Preparedness of Speech Language Pathologists and Occupational Therapists to Treat Pediatric Feeding Disorder: A Cross-Sectional Survey.

BACKGROUND: Pediatric feeding disorder (PFD) is increasingly common and is often treated by speech language pathologists (SLPs) and occupational therapists (OTs) in the community setting. However, the preparedness of these disciplines to effectively address PFD is relatively unknown. METHODS: A national (US), online survey was disseminated to providers who assess and treat PFD. For the present analysis, the responses of SLPs (N = 418) and OTs (N = 195) related to their clinical background, educational background, post-graduate training, and self-rated clinical effectiveness were statistically analyzed and compared across the two disciplines. RESULTS: Both SLPs and OTs report feeling underprepared to work with PFD clients immediately following their academic training, but time spent in post-graduate training and years of clinical practice both significantly (p < 0.0001) increased feelings of effectiveness in assessing and treating PFD. Most SLPs and OTs pursued self-directed learning activities to increase competence, with the most common activities being article review, podcasts, and peer case review, although SLPs were significantly more likely to use podcasts (p < 0.0001) and peer review (p = 0.0004) than OTs. The most common barriers for providers were financial, time, travel, and institutional support barriers. CONCLUSIONS: While PFD is a key practice area of both SLPs and OTs, both provider groups feel unprepared and under-supported in providing competent care to these patients upon graduation. Future research and policy should support advancements in training for current SLPs and OTs related to PFD and address current barriers to a specialized educational pathway.

Comparative stable isotope analyses of green sturgeon (Acipenser medirostris) and white sturgeon (A. transmontanus) in the San Francisco estuary.

Green sturgeon (Acipenser medirostris) and white sturgeon (A. transmontanus) are closely related, sympatric species that inhabit the San Francisco estuary. Green sturgeon have a more marine life history but both species spawn in the Sacramento River and reside for some duration in San Francisco Bay. These sturgeons are of conservation concern, yet little is known about their dietary competition when they overlap in space and time. To examine evidence of dietary differentiation, we collected whole blood and blood plasma from 26 green sturgeon and 35 white sturgeon in San Francisco Bay. Using carbon and nitrogen stable isotope analyses, we compared their relative trophic levels and foraging locations along the freshwater to marine gradient. Sampling blood plasma and whole blood allowed comparison of dietary integration over shorter and longer time scales, respectively. Plasma and whole blood δ13 C values confirmed green sturgeon had more marine dietary sources than white sturgeon. Plasma δ15 N values revealed white sturgeon fed at lower trophic levels than green sturgeon recently, however, whole blood δ15 N values demonstrated the two species fed at the same trophic level over longer time scales. Larger individuals of both species had higher δ13 C values than smaller individuals, reflecting more marine food sources in adulthood. Length did not affect δ15 N values of either species. Isotope analyses supported the more marine life history of green than white sturgeon and potentially highlight a temporary trophic differentiation of diet between species during and preceding the overlapping life stage in San Francisco Bay.

Effects of pubertal growth variation on knee mechanics during walking in female and male adolescents.

INTRODUCTION: Puberty substantially alters the body's mechanical properties, neuromuscular control, and sex differences therein, likely contributing to increased, sex-biased knee injury risk during adolescence. Female adolescents have higher risk for knee injuries than male adolescents of similar age engaging in similar physical activities, and much research has investigated sex differences in mechanical risk factors. However, few studies address the considerable variation in pubertal growth (timing, pace), knee mechanics, and injury susceptibility within sexes, or the impact of such growth variation on mechanical injury risk. OBJECTIVES: The present study tested for effects of variation in pubertal growth on established mechanical knee injury risk factors, examining relationships between and within sexes. METHODS: Pubertal growth indices describing variation in the timing and rate of pubertal growth were developed using principal component analysis and auxological data from serial stature measurements. Linear mixed models were applied to evaluate relationships between these indices and knee mechanics during walking in a sample of adolescents. RESULTS: Later developing female adolescents with slower pubertal growth had higher extension moments throughout stance, whereas earlier developers had higher valgus knee angles and moments. In male adolescents, faster and later growth were related to higher extension moments throughout gait. In both sexes, faster growers had higher internal rotation moments at foot-strike. CONCLUSIONS: Pubertal growth variation has important effects on mechanical knee injury risk in adolescence, affecting females and males differently. Earlier developing females exhibit greater injury risk via frontal plane factors, whereas later/faster developing males have elevated risk via sagittal plane mechanisms.

