The natural history of weight and swallowing outcomes in oropharyngeal cancer patients following radiation or concurrent chemoradiation therapy.

PURPOSE: Patients treated for oropharyngeal cancer (OPC) are at increased risk for functional decline due to cancer-related impairments and treatment toxicities, often leading to recommendations for enteral nutritional support. This study investigated the natural history of weight and swallowing outcomes in patients with and without feeding tube (FT) placement. METHODS: Data were collected from electronic medical records of OPC patients treated with (chemo)radiotherapy at a single regional cancer center between January 2013 and December 2015. Weight measurements, Functional Oral Intake Scale (FOIS) scores, Performance Status Scale for Head and Neck Cancer (PSS-HN) normalcy of diet scores, and M.D. Anderson Dysphagia Inventory (MDADI) composite scores were gathered at baseline and at 3-, 6-, and 12-months post-treatment. Patients were grouped based on FT placement and change over time was assessed using linear mixed effects analysis. RESULTS: Of 122 eligible patients, 38 (31.1%) received a FT (FT group). Compared with baseline, weight decreased significantly at 3 and 6 months in both groups and at 12 months for patients without a FT (NFT group). Swallowing-related quality of life (QoL) decreased significantly at 3 and 6 months only in the NFT group. CONCLUSION: OPC patients experience clinically relevant decreases in weight and swallowing-related QoL in the first-year post-treatment irrespective of FT placement. These findings will contribute to improved patient monitoring and communication within the clinical setting which may ultimately lead to better outcomes for those with OPC.

Impact of HIV and AIDS on rural elderly caregivers in Chiang Mai Province, Thailand.

The UN General Special Assembly on HIV/AIDS reported that Thailand's elderly are living on the edge of poverty. Those who become caregivers for the children who have been orphaned by AIDS incur even greater challenges. The 2007 Survey of Older Persons of Thailand (SOPT) concluded that there is a range of financial and social safety nets provided by the government, nongovernmental (NGO), and faith-based organizations (FBOs) to help the elderly caregivers and their families. The research offered limited studies on Thailand's elderly caring for these children. The purpose of this phenomenological study was to explore the social, religious and familial experiences of this population. In-depth interviews were conducted with 14 elderly caregivers participating in the Grandma Cares Program (GCP) located in the province of Chiang Mai. They were asked about their caregiving experiences, cultural and Buddhist beliefs, and programs that help them. Data were verified through member checking with a translator. The details of the caregivers' experiences and environments were transcribed and analyzed with Creswell's 6-step process to identify textural and structural themes and patterns. Results of this study indicated that caregivers gained comfort and strength from Buddha's teachings and cultural beliefs, but they would like more support.

Genetic relationships between spring emergence, canopy phenology, and biomass yield increase the accuracy of genomic prediction in Miscanthus.

Miscanthus has potential as a bioenergy crop but the rapid development of high-yielding varieties is challenging. Previous studies have suggested that phenology and canopy height are important determinants of biomass yield. Furthermore, while genome-wide prediction was effective for a broad range of traits, the predictive ability for yield was very low. We therefore developed models clarifying the genetic associations between spring emergence, consequent canopy phenology and dry biomass yield. The timing of emergence was a moderately strong predictor of early-season elongation growth (genetic correlation >0.5), but less so for growth later in the season and for the final yield (genetic correlation <0.1). In contrast, early-season canopy height was consistently more informative than emergence for predicting biomass yield across datasets for two species in Miscanthus and two growing seasons. We used the associations uncovered through these models to develop selection indices that are expected to increase the response to selection for yield by as much as 21% and improve the performance of genome-wide prediction by an order of magnitude. This multivariate approach could have an immediate impact in operational breeding programmes, as well as enable the integration of crop growth models and genome-wide prediction.

Influences of word predictability and type of masker noise on intelligibility of sung text in live concerts.

