Quality and quantity of genetic relatedness data affect the analysis of social structure

Kinship plays a fundamental role in the evolution of social systems and is considered a key driver of group living. To understand the role of kinship in the formation and maintenance of social bonds, accurate measures of genetic relatedness are critical. Genotype‐by‐sequencing technologies are rapidly advancing the accuracy and precision of genetic relatedness estimates for wild populations. The ability to assign kinship from genetic data varies depending on a species’ or population's mating system and pattern of dispersal, and empirical data from longitudinal studies are crucial to validate these methods. We use data from a long‐term behavioural study of a polygynandrous, bisexually philopatric marine mammal to measure accuracy and precision of parentage and genetic relatedness estimation against a known partial pedigree. We show that with moderate but obtainable sample sizes of approximately 4,235 SNPs and 272 individuals, highly accurate parentage assignments and genetic relatedness coefficients can be obtained. Additionally, we subsample our data to quantify how data availability affects relatedness estimation and kinship assignment. Lastly, we conduct a social network analysis to investigate the extent to which accuracy and precision of relatedness estimation improve statistical power to detect an effect of relatedness on social structure. Our results provide practical guidance for minimum sample sizes and sequencing depth for future studies, as well as thresholds for post hoc interpretation of previous analyses.     

Quantitative Timed-Up-and-Go Parameters in Relation to Cognitive Parameters and Health-Related Quality of Life in Mild-to-Moderate Parkinson's Disease

IntroductionThe instrumented-Timed-Up-and-Go test (iTUG) provides detailed information about the following movement patterns: sit-to-walk (siwa), straight walking, turning and walk-to-sit (wasi). We were interested in the relative contributions of respective iTUG sub-phases to specific clinical deficits most relevant for daily life in Parkinson’s disease (PD). More specifically, we investigated which condition–fast speed (FS) or convenient speed (CS)–differentiates best between mild- to moderate-stage PD patients and controls, which parameters of the iTUG sub-phases are significantly different between PD patients and controls, and how the iTUG parameters associate with cognitive parameters (with particular focus on cognitive flexibility and working memory) and Health-Related-Quality of Life (HRQoL).MethodsTwenty-eight PD participants (65.1±7.1 years, H&Y stage 1–3, medication OFF state) and 20 controls (66.1±7.5 years) performed an iTUG (DynaPort^®, McRoberts BV, The Netherlands) under CS and FS conditions. The PD Questionnaire 39 (PDQ-39) was employed to assess HRQoL. General cognitive and executive functions were assessed using the Montreal Cognitive Assessment and the Trail Making Test.ResultsThe total iTUG duration and sub-phases durations under FS condition differentiated PD patients slightly better from controls, compared to the CS condition. The following sub-phases were responsible for the observed longer total duration PD patients needed to perform the iTUG: siwa, turn and wasi. None of the iTUG parameters correlated relevantly with general cognitive function. Turning duration and wasi maximum flexion velocity correlated strongest with executive function. Walking back duration correlated strongest with HRQoL.DiscussionThis study confirms that mild- to moderate-stage PD patients need more time to perform the iTUG than controls, and adds the following aspects to current literature: FS may be more powerful than CS to delineate subtle movement deficits in mild- to moderate-stage PD patients; correlation levels of intra-individual siwa and wasi parameters may be interesting surrogate markers for the level of automaticity of performed movements; and sub-phases and kinematic parameters of the iTUG may have the potential to reflect executive functioning and HRQoL aspects of PD patients.     

Immunogenicity of outer membrane derivatives ofHaemophilus influenzae type b

We prepared outer membrane derivatives ofHaemophilus influenzae type b to determine whether the residual capsular and noncapsular surface components are immunogenic and protective. These fragments consist primarily of six major proteins and lipopolysaccharide. By transmission electron microscopy, they appeared as small, membrane-like fragments or larger, cellshaped double-track ghosts. Rabbits immunized with ghosts responded with increases in serum anticapsular antibody and bactericidal activity. Antisera absorbed with capsular antigen to remove anticapsular antibody remained bactericidal and passively protected infant rats. These data suggest that antibodies to noncapsular surface antigens are protective, and that outer membrane derivatives retain some of the constituents responsible for stimulating immunity.     

Molecular motors in axonal transport

Neurons require a large amount of intracellular transport. Cytoplasmic polypeptides and membrane-bounded organelles move from the perikaryon, down the length of the axon, and to the synaptic terminals. This movement occurs at distinct rates and is termed axonal transport. Axonal transport is divided into the slow transport of cytoplasmic proteins including glycolytic enzymes and cytoskeletal structures and the fast transport of membrane-bounded organelles along linear arrays of microtubules. The polypeptide compositions of the rate classes of axonal transport have been well characterized, but the underlying molecular mechanisms of this movement are less clear. Progress has been particularly slow toward understanding force-generation in slow transport, but recent developments have provided insight into the molecular motors involved in fast axonal transport. Recent advances in the cellular and molecular biology of one fast axonal transport motor, kinesin, have provided a clearer understanding of organelle movement along microtubules. The availability of cellular and molecular probes for kinesin and other putative axonal transport motors have led to a reevaluation of our understanding of intracellular motility.     

