Structure of a Wbl protein and implications for NO sensing by M. tuberculosis

Mycobacterium tuberculosis causes pulmonary tuberculosis (TB) and claims ~1.8 million human lives per annum. Host nitric oxide (NO) is important in controlling TB infection. M. tuberculosis WhiB1 is a NO-responsive Wbl protein (actinobacterial iron-sulfur proteins first identified in the 1970s). Until now, the structure of a Wbl protein has not been available. Here a NMR structural model of WhiB1 reveals that Wbl proteins are four-helix bundles with a core of three α-helices held together by a [4Fe-4S] cluster. The iron-sulfur cluster is required for formation of a complex with the major sigma factor (σA) and reaction with NO disassembles this complex. The WhiB1 structure suggests that loss of the iron-sulfur cluster (by nitrosylation) permits positively charged residues in the C-terminal helix to engage in DNA binding, triggering a major reprogramming of gene expression that includes components of the virulence-critical ESX-1 secretion system

How Attractive Is the Girl Next Door? An Assessment of Spatial Mate Acquisition and Paternity in the Solitary Cape Dune Mole-Rat, Bathyergus suillus

Behavioural observations of reproduction and mate choice in wild fossorial rodents are extremely limited and consequently indirect methods are typically used to infer mating strategies. We use a combination of morphological, reproductive, spatial, and genetic data to investigate the reproductive strategy of a solitary endemic species, the Cape dune mole-rat Bathyergus suillus. These data provide the first account on the population dynamics of this species. Marked sexual dimorphism was apparent with males being both significantly larger and heavier than females. Of all females sampled 36% had previously reproduced and 12% were pregnant at the time of capture. Post-partum sex ratio was found to be significantly skewed in favour of females. The paternity of fifteen litters (n = 37) was calculated, with sires assigned to progeny using both categorical and full probability methods, and including a distance function. The maximum distance between progeny and a putative sire was determined as 2149 m with males moving between sub-populations. We suggest that above-ground movement should not be ignored in the consideration of mate acquisition behaviour of subterranean mammals. Estimated levels of multiple paternity were shown to be potentially as high as 26%, as determined using sibship and sire assignment methods. Such high levels of multiple paternity have not been found in other solitary mole-rat species. The data therefore suggest polyandry with no evidence as yet for polygyny

Association of insularity and body condition to cloacal bacteria prevalence in a small shorebird

Do islands harbour less diverse disease communities than mainland? The island biogeography theory predicts more diverse communities on mainland than on islands due to more niches, more diverse habitats and availability of greater range of hosts. We compared bacteria prevalences ofCampylobacter,ChlamydiaandSalmonellain cloacal samples of a small shorebird, the Kentish plover (Charadrius alexandrinus) between two island populations of Macaronesia and two mainland locations in the Iberian Peninsula. Bacteria were found in all populations but, contrary to the expectations, prevalences did not differ between islands and mainland. Females had higher prevalences than males forSalmonellaand when three bacteria genera were pooled together. Bacteria infection was unrelated to bird's body condition but females from mainland were heavier than males and birds from mainland were heavier than those from islands. Abiotic variables consistent throughout breeding sites, like high salinity that is known to inhibit bacteria growth, could explain the lack of differences in the bacteria prevalence between areas. We argue about the possible drivers and implications of sex differences in bacteria prevalence in Kentish plovers

Viability selection creates negative heterozygosity–fitness correlations in female Black Grouse Lyrurus tetrix

There is widespread interest in the relationship between individual genetic diversity and fitness–related traits (heterozygosity–fitness correlations, HFC). Most studies found weak continuous increases of fitness with increasing heterozygosity while negative HFC have rarely been reported. Negative HFC are expected in cases of outbreeding depression and outbreeding is rare in natural populations; but negative HFC may also arise through viability selection acting on low heterozygosity individuals at an early stage producing a skew in the heterozygosity distribution leading to negative HFCs. We tested this idea using survival and clutch parameters (egg mass, egg volume, chick mass, clutch size) collected in female black grouse Lyrurus tetrix and carried out simulations to determine how survival selection may impact the HFCs measured using clutch parameters. We show that survival is positively related to both individual heterozygosity and female body mass. There is a positive effect of body mass on all clutch parameters, but the selective mortality of females with both low heterozygosity and low body mass led to over representation of high heterozygosity-low body mass females and hence a negative relationship between egg volume and heterozygosity. Using simulated data, we show that survival selection acting on both low body mass and low heterozygosity leads to a skew in the quality of females breeding, resulting in negative HFCs with egg volume. Our results indicate that survival selection can strongly influence the strength and direction of any HFC that occur later in life and that only an integration of all aspects of individuals’ reproductive investment and reproductive success can enable us to fully understand how heterozygosity can shape individual’s fitness

Viability selection creates negative heterozygosity–fitness correlations in female Black Grouse Lyrurus tetrix

