High Resolution 8 mm and 1 cm Polarization of IRAS 4A from the VLA Nascent Disk and Multiplicity (VANDAM) Survey

Magnetic fields can regulate disk formation, accretion and jet launching. Until recently, it has been difficult to obtain high resolution observations of the magnetic fields of the youngest protostars in the critical region near the protostar. The VANDAM survey is observing all known protostars in the Perseus Molecular Cloud. Here we present the polarization data of IRAS 4A. We find that with ~ 0.2'' (50 AU) resolution at {\lambda} = 8.1 and 10.3 mm, the inferred magnetic field is consistent with a circular morphology, in marked contrast with the hourglass morphology seen on larger scales. This morphology is consistent with frozen-in field lines that were dragged in by rotating material entering the infall region. The field morphology is reminiscent of rotating circumstellar material near the protostar. This is the first polarization detection of a protostar at these wavelengths. We conclude from our observations that the dust emission is optically thin with {\beta} ~ 1.3, suggesting that mm/cm-sized grains have grown and survived in the short lifetime of the protostar.Comment: Accepted to ApJL. 13 pages, 4 figure

The VLA/ALMA Nascent Disk and Multiplicity (VANDAM) Survey of Perseus Protostars. VI. Characterizing the Formation Mechanism for Close Multiple Systems

We present Atacama Large Millimeter/submillimeter Array (ALMA) observations of multiple protostar systems in the Perseus molecular cloud previously detected by the Karl G. Jansky Very Large Array (VLA). We observed 17 close ($<$600~AU separation) multiple systems at 1.3~mm in continuum and five molecular lines (i.e., \twco, \cateo, \thco, H$_2$CO, SO) to characterize the circum-multiple environments in which these systems are forming. We detect at least one component in the continuum for the 17 multiple systems. In three systems, one companion is not detected, and for two systems the companions are unresolved at our observed resolution. We also detect circum-multiple dust emission toward 8 out of 9 Class 0 multiples. Circum-multiple dust emission is not detected toward any of the 8 Class I multiples. Twelve systems are detected in the dense gas tracers toward their disks/inner envelopes. For these 12 systems, we use the dense gas observations to characterize their formation mechanism. The velocity gradients in the circum-multiple gas are clearly orthogonal to the outflow directions in 8 out of the 12 systems, consistent with disk fragmentation. Moreover, only two systems with separations $<$200~AU are \textit{inconsistent} with disk fragmentation, in addition to the two widest systems ($>$500~AU). Our results suggest that disk fragmentation via gravitational instability is an important formation mechanism for close multiple systems, but further statistics are needed to better determine the relative fraction formed via this method.Comment: 48 Pages, 26 Figures, 7 Tables, Accepted by Ap

Change in 1-year mortality after hip fracture surgery over the last decade in a European population

Objective: There are scarce data on the mortality after hip fracture surgery for patients treated in the most recent years. The objective of this study was to analyze whether the overall initiatives introduced over the last decade for elderly patients with hip fractures had a positive impact on the 1-year mortality. Methods: Patients treated during 2010–2012 were compared with patients treated during 2018–2020 for all-cause 1-year mortality. Variables influencing mortality were collected based on the literature, including demographic, comorbidity, cognitive status, and preinjury physical function. Crude mortalities were compared between periods, as well as with the expected mortality in the general population adjusted for age, gender, and year of surgery using the standardized mortality ratio (SMR). A multivariate model was used to identify mortality risk factors. Results: 591 patients older than 65 years were treated during 2010–2012 and 642 patients during 2018–2020. The mean age increased significantly between periods (78.9 vs. 82.6 years, respectively, p = 0.001) in both genders, together with an increase in comorbidity (p = 0.014). The in-hospital mortality risk had no significant difference between periods (2.5 vs. 2.0%, p = 0.339), but the 30-day mortality risk (8.3 vs. 5.5%, p = 0.031) and 1-year mortality risk (16.1 vs. 11.9%, p = 0.023) declined significantly. However, 1-year mortality in 2020 had an excess of 1.33 in SMR. Age older than 80 years, male gender, and Charlson comorbidity index > 2 were significant predictors of 1-year mortality. Conclusion: The important evolution achieved in the last decade for the management of patients with hip fracture surgery has led to a significant decline in 1-year mortality, but the 1-year mortality remains significantly higher compared to the general population of similar age and gender.Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature

Association of patients' geographic origins with viral hepatitis co-infection patterns, Spain

To determine if hepatitis C virus seropositivity and active hepatitis B virus infection in HIV-positive patients vary with patients' geographic origins, we studied co-infections in HIV-seropositive adults. Active hepatitis B infection was more prevalent in persons from Africa, and hepatitis C seropositivity was more common in persons from eastern Europe.Ministerio de Sanidad. Instituto de Salud Carlos II

A triple protostar system formed via fragmentation of a gravitationally unstable disk

Binary and multiple star systems are a frequent outcome of the star formation process(1,2) and as a result almost half of all stars with masses similar to that of the Sun have at least one companion star(3). Theoretical studies indicate that there are two main pathways that can operate concurrently to form binary/multiple star systems: large-scale fragmentation of turbulent gas cores and filaments(4,5) or smaller-scale fragmentation of a massive protostellar disk due to gravitational instability(6,7). Observational evidence for turbulent fragmentation on scales of more than 1,000 astronomical units has recently emerged(8,9). Previous evidence for disk fragmentation was limited to inferences based on the separations of more-evolved pre-main sequence and protostellar multiple systems(10-13). The triple protostar system L1448 IRS3B is an ideal system with which to search for evidence of disk fragmentation as it is in an early phase of the star formation process, it is likely to be less than 150,000 years old(14) and all of the protostars in the system are separated by less than 200 astronomical units. Here we report observations of dust and molecular gas emission that reveal a disk with a spiral structure surrounding the three protostars. Two protostars near the centre of the disk are separated by 61 astronomical units and a tertiary protostar is coincident with a spiral arm in the outer disk at a separation of 183 astronomical units(13). The inferred mass of the central pair of protostellar objects is approximately one solar mass, while the disk surrounding the three protostars has a total mass of around 0.30 solar masses. The tertiary protostar itself has a minimum mass of about 0.085 solar masses. We demonstrate that the disk around L1448 IRS3B appears susceptible to disk fragmentation at radii between 150 and 320 astronomical units, overlapping with the location of the tertiary protostar. This is consistent with models for a protostellar disk that has recently undergone gravitational instability, spawning one or two companion stars

Pranlukast Antagonizes CD49f and Reduces Sternness in Triple-Negative Breast Cancer Cells

Introduction: Cancer stem cells (CSCs) drive the initiation, maintenance, and therapy response of breast tumors. CD49f is expressed in breast CSCs and functions in the maintenance of stemness. Thus, blockade of CD49f is a potential therapeutic approach for targeting breast CSCs. In the present study, we aimed to repurpose drugs as CD49f antagonists. Materials and Methods: We performed consensus molecular docking using a subdomain of CD49f that is critical for heterodimerization and a collection of pharmochemicals clini-cally tested. Molecular dynamics simulations were employed to further characterize drug-target binding. Using MDA-MB-231 cells, we evaluated the effects of potential CD49f antagonists on 1) cell adhesion to laminin; 2) mammosphere formation; and 3) cell viability. We analyzed the effects of the drug with better CSC-selectivity on the activation of CD49f-downstream signaling by Western blot (WB) and co-immunoprecipitation. Expressions of the stem cell markers CD44 and SOX2 were analyzed by flow cytometry and WB, respectively. Transactivation of SOX2 promoter was evaluated by luciferase reporter assays. Changes in the number of CSCs were assessed by limiting-dilution xenotransplantation. Results: Pranlukast, a drug used to treat asthma, bound to CD49f in silico and inhibited the adhesion of CD49f+ MDA-MB-231 cells to laminin, indicating that it antagonizes CD49f-containing integrins. Molecular dynamics analysis showed that pranlukast binding induces con-formational changes in CD49f that affect its interaction with β1-integrin subunit and constrained the conformational dynamics of the heterodimer. Pranlukast decreased the clonogenicity of breast cancer cells on mammosphere formation assay but had no impact on the viability of bulk tumor cells. Brief exposure of MDA-MB-231 cells to pranlukast altered CD49f-dependent signaling, reducing focal adhesion kinase (FAK) and phosphatidylinositol 3-kinase (PI3K) activation. Further, pranlukast-treated cells showed decreased CD44 and SOX2 expression, SOX2 promoter transacti-vation, and in vivo tumorigenicity, supporting that this drug reduces the frequency of CSC. Conclusion: Our results support the function of pranlukast as a CD49f antagonist that reduces the CSC population in triple-negative breast cancer cells. The pharmacokinetics and toxicology of this drug have already been established, rendering a potential adjuvant therapy for breast cancer patients

