Functional convergence in gastric lysozymes of foregut-fermenting rodents, ruminants, and primates is not attributed to convergent molecular evolution.

Convergent evolution is a widespread phenomenon. While there are many examples of convergent evolution at the phenotypic scale, convergence at the molecular level has been more difficult to identify. A classic example of convergent evolution across scales is that of the digestive lysozyme found in ruminants and Colobine monkeys. These herbivorous species rely on foregut fermentation, which has evolved to function more optimally under acidic conditions. Here, we explored if rodents with similar dietary strategies and digestive morphologies have convergently evolved a lysozyme with digestive functions. At the phenotypic level, we find that rodents with bilocular stomach morphologies exhibited a lysozyme that maintained higher relative activities at low pH values, similar to the lysozymes of ruminants and Colobine monkeys. Additionally, the lysozyme of Peromyscus leucopus shared a similar predicted protonation state as that observed in previously identified digestive lysozymes. However, we found limited evidence of positive selection acting on the lysozyme gene in foregut-fermenting species and did not identify patterns of convergent molecular evolution in this gene. This study emphasizes that phenotypic convergence need not be the result of convergent genetic modifications, and we encourage further exploration into the mechanisms regulating convergence across biological scales.

Virus-encoded histone doublets are essential and form nucleosome-like structures.

The organization of genomic DNA into defined nucleosomes has long been viewed as a hallmark of eukaryotes. This paradigm has been challenged by the identification of "minimalist" histones in archaea and more recently by the discovery of genes that encode fused remote homologs of the four eukaryotic histones in Marseilleviridae, a subfamily of giant viruses that infect amoebae. We demonstrate that viral doublet histones are essential for viral infectivity, localize to cytoplasmic viral factories after virus infection, and ultimately are found in the mature virions. Cryogenic electron microscopy (cryo-EM) structures of viral nucleosome-like particles show strong similarities to eukaryotic nucleosomes despite the limited sequence identify. The unique connectors that link the histone chains contribute to the observed instability of viral nucleosomes, and some histone tails assume structural roles. Our results further expand the range of "organisms" that require nucleosomes and suggest a specialized function of histones in the biology of these unusual viruses.

Genome Sequences of Gordonia Phages BaxterFox, Kita, Nymphadora, and Yeezy.

Gordonia phages BaxterFox, Kita, Nymphadora, and Yeezy are newly characterized phages of Gordonia terrae, isolated from soil samples in Pittsburgh, Pennsylvania. These phages have genome lengths between 50,346 and 53,717 bp, and encode on average 84 predicted proteins. All have G+C content of 66.6%.

Genome Sequences of Gordonia Bacteriophages Obliviate, UmaThurman, and Guacamole.

We describe three newly isolated phages-Obliviate, UmaThurman, and Guacamole-that infect Gordonia terrae 3612. The three genomes are related to one another but are not closely related to other previously sequenced phages or prophages. The three phages are predicted to use integration-dependent immunity systems as described in several mycobacteriophages.

Genome Sequences of Gordonia terrae Phages Benczkowski14 and Katyusha.

Bacteriophages Katyusha and Benczkowski14 are newly isolated phages that infect Gordonia terrae 3612. Both have siphoviral morphologies with isometric heads and long tails (500 nm). The genomes are 75,380 bp long and closely related, and the tape measure genes (9 kbp) are among the largest to be identified.

Genome Sequences of Mycobacteriophages AlanGrant, Baee, Corofin, OrangeOswald, and Vincenzo, New Members of Cluster B.

AlanGrant, Baee, Corofin, OrangeOswald, and Vincenzo are newly isolated phages of Mycobacterium smegmatis mc(2)155 discovered in Pittsburgh, Pennsylvania, USA. All five phages share nucleotide similarity with cluster B mycobacteriophages but span considerable diversity with Corofin and OrangeOswald in subcluster B3, AlanGrant and Vincenzo in subcluster B4, and Baee in subcluster B5.

Impact of BPRS interview length on ratings reliability in a schizophrenia trial.

