlation between T3 autoantibodies and anti-thyroglobulin antibodies was poor. 1. T3 autoantibodies may be suppressed by antithyroid drugs. 2. Being a subpopulation of anti-thyroglobulin antibodies, T3 autoantibodies may be caused by an antigenic site within the big thyroglobulin molecule, whereas their titre was not correlated with that of the overall heterogenous anti-thyroglobulin antibodies.


Strategies for reliable exploitation of evolutionary concepts in high throughput biology.
The recent availability of the complete genome sequences of a large number of model organisms, together with the immense amount of data being produced by the new high-throughput technologies, means that we can now begin comparative analyses to understand the mechanisms involved in the evolution of the genome and their consequences in the study of biological systems. Phylogenetic approaches provide a unique conceptual framework for performing comparative analyses of all this data, for propagating information between different systems and for predicting or inferring new knowledge. As a result, phylogeny-based inference systems are now playing an increasingly important role in most areas of high throughput genomics, including studies of promoters (phylogenetic footprinting), interactomes (based on the presence and degree of conservation of interacting proteins), and in comparisons of transcriptomes or proteomes (phylogenetic proximity and co-regulation/co-expression). Here we review the recent developments aimed at making automatic, reliable phylogeny-based inference feasible in large-scale projects. We also discuss how evolutionary concepts and phylogeny-based inference strategies are now being exploited in order to understand the evolution and function of biological systems. Such advances will be fundamental for the success of the emerging disciplines of systems biology and synthetic biology, and will have wide-reaching effects in applied fields such as biotechnology, medicine and pharmacology.


Detection of linear ego-acceleration from optic flow.
Human observers are able to estimate various ego-motion parameters from optic flow, including rotation, translational heading, time-to-collision (TTC), time-to-passage (TTP), etc. The perception of linear ego-acceleration or deceleration, i.e., changes of translational velocity, is less well understood. While time-to-passage experiments indicate that ego-acceleration is neglected, subjects are able to keep their (perceived) speed constant under changing conditions, indicating that some sense of ego-acceleration or velocity change must be present. In this paper, we analyze the relation of ego-acceleration estimates and geometrical parameters of the environment using simulated flights through cylindrical and conic (narrowing or widening) corridors. Theoretical analysis shows that a logarithmic ego-acceleration parameter, called the acceleration rate ρ, can be calculated from retinal acceleration measurements. This parameter is independent of the geometrical layout of the scene; if veridical ego-motion is known at some instant in time, acceleration rate allows updating of ego-motion without further depth-velocity calibration. Results indicate, however, that subjects systematically confuse ego-acceleration with corridor narrowing and ego-deceleration with corridor widening, while veridically judging ego-acceleration in straight corridors. We conclude that judgments of ego-acceleration are based on first-order retinal flow and do not make use of acceleration rate or retinal acceleration.


Nursing students' knowledge and practice of infection control precautions: an educational intervention.
This paper is a report of the effectiveness of a purpose-designed education program in improving undergraduate nursing students' understanding and practice of infection control precautions. The severe acute respiratory syndrome outbreak in 2003 highlighted that healthcare workers were under-prepared for such an epidemic. While many in-service education sessions were arranged by institutions in response to the outbreak, preservice nursing education has overlooked preparation for handling such infectious disease epidemics. A quasi-experimental design was used and a 16-hour, purpose-designed infection control education programme was implemented for preservice nursing students in southern Taiwan. Self-administered questionnaires were distributed at three time points during the period September 2005 to April 2006 to examine the sustainability and effectiveness of the intervention. A total of 175 preservice nursing students participated in the study. Following the education programme, students in the intervention group showed a statistically significant improvement across time in their knowledge of these precautions [F(2, 180) = 13.53, P < 0.001] and confidence in resolving infection-related issues [F(1.79, 168.95) = 3.24] when compared with those in the control group. To improve nursing students' capacity in responding to infectious epidemics, an educational programme that integrates the theme of infection precautions, learning theory and teaching strategies is recommended for all nursing institutes.


Ca2+-movements in muscle modulated by the state of K+-channels in the sarcoplasmic reticulum membranes.
1. A procedure has been developed to load Ca2+ reversibly by the sarcoplasmic reticulum (SR) of mechanically skinned muscle fibres from the toad Bufo marinus under controlled conditions and was employed to investigate the effects of conditions known to reduce the K+ conductance located in the SR-membrane during Ca2+-loading on the amount of Ca2+ releasable by caffeine. 2. The amount of releasable Ca2+ was markedly increased compared to controls when 4-aminopyridine (4AP) (6 microM to 2 mM), tetraethylammonium (TEA), decamethonium (0.5 mM) or procaine (1 mM) were present in the Ca2+-loading solutions. All these substances are known to act as SR-K+-channel blockers. 3. The increased amount of releasable Ca2+ in the presence of the K+-channel blocker 4AP was observed both at low (0.3 mM) and at higher (1 mM) Mg2+ concentrations and was not affected by verapamil (20 microM), a known Ca2+-channel blocker of the sarcolemma nor by the Na+-K+ pump inhibitor, ouabain (1 mM). 4. In the presence of 0.1-5 microM ruthenium red, a known inhibitor of Ca2+ induced Ca2+ release from the SR, the amount of releasable Ca2+ was greatly increased by up to 300%. Addition of between 50 microM and 1.6 mM 4AP to ruthenium red Ca2+ loading solution modified differently the amount of releasable Ca2+, suggesting that the mechanism of action of 4AP is different from that of ruthenium red. 5. When all K+ ions in the loading solution were replaced by the less permeant Na+ ions the amount of releasable Ca2+ ions was also increased. 6. These results indicate that the amount of releasable Ca2+ from the SR is consistently modified under conditions aimed at interfering with the state of SR-K+-channels, suggesting that SR-K+-channels may play an important physiological role in the modulation of excitation-contraction coupling. One possible mechanism involving SR-K+-channels which could explain our results is discussed.


