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Identification of multiple immune-related genetic risk factors for sporadic AD (sAD) have put the immune system center stage in mechanisms underlying this disorder. Comprehensive analysis of microglia in different stages of AD in human brains revealed microglia activation to follow the progression of AD neuropathological changes and requiring the co-occurrence of beta-Amyloid (Aβ) and tau pathology. Carriers of AD-associated risk variants in TREM2 (Triggering receptor expressed on myeloid cells 2) showed a reduction of plaque-associated microglia and a substantial increase in dystrophic neurites and overall pathological tau compared with age and disease stage matched AD patients without TREM2 risk variants. These findings were substantiated by digital spatial profiling of the plaque microenvironment and targeted gene expression profiling on the NanoString nCounter system, which revealed striking brain region dependent differences in immune response patterns within individual cases. The demonstration of profound brain region and risk-variant specific differences in immune activation in human AD brains impacts the applicability of immune-therapeutic approaches for sAD and related neurodegenerative diseases.

The date of publication of volumes 9 and 10 of Achille Guenée’s “Histoire Naturelle des Insectes. Species Général des Lépidoptères” should be accepted as [1858], not 1857.

In Lewy body diseases—including Parkinson’s disease, without or with dementia, dementia with Lewy bodies, and Alzheimer’s disease with Lewy body co-pathology 1 —α-synuclein (α-Syn) aggregates in neurons as Lewy bodies and Lewy neurites 2 . By contrast, in multiple system atrophy α-Syn accumulates mainly in oligodendrocytes as glial cytoplasmic inclusions (GCIs) 3 . Here we report that pathological α-Syn in GCIs and Lewy bodies (GCI-α-Syn and LB-α-Syn, respectively) is conformationally and biologically distinct. GCI-α-Syn forms structures that are more compact and it is about 1,000-fold more potent than LB-α-Syn in seeding α-Syn aggregation, consistent with the highly aggressive nature of multiple system atrophy. GCI-α-Syn and LB-α-Syn show no cell-type preference in seeding α-Syn pathology, which raises the question of why they demonstrate different cell-type distributions in Lewy body disease versus multiple system atrophy. We found that oligodendrocytes but not neurons transform misfolded α-Syn into a GCI-like strain, highlighting the fact that distinct α-Syn strains are generated by different intracellular milieus. Moreover, GCI-α-Syn maintains its high seeding activity when propagated in neurons. Thus, α-Syn strains are determined by both misfolded seeds and intracellular environments. Distinct strains of misfolded α-synuclein proteins, which aggregate in neurons in Lewy body diseases or in oligodendrocytes in multiple system atrophy, are formed as a consequence of differences between intracellular environments.

Aim Andean forests are known to be a major diversity hotspot for vascular plants and vertebrates, but virtually nothing is known about the diversity of arthropods. We examined whether montane rain forests in southern Ecuador are also a diversity hotspot for arthropods, and chose geometrid moths as a model group. Location The study area in southern Ecuador (Province Zamora-Chinchipe, 79° W, 04° S) covers c. 40 km2, with 39 collecting sites within an elevational range of 1040-2677 m a.s.l. Thirty-five of the sites were situated in an area c. 2.5 km2. Additional qualitative sampling was carried out in the same area and up to an elevation of 3100 m. Methods Nocturnal moths were collected quantitatively and qualitatively using portable light towers consisting of two 15 W fluorescent tubes, and diurnal moths were collected qualitatively using an insect net. Insects were sampled in six fieldwork periods in the years 1999-2003. As diversity measures, Fisher's alpha of the log-series distribution as well as eight estimators of total species richness were applied. Results A total of 1266 species were recorded, 63% of which were identified to named species, whereas the remainder are likely to include many undescribed species. Quantitative samples at light towers collected 35,238 specimens representing 1223 species. The extrapolated species number for these data is 1420 (incidence coverage estimator). Twenty-one additional nocturnal species and 22 exclusively diurnal species were sampled qualitatively at elevations between 1040 and 3100 m. The pooled value of Fisher's alpha for all quantitative samples is 246 ± 3. Main conclusions The diversity of Geometridae documented here is much higher than anywhere else in the world, even without the inclusion of additional species from adjacent lowland rain forests. The number of recorded species in this small area corresponds to more than 6% of the known world fauna of geometrid moths. Our study emphasizes the importance of protecting the remaining montane Andean rain forests. For setting priorities in conservation, more studies on insect diversity are urgently required in other regions of the Andes, since montane forests are being destroyed at an alarming rate.

We describe the consistency testing of a new code for gravitational wave signal parameter estimation in known pulsar searches. The code uses an implementation of nested sampling to explore the likelihood volume. Using fake signals and simulated noise we compare this to a previous code that calculated the signal parameter posterior distributions on both a grid and using a crude Markov chain Monte Carlo (MCMC) method. We define a new parameterisation of two orientation angles of neutron stars used in the signal model (the initial phase and polarisation angle), which breaks a degeneracy between them and allows more efficient exploration of those parameters. Finally, we briefly describe potential areas for further study and the uses of this code in the future.

We report on gravitational wave discoveries from compact binary coalescences detected by Advanced LIGO and Advanced Virgo in the first half of the third observing run (O3a) between 1 April 2019 15:00 UTC and 1 October 2019 15:00 UTC. By imposing a false-alarm-rate threshold of two per year in each of the four search pipelines that constitute our search, we present 39 candidate gravitational wave events. At this threshold, we expect a contamination fraction of less than 10%. Of these, 26 candidate events were reported previously in near real-time through GCN Notices and Circulars; 13 are reported here for the first time. The catalog contains events whose sources are black hole binary mergers up to a redshift of ~ 0.8, as well as events whose components could not be unambiguously identified as black holes or neutron stars. For the latter group, we are unable to determine the nature based on estimates of the component masses and spins from gravitational wave data alone. The range of candidate event masses which are unambiguously identified as binary black holes (both objects ≥ 3 M⨀) is increased compared to GWTC-1, with total masses from ∼ 14M⨀ for GW190924 021846 to ∼ 150M⨀ for GW190521. For the first time, this catalog includes binary systems with significantly asymmetric mass ratios, which had not been observed in data taken before April 2019. We also find that 11 of the 39 events detected since April 2019 have positive effective inspiral spins under our default prior (at 90% credibility), while none exhibit negative effective inspiral spin. Given the increased sensitivity of Advanced LIGO and Advanced Virgo, the detection of 39 candidate events in ∼26 weeks of data (∼1.5 per week) is consistent with GWTC-1.

The astronomical event GW170817, detected in gravitational and electromagnetic waves, is used to determine the expansion rate of the Universe, which is consistent with and independent of existing measurements. Hubble constant from colliding neutron stars The gravitational-wave signature of merging black holes or neutron stars yields the distance to the merger. If a counterpart is observed and its recession velocity arising from the Hubble flow is known, then a calibration of the Hubble constant that is entirely independent of the usual 'distance ladder' is possible. The gravitational-wave event of 17 August 2017 (GW170817) corresponded to the merger of two neutron stars, and an associated 'kilonova' was seen. Daniel Holz and the LIGO–Virgo collaboration, along with a group of astronomers involved with the search for the counterpart, have determined that the Hubble constant calculated this way is about 70 kilometres per second per megaparsec. This is consistent with other determinations, but independent of them. On 17 August 2017, the Advanced LIGO 1 and Virgo 2 detectors observed the gravitational-wave event GW170817—a strong signal from the merger of a binary neutron-star system 3 . Less than two seconds after the merger, a γ-ray burst (GRB 170817A) was detected within a region of the sky consistent with the LIGO–Virgo-derived location of the gravitational-wave source 4 , 5 , 6 . This sky region was subsequently observed by optical astronomy facilities 7 , resulting in the identification 8 , 9 , 10 , 11 , 12 , 13 of an optical transient signal within about ten arcseconds of the galaxy NGC 4993. This detection of GW170817 in both gravitational waves and electromagnetic waves represents the first ‘multi-messenger’ astronomical observation. Such observations enable GW170817 to be used as a ‘standard siren’ 14 , 15 , 16 , 17 , 18 (meaning that the absolute distance to the source can be determined directly from the gravitational-wave measurements) to measure the Hubble constant. This quantity represents the local expansion rate of the Universe, sets the overall scale of the Universe and is of fundamental importance to cosmology. Here we report a measurement of the Hubble constant that combines the distance to the source inferred purely from the gravitational-wave signal with the recession velocity inferred from measurements of the redshift using the electromagnetic data. In contrast to previous measurements, ours does not require the use of a cosmic ‘distance ladder’ 19 : the gravitational-wave analysis can be used to estimate the luminosity distance out to cosmological scales directly, without the use of intermediate astronomical distance measurements. We determine the Hubble constant to be about 70 kilometres per second per megaparsec. This value is consistent with existing measurements 20 , 21 , while being completely independent of them. Additional standard siren measurements from future gravitational-wave sources will enable the Hubble constant to be constrained to high precision.

We present our current best estimate of the plausible observing scenarios for the Advanced LIGO, Advanced Virgo and KAGRA gravitational-wave detectors over the next several years, with the intention of providing information to facilitate planning for multi-messenger astronomy with gravitational waves. We estimate the sensitivity of the network to transient gravitational-wave signals for the third (O3), fourth (O4) and fifth observing (O5) runs, including the planned upgrades of the Advanced LIGO and Advanced Virgo detectors. We study the capability of the network to determine the sky location of the source for gravitational-wave signals from the inspiral of binary systems of compact objects, that is binary neutron star, neutron star–black hole, and binary black hole systems. The ability to localize the sources is given as a sky-area probability, luminosity distance, and comoving volume. The median sky localization area (90% credible region) is expected to be a few hundreds of square degrees for all types of binary systems during O3 with the Advanced LIGO and Virgo (HLV) network. The median sky localization area will improve to a few tens of square degrees during O4 with the Advanced LIGO, Virgo, and KAGRA (HLVK) network. During O3, the median localization volume (90% credible region) is expected to be on the order of 10 5 , 10 6 , 10 7 Mpc 3 for binary neutron star, neutron star–black hole, and binary black hole systems, respectively. The localization volume in O4 is expected to be about a factor two smaller than in O3. We predict a detection count of 1 - 1 + 12 ( 10 - 10 + 52 ) for binary neutron star mergers, of 0 - 0 + 19 ( 1 - 1 + 91 ) for neutron star–black hole mergers, and 17 - 11 + 22 ( 79 - 44 + 89 ) for binary black hole mergers in a one-calendar-year observing run of the HLV network during O3 (HLVK network during O4). We evaluate sensitivity and localization expectations for unmodeled signal searches, including the search for intermediate mass black hole binary mergers.

The first observational run of the Advanced LIGO detectors, from September 12, 2015 to January 19, 2016, saw the first detections of gravitational waves from binary black hole mergers. In this paper we present full results from a search for binary black hole merger signals with total masses up to 100M solar mass and detailed implications from our observations of these systems. Our search, based on general-relativistic models of gravitational wave signals from binary black hole systems, unambiguously identified two signals, GW150914 and GW151226, with a significance of greater than 5 alpha over the observing period. It also identified a third possible signal, LVT151012, with substantially lower significance, which has a 87 probability of being of astrophysical origin. We provide detailed estimates of the parameters of the observed systems. Both GW150914 and GW151226 provide an unprecedented opportunity to study the two-body motion of a compact-object binary in the large velocity, highly nonlinear regime. We do not observe any deviations from general relativity, and place improved empirical bounds on several high-order post-Newtonian coefficients. From our observations we infer stellar-mass binary black hole merger rates lying in the range 9-240 Gpc-3 yr-1. These observations are beginning to inform astrophysical predictions of binary black hole formation rates, and indicate that future observing runs of the Advanced detector network will yield many more gravitational wave detections.

We present possible observing scenarios for the Advanced LIGO, Advanced Virgo and KAGRA gravitational-wave detectors over the next decade, with the intention of providing information to the astronomy community to facilitate planning for multi-messenger astronomy with gravitational waves. We estimate the sensitivity of the network to transient gravitational-wave signals, and study the capability of the network to determine the sky location of the source. We report our findings for gravitational-wave transients, with particular focus on gravitational-wave signals from the inspiral of binary neutron star systems, which are the most promising targets for multi-messenger astronomy. The ability to localize the sources of the detected signals depends on the geographical distribution of the detectors and their relative sensitivity, and 90 % credible regions can be as large as thousands of square degrees when only two sensitive detectors are operational. Determining the sky position of a significant fraction of detected signals to areas of 5– 20 deg 2 requires at least three detectors of sensitivity within a factor of ∼ 2 of each other and with a broad frequency bandwidth. When all detectors, including KAGRA and the third LIGO detector in India, reach design sensitivity, a significant fraction of gravitational-wave signals will be localized to a few square degrees by gravitational-wave observations alone.