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1.
Ecol Evol ; 14(6): e11509, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38895575

ABSTRACT

Pathogen spillover corresponds to the transmission of a pathogen or parasite from an original host species to a novel host species, preluding disease emergence. Understanding the interacting factors that lead to pathogen transmission in a zoonotic cycle could help identify novel hosts of pathogens and the patterns that lead to disease emergence. We hypothesize that ecological and biogeographic factors drive host encounters, infection susceptibility, and cross-species spillover transmission. Using a rodent-ectoparasite system in the Neotropics, with shared ectoparasite associations as a proxy for ecological interaction between rodent species, we assessed relationships between rodents using geographic range, phylogenetic relatedness, and ectoparasite associations to determine the roles of generalist and specialist hosts in the transmission cycle of hantavirus. A total of 50 rodent species were ranked on their centrality in a network model based on ectoparasites sharing. Geographic proximity and phylogenetic relatedness were predictors for rodents to share ectoparasite species and were associated with shorter network path distance between rodents through shared ectoparasites. The rodent-ectoparasite network model successfully predicted independent data of seven known hantavirus hosts. The model predicted five novel rodent species as potential, unrecognized hantavirus hosts in South America. Findings suggest that ectoparasite data, geographic range, and phylogenetic relatedness of wildlife species could help predict novel hosts susceptible to infection and possible transmission of zoonotic pathogens. Hantavirus is a high-consequence zoonotic pathogen with documented animal-to-animal, animal-to-human, and human-to-human transmission. Predictions of new rodent hosts can guide active epidemiological surveillance in specific areas and wildlife species to mitigate hantavirus spillover transmission risk from rodents to humans. This study supports the idea that ectoparasite relationships among rodents are a proxy of host species interactions and can inform transmission cycles of diverse pathogens circulating in wildlife disease systems, including wildlife viruses with epidemic potential, such as hantavirus.

2.
Neurosci Lett ; 805: 137220, 2023 05 14.
Article in English | MEDLINE | ID: mdl-37019272

ABSTRACT

INTRODUCTION: This study examined whether altering body position (i.e., sitting or standing) affected the dynamics of physiological tremor for healthy older adults and persons with Parkinson's disease (PD). It was also of interest to determine how consistent the tremor was for both groups as determined by examining changes in within-subject variability of tremor amplitude, regularity and frequency. METHODS: Ten Parkinsonian participants (65.1 ± 3.2 yrs.) and twelve elderly persons (71.2 ± 2.6 yrs.) participated in this study. Tremor was collected from the index finger and hand segments using lightweight accelerometers during the performance of a bilateral pointing task. Persons performed the pointing task in a standing or sitting position. RESULTS: As expected, the tremor for the PD persons was greater in magnitude (mean RMS, peak power), more regular (lower SampEn), and more inconsistent from trial-to-trial (increased intra-individual variability, IIV) than the tremor recorded for the elderly. Further, when assessed during standing, the magnitude of the tremor for all individuals (elderly and PD) was greater, more variable, and less complex compared to the tremor when assessed during the sitting posture. The only measure which did not change within each group was the frequency of the major tremor peak which remained consistent, showing no significant change between limbs or as a function of the posture adopted. CONCLUSION: The findings revealed that tremor increased in amplitude and decreased in regularity for all individuals was assessed when standing compared to sitting. It is likely that these increases were task-related, reflecting the increased physical demands of performing the task when standing rather than being driven by specific age- or disease-related changes in the mechanisms underlying tremorgenesis. Further, the tremor for the PD individuals tended to be more variable from trial-by-trial in terms of both amplitude and regularity as compared to the elderly persons. Interestingly, the only tremor metric which showed no change within each group was the frequency of the major tremor peak which was consistent within both groups irrespective of the posture adopted.


