Molecular mechanism and physiological role of active-deactive transition of mitochondrial complex I

The unique feature ofmitochondrial complex I is the so-called A/D transition (active-deactive transition). The A-form catalyses rapid oxidation of NADH by ubiquinone (k ~10 min) and spontaneously converts into the D-form if the enzyme is idle at physiological temperatures. Such deactivation occurs in vitro in the absence of substrates or in vivo during ischaemia, when the ubiquinone pool is reduced. The D-form can undergo reactivation given both NADH and ubiquinone availability during slow (k ~1-10 min) catalytic turnover(s). We examined known conformational differences between the two forms and suggested a mechanism exerting A/D transition of the enzyme. In addition, we discuss the physiological role of maintaining the enzyme in the D-form during the ischaemic period. Accumulation of the D-form of the enzyme would prevent reverse electron transfer from ubiquinol to FMN which could lead to superoxide anion generation. Deactivation would also decrease the initial burst of respiration after oxygen reintroduction. Therefore the A/D transition could be an intrinsic protective mechanism for lessening oxidative damage during the early phase of reoxygenation. Exposure of Cys of mitochondrially encoded subunit ND3 makes the Dform susceptible for modification by reactive oxygen species and nitric oxide metabolites which arrests the reactivation of the D-form and inhibits the enzyme. The nature of thiol modification defines deactivation reversibility, the reactivation timescale, the status of mitochondrial bioenergetics and therefore the degree of recovery of the ischaemic tissues after reoxygenation.

Using extended contact to improve physiological responses and behavior toward people with schizophrenia

Extended contact has been shown to improve explicit and implicit attitudes toward a number of outgroups, but not yet toward people with mental health conditions. Using people with schizophrenia as the target group, this experiment is the first to demonstrate that extended contact can reduce explicit prejudice, buffer stress responses to future interactions, improve non-verbal behavior, and improve the quality of interactions in a manner detectable by the target group member. Participants watched a video of a brief, positive interaction between two strangers, one of whom they were led to believe had schizophrenia. Control participants watched the same video without being told that the person had schizophrenia. They then participated in a social interaction with a confederate whom they were led to believe had the disorder. Participants' cardiovascular and electrodermal activity were monitored immediately before the interaction. The interaction was also secretly recorded to allow independent judges to assess the participants' non-verbal behaviors. The confederate also rated the positivity of each interaction. Participants in the extended contact condition reported more positive attitudes toward people with schizophrenia, displayed more positive non-verbal behaviors, and had a more positive interaction with the confederate. Moreover, just prior to the interaction, participants in the extended contact condition displayed smaller anticipatory stress responses, as reflected in smaller changes in interbeat interval and non-specific skin conductance responses during this phase. Together, these findings support the use of the extended contact as an intervention that could lead to genuine changes in attitudes toward and treatment of people with severe mental health disorders.

Proteomic analysis reveals oxidative stress response as the main adaptative physiological mechanism in cows under different production systems

Three groups of cows representing three ranges of welfare in the production system were included in the study: two groups of Bruna dels Pirineus beef cattle maintained under different management systems (good and semiferal conditions) and a group of Alberes cows, a breed that lives in the mountains (hardest conditions).

In order to identify new stress/welfare biomarkers, serum from Bruna cows living in both environments was subjected to DIGE labelling, two-dimensional electrophoresis and MALDI-MS or ion trap MS. Identification was achieved for 15 proteins, which mainly belonged to three biological functions, the oxidative stress pathway (glutathione peroxidase (GPx) and paraoxonase (PON-1)), the acute phase protein family (Heremans Schmid glycoprotein alpha2 (α2-HSG)) and the complement system.

Biological validation included the Alberes breed. GPx and PON-1 were validated by an enzymatic assay and found to be higher and lower, respectively, in cows living in hard conditions. α2-HSG was validated by ELISA and found to be reduced in hard conditions. Other biomarkers of the redox status were also altered by living conditions: protein carbonyl content, superoxide dismutase (SOD) and glutathione reductase (GR).

Our results show that changes in the redox system are the main adaptation of cows living in challenging environmental conditions. This article is part of a Special Issue entitled: “Farm animal proteomics”.

The role of adiposity in cardiometabolic traits:a Mendelian randomization analysis

The association between adiposity and cardiometabolic traits is well known from epidemiological studies. Whilst the causal relationship is clear for some of these traits, for others it is not. We aimed to determine whether adiposity is causally related to various cardiometabolic traits using the Mendelian randomization approach.

Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture

Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.

Determining optimal duration of seed translocation periods for benthic mussel (Mytilus edulis) cultivation using physiological and behavioural measures of stress

During the benthic cultivation process of Mytilus edulis (blue mussels), wild mussel seed is often transplanted from naturally occurring subtidal beds to sheltered in-shore waters to be grown to a commercial size. The survival of these relaid mussels is ultimately a function of their quality and physiological condition upon relaying and it has been recognised that mussels can suffer from a loss in condition following transportation. We investigated whether the process of being transported to ongrowing plots had a negative effect on the physiological health and resultant behaviour of mussels by simulating transportation conditions in a controlled experiment. Mussels were kept, out of water, in plastic piping to recreate translocation conditions and further, we tested if depth held in a ship hold (0, 1.5 and 3 m) and length of time emersed (12, 24 and 48 h) affected mussel condition and behaviour. Physiological condition was assessed by quantifying mussel tissue pH and whole tissue glucose, glycogen, succinate and propionate concentrations. The rate of byssogenesis was also quantified to estimate recovery following a period of re-immersion. The depth at which mussels were held did not affect any of the physiological indicators of mussel stress but short-term byssus production was affected. Mussels held at 3 m produced fewer byssus threads during the first 72 h following re-immersion compared with mussels at 0 m (i.e. not buried) suggesting that depth held can impede recovery following transportation. Duration of emersion affected all stress indicators. Specifically, mussels held out of water for 48 h had a reduced physiological condition compared with those emersed for just 12 h. This work has practical implications for the benthic cultivation industry and based on these results we recommend that mussels are held out of water for less than 24 h prior to relaying to ensure physiological health and resultant condition is preserved.

