Habitat characteristics and species interference influence space use and nest‐site occupancy: implications for social variation in two sister species

Nest‐site selection is an important component of species socio‐ecology, being a crucial factor in establishment of group living. Consequently, nest‐site characteristics together with space‐use proxies may reveal the social organization of species, which is critical when direct observation of social interactions is hindered in nature. Importantly, nest‐site choice is expected to be under strong selective pressures and the object of intra‐ and interspecific competition. Although the bulk of research on sociality focuses on its ecological drivers, our study introduces interspecific competition as a potential factor that could influence social evolution. We investigated the influence of habitat and interspecific competition on the social organization of two sister species of the African four striped mouse, Rhabdomys dilectus dilectus and Rhabdomys bechuanae, in a similar macroenvironment. These species diverged in allopatry and occupy distinct environmental niches. We radiotracked 140 adults to identify their nest‐sites, determine nest characteristics and record groups that shared nest‐sites. Group cohesion was estimated from nest‐site fidelity, group association strength, and home range overlap within versus between group members. We compared the two species in sympatry versus parapatry to determine the impact of species interference on sociality. In parapatry, the two species selected distinct nest‐site types, interpreted as different anti‐predator strategies: R. bechuanae selected fewer, spaced, less concealed nest‐sites whereas R. d. dilectus selected clumped and less visible nest‐sites. Rhabdomys bechuanae also showed more cohesive and stable social groups than R. d. dilectus. In sympatry, compared to R. bechuanae, R. d. dilectus occupied similar nest‐sites, however slightly more exposed and clumped, and displayed similar nest‐site fidelity and group association strength. We conclude that although habitat selection may be an important driver of social divergence in Rhabdomys, species interference, by limiting R. d. dilectus movements and forcing nest‐site sharing may induce new ecological pressures that could influence its social evolution.     

Mitochondrial dynamics in the neonatal brain – a potential target following injury?

The impact of birth asphyxia and its sequelae, hypoxic–ischaemic (HI) brain injury, is long-lasting and significant, both for the infant and for their family. Treatment options are limited to therapeutic hypothermia, which is not universally successful and is unavailable in low resource settings. The energy deficits that accompany neuronal death following interruption of blood flow to the brain implicate mitochondrial dysfunction. Such HI insults trigger mitochondrial outer membrane permeabilisation leading to release of pro-apoptotic proteins into the cytosol and cell death. More recently, key players in mitochondrial fission and fusion have been identified as targets following HI brain injury. This review aims to provide an introduction to the molecular players and pathways driving mitochondrial dynamics, the regulation of these pathways and how they are altered following HI insult. Finally, we review progress on repurposing or repositioning drugs already approved for other indications, which may target mitochondrial dynamics and provide promising avenues for intervention following brain injury. Such repurposing may provide a mechanism to fast-track, low-cost treatment options to the clinic.     

A framework to evaluate whether to pool or separate behaviors in a multilayer network

A multilayer network approach combines different network layers,which are connected by interlayer edges,to create a single mathematical object.These networks can contain a variety of information types and represent different aspects of a system.However,the process for selecting which information to include is not always straightforward.Using data on 2 agonistic behaviors in a captive population of monk parakeets(Myiopsitta monachus),we developed a framework for investigating how pooling or splitting behaviors at the scale of dyadic relationships(between 2 individuals)affects individual-and group-level social properties.We designed 2 reference models to test whether randomizing the number of interactions across behavior types results in similar structural patterns as the observed data.Although the behaviors were correlated,the first reference model suggests that the 2 behaviors convey different information about some social properties and should therefore not be pooled.However,once we controlled for data sparsity,we found that the observed measures corresponded with those from the second reference model.Hence,our initial result may have been due to the unequal frequencies of each behavior.Overall,our findings support pooling the 2 behaviors.Awareness of how selected measurements can be affected by data properties is warranted,but nonetheless our framework disentangles these efforts and as a result can be used for myriad types of behaviors and questions.This framework will help researchers make informed and data-driven decisions about which behaviors to pool or separate,prior to using the data in subsequent multilayer network analyses.     

