Phylogenomics clarifies biogeographic and evolutionary history, and conservation status of West Indian tremblers and thrashers (Aves: Mimidae).

The West Indian avifauna has provided fundamental insights into island biogeography, taxon cycles, and the evolution of avian behavior. Our interpretations, however, should rely on robust hypotheses of evolutionary relationships and consistent conclusions about taxonomic status in groups with many endemic island populations. Here we present a phylogenetic study of the West Indian thrashers, tremblers, and allies, an assemblage of at least 5 species found on 29 islands, including what is considered the Lesser Antilles' only avian radiation. We improve on previous phylogenetic studies of this group by using double-digest restriction site-associated DNA sequencing (ddRAD-seq) to broadly sample loci scattered across the nuclear genome. A variety of analyses, based on either nucleotide variation in 2223 loci recovered in all samples or at 13,282 loci confidently scored as present or absent in all samples, converged on a single well-supported phylogenetic hypothesis. Results indicate that the resident West Indian taxa form a monophyletic group, exclusive of the Neotropical-Nearctic migratory Gray Catbird Dumetella carolinensis, which breeds in North America; this outcome differs from earlier studies suggesting that Gray Catbird was nested within a clade of island resident species. Thus, our findings imply a single colonization of the West Indies without the need to invoke a subsequent 'reverse colonization' of the mainland by West Indian taxa. Additionally, our study is the first to sample both endemic subspecies of the endangered White-breasted Thrasher Ramphocinclus brachyurus. We find that these subspecies have a long history of evolutionary independence with no evidence of gene flow, and are as genetically divergent from each other as other genera in the group. These findings support recognition of R. brachyurus (restricted to Martinique) and the Saint Lucia Thrasher R. sanctaeluciae as two distinct, single-island endemic species, and indicate the need to re-evaluate conservation plans for these taxa. Our results demonstrate the utility of phylogenomic datasets for generating robust systematic hypotheses.

FAMILY CONFLICT MODERATES EARLY PARENT-CHILD BEHAVIORAL TRANSACTIONS.

The reciprocal transactions that shape early parent-child relationships are influenced by contextual stress, such as family conflict. Although family conflict is a salient stressor to the family system, few studies have considered how parent-child transactions vary according to exposure to family conflict. The present study examined how family conflict alters early parent-child behavioral transactions. We utilized three waves of data from a multisite longitudinal study of low-income families (N = 2, 876), child age 14 months, 24 months, and 36 months, to identify behavioral transactions of positive and negative maternal (supportiveness, negative regard) and child (engagement, negativity) behaviors. Results indicated that family conflict at 14 months diminished the positive association between maternal supportiveness and child engagement, and amplified the inverse association between maternal negativity and child engagement. Family conflict at 14 months also was associated with increased stability of child negativity and subsequent increased maternal negative regard at 36 months, in part via increases in 24-month child negativity. In sum, family conflict occurring early in childhood predicted and moderated behavioral transactions between young children and their mothers.

A meta-analytic review of relationship-based interventions for low-income families with infants and toddlers: facilitating supportive parent-child interactions.

Relationship-based intervention programs are increasingly being implemented as a way to enhance parent-child interaction quality. In this meta-analytic review, we examined the effectiveness of 19 recent relationship-based interventions serving socioeconomically disadvantaged families with infants and toddlers (N = 6,807). This review specifically focused on intervention effectiveness in terms of improving supportive parenting behaviors, as measured by observational assessments of dyadic parent-child interactions. Meta-analytic results indicated significant, yet modest, effectiveness across all interventions (d = .23). Intervention characteristics such as participant randomization, breadth of intervention services offered, duration, child age at the start of the intervention, professional qualifications of the intervenor, and type of play task used during assessment were tested as possible moderators of effectiveness. Significant differences in effectiveness were found between randomized and nonrandomized interventions. Within the subsample of randomized interventions, programs that were shorter in duration, that provided direct services to the parent-child dyad, used intervenors with professional qualifications, and assessed parent-child interactions with free-play tasks were the most effective, highlighting important considerations for designing effective intervention protocol tailored to the needs of this high-risk population.

