Decay of Skin-Specific Gene Modules in Pangolins.

The mammalian skin exhibits a rich spectrum of evolutionary adaptations. The pilosebaceous unit, composed of the hair shaft, follicle, and the sebaceous gland, is the most striking synapomorphy. The evolutionary diversification of mammals across different ecological niches was paralleled by the appearance of an ample variety of skin modifications. Pangolins, order Pholidota, exhibit keratin-derived scales, one of the most iconic skin appendages. This formidable armor is intended to serve as a deterrent against predators. Surprisingly, while pangolins have hair on their abdomens, the occurrence of sebaceous and sweat glands is contentious. Here, we explore various molecular modules of skin physiology in four pangolin genomes, including that of sebum production. We show that genes driving wax monoester formation, Awat1/2, show patterns of inactivation in the stem pangolin branch, while the triacylglycerol synthesis gene Dgat2l6 seems independently eroded in the African and Asian clades. In contrast, Elovl3 implicated in the formation of specific neutral lipids required for skin barrier function is intact and expressed in the pangolin skin. An extended comparative analysis shows that genes involved in skin pathogen defense and structural integrity of keratinocyte layers also show inactivating mutations: associated with both ancestral and independent pseudogenization events. Finally, we deduce that the suggested absence of sweat glands is not paralleled by the inactivation of the ATP-binding cassette transporter Abcc11, as previously described in Cetacea. Our findings reveal the sophisticated and complex history of gene retention and loss as key mechanisms in the evolution of the highly modified mammalian skin phenotypes.

Convergent Cortistatin losses parallel modifications in circadian rhythmicity and energy homeostasis in Cetacea and other mammalian lineages.

The ancestors of Cetacea underwent profound morpho-physiological alterations. By displaying an exclusive aquatic existence, cetaceans evolved unique patterns of locomotor activity, vigilant behaviour, thermoregulation and circadian rhythmicity. Deciphering the molecular landscape governing many of these adaptations is key to understand the evolution of phenotypes. Here, we investigate Cortistatin (CORT), a neuropeptide displaying an important role in mammalian biorhythm regulation. This neuropeptide is a known neuroendocrine factor, stimulating slow-wave sleep, but also involved in the regulation of energy metabolism and hypomotility inducement. We assessed the functional status of CORT in 359 mammalian genomes (25 orders), including 30 species of Cetacea. Our findings indicate that cetaceans and other mammals with atypical biorhythms, thermal constraints and/or energy metabolism, have accumulated deleterious mutations in CORT. In light of the pleiotropic action of this neuropeptide, we suggest that this inactivation contributed to a plethora of phenotypic adjustments to accommodate adaptive solutions to specific ecological niches.

Functional or Vestigial? The Genomics of the Pineal Gland in Xenarthra.

Vestigial organs are historical echoes of past phenotypes. Determining whether a specific organ constitutes a functional or vestigial structure can be a challenging task, given that distinct levels of atrophy may arise between and within lineages. The mammalian pineal gland, an endocrine organ involved in melatonin biorhythmicity, represents a classic example, often yielding contradicting anatomical observations. In Xenarthra (sloths, anteaters, and armadillos), a peculiar mammalian order, the presence of a distinct pineal organ was clearly observed in some species (i.e., Linnaeus's two-toed sloth), but undetected in other closely related species (i.e., brown-throated sloth). In the nine-banded armadillo, contradicting evidence supports either functional or vestigial scenarios. Thus, to untangle the physiological status of the pineal gland in Xenarthra, we used a genomic approach to investigate the evolution of the gene hub responsible for melatonin synthesis and signaling. We show that both synthesis and signaling compartments are eroded and were probably lost independently among Xenarthra orders. Additionally, by expanding our analysis to 157 mammal genomes, we offer a comprehensive view showing that species with very distinctive habitats and lifestyles have convergently evolved a similar phenotype: Cetacea, Pholidota, Dermoptera, Sirenia, and Xenarthra. Our findings suggest that the recurrent inactivation of melatonin genes correlates with pineal atrophy and endorses the use of genomic analyses to ascertain the physiological status of suspected vestigial structures.

Assessing data bias in visual surveys from a cetacean monitoring programme.

Long-term monitoring datasets are fundamental to understand physical and ecological responses to environmental changes, supporting management and conservation. The data should be reliable, with the sources of bias identified and quantified. CETUS Project is a cetacean monitoring programme in the Eastern North Atlantic, based on visual methods of data collection. This study aims to assess data quality and bias in the CETUS dataset, by 1) applying validation methods, through photographic confirmation of species identification; 2) creating data quality criteria to evaluate the observer's experience; and 3) assessing bias to the number of sightings collected and to the success in species identification. Through photographic validation, the species identification of 10 sightings was corrected and a new species was added to the CETUS dataset. The number of sightings collected was biased by external factors, mostly by sampling effort but also by weather conditions. Ultimately, results highlight the importance of identifying and quantifying data bias, while also yielding guidelines for data collection and processing, relevant for species monitoring programmes based on visual methods.

