Evidence for a strong correlation between transcription factor protein disorder and organismic complexity

Studies of diverse phylogenetic lineages reveal that protein disorder increases in concert with organismic complexity but that differences nevertheless exist among lineages. To gain insight into this phenomenology, we analyzed all of the transcription factor (TF) families for which sequences are known for 17 species spanning bacteria, yeast, algae, land plants, and animals and for which the number of different cell types has been reported in the primary literature. Although the fraction of disordered residues in TF sequences is often moderately or poorly correlated with organismic complexity as gauged by cell-type number (r20.8). Furthermore, the correlation between the fraction of disordered residues and cell-type number becomes stronger when confined to the TF families participating in cell cycle, cell size, cell division, cell differentiation, or cell proliferation, and other important developmental processes. The data also indicate that evolutionarily simpler organisms allow for the detection of subtle differences in the conserved IDRs of TFs as well as changes in variable IDRs, which can influence the DNA recognition and multifunctionality of TFs through direct or indirect mechanisms. Although strong correlations cannot be taken as evidence for causeand-effect relationships, we interpret our data to indicate that increasing TF disorder likely was an important factor contributing to the evolution of organismic complexity and not merely a concurrent unrelated effect of increasing organismic complexity

Localized hypermutation is the major driver of meningococcal genetic variability during persistent asymptomatic carriage

© 2020 Green et al. Host persistence of bacteria is facilitated by mutational and recombina-torial processes that counteract loss of genetic variation during transmission and selection from evolving host responses. Genetic variation was investigated during persistent asymptomatic carriage of Neisseria meningitidis. Interrogation of whole-genome sequences for paired isolates from 25 carriers showed that de novo mutations were infrequent, while horizontal gene transfer occurred in 16% of carriers. Examination of multiple isolates per time point enabled separation of sporadic and transient allelic variation from directional variation. A comprehensive comparative analysis of directional allelic variation with hypermutation of simple sequence repeats and hyperrecombination of class 1 type IV pilus genes detected an average of seven events per carrier and 2:1 bias for changes due to localized hyper-mutation. Directional genetic variation was focused on the outer membrane with 69% of events occurring in genes encoding enzymatic modifiers of surface structures or outer membrane proteins. Multiple carriers exhibited directional and opposed switching of al-lelic variants of the surface-located Opa proteins that enables continuous expression of these adhesins alongside antigenic variation. A trend for switching from PilC1 to PilC2 expression was detected, indicating selection for specific alterations in the activities of the type IV pilus, whereas phase variation of restriction modification (RM) sys-tems, as well as associated phasevarions, was infrequent. We conclude that asymp-tomatic meningococcal carriage on mucosal surfaces is facilitated by frequent localized hypermutation and horizontal gene transfer affecting genes encoding surface modifiers such that optimization of adhesive functions occurs alongside escape of immune responses by antigenic variation. IMPORTANCE Many bacterial pathogens coexist with host organisms, rarely causing disease while adapting to host responses. Neisseria meningitidis, a major cause of meningitis and septicemia, is a frequent persistent colonizer of asymptomatic teen-agers/young adults. To assess how genetic variation contributes to host persistence, whole-genome sequencing and hypermutable sequence analyses were performed on multiple isolates obtained from students naturally colonized with meningococci. High frequencies of gene transfer were observed, occurring in 16% of carriers and affecting 51% of all nonhypermutable variable genes. Comparative analyses showed that hypermutable sequences were the major mechanism of variation, causing 2-fold more changes in gene function than other mechanisms. Genetic variation was focused on genes affecting the outer membrane, with directional changes in proteins responsible for bacterial adhesion to host surfaces. This comprehensive examination of genetic plasticity in individual hosts provides a significant new platform for ratio-nale design of approaches to prevent the spread of this pathogen

Simultaneous and alternate action observation and motor imagery combinations improve aiming performance

Motor imagery (MI) and action observation (AO) are techniques that have been shown to enhance motor skill learning. While both techniques have been used independently, recent research has demonstrated that combining action observation and motor imagery (AOMI) promotes better outcomes. However, little is known about the most effective way to combine these techniques. This study examined the effects of simultaneous (i.e., observing an action whilst imagining carrying out the action concurrently) and alternate (i.e., observing an action and then doing imagery related to that action consecutively) AOMI combinations on the learning of a dart throwing task. Participants (n = 50) were randomly allocated to one of five training groups: action observation (AO), motor imagery (MI), simultaneous action observation and motor imagery (S-AOMI), alternate action observation and motor imagery (A-AOMI) and a control group. Interventions were conducted three times per week for six weeks and pre- and post-measures of total score were collected. Results revealed that all intervention groups, with the exception of the AO and control groups, significantly improved performance following the intervention. Posthoc analyses showed that S-AOMI group improved to a significantly greater degree than the MI and AO groups, and participants in the A-AOMI group improved to a significantly greater degree than the AO group. Participants in the A-AOMI group did not improve to a significantly greater degree than the S-AOMI group. These findings suggest that combining AOMI, regardless of how it is combined, may be the beneficial method for improving the learning and performance of aiming skills

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

XXXV.—On hipposiderus caffer, Sund., and its closest Allies; with some notes on H. fuliginosus, Temm

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