Integration of Tmc1/2 into the mechanotransduction complex in zebrafish hair cells is regulated by Transmembrane O-methyltransferase (Tomt).

Transmembrane O-methyltransferase (TOMT / LRTOMT) is responsible for non-syndromic deafness DFNB63. However, the specific defects that lead to hearing loss have not been described. Using a zebrafish model of DFNB63, we show that the auditory and vestibular phenotypes are due to a lack of mechanotransduction (MET) in Tomt-deficient hair cells. GFP-tagged Tomt is enriched in the Golgi of hair cells, suggesting that Tomt might regulate the trafficking of other MET components to the hair bundle. We found that Tmc1/2 proteins are specifically excluded from the hair bundle in tomt mutants, whereas other MET complex proteins can still localize to the bundle. Furthermore, mouse TOMT and TMC1 can directly interact in HEK 293 cells, and this interaction is modulated by His183 in TOMT. Thus, we propose a model of MET complex assembly where Tomt and the Tmcs interact within the secretory pathway to traffic Tmc proteins to the hair bundle

A new view of k-essence

K-essence models, relying on scalar fields with non-canonical kinetic terms, have been proposed as an alternative to quintessence in explaining the observed acceleration of the Universe. We consider the use of field redefinitions to cast k-essence in a more familiar form. While k-essence models cannot in general be rewritten in the form of quintessence models, we show that in certain dynamical regimes an equivalence can be made, which in particular can shed light on the tracking behaviour of k-essence. In several cases, k-essence cannot be observationally distinguished from quintessence using the homogeneous evolution, though there may be small effects on the perturbation spectrum. We make a detailed analysis of two k-essence models from the literature and comment on the nature of the fine tuning arising in the models.Comment: 7 pages RevTeX4 file with four figures incorporate

Herschel/HIFI measurements of the ortho/para ratio in water towards Sagittarius B2(M) and W31C

We present Herschel/HIFI observations of the fundamental rotational transitions of ortho- and para-H16 2 O and H18 2 O in absorption towards Sagittarius B2(M) and W31C. The ortho/para ratio in water in the foreground clouds on the line of sight towards these bright continuum sources is generally consistent with the statistical high-temperature ratio of 3, within the observational uncertainties. However, somewhat unexpectedly, we derive a low ortho/para ratio of 2.35±0.35, corresponding to a spin temperature of ∼27 K, towards Sagittarius B2(M) at velocities of the expanding molecular ring. Water molecules in this region appear to have formed with, or relaxed to, an ortho/para ratio close to the value corresponding to the local temperature of the gas and dust

Home dialysis: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) controversies conference

Home dialysis modalities (home hemodialysis [HD] and peritoneal dialysis [PD]) are associated with greater patient autonomy and treatment satisfaction compared with in-center modalities, yet the level of home-dialysis use worldwide is low. Reasons for limited utilization are context-dependent, informed by local resources, dialysis costs, access to healthcare, health system policies, provider bias or preferences, cultural beliefs, individual lifestyle concerns, potential care-partner time, and financial burdens. In May 2021, KDIGO (Kidney Disease: Improving Global Outcomes) convened a controversies conference on home dialysis, focusing on how modality choice and distribution are determined and strategies to expand home-dialysis use. Participants recognized that expanding use of home dialysis within a given health system requires alignment of policy, fiscal resources, organizational structure, provider incentives, and accountability. Clinical outcomes across all dialysis modalities are largely similar, but for specific clinical measures, one modality may have advantages over another. Therefore, choice among available modalities is preference-sensitive, with consideration of quality of life, life goals, clinical characteristics, family or care-partner support, and living environment. Ideally, individuals, their care-partners, and their healthcare teams will employ shared decision-making in assessing initial and subsequent kidney failure treatment options. To meet this goal, iterative, high-quality education and support for healthcare professionals, patients, and care-partners are priorities. Everyone who faces dialysis should have access to home therapy. Facilitating universal access to home dialysis and expanding utilization requires alignment of policy considerations and resources at the dialysis-center level, with clear leadership from informed and motivated clinical teams

How much for a dime bag? An exploration of youth drug markets

Relatively little is known about how youth obtain marijuana and other drugs. The Drugs, Alcohol and Violence International (DAVI) study explored youthful drug markets among samples of school students, detained youth, and school dropouts (ages 14-17 years) in the greater metropolitan areas of Philadelphia, Toronto, Montreal, and Amsterdam. Students frequently reported sharing drugs, either getting them from others or giving them to others for free. Sharing was less common among the more drug-involved detainees and dropouts. Marijuana was typically obtained either outdoors or in a house or apartment. Few youth reported getting marijuana at school. In Amsterdam, where marijuana can be purchased in small quantities in coffeeshops, this was the most common place to get marijuana, even though 18 is the legal age for purchase. Alcohol was also most likely to be obtained in stores or restaurants across all the sites, even though none were of legal age except those in Amsterdam age 16 or older. Youth most often reported purchasing marijuana in nickel, dime or other small bags, which are not standardized units. The exception again was Amsterdam, where youth most often reported quantities in grams or joints, which is how it is sold in coffeeshops. The lack of standardization of units makes economic cost estimates suspect. Even standardized units such as alcohol present problems since youth report a wide range of ‘typical purchases.’ Survey data can, however, more aptly describe drug market characteristics such as general location of purchase, and relationship with the seller