Subject(s)
Essential Tremor , Parkinson Disease , Humans , Aged , Tremor , Parkinson Disease/complications , Posture/physiology , Hand
3.
J Reprod Infant Psychol ; 41(5): 528-539, 2023 11.
Article in English | MEDLINE | ID: mdl-35234553

ABSTRACT

OBJECTIVES: To investigate the impact of including the response option of 'Possibly' in the Distress question on the Matthey Generic Mood Questionnaire (MGMQ) during antenatal emotional health screening in English-speaking women. BACKGROUND: Some distress screening questions only allow respondents to choose between 'Yes' or 'No' to the presence of distress. The MGMQ, however, allows respondents to chose between 'Yes', 'Possibly', or 'No', which may be preferable if a participant is reluctant to state she definitely feels distressed. METHOD: In Study 1, women undergoing routine antenatal psychosocial screening were allocated to either completing the MGMQ Distress question with the usual three-option response format of 'Yes, Possibly, No' (N = 960), or just a 'Yes, No' response format (N = 771). The proportion of responses were compared in each group, as were the proportion then screening positive on the MGMQ's Bother question. In Study 2, women (N = 113) attending routine antenatal clinic appointments were asked about their preference between these response formats. RESULTS: Including 'Possibly' resulted in only a slight increase in the proportion giving a positive response to the Distress question, and then also screening positive on the Bother question. In Study 2, a substantial majority of women (80%) preferred having 'Possibly' in the response options. CONCLUSION: While the impact of including 'Possibly' is small, it allows for more women to communicate how they are feeling on the full MGMQ. Given the large majority of women preferring having 'Possibly' included, we believe that the Distress Question is enhanced by having this as a response option.


Subject(s)
Affect , Emotions , Humans , Female , Pregnancy , Surveys and Questionnaires , Mass Screening/methods , Prenatal Diagnosis
4.
Ticks Tick Borne Dis ; 14(2): 102106, 2023 03.
Article in English | MEDLINE | ID: mdl-36516481

ABSTRACT

Forest thinning is a management tool used in the New Jersey Pinelands and elsewhere to improve forest health and resilience, mitigate wildfire risk, and manage for wildlife. Forest thinning leads to warmer drier microclimates, which have been shown in both field and laboratory studies to reduce tick survival and reproduction. To directly assess the effects of forest thinning on the abundance and diversity of ticks and on the prevalence of tick-borne human pathogens, we sampled ticks weekly from March to November 2021 at three replicated pairs of thinned and unthinned forest sites composed primarily of pitch-pine, shortleaf pine, and various oak species. We characterized microclimate in the understory and forest floor at each sampling plot by deploying multiple data loggers to monitor temperature and relative humidity throughout the study period. As expected, we found that thinned plots were significantly drier and warmer than unthinned plots. We also found that average questing tick abundance was 92% lower in thinned as compared with unthinned plots. Of the three main tick species collected in unthinned plots (Amblyomma americanum, Ixodes scapularis, and Dermacentor albipictus) only A. americanum and a single I. scapularis were collected in thinned plots. Prevalence of Ehrlichia species in A. americanum did not differ between treatments, and the sole I. scapularis collected in a thinned plot was infected with Borrelia burgdorferi sensu lato. However, the significant and much lower tick abundance in thinned plots indicates a lower risk of human-tick encounters. Our results add to the growing evidence that landscape and forest management can reduce local tick abundance, thereby reducing tick-borne disease risk.


Subject(s)
Borrelia burgdorferi , Ixodes , Animals , Humans , New Jersey/epidemiology , Forests , Animals, Wild
5.
Eur Spine J ; 31(11): 2866-2874, 2022 11.
Article in English | MEDLINE | ID: mdl-35786771

ABSTRACT

PURPOSE: To determine the predictive validity of the STarT Back tool (SBT) undertaken at baseline and 6 weeks to classify Emergency Department (ED) patients with LBP into groups at low, medium or high risk of persistent disability at 3 months. A secondary aim was to evaluate the clinical effectiveness of pragmatic risk-matched treatment in an ED cohort at 3 months. METHODS: A prospective observational multi-centre study took place in the physiotherapy services linked to the ED in four teaching hospitals in Dublin, Ireland. Patients were stratified into low, medium and high-risk groups at their baseline assessment. Participants received stratified care, where the content of their treatment was matched to their risk profile. Outcomes completed at baseline and 3 months included pain and disability. Linear regression analyses assessed if baseline or 6-week SBT score were predictive of disability at 3 months. Changes in the primary outcome of disability were dichotomised into those who achieved/ did not achieve a 30% improvement in their RMDQ at 6 weeks and 3 months. RESULTS: The study enrolled 118 patients with a primary complaint of LBP ± leg pain with 67 (56.7%) completing their 6-week and 3-month follow-up. Baseline RMDQ and being in medium or high risk SBT group at 6 weeks were predictive of persistent disability at 3 months. A total of 54 (80.6%) participants reported a > 30% improvement at 3 months. CONCLUSION: Disability at baseline and SBT administered at 6 weeks more accurately predicted disability at 3 months than SBT at baseline in an ED population.


