High-resolution studies of class 0 protostars represent the key to constraining protostar fonnation models. VLA 16234-2417 represents the prototype of class 0 protostars, and it has been recently ...identified as a triple non-coeval system. We aim at deriving the physical properties of the jets in VLA16234-2417 using tracers of shocked gas. ALMA Cycle 0 Early Science observations of CO(2-1) in the extended configuration are presented in comparison with previous SMA CO(3-2) and Herschel-PACS OI 63 pm observations. Gas morphology and kinematics were analysed to constrain the physical structure and origin of the protostellar outflows. Our high-resolution ALMA observations seem to suggest there is a fast and collimated jet component associated with source B. This scenario would confirm that source B is younger than A, that it is in a very early stage of evolution, and that it drives a faster, more collimated, and more compact jet with respect to the large-scale slower outflow driven by A.
Objective
Longitudinal and cross‐sectional studies suggest that affective instability is inversely related to greater age in borderline personality disorder (BPD). However, existing studies relied on ...retrospective self‐reports of perceived instability. We examined affective instability in everyday life in patients with BPD and healthy controls (HCs) by age in a cross‐sectional e‐diary study.
Methods
Two hundred and sixty female participants between 14 and 53 years of age (130 patients with BPD and 130 HCs) carried an e‐diary over 4 days. The e‐diaries emitted a prompting signal in approximately hourly intervals asking participants to rate their current affective state, that is valence (ranging from pleasant to unpleasant) and tense arousal (ranging from calm/relaxed to restless/under tension).
Results
Multilevel analyses revealed a significant interaction of age and group predicting affective instability (valence: F(1,255.6) = 7.59; P < 0.01; tense arousal: F(1,252) = 6.08; P < 0.01), suggesting that affective instability significantly declines with greater age in patients with BPD. Controlling for the number of comorbid disorders and BPD severity did not change the results, illustrating an inverse relationship between age and affective instability in BPD (significant interaction of age*group for valence: F(1,238.7) = 5.74; P < 0.02 and tense arousal: F(1,235.2) = 5.28; P < 0.02).
Conclusion
Affective instability during daily life declines with greater age in BPD. This decline is irrespective of comorbidity and BPD severity.
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.
Plasmid pMET7C containing a 6.05 kb DNA insert from Clostridium acetobutylicum P262 made Escherichia coli F19 cells sensitive to metronidazole. The nucleotide sequence of the C. acetobutylicum DNA ...controlling metronidazole sensitivity in E. coli F19 revealed an ORF of 972 bp which encoded a protein of 324 amino acids with a calculated Mr of 35,000. The amino acid sequence encoded by the ORF contained a helix-turn-helix DNA-binding domain and was homologous to the catabolite control protein, CcpA, from Bacillus subtilis and Bacillus megaterium, a tRNA repressor of E. coli encoded by the shl gene, and the GalR, Lacl and PurR repressors of E. coli. The C. acetobutylicum ORF, which was termed regA, complemented a B. subtilis ccpA mutant and an E. coli shl mutant, but was unable to complement E. coli galR, lacl or purR mutants. To determine whether the regA gene product was involved in the regulation of amylase gene expression in C. acetobutylicum, a starch-degrading enzyme gene (staA) from C. acetobutylicum NCIMB 8052 was cloned. The RegA protein inhibited the degradation of starch by the C. acetobutylicum staA gene product in E. coli.
Cyclotron lines, also called cyclotron resonant scattering features are spectral features, generally appearing in absorption, in the X-ray spectra of objects containing highly magnetized neutron ...stars, allowing the direct measurement of the magnetic field strength in these objects. Cyclotron features are thought to be due to resonant scattering of photons by electrons in the strong magnetic fields. The main content of this contribution focusses on electron cyclotron lines as found in accreting X-ray binary pulsars (XRBP) with magnetic fields on the order of several 1012 Gauss. Also, possible proton cyclotron lines from single neutron stars with even stronger magnetic fields are briefly discussed. With regard to electron cyclotron lines, we present an updated list of XRBPs that show evidence of such absorption lines. The first such line was discovered in a 1976 balloon observation of the accreting binary pulsar Hercules X-1, it is considered to be the first direct measurement of the magnetic field of a neutron star. As of today (end 2018), we list 35 XRBPs showing evidence of one ore more electron cyclotron absorption line(s). A few have been measured only once and must be confirmed (several more objects are listed as candidates). In addition to the Tables of objects, we summarize the evidence of variability of the cyclotron line as a function of various parameters (especially pulse phase, luminosity and time), and add a discussion of the different observed phenomena and associated attempts of theoretical modeling. We also discuss our understanding of the underlying physics of accretion onto highly magnetized neutron stars. For proton cyclotron lines, we present tables with seven neutron stars and discuss their nature and the physics in these objects.
