Matrix metalloproteinases-2,-3,-7,-9 and-10, but not MMP-11, are differentially expressed in normal, benign tumorigenic and malignant human keratinocyte cell lines

In order to investigate the correlations between constitutive proteinase expression and the degree of tumorigenicity of cancer cells we have studied a model system of three keratinocyte cell lines. RT-PCR studies showed that the cell lines express the genes of matrix metalloproteinase-2, -3, -7, -9, -10 and -11, indicating that they are able to synthesize the corresponding enzymes. Actual MMP synthesis was proven by zymography and Western blotting. In conditioned media gelatinolytic activities or immunoreactive forms of MMP-2, -3, -7, -9, -10 and -11 were detected. The signal intensities showed that MMP secretion increases in the order HaCaT < A5 less than or equal to II-4RT, whereas only MMP-11 is secreted by all cell lines in equal amounts, Intracellularly, enhanced levels of one or both of the tumorigenic variants were only found for MMP-3 -9 and -10, suggesting special functions of these intracellular MMP pools for the tumorigenic cell lines. For MMP-11 exclusive expression in stromal fibroblasts of tumor tissues is widely accepted; however, our results and three other recent reports demonstrate that this concept is not generally valid. In conclusion, the three keratinocyte cell lines investigated here represent an excellent model for studying constitutive expression and secretion of MMPs in correlation to the degree of in vivo tumorigenicity

Inpatient and outpatient loop electrosurgery excision procedure for cervical intraepithelial neoplasia: a retrospective analysis

Purpose: To determine whether the outpatient loop electrosurgical excision procedure (LEEP) conization (out-LEEP) is as effective and safe as inpatient LEEP conization (in-LEEP) with regard to the complete removal of cervical dysplasia, recurrence-free survival and post-operative morbidity. Methods: 233 patients were included in this retrospective cohort study from January 2002 to December 2007. 181 had outpatient treatment and 52 inpatient treatment. We used Mann-Whitney U test, two-sided Fisher's exact test, Chi-square test, log rank test and Kaplan-Meier curve. Results: Incomplete excision was found in 16/52 (30.8%) cases in the inpatient group and 46/181 (25.4%) in the outpatient group (P=0.48). Six patients had post-operative complications: two cases of secondary haemorrhage in each group (in-LEEP 3.8%, out-LEEP 1.1%, P=0.22) and two cases of cervical stenosis amongst inpatients (3.8%, P=0.049). Alteration of specimen by thermal artifact were reported in 4/52 (7.7%) of in-LEEP cones and 10/181 (5.5%) of out-LEEP cones (P=0.52). Measurements of cones in both groups were comparable with a mean depth of 9.35mm (±5.5mm) and 8.4mm (±3.4mm), respectively. Conclusion: Our results suggest that efficacy and safety of ambulatory LEEP conization is comparable as in inpatient procedur

Mitochondrial DNA mutations in renal cell carcinomas revealed no general impact on energy metabolism

Previously, renal cell carcinoma tissues were reported to display a marked reduction of components of the respiratory chain. To elucidate a possible relationship between tumourigenesis and alterations of oxidative phosphorylation, we screened for mutations of the mitochondrial DNA (mtDNA) in renal carcinoma tissues and patient-matched normal kidney cortex. Seven of the 15 samples investigated revealed at least one somatic heteroplasmic mutation as determined by denaturating HPLC analysis (DHPLC). No homoplasmic somatic mutations were observed. Actually, half of the mutations presented a level of heteroplasmy below 25%, which could be easily overlooked by automated sequence analysis. The somatic mutations included four known D-loop mutations, four so far unreported mutations in ribosomal genes, one synonymous change in the ND4 gene and four nonsynonymous base changes in the ND2, COI, ND5 and ND4L genes. One renal cell carcinoma tissue showed a somatic A3243G mutation, which is a known frequent cause of MELAS syndrome (mitochondrial encephalomyopathy, lactic acidosis, stroke-like episode) and specific compensatory alterations of enzyme activities of the respiratory chain in the tumour tissue. No difference between histopathology and clinical progression compared to the other tumour tissues was observed. In conclusion, the low abundance as well as the frequently observed low level of heteroplasmy of somatic mtDNA mutations indicates that the decreased aerobic energy capacity in tumour tissue seems to be mediated by a general nuclear regulated mechanism