Characterising Mitochondrial Capture in an Iberian Shrew.

Mitochondrial introgression raises questions of biogeography and of the extent of reproductive isolation and natural selection. Previous phylogenetic work on the Sorex araneus complex revealed apparent mitonuclear discordance in Iberian shrews, indicating past hybridisation of Sorex granarius and the Carlit chromosomal race of S. araneus, enabling introgression of the S. araneus mitochondrial genome into S. granarius. To further study this, we genetically typed 61 Sorex araneus/coronatus/granarius from localities in Portugal, Spain, France, and Andorra at mitochondrial, autosomal, and sex-linked loci and combined our data with the previously published sequences. Our data are consistent with earlier data indicating that S. coronatus and S. granarius are the most closely related of the three species, confirming that S. granarius from the Central System mountain range in Spain captured the mitochondrial genome from a population of S. araneus. This mitochondrial capture event can be explained by invoking a biogeographical scenario whereby S. araneus was in contact with S. granarius during the Younger Dryas in central Iberia, despite the two species currently having disjunct distributions. We discuss whether selection favoured S. granarius with an introgressed mitochondrial genome. Our data also suggest recent hybridisation and introgression between S. coronatus and S. granarius, as well as between S. araneus and S. coronatus.

A drastic shift in the energetic landscape of toothed whale sperm cells.

Mammalian spermatozoa are a notable example of metabolic compartmentalization.1 Energy in the form of ATP production, vital for motility, capacitation, and fertilization, is subcellularly separated in sperm cells. While glycolysis provides a local, rapid, and low-yielding input of ATP along the flagellum fibrous sheath, oxidative phosphorylation (OXPHOS), far more efficient over a longer time frame, is concentrated in the midpiece mitochondria.2 The relative weight of glycolysis and OXPHOS pathways in sperm function is variable among species and sensitive to oxygen and substrate availability.3-5 Besides partitioning energy production, sperm cell energetics display an additional singularity: the occurrence of sperm-specific gene duplicates and alternative spliced variants, with conserved function but structurally bound to the flagellar fibrous sheath.6,7 The wider selective forces driving the compartmentalization and adaptability of this energy system in mammalian species remain largely unknown, much like the impact of ecosystem resource availability (e.g., carbohydrates, fatty acids, and proteins) and dietary adaptations in reproductive physiology traits.8 Here, we investigated the Cetacea, an iconic group of fully aquatic and carnivorous marine mammals, evolutionarily related to extant terrestrial herbivores.9 In this lineage, episodes of profound trait remodeling have been accompanied by clear genomic signatures.10-14 We show that toothed whales exhibit impaired sperm glycolysis, due to gene and exon erosion, and demonstrate that dolphin spermatozoa motility depends on endogenous fatty acid ß-oxidation, but not carbohydrates. Such unique energetic rewiring substantiates the observation of large mitochondria in toothed whale spermatozoa and emphasizes the radical physiological reorganization imposed by the transition to a carbohydrate-depleted marine environment.

A dataset of cetacean occurrences in the Eastern North Atlantic.

The CETUS project is a cetacean monitoring program that takes advantage of cargo ships to undertake survey routes between Continental Portugal, Macaronesian archipelagos and West Africa. From 2012 to 2017, over 50 volunteers participated in the program, actively surveying more than 124.000 km, mostly beyond national jurisdictions in the high seas, for which little or no previous data existed. In total, the collection comprises 3058 georeferenced transect lines and 8913 positions, which are associated with 2833 cetacean sightings, 362 occurrences of other pelagic megafauna, 5260 estimates of marine traffic and 8887 weather observations. This dataset may provide new insights into the distribution of marine mammals in the Eastern North Atlantic and was published following the OBIS-ENV-DATA format (with the most recent biodiversity data standards at the time of writing). Consequently, it may serve as a model for similar visual line transect data collections yet to be published.

Improvement of diastolic function after regression of left ventricular hypertrophy.