Effect of luminance on suprathreshold contrast perception.
Perceived contrast was measured under natural viewing conditions with the use of contrast-matching and magnitude-estimation paradigms and found to be independent of luminance over a range of luminances from 37.5 down to 8 cd/m2. However, this contrast constancy broke down when the dimmer target was below 8 cd/m2. The perceived contrast of the dimmer target then fell below that expected from contrast constancy. The extended range of contrast constancy previously reported [J. Physiol. 252, 627 (1975); Vision Res. 16, 1419 (1976)] has been thought to imply neural mechanisms with unlimited constancy, but these researchers permitted differential adaptation to the brighter and dimmer targets, which were seen haploscopically (by different eyes). As our natural-viewing procedure ensured that both bright and dim targets were presented to retinal areas in a roughly constant state of adaptation, our failure to find extended contrast constancy implies an important limitation on the neural processing of contrast.


Hypocholesterolemic effect of soymilk supplementation with usual diet in premenopausal normolipidemic Japanese women.
The hypocholesterolemic effect of soy protein concentrates on normolipidemic subjects still remains unclear. Our objective is to assess the effect of soymilk supplementation, a whole soy product, with usual diet on serum lipids in normolipidemic subjects. We conducted a randomized controlled trial on 60 premenopausal normolipidemic Japanese women. After excluding 8 subjects whose initial serum concentration of total cholesterol or triacylglycerol was higher than 220 mg/dL (5.69 mmol/L) or 160 mg/dL (1.81 mmol/L), respectively, we encouraged the subjects in the soymilk-supplemented group (n = 27) to consume 400 mL (408 g) of commercial regular soymilk daily during two menstrual cycles. There were no significant differences in variables, including nutrient intake, between the soymilk-supplemented and control (n = 25) groups before the intervention. After the trial, we observed a significant decrease of 10.9 mg/dL, or 5.3%, in serum concentration of total cholesterol in the soymilk-supplemented group. During the intervention, nutrient intake assessment showed significant increases in nutrient densities of vitamin E, polyunsaturated fatty acids, isoflavones, and P/S ratio and decreases in total energy and nutrient densities of vitamin C and green tea in this group. A statistically significant decrease in serum total cholesterol could still be observed even after excluding the estimated hypocholesterolemic effects of soymilk's polyunsaturated fatty acids. Our results suggest the hypocholesterolemic effect of soymilk, a traditional whole soy product, in Asian countries in normolipidemic subjects.


Influence of adrenocorticotropin and adrenalectomy on gonadotropin secretion in immature rats.
We examined the effects and mechanisms of action of ACTH and ACTH fragments on gonadotropin secretion in immature rats. ACTH administered by daily injection or continuous infusion (osmotic minipumps) attenuated the postcastration rise in serum LH. Pituitary LH concentration was either unchanged or increased in ACTH-treated rats and pituitary sensitivity to gonadotropin-releasing hormone (GnRH) was reduced by ACTH treatment. A fragment of ACTH (ACTH 4-10), which is less steroidogenic, did not alter levels of serum LH, and ACTH did not reduce LH secretion in adrenalectomized castrates. Serum and pituitary concentrations of prolactin were normal in ACTH-treated animals. These studies demonstrate that the suppression of gonadotropin secretion by ACTH is mediated by the adrenal gland. This mechanism causes a decreased pituitary sensitivity to GnRH, but LH synthesis does not appear to be affected. Prolactin does not play a role in this mechanism.


Medical treatment of vestibular disorders.
The lifelong prevalence of rotatory vertigo is 30%. Despite this high figure, patients with vertigo generally receive either inappropriate or inadequate treatment. However, the majority of vestibular disorders have a benign cause, take a favorable natural course, and respond positively to therapy. This review puts special emphasis on the medical rather than the physical, operative, or psychotherapeutic treatments available. A selected review of recent reports and studies on the medical treatment of peripheral and central vestibular disorders. In vestibular neuritis, recovery of the peripheral vestibular function can be improved by oral corticosteroids; in Menière's disease, there is first evidence that high-dose, long-term administration of betahistine reduces attack frequency; carbamazepine or oxcarbamazepine is the treatment of first choice in vestibular paroxysmia, a disorder mainly caused by neurovascular cross-compression; the potassium channel blocker aminopyridine provides a new therapeutic principle for treatment of downbeat nystagmus, upbeat nystagmus, and episodic ataxia type 2.