E-cigarette exposure with or without heating the e-liquid induces differential remodeling in the lungs and right heart of mice.

Various cardiopulmonary pathologies associated with electronic cigarette (EC) vaping have been reported. This study investigated the differential adverse effects of heating-associated by-products versus the intact components of EC aerosol to the lungs and heart of mice. We further dissected the roles of caspase recruitment domain-containing protein 9 (CARD9)-associated innate immune response and NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome in EC exposure-induced cardiopulmonary injury. C57BL/6 wild type (WT), CARD9-/-, and NLRP3-/- mice were exposed to EC aerosol 3 h/day, 5 days/week for 6 month with or without heating the e-liquid with exposure to ambient air as the control. In WT mice, EC exposure with heating (EwH) significantly increased right ventricle (RV) free wall thickness at systole and diastole. However, EC exposure without heating (EwoH) caused a significant decrease in the wall thickness at systole. RV fractional shortening was also markedly reduced following EwH in WT and NLRP3-/- mice. Further, EwH activated NF-κB and p38 MAPK inflammatory signaling in the lungs, but not in the RV, in a CARD9- and NLRP3-dependent manner. Levels of circulatory inflammatory mediators were also elevated following EwH, indicating systemic inflammation. Moreover, EwoH activated TGF-ß1/SMAD2/3/α-SMA fibrosis signaling in the lungs but not the RV of WT mice. In conclusion, EC aerosol exposure following EwH or EwoH induced differential cardiopulmonary remodeling and CARD9 innate immune response and NLRP3 inflammasome contributed to the adverse effects.

Application of theoretical frameworks on human papillomavirus vaccine interventions in the United States: systematic review and meta-analysis.

PURPOSE: Theoretical frameworks are useful tools to explain the dynamics of behavioral change, develop, and implement intervention studies. The purpose of this systematic review and meta-analysis is to evaluate the application of theoretical frameworks and models to HPV vaccination intervention studies in the United States (US) from January 2006 to December 2019. METHODS: A comprehensive search across databases, including PubMed, EMBASE, ERIC, CINAHL, Academic Search Complete, Scopus, Web of Science, and PsycINFO, was conducted. Articles were included in the systematic analysis if at least one theory was used to develop the intervention phase. All intervention studies targeting populations in the US without restrictions of age, income, sex, and ethnicity were included. Articles were included in the meta-analysis if vaccine uptake and/or vaccine completion was addressed. RESULTS: The Health Belief Model, Motivational Interviewing, Theory of Planned Behavior, and Information-Motivation-Behavioral Skills were the most used theories. Based on theory integrity, theory rationale, and theory operationalization, most of the studies (60%) were rated high for the application of the theoretical frameworks. Our results suggest a preference for theoretical frameworks targeting individual change rather than community change and the existence of gender disparities in the application of theoretical frameworks. The association between theory and increase of likelihood in vaccine uptake and completion was not supported. CONCLUSION: This review spotlights common issues in the application of theoretical frameworks in HPV vaccine interventions in the US. Our results suggest we are still in a developmental phase on several aspects of theory application to HPV vaccination.

N-terminal alternative splicing of GluN1 regulates the maturation of excitatory synapses and seizure susceptibility.

