BAsE-Seq: a method for obtaining long viral haplotypes from short sequence reads

Epidemiologists aim to inform the design of public health interventions with evidence on the evolution, emergence and spread of infectious diseases. Sequencing of pathogen genomes, together with date, location, clinical manifestation and other relevant data about sample origins, can contribute to describing nearly every aspect of transmission dynamics, including local transmission and global spread. The analyses of these data have implications for all levels of clinical and public health practice, from institutional infection control to policies for surveillance, prevention and treatment. This review highlights the range of epidemiological questions that can be addressed from the combination of genome sequence and traditional ‘line lists’ (tables of epidemiological data where each line includes demographic and clinical features of infected individuals). We identify opportunities for these data to inform interventions that reduce disease incidence and prevalence. By considering current limitations of, and challenges to, interpreting these data, we aim to outline a research agenda to accelerate the genomics-driven transformation in public health microbiology.     

Identification of 2 loci associated with development of myxomatous mitral valve disease in Cavalier King Charles Spaniels

Myxomatous mitral valve disease (MMVD) is the most common heart disease in dogs. It is characterized by chronic progressive degenerative lesions of the mitral valve. The valve leaflets become thickened and prolapse into the left atrium resulting in mitral regurgitation (MR). MMVD is most prevalent in small to medium sized dog breeds, Cavalier King Charles Spaniels (CKCS) in particular. The onset of MMVD is highly age dependent, and at the age of 10 years, nearly all CKCS are affected. The incidence of a similar disease in humans-mitral valve prolapse-is 1-5%. By defining CKCSs with an early onset of MMVD as cases and old dogs with no or mild signs of MMVD as controls, we conducted a genome-wide association study (GWAS) to identify loci associated with development of MMVD. We have identified a 1.58 Mb region on CFA13 (P(genome) = 4.0 × 10(-5)) and a 1.68 Mb region on CFA14 (P(genome) = 7.9 × 10(-4)) associated with development of MMVD. This confirms the power of using the dog as a model to uncover potential candidate regions involved in the molecular mechanisms behind complex traits.     

Intrinsic Heart Regeneration in Adult Vertebrates May be Strictly Limited to Low-Metabolic Ectotherms

The heart has a high-metabolic rate, and its “around-the-clock” vital role to sustain life sets it apart in a regenerative setting from other organs and appendages. The landscape of vertebrate species known to perform intrinsic heart regeneration is strongly biased toward ectotherms—for example, fish, salamanders, and embryonic/neonatal ectothermic mammals. It is hypothesized that intrinsic heart regeneration is exclusively limited to the low-metabolic hearts of ectotherms. The biomedical field of regenerative medicine seeks to devise biologically inspired regenerative therapies to diseased human hearts. Falsification of the ectothermy dependency for heart regeneration hypothesis may be a crucial prerequisite to meaningfully seek inspiration in established ectothermic regenerative animal models. Otherwise, engineering approaches to construct artificial heart components may constitute a more viable path toward regenerative therapies. A more strict definition of regenerative phenomena is generated and several testable sub-hypotheses and experimental avenues are put forward to elucidate the link between heart regeneration and metabolism. Also see the video abstract here https://youtu.be/fZcanaOT5z8 .     

The respiratory consequences of feeding in amphibians and reptiles

Many ectothermic vertebrates ingest very large meals at infrequent intervals. The digestive processes associated with these meals, often coupled with an extensive hypertrophy of the gastrointestinal organs, are energetically expensive and metabolic rate, therefore, increases substantially after feeding (specific dynamic action, SDA). Here, we review the cardio-respiratory consequences of SDA in amphibians and reptiles. For some snakes, the increased oxygen uptake during SDA is of similar magnitude to that of muscular exercise, and the two physiological states, therefore, exert similar and profound demands on oxygen transport by the cardiorespiratory systems. In several species, SDA is attended by increases in heart rate and overall systemic blood flows, but changes in blood flow distribution remain to be investigated. In snakes, the regulation of heart rate appears to involve a non-adrenergic-non-cholinergic mechanism, which may be a regulatory peptide released from the gastrointestinal system during digestion. Digestion is also associated with a net acid secretion to the stomach that causes an increase in plasma HCO3- concentration (the 'alkaline tide'). Experiments on chronically cannulated amphibians and reptiles, show that this metabolic alkalosis is countered by an increased P(CO2), so that the change in arterial pH is reduced. This respiratory compensation of arterial pH is accomplished through a reduction in ventilation relative to metabolism, but the estimated reductions in lung P(O2) are relatively small. The SDA response is also associated with haematological changes, but large interspecific differences exist. The studies on cardiorespiratory responses to digestion may allow for a further understanding of the physiological and structural constraints that limits the ability of reptiles and amphibians to sustain high metabolic rates.     

Respiratory consequences of feeding in the snake Python molorus

Snakes can ingest large meals and exhibit marked increases in metabolic rate during digestion. Because postprandial oxygen consumption in some snakes may surpass that attained during exercise, studies of digestion offers an alternative avenue to understand the cardio-respiratory responses to elevated metabolic rate in reptiles. The effects of feeding on metabolic rate, arterial oxygen levels, and arterial acid-base status in the snake Python molorus are described. Four snakes (180-250 g) were cannulated in the dorsal aorta and blood samples were obtained during 72 h following ingestion of a meal (rat pups) exceeding 20% of body weight. Oxygen consumption increased from a fasting value of 1.71 +/- 0.08 to 5.54 +/- 0.42 ml kg-1 min-1 at 48 h following feeding, and the respiratory gas exchange ratio increased from 0.67 +/- 0.02 to a maximum of 0.92 +/- 0.03 at 32 h. Plasma lactate was always less than 0.5 mM, so the postprandial increase in metabolic rate was met by aerobic respiration. In fasting animals, arterial PO2 was 66 +/- 4 mmHg and haemoglobin-O2 saturation was 92 +/- 3%; similar values were recorded during digestion, but haematocrit decreased from 15.8 +/- 1.0 to 9.8 +/- 0.8 due to repeated blood sampling. Plasma [HCO3-] increased from a fasting level of 19.3 +/- 0.8 to 25.8 +/- 1.0 mmol l-1 at 24 h after feeding. However, because arterial PCO2 increased from 21.1 +/- 0.5 to 27.9 +/- 1.4 mmHg, there was no significant change in arterial pH from the fasting value of 7.52 +/- 0.01. Acid-base status returned to pre-feeding levels at 72 h following feeding. The increased arterial PCO2 is most likely explained by a reduction in ventilation relative to metabolism, but we predict that lung PO2 does not decrease below 115 mmHg. Although ingestion of large meals is associated with large metabolic changes in pythons, the attendant changes in blood gases are relatively small. In particular, the small changes in plasma [HCO3-] and stable pH show that pythons respond very differently to digestion than alligators where very large alkaline tides have been observed. It is unclear why pythons and alligators differ in the magnitude of their responses, but given these interspecific differences it seems worthwhile to describe arterial blood gases during digestion in other species of ectothermic vertebrates.