Subject(s)
Low Back Pain , Humans , Low Back Pain/therapy , Disability Evaluation , Treatment Outcome , Prospective Studies , Emergency Service, Hospital
6.
J Hum Nutr Diet ; 33(6): 876-880, 2020 12.
Article in English | MEDLINE | ID: mdl-32975829

ABSTRACT

BACKGROUND: Portable gluten sensors are now commercially available to the public, although there is genuine uncertainty within the medical community over whether they should be used for coeliac disease management. The present study described qualitatively the experience of using a portable gluten sensor for 15 adults and 15 adolescents with coeliac disease participating in a 3-month pilot clinical trial. METHODS: Participants were 30 individuals, aged 13-70 years, with biopsy-confirmed coeliac disease on a gluten-free diet. All received a portable gluten sensor and were randomised to low, medium, and high numbers of single-use capsules. Open-ended questions addressed likes and dislikes using the portable gluten sensor after 3 months. Major themes were identified and described. RESULTS: Participants liked that the portable gluten sensor provided extra assurance to check foods presented as gluten-free, the convenient size and portability, the added sense of control, and overall peace-of-mind. Participants disliked having attention drawn to them when using the sensor and feeling as if they were deterring others from eating. Participants also disliked the physical difficulty associated with using the capsules, questionable accuracy and the inability to test fermented foods. Adults were more enthusiastic about the sensor than adolescents. CONCLUSIONS: Positive and negative experiences may be expected when using commercially available portable gluten sensors to help manage coeliac disease. As future versions of this and other gluten sensors become available, it will be important to investigate the relationship between users' experience with the sensors and long-term outcomes such as mucosal healing and quality of life.


Subject(s)
Celiac Disease/psychology , Diet, Gluten-Free/instrumentation , Diet, Gluten-Free/psychology , Food Analysis/instrumentation , Patient Acceptance of Health Care/psychology , Adolescent , Adult , Aged , Celiac Disease/diet therapy , Emotions , Feeding Behavior/psychology , Female , Glutens/analysis , Humans , Male , Middle Aged , Pilot Projects , Qualitative Research , Quality of Life , Young Adult
7.
BMC Pregnancy Childbirth ; 20(1): 451, 2020 Aug 07.
Article in English | MEDLINE | ID: mdl-32767969

ABSTRACT

BACKGROUND: One in five women experience psychological distress in the perinatal period. To support women appropriately, Australian guidelines recommend routine depression screening and psychosocial risk assessment by midwives in pregnancy. However, there is some evidence that current screening processes results in higher rates of false positives. The Perinatal Integrated Psychosocial Assessment (PIPA) Project compared two models of psychosocial assessment and referral - Usual Care and the PIPA model - with a view to improving referral decisions. This paper describes midwives' perspectives on psychosocial assessment, depression screening and referral at the antenatal booking appointment and compares midwives' experiences with, and perspectives on, the two models of care under investigation. METHODS: A two-phase, convergent mixed methods design was used. Midwives providing antenatal care completed a self-report survey in phase one prior to implementation of the new model of psychosocial assessment (n = 26) and again in phase two, following implementation (n = 27). Sixteen midwives also participated in two focus groups in phase two. Quantitative and qualitative data were compared and integrated in the presentation of results and interpretation of findings. RESULTS: Midwives supported psychosocial assessment believing it was a catalyst for 'Opening the door" to conversations with women. Midwives were comfortable asking the questions and tailored their approach to build rapport and trust. Overall. midwives expressed favourable views towards the PIPA model. A greater proportion of midwives relied mostly or entirely on the suggested wording for the psychosocial questions in the PIPA model compared to Usual Care (44.4% vs 12.0%, χ2=5.17, p=.023, φ =-.36). All midwives reported finding the referral or action message displayed at the end of the PIPA psychosocial assessment to be 'somewhat' or 'very' helpful, compared to 42.3% in Usual Care (χ2 = 18.36, p < .001, φ = -.64). Midwives were also more likely to act on or implement the message often or all of the time) in the PIPA model (PIPA = 69.2% vs Usual Care = 32.0%, (χ2 = 5.66, p < .017, φ = -.37). CONCLUSION: The study identified benefits of the new model and can inform improvements in psychosocial screening, referral and related care processes within maternity settings. The study demonstrates that psychosocial assessment can, over time, become normalised and embedded in practice.