Developing a list of invasive alien species likely to threaten biodiversity and ecosystems in the European Union.
The European Union (EU) has recently published its first list of invasive alien species (IAS) of EU concern to which current legislation must apply. The list comprises species known to pose great threats to biodiversity and needs to be maintained and updated. Horizon scanning is seen as critical to identify the most threatening potential IAS that do not yet occur in Europe to be subsequently risk assessed for future listing. Accordingly, we present a systematic consensus horizon scanning procedure to derive a ranked list of potential IAS likely to arrive, establish, spread and have an impact on biodiversity in the region over the next decade. The approach is unique in the continental scale examined, the breadth of taxonomic groups and environments considered, and the methods and data sources used. International experts were brought together to address five broad thematic groups of potential IAS. For each thematic group the experts first independently assembled lists of potential IAS not yet established in the EU but potentially threatening biodiversity if introduced. Experts were asked to score the species within their thematic group for their separate likelihoods of i) arrival, ii) establishment, iii) spread, and iv) magnitude of the potential negative impact on biodiversity within the EU. Experts then convened for a 2-day workshop applying consensus methods to compile a ranked list of potential IAS. From an initial working list of 329 species, a list of 66 species not yet established in the EU that were considered to be very high (8 species), high (40 species) or medium (18 species) risk species was derived. Here, we present these species highlighting the potential negative impacts and the most likely biogeographic regions to be affected by these potential IAS.


Urinary bisphenol A concentrations and adiposity measures at age 7 years in a prospective birth cohort.
Bisphenol A (BPA) exposure during early life may increase risk of childhood obesity, however, prospective evidence of birth cohort is limited and inconclusive. We aimed to explore the associations of maternal and childhood BPA exposure with child adiposity measures, including body mass index, waist circumference and skinfold thickness and waist to height ratio of children at 7 years. 430 mother-child pairs were examined from a population-based prospective cohort in a rural area of East China. BPA concentrations of spot urine samples were quantified in mothers and their children aged 3 and 7 years. Maternal urinary BPA concentration was significantly positively associated with waist circumference in children aged 7 years (β = 0.508 cm, 95% CI: 0.067, 0.950). These significant associations were not modified by child sex, but they were only observed among girls in sex-stratified analyses. Risk of central obesity related to prenatal BPA exposure was significantly higher in the second and the third tertile than those in the first tertile (odds ratio, OR = 2.510, 95% CI = 1.146, 5.499; OR = 2.584, 95% CI = 1.186, 5.631, respectively; p for trend = 0.022). The present findings suggested that prenatal exposure to BPA may enhance waist circumference of children and thereby increase risk of central obesity in school-age girls.


Presence of Human Herpesvirus 6B in the Pancreas of Subjects With and Without Type 1 Diabetes.
The aims of this study were to investigate the presence of human herpesvirus 6 (HHV6) A and B in human pancreata and to search for signs of active infection in this organ of subjects with and without type 1 diabetes (T1D). Pancreata from brain-dead organ donors with and without T1D were examined for the presence of HHV6 genomic sequences by polymerase chain reaction (PCR), transcripts by reverse transcriptase-PCR, and protein by immunohistochemistry. Quantitative PCR of isolated pancreatic islets and exocrine cell clusters was used to determine the intrapancreatic location of HHV6 DNA. Human herpesvirus 6B genomic sequences were present in 1 of 2 donors who died of acute-onset T1D, 4 of 6 donors with long-standing T1D, and 9 of 12 nondiabetic donors. Higher copy numbers of HHV6B DNA were present in isolated islets than in exocrine tissue from the same donors. No signs of active HHV6 transcription were found. Human herpesvirus 6A was not present in any tested pancreas. The herein presented data demonstrate, for the first time, the presence of a latent HHV6B infection in the pancreas and islets of Langerhans. Whether this virus can contribute to disease in the pancreas remains to be determined.


A phenomenological study of breastfeeding WIC recipients in South Carolina.
The purpose of this phenomenological study was to describe the phenomenon of breastfeeding in a low-income group of mothers and to determine its meaning to the mothers. Eleven mothers who had breastfeeding experience were interviewed. The focal meaning of support as related to breastfeeding emerged during data analysis from the participants' lived experience. In all participant interviews the recurring concept was support. Major themes included informational support, emotional support, and instrumental support. The article suggests implications for advanced practice.