Vocal music is often intended to convey meaning, but how effectively this is achieved is poorly understood. This study systematically assessed the influence of three non-phonetic factors on the intelligibility of sung words in six public concerts in different venues: word predictability from sentence context, type of masker noise (spoken babble, sung vowels, [∫(w)]), and signal-to-noise ratio (SNR). Stimuli were sung live by a professional a cappella ensemble with one male singing target sentences and five others (two female) producing the masker sounds. The concert audiences (N = 319) reported the final word of each sentence using a handheld voting device, from four phonetically- and semantically-controlled written alternatives projected onto a screen after the sentence was sung. Although overall accuracy differed between performances, intelligibility patterns were robust across concerts. They included predicted main effects of masker noise type ([∫(w)] masking least disruptive, babble most), SNR (high > low), semantic predictability (high > low), listener age (young > old), and listener language status (native > non-native), and some strong interactions. These results suggest that, despite acoustic differences between sung and spoken words and the unusual and varied experimental venues, key findings from traditional speech research apply to sung words, given appropriate musical composition.

Rhythmic variance influences the speed but not the accuracy of complex averaging decisions.

When a rhythm makes an event predictable, that event is perceived faster, and typically more accurately. However, the experiments showing this used simple tasks, and most manipulated temporal expectancy by using periodic or aperiodic precursors unrelated to stimulus and task. Three experiments tested the generality of these observations in a complex task in which rhythm was intrinsic to, rather than a precursor of, the information needed to respond: listeners averaged the laterality of a stream of noise bursts. We varied presentation rate, degree of periodicity, and average lateralisation. Decisions following a probe tone were fastest after periodic stimuli, and slowest after the most aperiodic stimuli. Without a probe tone, listeners responded sooner during periodic sequences, thus hearing less information. Periodicity did not benefit accuracy overall. This gain in speed but not accuracy for less information is not reported for simpler tasks. Neural entrainment supplemented by cognitive factors provide a tentative explanation. When the task is inherently complex and demands high attention over long durations, both expected-periodic and unexpected-aperiodic stimuli can increase response amplitude, enhancing stimulus representation, but periodicity increases confidence to respond early. Drift diffusion modelling supports this proposal: aperiodicity modulated the decision threshold, but not the drift rate or non-decision time. Together, these new data and the literature point towards task-dependent effects of temporal expectation on decision-making, showing interactions between rhythmic variance, task complexity, and sources of expectation about stimuli. We suggest the implications are worth exploring to extend understanding of rhythmicity on decision-making to everyday situations.

Bacterial endophytic community composition varies by hemp cultivar in commercially sourced seed.

The seed-endophytic bacterial community is a potentially beneficial and heritable fraction of the plant microbiome. Its utilization as a sustainable crop improvement strategy could be especially valuable for species such as hemp, where production is being scaled up and new challenges will be faced in managing crop productivity and health. However, little is known about the makeup and variation of the hemp seed microbiome. This study profiled the endophytic bacterial communities harboured by 16 hemp cultivars sourced from commercial suppliers in Europe. A 16S rDNA amplicon sequencing approach identified 917 amplicon sequence variants across samples. Taxonomic classification of sequences revealed 4 phyla and 87 genera to be represented in the dataset. Several genera were widespread while some were specific to one or a few cultivars. Flavobacterium, Pseudomonas, and Pantoea were notable in their high overall abundance and prevalence, but community composition was variable and no one taxon was universally abundant, suggesting a high degree of flexibility in community assembly. Taxonomic composition and alpha diversity differed among cultivars, though further work is required to understand the relative influence of hemp genetic factors on community structure. The taxonomic profiles presented here can be used to inform further work investigating the functional characteristics and potential plant-growth-promoting traits of seed-borne bacteria in hemp.

Accelerating the domestication of a bioenergy crop: identifying and modelling morphological targets for sustainable yield increase in Miscanthus.