Uptake of infant and preschool immunisations in Scotland and England during the COVID-19 pandemic: An observational study of routinely collected data

BackgroundIn 2020, the SARS-CoV-2 (COVID-19) pandemic and lockdown control measures threatened to disrupt routine childhood immunisation programmes with early reports suggesting uptake would fall. In response, public health bodies in Scotland and England collected national data for childhood immunisations on a weekly or monthly basis to allow for rapid analysis of trends. The aim of this study was to use these data to assess the impact of different phases of the pandemic on infant and preschool immunisation uptake rates.Methods and findingsWe conducted an observational study using routinely collected data for the year prior to the pandemic (2019) and immediately before (22 January to March 2020), during (23 March to 26 July), and after (27 July to 4 October) the first UK “lockdown”. Data were obtained for Scotland from the Public Health Scotland “COVID19 wider impacts on the health care system” dashboard and for England from ImmForm.Five vaccinations delivered at different ages were evaluated; 3 doses of “6-in-1” diphtheria, tetanus, pertussis, polio, Haemophilus influenzae type b, and hepatitis B vaccine (DTaP/IPV/Hib/HepB) and 2 doses of measles, mumps, and rubella (MMR) vaccine. This represented 439,754 invitations to be vaccinated in Scotland and 4.1 million for England. Uptake during the 2020 periods was compared to the previous year (2019) using binary logistic regression analysis. For Scotland, uptake within 4 weeks of a child becoming eligible by age was analysed along with geographical region and indices of deprivation. For Scotland and England, we assessed whether immunisations were up-to-date at approximately 6 months (all doses 6-in-1) and 16 to 18 months (first MMR) of age.We found that uptake within 4 weeks of eligibility in Scotland for all the 5 vaccines was higher during lockdown than in 2019. Differences ranged from 1.3% for first dose 6-in-1 vaccine (95.3 versus 94%, odds ratio [OR] compared to 2019 1.28, 95% confidence intervals [CIs] 1.18 to 1.39) to 14.3% for second MMR dose (66.1 versus 51.8%, OR compared to 2019 1.8, 95% CI 1.74 to 1.87). Significant increases in uptake were seen across all deprivation levels.In England, fewer children due to receive their immunisations during the lockdown period were up to date at 6 months (6-in-1) or 18 months (first dose MMR). The fall in percentage uptake ranged from 0.5% for first 6-in-1 (95.8 versus 96.3%, OR compared to 2019 0.89, 95% CI 0.86– to 0.91) to 2.1% for third 6-in-1 (86.6 versus 88.7%, OR compared to 2019 0.82, 95% CI 0.81 to 0.83).The use of routinely collected data used in this study was a limiting factor as detailed information on potential confounding factors were not available and we were unable to eliminate the possibility of seasonal trends in immunisation uptake.ConclusionsIn this study, we observed that the national lockdown in Scotland was associated with an increase in timely childhood immunisation uptake; however, in England, uptake fell slightly. Reasons for the improved uptake in Scotland may include active measures taken to promote immunisation at local and national levels during this period and should be explored further. Promoting immunisation uptake and addressing potential vaccine hesitancy is particularly important given the ongoing pandemic and COVID-19 vaccination campaigns.

Fiona McQuaid and colleagues assess the uptake of infant and pre-school immunisations in Scotland and England during the COVID-19 pandemic.     