Peer Communication about Antisocial Activities as a Mediator of Interparental Conflict in Mid-Adolescence and Externalizing Problems in Late Adolescence.

The current study investigated whether adolescent peer communication about antisocial activities mediates the association between interparental conflict within the family system in mid-adolescence and externalizing problems in late adolescence. Participants were 115 families in which an adolescent and caregiver participated in a longitudinal study. Adolescents (53 girls, 62 boys) completed measures of interparental conflict and externalizing problems in 8th grade (age 14). Afterward, adolescents received a BlackBerry device configured to capture all text messages sent and received. During the 9th grade, four days of text messages were coded for peer communication about antisocial topics. Adolescents again completed a measure of externalizing problems in 11th grade (age 17). Results indicated that interparental conflict in 8th grade correlated positively with adolescents' externalizing problems in 11th grade, but only for girls. In addition, the frequency of communication about antisocial activities mediated the link between interparental conflict and girls' externalizing problems. The findings support the idea that adolescent girls' communications about antisocial activities with their peers may contribute to the link between interparental conflict and girls' externalizing problems.

A backbone-dependent rotamer library with high (ϕ, ψ) coverage using metadynamics simulations.

Backbone-dependent rotamer libraries are commonly used to assign the side chain dihedral angles of amino acids when modeling protein structures. Most rotamer libraries are created by curating protein crystal structure data and using various methods to extrapolate the existing data to cover all possible backbone conformations. However, these rotamer libraries may not be suitable for modeling the structures of cyclic peptides and other constrained peptides because these molecules frequently sample backbone conformations rarely seen in the crystal structures of linear proteins. To provide backbone-dependent side chain information beyond the α-helix, ß-sheet, and PPII regions, we used explicit-solvent metadynamics simulations of model dipeptides to create a new rotamer library that has high coverage in the (ϕ, ψ) space. Furthermore, this approach can be applied to build high-coverage rotamer libraries for noncanonical amino acids. The resulting Metadynamics of Dipeptides for Rotamer Distribution (MEDFORD) rotamer library predicts the side chain conformations of high-resolution protein crystal structures with similar accuracy (~80%) to a state-of-the-art rotamer library. Our ability to test the accuracy of MEDFORD at predicting the side chain dihedral angles of amino acids in noncanonical backbone conformation is restricted by the limited structural data available for cyclic peptides. For the cyclic peptide data that are currently available, MEDFORD and the state-of-the-art rotamer library perform comparably. However, the two rotamer libraries indeed make different rotamer predictions in noncanonical (ϕ, ψ) regions. For noncanonical amino acids, the MEDFORD rotamer library predicts the χ1 values with approximately 75% accuracy.

Binary combinatorial scanning reveals potent poly-alanine-substituted inhibitors of protein-protein interactions.

Establishing structure-activity relationships is crucial to understand and optimize the activity of peptide-based inhibitors of protein-protein interactions. Single alanine substitutions provide limited information on the residues that tolerate simultaneous modifications with retention of biological activity. To guide optimization of peptide binders, we use combinatorial peptide libraries of over 4,000 variants-in which each position is varied with either the wild-type residue or alanine-with a label-free affinity selection platform to study protein-ligand interactions. Applying this platform to a peptide binder to the oncogenic protein MDM2, several multi-alanine-substituted analogs with picomolar binding affinity were discovered. We reveal a non-additive substitution pattern in the selected sequences. The alanine substitution tolerances for peptide ligands of the 12ca5 antibody and 14-3-3 regulatory protein are also characterized, demonstrating the general applicability of this new platform. We envision that binary combinatorial alanine scanning will be a powerful tool for investigating structure-activity relationships.

Provision of social support to individuals with chronic fatigue syndrome.