To accelerate domestication of Miscanthus, an important energy crop, 244 replicated genotypes, including two different species and their hybrids, were analysed for morphological traits and biomass yield over three growing seasons following an establishment phase of 2 years in the largest Miscanthus diversity trial described to date. Stem and leaf traits were selected that contributed both directly and indirectly to total harvested biomass yield, and there was variation in all traits measured. Morphological diversity within the population was correlated with dry matter yield (DMY) both as individual traits and in combination, in order to determine the respective contributions of the traits to biomass accumulation and to identify breeding targets for yield improvement. Predictive morphometric analysis was possible at year 3 within Miscanthus sinensis genotypes but not between M. sinensis, Miscanthus sacchariflorus, and interspecific hybrids. Yield is a complex trait, and no single simple trait explained more than 33% of DMY, which varied from 1 to 5297 g among genotypes within this trial. Associating simple traits increased the power of the morphological data to predict yield to 60%. Trait variety, in combination, enabled multiple ideotypes, thereby increasing the potential diversity of the crop for multiple growth locations and end uses. Both triploids and interspecific hybrids produced the highest mature yields, indicating that there is significant heterosis to be exploited within Miscanthus that might be overlooked in early selection screens within years 1-3. The potential for optimizing biomass yield by selecting on the basis of morphology is discussed.

Perceptual learning of phonetic information that indicates morphological structure.

Familiarity with a talker or accent can facilitate speech perception, but little is known about the acoustic-phonetic knowledge that is acquired during exposure to an unfamiliar talker, particularly with respect to how a talker realises grammatical and prosodic distinctions. The present experiment used relatively natural stimuli and tasks to investigate listeners' adaptation to a phonetic variant that is systematically associated with a morphological context, specifically the English /ri:/ prefix. Results showed that listeners who had previously been exposed to the atypical variant in /ri:/ prefixes in stories scored higher than control listeners in an intelligibility-in-noise task that included instances of the atypical variant. Perceptual learning was partly specific to the /ri:/ prefix, though there was weak generalisation of learning to word-initial /ri:/ syllables that were not prefixes. These results emphasise the value of developing context-sensitive, probabilistic models of speech perception which include multiple, parallel levels of representation.

Barriers to accessing and continuing mental health treatment among individuals with dissociative symptoms.

Background: Dissociative disorders (DDs) are characterized by interruptions of identity, thought, memory, emotion, perception, and consciousness. Patients with DDs are at high risk for engaging in dangerous behaviours, such as self-harm and suicidal acts; yet, only between 28% and 48% of individuals with DDs receive mental health treatment. Patients that do pursue treatment are often misdiagnosed, repeatedly hospitalized, and experience disbelief from providers about their trauma history and dissociative symptoms. Lack of dissociation-specific treatment can result in poor quality of life, severe symptoms requiring utilization of hospitalization and intensive outpatient treatment, and high rates of disability. Objective: Given the extensive and debilitating symptoms experienced by individuals with DDs and the infrequent utilization of treatment, the current study explored barriers to accessing and continuing mental health treatment for individuals with dissociative symptoms and DDs. Method: A total of 276 participants with self-reported dissociative symptoms were recruited via online social media platforms. Participants completed a survey which featured 35 possible barriers to accessing treatment and 45 possible reasons for discontinuing treatment, along with open text boxes for adding barriers/reasons that were not listed. Results: Results showed 97% of participants experienced one or more barriers to accessing treatment (M = 9 barriers) and 92% stopped treatment with a provider due to at least one of the reasons captured in the survey (e.g. limited insurance coverage, poor therapeutic alliance, disbelief from providers, etc.; M = 7 barriers). Conclusions: The most frequently endorsed barriers were structural barriers, such as those related to finances, insurance, and lack of provider availability. It is imperative more service providers are trained to treat dissociation and that insurers and health care systems recognize the need for specialized, dissociation-focused treatment.

