Paternal care and litter size coevolution in mammals

Biparental care of offspring occurs in diverse mammalian genera and is particularly common among species with socially monogamous mating systems.Despite numerouswell-documented examples, however, the evolutionary causes and consequences of paternal care in mammals are not well understood. Here, we investigate the evolution of paternal care in relation to offspring production. Using comparative analyses to test for evidence of evolutionary associations between male care and life-history traits, we explore if biparental care is likely to have evolved because of the importance of male care to offspring survival, or if evolutionary increases in offspring production are likely to result from the evolution of biparental care. Overall, we find no evidence that paternal care has evolved in response to benefits of supporting females to rear particularly costly large offspring or litters. Rather, our findings suggest that increases in offspring production are more likely to follow the evolution of paternal care, specifically where males contribute depreciable investment such as provisioning young. Through coevolution with litter size, we conclude that paternal care inmammals is likely to play an important role in stabilizing monogamous mating systems and could ultimately promote the evolution of complex social behaviours

The Acute Physiological and Perceptual Responses to Blood-flow Restriction Applied During Un-resisted Knee Exercise: A Potential Treatment Adjunct for Physiotherapists

Purpose: Blood-flow restriction [BfR] training involves the temporary, artificial reduction of blood flow through a limb. Evidence suggests that BfR combined with low-intensity resistance exercise can minimise the loss of thigh muscle size and strength during periods of impaired weight-bearing. However, evidence is scarce as to the specific utility of adding BfR to un-resisted or ‘no-load’ exercise during injury rehabilitation. Therefore, this case series examined the effects of applying BfR during a no-load lower-limb knee exercise completed by athletes recovering from significant lower limb injuries. Methods: Three professional rugby players provided consent to incorporate BfR training into their injury rehabilitation programmes. (Case one; four weeks post tibia and fibula fracture. Case two; five weeks post Achilles tendon rupture. Case three; immediately following MRI diagnosis of an osseous stress injury of the knee). During the control exercise session, players performed three sets of a seated, un-resisted, single-leg knee-extension exercise. At subsequent sessions, a 21.5 cm wide blood-pressure cuff was used to superimpose BfR over the same exercise. BfR was applied intermittently or continuously across the upper thigh via 100 mmHg or 120 mmHg cuff pressure. Near infra-red spectroscopy [NIRS] monitored tissue oxygen saturation [SmO2] and total haemoglobin mass [tHb] of the vastus lateralis muscle before and during the exercise of each lower-limb. The relative change in SmO2 and tHb generated during each exercise session was then calculated. Session rate of perceived exertion [RPE] was monitored via a 10-point visual scale. Descriptive statistics were then used to indicate trends among these variables. Results: BfR training was delivered four to five times per week for periods of 4 to 12 weeks. NIRS data from thirty BfRT sessions (five sessions per leg, per player) were obtained. Mean resting values for vastus lateralis SmO2 and tHb were 54.3% and 12.72 g/dL respectively. During the control exercise session, SmO2 increased by a mean of 4.68 points, whilst tHb decreased slightly (-0.04 g/dL). In contrast, the addition of continuous BfR at 120 mmHg generated a mean drop in SmO2 of 22.31 points, whilst tHb increased (+0.23 g/dL). No adverse events or pain occurred during any exercise session. The control session generated a mean session RPE of 0.94 out of 10. Session RPE during BfR training ranged between 3.6 and 4.9. Conclusion(s): In a case series of injured athletes, data indicated that adding BfR to a ‘no-load’ knee extension exercise generated oxygen desaturation of the vastus lateralis muscle and increased perceptual exertion. Lower-limb BfR training was delivered in a safe, tolerable way as part of a multi-modal, intensive injury rehabilitation programme. Implications: BfR training may provide Physiotherapists with a novel Method of generating exercise-induced physiological stress within muscle tissue during exercise, without the need to add any external resistance. Achieving sufficient physiological stress during the very early stages of injury rehabilitation via no-load BfR training may promote a muscular response that limits the longitudinal muscle disuse atrophy seen during periods of impaired weight-bearing. Further research is warranted to substantiate this and to explore the utility of no-load BfR training within non-athletic, clinical populations. Funding acknowledgements: This study was funded via a PhD studentship awarded by Manchester Metropolitan University