Self-esteem instability and affective instability in everyday life after remission from borderline personality disorder.
Borderline personality disorder (BPD) is defined by a pervasive pattern of instability. According to prior findings and clinical theories, self-esteem instability and affective instability are key features of BPD. Previous e-diary studies showed that instability in self-esteem is heightened and that it is highly intertwined with affective instability in BPD in comparison to healthy controls (HC). The present study sought to extend these findings by adding symptomatologically remitted BPD patients (BPD-REM), i.e. former patients with BPD who met four or fewer BPD criteria within the past year, as a comparison group. To examine differences regarding self-esteem instability and affective instability, we used e-diaries for repeatedly collecting data on self-esteem, valence, and tense arousal 12 times a day for four consecutive days while participants underwent their daily life activities. Determining three different state-of-the-art instability indices and applying multilevel analyses, we compared 35 BPD-REM participants with previously reported 60 acute BPD patients (BPD-ACU) and 60 HC. Our results revealed that self-esteem instability was significantly lower in the BPD-REM compared to the BPD-ACU group, irrespective of the instability index. In contrast, there were no significant differences regarding affective instability between the BPD-REM participants and those in the BPD-ACU group. The comparison between the BPD-REM with the HC indicated both a significantly higher instability in self-esteem as well as significantly heightened affective instability in the BPD-REM participants. Moreover, even though the associations were not significant, we found tentative support for the assumption that affective changes that are accompanied by changes in self-esteem are experienced as more burdensome and negatively impact the quality of life of remitted BPD participants. This study builds on growing evidence for the importance of self-esteem instability in BPD. Whereas affective instability has been reported in various psychiatric disorders and might indeed constitute a transdiagnostic marker of affective dysregulation, our results indicate that self-esteem instability might be a specific symptom that construes the unique pathology in BPD.


Suicide Ideation and Neurocognition Among 9- and 10-Year Old Children in the Adolescent Brain Cognitive Development (ABCD) Study.
During the past decade, the pediatric suicide rate has nearly tripled. Yet, little is known about suicide behavior (SB) in children. Identification of risk factors associated with SB during childhood may be critical to preventing future attempts. The purpose of this study was to examine the relationship between neurocognitive performance and suicide ideation (SI) in children. The present study utilized baseline data from 11,875 participants in the Adolescent Brain Cognitive Development (ABCD) study, a longitudinal study that follows 9- and 10-year-old children through late adolescence to examine factors that influence developmental trajectories. Suicidality was assessed by the Kiddie Schedule for Affective Disorder and Schizophrenia (KSADS) suicide module completed by the parent. Neurocognitive ability was assessed using the NIH Toolbox Cognition measures administered to the youth. Children with a history of SI reported by their parent or concordant parent and youth report of SI demonstrated lower performance on the NIH Toolbox Picture Sequence Memory Test compared to children without SI. The difference in performance on the memory task remained significant when including demographic characteristics, family history of suicide, and internalizing symptoms in the model as covariates. To our knowledge, this is the first study to identify decreased episodic memory in children with SI. These findings are similar to results from adult and adolescent studies which have reported decreased memory performance among suicide attempters. Deficits in episodic memory may impact a child's ability to problem-solve and generate potential future outcomes, which may increase the risk for SB. Early identification of memory deficits in children may inform suicide prevention and intervention efforts.Highlights6% of parents and children reported a history of active suicide ideation in children.Children with a history of suicide ideation had lower episodic memory performance.Early identification of memory deficits may inform suicide intervention efforts.


Paclitaxel (Taxol) for the treatment of lymphoma.
Paclitaxel (Taxol) was recently tested in patients with relapsed and refractory lymphoma in two phase II clinical trials using two different infusion schedules. The first, reported from the NCI (USA), used a 96-hour intravenous continuous infusion schedule, and the second, from our group, used a 3-hour infusion. In the NCI trial, 29 evaluable patients were treated with 140 mg/m2 every three weeks, which achieved a 17% response rate (all PRs); while we treated 96 evaluable patients with 200 mg/m/ every three weeks, which achieved a 25% response rate (10 CRs and 14 PRs, 95% CI: 17%-35%). In our trial, patients with relapsed (not primary refractory) intermediate-grade lymphoma had a response rate of 50%, and those with relapsed low-grade lymphoma had a response rate of 31%. In a follow-up trial, 12 patients who failed to respond to 3-hour infusion of paclitaxel were crossed over to receive paclitaxel by 96-hour infusion. None of the 12 evaluable patients achieved a major clinical response. Similarly, of 25 patients treated with cyclosporine A and paclitaxel after failing therapy with single-agent paclitaxel, only one patient (4%) responded. We conclude that paclitaxel has a promising single-agent activity, most prominently in patients with relapsed intermediate-grade lymphoma. Paclitaxel-based combination programs are currently being evaluated in our institution.


Effects of electroacupuncture and twirling reinforcing-reducing manipulations on volume of microcirculatory blood flow in cerebral pia mater.
Effects of electroacupuncture (EA) and routine acupuncture with twirling reinforcing and reducing manipulation of the needle (RA) both at Zusanli point (St 36) on volume of microcirculatory blood flow in the cerebral pia mater were observed by fenestration of the cranial bone and laser Doppler microcirculatory blood flow analyser. Results showed that both RA and EA could increase the volume of microcirculatory blood flow in the cerebral pia mater; and that the increase in the EA group was superior to that in RA group. This suggests that a moderate and effective stimulation is a key to the production of a regulative effect on the organism.