The Dunkin Hartley is the most common guinea pig strain used in biomedical research, particularly for studies of asthma, allergy, infectious disease, reproduction, and osteoarthritis. Minimally ...invasive blood tests, such as complete blood counts and serum biochemistry profiles, are often collected for diagnostics and laboratory analyses. However, reference intervals for these assays have not yet been well-documented in this strain. The purpose of this study was to establish reference intervals for hematologic and biochemical parameters of Dunkin Hartley guinea pigs and determine age- and sex-related differences. Hematologic and biochemical parameters were retrospectively obtained from 145 male and 68 female guinea pigs between 2 and 15 months of age. All blood parameters were analyzed by a veterinary clinical pathology laboratory. Reference intervals were established according to the American Society for Veterinary Clinical Pathology guidelines. Age- and sex-related differences were determined using unpaired t-tests or nonparametric Mann-Whitney tests. Hematocrit, red blood cell distribution width, mean platelet volume, white blood cell count, heterophils, monocytes, eosinophils, glucose, blood urea nitrogen, creatinine, calcium, magnesium, total protein, albumin, globulin, cholesterol, aspartate aminotransferase, gamma glutamyl transferase, and bicarbonate increased with age. Mean corpuscular hemoglobin concentration, cellular hemoglobin concentration mean, platelets, lymphocytes, phosphorus, albumin/globulin ratio, alkaline phosphatase, anion gap, and calculated osmolality decreased with age. Males had higher hemoglobin, hematocrit, red blood cell count, mean corpuscular hemoglobin concentration, white blood cell count, heterophils, Foa-Kurloff cells, alanine aminotransferase, and bicarbonate and lower mean corpuscular volume, red blood cell distribution width, platelets, mean platelet volume, eosinophils, total protein, albumin, globulin, cholesterol, potassium, anion gap, calculated osmolality, and iron compared to females. Establishing age and sex differences in hematologic and biochemical parameters of Dunkin Hartley guinea pigs provides valuable insight into their physiology to better evaluate diagnostics and experimental results.
Clinical mRNA delivery remains challenging, in large part because how physiology alters delivery in vivo remains underexplored. For example, mRNA delivered by lipid nanoparticles (LNPs) is being ...considered to treat inflammation, but whether inflammation itself changes delivery remains understudied. Relationships between immunity, endocytosis, and mRNA translation lead to hypothesize that toll‐like receptor 4 (TLR4) activation reduced LNP‐mediated mRNA delivery. Therefore, LNP uptake, endosomal escape, and mRNA translation with and without TLR4 activation are quantified. In vivo DNA barcoding is used to discover a novel LNP that delivers mRNA to Kupffer cells at clinical doses; unlike most LNPs, this LNP does not preferentially target hepatocytes. TLR4 activation blocks mRNA translation in all tested cell types, without reducing LNP uptake; inhibiting TLR4 or its downstream effector protein kinase R improved delivery. The discrepant effects of TLR4 on i) LNP uptake and ii) translation suggests TLR4 activation can “override” LNP targeting, even after mRNA is delivered into target cells. Given near‐future clinical trials using mRNA to modulate inflammation, this highlights the need to understand inflammatory signaling in on‐ and off‐target cells. More generally, this suggests an LNP which delivers mRNA to one inflammatory disease may not deliver mRNA to another.
Lipid nanoparticle (LNP)‐mediated mRNA delivery is being considered to treat inflammation, but whether inflammation itself changes delivery remains unclear. Relationships between immunity and endocytosis lead to the hypothesis that toll‐like receptor 4 (TLR4) affects LNP delivery. It is found that low doses of a TLR4 agonist reduce mRNA delivery, illustrating the need to understand how dysregulated cell signaling affects nanoparticle delivery.
Dysfunctional endothelium causes more disease than any other cell type. Systemically administered RNA delivery to nonliver tissues remains challenging, in large part because there is no ...high-throughput method to identify nanoparticles that deliver functional mRNA to cells in vivo. Here we report a system capable of simultaneously quantifying how >100 lipid nanoparticles (LNPs) deliver mRNA that is translated into functional protein. Using this system (named FIND), we measured how >250 LNPs delivered mRNA to multiple cell types in vivo and identified 7C2 and 7C3, two LNPs that efficiently deliver siRNA, single-guide RNA (sgRNA), and mRNA to endothelial cells. The 7C3 delivered Cas9 mRNA and sgRNA to splenic endothelial cells as efficiently as hepatocytes, distinguishing it from LNPs that deliver Cas9 mRNA and sgRNA to hepatocytes more than other cell types. These data demonstrate that FIND can identify nanoparticles with novel tropisms in vivo.
N
-acetylcytidine (ac
C) is an ancient and highly conserved RNA modification that is present on tRNA and rRNA and has recently been investigated in eukaryotic mRNA
. However, the distribution, ...dynamics and functions of cytidine acetylation have yet to be fully elucidated. Here we report ac
C-seq, a chemical genomic method for the transcriptome-wide quantitative mapping of ac
C at single-nucleotide resolution. In human and yeast mRNAs, ac
C sites are not detected but can be induced-at a conserved sequence motif-via the ectopic overexpression of eukaryotic acetyltransferase complexes. By contrast, cross-evolutionary profiling revealed unprecedented levels of ac
C across hundreds of residues in rRNA, tRNA, non-coding RNA and mRNA from hyperthermophilic archaea. Ac
C is markedly induced in response to increases in temperature, and acetyltransferase-deficient archaeal strains exhibit temperature-dependent growth defects. Visualization of wild-type and acetyltransferase-deficient archaeal ribosomes by cryo-electron microscopy provided structural insights into the temperature-dependent distribution of ac
C and its potential thermoadaptive role. Our studies quantitatively define the ac
C landscape, providing a technical and conceptual foundation for elucidating the role of this modification in biology and disease
.
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