The VLA Nascent Disk And Multiplicity (VANDAM) Survey of Perseus Protostars. Resolving the Sub-Arcsecond Binary System in NGC 1333 IRAS2A

We are conducting a Jansky VLA Ka-band (8 mm and 1 cm) and C-band (4 cm and 6.4 cm) survey of all known protostars in the Perseus Molecular Cloud, providing resolution down to $\sim$0.06'' and $\sim$0.35" in Ka-band and C-band, respectively. Here we present first results from this survey that enable us to examine the source NGC 1333 IRAS2A in unprecedented detail and resolve it into a proto-binary system separated by 0.621"$\pm$0.006" ($\sim$143 AU) at 8 mm, 1 cm, and 4 cm. These 2 sources (IRAS2A VLA1 and VLA2) are likely driving the two orthogonal outflows known to originate from IRAS2A. The brighter source IRAS2A VLA1 is extended perpendicular to its outflow in the VLA data, with a deconvolved size of 0.055" ($\sim$13 AU), possibly tracing a protostellar disk. The recently reported candidate companions (IRAS2A MM2 and MM3) are not detected in either our VLA data, CARMA 1.3 mm data, or SMA 850 $\mu$m data. SMA CO ($J=3\rightarrow2$), CARMA CO ($J=2\rightarrow1$), and lower resolution CARMA CO ($J=1\rightarrow0$) observations are used to examine the outflow origins and the nature of the candidate companions to IRAS2A VLA1. The CO ($J=3\rightarrow2$) and ($J=2\rightarrow1$) data show that IRAS2A MM2 is coincident with a bright CO emission spot in the east-west outflow, and IRAS2A MM3 is within the north-south outflow. In contrast, IRAS2A VLA2 lies at the east-west outflow symmetry point. We propose that IRAS2A VLA2 is the driving source of the East-West outflow and a true companion to IRAS2A VLA1, whereas IRAS2A MM2 and MM3 may not be protostellar.Comment: Accepted to ApJ, 27 pages, 6 Figures, 2 Table

Ratones knock-out del receptor lpa1 de ácido lisofosfatídico presentan un acusado déficit de la isoenzima glutaminasa KGA (GLS) y una morfología alterada en las espinas dendríticas de hipocampo y corteza

