α-Hemolysin as a Candidate for a Vaccine for \u3cem\u3eStaphylococcus aureus\u3c/em\u3e in Bovine Mastitis

Staphylococcus aureus is a Gram-positive bacteria responsible for many types of infections. It is abundant in nature, even present on our own skin, usually harmless. However, it is the leading cause of infection in humans. S. aureus also harms animals, and in dairy cows, causes Bovine mastitis. This disease results in a decreased quality and quantity of milk, inflammation of the mammary glands, and can even be transmitted to humans.(1) Because of this, there are massive economic ramifications estimated at $629 million annually.(2) This study focuses on a virulent factor known as a-hemolysin (Hla) and cloning this into S. aureus bacteria to make a vaccine to treat bovine mastitis. This is a protein present on the cell membrane of S. aureus, known for its cytotoxic properties. To harm eukaryotic cells, research suggests that Hla has a close relationship with a eukaryotic cell receptor known as ADAM10. Normally, this receptor has a role in the development of the nervous system, and in precursor formation of the amyloid protein. When S. aureus is exposed to these cell receptors, a bridge is formed between the Hla protein of the bacteria and the surface receptor ADAM10. After the link is formed, the Hla protein drills a pore into the eukaryotic cell causing it to lyse. (3) This makes the Hla protein a great candidate for a vaccine, as if this interaction could be prevented, then harm would be reduced in the host cell

Evaluation of EPAS1 variants for association with bovine congestive heart failure [version 1; peer review: 2 approved]

Background: Bovine congestive heart failure (BCHF) has become increasingly prevalent in feedlot cattle in the Western Great Plains of North America. BCHF is an untreatable complex condition involving pulmonary hypertension that culminates in right ventricular failure and death. A protein variant of hypoxia-inducible factor 2 alpha (HIF2α, encoded by the endothelial PAS domain-containing protein 1 gene, EPAS1) was previously reported to be associated with pulmonary hypertension at altitudes exceeding 2,000 m. Our aim was to evaluate EPAS1 haplotypes for association with BCHF in feedlot cattle raised at moderate altitudes (1,200 m). Methods: Paired samples of clinical cases and unaffected controls were collected at four feedlots in Nebraska and Wyoming. Each pair (n =102) was matched for source, pen, breed type, sex, arrival date, and management conditions. Cases were identified by animal caretakers, euthanized, and diagnosis was confirmed at necropsy. Cases were derived from 30 different ranch operations, with the largest source contributing 32. Animals were tested for eight EPAS1 haplotypes encoding 36 possible different diploid combinations. Results: The common, ancestral EPAS1 haplotype encoding HIF2α with alanine (A) at position 606 and glycine (G) at position 610 was equally frequent in cases and controls (0.67). The EPAS1 variant haplotype reported to be associated with disease (encoding threonine (T) at position 606 and serine (S) at position 610) was not enriched in cases compared with controls (0.21 and 0.25, respectively). Frequencies of other EPAS1 haplotypes (e.g., encoding Q270, L362, or G671) were each less than 0.05 overall. McNemar’s test with 45 discordant pairs showed the linked T606/S610 variant was not associated with BCHF (OR = 0.73, CI 0.38 -1.4, p-value = 0.37). Conclusions: HIF2α polypeptide variants were not significantly associated with BCHF in feedlot cattle at moderate altitudes. Thus, a wider search is needed to identify genetic risk factors underlying this disease

Liquor licences issued to Australian schools

BACKGROUND: Children's positive socialisation to alcohol is associated with early initiation of drinking and alcohol-related harm in adult life. Internationally, there have been reports of adults' alcohol consumption at school events in the presence of children. The aim of this research was to identify the conditions under which Australian schools are required to apply for a liquor licence and the associated prevalence of liquor licences for these events where children were likely to be present. METHODS: A document review was conducted to examine temporary liquor licensing legislation. Quantitative analysis was used to examine relevant licensing data. Coding criteria was developed to determine school type, student year levels and the likely presence of children. RESULTS: Four jurisdictions provided data on 1817 relevant licences. The average annual licences/100 schools was highest amongst Independent schools followed by Catholic and public (government) schools. The rates were highest in Queensland and Victoria where children were present at 61% and 32% of events respectively. CONCLUSIONS: While there are legislative differences across jurisdictions, the prevalence of adults' alcohol use at school events in the presence of children may reflect the various education department policies and principals' and school communities' beliefs and attitudes. Licences are not required for all events where liquor is consumed so the prevalence of adults' use of alcohol at school events is likely to be higher than our analyses imply. Such practices may undermine teaching about alcohol use in the school curriculum and health promotion efforts to develop alcohol-free events when children are present

