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A myelopoiesis gene signature in circulating leucocytes, exemplified by increased myeloperoxidase (MPO) and proteinase 3 (PR3) mRNA levels, has been reported in patients with active anti-neutrophil cytoplasm antibody associated vasculitis (AAV) and to a lesser extent during remission. We hypothesized that this signature could predict disease relapse. mRNA levels of PR3, MPO, selected myelopoiesis transcription factors (CEBPA, CEBPB, SPIB, SPI1) and microRNAs (miRNAs) from patient and control peripheral blood mononuclear cells (PBMCs) and polymorphonuclear cells (PMNs) were analyzed and associated with clinical data. Patients in stable remission had higher mRNA levels for PR3 (PBMCs, PMNs) and MPO (PBMCs). PR3 and SPIB mRNA correlated positively in control but negatively in patient PBMCs. Statistically significant correlations existed between PR3 mRNA and several miRNAs in controls, but not in patients. PR3/MPO mRNA levels were not associated with previous or future relapses but correlated to steroid treatment. Prednisolone doses were negatively linked to SPIB and miR-155-5p, miR-339-5p (PBMCs) and to miR-221, miR-361, miR-505 (PMNs). PR3 mRNA in PBMCs correlated with time since last flare, blood leucocyte count and estimated glomerular filtration rate. Our results show that elevated leucocyte PR3 mRNA levels in AAV patients in remission do not predict relapse. The origin seems multifactorial, but to an important part explainable by prednisolone action. Gene signatures in patients with AAV undergoing steroid treatment should therefore be interpreted accordingly

Genetic diversity, biogeography and the morpho-genetic relationship in extant planktonic foraminifera

Planktonic foraminifera are widely used as proxies for the reconstruction of past ocean conditions, a method that requires exact species classification and knowledge of their ecological adaptations. Species classification traditionally was conducted using morphological characteristics of the calcite shell. The application of genetic approaches on living planktonic foraminifera, however, challenged the classical species concept, by discovering a large number of cryptic species within the morphospecies. The present dissertation aims at establishing a connection between the fossil record and the genetic background of extant species by finding out to what degree morphologically defined species reflect real biological diversity. Molecular genetic techniques in combination with morphometric analyses were used to examine the extent of cryptic diversity in selected morphospecies and its relation to morphological traits. Furthermore, the biogeographic distribution patterns of extant species were analyzed in order to differentiate between species with local adaptations and endemism versus species with global dispersal and gene flow

Assessment of nasal and oral flow of amniotic fluid in 46 non-anomalous fetuses with sonographic and echocardiographic examination

Objectives: The aim of the paper was to assess nasal and oral amniotic fluid flows, with the use of color ultrasound and spectral Doppler, in normal fetuses. Material and methods: Forty-six fetuses of singleton gestations were studied prospectively. Spectrum imaging and maximal nasal fluid flow velocities were described. Episodes of regurgitation (external flow from the mouth), swallowing (internal flow at the level of oropharynx and then entrance to the esophagus) were evaluated in two groups: Fetuses < 27 weeks of gestation and 27 weeks of gestation and older. Statistical analysis was done using Fischer exact test and t-test at p = 0.05. Results: Twenty-one fetuses were < 27 weeks of gestational age and presented mean maximal both inspiratory and expiratory nasal fluid flow velocities significantly lower than twenty-five fetuses who were ≥ 27 weeks of gestational age (p = 0.035 and p = 0.031 respectively, t-test). Episodes of regurgitation were observed more frequently in group of “younger” fetuses (p = 0.006, Fischer exact test). There was no statistically significant relationship between irregular nasal flow spectrum by color Doppler and gestational age group (p = 0.264, Fischer exact test). Conclusions: Episodes of regurgitation occurred in normal fetuses < 27th week of gestation. Fast amniotic nasal fluid flows without episodes of regurgitation were observed more frequently in fetuses ≥ 27 weeks and it could be interpreted as an additional sonographic feature of prenatal maturation

Success Attributions and More: Multidimensional Extensions of the Sexual Attribution Bias to Failure Attributions, Social Emotions, and the Desire for Social Interaction

According to the recently discovered sexual attribution bias (SAB), young adults attribute the success of same-aged, same-sex attractive stimulus persons in a more derogative way than the success of less attractive same-sex persons, whereas this pattern is reversed for members of the opposite sex. Because this bias has so far only been investigated with respect to attributions in success scenarios, two studies examined its potential transferability to other psychological variables and settings: Study 1 (N = 419)demonstrated analogous biases for emotions and the desire for social interaction, and Study 2 (N = 509) revealed that the SAB can also be extended to failure scenarios

Obesity is Associated with More Disability at Presentation and After Treatment in Low Back Pain but Not in Neck Pain: Findings from the OIOC Registry

