The clustering of galaxies in the SDSS-III Baryon Oscillation Spectroscopic Survey: constraints on the time variation of fundamental constants from the large-scale two-point correlation function

We obtain constraints on the variation of the fundamental constants from the full shape of the redshift-space correlation function of a sample of luminous galaxies drawn from the Data Release 9 of the Baryonic Oscillations Spectroscopic Survey. We combine this information with data from recent CMB, BAO and H_0 measurements. We focus on possible variations of the fine structure constant \alpha and the electron mass m_e in the early universe, and study the degeneracies between these constants and other cosmological parameters, such as the dark energy equation of state parameter w_DE, the massive neutrinos fraction f_\nu, the effective number of relativistic species N_eff, and the primordial helium abundance Y_He. When only one of the fundamental constants is varied, our final bounds are \alpha / \alpha_0 = 0.9957_{-0.0042}^{+0.0041} and m_e /(m_e)_0 = 1.006_{-0.013}^{+0.014}. For their joint variation, our results are \alpha / \alpha_0 = 0.9901_{-0.0054}^{+0.0055} and m_e /(m_e)_0 = 1.028 +/- 0.019. Although when m_e is allowed to vary our constraints on w_DE are consistent with a cosmological constant, when \alpha is treated as a free parameter we find w_DE = -1.20 +/- 0.13; more than 1 \sigma away from its standard value. When f_\nu and \alpha are allowed to vary simultaneously, we find f_\nu < 0.043 (95% CL), implying a limit of \sum m_\nu < 0.46 eV (95% CL), while for m_e variation, we obtain f_nu < 0.086 (95% CL), which implies \sum m_\nu < 1.1 eV (95% CL). When N_eff or Y_He are considered as free parameters, their simultaneous variation with \alpha provides constraints close to their standard values (when the H_0 prior is not included in the analysis), while when m_e is allowed to vary, their preferred values are significantly higher. In all cases, our results are consistent with no variations of \alpha or m_e at the 1 or 2 \sigma level.Comment: 18 pages, 16 figures. Submitted to MNRA

Mitophagy-Related Cell Death Mediated by Vacquinol-1 and TRPM7 Blockade in Glioblastoma IV

Glioblastoma IV (GBM) is one of the deadliest malignant diseases in adults and is characterized by a high mutation rate and multiple traits to suppress inborn and acquired immunity. We here approached autophagy-related cell death in newly established GBM cell lines derived from individual tumor isolates. Treatment with a small molecule, termed Vacquinol-1 (Vac) exhibited 100% GBM cell death, which was related to mitochondrial dysfunction, calcium-induced endoplasmic reticulum (ER)-stress, and autophagy. The toxicity of Vac was significantly increased by the inhibition of transient receptor potential cation channel, subfamily M, member 7 (TRPM7). TRPM7 is overexpressed in GBM as well as in many other tumors and thus may be a potential target by the natural compound carvacrol. Of note, at higher concentrations, Vac also induced growth inhibition and cell death in non-transformed cell types. However, in the presence of the TRPM7 inhibitor carvacrol, the tumor-selective effect of Vac was very much increased. Results given in the present study are based on long-term video microscopy using IncuCyteZOOM®, calcium measurements, and 3D ultrastructural analysis using the cryofixed material

NMDA receptor antagonists reduce amyloid-β deposition by modulating calpain-1 signaling and autophagy, rescuing cognitive impairment in 5XFAD mice

