Segmental relaxation was measured for a series of polysytrenes (PS) of varying molecular weight. The normalized Arrhenius plots of segmental relaxation times (fragility curves) become less steep for ...shorter chain lengths. Since the shape of the relaxation function is invariant to molecular weight, such behavior is a deviation from the usual correlation between time and temperature dependencies. Although the dependence of relaxation times on T g-normalized temperature is weaker (less fragile), lower molecular weight PS has a larger heat capacity change at T g. This result is at odds with an interpretation of temperature dependencies in terms of the degrees of freedom available to the glass upon transition to the viscous liquid.
Affective instability is widely regarded as being the core problem in patients with borderline personality disorder (BPD) and the driving force behind the severe clinical manifestations of BPD ...symptoms. In ICD-10, BPD is even labelled as emotionally unstable personality disorder. In the last years, the advent of electronic diaries, in combination with sophisticated statistical analyses, enabled studying affective instability in everyday life. Surprisingly, most recent studies using state-of-the-art methodology to assess and model affective instability in BPD failed to show any specificity, supporting the idea of a transdiagnostic construct. In addition, dysfunctional emotion regulation strategies revealed results contradictory to current clinical beliefs. Using multiple data sets and multilevel modelling, we will demonstrate that to understand affective instability it is important: – to statically model basic subcomponents of affective dynamics simultaneously; – in combination with dysfunctional regulation strategies; – cognitive processes in everyday life. Altogether, current research suggests that the dynamics of affective states and their intentional regulation are even more important to psychological health and maladjustment, than the affective states itself. Current initiatives to fundamentally improve psychopathological research are looking at basic physiological processes spanning across disorders. However, these approaches do fall short in understanding human behaviours as dynamical processes that unfold in the broadest setting imaginable – everyday life. Only the combination of basic physiological processes and methods assessing dynamical affective mechanisms in everyday life will enhance our understanding how dysregulations and dysfunctions of fundamental aspects of behaviour cut across traditional disorders.
Innate immune responses to pathogens are driven by co-presentation of multiple pathogen-associated molecular patterns (PAMPs). Combinations of PAMPs can trigger synergistic immune responses, but the ...underlying molecular mechanisms of synergy are poorly understood. Here, we used synthetic particulate carriers co-loaded with monophosphoryl lipid A (MPLA) and CpG as pathogen-like particles (PLPs) to dissect the signaling pathways responsible for dual adjuvant immune responses. PLP-based co-delivery of MPLA and CpG to GM-CSF-driven mouse bone marrow-derived antigen-presenting cells (BM-APCs) elicited synergistic interferon-β (IFN-β) and interleukin-12p70 (IL-12p70) responses, which were strongly influenced by the biophysical properties of PLPs. Mechanistically, we found that MyD88 and interferon regulatory factor 5 (IRF5) were necessary for IFN-β and IL-12p70 production, while TRIF signaling was required for the synergistic response. Both the kinetics and magnitude of downstream TRAF6 and IRF5 signaling drove the synergy. These results identify the key mechanisms of synergistic Toll-like receptor 4 (TLR4)-TLR9 co-signaling in mouse BM-APCs and underscore the critical role of signaling kinetics and biophysical properties on the integrated response to combination adjuvants.
Affective dysregulation is widely regarded as being the core problem in patients with borderline personality disorder (BPD). Moreover, BPD is the disorder mainly associated with affective ...dysregulation. However, the empirical confirmation of the specificity of affective dysregulation for BPD is still pending. We used a validated approach from basic affective science that allows for simultaneously analyzing three interdependent components of affective dysregulation that are disturbed in patients with BPD: homebase, variability, and attractor strength (return to baseline).
We applied two types of multilevel models on two e-diary datasets to investigate group differences regarding three subcomponents between BPD patients (n = 43; n = 51) and patients with posttraumatic stress disorder (PTSD; n = 28) and those with bulimia nervosa (BN; n = 20) as clinical control groups in dataset 1, and patients with panic disorder (PD; n = 26) and those with major depression (MD; n = 25) as clinical control groups in dataset 2. In addition, healthy controls (n = 28; n = 40) were included in the analyses. In both studies, e-diaries were used to repeatedly collect data about affective experiences during participants' daily lives. In study 1 a high-frequency sampling strategy with assessments in 15 min-intervals over 24 h was applied, whereas the assessments occurred every waking hour over 48 h in study 2. The local ethics committees approved both studies, and all participants provided written informed consent.
In contradiction to our hypotheses, BPD patients did not consistently show altered affective dysregulation compared to the clinical patient groups. The only differences in affective dynamics in BPD patients emerged with regard to one of three subcomponents, affective homebase. However, these results were not even consistent. Conversely, comparing the patients to healthy controls revealed a pattern of more negative affective homebases, higher levels of affective variability, and (partially) reduced returns to baseline in the patient groups.