Antecedentes: Los trastornos disociativos (TD) se caracterizan por interrupciones en la identidad, pensamiento, memoria, emoción, percepción y conciencia. Los pacientes con TD tienen un alto riesgo de participar en conductas peligrosas, como autolesiones y actos suicidas; sin embargo, solo entre el 28­48% de las personas con TD reciben tratamiento de salud mental. Los pacientes que buscan tratamiento a menudo son mal diagnosticados, hospitalizados repetidamente y experimentan incredulidad por parte de los proveedores sobre su historial de trauma y síntomas disociativos. La falta de un tratamiento específico para la disociación puede resultar en una mala calidad de vida, síntomas graves que requieren hospitalización y tratamiento ambulatorio intensivo y altas tasas de discapacidad.Objetivo: Dados los síntomas extensos y debilitantes que experimentan las personas con TD y la utilización poco frecuente del tratamiento, el presente estudio exploró las barreras para acceder y continuar el tratamiento de salud mental para las personas con síntomas disociativos y TD.Método: Un total de 276 participantes con síntomas disociativos auto-reportados fueron reclutados a través de plataformas de redes sociales en línea. Los participantes completaron una encuesta que presentaba 35 posibles barreras para acceder al tratamiento y 45 posibles razones para interrumpir el tratamiento, junto con cuadros de texto abiertos para agregar barreras/razones no incluidas en la lista.Resultados: Los resultados mostraron que el 97% de los participantes experimentó una o más barreras para acceder al tratamiento (M = 9 barreras) y el 92% interrumpió el tratamiento con un proveedor debido al menos a una de las razones capturadas en la encuesta (por ejemplo, cobertura de seguro médico limitada, pobre alianza terapéutica, incredulidad por parte de los proveedores, etc.; M = 7 barreras).Conclusiones: Las barreras confirmadas con mayor frecuencia fueron las barreras estructurales, como las relacionadas con las finanzas, los seguros médicos y la falta de disponibilidad de proveedores. Es imperativo que más proveedores de servicios estén capacitados para tratar la disociación y que las aseguradoras y los sistemas de atención médica reconozcan la necesidad de un tratamiento especializado centrado en la disociación.

Evaluating "The REST of Your Life," a Workplace Health Program to Improve Employee Sleep, Health, Energy, and Productivity.

PURPOSE: Sleep is critical for employee health, well-being, and productivity. Our purpose is to evaluate a sleep-focused interactive workplace health promotion program. DESIGN: We evaluate sleep and mental health before and after exposure to the program using a pre/post quasi-experimental pilot study design with surveys administered at baseline and 1-, 6-, and 12 months post-exposure (Phase 1). We design program evaluation surveys for dissemination when the program is offered broadly to hospital employees (Phase 2). SETTING: The study was conducted at a large teaching hospital in the Southeast U.S. in 2016. SUBJECTS: Subjects were full-time hospital employees. INTERVENTION: The program was presented to subjects in one four-hour interactive session. MEASURES: In Phase 1 (n = 55), surveys included the validated Apnea Risk Evaluation System, Dysfunctional Beliefs About Sleep, Generalized Anxiety Disorder-7, Pittsburgh Sleep Quality Index and Patient Health Questionnaire. Phase 2 (n = 3935) utilized program evaluation surveys. ANALYSIS: We compare survey responses between pre- and post-program using a repeated measures analysis of variance with post-hoc tests. RESULTS: Statistically significant improvement in all sleep and mental health domains was demonstrated. In Phase 2, 81.9% reported "strongly agree" to willingness to recommend the program to co-workers. CONCLUSION: We demonstrate improvement in employee sleep and mental health after exposure to a novel workplace health promotion program to improve sleep.

Patient-led Remote IntraCapillary pharmacoKinetic Sampling (fingerPRICKS) for Therapeutic Drug Monitoring in patients with Inflammatory Bowel Disease.