Cryptic kin discrimination during communal lactation in mice favours cooperation between relatives

Breeding females can cooperate by rearing their offspring communally, sharing synergistic benefits of offspring care but risking exploitation by partners. In lactating mammals, communal rearing occurs mostly among close relatives. Inclusive fitness theory predicts enhanced cooperation between related partners and greater willingness to compensate for any partner under-investment, while females are less likely to bias investment towards own offspring. We use a dual isotopic tracer approach to track individual milk allocation when familiar pairs of sisters or unrelated house mice reared offspring communally. Closely related pairs show lower energy demand and pups experience better access to non-maternal milk. Lactational investment is more skewed between sister partners but females pay greater energetic costs per own offspring reared with an unrelated partner. The choice of close kin as cooperative partners is strongly favoured by these direct as well as indirect benefits, providing a driver to maintain female kin groups for communal breeding

Neural correlates of hyperalgesia in the monosodium iodoacetate model of osteoarthritis pain

Background: The mechanisms driving osteoarthritic pain remain poorly understood, but there is increasing evidence for a role of the central nervous system in the chronification of pain.We used functional magnetic resonance imaging to investigate the influence of a model of unilateral knee osteoarthritis on nociceptive processing. Results: Four to five weeks post intra-articular injection of monosodium iodoacetate (MIA, 1 mg) into the left knee, Sprague Dawley rats were anesthetized for functional magnetic resonance imaging studies to characterize the neural response to a noxious stimulus (intra-articular capsaicin injection). In a two-arm cross-over design, 5 mM/50 ml capsaicin was injected into either the left knee (n¼8, CAPS-MIA) or right control knee (n¼8, CAPS-CON), preceded by contralateral vehicle (SAL) injection. To assess neural correlates of mechanical hyperalgesia, hindpaws were stimulated with von Frey hairs (8 g: MIA; 15 g: control knee, based on behavioral withdrawal responses). The CAPS-MIA group exhibited significant activation of the periaqueductal gray, unilateral thalamus and bilateral mensencephalon, superior-colliculus, and hippocampus, with no significant activation in the other groups/conditions. Capsaicin injection increased functional connectivity in the mid-brain network and mediodorsal thalamic nucleus, hippocampus, and globus pallidus, which was significantly stronger in CAPS-MIA compared to CAPS-CON groups. Mechanical stimulation of the hyperalgesic (ipsilateral to MIA knee) and normalgesic (contralateral) hindpaws evoked qualitatively different brain activation with more widespread brainstem and anterior cingulate (ACC) activation when stimulating the hyperalgesic paw, and clearer frontal sensory activation from the normalgesic paw. Conclusions: We provide evidence for modulation of nociceptive processing in a chronic knee osteoarthritis pain model with stronger brain activation and alteration of brain networks induced by the pro-nociceptive stimulus. We also report a shift to a medial pain activation pattern following stimulation of the hyperalgesic hindpaw. Taken together, our data support altered neural pain processing as a result of peripheral and central pain sensitization in this model

Inter-laboratory proficiency testing scheme for tumour next-generation sequencing in Ontario: A pilot study

Background A pilot inter-laboratory proficiency scheme for 5 Ontario clinical laboratories testing tumour samples for the Ontario-wide Cancer Targeted Nucleic Acid Evaluation (OCTANE) study was undertaken to assess proficiency in the identification and reporting of next-generation sequencing (NGS) test results in solid tumour testing from archival formalin-fixed, paraffin-embedded (FFPE) tissue. Methods One laboratory served as the reference centre and provided samples to 4 participating laboratories. An analyte-based approach was applied: each participating laboratory received 10 FFPE tissue specimens profiled at the reference centre, with tumour site and histology provided. Laboratories performed testing per their standard NGS tumour test protocols. Items returned for assessment included genes and variants that would be typically reported in routine clinical testing and variant call format (VCF) files to allow for assessment of NGS technical quality. Results Two main aspects were assessed: Technical quality and accuracy of identification of exonic variants Site-specific reporting practices Technical assessment included evaluation of exonic variant identification, quality assessment of the VCF files to evaluate base calling, variant allele frequency, and depth of coverage for all exonic variants. Concordance at 100% was observed from all sites in the technical identification of 98 exonic variants across the 10 cases. Variability between laboratories in the choice of variants considered clinically reportable was significant. Of the 38 variants reported as clinically relevant by at least 1 site, only 3 variants were concordantly reported by all participating centres as clinically relevant. Conclusions Although excellent technical concordance for NGS tumour profiling was observed across participating institutions, differences in the reporting of clinically relevant variants were observed, highlighting reporting as a gap where consensus on the part of Ontario laboratories is needed