Signal detection in clinical trials relies on ratings reliability. We conducted a reliability analysis of site-independent rater scores derived from audio-digital recordings of site-based rater interviews of the structured Brief Psychiatric Rating Scale (BPRS) in a schizophrenia study. "Dual" ratings assessments were conducted as part of a quality assurance program in a 12-week, double-blind, parallel-group study of PF-02545920 compared to placebo in patients with sub-optimally controlled symptoms of schizophrenia (ClinicalTrials.gov identifier NCT01939548). Blinded, site-independent raters scored the recorded site-based BPRS interviews that were administered in relatively stable patients during two visits prior to the randomization visit. We analyzed the impact of BPRS interview length on "dual" scoring variance and discordance between trained and certified site-based raters and the paired scores of the independent raters. Mean total BPRS scores for 392 interviews conducted at the screen and stabilization visits were 50.4±7.2 (SD) for site-based raters and 49.2±7.2 for site-independent raters (t=2.34; p=0.025). "Dual" rated total BPRS scores were highly correlated (r=0.812). Mean BPRS interview length was 21:05±7:47min ranging from 7 to 59min. 89 interviews (23%) were conducted in less than 15min. These shorter interviews had significantly greater "dual" scoring variability (p=0.0016) and absolute discordance (p=0.0037) between site-based and site-independent raters than longer interviews. In-study ratings reliability cannot be guaranteed by pre-study rater certification. Our findings reveal marked variability of BPRS interview length and that shorter interviews are often incomplete yielding greater "dual" scoring discordance that may affect ratings precision.

Audio-digital recordings used for independent confirmation of site-based MADRS interview scores.

Signal detection requires ratings reliability throughout a clinical trial. The confirmation of site-based rater scores by a second, independent and blinded rater is a reasonable metric of ratings reliability. We used audio-digital pens to record site-based interviews of the Montgomery-Asberg Depression Rating Scale (MADRS) in a double-blind, placebo controlled trial of a novel antidepressant in treatment resistant depressed patients. Blinded, site-independent raters generated "dual" scores that revealed high correlations between site-based and site-independent raters (r=0.940 for all ratings) and high sensitivity, specificity, predictive values, and kappa coefficients for treatment response and non-response outcomes using the site-based rater scores as the standard. The blinded raters achieved an 89.4% overall accuracy and 0.786 kappa for matching the treatment response or non-response outcomes of the site-based raters. A limitation of this method is that independent ratings depend on the quality of site-based interviews and patient responses to the site-based interviewers. Nonetheless, this quality assurance strategy may have broad applicability for studies that use subjective measures and wherever ratings reliability is a concern. "Dual" scoring of recorded site-based ratings can be a relatively unobtrusive surveillance strategy to confirm scores and to identify and remediate rater "outliers" during a study.

Visual object pattern separation varies in older adults.

Young and nondemented older adults completed a visual object continuous recognition memory task in which some stimuli (lures) were similar but not identical to previously presented objects. The lures were hypothesized to result in increased interference and increased pattern separation demand. To examine variability in object pattern separation deficits, older adults were divided into impaired and unimpaired groups based on performance on a standardized serial list-learning task. Impaired older adults showed intact recognition memory, but were impaired relative to young and unimpaired older adults when identifying similar lure stimuli, demonstrating that object pattern separation varies in older adults.

The effect of interference on temporal order memory for random and fixed sequences in nondemented older adults.

Two experiments tested the effect of temporal interference on order memory for fixed and random sequences in young adults and nondemented older adults. The results demonstrate that temporal order memory for fixed and random sequences is impaired in nondemented older adults, particularly when temporal interference is high. However, temporal order memory for fixed sequences is comparable between older adults and young adults when temporal interference is minimized. The results suggest that temporal order memory is less efficient and more susceptible to interference in older adults, possibly due to impaired temporal pattern separation.

Vision-fair neuropsychological assessment in normal aging, Parkinson's disease and Alzheimer's disease.

We examined performance of healthy older and younger adults and individuals with Alzheimer's disease (AD) and Parkinson's disease (PD) on digit cancellation, a task putatively sensitive to cognitive impairment, but possibly affected by visual impairment, particularly in contrast sensitivity. Critical contrast thresholds were established to create custom stimulus arrays that were proximally matched across individuals. Age- and PD-related differences in search were fully accounted for by the sensory deficit. Increased contrast benefited AD patients, but could not override cognitive impairment. We conclude that visually fair neuropsychological testing can effectively compensate for normal age- and PD-related visual changes that affect cognitive performance.

Visual object pattern separation deficits in nondemented older adults.

Young and nondemented older adults were tested on a continuous recognition memory task requiring visual pattern separation. During the task, some objects were repeated across trials and some objects, referred to as lures, were presented that were similar to previously presented objects. The lures resulted in increased interference and an increased need for pattern separation. For each object, the participant was asked to indicate whether (1) this was the first time the object was seen (new), (2) the object was seen previously (old), or (3) the object was similar to a previous object (similar). Older adults were able to correctly identify objects as old or new as well as young adults; however, older adults were impaired when identifying lures as similar. Therefore, pattern separation may be less efficient in older adults resulting in poorer recognition memory performance when interference is increased.