Feline hypersomatotropism and acromegaly tumorigenesis: a potential role for the AIP gene

Acromegaly in humans is usually sporadic, however up to 20% of familial isolated pituitary adenomas are caused by germline sequence variants of the aryl-hydrocarbon-receptor interacting protein (AIP) gene. Feline acromegaly has similarities to human acromegalic families with AIP mutations. The aim of this study was to sequence the feline AIP gene, identify sequence variants and compare the AIP gene sequence between feline acromegalic and control cats, and in acromegalic siblings. The feline AIP gene was amplified through PCR using whole blood genomic DNA from 10 acromegalic and 10 control cats, and 3 sibling pairs affected by acromegaly. PCR products were sequenced and compared with the published predicted feline AIP gene. A single nonsynonymous SNP was identified in exon 1 (AIP:c.9T > G) of two acromegalic cats and none of the control cats, as well as both members of one sibling pair. The region of this SNP is considered essential for the interaction of the AIP protein with its receptor. This sequence variant has not previously been reported in humans. Two additional synonymous sequence variants were identified (AIP:c.481C > T and AIP:c.826C > T). This is the first molecular study to investigate a potential genetic cause of feline acromegaly and identified a nonsynonymous AIP single nucleotide polymorphism in 20% of the acromegalic cat population evaluated, as well as in one of the sibling pairs evaluated

Prospective evaluation of a protocol for transitioning porcine lente insulintreated diabetic cats to human recombinant protamine zinc insulin

Objectives The objective was to evaluate a nadir-led protocol for transitioning porcine lente insulin suspension (PLIS)-treated diabetic cats onto human recombinant protamine zinc insulin (PZIR). Methods Recently diagnosed (<5 months) diabetic cats, treated with PLIS q12h for 6 weeks, were recruited. Fructosamine, 24 h blood glucose curve (BGC), quality of life assessment (DIAQoL-pet score) and Diabetic Clinical Score (DCS) were assessed at enrolment (PLIS-treated) and 2, 4 and 12 weeks after transitioning to PZIR (starting dose 0.2-0.7 U/kg q12h). Short duration of insulin action was defined as <9 h. Linear mixed effects modelling assessed for change in fructosamine, mean blood glucose (MBG) during BGCs, DIAQoL-pet score, DCS and q12h insulin dose. McNemar's tests compared the proportion of cats with hypoglycaemia at week 0 (PLIS-treated) and week 4 (PZIR-treated). Results Twenty-two cats were recruited. Median PLIS dose at enrolment was 0.5 U/kg (interquartile range 0.3-0.7 U/kg) q12h, equalling median PZIR starting dose (0.5 U/kg; interquartile range 0.3-0.7 U/kg q12h). Transitioning was followed by significant decreases in fructosamine (P = 0.00007), insulin dose (P = 0.02), DCS (P = 8.1 x 10(-8)) and DIAQoL-pet score (P = 0.003), indicating improved quality of life. MBG did not alter significantly (P = 0.1). Five cats (22.7%) achieved remission. Hypoglycaemia was recorded in 30/190 12 h BGCs (15.8%) and five cats experienced clinical hypoglycaemia. The proportion of cats with hypoglycaemia did not differ between PLIS (week 0) and PZIR (week 4) (P = 1.0). Duration of action was analysed in 19 cats. Six cats (31.6%) showed short duration of action on PLIS, compared with two cats (10.5%) after 4 weeks on PZIR. All six cats with short PLIS duration showed duration of 9 h on PZIR. Conclusions and relevance Used alongside a low-carbohydrate diet, transitioning to PZIR was associated with significantly improved clinical signs and quality of life, with some cats achieving remission. Transition to PZIR should be considered for cats with short duration of action on PLIS

Serum anti-Müllerian hormone concentrations before and after treatment of an ovarian granulosa cell tumour in a cat