BACKGROUND AND AIMS: Because of COVID-19 public health restrictions, telemedicine has replaced conventional outpatient follow up for most patients with chronic immune-mediated inflammatory disorders treated with biologic drugs. Innovative solutions to facilitate remote therapeutic drug monitoring are therefore required. Low-volume intracapillary blood sampling can be undertaken by patients at home and samples returned by post to central laboratories. We sought to report the effect of the COVID-19 pandemic on requests for therapeutic drug monitoring and the equivalence, acceptability and effectiveness of low volume Patient-led Remote IntraCapillary pharmacoKinetic Sampling [fingerPRICKS] compared to conventional venepuncture. METHODS: We undertook a cross-sectional blood sampling methods comparison study and compared sample types using linear regression models. Drug and antidrug antibody levels were measured using standard ELISAs. Acceptability was assessed using a purpose-designed questionnaire. RESULTS: Therapeutic drug monitoring requests for adalimumab (96.5 [70.5-106] per week to 52 [33.5-57.0], p < 0.001) but not infliximab (184.5 [161.2-214.2] to 161 [135-197.5], p = 0.34) reduced during the first UK stay-at-home lockdown compared with the preceding 6 months. Fingerprick sampling was equivalent to conventional venepuncture for adalimumab, infliximab, vedolizumab and ustekinumab drug, and anti-adalimumab and anti-infliximab antibody levels. The median [interquartile range] volume of serum obtained using intracapillary sampling was 195 µL [130-210]. More than 87% [90/103] of patients agreed that intracapillary testing was easy and 69% [71/103] preferred it to conventional venepuncture. In routine care, 75.3% [58/77] of patients returned two blood samples within 14 days to permit remote assessment of biologic therapeutic drug monitoring. CONCLUSIONS: Therapeutic drug monitoring can be undertaken using patient-led remote intracapillary blood sampling and has the potential to be a key adjunct to telemedicine in patients with immune-mediated inflammatory diseases.

Influence of Turn-Taking in Musical and Spoken Activities on Empathy and Self-Esteem of Socially Vulnerable Young Teenagers.

This study describes a preliminary test of the hypothesis that, when people engage in musical and linguistic activities designed to enhance the interactive, turn-taking properties of typical conversation, they benefit in ways that enhance empathy and self-esteem, relative to people who experience activities that are similar except that synchronous action is emphasized, with no interactional turn-taking. Twenty-two 12-14 year olds identified as socially vulnerable (e.g., for anxiety) received six enjoyable 1-h sessions of musical improvisation, language games that developed sensitivity to linguistic rhythm and melody, and cross-over activities like rap. The Turn-taking group (n = 11), practiced characteristics of conversation in language games, and these were also introduced into musical activities. This involved much turn-taking and predicting what others would do. A matched control group, the Synchrony group, did similar activities but in synchrony, with less prediction and no turn-taking. Task complexity increased over the six sessions. Psychometric testing before and after the series showed that the Turn-taking group increased in empathy on self-report (Toronto Empathy Questionnaire) and behavioral ('Reading the Mind in the Eyes') measures, and in the General subtest of the Culture-Free Self-Esteem Inventory. While more work is needed to confirm the conclusions for relevant demographic groups, the current results point to the social value of musical and linguistic activities that mimic entrained, tightly coordinated parameters of everyday conversational interaction, in which, at any one time, individuals act as equal participants who have different roles.

Musical improvisation enhances interpersonal coordination in subsequent conversation: Motor and speech evidence.

This study explored the effects of musical improvisation between dyads of same-sex strangers on subsequent behavioural alignment. Participants-all non-musicians-conversed before and after either improvising music together (Musical Improvisation-MI-group) or doing a motoric non-rhythmic cooperative task (building a tower together using wooden blocks; the Hands-Busy-HB-group). Conversations were free, but initially guided by an adaptation of the Fast Friends Questionnaire for inducing talk among students who are strangers and meeting for the first time. Throughout, participants' motion was recorded with an optical motion-capture system (Mocap) and analysed in terms of speed cross-correlations. Their conversations were also recorded on separate channels using headset microphones and were analysed in terms of the periodicity displayed by rhythmic peaks in the turn transitions across question and answer pairs (Q+A pairs). Compared with their first conversations, the MI group in the second conversations showed: (a) a very rapid, partially simultaneous anatomical coordination between 0 and 0.4 s; (b) delayed mirror motoric coordination between 0.8 and 1.5 s; and (c) a higher proportion of Periodic Q+A pairs. In contrast, the HB group's motoric coordination changed slightly in timing but not in degree of coordination between the first and second conversations, and there was no significant change in the proportion of periodic Q+A pairs they produced. These results show a convergent effect of prior musical interaction on joint body movement and use of shared periodicity across speech turn-transitions in conversations, suggesting that interaction in music and speech may be mediated by common processes.