Polyandrous females avoid costs of inbreeding

Why do females typically mate with more than one male? Female mating patterns have broad implications for sexual selection, speciation and conflicts of interest between the sexes, and yet they are poorly understood. Matings inevitably have costs, and for females, the benefits of taking more than one mate are rarely obvious. One possible explanation is that females gain benefits because they can avoid using sperm from genetically incompatible males, or invest less in the offspring of such males. It has been shown that mating with more than one male can increase offspring viability, but we present the first clear demonstration that this occurs because females with several mates avoid the negative effects of genetic incompatibility. We show that in crickets, the eggs of females that mate only with siblings have decreased hatching success. However, if females mate with both a sibling and a non-sibling they avoid altogether the low egg viability associated with sibling matings. If similar effects occur in other species, inbreeding avoidance may be important in understanding the prevalence of multiple mating

Assembly of infectious enteroviruses depends on multiple, conserved genomic RNA-coat protein contacts.

Picornaviruses are important viral pathogens, but despite extensive study, the assembly process of their infectious virions is still incompletely understood, preventing the development of anti-viral strategies targeting this essential part of the life cycle. We report the identification, via RNA SELEX and bioinformatics, of multiple RNA sites across the genome of a typical enterovirus, enterovirus-E (EV-E), that each have affinity for the cognate viral capsid protein (CP) capsomer. Many of these sites are evolutionarily conserved across known EV-E variants, suggesting they play essential functional roles. Cryo-electron microscopy was used to reconstruct the EV-E particle at ~2.2 Å resolution, revealing extensive density for the genomic RNA. Relaxing the imposed symmetry within the reconstructed particles reveals multiple RNA-CP contacts, a first for any picornavirus. Conservative mutagenesis of the individual RNA-contacting amino acid side chains in EV-E, many of which are conserved across the enterovirus family including poliovirus, is lethal but does not interfere with replication or translation. Anti-EV-E and anti-poliovirus aptamers share sequence similarities with sites distributed across the poliovirus genome. These data are consistent with the hypothesis that these RNA-CP contacts are RNA Packaging Signals (PSs) that play vital roles in assembly and suggest that the RNA PSs are evolutionarily conserved between pathogens within the family, augmenting the current protein-only assembly paradigm for this family of viruses

Revealing the density of encoded functions in a viral RNA

Nikesh Patel, et al, ‘Revealing the density of encoded functions in a viral RNA’, Proceedings of the National Academy of Sciences of the United States of America (PNAS), Vol. 112 (7): 2227-2232, February 2015, doi: http:dx.doi.org/10. 1073/pnas.1420812112. This article is freely available online through the PNAS open access option.We present direct experimental evidence that assembly of a single-stranded RNA virus occurs via a packaging signal-mediated mechanism. We show that the sequences of coat protein recognition motifs within multiple, dispersed, putative RNA packaging signals, as well as their relative spacing within a genomic fragment, act collectively to influence the fidelity and yield of capsid self-assembly in vitro. These experiments confirm that the selective advantages for viral yield and encapsidation specificity, predicted from previous modeling of packaging signal-mediated assembly, are found in Nature. Regions of the genome that act as packaging signals also function in translational and transcriptional enhancement, as well as directly coding for the coat protein, highlighting the density of encoded functions within the viral RNA. Assembly and gene expression are therefore direct molecular competitors for different functional folds of the same RNA sequence. The strongest packaging signal in the test fragment, encodes a region of the coat protein that undergoes a conformational change upon contact with packaging signals. A similar phenomenon occurs in other RNA viruses for which packaging signals are known. These contacts hint at an even deeper density of encoded functions in viral RNA, which if confirmed, would have profound consequences for the evolution of this class of pathogensPeer reviewedFinal Published versio