Case summary A 15-year-old female cat was presented for investigation of progressive behavioural changes, polyuria, polydipsia and periuria. An ovarian granulosa cell tumour was identified and the cat underwent therapeutic ovariohysterectomy (OHE). The cat’s clinical signs resolved, but 6 months later it was diagnosed as having an anaplastic astrocytoma and was euthanased. Serum anti-Müllerian hormone (AMH) concentration prior to OHE was increased vs a control group of entire and neutered female cats. Following OHE, serum AMH concentration decreased to <1% of the original value. Relevance and novel information Serum AMH measurement may represent a novel diagnostic and monitoring tool for functional ovarian neoplasms in cats

Pilot study assessing the use of cabergoline for the treatment of cats with hypersomatotropism and diabetes mellitus

Abstract Objectives An affordable and effective treatment is needed to manage feline hypersomatotropism. The aim of this study was to assess whether treatment with oral cabergoline for 90 days in cats with hypersomatotropism and diabetes mellitus improved diabetic and insulin-like growth factor 1 (IGF-1) control. Methods This was a prospective cohort non-blinded pilot study enrolling client-owned cats with spontaneously occurring diabetes mellitus and hypersomatotropism. Cats received oral cabergoline (5–10 µg/kg q24h) for 90 consecutive days. Serum IGF-1 and fructosamine concentrations were measured on days 1, 30 and 90. Quality of life was determined using the DIAQoL-pet questionnaire on days 1 and 90. Results Nine cats were enrolled and eight completed the study. There was no significant change in the following: IGF-1 (day 1 median 2001 ng/ml [range 890–2001 ng/ml]; day 30 median 2001 ng/ml [range 929–2001 ng/ml]; day 90 median 1828 ng/ml [range 1035–2001 ng/ml]; χ2(2) = 0.667, P = 0.805); fructosamine (day 1 median 499 µmol/l [range 330–887 µmol/l], day 30 median 551 µmol/l [range 288–722 µmol/l], day 90 median 503 [range 315–851 µmol/l]; χ2(2) = 0.581, P = 0.764); or DIAQoL-pet score (median on day 1 –2.79 (range –4.62 to –0.28], median on day 90 –3.24 [range –4.41 to –0.28]; P = 0.715). There was a significant change of insulin dose (χ2(2) = 8.667, P = 0.008) with cats receiving higher insulin doses at day 90 compared with day 1 (median on day 1 was 0.98 [range 0.63–1.49] and median on day 90 was 1.56 [range 0.49–2.55] units/kg q12h; P = 0.026). Conclusions and relevance Cabergoline did not improve diabetic control or normalise insulin-like growth factor concentration, or improve patient quality of life

Geochemical approaches to the quantification of dispersed volcanic ash in marine sediment

Volcanic ash has long been recognized in marine sediment, and given the prevalence of oceanic and continental arc volcanism around the globe in regard to widespread transport of ash, its presence is nearly ubiquitous. However, the presence/absence of very fine-grained ash material, and identification of its composition in particular, is challenging given its broad classification as an “aluminosilicate” component in sediment. Given this challenge, many studies of ash have focused on discrete layers (that is, layers of ash that are of millimeter-to-centimeter or greater thickness, and their respective glass shards) found in sequences at a variety of locations and timescales and how to link their presence with a number of Earth processes. The ash that has been mixed into the bulk sediment, known as dispersed ash, has been relatively unstudied, yet represents a large fraction of the total ash in a given sequence. The application of a combined geochemical and statistical technique has allowed identification of this dispersed ash as part of the original ash contribution to the sediment. In this paper, we summarize the development of these geochemical/statistical techniques and provide case studies from the quantification of dispersed ash in the Caribbean Sea, equatorial Pacific Ocean, and northwest Pacific Ocean. These geochemical studies (and their sedimentological precursors of smear slides) collectively demonstrate that local and regional arc-related ash can be an important component of sedimentary sequences throughout large regions of the ocean

