Observations of neutron-star mergers with distinct messengers, including gravitational waves and electromagnetic signals, can be used to study the behavior of matter denser than an atomic nucleus and ...to measure the expansion rate of the Universe as quantified by the Hubble constant. We performed a joint analysis of the gravitational-wave event GW170817 with its electromagnetic counterparts AT2017gfo and GRB170817A, and the gravitational-wave event GW190425, both originating from neutron-star mergers. We combined these with previous measurements of pulsars using x-ray and radio observations, and nuclear-theory computations using chiral effective field theory, to constrain the neutron-star equation of state. We found that the radius of a 1.4-solar mass neutron star is Formula: see text km at 90% confidence and the Hubble constant is Formula: see text at 1σ uncertainty.
Abstract
Kilonovae produced by the coalescence of compact binaries with at least one neutron star are promising standard sirens for an independent measurement of the Hubble constant (
H
0
). Through ...their detection via follow-up of gravitational-wave (GW), short gamma-ray bursts (sGRBs) or optical surveys, a large sample of kilonovae (even without GW data) can be used for
H
0
contraints. Here, we show measurement of
H
0
using light curves associated with four sGRBs, assuming these are attributable to kilonovae, combined with GW170817. Including a systematic uncertainty on the models that is as large as the statistical ones, we find
$${H}_{0}=73.{8}_{-5.8}^{+6.3}\ {\rm{km}}\ {{\rm{s}}}^{-1}\ {{\rm{Mpc}}}^{-1}$$
H
0
=
73
.
8
−
5.8
+
6.3
km
s
−
1
Mpc
−
1
and
$${H}_{0}=71.{2}_{-3.1}^{+3.2}\ {\rm{km}}\ {{\rm{s}}}^{-1}\ {{\rm{Mpc}}}^{-1}$$
H
0
=
71
.
2
−
3.1
+
3.2
km
s
−
1
Mpc
−
1
for two different kilonova models that are consistent with the local and inverse-distance ladder measurements. For a given model, this measurement is about a factor of 2-3 more precise than the standard-siren measurement for GW170817 using only GWs.
Abstract
The observation of a compact object with a mass of 2.50–2.67
M
⊙
on 2019 August 14, by the LIGO Scientific and Virgo collaborations (LVC) has the potential to improve our understanding of ...the supranuclear equation of state. While the gravitational-wave analysis of the LVC suggests that GW190814 likely was a binary black hole system, the secondary component could also have been the heaviest neutron star observed to date. We use our previously derived nuclear-physics-multimessenger astrophysics framework to address the nature of this object. Based on our findings, we determine GW190814 to be a binary black hole merger with a probability of >99.9%. Even if we weaken previously employed constraints on the maximum mass of neutron stars, the probability of a binary black hole origin is still ∼81%. Furthermore, we study the impact that this observation has on our understanding of the nuclear equation of state by analyzing the allowed region in the mass–radius diagram of neutron stars for both a binary black hole or neutron star–black hole scenario. We find that the unlikely scenario in which the secondary object was a neutron star requires rather stiff equations of state with a maximum speed of sound
times the speed of light, while the binary black hole scenario does not offer any new insight.
Abstract
The auditory cortex exerts a powerful, yet heterogeneous, effect on subcortical targets. Auditory corticofugal projections emanate from layers 5 and 6 and have complementary physiological ...properties. While several studies suggested that layer 5 corticofugal projections branch widely, others suggested that multiple independent projections exist. Less is known about layer 6; no studies have examined whether the various layer 6 corticofugal projections are independent. Therefore, we examined branching patterns of layers 5 and 6 auditory corticofugal neurons, using the corticocollicular system as an index, using traditional and novel approaches. We confirmed that dual retrograde injections into the mouse inferior colliculus and auditory thalamus co-labeled subpopulations of layers 5 and 6 auditory cortex neurons. We then used an intersectional approach to relabel layer 5 or 6 corticocollicular somata and found that both layers sent extensive branches to multiple subcortical structures. Using a novel approach to separately label layers 5 and 6 axons in individual mice, we found that layers 5 and 6 terminal distributions partially spatially overlapped and that giant terminals were only found in layer 5-derived axons. Overall, the high degree of branching and complementarity in layers 5 and 6 axonal distributions suggest that corticofugal projections should be considered as 2 widespread systems, rather than collections of individual projections.