The majority of NMDA receptors (NMDARs) in the brain are composed of 2 GluN1 and 2 GluN2 subunits. The inclusion or exclusion of 1 N-terminal and 2 C-terminal domains of GluN1 results in 8 splicing variants that exhibit distinct temporal and spatial patterns of expression and functional properties. However, previous functional analyses of Grin1 variants have been done using heterologous expression and the in vivo function of Grin1 splicing is unknown. Here we show that N-terminal splicing of GluN1 has important functions in the maturation of excitatory synapses. The inclusion of exon 5 of Grin1 is up-regulated in several brain regions such as the thalamus and neocortex. We find that deletion of Grin1 exon 5 disrupts the developmental remodeling of NMDARs in thalamic neurons and the effect is distinct from that of Grin2a (GluN2A) deletion. Deletion of Grin2a or exon 5 of Grin1 alone partially attenuates the shortening of NMDAR-mediated excitatory postsynaptic currents (NMDAR-EPSCs) during early life, whereas deletion of both Grin2a and exon 5 of Grin1 completely abolishes the developmental change in NMDAR-EPSC decay time. Deletion of exon 5 of Grin1 leads to an overproduction of excitatory synapses in layer 5 pyramidal neurons in the cortex and increases seizure susceptibility in adult mice. Our findings demonstrate that N-terminal splicing of GluN1 has important functions in synaptic maturation and neuronal network excitability.

Eye-tracking to examine differences in alcohol product appeal by sex among young people.

Background: Advertising of traditional alcopops contains elements that appeal to youth, especially females. Supersized alcopops are marketed differently than traditional alcopops and contain up to 5.5 standard alcoholic drinks. Young females are more likely to underestimate the alcohol content of supersized alcopops, putting them at higher risk of overconsumption. Similar to supersized alcopops, beer is packaged in large cans and in the same areas of store shelves.Objective: This study examined among young people whether supersized alcopops versus beer products disproportionately appealed to females.Methods: Eleven adolescents (13-17 years old) and 72 college students (21-26 years old) were recruited during 2019-2020. Participants viewed 19 photos of convenience store display cases containing both supersized alcopop and beer products. While viewing each image, participants were instructed to click on the beverage that looked the "coolest" (i.e. most appealing). Eye-tracking hardware and software measured the amount of time participants visually fixated on each product. Participants completed a survey to record demographic characteristics.Results: Compared to males (n=25), females (n=58) fixated on supersized alcopops for 6.8 seconds longer (95%CI 0.3,13.3). Females also had 3.7 times the odds of selecting a supersized alcopop as the product they found most appealing compared to males (95%CI 1.68,8.01), adjusting for amount of time visually fixating on supersized alcopops, which was also a significant predictor.Conclusions: Young females' strong preference for supersized alcopops is concerning given they disproportionately underestimate their potency, relative to males, and are more likely to obtain dangerously high BAC levels from consuming one or two supersized alcopops.

Prolonging the Response Movement Reduces Commission Errors in a High-Go, Low-No-Go Target Detection Task and Composite Metrics of Performance Miss This Effect.

OBJECTIVE: Expand research on the Sustained Attention to Response Task (SART) to a more applied agricultural target detection/selection task and examine the utility of various performance metrics, including composite measures of speed and accuracy, in a High-Go/Low-No-Go stimuli task. BACKGROUND: Modified SARTs have been utilized to investigate mechanisms, such as failures of response inhibition, occurring in friendly fire and collateral damage incidents. Researchers have demonstrated that composite measures of speed and accuracy are useful for Low Go/High No-Go stimuli tasks, but this has not been demonstrated for High-Go/Low-No-Go tasks, such as the SART. METHOD: Participants performed a modified SART, where they selected ("sprayed") images of weeds (Go stimuli) that appeared on a computer screen, while withholding to rarer soybean plant images (No-Go stimuli). RESULTS: Response time was a function of distance from a central starting point. Participants committed commission errors (sprayed the soybeans) at a significantly higher rate when the stimuli appeared under the cursor centered on the screen for each trial. Participant's omission errors (failure to spray a weed) increased significantly as a function of distance. The composite measures examined were primarily influenced by response time and omission errors limiting their utility when commission errors are of particular interest. CONCLUSION: Participants are far more accurate in their decision making when required to execute a longer duration motor task in High-Go/Low-No-Go experiments. APPLICATION: Demonstrates a serious human factors liability of target detection and snap-to-target systems.

Comparison of a Sucrose-Based and Rice-Based Sports Beverage on Hydration Status During a 19.3-km Foot March in ROTC Cadets.