Central Coherence in Eating Disorders: A Synthesis of Studies Using the Rey Osterrieth Complex Figure Test

BackgroundLarge variability in tests and differences in scoring systems used to study central coherence in eating disorders may lead to different interpretations, inconsistent findings and between study discrepancies. This study aimed to address inconsistencies by collating data from several studies from the same research group that used the Rey Osterrieth Complex Figure Test (Rey Figure) in order to produce norms to provide benchmark data for future studies.MethodData was collated from 984 participants in total. Anorexia Nervosa, Bulimia Nervosa, recovered Anorexia Nervosa, unaffected family members and healthy controls were compared using the Rey Figure.ResultsPoor global processing was observed across all current eating disorder sub-groups and in unaffected relatives. There was no difference in performance between recovered AN and HC groups.ConclusionsThis is the largest dataset reported in the literature and supports previous studies implicating poor global processing across eating disorders using the Rey Figure. It provides robust normative data useful for future studies.     

Arabidopsis cryptochrome 2 completes its posttranslational life cycle in the nucleus

CRY2 is a blue light receptor regulating light inhibition of hypocotyl elongation and photoperiodic flowering in Arabidopsis thaliana. The CRY2 protein is found primarily in the nucleus, and it is known to undergo blue light-dependent phosphorylation and degradation. However, the subcellular location where CRY2 exerts its function or undergoes blue light-dependent phosphorylation and degradation remains unclear. In this study, we analyzed the function and regulation of conditionally nuclear-localized CRY2. Our results show that CRY2 mediates blue light inhibition of hypocotyl elongation and photoperiodic promotion of floral initiation in the nucleus. Consistent with this result and a hypothesis that blue light-dependent phosphorylation is associated with CRY2 function, we demonstrate that CRY2 undergoes blue light-dependent phosphorylation in the nucleus. CRY2 phosphorylation is required for blue light-dependent CRY2 degradation, but only a limited quantity of CRY2 is phosphorylated at any given moment in seedlings exposed to blue light, which explains why continuous blue light illumination is required for CRY2 degradation. Finally, we showed that CRY2 is ubiquitinated in response to blue light and that ubiquitinated CRY2 is degraded by the 26S proteasome in the nucleus. These findings demonstrate that a photoreceptor can complete its posttranslational life cycle (from protein modification, to function, to degradation) inside the nucleus.     

Maternal control of pattern formation in Xenopus laevis

We review the essential role of maternal factors in pattern formation for Xenopus laevis, focusing on VegT, Vg1, and Wnt11. Results from loss of function experiments demonstrate a clear requirement for these genes in germ layer specification, dorsal-ventral axis formation, and convergence extension. We also discuss these genes in the broader context of metazoan development, exploring whether and how their functions in the X. laevis model organism may or may not be conserved in other species. Wnt11 signaling in particular provides a classic example where understanding context in development is crucial to understanding function. Genomic sequencing, gene expression, and functional screening data that are becoming available in more species are providing invaluable aid to decoding and modeling signaling pathways. More work is needed to develop a comprehensive catalog of the Wnt signaling, T-box, and TGF-beta genes in metazoans both near and far in evolutionary distance. We finally discuss some specific experimental and modeling efforts that will be needed to understand the behavior of these signaling networks in vivo so that we can interpret these critical pathways in an evolutionary framework.     

Induction of apoptosis and activation of NF-kappaB by CD95 require different signalling thresholds

Mutations in the death domain of the death receptor CD95 (APO-1/Fas) cause lymphoproliferation and autoimmune disease in both lpr(cg) mice and in patients with autoimmune lymphoproliferative syndrome (ALPS) type Ia. By testing lymphocytes from ALPS type Ia patients, comparing heterozygous with homozygous lpr(cg) mice and coexpressing wild-type and mutant CD95 receptors, we demonstrate that induction of apoptosis requires two wild-type alleles of CD95. By contrast, nuclear factor-kappaB (NF-kappaB) can be fully activated in cells expressing both a mutant and a wild-type CD95 allele, suggesting different thresholds to activate the two signalling pathways. This was confirmed by testing lymphocytes from heterozygous lpr mice, which showed reduced sensitivity to CD95-mediated apoptosis but normal activation of NF-kappaB when compared with wild-type mice. Mutations in CD95 may eliminate the tumour-suppressive function of CD95, at the same time allowing induction of survival or proliferative pathways, which could contribute to the increased risk for lymphoma seen in ALPS type Ia patients.