Overstimulation of N-methyl-D-aspartate receptors (NMDARs) is the leading cause of brain excitotoxicity and often contributes to neurodegenerative diseases such as Alzheimer's Disease (AD), the most common form of dementia. This study aimed to evaluate a new NMDA receptor antagonist (UB-ALT-EV) and memantine in 6-month-old female 5XFAD mice that were exposed orally to a chronic low-dose treatment. Behavioural and cognitive tests confirmed better cognitive performance in both treated groups. Calcium-dependent protein calpain-1 reduction was found after UB-ALT-EV treatment but not after memantine. Changes in spectrin breakdown products (SBDP) and the p25/p35 ratio confirmed diminished calpain-1 activity. Amyloid β (Aβ) production and deposition was evaluated in 5XFAD mice and demonstrated a robust effect of NMDAR antagonists on reducing Aβ deposition and the number and size of Thioflavin-S positive plaques. Furthermore, glycogen synthase kinase 3β (GSK3β) active form and phosphorylated tau (AT8) levels were diminished after UB-ALT-EV treatment, revealing tau pathology improvement. Because calpain-1 is involved in autophagy activation, autophagic proteins were studied. Strikingly, results showed changes in the protein levels of unc-51-like kinase (ULK1), beclin-1, microtubule-associated protein 1A/1B-light chain 3(LC3B-II)/LC3B-I ratio and lysosomal-associated membrane protein 1 (LAMP1) after NMDAR antagonist treatments, suggesting an accumulation of autophagolysosomes in 5XFAD mice, reversed by UB-ALT-EV. Likewise, treatment with UB-ALT-EV recovered a WT mice profile in apoptosis markers Bcl-2, Bax, and caspase-3. In conclusion, our results revealed the potential neuroprotective effect of UB-ALT-EV by attenuating NMDA-mediated apoptosis and reducing Aβ deposition and deposition jointly with the autophagy rescue to finally reduce cognitive alterations in a mice model of familial AD

Female Behaviour Drives Expression and Evolution of Gustatory Receptors in Butterflies

Secondary plant compounds are strong deterrents of insect oviposition and feeding, but may also be attractants for specialist herbivores. These insect-plant interactions are mediated by insect gustatory receptors (Grs) and olfactory receptors (Ors). An analysis of the reference genome of the butterfly Heliconius melpomene, which feeds on passion-flower vines (Passiflora spp.), together with whole-genome sequencing within the species and across the Heliconius phylogeny has permitted an unprecedented opportunity to study the patterns of gene duplication and copy-number variation (CNV) among these key sensory genes. We report in silico gene predictions of 73 Gr genes in the H. melpomene reference genome, including putative CO2, sugar, sugar alcohol, fructose, and bitter receptors. The majority of these Grs are the result of gene duplications since Heliconius shared a common ancestor with the monarch butterfly or the silkmoth. Among Grs but not Ors, CNVs are more common within species in those gene lineages that have also duplicated over this evolutionary time-scale, suggesting ongoing rapid gene family evolution. Deep sequencing (∼1 billion reads) of transcriptomes from proboscis and labial palps, antennae, and legs of adult H. melpomene males and females indicates that 67 of the predicted 73 Gr genes and 67 of the 70 predicted Or genes are expressed in these three tissues. Intriguingly, we find that one-third of all Grs show female-biased gene expression (n = 26) and nearly all of these (n = 21) are Heliconius-specific Grs. In fact, a significant excess of Grs that are expressed in female legs but not male legs are the result of recent gene duplication. This difference in Gr gene expression diversity between the sexes is accompanied by a striking sexual dimorphism in the abundance of gustatory sensilla on the forelegs of H. melpomene, suggesting that female oviposition behaviour drives the evolution of new gustatory receptors in butterfly genomes

Immune phenotypes predict survival in patients with glioblastoma multiforme

Background: Glioblastoma multiforme (GBM), a common primary malignant brain tumor, rarely disseminates beyond the central nervous system and has a very bad prognosis. The current study aimed at the analysis of immunological control in individual patients with GBM. Methods: Immune phenotypes and plasma biomarkers of GBM patients were determined at the time of diagnosis using flow cytometry and ELISA, respectively. Results: Using descriptive statistics, we found that immune anomalies were distinct in individual patients. Defined marker profiles proved highly relevant for survival. A remarkable relation between activated NK cells and improved survival in GBM patients was in contrast to increased CD39 and IL-10 in patients with a detrimental course and very short survival. Recursive partitioning analysis (RPA) and Cox proportional hazards models substantiated the relevance of absolute numbers of CD8 cells and low numbers of CD39 cells for better survival. Conclusions: Defined alterations of the immune system may guide the course of disease in patients with GBM and may be prognostically valuable for longitudinal studies or can be applied for immune intervention