Aryl hydrocarbon receptor-induced signals up-regulate IL-22 production and inhibit inflammation in the gastrointestinal tract.
The pathogenesis of inflammatory bowel disease (IBD) is believed to involve an altered balance between effector and regulatory T cells. Aryl hydrocarbon receptor (AhR), a ligand-dependent transcription factor that mediates the toxicity of dioxins, controls T-cell responses. We investigated the role of AhR in inflammation and pathogenesis of IBD in humans and mouse models. AhR expression was evaluated in intestinal tissue samples from patients with IBD and controls by real-time polymerase chain reaction (PCR) and flow cytometry. Intestinal lamina propria mononuclear cells (LPMCs) were activated in the presence or absence of the AhR agonist 6-formylindolo(3, 2-b)carbazole (Ficz). Colitis was induced in mice using trinitrobenzene sulfonic acid (TNBS), dextran sulfate sodium (DSS), or T-cell transfer. Mice were given injections of Ficz or the AhR antagonist 2-metyl-2H-pyrazole-3-carboxylic acid; some mice first received injections of a blocking antibody against interleukin (IL)-22. Cytokines were quantified by real-time PCR and flow cytometry. Intestine tissue from patients with IBD expressed significantly less AhR than controls. In LPMCs from patients with IBD, incubation with Ficz reduced levels of interferon gamma (IFN)-γ and up-regulated IL-22. Mice injected with Ficz were protected against TNBS-, DSS-, and T-cell transfer-induced colitis; they had marked down-regulation of inflammatory cytokines and induction of IL-22. Mice given AhR antagonist produced more inflammatory cytokines and less IL-22 and developed a severe colitis. Neutralization of endogenous IL-22 disrupted the protective effect of Ficz on TNBS-induced colitis. AhR is down-regulated in intestinal tissue of patients with IBD; AhR signaling, via IL-22, inhibits inflammation and colitis in the gastrointestinal tract of mice. AhR-related compounds might be developed to treat patients with IBDs.


Sustained-release niacin for prevention of migraine headache.
Considerable advances in the diagnosis and treatment of migraine headache have occurred during the past decade, but treatment options for acute migraine attacks have expanded at a faster rate than those for prophylaxis. We describe a patient whose migraine headaches responded dramatically to sustained-release niacin as preventive treatment. Niacin is not generally considered to be effective for migraine prevention. However, low plasma levels of serotonin have been implicated in migraine pathogenesis, and niacin may act as a negative feedback regulator on the kynurenine pathway to shunt tryptophan into the serotonin pathway, thus increasing plasma serotonin levels. Sustained-release niacin merits further study as a potentially useful preventive therapy for migraine headache.


[D-Arg(1),D-Trp(5,7,9),Leu(11)]Substance P inhibits bombesin-induced mitogenic signal transduction mediated by both G(q) and G(12) in Swiss 3T3cells.
Substance P (SP) analogues including [d-Arg(1),d-Trp(5,7,9), Leu(11)]SP are broad spectrum neuropeptide antagonists and potential anticancer agents, but their mechanism of action is not fully understood. Here, we examined the mechanism of action of [d-Arg(1), d-Trp(5,7,9),Leu(11)]SP as an inhibitor of G protein-coupled receptor (GPCR)-mediated signal transduction and cellular DNA synthesis in Swiss 3T3 cells. Addition of [d-Arg(1),d-Trp(5,7,9), Leu(11)]SP, at 10 micrometer, caused a striking rightward shift in the dose-response curves of DNA synthesis induced by bombesin, bradykinin, or vasopressin and markedly inhibited the activation of p42(mapk) (ERK-2) and p44(mapk) (ERK-1) induced by these GPCR agonists. In addition, this SP analogue also prevented the protein kinase C-dependent activation of protein kinase D induced by these agonists. [d-Arg(1),d-Trp(5,7,9),Leu(11)]SP, at a concentration (10 micrometer) that inhibited these G(q)-mediated events, also prevented GPCR agonist-induced responses mediated through the G proteins of the G(12) subfamily. These include bombesin-induced assembly of focal adhesions, formation of parallel arrays of actin stress fibers, increase in the tyrosine phosphorylation of focal adhesion kinase (FAK), p130(Cas), and paxillin, and formation of a complex between FAK and Src. We conclude that [d-Arg(1),d-Trp(5,7,9),Leu(11)]SP acts as a mitogenic antagonist of neuropeptide GPCRs blocking signal transduction via both G(q) and G(12).


First-principles studies on the electronic and photocatalytic water splitting properties of surface functionalized Y2C-based MXenes.
Recently, MXenes, an emerging family of two-dimensional (2D) materials, have attracted increasing interest for photocatalytic water splitting due to their various excellent physical and chemical properties, such as large specific surface area, good hydrophilicity, and remarkable light absorption ability. However, the photocatalysts of MXenes with symmetric structures are limited by rapid recombination of photo-generated carriers and the prerequisite of a large band gap no less than 1.23 eV. Differently, Janus MXenes with different surface functional groups facilitate the separation of photo-generated electrons and holes with the help of the intrinsic electric field. And, at the same time, there is no prerequisite for the band gap of Janus MXene photocatalysts as long as they possess appropriate band edge positions. Here, we explored the structural, electronic and photocatalytic water splitting properties of symmetric Y2CT2 and Janus Y2CTT' MXenes (T, T' = H, F, Cl, OH) using the density functional theory (DFT) method. Our calculations show that all the investigated Y2CT2 are not suitable photocatalysts for photocatalytic water splitting at all pH values (pH = 0, 7, and 14). In contrast, all the investigated Janus Y2CTT' MXenes are good water splitting photocatalysts with high optical absorption coefficients and remarkable solar-to-hydrogen (STH) efficiencies larger than 18% at pH = 14. Moreover, the STH efficiencies are larger than 18% even at all investigated pH values for Y2CHCl (18.5-22.6%), Y2 CFCl (∼18.7%), and Y2 C(OH)Cl (∼19.4%). Based on the first-principles calculations, we here for the first time propose an easy strategy to design Janus MXene photocatalyst candidates with possible high STH efficiency according to the electronic properties of their symmetric counterparts. Our study is helpful for the future design of Janus MXenes and more generally Janus 2D photocatalysts for water splitting with high STH efficiency.