Generalised-Lorentzian Thermodynamics

We extend the recently developed non-gaussian thermodynamic formalism \cite{tre98} of a (presumably strongly turbulent) non-Markovian medium to its most general form that allows for the formulation of a consistent thermodynamic theory. All thermodynamic functions, including the definition of the temperature, are shown to be meaningful. The thermodynamic potential from which all relevant physical information in equilibrium can be extracted, is defined consistently. The most important findings are the following two: (1) The temperature is defined exactly in the same way as in classical statistical mechanics as the derivative of the energy with respect to the entropy at constant volume. (2) Observables are defined in the same way as in Boltzmannian statistics as the linear averages of the new equilibrium distribution function. This lets us conclude that the new state is a real thermodynamic equilibrium in systems capable of strong turbulence with the new distribution function replacing the Boltzmann distribution in such systems. We discuss the ideal gas, find the equation of state, and derive the specific heat and adiabatic exponent for such a gas. We also derive the new Gibbsian distribution of states. Finally we discuss the physical reasons for the development of such states and the observable properties of the new distribution function.Comment: 13 pages, 1 figur

Electron and proton heating by solar wind turbulence

Previous formulations of heating and transport associated with strong magnetohydrodynamic (MHD) turbulence are generalized to incorporate separate internal energy equations for electrons and protons. Electron heat conduction is included. Energy is supplied by turbulent heating that affects both electrons and protons, and is exchanged between them via collisions. Comparison to available Ulysses data shows that a reasonable accounting for the data is provided when (i) the energy exchange timescale is very long and (ii) the deposition of heat due to turbulence is divided, with 60% going to proton heating and 40% into electron heating. Heat conduction, determined here by an empirical fit, plays a major role in describing the electron data

Electron scale structures and magnetic reconnection signatures in the turbulent magnetosheath

Collisionless space plasma turbulence can generate reconnecting thin current sheets as suggested by recent results of numerical magnetohydrodynamic simulations. The MMS mission provides the first serious opportunity to check if small ion-electron-scale reconnection, generated by turbulence, resembles the reconnection events frequently observed in the magnetotail or at the magnetopause. Here we investigate field and particle observations obtained by the MMS fleet in the turbulent terrestrial magnetosheath behind quasi-parallel bow shock geometry. We observe multiple small-scale current sheets during the event and present a detailed look of one of the detected structures. The emergence of thin current sheets can lead to electron scale structures where ions are demagnetized. Within the selected structure we see signatures of ion demagnetization, electron jets, electron heating and agyrotropy suggesting that MMS spacecraft observe reconnection at these scales

Gas Accretion and Galactic Chemical Evolution: Theory and Observations

This chapter reviews how galactic inflows influence galaxy metallicity. The goal is to discuss predictions from theoretical models, but particular emphasis is placed on the insights that result from using models to interpret observations. Even as the classical G-dwarf problem endures in the latest round of observational confirmation, a rich and tantalizing new phenomenology of relationships between $M_*$, $Z$, SFR, and gas fraction is emerging both in observations and in theoretical models. A consensus interpretation is emerging in which star-forming galaxies do most of their growing in a quiescent way that balances gas inflows and gas processing, and metal dilution with enrichment. Models that explicitly invoke this idea via equilibrium conditions can be used to infer inflow rates from observations, while models that do not assume equilibrium growth tend to recover it self-consistently. Mergers are an overall subdominant mechanism for delivering fresh gas to galaxies, but they trigger radial flows of previously-accreted gas that flatten radial gas-phase metallicity gradients and temporarily suppress central metallicities. Radial gradients are generically expected to be steep at early times and then flattened by mergers and enriched inflows of recycled gas at late times. However, further theoretical work is required in order to understand how to interpret observations. Likewise, more observational work is needed in order to understand how metallicity gradients evolve to high redshifts.Comment: Invited review to appear in Gas Accretion onto Galaxies, Astrophysics and Space Science Library, eds. A. J. Fox & R. Dav\'e, to be published by Springer. 29 pages, 2 figure