Background
Angelman syndrome (AS) is a neurogenetic disorder that causes severe intellectual disability, expressive language deficits, motor impairment, ataxia, sleep problems, epileptic seizures and ...a happy disposition. People with AS frequently experience gastrointestinal (GI) symptoms.
Method
This study used data from the Global Angelman Syndrome Registry to explore the relationship between early and current GI symptoms and co‐morbidity in children and adolescents with AS (n = 173). Two groups that experienced a high (n = 91) and a low (n = 82) frequency of GI symptoms were examined in relation to feeding and GI history in infancy, sleep and toileting problems, levels of language and communication and challenging behaviours. Predictors of GI symptoms were then investigated using a series of logistic regressions.
Results
This analysis found that constipation and gastroesophageal reflux affected 84% and 64%, of the sample, respectively. The high frequency of GI symptoms were significantly associated with: ‘refusal to nurse’, ‘vomiting’, ‘arching’, ‘difficulty gaining weight’, gastroesophageal reflux, ‘solid food transition’, frequency of night‐time urinary continence and sleep hyperhidrosis during infancy. GI symptoms were not significantly associated with sleep, toileting, language or challenging behaviours. Significant predictors of high frequency GI symptoms were gastroesophageal reflux and sleep hyperhidrosis.
Conclusions
Future research needs to investigate the association between AS and GI co‐morbidity in adults with AS.
Endosymbiotic bacteria were identified in the parasitic ciliate Ichthyophthirius multifiliis, a common pathogen of freshwater fish. PCR amplification of DNA prepared from two isolates of I. ...multifiliis, using primers that bind conserved sequences in bacterial 16S rRNA genes, generated an ~1,460-bp DNA product, which was cloned and sequenced. Sequence analysis demonstrated that 16S rRNA gene sequences from three classes of bacteria were present in the PCR product. These included Alphaproteobacteria (Rickettsiales), Sphingobacteria, and Flavobacterium columnare. DAPI (4',6-diamidino-2-phenylindole) staining showed endosymbionts dispersed throughout the cytoplasm of trophonts and, in most, but not all theronts. Endosymbionts were observed by transmission electron microscopy in the cytoplasm, surrounded by a prominent, electron-translucent halo characteristic of RICKETTSIA: Fluorescence in situ hybridization demonstrated that bacteria from the Rickettsiales and Sphingobacteriales classes are endosymbionts of I. multifiliis, found in the cytoplasm, but not in the macronucleus or micronucleus. In contrast, F. columnare was not detected by fluorescence in situ hybridization. It likely adheres to I. multifiliis through association with cilia. The role that endosymbiotic bacteria play in the life history of I. multifiliis is not known.
Ankylosing spondylitis (AS) is a common and highly heritable inflammatory arthropathy. Although the gene
HLA-B27 is almost essential for the inheritance of the condition, it alone is not sufficient ...to explain the pattern of familial recurrence of the disease. We have previously demonstrated suggestive linkage of AS to chromosome 2q13, a region containing the interleukin 1 (IL-1) family gene cluster, which includes several strong candidates for involvement in the disease. In the current study, we describe strong association and transmission of IL-1 family gene cluster single-nucleotide polymorphisms and haplotypes with AS.
The Hurst exponent of Fermi gamma-ray bursts MacLachlan, G. A.; Shenoy, A.; Sonbas, E. ...
Monthly Notices of the Royal Astronomical Society,
12/2013, Letnik:
436, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Using a wavelet decomposition technique, we have extracted the Hurst exponent for a sample of 46 long and 22 short gamma-ray bursts (GRBs) detected by the Gamma-ray Burst Monitor aboard the Fermi ...satellite. This exponent is a scaling parameter that provides a measure of long-range behaviour in a time series. The mean Hurst exponent for the short GRBs is significantly smaller than that for the long GRBs. The separation may serve as an unbiased criterion for distinguishing short and long GRBs. PUBLICATION ABSTRACT
Histone H3 lysine 9 methylation Me(Lys9)H3 is an epigenetic mark for heterochromatin-dependent gene silencing, mediated by direct binding to chromodomain-containing proteins such as Heterochromatin ...Protein 1. In the ciliate
Tetrahymena, two chromodomain proteins, Pdd1p and Pdd3p, are involved in the massive programmed DNA elimination that accompanies macronuclear development. We report that both proteins bind H3(Lys9)Me in vitro. In vivo, H3(Lys9)Me is confined to the time period and location where DNA elimination occurs, and associates with eliminated sequences. Loss of parental Pdd1p expression drastically reduces H3(Lys9)Me. Finally, tethering Pdd1p is sufficient to promote DNA excision. These results extend the range of H3(Lys9)Me involvement in chromatin activities outside transcriptional regulation and also strengthen the link between heterochromatin formation and programmed DNA elimination.