Economic analysis of carboplatin versus cisplatin in lung and ovarian cancer.
To conduct an economic analysis on the use of carboplatin versus cisplatin over multiple courses in patients with lung [nonsmall cell lung cancer (NSCLC) and small cell lung cancer (SCLC)] or ovarian cancer. This 1-year study was a prospective, multicentre, cost-minimisation evaluation. Direct medical resource utilisation and costs associated with carboplatin and cisplatin administration over 3 to 6 courses of treatment were measured and compared. The perspective of this evaluation was that of the payer. A convenience sample of 16 sites representing a mix of cancer centres, outpatient clinics, medical centres and managed-care sites in a general practice oncology setting participated. Patients were included in this study if they were newly diagnosed with NSCLC, SCLC or ovarian cancer, had not received prior chemotherapy, received either carboplatin or cisplatin as their treatment (additional chemotherapy agents were allowed), and received at least 3 courses of carboplatin or cisplatin therapy up to a maximum of 6 courses. Patients receiving more than 6 courses of therapy were included in this study, but data collection on those patients stopped after the sixth course. Individuals involved with data collection at all sites were trained via on-site and/or teleconference training. Site visits were made to assure reliability of at least 0.80. Data were collected and compiled via a fax transmission process that scans directly through optical mark and character recognition into a computer database. Outcome measures included costs of: medications, emergency room visits, physician/clinic/laboratory visits, home healthcare visits, transfusions, special procedures, consultations, hospitalisations and other/miscellaneous costs. Of 220 patients, 164 met the study criteria (response rate = 74.2%) with 95 patients in the carboplatin group (NSCLC = 45, SCLC = 18, ovarian = 32) and 69 in the cisplatin group (NSCLC = 36, SCLC = 21, ovarian = 12). The average number of courses were: NSCLC = 4.3 and 4.2, SCLC = 4.3 and 4.8, and ovarian = 4.7 and 5.1, respectively, for carboplatin and cisplatin. The total costs (treatment and toxicity) associated with the use of carboplatin were higher in NSCLC, similar in SCLC but lower in ovarian cancer. These results indicate that overall treatment costs may vary depending on cancer type, even when the same drugs are used. The total costs (treatment plus toxicity costs) associated with the use of carboplatin were higher than those of cisplatin in patients with NSCLC, similar in SCLC, but lower in ovarian cancer.


Molecular genetics of essential hypertension: recent results and emerging strategies.
Efforts to identify hypertension-predisposition genetic loci have focused largely on candidate gene strategies, in which specific candidates have been tested for linkage and association with blood pressure or the diagnosis of hypertension. A variety of candidate genes have been investigated, including loci involving the renin-angiotensin-aldosterone system, sodium epithelial channel, catecholaminergic/adrenergic function, renal kallikrein system, alpha-adducin, and others involving lipoprotein metabolism, hormone receptors, and growth factors. These studies, and more recently, several genome-wide scans, have yielded highly promising results suggesting a number of potential candidate genes and genomic regions that may contribute to blood pressure variation. The results also point to the need for more robust phenotypes that are intermediate in the pathogenetic development of high blood pressure. Additional methods and strategies for improving genetic studies of human hypertension include comparative genomics, in which results from animal studies are used to target potential blood pressure loci, the use of newly developed quantitative tests of linkage and association, comprehensive single-nucleotide polymorphism discovery in candidate loci, and the use of single-nucleotide polymorphisms in cladistic/haplotype analyses and genome-wide searches.