Information transfer through disordered media by diffuse waves

We consider the information content h of a scalar multiple-scattered, diffuse wave field $\psi(\vec{r})$ and the information capacity C of a communication channel that employs diffuse waves to transfer the information through a disordered medium. Both h and C are shown to be directly related to the mesoscopic correlations between the values of $\psi(\vec{r})$ at different positions $\vec{r}$ in space, arising due to the coherent nature of the wave. For the particular case of a communication channel between two identical linear arrays of $n \gg 1$ equally-spaced transmitters/receivers (receiver spacing a), we show that the average capacity $\propto n$ and obtain explicit analytic expressions for $/n$ in the limit of $n \to \infty$ and $k \ell \to \infty$, where $k= 2\pi/ \lambda$, $\lambda$ is the wavelength, and $\ell$ is the mean free path. Modification of the above results in the case of finite but large n and $k \ell$ is discussed as well.Comment: REVTeX 4, 12 pages, 7 figure

Prefrontal involvement in imitation learning of hand actions : effects of practice and expertise.

In this event-related fMRI study, we demonstrate the effects of a single session of practising configural hand actions (guitar chords) on cortical activations during observation, motor preparation, and imitative execution. During the observation of non-practised actions, the mirror neuron system (MNS), consisting of inferior parietal and ventral premotor areas, was more strongly activated than for the practised actions. This finding indicates a strong role of the MNS in the early stages of imitation learning. In addition, the dorsolateral prefrontal cortex (DLPFC) was selectively involved during observation and motor preparation of the non-practised chords. This finding confirms Buccino et al.’s (2004a) model of imitation learning: for actions that are not yet part of the observer’s motor repertoire, DLPFC engages in operations of selection and combination of existing, elementary representations in the MNS. The pattern of prefrontal activations further supports Shallice’s (2004) proposal of a dominant role of the left DLPFC in modulating lower-level systems, and of a dominant role of the right DLPFC in monitoring operations

Impact of newly constructed primary healthcare centres on antenatal care attendance, facility delivery and all-cause mortality: quasi-experimental evidence from Taabo health and demographic surveillance system, Côte d'Ivoire

OBJECTIVES: Access to quality care remains limited, particularly in low-income and middle-income countries. Although better health outcomes for families living in close proximity to healthcare facilities have been documented in cross-sectional studies, evidence on the extent to which additional health facilities can contribute to improved population health remains scanty. We aimed to estimate the causal impact of newly constructed primary healthcare facilities within a health and demographic surveillance (HDSS) site in Cote d'Ivoire. DESIGN: We conducted a quasi-experimental study. Logistic and Cox proportional hazards regression models were used to estimate the impact of new healthcare facilities on healthcare-seeking behaviour and all-cause mortality. SETTING: Data were collected prospectively through the Taabo HDSS located in south-central Cote d'Ivoire between 2010 and 2018. PARTICIPANTS: We analysed 2957 deaths across 440 973 person-year observations as well as 14 132 live births. PRIMARY OUTCOME MEASURES: The primary outcomes were antenatal care (ANC) attendance, facility delivery and mortality. Logistic and Cox proportional hazards models were employed to estimate the impact of the new health facilities on ANC attendance, facility delivery and child as well as adult mortality. RESULTS: Average distance to the nearest healthcare facility declined from 5.5 km before to 2.8 km after opening of four new healthcare facilities in targeted villages. No improvement was observed for ANC attendance, institutional deliveries and adult mortality. New facilities reduced the risk of post-neonatal infant mortality by 46% (HR 0.54, 95% CI 0.31 to 0.94, p<0.05), suggesting a mortality gradient of 2 deaths per 1000 for each additional km (Coef=0.002, 95% CI 0.000 to 0.004, p<0.05). CONCLUSIONS: Our results suggest that new facilities do not necessarily improve healthcare utilisation and health outcomes. Further research is needed to identify the best ways to ensure access to quality care in resource-constrained settings

Exaggerated aggression and decreased anxiety in mice deficient in brain serotonin