Subject(s)
Attitude of Health Personnel , Depression/diagnosis , Depression/psychology , Midwifery , Models, Psychological , Pregnancy Complications/diagnosis , Pregnancy Complications/psychology , Adult , Female , Humans , Middle Aged , Pregnancy , Young Adult
8.
Nat Commun ; 11(1): 1269, 2020 03 09.
Article in English | MEDLINE | ID: mdl-32152267

ABSTRACT

Multicellular rosettes are transient epithelial structures that serve as intermediates during diverse organ formation. We have identified a unique contributor to rosette formation in zebrafish Kupffer's vesicle (KV) that requires cell division, specifically the final stage of mitosis termed abscission. KV utilizes a rosette as a prerequisite before forming a lumen surrounded by ciliated epithelial cells. Our studies identify that KV-destined cells remain interconnected by cytokinetic bridges that position at the rosette's center. These bridges act as a landmark for directed Rab11 vesicle motility to deliver an essential cargo for lumen formation, CFTR (cystic fibrosis transmembrane conductance regulator). Here we report that premature bridge cleavage through laser ablation or inhibiting abscission using optogenetic clustering of Rab11 result in disrupted lumen formation. We present a model in which KV mitotic cells strategically place their cytokinetic bridges at the rosette center, where Rab11-associated vesicles transport CFTR to aid in lumen establishment.


Subject(s)
Cell Division/physiology , Cell Polarity/physiology , Embryo, Nonmammalian/physiology , Embryonic Development/physiology , Kupffer Cells/physiology , Organogenesis/physiology , Zebrafish/embryology , Animals , Cell Line , Cell Movement , Cilia/physiology , Cystic Fibrosis Transmembrane Conductance Regulator/metabolism , Embryo, Nonmammalian/metabolism , Embryonic Development/genetics , Epithelial Cells/metabolism , Gene Expression Regulation, Developmental , Kupffer Cells/cytology , Mitosis , Zebrafish Proteins/genetics , Zebrafish Proteins/metabolism , rab GTP-Binding Proteins/genetics , rab GTP-Binding Proteins/metabolism
9.
J Hum Nutr Diet ; 32(3): 311-320, 2019 06.
Article in English | MEDLINE | ID: mdl-30834587

ABSTRACT

BACKGROUND: Certain approaches to managing a strict gluten-free diet (GFD) for coeliac disease (CD) may lead to impaired psychosocial well-being, a diminished quality of life (QOL) and disordered eating. The present study aimed to understand adolescents' approaches to managing a GFD and the association with QOL. METHODS: Thirty adolescents with CD (13-17 years old) following the GFD for at least 1 year completed the Celiac Dietary Adherence Test (CDAT) and QOL survey. Their approaches to GFD management were explored using a semi-structured interview, where key themes were developed using an iterative process, and further analysed using a psychosocial rubric to classify management strategies and QOL. CDAT ratings were compared across groups. RESULTS: Gluten-free diet management strategies were classified on a four-point scale. Adaptive eating behaviours were characterised by greater flexibility (versus rigidity), trust (versus avoidance), confidence (versus controlling behaviour) and awareness (versus preoccupation) with respect to maintaining a GFD. Approximately half the sample (53.3%) expressed more maladaptive approaches to maintaining a GFD and those who did so were older with lower CD-Specific Pediatric Quality of Life (CDPQOL) scores, mean subscale differences ranging from 15.0 points for Isolation (t = 2.4, P = 0.03, d.f. = 28) to 23.4 points for Limitations (t = 3.0, P = 0.01, d.f. = 28). CONCLUSIONS: Adolescents with CD who manage a GFD with maladaptive eating behaviours similar to known risk factors for feeding and eating disorders experience diminished QOL. In accordance with CD management recommendations, we recommend ongoing follow-up with gastroenterologists and dietitians and psychosocial support referrals, as needed.