Jumping Exercise Combined With Collagen Supplementation Preserves Bone Mineral Density in Elite Cyclists.
This study assessed the effect of combined jump training and collagen supplementation on bone mineral density (BMD) in elite road-race cyclists. In this open-label, randomized study with two parallel groups, 36 young (21 ± 3 years) male (n = 8) and female (n = 28) elite road-race cyclists were allocated to either an intervention (INT: n = 18) or a no-treatment control (CON: n = 18) group. The 18-week intervention period, conducted during the off-season, comprised five 5-min bouts of jumping exercise per week, with each bout preceded by the ingestion of 15 g hydrolyzed collagen. Before and after the intervention, BMD of various skeletal sites and trabecular bone score of the lumbar spine were assessed by dual-energy X-ray absorptiometry, along with serum bone turnover markers procollagen Type I N propeptide and carboxy-terminal cross-linking telopeptide of Type I collagen. BMD of the femoral neck decreased in CON (from 0.789 ± 0.104 to 0.774 ± 0.095 g/cm2), while being preserved in INT (from 0.803 ± 0.058 to 0.809 ± 0.066 g/cm2; Time × Treatment, p < .01). No differences between treatments were observed for changes in BMD at the total hip, lumbar spine, and whole body (Time × Treatment, p > .05 for all). Trabecular bone score increased from 1.38 ± 0.08 to 1.40 ± 0.09 in CON and from 1.46 ± 0.08 to 1.47 ± 0.08 in INT, respectively (time effect: p < .01), with no differences between treatments (Time × Treatment: p = .33). Serum procollagen Type I N propeptide concentrations decreased to a similar extent in CON (83.6 ± 24.8 to 71.4 ± 23.1 ng/ml) and INT (82.8 ± 30.7 to 66.3 ± 30.6; time effect, p < .001; Time × Treatment, p = .22). Serum carboxy-terminal cross-linking telopeptide of Type I collagen concentrations did not change over time, with no differences between treatments (time effect, p = .08; Time × Treatment, p = .58). In conclusion, frequent short bouts of jumping exercise combined with collagen supplementation beneficially affects femoral neck BMD in elite road-race cyclists.


Picosecond time-resolved resonance Raman studies of hemoglobin: implications for reactivity.
Picosecond time-resolved Raman spectra of hemoglobin generated with blue pulses (20 to 30 picoseconds) that were resonant with the Soret band and of sufficient intensity to completely photodissociate the starting liganded sample are reported. For both R- and T-state liganded hemoglobins, the peak frequencies in the spectrum of the deoxy transient were the same at approximately 25 picoseconds as those observed at 10 nanoseconds subsequent to photodissociation. In particular, the large R-T differences in the frequency of the stretching mode for the iron-proximal histidine bond (VFe-His) detected in previously reported nanosecond-resolved spectra were also evident in the picosecond-resolved spectra. The implications of this finding with respect to the distribution of strain energy in the liganded protein and the origin of the time course for geminate recombination are discussed. On the basis of these results, a microscopic model is proposed in which delocalization of strain energy is strongly coupled to the coordinate of the iron. The model is used to explain the origin of the R-T differences in the rates of ligand dissociation.


On How Fas Apoptosis-Independent Pathways Drive T Cell Hyperproliferation and Lymphadenopathy in lpr Mice.
Fas induces massive apoptosis in T cells after repeated in vitro T cell receptor (TCR) stimulation and is critical for lymphocyte homeostasis in Fas-deficient (lpr) mice. Although the in vitro Fas apoptotic mechanism has been defined, there is a large conceptual gap between this in vitro phenomenon and the pathway that leads to in vivo development of lymphadenopathy and autoimmunity. A striking abnormality in lpr mice is the excessive proliferation of CD4+ and CD8+ T cells, and more so of the double-negative TCR+CD4-CD8-B220+ T cells. The basis of lpr T cell hyperproliferation remains elusive, as it cannot be explained by Fas-deficient apoptosis. T cell-directed p21 overexpression reduces hyperactivation/hyperproliferation of all lpr T cell subtypes and lymphadenopathy in lpr mice. p21 controls expansion of repeatedly stimulated T cells without affecting apoptosis. These results confirm a direct link between hyperactivation/hyperproliferation, autoreactivity, and lymphadenopathy in lpr mice and, with earlier studies, suggest that Fas apoptosis-independent pathways control lpr T cell hyperproliferation. lpr T cell hyperproliferation could be an indirect result of the defective apoptosis of repeatedly stimulated lpr T cells. Nonetheless, in this perspective, we argue for an alternative setting, in which lack of Fas would directly cause lpr T cell hyperactivation/hyperproliferation in vivo. We propose that Fas/Fas ligand (FasL) acts as an activation inhibitor of recurrently stimulated T cells, and that its disruption causes overexpansion of T cells in lpr mice. Research to define the underlying mechanism of this Fas/FasL effect could resolve the phenotype of lpr mice and lead to therapeutics for related human syndromes.


Protective effects of polysaccharides from soybean meal against X-ray radiation induced damage in mouse spleen lymphocytes.
The aim of this study was to investigate radioprotective effect of the polysaccharides from soybean meal (SMP) against X-ray radiation-induced damage in mouse spleen lymphocytes. MTT and comet assay were performed to evaluate SMP's ability to prevent cell death and DNA damage induced by radiation. The results show that, X-ray radiation (30 KV, 10 mA, 8 min (4 Gy)) can significantly increase cell death and DNA fragmentation of mouse spleen lymphocytes. Pretreatment with SMP for 2 h before radiation could increase cell viability, moreover, the SMP can reduce X-ray radiation-induced DNA damage. The percentage of tail DNA and the tail moment of the SMP groups were significantly lower than those of the radiation alone group (p < 0.05). These results suggest SMP may be a good candidate as a radioprotective agent.