Neuronal postdevelopmentally acting SAX-7S/L1CAM can function as cleaved fragments to maintain neuronal architecture in Caenorhabditis elegans

Whereas remarkable advances have uncovered mechanisms that drive nervous system assembly, the processes responsible for the lifelong maintenance of nervous system architecture remain poorly understood. Subsequent to its establishment during embryogenesis, neuronal architecture is maintained throughout life in the face of the animal’s growth, maturation processes, the addition of new neurons, body movements, and aging. The Caenorhabditis elegans protein SAX-7, homologous to the vertebrate L1 protein family of neural adhesion molecules, is required for maintaining the organization of neuronal ganglia and fascicles after their successful initial embryonic development. To dissect the function of sax-7 in neuronal maintenance, we generated a null allele and sax-7S-isoform-specific alleles. We find that the null sax-7(qv30) is, in some contexts, more severe than previously described mutant alleles and that the loss of sax-7S largely phenocopies the null, consistent with sax-7S being the key isoform in neuronal maintenance. Using a sfGFP::SAX-7S knock-in, we observe sax-7S to be predominantly expressed across the nervous system, from embryogenesis to adulthood. Yet, its role in maintaining neuronal organization is ensured by postdevelopmentally acting SAX-7S, as larval transgenic sax-7S(+) expression alone is sufficient to profoundly rescue the null mutants’ neuronal maintenance defects. Moreover, the majority of the protein SAX-7 appears to be cleaved, and we show that these cleaved SAX-7S fragments together, not individually, can fully support neuronal maintenance. These findings contribute to our understanding of the role of the conserved protein SAX-7/L1CAM in long-term neuronal maintenance and may help decipher processes that go awry in some neurodegenerative conditions.     

Updating age-specific contact structures to match evolving demography in a dynamic mathematical model of tuberculosis vaccination

We investigated the effects of updating age-specific social contact matrices to match evolving demography on vaccine impact estimates. We used a dynamic transmission model of tuberculosis in India as a case study. We modelled four incremental methods to update contact matrices over time, where each method incorporated its predecessor: fixed contact matrix (M0), preserved contact reciprocity (M1), preserved contact assortativity (M2), and preserved average contacts per individual (M3). We updated the contact matrices of a deterministic compartmental model of tuberculosis transmission, calibrated to epidemiologic data between 2000 and 2019 derived from India. We additionally calibrated the M0, M2, and M3 models to the 2050 TB incidence rate projected by the calibrated M1 model. We stratified age into three groups, children (<15y), adults (≥15y, <65y), and the elderly (≥65y), using World Population Prospects demographic data, between which we applied POLYMOD-derived social contact matrices. We simulated an M72-AS01_E-like tuberculosis vaccine delivered from 2027 and estimated the per cent TB incidence rate reduction (IRR) in 2050 under each update method. We found that vaccine impact estimates in all age groups remained relatively stable between the M0–M3 models, irrespective of vaccine-targeting by age group. The maximum difference in impact, observed following adult-targeted vaccination, was 7% in the elderly, in whom we observed IRRs of 19% (uncertainty range 13–32), 20% (UR 13–31), 22% (UR 14–37), and 26% (UR 18–38) following M0, M1, M2 and M3 updates, respectively. We found that model-based TB vaccine impact estimates were relatively insensitive to demography-matched contact matrix updates in an India-like demographic and epidemiologic scenario. Current model-based TB vaccine impact estimates may be reasonably robust to the lack of contact matrix updates, but further research is needed to confirm and generalise this finding.     

The identification of a selective dopamine D2 partial agonist,D3 antagonist displaying high levels of brain exposure

The identification of a highly selective D₂ partial agonist, D₃ antagonist tool molecule which demonstrates high levels of brain exposure and selectivity against an extensive range of dopamine, serotonin, adrenergic, histamine, and muscarinic receptors is described.     

Influence of non-bonded parameters on the quality of NMR structures: A new force field for NMR structure calculation

The effects of different non-bonded parameters of force fields for NMR structure calculation on the quality of the resulting NMR solution structures were investigated using Interleukin 4 as a model system. NMR structure ensembles were calculated with an ab initio protocol using torsion angle dynamics. The calculations were repeated with five different non-bonded energy functions and parameters. The resulting ensembles were compared with the available X-ray structures, and their quality was assessed with common structure validation programs. In addition, the impact of torsion angle restraints and dihedral energy terms for the sidechains and the backbone was studied. The further improvement of the quality by refinement in explicit solvent was demonstrated. The optimal parameters, including those necessary for water refinement, are available in the new version of the PARALLHDG force field.