OBJECTIVE: To evaluate the diastolic function after regression of left ventricular hypertrophy, in mild to moderate hypertension treated with angiotensin converting enzyme(ACE) inhibitor and, if necessary, with a diuretic. METHODS: Ninety-eight hypertensive patients with left ventricular hypertrophy (LVH) and abnormal left ventricle diastolic function indexes received captopril (Capotena) 50 to 200 mg/day plus chlortalidone during 12 months to reach blood pressure control, defined as a diastolic blood pressure < or =90 and systolic blood pressure < or =140 mm Hg. Left ventricular (LV) mass index was calculated by M mode and two-dimensional echocardiography, and left ventricular diastolic function was assessed by transmitral pulsed Doppler ultrasound every 3 months. RESULTS: Sixty-three patients were women and 35 were men, mean age was 53.4 +/- 8.4 years (range 34-70). Thirty-six patients had mild (36.7%) and 62 (63.3%) moderate hypertension. Treatment reduced significantly both systolic pressure from 165 +/- 13 to 137 +/- 12.9 mm Hg (p<0.05) and diastolic pressure from 99 +/- 8.6 to 86 +/- 6.37 mm Hg (p<0.05). LV mass index decreased from 155.4 +/- 32.9 to 121.7 +/- 29.14 g/m2 (p<0.05). Late diastolic filling velocity (A wave) and the ratio of E/A waves improved (p<0.05), but early diastolic filling velocity (E wave) and isovolumetric relaxation time did not change with treatment. CONCLUSIONS: Some indexes of diastolic function improved after regression of left ventricular hypertrophy and good blood pressure control with captopril and chlortalidone.

MIMO transmit scheme based on morphological perceptron with competitive learning.

This paper proposes a new multi-input multi-output (MIMO) transmit scheme aided by artificial neural network (ANN). The morphological perceptron with competitive learning (MP/CL) concept is deployed as a decision rule in the MIMO detection stage. The proposed MIMO transmission scheme is able to achieve double spectral efficiency; hence, in each time-slot the receiver decodes two symbols at a time instead one as Alamouti scheme. Other advantage of the proposed transmit scheme with MP/CL-aided detector is its polynomial complexity according to modulation order, while it becomes linear when the data stream length is greater than modulation order. The performance of the proposed scheme is compared to the traditional MIMO schemes, namely Alamouti scheme and maximum-likelihood MIMO (ML-MIMO) detector. Also, the proposed scheme is evaluated in a scenario with variable channel information along the frame. Numerical results have shown that the diversity gain under space-time coding Alamouti scheme is partially lost, which slightly reduces the bit-error rate (BER) performance of the proposed MP/CL-NN MIMO scheme.

Intraluminal aortoplasty vs. surgical aortic resection in congenital aortic coarctation. A clinical random study in pediatric patients.

BACKGROUND: Our objective was to compare results of two therapeutic modalities to treat congenital aortic coarctation: intraluminal aortoplasty without endoluminal stent installation (patients in group A) vs. surgical aortic resection (patients in group B). Trans-coarctation gradient pressure was evaluated prior to and immediately after treatment. Re-coarctation, aneurysm formation, in-hospital morbidity and mortality, and complications related to treatment were also evaluated. METHODS: A clinical, randomized, multicenter study was performed in pediatric patients with congenital aortic coarctation. Immediate and mid- to late therapeutic results were evaluated. With regard to statistics, we evaluated event variations by Kaplan-Meier model, nonparametric Wilcoxon test, Mann-Whitney U test, two-tailed Student t and chi-square tests, and Fisher analysis. Significance was considered relevant when p<0.05. RESULTS: There were no differences in demographic variables, procedure failure, complications, mortality, or aortic aneurysm between groups A and B, respectively. Intraluminal angioplasty and surgical aortic resection were similarly effective in reducing trans-coarctation pressure gradient, as well as arterial systemic pressure. However, differences were found between groups A and B at follow-up. Group A showed higher re-coarctation (50 vs. 21%). Absence of peripheral arterial pulses in limbs was higher in group A (50 vs. 21%), as well as persistence of arterial hypertension (49 vs. 19%); these differences were significant (p<0.05). On the other hand, complications observed after surgical aortic resection were more serious than post-angioplasty complications, but these differences were not statistically significant. CONCLUSIONS: Although re-coarctation and persistency of arterial hypertension were less frequent after surgical aortic resection, complications observed with this procedure are more serious than complications related to angioplasty, although these differences are not statistically significant.