Recent data have found that aging-related hearing loss (ARHL) is associated with the development of Alzheimer's Disease (AD). However, the nature of the relationship between these two disorders is ...not clear. There are multiple potential factors that link ARHL and AD, and previous investigators have speculated that shared metabolic dysregulation may underlie the propensity to develop both disorders. Here, we investigate the distribution of serum lipidomic biomarkers in AD subjects with or without hearing loss in a publicly available dataset. Serum levels of 349 known lipids from 16 lipid classes were measured in 185 AD patients. Using previously defined co-regulated sets of lipids, both age- and sex-adjusted, we found that lipid sets enriched in phosphatidylcholine and phosphatidylethanolamine showed a strong inverse association with hearing loss. Examination of biochemical classes confirmed these relationships and revealed that serum phosphatidylcholine levels were significantly lower in AD subjects with hearing loss. A similar relationship was not found in normal subjects. These data suggest that a synergistic relationship may exist between AD, hearing loss and metabolic biomarkers, such that in the context of a pathological state such as AD, alterations in serum metabolic profiles are associated with hearing loss. These data also point to a potential role for phosphatidylcholine, a molecule with antioxidant properties, in the underlying pathophysiology of ARHL in the context of AD, which has implications for our understanding and potential treatment of both disorders.
This study examines the effect of some economic and non-economic factors on corruption. It tests a number of hypotheses formulated around the impact of specific dimensions on increasing or reducing ...corruption in the Middle East and North Africa Region over a time series from 2008 to 2018. The objective of this study is to illuminate the impact of several independent factors (average income, economic freedom, education, income distribution and globalization) on corruption increase or decrease in the MENA region taking a few countries as a sample case. To reach this end, secondary data is employed and retrieved from secondary sources using published reports and indexes and official websites and databases maintained by various research institutions. The results are tested using panel data regression analysis as a statistical tool for data analysis and hypotheses testing. Findings indicate a significant effect of the presented economic and non-economic determinants on corruption in these sample countries except income distribution which shows an insignificance effect.
Objective:
Activated microglia play a central role in the inflammatory and excitotoxic component of various acute and chronic neurological disorders. However, the mechanisms leading to their ...activation in the latter context are poorly understood, particularly the involvement of N‐methyl‐D‐aspartate receptors (NMDARs), which are critical for excitotoxicity in neurons. We hypothesized that microglia express functional NMDARs and that their activation would trigger neuronal cell death in the brain by modulating inflammation.
Methods and Results:
We demonstrate that microglia express NMDARs in the murine and human central nervous system and that these receptors are functional in vitro. We show that NMDAR stimulation triggers microglia activation in vitro and secretion of factors that induce cell death of cortical neurons. These damaged neurons are further shown to activate microglial NMDARs and trigger a release of neurotoxic factors from microglia in vitro, indicating that microglia can signal back to neurons and possibly induce, aggravate, and/or maintain neurologic disease. Neuronal cell death was significantly reduced through pharmacological inhibition or genetically induced loss of function of the microglial NMDARs. We generated Nr1 LoxP+/+LysM Cre+/− mice lacking the NMDAR subunit NR1 in cells of the myeloid lineage. In this model, we further demonstrate that a loss of function of the essential NMDAR subunit NR1 protects from excitotoxic neuronal cell death in vivo and from traumatic brain injury.
Interpretation:
Our findings link inflammation and excitotoxicity in a potential vicious circle and indicate that an activation of the microglial NMDARs plays a pivotal role in neuronal cell death in the perinatal and adult brain. ANN NEUROL 2012;72:536–549
Autosomal recessive primary microcephaly (MCPH), historically referred to as Microcephalia vera, is a genetically and clinically heterogeneous disease. Patients with MCPH typically exhibit congenital ...microcephaly as well as mental retardation, but usually no further neurological findings or malformations. Their microcephaly with grossly preserved macroscopic organization of the brain is a consequence of a reduced brain volume, which is evident particularly within the cerebral cortex and thus results to a large part from a reduction of grey matter. Some patients with MCPH further provide evidence of neuronal heterotopias, polymicrogyria or cortical dysplasia suggesting an associated neuronal migration defect. Genetic causes of MCPH subtypes 1-7 include mutations in genes encoding microcephalin, cyclin-dependent kinase 5 regulatory associated protein 2 (CDK5RAP2), abnormal spindle-like, microcephaly associated protein (ASPM), centromeric protein J (CENPJ), and SCL/TAL1-interrupting locus (STIL) as well as linkage to the two loci 19q13.1-13.2 and 15q15-q21. Here, we provide a timely overview of current knowledge on mechanisms leading to microcephaly in humans with MCPH and abnormalities in cell division/cell survival in corresponding animal models. Understanding the pathomechanisms leading to MCPH is of high importance not only for our understanding of physiologic brain development (particularly of cortex formation), but also for that of trends in mammalian evolution with a massive increase in size of the cerebral cortex in primates, of microcephalies of other etiologies including environmentally induced microcephalies, and of cancer formation.
Autosomal recessive primary microcephaly (MCPH) is a rare neurodevelopmental disorder characterized by a pronounced reduction of brain volume and intellectual disability. A current model for the ...microcephaly phenotype invokes a stem cell proliferation and differentiation defect, which has moved the disease into the spotlight of stem cell biology and neurodevelopmental science. Homozygous mutations of the Cyclin-dependent kinase-5 regulatory subunit-associated protein 2 gene CDK5RAP2 are one genetic cause of MCPH. To further characterize the pathomechanism underlying MCPH, we generated a conditional Cdk5rap2 LoxP/hCMV Cre mutant mouse. Further analysis, initiated on account of a lack of a microcephaly phenotype in these mutant mice, revealed the presence of previously unknown splice variants of the Cdk5rap2 gene that are at least in part accountable for the lack of microcephaly in the mice.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective
To identify the cause of a so‐far unreported phenotype of infantile‐onset multisystem neurologic, endocrine, and pancreatic disease (IMNEPD).
Methods
We characterized a consanguineous ...family of Yazidian‐Turkish descent with IMNEPD. The two affected children suffer from intellectual disability, postnatal microcephaly, growth retardation, progressive ataxia, distal muscle weakness, peripheral demyelinating sensorimotor neuropathy, sensorineural deafness, exocrine pancreas insufficiency, hypothyroidism, and show signs of liver fibrosis. We performed whole‐exome sequencing followed by bioinformatic analysis and Sanger sequencing on affected and unaffected family members. The effect of mutations in the candidate gene was studied in wild‐type and mutant mice and in patient and control fibroblasts.
Results
In a consanguineous family with two individuals with IMNEPD, we identified a homozygous frameshift mutation in the previously not disease‐associated peptidyl‐tRNA hydrolase 2 (PTRH2) gene. PTRH2 encodes a primarily mitochondrial protein involved in integrin‐mediated cell survival and apoptosis signaling. We show that PTRH2 is highly expressed in the developing brain and is a key determinant in maintaining cell survival during human tissue development. Moreover, we link PTRH2 to the mTOR pathway and thus the control of cell size. The pathology suggested by the human phenotype and neuroimaging studies is supported by analysis of mutant mice and patient fibroblasts.
Interpretation
We report a novel disease phenotype, show that the genetic cause is a homozygous mutation in the PTRH2 gene, and demonstrate functional effects in mouse and human tissues. Mutations in PTRH2 should be considered in patients with undiagnosed multisystem neurologic, endocrine, and pancreatic disease.
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