ABSTRACT: Heileson, JL, Peterson, M, Adair, KE, and Funderburk, LK. Comparison of a sucrose-based and rice-based sports beverage on hydration status during a 19.3-km foot march in ROTC cadets. J Strength Cond Res 36(4): 1105-1110, 2022-The purpose of this field study was to determine whether a rice-based sport beverage (RB) maintains hydration status compared to a sucrose-based sports beverage (SB) during a load-bearing 19.3-km foot march. Eighteen Reserve Officer Training Corps (ROTC) cadets (male, n = 11; female, n = 7) were randomly assigned to consume either 2.84 L of an RB (carbohydrate, 114 g; sodium, 1306 mg) or SB (carbohydrate, 170 g; sodium, 1136 mg) throughout the duration of the foot march (temperature 14.44° C, humidity 50%). The sports beverages were distributed once before the event and then every 3.2 km for a total of 6 servings (0.47 L each). Pre- and post-urine specific gravity (USG) and body mass were used to assess hydration status. A survey was used to determine subjective ratings of perceived exertion and gastrointestinal (GI) discomfort. The level of significance was set at p < 0.05 for all analyses. Sixteen cadets completed the study. Based on USG, both beverages significantly improved hydration status (USG = 1.017 ± 0.010 pre-march vs. 1.011 ± 0.008 post-march, p = 0.04); however, there was no difference between groups (change in USG = -0.009 ± 0.012 for RB group vs. -0.003 ± 0.008 for SB group, p = 0.92). Ratings for perceived exertion and GI discomfort scores were similar between groups. In conclusion, the RB was as effective as the SB at maintaining hydration status and could potentially reduce GI discomfort. Athletes and military personnel concerned with ensuring appropriate hydration during moderate-intensity endurance events can achieve similar fluid balance from a rice-based sports beverage that is lower in calories, carbohydrate, and sugar.

Family satisfaction in a neuro trauma ICU.

OBJECTIVE: The purpose of this quality improvement initiative was to evaluate satisfaction of family members of patients in a neuro trauma ICU (NTICU). METHODS: Adult patients (age 18+) admitted to the NTICU for at least 24 hours between June 2017 and November 2018 were identified. Near or at the time of discharge from the NTICU, the health unit coordinator or registered nurse identified the family member who was either the next-of-kin, surrogate decision-maker, or person who had been most frequently present at the patient's bedside. This person was provided a packet containing a letter of consent and the Critical Care Family Satisfaction Survey (CCFSS). RESULTS: Surveys were completed by 78 family members, the majority of whom were the wife of the patient (n = 35, 44%), 60 years and older (n = 48, 60.8%). Fifty-seven percent of patients (n = 45) were in the ICU less than 3 days and 59% (n = 47) of medical events were injury-related. Total CCFSS scores ranged from 69 to 100 (median 95). The item with the largest number of dissatisfied responses was "Noise level in the critical care unit" (n = 4, 5.3% not satisfied). Open-ended question comments were primarily positive (n = 60, 66%), with 32% (n = 29) representing areas for improvement. CONCLUSIONS: Results of this satisfaction survey have been disseminated to leadership and have been taken into consideration in the planning of a new hospital building currently being built, including ICU patient rooms that allow for more privacy and reduced noise, and more comfortable family rooms. RELEVANCE TO CLINICAL PRACTICE: Family members are a very useful source of feedback for ICU care. Several concerns identified by family members in this study are likely to be relevant to other sites. These included: communication between health care providers and family about patient status, noise in the ICU, peaceful waiting areas for family, and slow transfers.

Effect of Compression Therapy in the Treatment of Tibial Stress Syndrome in Military Service Members.