Correction: Musical improvisation enhances interpersonal coordination in subsequent conversation: Motor and speech evidence.

[This corrects the article DOI: 10.1371/journal.pone.0250166.].

Differential expression of starch and sucrose metabolic genes linked to varying biomass yield in Miscanthus hybrids.

BACKGROUND: Miscanthus is a commercial lignocellulosic biomass crop owing to its high biomass productivity and low chemical input requirements. Within an interspecific Miscanthus cross, progeny with high biomass yield were shown to have low concentrations of starch and sucrose but high concentrations of fructose. We performed a transcriptional RNA-seq analysis between selected Miscanthus hybrids with contrasting values for these phenotypes to clarify how these phenotypes are genetically controlled. RESULTS: We observed that genes directly involved in the synthesis and degradation of starch and sucrose were down-regulated in high-yielding Miscanthus hybrids. At the same time, glycolysis and export of triose phosphates were up-regulated in high-yielding Miscanthus hybrids. These differentially expressed genes and biological functions were regulated by a well-connected network of less than 25 co-regulated transcription factors. CONCLUSIONS: Our results evidence a direct relationship between high expression of essential enzymatic genes in the starch and sucrose pathways and co-expression with their transcriptional regulators, with high starch concentrations and lower biomass production. The strong interconnectivity between gene expression and regulators, chemotype and agronomic traits opens the door to use the expression of well-characterised genes associated with carbohydrate metabolism, particularly in the starch and sucrose pathway, for the early selection of high biomass-yielding genotypes from large Miscanthus populations.

Cognitive bias in forensic pathology decisions.

Forensic pathologists' decisions are critical in police investigations and court proceedings as they determine whether an unnatural death of a young child was an accident or homicide. Does cognitive bias affect forensic pathologists' decision-making? To address this question, we examined all death certificates issued during a 10-year period in the State of Nevada in the United States for children under the age of six. We also conducted an experiment with 133 forensic pathologists in which we tested whether knowledge of irrelevant non-medical information that should have no bearing on forensic pathologists' decisions influenced their manner of death determinations. The dataset of death certificates indicated that forensic pathologists were more likely to rule "homicide" rather than "accident" for deaths of Black children relative to White children. This may arise because the base-rate expectation creates an a priori cognitive bias to rule that Black children died as a result of homicide, which then perpetuates itself. Corroborating this explanation, the experimental data with the 133 forensic pathologists exhibited biased decisions when given identical medical information but different irrelevant non-medical information about the race of the child and who was the caregiver who brought them to the hospital. These findings together demonstrate how extraneous information can result in cognitive bias in forensic pathology decision-making.

Engineering the isobutanol biosynthetic pathway in Escherichia coli by comparison of three aldehyde reductase/alcohol dehydrogenase genes.

Biofuels synthesized from renewable resources are of increasing interest because of global energy and environmental problems. We have previously demonstrated production of higher alcohols from Escherichia coli using a 2-keto acid-based pathway. Here, we have compared the effect of various alcohol dehydrogenases (ADH) for the last step of the isobutanol production. E. coli has the yqhD gene which encodes a broad-range ADH. Isobutanol production significantly decreased with the deletion of yqhD, suggesting that the yqhD gene on the genome contributed to isobutanol production. The adh genes of two bacteria and one yeast were also compared in E. coli harboring the isobutanol synthesis pathway. Overexpression of yqhD or adhA in E. coli showed better production than ADH2, a result confirmed by activity measurements with isobutyraldehyde.