Validation of the EuroSCORE model in patients undergoing heart surgery in Regional Hospital of High Speciality of Bajio / Validación del modelo EuroSCORE en pacientes sometidos a cirugía cardiaca en el Hospital Regional de Alta Especialidad del Bajío

Abstract: Introduction: EuroSCORE is a probabilistic model with good performance in the prognosis of mortality in heart surgery in many latitudes. It is recommendable to validate it in hospitals where it is employed. Objective: To validate the EuroSCORE model in adult patients at the Hospital Regional de Alta Especialidad del Bajío (HRAEB) of León, Guanajuato, Mexico. Material and methods: We conducted an observational transversal, and retrospective study, accomplishing this through the review of the clinical files of patients submitted to heart surgery with and without extracorporeal circulation pump from 01/01/2008 to 12/31/2013 at the HRAEB. This included mortality up to hospital discharge, utilizing the on-line calculator of the EuroSCORE program to estimate risk of death. In order to validate the EuroSCORE model, we assessed discrimination and calibration through the Area Under the receiver operating characteristics (ROC) curve and χ2 test with Hosmer-Lemeshow (H-L) goodness-of-fit, respectively. Results: A total of 342 patients, aged 50.02 ± 16.66 years, 181 males (52.9%) and 161 women (47.1%). The area under the ROC curve of the additive model was 0.763, and of the Hosmer-Lemeshow test was 5.30, with p = 0.62. The area under the ROC curve of the logistic model was 0.761 and of the Hosmer-Lemeshow test, 8.78, with p = 0.36. Conclusion: The EuroSCORE model is a reliable score for estimating the probabilities of death in adult patients submitted to heart surgery with or without the pump at the HRAEB.

Resumen: Introducción: EuroSCORE es un modelo probabilístico con buen desempeño en el pronóstico de mortalidad en cirugía cardiaca en muchas latitudes. Es recomendable validarlo en los hospitales donde se emplea. Objetivo: Validar el modelo EuroSCORE en pacientes adultos en el Hospital Regional de Alta Especialidad del Bajío (HRAEB) de León, Guanajuato, México. Material y métodos: Se realizó un estudio observacional transversal y retrospectivo, que se completó con la revisión de los expedientes clínicos de pacientes sometidos a cirugía cardiaca con y sin bomba de circulación extracorpórea desde el 01/01/2008 hasta el 31/12/2013 en el HRAEB. Esto incluyó la mortalidad hasta el alta hospitalaria, utilizando la calculadora en línea del programa EuroSCORE para estimar el riesgo de muerte. Para validar el modelo EuroSCORE, evaluamos la discriminación y la calibración a través de la curva de características de operación del receptor (ROC) y la prueba de χ2 con la efectividad de ajuste de Hosmer-Lemeshow (H-L), respectivamente. Resultados: Un total de 342 pacientes, de 50.02 ± 16.66 años, 181 hombres (52.9%) y 161 mujeres (47.1%). El área bajo la curva ROC del modelo aditivo fue de 0.763, y la de la prueba Hosmer-Lemeshow fue de 5.30, con p = 0.62. El área bajo la curva ROC del modelo logístico fue 0.761 y de la prueba Hosmer-Lemeshow, 8.78, con p = 0.36. Conclusión: El modelo EuroSCORE es una herramienta confiable para estimar las probabilidades de muerte en pacientes adultos sometidos a cirugía cardiaca con o sin bomba en el HRAEB.

Improvement of diastolic function after regression of left ventricular hypertrophy / Mejora de la función diastólica tras regresión de la hipertrofia ventricular izquierda

OBJECTIVE: To evaluate the diastolic function after regression of left ventricular hypertrophy, in mild to moderate hypertension treated with angiotensin converting enzyme(ACE) inhibitor and, if necessary, with a diuretic. METHODS: Ninety-eight hypertensive patients with left ventricular hypertrophy (LVH) and abnormal left ventricle diastolic function indexes received captopril (Capotena) 50 to 200 mg/day plus chlortalidone during 12 months to reach blood pressure control, defined as a diastolic blood pressure < or =90 and systolic blood pressure < or =140 mm Hg. Left ventricular (LV) mass index was calculated by M mode and two-dimensional echocardiography, and left ventricular diastolic function was assessed by transmitral pulsed Doppler ultrasound every 3 months. RESULTS: Sixty-three patients were women and 35 were men, mean age was 53.4 +/- 8.4 years (range 34-70). Thirty-six patients had mild (36.7%) and 62 (63.3%) moderate hypertension. Treatment reduced significantly both systolic pressure from 165 +/- 13 to 137 +/- 12.9 mm Hg (p<0.05) and diastolic pressure from 99 +/- 8.6 to 86 +/- 6.37 mm Hg (p<0.05). LV mass index decreased from 155.4 +/- 32.9 to 121.7 +/- 29.14 g/m2 (p<0.05). Late diastolic filling velocity (A wave) and the ratio of E/A waves improved (p<0.05), but early diastolic filling velocity (E wave) and isovolumetric relaxation time did not change with treatment. CONCLUSIONS: Some indexes of diastolic function improved after regression of left ventricular hypertrophy and good blood pressure control with captopril and chlortalidone.