CONTEXT: Tibial stress syndrome (TSS) is an overuse injury of the lower extremities. There is a high incidence rate of TSS among military recruits. Compression therapy is used to treat a wide array of musculoskeletal injuries. The purpose of this study was to investigate the use of compression therapy as a treatment for TSS in military service members. DESIGN: A parallel randomized study design was utilized. METHODS: Military members diagnosed with TSS were assigned to either a relative rest group or compression garment group. Both groups started the study with 2 weeks of lower extremity rest followed by a graduated running program during the next 6 weeks. The compression garment group additionally wore a shin splints compression wrap during the waking hours of the first 2 weeks and during activity only for the next 6 weeks. Feelings of pain, TSS symptoms, and the ability to run 2 miles pain free were assessed at baseline, 4 weeks, and 8 weeks into the study. RESULTS: Feelings of pain and TSS symptoms decreased during the 8-week study in both groups (P < .05), but these changes were not significantly different between groups (P > .05). The proportion of participants who were able to run 2 miles pain free was significantly different (P < .05) between the 2 groups at the 8-week time point with the compression garment group having a significantly increased ability to complete the run without pain. CONCLUSIONS: Although perceptions of pain at rest were not different between groups, the functional ability of running 2 miles pain free was significantly improved in the compression garment group. These findings suggest that there is a moderate benefit to using compression therapy as an adjunct treatment for TSS, promoting a return to training for military service members.

Efficacy of L-Leucine Supplementation Coupled with a Calorie-Restricted Diet to Promote Weight Loss in Mid-Life Women.

OBJECTIVE: This study evaluated the effect of leucine supplementation coupled with a calorie-restricted diet over a 12-week period in mid-life overweight and obese women on body composition and resting metabolic rate (RMR). METHOD: This study was a randomized, single-blind, placebo-controlled trial in which 34 women were randomly assigned to either 10 g leucine (LEU) or placebo daily, while following a calorie-restricted diet A dual energy x-ray absorptiometry (DXA) analysis, metabolic rate assessment via a BodyGem® and anthropometrics were performed at baseline and after the 12-week study to determine changes in fat mass, lean mass and RMR. Main variables were analyzed using 2 (condition) by 2 (time) mixed design ANOVAs with repeated measures. Odds ratio was calculated by counting the number of individuals gaining or maintaining lean mass (p ≤ .05). RESULTS: Both groups lost a significant amount of weight due to both fat and lean mass loss, but there was no significant difference between groups, with RMR remaining unchanged over the course of the study and not significantly different between groups. The loss in lean mass was noticeably less, though not statistically significant (p = 0.644) for the women in the LEU group, with 38% vs. 6%, gaining or retaining lean mass during the intervention relative to the placebo. CONCLUSIONS: Our findings demonstrate that a greater proportion of mid-life overweight or obese women taking LEU supplements gained or maintained lean mass during intentional weight loss, though it did not reach a level of statistical significance.

Assessment of operant learning and memory in mice born through ICSI.