Applying imagined contact to improve physiological responses in anticipation of intergroup interactions and the perceived quality of these interactions

This experiment (N 5 49) is the first to show that imagined contact can bufferanticipatory physiological responses to future interactions, and improve the qualityof these interactions. Participants imagined a positive interaction with a person withschizophrenia, or in a control condition, a person who did not have schizophrenia. They then interacted with a confederate whom they believed had schizophrenia. Participants in the imagined contact condition reported more positive attitudes andless avoidance of people with schizophrenia, displayed smaller anticipatory physio-logical responses, specifically smaller changes in interbeat interval and skin conduct-ance responses, and had a more positive interaction according to the confederate.These findings support applying imagined contact to improve interactions with people with severe mental illnesses.

Investigation of physiological properties of nerves and muscles using electromyography.

The measurement and representation of the electrical activity of muscles [electromyography (EMG)] have a long history from the Victorian Era until today. Currently, EMG has uses both as a research tool, in noninvasively recording muscle activation, and clinically in the diagnosis and assessment of nerve and muscle disease and injury as well as in assessing the recovery of neuromuscular function after nerve damage. In the present report, we describe the use of a basic EMG setup in our teaching laboratories to demonstrate some of these current applications. Our practical also illustrates some fundamental physiological and structural properties of nerves and muscles. Learning activities include 1) displaying the recruitment of muscle fibers with increasing force development; 2) the measurement of conduction velocity of motor nerves; 3) the assessment of reflex delay and demonstration of Jendrassik's maneuver; and 4) a Hoffman reflex experiment that illustrates the composition of mixed nerves and the differential excitability thresholds of fibers within the same nerve, thus aiding an understanding of the reflex nature of muscle control. We can set up the classes at various levels of inquiry depending on the needs/professional requirements of the class. The results can then provide an ideal platform for a discovery learning session/tutorial on how the central nervous system controls muscles, giving insights on how supraspinal control interacts with reflexes to give smooth, precise muscular activation.

Expertly validated models and phylogenetically-controlled analysis suggests responses to climate change are related to species traits in the Order Lagomorpha

Climate change during the last five decades has impacted significantly on natural ecosystems and the rate of current climate change is of great concern among conservation biologists. Species Distribution Models (SDMs) have been used widely to project changes in species’ bioclimatic envelopes under future climate scenarios. Here, we aimed to advance this technique by assessing future changes in the bioclimatic envelopes of an entire mammalian order, the Lagomorpha, using a novel framework for model validation based jointly on subjective expert evaluation and objective model evaluation statistics. SDMs were built using climatic, topographical and habitat variables for all 87 lagomorph species under past and current climate scenarios. Expert evaluation and Kappa values were used to validate past and current models and only those deemed ‘modellable’ within our framework were projected under future climate scenarios (58 species). Phylogenetically-controlled regressions were used to test whether species traits correlated with predicted responses to climate change. Climate change is likely to impact more than two-thirds of lagomorph species, with leporids (rabbits, hares and jackrabbits) likely to undertake poleward shifts with little overall change in range extent, whilst pikas are likely to show extreme shifts to higher altitudes associated with marked range declines, including the likely extinction of Kozlov’s Pika (Ochotona koslowi). Smaller-bodied species were more likely to exhibit range contractions and elevational increases, but showing little poleward movement, and fecund species were more likely to shift latitudinally and elevationally. Our results suggest that species traits may be important indicators of future climate change and we believe multi-species approaches, as demonstrated here, are likely to lead to more effective mitigation measures and conservation management. We strongly advocate studies minimising data gaps in our knowledge of the Order, specifically collecting more specimens for biodiversity archives and targeting data deficient geographic regions.

Biogeography, macroecology and species’ traits mediate competitive interactions in the order Lagomorpha

1. In addition to abiotic determinants, biotic factors, including competitive, interspecific interactions, limit species’ distributions. Environmental changes in human disturbance, land use and climate are predicted to have widespread impacts on interactions between species, especially in the order Lagomorpha due to the higher latitudes and more extreme environmental conditions they occupy.
2. We reviewed the published literature on interspecific interactions in the order Lagomorpha, and compared the biogeography, macroecology, phylogeny and traits of species known to interact with those of species with no reported interactions, to investigate how projected future environmental change may affect interactions and potentially alter species’ distributions.
3. Thirty-three lagomorph species have competitive interactions reported in the literature; the majority involve hares (Lepus sp.) or the eastern cottontail rabbit (Sylvilagus floridanus). Key regions for interactions are located between 30-50°N of the Equator, and include eastern Asia (southern Russia on the border of Mongolia) and North America (north western USA).
4. Closely related, large-bodied, similarly sized species occurring in regions of human-modified, typically agricultural landscapes, or at high elevations are significantly more likely to have reported competitive interactions than other lagomorph species.
5. We identify species’ traits associated with competitive interactions, and highlight some potential impacts that future environmental change may have on interspecific interactions. Our approach using bibliometric and biological data is widely applicable, and with relatively straightforward methodologies, can provide insights into interactions between species.
6. Our results have implications for predicting species’ responses to global change, and we advise that capturing, parameterizing and incorporating interspecific interactions into analyses (for example, species distribution modelling) may be more important than suggested by the literature.