The present study evaluated a buddy program designed to provide support for individuals with chronic fatigue syndrome (CFS). The intervention involved weekly visits by a student paraprofessional, who helped out with tasks that needed to be done in an effort to reduce some of the taxing demands and responsibilities that participants regularly encountered. This model of rehabilitation focused on avoiding overexertion in persons with CFS, aiming to avoid setbacks and relapses while increasing their tolerance for activity. Participants with CFS were randomly assigned to either a 4-month buddy intervention or a control condition. Posttest results showed that individuals who received a student buddy intervention had significantly greater reductions in fatigue severity and increases in vitality than individuals in the control condition. There were no significant changes between groups for physical functioning and stress. Buddy interventions that help patients with CFS reduce overexertion and possibly remain within their energy envelopes can be thought of as representing a different paradigm than nonpharmacologic interventions that focus only on increasing levels of activity through graded exercise.

Intrusive parenting, teacher sensitivity, and negative emotionality on the development of emotion regulation in early head start toddlers.

Toddler emotion regulation develops within the context of relationships but is also influenced by toddlers' individual characteristics. Drawing on transactional and differential susceptibility frameworks, this study examined direct and interactive associations of intrusive parenting, teacher sensitivity, and negative emotionality on toddler emotion regulation development in a sample of Early Head Start families utilizing center-based child care. Latent growth models indicated that, after controlling for a series of family and child care covariates, intrusive parenting at 14 months had diminishing effects on trajectories of emotion regulation across toddlerhood (14 to 36 months), whereas teacher sensitivity in child care was promotive for emotion regulation growth. Toddlers with high negative emotionality were not more susceptible to the effects of intrusive parenting or teacher sensitivity on emotion regulation development, however, results suggested emerging evidence for individual differences in the protective nature of teacher sensitivity in the context of high intrusion at home. Results are discussed in terms of their implications for informing parents and early care and education providers in nurturing relationships with the children who may be the most challenging to care for but may stand to make the greatest gains in emotion regulation development in quality caregiving settings.

Enhanced tactile spatial acuity and cortical processing during acute hand deafferentation.

Acute deafferentation of a limb results in bilateral cortical reorganization, but the behavioral consequences of this phenomenon are unknown. Here we found rapid improvements in tactile spatial acuity and changes in cortical processing for the left hand during cutaneous anesthesia of the right hand. The site-specific improvement in tactile spatial acuity may represent a behavioral compensatory gain.

Population Viability and Vital Rate Sensitivity of an Endangered Avian Cooperative Breeder, the White-Breasted Thrasher (Ramphocinclus brachyurus).

Social behaviors can significantly affect population viability, and some behaviors might reduce extinction risk. We used population viability analysis to evaluate effects of past and proposed habitat loss on the White-breasted Thrasher (Ramphocinclus brachyurus), a cooperatively breeding songbird with a global population size of <2000 individuals. We used an individual-based approach to build the first demographic population projection model for this endangered species, parameterizing the model with data from eight years of field study before and after habitat loss within the stronghold of the species' distribution. The recent habitat loss resulted in an approximately 18% predicted decline in population size; this estimate was mirrored by a separate assessment using occupancy data. When mortality rates remained close to the pre-habitat loss estimate, quasi-extinction probability was low under extant habitat area, but increased with habitat loss expected after current plans for resort construction are completed. Post-habitat loss mortality rate estimates were too high for projected populations to persist. Vital rate sensitivity analyses indicated that population growth rate and population persistence were most sensitive to juvenile mortality. However, observed values for adult mortality were closest to the threshold value above which populations would crash. Adult mortality, already relatively low, may have the least capacity to change compared to other vital rates, whereas juvenile mortality may have the most capacity for improvement. Results suggest that improving mortality estimates and determining the cause(s) of juvenile mortality should be research priorities. Despite predictions that aspects of cooperative systems may result in variation in reproduction or juvenile mortality being the most sensitive vital rates, adult mortality was the most sensitive in half of the demographic models of other avian cooperative breeders. Interestingly, vital rate sensitivity differed by model type. However, studies that explicitly modeled the species' cooperative breeding system found reproduction to be the most sensitive rate.