STUDY QUESTION: Are there differences in operant learning and memory between mice born through ICSI and naturally conceived control (CTL) mice? SUMMARY ANSWER: ICSI females exhibited deficits in the acquisition reward learning relative to CTL females, and ICSI males exhibited deficiencies in discrimination learning and memory relative to CTL males. WHAT IS KNOWN ALREADY: Some human outcome studies have suggested that ICSI might be associated with an increased risk of certain cognitive disorders, but only one of two behavioral studies with ICSI mouse models have reported differences between ICSI and CTL females. No studies to date have investigated associative learning in ICSI mice. STUDY DESIGN, SIZE, DURATION: Groups of 36 ICSI mice (18 male, 18 female) and 37 CTL mice (19 male, 18 female) aged 3-6 months were compared in a series of operant learning procedures that assessed acquisition of a new behavior, discrimination learning and memory. In total, 16 ICSI mice (9 male, 7 female) and 17 CTL mice (10 male, 7 female) received follow-up discrimination learning and memory assessments at 12 months of age (6 months after the end of initial training) to evaluate retention and reacquisition of learned performances. PARTICIPANTS/MATERIALS, SETTING, METHODS: Mice received daily operant learning sessions in experimental chambers in which all stimulus events and the recording of responses were automated. Food rewards were delivered for responding under different conditions of reinforcement, which varied by procedure. Subjects received a successive series of sessions of nose poke acquisition training, discrimination training and the delayed-non-matching-to-position memory procedure. Mixed repeated measures ANOVAs in which the between-subjects factor was group (ICSI vs CTL) and the within-subjects factor was repeated exposures to learning procedures (i.e. sessions) were used to analyze data. MAIN RESULTS AND THE ROLE OF CHANCE: In comparisons between all mice (i.e. males and females combined), CTL mice exhibited superior performance relative to ICSI in response acquisition (P = 0.03), discrimination (P = 0.001) and memory (P = 0.007). Sex-specific comparisons between the groups yielded evidence of sexual dimorphism. ICSI females exhibited a deficit in acquisition learning relative to CTL females (P < 0.001), but there was not a significant difference between CTL and ICSI males. In the discrimination and memory tasks, ICSI males exhibited deficits relative to CTL males (P = 0.002 and P = 0.02, respectively) but the differences between females in these tasks were not significant. There was no difference in discrimination or memory retention/re-acquisition assessments conducted with mice at 12 months of age. ICSI males and females weighed significantly more than CTL counterparts at all points during the experiment. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: The study was not blinded. All learning assessments utilized food reward; other assessments of operant, Pavlovian and nonassociative learning are needed to fully characterize learning in ICSI mice and speculate regarding the implications for cognitive function in humans conceived via ICSI. WIDER IMPLICATIONS OF THE FINDINGS: Studying learning and memory processes in mouse models have the potential to shed light on ICSI outcomes at the level of cognitive function. Future research should use multiple learning paradigms, assess both males and females, and investigate the effects of variables related to the ICSI procedure. Studying cognitive function in ICSI is an interdisciplinary endeavor and requires co-ordination between researchers at the genetic and psychological levels of analysis. STUDY FUNDING/COMPETING INTEREST(S): This work was supported, in part, by grants from the NIH (P30GM110767, HD071736 and HD085506 to W.Y.), the Templeton Foundation (61174 to W.Y.) and a New Scholarly Endeavor Grant from the University of Nevada, Reno Office of Research and Innovation (to M.L., Y.W., H.Z., L.H. and W.Y.). The authors declare no competing interests.

Acute partial sleep deprivation and high-intensity interval exercise effects on postprandial endothelial function.

PURPOSE: Acute-total and chronic-partial sleep deprivation increase the risks for cardiovascular disease (CVD). Cardiovascular function assessed by flow mediated dilation (FMD) is reduced after sleep deprivation. High-intensity interval exercise (HIIE) improves postprandial FMD. Sleep-deprived individuals may practice HIIE followed by a high-fat breakfast. This study investigated the acute-partial sleep deprivation (APSD) and HIIE interaction on postprandial FMD. METHODS: Fifteen healthy males (age 31 ± 5 years) participated in: (a) reference sleep (~ 9.5 h) with no HIIE (RS), (b) RS and HIIE (RSX), and (c) APSD and HIIE (SSX). HIIE was performed in 3:2 min intervals at 90% and 40% of VO2 reserve. FMD was assessed the night before (D1), the morning of the next day (D2), 1 h (1hrPE) and 4 h post HIIE (4hrPE). RESULTS: FMD% change was lower at RS compared to both RSX (F1,14 = 23.96, p < 0.001, η2 = 0.631) and SSX (F1,14 = 4.8, p = 0.47, η2 = 0.253) at 1hrPE. RSX and SSX did not differ at 1hrPE (F1,14 = 0.2, p = 0.889, η2 = 0.001), but SSX elicited greater FDM responses. Absolute FMD change was lower at RS compared to both RSX (F1,14 = 21.5, p < 0.001, η2 = 0.606) and SSX (F1,14 = 7.01, p = 0.019, η2 = 0.336) at 1hrPE. RSX and SSX did not differ at 1hrPE (F1,14 = .03, p = 0.858, η2 = 0.002), but SSX elicited greater FDM responses. CONCLUSIONS: HIIE short-term effects on cardiovascular function remain cardioprotective even after an acute-partial sleep deprivation.

The Mycobacterium tuberculosis regulatory network and hypoxia.