Veterans make up a quarter of the deaths in the United States (US). However, little is known about their knowledge and preferences about end-of-life care and pain management. Given this, we were ...interested in how veterans’ military experiences impact their end-of-life experiences and attitudes. Our exploratory study addressed the knowledge and perceptions of hospice and pain management at the end of life. The quantitative aspect was a survey using descriptive statistics that used a small (n = 14) subgroup from a randomly selected sample in the continental US. A small population-based sample (N = 123) used a blended sampling frame of randomly selected validated cell phone and landline numbers. The qualitative aspect examined eight targeted interviews of urban dwelling older veterans over age 60 residing in Northeast Ohio to get a deeper understanding of their knowledge and attitudes toward end-of-life care. Our findings suggest that veterans did not understand the difference between hospice and palliative care and expressed concerns regarding pain medication use at the end of life. Future research examining the concept of stoicism at the end of life among veterans and educational interventions are needed.
Objectives
To evaluate the effect of tartaric acid (TTA) on Madin–Darby canine kidney (MDCK) cells compared to human kidney (HK)‐2 cells. Secondarily, to evaluate the effects of probenecid, an ...organic anion transporter (OAT)‐1 inhibitor, as well as human (h)OAT‐4 transfection into MDCK cells to prevent TTA‐induced cytotoxicity through decreasing accumulation via OAT‐1 uptake inhibition or increasing OAT‐4‐mediated TTA efflux.
Design
Seventy‐two‐hour TTA concentration response and inhibitor studies in immortalized cell lines.
Setting
School of Pharmacy biomedical research laboratory and tissue culture facility.
Animals/Samples
MDCK and HK‐2 immortalized cell lines.
Interventions
Both cell lines were treated with increasing concentrations of TTA for 72 hours. Additionally, MDCK cells were co‐incubated with TTA and increasing concentrations of probenecid or had been transfected with hOAT‐4 and subsequently treated with TTA for 72 hours.
Measurements and Main Results
Media and samples were collected and lactate dehydrogenase (LDH) release was measured. LDH release was measured to assess TTA‐induced cytotoxicity after 72 hours. LDH was not significantly increased in the HK‐2 cells at any concentration but was significantly increased in the MDCK cells from 10 to 100 mM. LDH concentrations were significantly decreased (61%) in MDCK cells incubated with 50 mM TTA and probenecid when compared to TTA alone. hOAT‐4 MDCK cell transfection also significantly reduced LDH release (57%) when comparing the transfected MDCK cells to the nontransfected MDCK cells treated with 50 mM TTA.
Conclusions
TTA is a species‐specific nephrotoxicant in dogs due to an interspecies difference in OAT‐4 expression. Inhibiting TTA uptake in MDCK cells in vitro using the OAT‐specific inhibitor, probenecid, prevents TTA‐induced cytotoxicity.
I revisit Rittel and Weber's essay on the ‘wicked problem,’ and relate it to more recent theories about rationality and professionalism. Perhaps the most provocative challenge comes from Deleuze and ...Guattari's difficult commentary on ‘the rhizome,’ which has currency within much design studio culture. I posit the controversial conclusion that ‘wickedness’ is not aberrant. It is formulations of professionalism which pay homage to the idea of formal rules, goal setting, and calculation as representing the norm of rationality, that present as deviations.
Two key features of myeloma cells are the deregulation of the cell cycle and the dependency on the expression of the BCL2 family of anti-apoptotic proteins. The cell division cycle 7 (CDC7) is an ...essential S-phase kinase and emerging CDC7 inhibitors are effective in a variety of preclinical cancer models. These compounds also inhibit CDK9 which is relevant for MCL-1 expression. The activity and mechanism of action of the dual CDC7/CDK9 inhibitor PHA-767491 was assessed in a panel of multiple myeloma cell lines, in primary samples from patients, in the presence of stromal cells and in combination with drugs used in current chemotherapeutic regimens. We report that in all conditions myeloma cells undergo cell death upon PHA-767491 treatment and we report an overall additive effect with melphalan, bortezomib and doxorubicin, thus supporting further assessment of targeting CDC7 and CDK9 in multiple myeloma.
Hereditary transthyretin-mediated amyloidosis (hATTR) is challenging to diagnose early owing to the heterogeneity of clinical presentation, which differs according to the
TTR
gene variant and its ...penetrance in each individual. The TTR variants seen most frequently in the UK and Ireland (T80A, V142I and V50M) differ to those commonly occurring in other geographic locations and warrant a specific consideration for diagnosis and genetic testing. In addition, recent availability of treatment for this condition has reinforced the need for a more consistent approach to the management of patients, including access to specialist services, genetic testing and counselling, and clinical investigation for families living in the UK and Ireland. A multidisciplinary panel of experts from the UK and Ireland was convened to identify the current challenges, provide recommendations, and develop a consensus for the diagnosis and screening of people with, or at risk of, hATTR. Over a series of meetings, experts shared their current practices and drafted, refined and approved a consensus statement. This consensus statement provides recommendations for three different groups: (1) people with symptoms raising a possibility of hATTR amyloidosis; (2) people with biopsy-confirmed hATTR amyloidosis; and (3) people without symptoms who may have hATTR amyloidosis (i.e. relatives of people with identified TTR variants). For each group, recommendations are made for the required steps for the diagnosis and follow-up of symptomatic patients, and for guidance on the specialist support for counselling and pre-symptomatic genetic testing of at-risk individuals. This guidance is intended to be practical and based on available evidence. The aim is for regional amyloid specialist centres to provide timely diagnosis, clinical screening, and treatment for individuals and their families with hATTR amyloidosis.
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