Subject(s)
Celiac Disease/psychology , Diet, Gluten-Free/psychology , Feeding Behavior/psychology , Patient Compliance/psychology , Quality of Life , Adaptation, Psychological , Adolescent , Celiac Disease/diet therapy , Cross-Sectional Studies , Feeding and Eating Disorders/psychology , Female , Humans , Male , Qualitative Research , Risk Factors , Surveys and Questionnaires
10.
Cell Rep ; 26(3): 775-787.e5, 2019 01 15.
Article in English | MEDLINE | ID: mdl-30650366

ABSTRACT

Accurate meiotic chromosome segregation critically depends on the formation of inter-homolog crossovers initiated by double-strand breaks (DSBs). Inaccuracies in this process can drive aneuploidy and developmental defects, but how meiotic cells are protected from unscheduled DNA breaks remains unexplored. Here we define a checkpoint response to persistent meiotic DSBs in C. elegans that phosphorylates the synaptonemal complex (SC) to switch repair partner from the homolog to the sister chromatid. A key target of this response is the core SC component SYP-1, which is phosphorylated in response to ionizing radiation (IR) or unrepaired meiotic DSBs. Failure to phosphorylate (syp-16A) or dephosphorylate (syp-16D) SYP-1 in response to DNA damage results in chromosome non-dysjunction, hyper-sensitivity to IR-induced DSBs, and synthetic lethality with loss of brc-1BRCA1. Since BRC-1 is required for inter-sister repair, these observations reveal that checkpoint-dependent SYP-1 phosphorylation safeguards the germline against persistent meiotic DSBs by channelling repair to the sister chromatid.


Subject(s)
Cell Cycle Checkpoints/genetics , DNA Breaks, Double-Stranded , DNA Damage/genetics , DNA-Binding Proteins/metabolism , Animals , Caenorhabditis elegans , Meiosis
11.
BJA Educ ; 19(6): 191-197, 2019 Jun.
Article in English | MEDLINE | ID: mdl-33456890
12.
BMC Public Health ; 18(1): 1300, 2018 Nov 27.
Article in English | MEDLINE | ID: mdl-30482163

ABSTRACT

BACKGROUND: Mass reach physical activity campaigns are designed to deliver physical-activity related messages to a large population across different media including print, television, radio, and websites. Few evaluations have examined the short-term effects of a mass reach campaign on participants who were engaged with the campaign. The current research examined the short-term effects of the ParticipACTION 150 Play List, a mass reach physical activity campaign, on participants who registered with the campaign website. METHODS: Participants (N = 7801) completed a registration questionnaire measuring demographic information, awareness and recall of physical activity and sport advertising, and self-reported number of activities tried or planned to try from the 150 Play List. A follow-up survey was completed by 1298 participants from the original sample. Additional questions assessed experience with the 150 Play List and attitudes towards campaign advertisements. RESULTS: Approximately 14.5% of participants cited the ParticipACTION 150 Play List and 23.6% mentioned a 'getting active' message when recalling advertisements. Those who named the 150 Play List or getting active reported more activities tried and more activities planned than those who did not. They were also more likely to say they had tried a new activity and planned ongoing participation. It was also found that participants with a disability were more likely to have tried a new activity compared to those not in a minority group. Other correlates of trying new activities at follow-up were younger age, more positive reported experience with the 150 Play List, and more favourable attitudes towards campaign advertisements. Those who did not intend continued participation, or who were unsure at baseline and then decided against continued participation at follow-up, reported they were less sedentary or encouraging others to be active. CONCLUSIONS: This research addresses the gap in evidence regarding the efficacy of mass reach physical activity campaigns by informing whether a year-long campaign like the 150 Play List can be effective in influencing the behavior of those engaged with the campaign. The results reinforce the idea that 'top of mind' awareness should be measured. Investigating intention profiles can help inform campaign impacts and continuation intentions.


Subject(s)
Advertising , Exercise , Health Promotion/methods , Mass Media , Adult , Awareness , Exercise/psychology , Female , Follow-Up Studies , Humans , Intention , Logistic Models , Male , Mental Recall , Middle Aged , Program Evaluation , Surveys and Questionnaires
13.
BMC Bioinformatics ; 19(Suppl 8): 211, 2018 06 13.
Article in English | MEDLINE | ID: mdl-29897319

ABSTRACT

BACKGROUND: Suicide is an alarming public health problem accounting for a considerable number of deaths each year worldwide. Many more individuals contemplate suicide. Understanding the attributes, characteristics, and exposures correlated with suicide remains an urgent and significant problem. As social networking sites have become more common, users have adopted these sites to talk about intensely personal topics, among them their thoughts about suicide. Such data has previously been evaluated by analyzing the language features of social media posts and using factors derived by domain experts to identify at-risk users. RESULTS: In this work, we automatically extract informal latent recurring topics of suicidal ideation found in social media posts. Our evaluation demonstrates that we are able to automatically reproduce many of the expertly determined risk factors for suicide. Moreover, we identify many informal latent topics related to suicide ideation such as concerns over health, work, self-image, and financial issues. CONCLUSIONS: These informal topics topics can be more specific or more general. Some of our topics express meaningful ideas not contained in the risk factors and some risk factors do not have complimentary latent topics. In short, our analysis of the latent topics extracted from social media containing suicidal ideations suggests that users of these systems express ideas that are complementary to the topics defined by experts but differ in their scope, focus, and precision of language.