From the sxtA4 Gene to Saxitoxin Production: What Controls the Variability Among Alexandrium minutum and Alexandrium pacificum Strains?
Paralytic shellfish poisoning (PSP) is a human foodborne syndrome caused by the consumption of shellfish that accumulate paralytic shellfish toxins (PSTs, saxitoxin group). In PST-producing dinoflagellates such as Alexandrium spp., toxin synthesis is encoded in the nuclear genome via a gene cluster (sxt). Toxin production is supposedly associated with the presence of a 4th domain in the sxtA gene (sxtA4), one of the core genes of the PST gene cluster. It is postulated that gene expression in dinoflagellates is partially constitutive, with both transcriptional and post-transcriptional processes potentially co-occurring. Therefore, gene structure and expression mode are two important features to explore in order to fully understand toxin production processes in dinoflagellates. In this study, we determined the intracellular toxin contents of twenty European Alexandrium minutum and Alexandrium pacificum strains that we compared with their genome size and sxtA4 gene copy numbers. We observed a significant correlation between the sxtA4 gene copy number and toxin content, as well as a moderate positive correlation between the sxtA4 gene copy number and genome size. The 18 toxic strains had several sxtA4 gene copies (9-187), whereas only one copy was found in the two observed non-toxin producing strains. Exploration of allelic frequencies and expression of sxtA4 mRNA in 11 A. minutum strains showed both a differential expression and specific allelic forms in the non-toxic strains compared with the toxic ones. Also, the toxic strains exhibited a polymorphic sxtA4 mRNA sequence between strains and between gene copies within strains. Finally, our study supported the hypothesis of a genetic determinism of toxin synthesis (i.e., the existence of several genetic isoforms of the sxtA4 gene and their copy numbers), and was also consistent with the hypothesis that constitutive gene expression and moderation by transcriptional and post-transcriptional regulation mechanisms are the cause of the observed variability in the production of toxins by A. minutum.


A 16-week randomized controlled trial evaluating the physical activity guidelines for adults with spinal cord injury.
Randomized controlled trial. To evaluate the effectiveness of the physical activity guidelines (PAG) for adults with spinal cord injury (SCI) to improve aspects of physical fitness. Community exercise facility. Twenty-three participants (age: 40.4±11.6 years, C1-T11, 12.0±10.0 years post injury) were randomized into PAG training (n=12) or active control (CON, n=11) groups. PAG training was 2x per week for 16 weeks and involved 20 min of aerobic exercise at a moderate to vigorous intensity and three sets of 10 repetitions (at 50-70% 1 repetition maximum; 1RM). Pre- and post-testing included peak exercise and aerobic endurance tests on an arm ergometer and 1RM testing. Nineteen participants (PAG, n=11; CON, n=8) completed the 16-week training program and post-testing. There was a significant (P<0.05) increase in peak aerobic capacity (relative VO2peak: 17.2%, absolute VO2peak: 9.9%) and submaximal power output (26.3%) in the PAG group only. Increases in strength ranged from 11.5-38.9% and were significantly (P<0.05) different from CON for vertical bench press, seated row, and rickshaw press. Adherence to the exercise program was 85.2±8.3% for PAG, 44.4±34.3% for CON (P<0.01). The PAG for adults with SCI are sufficient to improve aspects of aerobic and muscular fitness and should be promoted as a means to improve physical capacity. Ontario Neurotrauma Foundation (ONF), Natural Sciences and Engineering Research Council (NSERC) of Canada.


A single thiourea group is not enough to get stable thiourea lipoplexes.
The preparation of a new family of lipothiourea is reported using an automatic synthetic workstation. In these compounds the headgroups were made from single thiourea derivatives. The physicochemical properties and the transfection efficiency of several members of the family were studied. It was found that in the presence of DMPC small lipoplexes could be prepared. In opposite to the previously described di- and tri-lipothioureas most of these liposomes are unstable overtime. In addition, even the stable ones show no transfecting efficiency. All these data demonstrate that at least two thiourea groups are necessary to produce stable lipoplexes, to condense DNA and to give efficient transfection.


Motor Planning of Vertical Arm Movements in Healthy Older Adults: Does Effort Minimization Persist With Aging?
Several sensorimotor modifications are known to occur with aging, possibly leading to adverse outcomes such as falls. Recently, some of those modifications have been proposed to emerge from motor planning deteriorations. Motor planning of vertical movements is thought to engage an internal model of gravity to anticipate its mechanical effects on the body-limbs and thus to genuinely produce movements that minimize muscle effort. This is supported, amongst other results, by direction-dependent kinematics where relative durations to peak accelerations and peak velocity are shorter for upward than for downward movements. The present study compares the motor planning of fast and slow vertical arm reaching movements between 18 young (24 ± 3 years old) and 17 older adults (70 ± 5 years old). We found that older participants still exhibit strong directional asymmetries (i.e., differences between upward and downward movements), indicating that optimization processes during motor planning persist with healthy aging. However, the size of these differences was increased in older participants, indicating that gravity-related motor planning changes with age. We discuss this increase as the possible result of an overestimation of gravity torque or increased weight of the effort cost in the optimization process. Overall, these results support the hypothesis that feedforward processes and, more precisely, optimal motor planning, remain active with healthy aging.