Validation of a brief telephone battery for neurocognitive assessment of patients with pulmonary arterial hypertension.

BACKGROUND: The effects of pulmonary arterial hypertension on brain function are not understood, despite patients' frequent complaints of cognitive difficulties. Using clinical instruments normally administered during standard in-person assessment of neurocognitive function in adults, we assembled a battery of tests designed for administration over the telephone. The purpose was to improve patient participation, facilitate repeated test administration, and reduce the cost of research on the neuropsychological consequences of acute and chronic cardiorespiratory diseases. We undertook this study to validate telephone administration of the tests. METHODS: 23 adults with pulmonary arterial hypertension underwent neurocognitive assessment using both standard in-person and telephone test administration, and the results of the two methods compared using interclass correlations. RESULTS: For most of the tests in the battery, scores from the telephone assessment correlated strongly with those obtained by in-person administration of the same tests. Interclass correlations between 0.5 and 0.8 were observed for tests that assessed attention, memory, concentration/working memory, reasoning, and language/crystallized intelligence (p < or = 0.05 for each). Interclass correlations for the Hayling Sentence Completion test of executive function approached significance (p = 0.09). All telephone tests were completed within one hour. CONCLUSION: Administration of this neurocognitive test battery by telephone should facilitate assessment of neuropsychological deficits among patients with pulmonary arterial hypertension living across broad geographical areas, and may be useful for monitoring changes in neurocognitive function in response to PAH-specific therapy or disease progression.

Factors Affecting the Sustainability of Self-Run Recovery Homes in the United States.

This study examined the sustainability rates of 214 self-run substance abuse recovery homes called Oxford Houses (OHs) over a six-year period. We list five factors needed to sustain an OH: affordable housing, residents following OH principles, resident income, institutional support, and community support. Results indicated a high sustainability rate (86.9%) in which 186 OHs remained open and 28 OHs closed. Reasons for houses closing (N = 14) included lack of affordable housing, which we classified as an external factor. Houses that closed because of internal factors (N = 13) included residents who were unable to adhere to OH rules, and insufficient income of residents. No house-level differences for income, sense of community, average lengths of stay, house age, or neighborhood characteristics were found between the houses that closed versus houses that remained open. Because the OH system relies on residents to sustain individual houses located in ordinary residential neighborhoods, these findings suggest that OH sustainability depends on locale, primarily access to affordable housing and adequate job opportunities for residents.

Cortical excitability changes induced by deafferentation of the contralateral hemisphere.

Short-term deprivation of sensory input by ischaemic nerve block (INB) leads to functional reorganization in the deafferented motor cortex. Here, we show that INB also elicits functional changes in homotopic regions of the cortex contralateral to the deafferented one. We measured motor evoked potential (MEP) amplitudes elicited by transcranial magnetic stimulation (TMS) in small hand and biceps brachii muscles before, during and after INB of the right hand. INB increased excitability of the cortical representation of (i) the intact hand and (ii) body parts proximal to the deafferented hand (upper arm), in the absence of excitability changes in other body part representations such as thorax or leg muscles. This effect persisted throughout the entire period of deafferentation and returned to baseline values afterward. Motor responses to brainstem electrical stimulation remained unchanged during INB, indicating that the effect is probably of cortical origin. Lorazepam, a GABA(A) receptor agonist, blocked this increased excitability. Interhemispheric inhibition between hand muscles decreased during INB. After chronic deafferentation in amputees, MEP amplitudes and motor output curves in small hand muscles were depressed and motor thresholds were elevated compared with aged-matched controls. These results indicate that acute hand deafferentation can elicit a focal increase in excitability in the hand motor representation contralateral to the deafferented cortex that is influenced by transcallosal interactions and GABAergic transmission, and is balanced in the setting of chronic deafferentation.