Subject(s)
Information Storage and Retrieval , Internet , Social Media , Suicidal Ideation , Adolescent , Algorithms , Automation , Female , Humans , Language , Male , Middle Aged , Risk Factors
14.
Psychol Med ; 48(9): 1454-1463, 2018 07.
Article in English | MEDLINE | ID: mdl-28994360

ABSTRACT

BACKGROUND: Childhood trauma is a risk factor for psychosis. Deficits in response inhibition are common to psychosis and trauma-exposed populations, and associated brain functions may be affected by trauma exposure in psychotic disorders. We aimed to identify the influence of trauma-exposure on brain activation and functional connectivity during a response inhibition task. METHODS: We used functional magnetic resonance imaging to examine brain function within regions-of-interest [left and right inferior frontal gyrus (IFG), right dorsolateral prefrontal cortex, right supplementary motor area, right inferior parietal lobule and dorsal anterior cingulate cortex], during the performance of a Go/No-Go Flanker task, in 112 clinical cases with psychotic disorders and 53 healthy controls (HCs). Among the participants, 71 clinical cases and 21 HCs reported significant levels of childhood trauma exposure, while 41 clinical cases and 32 HCs did not. RESULTS: In the absence of effects on response inhibition performance, childhood trauma exposure was associated with increased activation in the left IFG, and increased connectivity between the left IFG seed region and the cerebellum and calcarine sulcus, in both cases and healthy individuals. There was no main effect of psychosis, and no trauma-by-psychosis interaction for any other region-of-interest. Within the clinical sample, the effects of trauma-exposure on the left IFG activation were mediated by symptom severity. CONCLUSIONS: Trauma-related increases in activation of the left IFG were not associated with performance differences, or dependent on clinical diagnostic status; increased IFG functionality may represent a compensatory (overactivation) mechanism required to exert adequate inhibitory control of the motor response.


Subject(s)
Child Abuse/psychology , Magnetic Resonance Imaging , Prefrontal Cortex/physiopathology , Psychotic Disorders/physiopathology , Adult , Brain Mapping , Case-Control Studies , Child , Female , Functional Laterality , Humans , Male , Middle Aged , Neural Pathways/physiopathology , Neuropsychological Tests
15.
Oncogene ; 36(34): 4943-4950, 2017 08 24.
Article in English | MEDLINE | ID: mdl-28436950

ABSTRACT

The MRN (MRE11-RAD50-NBS1) complex is essential for repair of DNA double-strand breaks and stalled replication forks. Mutations of the MRN complex subunit MRE11 cause the hereditary cancer-susceptibility disease ataxia-telangiectasia-like disorder (ATLD). Here we show that MRE11 directly interacts with PIH1D1, a subunit of heat-shock protein 90 cochaperone R2TP complex, which is required for the assembly of large protein complexes, such as RNA polymerase II, small nucleolar ribonucleoproteins and mammalian target of rapamycin complex 1. The MRE11-PIH1D1 interaction is dependent on casein kinase 2 (CK2) phosphorylation of two acidic sequences within the MRE11 C terminus containing serines 558/561 and 688/689. Conversely, the PIH1D1 phospho-binding domain PIH-N is required for association with MRE11 phosphorylated by CK2. Consistent with these findings, depletion of PIH1D1 resulted in MRE11 destabilization and affected DNA-damage repair processes dependent on MRE11. Additionally, mutations of serines 688/689, which abolish PIH1D1 binding, also resulted in decreased MRE11 stability. As depletion of R2TP frequently leads to instability of its substrates and as truncation mutation of MRE11 lacking serines 688/689 leads to decreased levels of the MRN complex both in ATLD patients and an ATLD mouse model, our results suggest that the MRN complex is a novel R2TP complex substrate and that their interaction is regulated by CK2 phosphorylation.