Background: The influence on the treatment response in patients with low back pain (LBP) and neck pain (NP) is unknown. The aim of the study was to investigate the influence of body weight in patients with low back pain (LBP) and neck pain (NP) on baseline and end of treatment disability. Methods: Cross-sectional analysis of baseline factors. Longitudinal analysis of prospectively collected patient information at an outpatient physical therapy registry (data from June 2010 to December 2012). WHO-BMI classification was used: underweight, lean, overweight, obesity class I, obesity class II and III. The influence of body weight and a predefined set of confounders was analyzed by multiple regression models. Results: In LBP, disability increased with increasing BMI [lean = reference, obesity class I Beta 5.41 (95 % CI 0.75; 10.07), obesity class II-III Beta 7.58 (95 % CI 2.13; 13.03)]. Compared to lean patients, disability after treatment improved in overweight subjects [Beta −3.90 (95 % CI −7.4; −0.41)] but not in subjects with obesity class II–III [Beta 3.43 (95 % CI −3.81; 10.68)]. There were insufficient patients in the sample with severe obesity and therefore this trend has to be confirmed. The likelihood for meaningful important change (MID) was similar in all BMI subgroups. For patients with NP, BMI was not associated with baseline disability, and did not predict end of treatment disability or the likelihood of a MID. These findings must be interpreted with caution as BMI subgroups did not meet the required sample size. Conclusion: Overweight and obesity are associated with higher levels of disability before treatment in LBP patients, but not in NP. In severely obese patients class II–III with LBP the rate of MID was lowest indicating that these patients experienced the least treatment response compared to the other groups. Further studies should address the impact of severe obesity on the prognosis of LBP. In patients with LBP, severe obesity may be an important factor to consider during the physical therapy treatment. In particular, combined treatment strategies combining weight management, cardiovascular fitness, and low back pain rehabilitation should be investigated

Insights into vertebrate head development: From cranial neural crest to the modelling of neurocristopathies

Although the vertebrate head has evolved to a wide collection of adaptive shapes, the fundamental signalling pathways and cellular events that outline the head skeleton have proven to be highly conserved. This conservation suggests that major morphological differences are due to changes in differentiation and morphogenetic programs downstream of a well-maintained developmental prepattern. Here we provide a brief examination of the mechanisms and pathways responsible for vertebrate head development, as well as an overview of the animal models suitable for studying face development. In addition, we describe the criteria for neurocristopathy classifica-tion, highlighting the contribution of zebrafish to the modelling of Treacher Collins/Franceschetti Syndrome, an emblematic neurocristopathy. The contributions from our laboratory reveal that proper zebrafish head development depends on the fine-tuning of developmental-gene expression mediated by nucleic acid binding proteins able to regulate DNA conformation and / or the neuroepithelium redox state.Fil: Weiner, Andrea Maria Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Coux, Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Armas, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Calcaterra, Nora Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentin

What's new about CNBP? Divergent functions and activities for a conserved nucleic acid binding protein

Background: Cellular nucleic acid binding protein (CNBP) is a conserved single-stranded nucleic acid binding protein present in most eukaryotes, but not in plants. Expansions in the CNBP gene cause myotonic dystrophy type 2. Initially reported as a transcriptional regulator, CNBP was then also identified acting as a translational regulator. Scope of review: The focus of this review was to link the CNBP structural features and newly reported biochemical activities with the recently described biological functions, in the context of its pathological significance. Major conclusions: Several post-translational modifications affect CNBP subcellular localization and activity. CNBP participates in the transcriptional and translational regulation of a wide range of genes by remodeling single-stranded nucleic acid secondary structures and/or by modulating the activity of trans-acting factors. CNBP is required for proper neural crest and heart development, and plays a role in cell proliferation control. Besides, CNBP has been linked with neurodegenerative, inflammatory, and congenital diseases, as well as with tumor processes. General significance: This review provides an insight into the growing functions of CNBP in cell biology. A unique and robust mechanistic or biochemical connection among these roles has yet not been elucidated. However, the ability of CNBP to dynamically integrate signaling pathways and to act as nucleic acid chaperone may explain most of the roles and functions identified so far.Fil: Armas, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Coux, Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Weiner, Andrea Maria Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Calcaterra, Nora Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentin

Astrometric Weak Lensing with Gaia DR3 and Future Catalogs: Searches for Dark Matter Substructure

Small-scale dark matter structures lighter than a billion solar masses are an important probe of primordial density fluctuations and dark matter microphysics. Due to their lack of starlight emission, their only guaranteed signatures are gravitational in nature. We report on results of a search for astrometric weak lensing by compact dark matter subhalos in the Milky Way with Gaia DR3 data. Using a matched-filter analysis to look for correlated imprints of time-domain lensing on the proper motions of background stars in the Magellanic Clouds, we exclude order-unity substructure fractions in halos with masses $M_{l}$ between $10^{7} \, M_{\odot}$ and $10^{9} \, M_{\odot}$ and sizes of one parsec or smaller. We forecast that a similar approach based on proper accelerations across the entire sky with data from Gaia DR4 may be sensitive to substructure fractions of $f_{l} \gtrsim 10^{-3}$ in the much lower mass range of $10 \, M_{\odot} \lesssim M_{l} \lesssim 3 \times 10^{3} \, M_{\odot}$. We further propose an analogous technique for stacked star-star lensing events in the regime of large impact parameters. Our first implementation is not yet sufficiently sensitive but serves as a useful diagnostic and calibration tool; future data releases should enable average stellar mass measurements using this stacking method.Comment: 16 pages, 8 figure