Human and mouse essentiality screens as a resource for disease gene discovery

The identification of causal variants in sequencing studies remains a considerable challenge that can be partially addressed by new gene-specific knowledge. Here, we integrate measures of how essential a gene is to supporting life, as inferred from viability and phenotyping screens performed on knockout mice by the International Mouse Phenotyping Consortium and essentiality screens carried out on human cell lines. We propose a cross-species gene classification across the Full Spectrum of Intolerance to Loss-of-function (FUSIL) and demonstrate that genes in five mutually exclusive FUSIL categories have differing biological properties. Most notably, Mendelian disease genes, particularly those associated with developmental disorders, are highly overrepresented among genes non-essential for cell survival but required for organism development. After screening developmental disorder cases from three independent disease sequencing consortia, we identify potentially pathogenic variants in genes not previously associated with rare diseases. We therefore propose FUSIL as an efficient approach for disease gene discovery. Discovery of causal variants for monogenic disorders has been facilitated by whole exome and genome sequencing, but does not provide a diagnosis for all patients. Here, the authors propose a Full Spectrum of Intolerance to Loss-of-Function (FUSIL) categorization that integrates gene essentiality information to aid disease gene discovery

Observation of gravitational waves from the coalescence of a 2.5–4.5 M ⊙ compact object and a neutron star

We report the observation of a coalescing compact binary with component masses 2.5–4.5 M ⊙ and 1.2–2.0 M ⊙ (all measurements quoted at the 90% credible level). The gravitational-wave signal GW230529_181500 was observed during the fourth observing run of the LIGO–Virgo–KAGRA detector network on 2023 May 29 by the LIGO Livingston observatory. The primary component of the source has a mass less than 5 M ⊙ at 99% credibility. We cannot definitively determine from gravitational-wave data alone whether either component of the source is a neutron star or a black hole. However, given existing estimates of the maximum neutron star mass, we find the most probable interpretation of the source to be the coalescence of a neutron star with a black hole that has a mass between the most massive neutron stars and the least massive black holes observed in the Galaxy. We provisionally estimate a merger rate density of 55−47+127Gpc−3yr−1 for compact binary coalescences with properties similar to the source of GW230529_181500; assuming that the source is a neutron star–black hole merger, GW230529_181500-like sources may make up the majority of neutron star–black hole coalescences. The discovery of this system implies an increase in the expected rate of neutron star–black hole mergers with electromagnetic counterparts and provides further evidence for compact objects existing within the purported lower mass gap

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

Opera participants’ perceptions of brand resonance

Brand resonance is a marketing concept under-explored in the performing arts context. This paper responds by analysing focus group findings from a large Opera group, “Big Opera[1]” (For research integrity and anonymity requirements of focus group research, the company pseudonym is Big Opera) on how decision-makers can enhance brand resonance. Opera patronage was dwindling before the COVID-19 pandemic, which was further crystallized during the pandemic. As the performing arts sector tries to revive, it is useful to understand how brand resonance concepts can be used to reinvigorate patronage at the opera. A qualitative study of four opera focus groups, which included 24 participants with varying levels of attendance was conducted to examine brand resonance. The study reveals that when customers have brand attachment and love, developed through intense experiences at the opera, facilitated by engagement with the brand, and community, then brand loyalty develops for the opera by intention to re-purchase. The paper contributes to the literature by making recommendations on how to enhance brand resonance thereby increasing attendance. Intense experiences at the opera and engagement can be enhanced by offering packaged deals, such as accommodation and dinner, or drinks and canapés packages, backstage access, the development of a social club, social media brand community and loyalty programs to increase brand loyalty

Strategies and behaviors used by mothers in interactions with their young children during a mealtime in peri-urban areas of Huánuco, Peru

This study aimed to gain an in-depth understanding about different strategies used by mothers to feed their 6-23-month-old children, as well as to learn about mothers’ behaviors in response to situations of food refusal by her child, in order to generate evidence that contributes to the information gap on responsive feeding in Peru. The study was conducted in the city of Huánuco, a peri-urban area of Peru, with mothers of children in the complementary feeding stage participating. An in-depth 5-hour home observation was conducted in eight mother-child dyads. Both the mothers’ and children’s mealtime and food-related behaviors were coded and an inductive thematic analysis was applied. The primary objective of many of the strategies used by the mothers was to get their child to eat a little more. Six strategies were identified: pressure, encouragement, facilitating intake, acceptance, negotiation and reasoning. Certain differences were found in the strategies employed by the mother according to the age of her child, with mothers of younger children using more encouragement and mothers of older children using more pressure for their child to eat. The mothers’ behavior in response to the child's refusal of food was both responsive and non-responsive (controlling), depending on the reason for the refusal. The findings are of great value for understanding about the feeding interactions of mother-child dyads in Peru and they start to address the information gap and can support the development of nutritional intervention strategies for use with children. </p

Seagrass ecosystem services – what's next?

Seagrasses, marine flowering plants, provide a wide range of ecosystem services, defined here as natural processes and components that directly or indirectly benefit human needs. Recent research has shown that there are still many gaps in our comprehension of seagrass ecosystem service provision. Furthermore, there seems to be little public knowledge of seagrasses in general and the benefits they provide. This begs the questions: how do we move forward with the information we have? What other information do we need and what actions do we need to take in order to improve the situation and appreciation for seagrass? Based on the outcomes from an international expert knowledge eliciting workshop, three key areas to advance seagrass ecosystem service research were identified: 1) Variability of ecosystem services within seagrass meadows and among different meadows; 2) Seagrass ecosystem services in relation to, and their connection with, other coastal habitats; and 3) Improvement in the communication of seagrass ecosystem services to the public. Here we present ways forward to advance seagrass ecosystem service research in order to raise the profile of seagrass globally, as a means to establish more effective conservation and restoration of these important coastal habitats around the world. © 2017 The Author

Policy mapping of double-duty actions that address multiple forms of malnutrition in Peru. Abstract of the 22nd International Congress of Nutrition, Tokyo (Japan), December 6-11, 2022

22nd International Congress of Nutritio