There is widespread interest in the relationship between individual genetic diversity and fitness–related traits (heterozygosity–fitness correlations, HFC). Most studies found weak continuous increases of fitness with increasing heterozygosity while negative HFC have rarely been reported. Negative HFC are expected in cases of outbreeding depression and outbreeding is rare in natural populations; but negative HFC may also arise through viability selection acting on low heterozygosity individuals at an early stage producing a skew in the heterozygosity distribution leading to negative HFCs. We tested this idea using survival and clutch parameters (egg mass, egg volume, chick mass, clutch size) collected in female black grouse Lyrurus tetrix and carried out simulations to determine how survival selection may impact the HFCs measured using clutch parameters. We show that survival is positively related to both individual heterozygosity and female body mass. There is a positive effect of body mass on all clutch parameters, but the selective mortality of females with both low heterozygosity and low body mass led to over representation of high heterozygosity-low body mass females and hence a negative relationship between egg volume and heterozygosity. Using simulated data, we show that survival selection acting on both low body mass and low heterozygosity leads to a skew in the quality of females breeding, resulting in negative HFCs with egg volume. Our results indicate that survival selection can strongly influence the strength and direction of any HFC that occur later in life and that only an integration of all aspects of individuals’ reproductive investment and reproductive success can enable us to fully understand how heterozygosity can shape individual’s fitness

Familial t(1;11) translocation is associated with disruption of white matter structural integrity and oligodendrocyte–myelin dysfunction

Although the underlying neurobiology of major mental illness (MMI) remains unknown, emerging evidence implicates a role for oligodendrocyte–myelin abnormalities. Here, we took advantage of a large family carrying a balanced t(1;11) translocation, which substantially increases risk of MMI, to undertake both diffusion tensor imaging and cellular studies to evaluate the consequences of the t(1;11) translocation on white matter structural integrity and oligodendrocyte–myelin biology. This translocation disrupts among others the DISC1 gene which plays a crucial role in brain development. We show that translocation-carrying patients display significant disruption of white matter integrity compared with familial controls. At a cellular level, we observe dysregulation of key pathways controlling oligodendrocyte development and morphogenesis in induced pluripotent stem cell (iPSC) derived case oligodendrocytes. This is associated with reduced proliferation and a stunted morphology in vitro. Further, myelin internodes in a humanized mouse model that recapitulates the human translocation as well as after transplantation of t(1;11) oligodendrocyte progenitors were significantly reduced when compared with controls. Thus we provide evidence that the t(1;11) translocation has biological effects at both the systems and cellular level that together suggest oligodendrocyte–myelin dysfunction

Successful breeding predicts divorce in plovers

When individuals breed more than once, parents are faced with the choice of whether to re-mate with their old partner or divorce and select a new mate. Evolutionary theory predicts that, following successful reproduction with a given partner, that partner should be retained for future reproduction. However, recent work in a polygamous bird, has instead indicated that successful parents divorced more often than failed breeders (Halimubieke et al. in Ecol Evol 9:10734–10745, 2019), because one parent can benefit by mating with a new partner and reproducing shortly after divorce. Here we investigate whether successful breeding predicts divorce using data from 14 well-monitored populations of plovers (Charadrius spp.). We show that successful nesting leads to divorce, whereas nest failure leads to retention of the mate for follow-up breeding. Plovers that divorced their partners and simultaneously deserted their broods produced more offspring within a season than parents that retained their mate. Our work provides a counterpoint to theoretical expectations that divorce is triggered by low reproductive success, and supports adaptive explanations of divorce as a strategy to improve individual reproductive success. In addition, we show that temperature may modulate these costs and benefits, and contribute to dynamic variation in patterns of divorce across plover breeding systems

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

Toward developing a genome-wide microsatellite marker set for linkage analysis in the rhesus macaque (Macaca mulatta): identification of 76 polymorphic markers.

Linkage analysis can be problematic in humans because of the lack of large, multigenerational pedigrees and the difficulties in obtaining phenotypic data on all family members. In contrast, large, captive colonies of rhesus macaque are a potentially valuable resource for linkage studies because detailed phenotypic and genealogical data are kept, inbreeding is avoided, and DNA samples can usually be obtained. Microsatellite marker sets for genome-wide screening are available in a number of species, but not for the rhesus macaque. We tested primers to 400 human microsatellite markers from a genome-wide mapping set using DNA from nine unrelated female rhesus macaques. We found that 76 (19%) of the primers amplified a polymorphic product using the standard protocols for human DNA. The average heterozygosity of the markers in humans was 0.80, compared to 0.65 in the rhesus macaques. This study provides preliminary data, which could be used toward the development of a linkage mapping set in this species. There would be a need, however, to confirm the Mendelian inheritance of the markers

Toward developing a genome-wide microsatellite marker set for linkage analysis in the rhesus macaque (Macaca mulatta): identification of 76 polymorphic markers.

Linkage analysis can be problematic in humans because of the lack of large, multigenerational pedigrees and the difficulties in obtaining phenotypic data on all family members. In contrast, large, captive colonies of rhesus macaque are a potentially valuable resource for linkage studies because detailed phenotypic and genealogical data are kept, inbreeding is avoided, and DNA samples can usually be obtained. Microsatellite marker sets for genome-wide screening are available in a number of species, but not for the rhesus macaque. We tested primers to 400 human microsatellite markers from a genome-wide mapping set using DNA from nine unrelated female rhesus macaques. We found that 76 (19%) of the primers amplified a polymorphic product using the standard protocols for human DNA. The average heterozygosity of the markers in humans was 0.80, compared to 0.65 in the rhesus macaques. This study provides preliminary data, which could be used toward the development of a linkage mapping set in this species. There would be a need, however, to confirm the Mendelian inheritance of the markers