We have taken the first steps towards a complete reconstruction of the Mycobacterium tuberculosis regulatory network based on ChIP-Seq and combined this reconstruction with system-wide profiling of messenger RNAs, proteins, metabolites and lipids during hypoxia and re-aeration. Adaptations to hypoxia are thought to have a prominent role in M. tuberculosis pathogenesis. Using ChIP-Seq combined with expression data from the induction of the same factors, we have reconstructed a draft regulatory network based on 50 transcription factors. This network model revealed a direct interconnection between the hypoxic response, lipid catabolism, lipid anabolism and the production of cell wall lipids. As a validation of this model, in response to oxygen availability we observe substantial alterations in lipid content and changes in gene expression and metabolites in corresponding metabolic pathways. The regulatory network reveals transcription factors underlying these changes, allows us to computationally predict expression changes, and indicates that Rv0081 is a regulatory hub.

Eye movements and retinotopic tuning in developmental prosopagnosia.

Despite extensive investigation, the causes and nature of developmental prosopagnosia (DP)-a severe face identification impairment in the absence of acquired brain injury-remain poorly understood. Drawing on previous work showing that individuals identified as being neurotypical (NT) show robust individual differences in where they fixate on faces, and recognize faces best when the faces are presented at this location, we defined and tested four novel hypotheses for how atypical face-looking behavior and/or retinotopic face encoding could impair face recognition in DP: (a) fixating regions of poor information, (b) inconsistent saccadic targeting, (c) weak retinotopic tuning, and (d) fixating locations not matched to the individual's own face tuning. We found no support for the first three hypotheses, with NTs and DPs consistently fixating similar locations and showing similar retinotopic tuning of their face perception performance. However, in testing the fourth hypothesis, we found preliminary evidence for two distinct phenotypes of DP: (a) Subjects characterized by impaired face memory, typical face perception, and a preference to look high on the face, and (b) Subjects characterized by profound impairments to both face memory and perception and a preference to look very low on the face. Further, while all NTs and upper-looking DPs performed best when faces were presented near their preferred fixation location, this was not true for lower-looking DPs. These results suggest that face recognition deficits in a substantial proportion of people with DP may arise not from aberrant face gaze or compromised retinotopic tuning, but from the suboptimal matching of gaze to tuning.

Characterization of a cAMP responsive transcription factor, Cmr (Rv1675c), in TB complex mycobacteria reveals overlap with the DosR (DevR) dormancy regulon.

Mycobacterium tuberculosis (Mtb) Cmr (Rv1675c) is a CRP/FNR family transcription factor known to be responsive to cAMP levels and during macrophage infections. However, Cmr's DNA binding properties, cellular targets and overall role in tuberculosis (TB) complex bacteria have not been characterized. In this study, we used experimental and computational approaches to characterize Cmr's DNA binding properties and identify a putative regulon. Cmr binds a 16-bp palindromic site that includes four highly conserved nucleotides that are required for DNA binding. A total of 368 binding sites, distributed in clusters among ~200 binding regions throughout the Mycobacterium bovis BCG genome, were identified using ChIP-seq. One of the most enriched Cmr binding sites was located upstream of the cmr promoter, and we demonstrated that expression of cmr is autoregulated. cAMP affected Cmr binding at a subset of DNA loci in vivo and in vitro, including multiple sites adjacent to members of the DosR (DevR) dormancy regulon. Our findings of cooperative binding of Cmr to these DNA regions and the regulation by Cmr of the DosR-regulated virulence gene Rv2623 demonstrate the complexity of Cmr-mediated gene regulation and suggest a role for Cmr in the biology of persistent TB infection.

Differences in solution dynamics between lens ß-crystallin homodimers and heterodimers probed by hydrogen-deuterium exchange and deamidation.