Our results indicate that affective dysregulation constitutes a transdiagnostic mechanism that manifests in similar ways in several different mental disorders. We point out promising prospects that might help to elucidate the common and distinctive mechanisms that underlie several different disorders and that should be addressed in future studies.
mce3 is one of the four virulence-related mce operons of Mycobacterium tuberculosis. In a previous work we showed that the overexpression of Mce3R in Mycobacterium smegmatis and M. tuberculosis ...abolishes the expression of lacZ fused to the mce3 promoter, indicating that Mce3R represses mce3 transcription.
We obtained a knockout mutant strain of M. tuberculosis H37Rv by inserting a hygromycin cassette into the mce3R gene. The mutation results in a significant increase in the expression of mce3 genes either in vitro or in a murine cell macrophages line as it was determined using promoter-lacZ fusions in M. tuberculosis. The abundance of mce1, mce2 and mce4 mRNAs was not affected by this mutation as it was demonstrated by quantitative RT-PCR. The mce3R promoter activity in the presence of Mce3R was significantly reduced compared with that in the absence of the regulator, during the in vitro culture of M. tuberculosis.
Mce3R repress the transcription of mce3 operon and self regulates its own expression but does not affect the transcription of mce1, mce2 and mce4 operons of M. tuberculosis.
The segmental relaxation properties of a low molecular weight (4.6 kg/mol), cyclic polystyrene (PS) were characterized. The sample was obtained by fractionation using HPLC at the chromatographic ...critical condition, which yields a ring uncontaminated by its linear precursor. Both the glass temperature and the temperature dependence of the segmental relaxation times for the ring PS were equivalent to the high molecular weight limiting values for the linear polymer. These results are interpreted by considering the configurational mobility of a polymer lacking chain ends.
The ability to visualize mRNA in single living cells and monitor in real-time the changes of mRNA level and localization can provide unprecedented opportunities for biological and disease studies. ...However, the mRNA detection specificity and sensitivity are critically dependent on the selection of target sequences and their accessibility. We carried out an extensive study of the target accessibility of BMP-4 mRNA using 10 different designs of molecular beacons (MBs), and identified the optimal beacon design. Specifically, for MB design 1 and 8 (MB1 and MB8), the fluorescent intensities from BMP-4 mRNA correlated well with the GFP signal after upregulating BMP-4 and co-expressing GFP using adenovirus, and the knockdown of BMP-4 mRNA using siRNA significantly reduced the beacon signals, demonstrating detection specificity. The beacon specificity was further confirmed using blocking RNA and in situ hybridization. We found that fluorescence signal from MBs depends critically on target sequences; the target sequences corresponding to siRNA sites may not be good sites for beacon-based mRNA detection, and vice versa. Possible beacon design rules are identified and approaches for enhancing target accessibility are discussed. This has significant implications to MB design for live cell mRNA detection.
•Detecting M. bovis antibodies in cattle sera after a tuberculin skin test (TST) may improve bovine tuberculosis control.•Used as an anamnestic test, the ELISA reported herein had high levels of ...specificity and positive predictive value.•The ELISA fulfilled the World Organization for Animal Health criteria.•This serological ELISA used 15–17 days after a negative TST could be used on dairy farms to improve livestock health.
Programs for the eradication of bovine tuberculosis (bTB) focus on the tuberculin skin test (TST) and slaughter of reactor cattle. However, the disease remains an animal health concern in several countries and improving the efficiency of the TST has become a critical issue. The detection of Mycobacterium bovis antibodies in serum, within weeks after the TST, may be a rapid and inexpensive way to improve bTB control. This study reports the validation of an enzyme-linked immunosorbent assay (ELISA) to detect bovine tuberculosis as an ancillary test to TST in dairy farms in Argentina.
The estimated validation parameters were within the established requirements of the World Organization for Animal Health (OIE). The test demonstrated high repeatability, with coefficients of variation <25%. High test reproducibility through interlaboratory testing was also found, with an estimated Pearson coefficient of 0.9648 (95% confidence intervals 0.9315–0.9820). The ELISA detected tuberculous cattle unidentified by the TST. Of 43 animals sent to slaughterhouses that were ELISA positive 15–17 days after a negative TST, 36 were confirmed as infected with M. bovis by histopathology and IS6110 PCR. According to ROC curve analysis of results of 145 cattle from M. bovis-free herds and the 36 M. bovis-infected cattle, at a corrected optical density cut-off point of 0.3853, specificity was 95.95% and the positive predictive value at this cut-off was 83.72%. The ELISA detection test validated in this study could be readily applied in dairy farms, to complement a prior TST and improve livestock health.
PDF