Objectives: The objective of the present study was to utilize mice with knocked-down lysophosphatidic acid 1 (LPA1) receptor to ascertain changes in glutamatergic transmission that may help to explain part of the cognitive and memory deficits shown by these KO-LPA1 mice. Material & methods: A well characterized KO-LPA1 mouse strain was used as animal model and compared with wild-type (WT) and heterozygous animals. Expression studies were implemented by immunohistochemistry and Western analysis of mouse brain regions, real-time quantitative RT-PCR of GA isoforms, enzymatic analysis of regional GA activity and Golgi staining to assess dendritic spine morphology and density. Results: A strong reduction of KGA immunoreactivity was mostly revealed in cerebral cortex and hippocampus of KO-LPA1 mice versus WT and heterozygous animals. In contrast, neither mRNA levels nor enzyme activity were significantly altered in KO mice suggesting compensatory mechanisms for neurotransmitter Glu synthesis. Interestingly, Golgi staining of hippocampal and cortical neurons revealed a clear morphology change toward a less-mature undifferentiated spine phenotype, without changes in the total number of spines. Conclusions: The molecular mechanisms underlying KGA downregulation in null LPA1 mutant mice are unknown. However, LPA increases neuronal differentiation, arborization and neurite outgrowth of developing neurons, while Gln-derived Glu, through GA reaction, has been also involved in neuronal growth and differentiation. It is tempting to speculate that downregulation of KGA protein in KO-LPA1 mice induce morphological changes in dendritic spines of cortical and hippocampal neurons which, in turn, may account for memory and cognitive deficits shown by KO-LPA1 mice.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. Acknowledgements: Red de Trastornos Adictivos, RTA, (RD12/0028/0013/) RETICS, ISCIII, y Consejería Innovación, Ciencia y Empresa, Junta de Andalucía (Proyecto de Excelencia CVI-6656)

Transcriptomic differences in MSA clinical variants

Background: Multiple system atrophy (MSA) is a rare oligodendroglial synucleinopathy of unknown etiopathogenesis including two major clinical variants with predominant parkinsonism (MSA-P) or cerebellar dysfunction (MSA-C). Objective: To identify novel disease mechanisms we performed a blood transcriptomic study investigating differential gene expression changes and biological process alterations in MSA and its clinical subtypes. Methods: We compared the transcriptome from rigorously gender and age-balanced groups of 10 probable MSA-P, 10 probable MSA-C cases, 10 controls from the Catalan MSA Registry (CMSAR), and 10 Parkinson Disease (PD) patients. Results: Gene set enrichment analyses showed prominent positive enrichment in processes related to immunity and inflammation in all groups, and a negative enrichment in cell differentiation and development of the nervous system in both MSA-P and PD, in contrast to protein translation and processing in MSA-C. Gene set enrichment analysis using expression patterns in different brain regions as a reference also showed distinct results between the different synucleinopathies. Conclusions: In line with the two major phenotypes described in the clinic, our data suggest that gene expression and biological processes might be differentially affected in MSA-P and MSA-C. Future studies using larger sample sizes are warranted to confirm these results

Differences in the signaling pathways of α1A- and α1B-adrenoceptors are related to different endosomal targeting

Aims: To compare the constitutive and agonist-dependent endosomal trafficking of α1A- and α1B-adrenoceptors (ARs) and to establish if the internalization pattern determines the signaling pathways of each subtype. Methods: Using CypHer5 technology and VSV-G epitope tagged α1A- and α1B-ARs stably and transiently expressed in HEK 293 cells, we analyzed by confocal microscopy the constitutive and agonist-induced internalization of each subtype, and the temporal relationship between agonist induced internalization and the increase in intracellular calcium (determined by FLUO-3 flouorescence), or the phosphorylation of ERK1/2 and p38 MAP kinases (determined by Western blot). Results and Conclusions: Constitutive as well as agonist-induced trafficking of α1A and α1B ARs maintain two different endosomal pools of receptors: one located close to the plasma membrane and the other deeper into the cytosol. Each subtype exhibited specific characteristics of internalization and distribution between these pools that determines their signaling pathways: α1A-ARs, when located in the plasma membrane, signal through calcium and ERK1/2 pathways but, when translocated to deeper endosomes, through a mechanism sensitive to β-arrestin and concanavalin A, continue signaling through ERK1/2 and also activate the p38 pathway. α1B-ARs signal through calcium and ERK1/2 only when located in the membrane and the signals disappear after endocytosis and by disruption of the membrane lipid rafts by methyl-β-cyclodextrin