BACKGROUND: Lens transparency is due to the ordered arrangement of the major structural proteins, called crystallins. ßB2 crystallin in the lens of the eye readily forms dimers with other ß-crystallin subunits, but the resulting heterodimer structures are not known and were investigated in this study. METHODS: Structures of ßA3 and ßB2 crystallin homodimers and the ßA3/ßB2 crystallin heterodimers were probed by measuring changes in solvent accessibility using hydrogen-deuterium exchange with mass spectrometry. We further mimicked deamidation in ßB2 and probed the effect on the ßA3/ßB2 heterodimer. Results were confirmed with chemical crosslinking and NMR. RESULTS: Both ßA3 and ßB2 had significantly decreased deuterium levels in the heterodimer compared to their respective homodimers, suggesting that they had less solvent accessibility and were more compact in the heterodimer. The compact structure of ßB2 was supported by the identification of chemical crosslinks between lysines in ßB2 within the heterodimer that were inconsistent with ßB2's extended homodimeric structure. The compact structure of ßA3 was supported by an overall decrease in mobility of ßA3 in the heterodimer detected by NMR. In ßB2, peptides 70-84 and 121-134 were exposed in the homodimer, but buried in the heterodimer with ≥50% decreases in deuterium levels. Homologous peptides in ßA3, 97-109 and 134-149, had 25-50% decreases in deuterium levels in the heterodimer. These peptides are probable sites of interaction between ßB2 and ßA3 and are located at the predicted interface between subunits with bent linkers. Deamidation at Q184 in ßB2 at this predicted interface led to a less compact ßB2 in the heterodimer. The more compact structure of the ßA3/ßB2 heterodimer was also more heat stable than either of the homodimers. CONCLUSIONS: The major structural proteins in the lens, the ß-crystallins, are not static, but dynamic in solution, with differences in accessibility between the homo-and hetero-dimers. This structural flexibility, particularly of ßB2, may facilitate formation of different size higher-ordered structures found in the transparent lens. GENERAL SIGNIFICANCE: Understanding complex hetero-oligomer interactions between ß-crystallins in normal lens and how these interactions change during aging is fundamental to understanding the cause of cataracts. This article is part of a Special Issue entitled Crystallin Biochemistry in Health and Disease.

Decoding ChIP-seq with a double-binding signal refines binding peaks to single-nucleotides and predicts cooperative interaction.

The comprehension of protein and DNA binding in vivo is essential to understand gene regulation. Chromatin immunoprecipitation followed by sequencing (ChIP-seq) provides a global map of the regulatory binding network. Most ChIP-seq analysis tools focus on identifying binding regions from coverage enrichment. However, less work has been performed to infer the physical and regulatory details inside the enriched regions. This research extends a previous blind-deconvolution approach to develop a post-peak-calling algorithm that improves binding site resolution and predicts cooperative interactions. At the core of our new method is a physically motivated model that characterizes the binding signal as an extreme value distribution. This model suggests a mathematical framework to study physical properties of DNA shearing from the ChIP-seq coverage. The model explains the ChIP-seq coverage with two signals: The first considers DNA fragments with only a single binding event, whereas the second considers fragments with two binding events (a double-binding signal). The model incorporates motif discovery and is able to detect multiple sites in an enriched region with single-nucleotide resolution, high sensitivity, and high specificity. Our method improves peak caller sensitivity, from less than 45% up to 94%, at a false positive rate < 11% for a set of 47 experimentally validated prokaryotic sites. It also improves resolution of highly enriched regions of large-scale eukaryotic data sets. The double-binding signal provides a novel application in ChIP-seq analysis: the identification of cooperative interaction. Predictions of known cooperative binding sites show a 0.85 area under an ROC curve.

Eye-Tracking Causality.

How do people make causal judgments? What role, if any, does counterfactual simulation play? Counterfactual theories of causal judgments predict that people compare what actually happened with what would have happened if the candidate cause had been absent. Process theories predict that people focus only on what actually happened, to assess the mechanism linking candidate cause and outcome. We tracked participants' eye movements while they judged whether one billiard ball caused another one to go through a gate or prevented it from going through. Both participants' looking patterns and their judgments demonstrated that counterfactual simulation played a critical role. Participants simulated where the target ball would have gone if the candidate cause had been removed from the scene. The more certain participants were that the outcome would have been different, the stronger the causal judgments. These results provide the first direct evidence for spontaneous counterfactual simulation in an important domain of high-level cognition.