Role of voice rest following laser resection of vocal fold lesions: A randomized controlled trial.

OBJECTIVES/HYPOTHESIS: Voice rest is often prescribed following phonosurgery by most surgeons despite limited empiric evidence to support its practice. This study assessed the effect of postphonosurgery voice rest on vocal outcomes. STUDY DESIGN: Prospective, randomized controlled trial. METHODS: Patients with unilateral vocal fold lesions undergoing CO2 laser excision were recruited in a prospective manner and randomized into one of two groups: 1) an experimental arm consisting of 7 days of absolute voice rest, or 2) a control arm consisting of no voice rest. The primary outcome measure was the Voice Handicap Index-10 (VHI-10) questionnaire. Secondary outcomes included aerodynamic measurements (maximum phonation time), acoustic measures (fundamental frequency, jitter, shimmer, and harmonic-to-noise ratio), and auditory-perceptual measures. Primary and secondary outcomes were assessed preoperatively and reassessed postoperatively at the 1- and 3-month follow-up. Patient compliance to voice rest instructions were controlled for using subjective and objective parameters. RESULTS: Thirty patients were enrolled with 15 randomized to each arm of the study. Statistical analysis for the entire cohort showed a significant improvement in the mean preoperative VHI-10 compared to postoperative assessments at 1-month (19.0 vs. 7.3, P < .05) and 3-month (19.0 vs. 6.2, P < .05) follow-up. However, between-group comparisons showed no significant difference in postoperative VHI-10 at either time point. Similarly, secondary outcome measures yielded no significant difference in between-group comparisons. CONCLUSIONS: Our study shows no significant benefit to voice rest on postoperative voice outcomes as determined by patient self-perception, acoustic variables, and auditory-perceptual analysis. LEVEL OF EVIDENCE: 1b CLINICAL TRIAL NUMBER: NCT02788435 (clinicaltrials.gov) Laryngoscope, 130:1750-1755, 2020.

Siva-1 promotes K-48 polyubiquitination of TRAF2 and inhibits TCR-mediated activation of NF-kappaB.

The proapoptotic protein Siva-1 plays an important role in some of the extrinsic and intrinsic apoptosis signaling pathways in cancer cells. Previously, we showed that Siva-1 inhibited the activity of the prosurvival transcription factor NF-kappaB. In the present study, upon TCR cross-linking of Jurkat T leukemia cells, we demonstrated that the inhibitory target of Siva-1 is upstream of the IKK complex in the NF-kappaB signaling pathway. Additionally, Siva-1 also suppressed the activity of another crucial transcription factor AP-1, and a common mediator of both these pathways is the adaptor protein TRAF2. Further, we observed that Siva-1 indeed interacted with TRAF2 and negatively regulated its activity by promoting K48-hnked polyubiquitination. Siva-1 specifically interacted with the ring finger domain of TRAF2, which is essential for its E3 hgase activity and its ability to subsequently activate NF-kappaB. TCR cross-linking of Jurkat T cells that lacked Siva-1 revealed significantly lowered K48- but elevated K63-ubiquitinated TRAF2 levels upon TCR cross-linking, suggesting that the differential pattern of ubiquitination in these cells essentially contributed to a robust and sustained activation of NF-kappaB. The above results demonstrated an important role for endogenous Siva-1 in negatively regulating NF-kappaB activation by targeting TRAF2.

Offending behaviour in adults with Asperger syndrome.

Considerable speculation is evident both within the scientific literature and popular media regarding possible links between Asperger syndrome and offending. A survey methodology that utilised quantitative data collection was employed to investigate the prevalence of offending behaviour amongst adults with Asperger Syndrome in a large geographical area of South Wales, UK; qualitative interviews were then conducted with a sub-sample of those identified. A small number of participants meeting the study criteria were identified. For those who had offended, their experience of the criminal justice system was essentially negative. Possible implications of the results were discussed.