Serotonin is a major neurotransmitter in the central nervous system (CNS). Dysregulation of serotonin transmission in the CNS is reported to be related to different psychiatric disorders in humans including depression, impulsive aggression and anxiety disorders. The most frequently prescribed antidepressants and anxiolytics target the serotonergic system. However, these drugs are not effective in 20–30% of cases. The causes of this failure as well as the molecular mechanisms involved in the origin of psychological disorders are poorly understood. Biosynthesis of serotonin in the CNS is initiated by tryptophan hydroxylase 2 (TPH2). In this study, we used Tph2-deficient (Tph2−/−) mice to evaluate the impact of serotonin depletion in the brain on mouse behavior. Tph2−/− mice exhibited increased depression-like behavior in the forced swim test but not in the tail suspension test. In addition, they showed decreased anxiety-like behavior in three different paradigms: elevated plus maze, marble burying and novelty-suppressed feeding tests. These phenotypes were accompanied by strong aggressiveness observed in the resident–intruder paradigm. Despite carrying only one copy of the gene, heterozygous Tph2+/− mice showed only 10% reduction in brain serotonin, which was not sufficient to modulate behavior in the tested paradigms. Our findings provide unequivocal evidence on the pivotal role of central serotonin in anxiety and aggression

Influence of magnetic field on paramagnetic-ferromagnetic transition in La1−x_{1-x}Cax_{x}MnO3_{3} (x≈0.25x\approx 0.25) crystal: ultrasonic and transport studies

The ultrasonic properties of La$_{1-x}$Ca$_{x}$MnO$_{3}$ ($x\approx 0.25$) with the Curie temperature $T_C$ about 200 K are studied. Temperature dependences of longitudinal and transverse sound velocities were measured in zero magnetic field and for different constant magnetic fields as well. The ultrasonic study is supported by magnetic, resistive, magnetoresistive, structural and other measurements of the sample that facilitate interpretation of the results obtained. The magnetic field influence on sound properties found in this study presents some new features of the interplay between the elastic and magnetic properties of these compounds. It is shown that the paramagnetic-ferromagnetic transition in the sample studied is first order, but can become second order under the influence of applied magnetic field.Comment: submitted to Phys. Rev.

A Comparison of Stripe Modulations in La1.875_{1.875}Ba0.125_{0.125}CuO4_4 and La1.48_{1.48}Nd0.4_{0.4}Sr0.12_{0.12}CuO4_4

We report combined soft and hard x-ray scattering studies of the electronic and lattice modulations associated with stripe order in La$_{1.875}$Ba$_{0.125}$CuO$_4$ and La$_{1.48}$Nd$_{0.4}$Sr$_{0.12}$CuO$_4$. We find that the amplitude of both the electronic modulation of the hole density and the strain modulation of the lattice is significantly larger in La$_{1.875}$Ba$_{0.125}$CuO$_4$ than in La$_{1.48}$Nd$_{0.4}$Sr$_{0.12}$CuO$_4$ and is also better correlated. The in-plane correlation lengths are isotropic in each case; for La$_{1.875}$Ba$_{0.125}$CuO$_4$, $\xi^{hole}=255\pm 5$ \AA\ whereas for La$_{1.48}$Nd$_{0.4}$Sr$_{0.12}$CuO$_4$F, $\xi^{hole}=111\pm 7$ \AA. We find that the modulations are temperature independent in La$_{1.875}$Ba$_{0.125}$CuO$_4$ in the low temperature tetragonal phase. In contrast, in La$_{1.48}$Nd$_{0.4}$Sr$_{0.12}$CuO$_4$, the amplitude grows smoothly from zero, beginning 13 K below the LTT phase transition. We speculate that the reduced average tilt angle in La$_{1.875}$Ba$_{0.125}$CuO$_4$ results in reduced charge localization and incoherent pinning, leading to the longer correlation length and enhanced periodic modulation amplitude.Comment: 6 pages, 4 figure

Evidence for CuO conducting band splitting in the nodal direction of Bi-2212

Using angle-resolved photoemission spectroscopy with ultimate momentum resolution we have explicitly resolved the bilayer splitting in the nodal direction of Bi-2212. The splitting is observed in a wide doping range and, within the experimental uncertainty, its size does not depend on doping. The value of splitting derived from the experiment is in good agreement with that from band structure calculations which implies the absence of any electronic confinement to single planes within bilayers of Bi-2212. Other consequences of this finding are also discussed.Comment: Fermi surface map with well resolved nodal splitting is adde