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Genome remodelling in a basal-like breast cancer metastasis and xenograft

Massively parallel DNA sequencing technologies provide an unprecedented ability to screen entire genomes for genetic changes associated with tumour progression. Here we describe the genomic analyses of four DNA samples from an African-American patient with basal-like breast cancer: peripheral blood, the primary tumour, a brain metastasis and a xenograft derived from the primary tumour. The metastasis contained two de novo mutations and a large deletion not present in the primary tumour, and was significantly enriched for 20 shared mutations. The xenograft retained all primary tumour mutations and displayed a mutation enrichment pattern that resembled the metastasis. Two overlapping large deletions, encompassing CTNNA1, were present in all three tumour samples. The differential mutation frequencies and structural variation patterns in metastasis and xenograft compared with the primary tumour indicate that secondary tumours may arise from a minority of cells within the primary tumour

Search for gravitational-lensing signatures in the full third observing run of the LIGO-Virgo network

Gravitational lensing by massive objects along the line of sight to the source causes distortions of gravitational wave-signals; such distortions may reveal information about fundamental physics, cosmology and astrophysics. In this work, we have extended the search for lensing signatures to all binary black hole events from the third observing run of the LIGO--Virgo network. We search for repeated signals from strong lensing by 1) performing targeted searches for subthreshold signals, 2) calculating the degree of overlap amongst the intrinsic parameters and sky location of pairs of signals, 3) comparing the similarities of the spectrograms amongst pairs of signals, and 4) performing dual-signal Bayesian analysis that takes into account selection effects and astrophysical knowledge. We also search for distortions to the gravitational waveform caused by 1) frequency-independent phase shifts in strongly lensed images, and 2) frequency-dependent modulation of the amplitude and phase due to point masses. None of these searches yields significant evidence for lensing. Finally, we use the non-detection of gravitational-wave lensing to constrain the lensing rate based on the latest merger-rate estimates and the fraction of dark matter composed of compact objects

Search for eccentric black hole coalescences during the third observing run of LIGO and Virgo

Despite the growing number of confident binary black hole coalescences observed through gravitational waves so far, the astrophysical origin of these binaries remains uncertain. Orbital eccentricity is one of the clearest tracers of binary formation channels. Identifying binary eccentricity, however, remains challenging due to the limited availability of gravitational waveforms that include effects of eccentricity. Here, we present observational results for a waveform-independent search sensitive to eccentric black hole coalescences, covering the third observing run (O3) of the LIGO and Virgo detectors. We identified no new high-significance candidates beyond those that were already identified with searches focusing on quasi-circular binaries. We determine the sensitivity of our search to high-mass (total mass M>70 M⊙) binaries covering eccentricities up to 0.3 at 15 Hz orbital frequency, and use this to compare model predictions to search results. Assuming all detections are indeed quasi-circular, for our fiducial population model, we place an upper limit for the merger rate density of high-mass binaries with eccentricities 0<e≤0.3 at 0.33 Gpc−3 yr−1 at 90\% confidence level

Ultralight vector dark matter search using data from the KAGRA O3GK run

Among the various candidates for dark matter (DM), ultralight vector DM can be probed by laser interferometric gravitational wave detectors through the measurement of oscillating length changes in the arm cavities. In this context, KAGRA has a unique feature due to differing compositions of its mirrors, enhancing the signal of vector DM in the length change in the auxiliary channels. Here we present the result of a search for U(1)B−L gauge boson DM using the KAGRA data from auxiliary length channels during the first joint observation run together with GEO600. By applying our search pipeline, which takes into account the stochastic nature of ultralight DM, upper bounds on the coupling strength between the U(1)B−L gauge boson and ordinary matter are obtained for a range of DM masses. While our constraints are less stringent than those derived from previous experiments, this study demonstrates the applicability of our method to the lower-mass vector DM search, which is made difficult in this measurement by the short observation time compared to the auto-correlation time scale of DM