Subject(s)
Apoptosis Regulatory Proteins/metabolism , Casein Kinase II/metabolism , DNA-Binding Proteins/metabolism , Animals , Ataxia Telangiectasia/metabolism , Ataxia Telangiectasia Mutated Proteins/metabolism , Cell Nucleus/metabolism , DNA Damage/physiology , DNA Repair/physiology , DNA Repair Enzymes/metabolism , Heat-Shock Proteins/metabolism , Humans , Mice , Mutation/physiology , Nuclear Proteins/metabolism , Phosphorylation/physiology , Protein Binding/physiology , RNA Polymerase II/metabolism , Ribonucleoproteins, Small Nucleolar/metabolism , Serine/metabolism , TOR Serine-Threonine Kinases/metabolism
16.
Astrophys J Lett ; 806(1)2015 Jun 10.
Article in English | MEDLINE | ID: mdl-26722621

ABSTRACT

We report the discovery in space of a disilicon species, SiCSi, from observations between 80 and 350 GHz with the IRAM 30m radio telescope. Owing to the close coordination between laboratory experiments and astrophysics, 112 lines have now been detected in the carbon-rich star CW Leo. The derived frequencies yield improved rotational and centrifugal distortion constants up to sixth order. From the line profiles and interferometric maps with the Submillimeter Array, the bulk of the SiCSi emission arises from a region of 6″ in radius. The derived abundance is comparable to that of SiC2. As expected from chemical equilibrium calculations, SiCSi and SiC2 are the most abundant species harboring a Si-C bond in the dust formation zone and certainly both play a key role in the formation of SiC dust grains.

17.
J Chem Phys ; 141(4): 044310, 2014 Jul 28.
Article in English | MEDLINE | ID: mdl-25084913

ABSTRACT

The gas-phase optical spectra of three silicon-terminated carbon chain radicals, SiCnH (n = 3 - 5), formed in a jet-cooled discharge of silane and acetylene, have been investigated by resonant two-color two-photon ionization and laser-induced fluorescence/dispersed fluorescence. Analysis of the spectra was facilitated by calculations performed using equation-of-motion coupled cluster methods. For SiC3H and SiC5H, the observed transitions are well-described as excitations from a (2)Π ground state to a (2)Σ state, in which vibronic coupling, likely involving a higher-lying Π state with a very large predicted f-value (close to unity), is persistent. The lowest (2)Σ states of both species are characterized by a rare silicon triple bond, which was identified previously [T. C. Smith, H. Y. Li, D. J. Clouthier, C. T. Kingston, and A. J. Merer, J. Chem. Phys. 112, 3662 (2000)] in the lowest (2)Σ state of SiCH. Although a strong Π - Π transition is predicted for SiC4H, the observed spectrum near 505 nm more likely corresponds to excitation to a relatively dark Σ state which is vibronically coupled to a nearby Π state. In contrast to the chains with an odd number of carbon atoms, which exhibit relatively sharp spectral features and lifetimes in the 10-100 ns range, SiC4H shows intrinsically broadened spectral features consistent with a ∼100 fs lifetime, and a subsequent long-lived decay (>50 µs) which we ascribe to mixing with a nearby quartet state arising from the same electronic configuration. The spin-orbit coupling constants for both SiC3H and SiC5H radicals were determined to be approximately 64 cm(-1), similar to that of SiCH (69.8 cm(-1)), suggesting that the unpaired electron in these species is localized on the silicon atom. Motivated by the new optical work, the rotational spectrum of linear SiC3H was detected by cavity Fourier-transform microwave spectroscopy in the 13-34 GHz range. Each rotational transition from the [Formula: see text] ground state exhibits well-resolved Λ-doubling and hyperfine structure; the derived rotational constant of B = 2.605 GHz is in excellent agreement with our calculations.