Coaching to strengthen critical success factors in integrative care for chronic fatigue patients: the Patient Needs-Resources Model

Theoretical and empirical studies discover that an integrative approach is particularly important in chronic disorders and multiple long-term conditions, such as chronic fatigue. Chronic fatigue syndrome (CFS) is a classic example of a potentially severe, multisystemic illness with a wide diversity of symptoms and the corresponding diagnostic complexity. The prevalence of CFS-like syndromes expanded in the context of the COVID-19 pandemic, increasing the disorder and treatment burden. Thus, this article aimed to draw attention to the possibilities to strengthen the integrative approach to diagnosing and treating chronic disorders and multiple long-term conditions. The main critical success factors identified for integrative approaches were: a holistic approach, that provides a more comprehensive diagnostic and personalized treatment strategy, a multidisciplinary team, and patient engagement. The strengths and weaknesses of these factors were explored and coaching was identified as a potential unifying and reinforcing element. Coaching has a wide spectrum of manifestations clearly representing a holistic approach, that has been successfully used in multidisciplinary team building. Moreover, coaching exposes support addressing the patient engagement issues identified by the Patient Needs-Resources Model (PN-R Model) such as low levels of self-efficacy, optimism, and subjective well-being. Coaching may assist patients to identify and prioritize their goals, becoming aware of their personal resources, developing strategies for managing symptoms, and building skills to increase their self-efficacy and active engagement in the treatment process. Therefore, the authors emphasize coaching as a perspective element of optimization of patient care, that requires additional theoretical and long-term empirical research

Introgression reshapes recombination distribution in grapevine interspecific hybrids

In grapevine interspecific hybrids, meiotic recombination is suppressed in homeologous regions and enhanced in homologous regions of recombined chromosomes, whereas crossover rate remains unchanged when chromosome pairs are entirely homeologous

HSV-1 and Cellular miRNAs in CSF-Derived Exosomes as Diagnostically Relevant Biomarkers for Neuroinflammation

Virus-associated chronic inflammation may contribute to autoimmunity in a number of diseases. In the brain, autoimmune encephalitis appears related to fluctuating reactivation states of neurotropic viruses. In addition, viral miRNAs and proteins can be transmitted via exosomes, which constitute novel but highly relevant mediators of cellular communication. The current study questioned the role of HSV-1-encoded and host-derived miRNAs in cerebrospinal fluid (CSF)-derived exosomes, enriched from stress-induced neuroinflammatory diseases, mainly subarachnoid hemorrhage (SAH), psychiatric disorders (AF and SZ), and various other neuroinflammatory diseases. The results were compared with CSF exosomes from control donors devoid of any neuroinflammatory pathology. Serology proved positive, but variable immunity against herpesviruses in the majority of patients, except controls. Selective ultrastructural examinations identified distinct, herpesvirus-like particles in CSF-derived lymphocytes and monocytes. The likely release of extracellular vesicles and exosomes was most frequently observed from CSF monocytes. The exosomes released were structurally similar to highly purified stem-cell-derived exosomes. Exosomal RNA was quantified for HSV-1-derived miR-H2-3p, miR-H3-3p, miR-H4-3p, miR-H4-5p, miR-H6-3p, miR-H27 and host-derived miR-21-5p, miR-146a-5p, miR-155-5p, and miR-138-5p and correlated with the oxidative stress chemokine IL-8 and the axonal damage marker neurofilament light chain (NfL). Replication-associated miR-H27 correlated with neuronal damage marker NfL, and cell-derived miR-155-5p correlated with oxidative stress marker IL-8. Elevated miR-138-5p targeting HSV-1 latency-associated ICP0 inversely correlated with lower HSV-1 antibodies in CSF. In summary, miR-H27 and miR-155-5p may constitute neuroinflammatory markers for delineating frequent and fluctuating HSV-1 replication and NfL-related axonal damage in addition to the oxidative stress cytokine IL-8 in the brain. Tentatively, HSV-1 remains a relevant pathogen conditioning autoimmune processes and a psychiatric clinical phenotype.</p

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta