Early-onset progressive retinal atrophy associated with an IQCB1 variant in African black-footed cats (Felis nigripes)

African black-footed cats (Felis nigripes) are endangered wild felids. One male and full-sibling female African black-footed cat developed vision deficits and mydriasis as early as 3 months of age. The diagnosis of early-onset progressive retinal atrophy (PRA) was supported by reduced direct and consensual pupillary light reflexes, phenotypic presence of retinal degeneration, and a non-recordable electroretinogram with negligible amplitudes in both eyes. Whole genome sequencing, conducted on two unaffected parents and one affected offspring was compared to a variant database from 51 domestic cats and a Pallas cat, revealed 50 candidate variants that segregated concordantly with the PRA phenotype. Testing in additional affected cats confirmed that cats homozygous for a 2 base pair (bp) deletion within IQ calmodulin-binding motif-containing protein-1 (IQCB1), the gene that encodes for nephrocystin-5 (NPHP5), had vision loss. The variant segregated concordantly in other related individuals within the pedigree supporting the identification of a recessively inherited early-onset feline PRA. Analysis of the black-footed cat studbook suggests additional captive cats are at risk. Genetic testing for IQCB1 and avoidance of matings between carriers should be added to the species survival plan for captive management

Integrated Analyses of microRNAs Demonstrate Their Widespread Influence on Gene Expression in High-Grade Serous Ovarian Carcinoma

The Cancer Genome Atlas (TCGA) Network recently comprehensively catalogued the molecular aberrations in 487 high-grade serous ovarian cancers, with much remaining to be elucidated regarding the microRNAs (miRNAs). Here, using TCGA ovarian data, we surveyed the miRNAs, in the context of their predicted gene targets.Integration of miRNA and gene patterns yielded evidence that proximal pairs of miRNAs are processed from polycistronic primary transcripts, and that intronic miRNAs and their host gene mRNAs derive from common transcripts. Patterns of miRNA expression revealed multiple tumor subtypes and a set of 34 miRNAs predictive of overall patient survival. In a global analysis, miRNA:mRNA pairs anti-correlated in expression across tumors showed a higher frequency of in silico predicted target sites in the mRNA 3'-untranslated region (with less frequency observed for coding sequence and 5'-untranslated regions). The miR-29 family and predicted target genes were among the most strongly anti-correlated miRNA:mRNA pairs; over-expression of miR-29a in vitro repressed several anti-correlated genes (including DNMT3A and DNMT3B) and substantially decreased ovarian cancer cell viability.This study establishes miRNAs as having a widespread impact on gene expression programs in ovarian cancer, further strengthening our understanding of miRNA biology as it applies to human cancer. As with gene transcripts, miRNAs exhibit high diversity reflecting the genomic heterogeneity within a clinically homogeneous disease population. Putative miRNA:mRNA interactions, as identified using integrative analysis, can be validated. TCGA data are a valuable resource for the identification of novel tumor suppressive miRNAs in ovarian as well as other cancers

Multirater Agreement of the Causes of Anterior Cruciate Ligament Reconstruction Failure

BackgroundAnterior cruciate ligament (ACL) reconstruction failure occurs in up to 10% of cases. Technical errors are considered the most common cause of graft failure despite the absence of validated studies. Limited data are available regarding the agreement among orthopaedic surgeons regarding the causes of primary ACL reconstruction failure and accuracy of graft tunnel placement.HypothesisExperienced knee surgeons have a high level of interobserver reliability in the agreement about the causes of primary ACL reconstruction failure, anatomic graft characteristics, and tunnel placement.Study designCohort study (diagnosis); Level of evidence, 3.MethodsTwenty cases of revision ACL reconstruction were randomly selected from the Multicenter ACL Revision Study (MARS) database. Each case included the patient's history, standardized radiographs, and a concise 30-second arthroscopic video taken at the time of revision demonstrating the graft remnant and location of the tunnel apertures. All 20 cases were reviewed by 10 MARS surgeons not involved with the primary surgery. Each surgeon completed a 2-part questionnaire dealing with each surgeon's training and practice, as well as the placement of the femoral and tibial tunnels, condition of the primary graft, and the surgeon's opinion as to the causes of graft failure. Interrater agreement was determined for each question with the kappa coefficient and the prevalence-adjusted, bias-adjusted kappa (PABAK).ResultsThe 10 reviewers have been in practice an average of 14 years and have performed at least 25 ACL reconstructions per year, and 9 were fellowship trained in sports medicine. There was wide variability in agreement among knee experts as to the specific causes of ACL graft failure. When participants were specifically asked about technical error as the cause for failure, interobserver agreement was only slight (PABAK = 0.26). There was fair overall agreement on ideal femoral tunnel placement (PABAK = 0.55) but only slight agreement on whether a femoral tunnel was too anterior (PABAK = 0.24) and fair agreement on whether it was too vertical (PABAK = 0.46). There was poor overall agreement for ideal tibial tunnel placement (PABAK = 0.17).ConclusionThis study suggests that more objective criteria are needed to accurately determine the causes of primary ACL graft failure as well as the ideal femoral and tibial tunnel placement in patients undergoing revision ACL reconstruction

A search using GEO600 for gravitational waves coincident with fast radio bursts from SGR 1935+2154

The magnetar SGR 1935+2154 is the only known Galactic source of fast radio bursts (FRBs). FRBs from SGR 1935+2154 were first detected by the Canadian Hydrogen Intensity Mapping Experiment (CHIME)/FRB and the Survey for Transient Astronomical Radio Emission 2 in 2020 April, after the conclusion of the LIGO, Virgo, and KAGRA Collaborations' O3 observing run. Here, we analyze four periods of gravitational wave (GW) data from the GEO600 detector coincident with four periods of FRB activity detected by CHIME/FRB, as well as X-ray glitches and X-ray bursts detected by NICER and NuSTAR close to the time of one of the FRBs. We do not detect any significant GW emission from any of the events. Instead, using a short-duration GW search (for bursts ≤1 s) we derive 50% (90%) upper limits of 1048 (1049) erg for GWs at 300 Hz and 1049 (1050) erg at 2 kHz, and constrain the GW-to-radio energy ratio to ≤1014−1016. We also derive upper limits from a long-duration search for bursts with durations between 1 and 10 s. These represent the strictest upper limits on concurrent GW emission from FRBs

Search for continuous gravitational waves from known pulsars in the first part of the fourth LIGO-Virgo-KAGRA observing run

Continuous gravitational waves (CWs) emission from neutron stars carries information about their internal structure and equation of state, and it can provide tests of general relativity. We present a search for CWs from a set of 45 known pulsars in the first part of the fourth LIGO–Virgo–KAGRA observing run, known as O4a. We conducted a targeted search for each pulsar using three independent analysis methods considering single-harmonic and dual-harmonic emission models. We find no evidence of a CW signal in O4a data for both models and set upper limits on the signal amplitude and on the ellipticity, which quantifies the asymmetry in the neutron star mass distribution. For the single-harmonic emission model, 29 targets have the upper limit on the amplitude below the theoretical spin-down limit. The lowest upper limit on the amplitude is 6.4 × 10−27 for the young energetic pulsar J0537−6910, while the lowest constraint on the ellipticity is 8.8 × 10−9 for the bright nearby millisecond pulsar J0437−4715. Additionally, for a subset of 16 targets, we performed a narrowband search that is more robust regarding the emission model, with no evidence of a signal. We also found no evidence of nonstandard polarizations as predicted by the Brans–Dicke theory

Swift-BAT GUANO follow-up of gravitational-wave triggers in the Third LIGO–Virgo–KAGRA Observing Run

We present results from a search for X-ray/gamma-ray counterparts of gravitational-wave (GW) candidates from the third observing run (O3) of the LIGO–Virgo–KAGRA network using the Swift Burst Alert Telescope (Swift-BAT). The search includes 636 GW candidates received with low latency, 86 of which have been confirmed by the offline analysis and included in the third cumulative Gravitational-Wave Transient Catalogs (GWTC-3). Targeted searches were carried out on the entire GW sample using the maximum-likelihood Non-imaging Transient Reconstruction and Temporal Search pipeline on the BAT data made available via the GUANO infrastructure. We do not detect any significant electromagnetic emission that is temporally and spatially coincident with any of the GW candidates. We report flux upper limits in the 15–350 keV band as a function of sky position for all the catalog candidates. For GW candidates where the Swift-BAT false alarm rate is less than 10−3 Hz, we compute the GW–BAT joint false alarm rate. Finally, the derived Swift-BAT upper limits are used to infer constraints on the putative electromagnetic emission associated with binary black hole mergers

Search for gravitational waves associated with the August 2006 timing glitch of the Vela pulsar

The physical mechanisms responsible for pulsar timing glitches are thought to excite quasinormal mode oscillations in their parent neutron star that couple to gravitational-wave emission. In August 2006, a timing glitch was observed in the radio emission of PSR B0833-45, the Vela pulsar. At the time of the glitch, the two colocated Hanford gravitational-wave detectors of the Laser Interferometer Gravitational-wave observatory (LIGO) were operational and taking data as part of the fifth LIGO science run (S5). We present the first direct search for the gravitational-wave emission associated with oscillations of the fundamental quadrupole mode excited by a pulsar timing glitch. No gravitational-wave detection candidate was found. We place Bayesian 90% confidence upper limits of 6.3×10-21 to 1.4×10-20 on the peak intrinsic strain amplitude of gravitational-wave ring-down signals, depending on which spherical harmonic mode is excited. The corresponding range of energy upper limits is 5.0×1044 to 1.3×1045 erg