18.
Br J Dermatol ; 167(5): 1032-6, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22709541

ABSTRACT

BACKGROUND: Rosacea is a chronic inflammatory condition that affects the skin of the face and the eyes. Erythematotelangiectatic rosacea is characterized by flushing, oedema and telangiectasia. Patients with rosacea demonstrate elevated densities of Demodex mites in their skin compared with controls. A bacterium (Bacillus oleronius) isolated from Demodex mites from a patient with papulopustular rosacea has been demonstrated to produce antigenic proteins that may play a role in papulopustular and ocular rosacea. OBJECTIVES: To establish whether there was a correlation between the reactivity of sera from patients with erythematotelangiectatic rosacea to Bacillus antigens, and to characterize the proteins to which these patients showed reactivity. METHODS: Serum samples from patients with erythematotelangiectatic rosacea and controls were examined for reactivity to Bacillus proteins by Western blot analysis. Proteins to which the sera reacted were excised from gels, trypsin digested, and putative identities were assigned following liquid chromatography-mass spectrometry (LC-MS) analysis. RESULTS: Eighty per cent (21/26) of patients with erythematotelangiectatic rosacea showed serum reactivity to the 62- and 83-kDa proteins of B. oleronius, compared with 40% (9/22) of controls (P = 0·004). The 62-kDa protein was characterized by LC-MS and showed homology to groEL chaperonin, which provokes a strong immune response in mammals. The 83-kDa protein showed homology to aconitate hydratase, of which expression is increased in bacteria under oxidative stress, and which is highly immunogenic. CONCLUSIONS: The majority of patients with erythematotelangiectatic rosacea show serum reactivity to two proteins from B. oleronius, suggesting that this bacterium may play a role in the induction of this condition. The two proteins to which patient sera reacted were found to be similar to a heat shock protein and an enzyme involved in regulating the stress response of the bacterium.


Subject(s)
Antigens, Bacterial/immunology , Bacillus/immunology , Bacterial Proteins/immunology , Mite Infestations/immunology , Mites/microbiology , Rosacea/immunology , Aconitate Hydratase/immunology , Adult , Aged , Aged, 80 and over , Animals , Bacillus/isolation & purification , Blotting, Western , Chaperonin 60/immunology , Chromatography, High Pressure Liquid/methods , Cross Reactions , Female , Humans , Male , Mass Spectrometry/methods , Middle Aged , Rosacea/microbiology , Young Adult
19.
J Chem Phys ; 136(19): 194307, 2012 May 21.
Article in English | MEDLINE | ID: mdl-22612095

ABSTRACT

We report the measurement of a jet-cooled electronic spectrum of the silicon trimer. Si(3) was produced in a pulsed discharge of silane in argon, and the excitation spectrum examined in the 18 000-20 800 cm(-1) region. A combination of resonant two-color two-photon ionization (R2C2PI) time-of-flight mass spectroscopy, laser-induced fluorescence/dispersed fluorescence, and equation-of-motion coupled-cluster calculations have been used to establish that the observed spectrum is dominated by the 1(3)A(1)" - ã (3)A(2)' transition of the D(3h) isomer. The spectrum has an origin transition at 18,600 ± 4 cm(-1) and a short progression in the symmetric stretch with a frequency of ∼445 cm(-1), in good agreement with a predicted vertical transition energy of 2.34 eV for excitation to the 1(3)A(1)" state, which has a calculated symmetric stretching frequency of 480 cm(-1). In addition, a ∼505 cm(-1) ground state vibrational frequency determined from sequence bands and dispersed fluorescence is in agreement with an earlier zero-electron kinetic energy study of the lowest D(3h) state and with theory. A weaker, overlapping band system with a ∼360 cm(-1) progression, observed in the same mass channel (m/z = 84) by R2C2PI but under different discharge conditions, is thought to be due to transitions from the (more complicated) singlet C(2v) ground state ((1)A(1)) state of Si(3). Evidence of emission to this latter state in the triplet dispersed fluorescence spectra suggests extensive mixing in the excited triplet and singlet manifolds. Prospects for further spectroscopic characterization of the singlet system and direct measurement of the energy separation between the lowest singlet and triplet states are discussed.

20.
Minerva Pediatr ; 64(1): 71-81, 2012 Feb.
Article in English | MEDLINE | ID: mdl-22350048

ABSTRACT

Celiac disease is an underdiagnosed condition in children with variable manifestations. Presenting symptoms in children are changing over time, are impacted by age and geography, and are distinct from those of adults with this disease. Prompt diagnosis of celiac disease in affected children may avoid growth and nutritional deficits in addition to preventing long term disease complications such as infertility and malignancy. Diagnosis and management of celiac disease in children requires expert medical and nutritional care to maximize positive outcomes.


Subject(s)
Celiac Disease , Celiac Disease/diagnosis , Celiac Disease/etiology , Celiac Disease/therapy , Child , Humans
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