bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mammalian Clusterin associated protein 1 is an evolutionarily conserved protein required for ciliogenesis
Authors: Pasek Raymond C , Berbari Nicolas F , Lewis Wesley R , Kesterson Robert A , Yoder Bradley K 
Published: November 2012

Abstract

Background
Clusterin associated protein 1 (CLUAP1) was initially characterized as a protein that interacts with clusterin, and whose gene is frequently upregulated in colon cancer. Although the consequences of these observations remain unclear, research of CLUAP1 homologs in C. elegans and zebrafish indicates that it is needed for cilia assembly and maintenance in these models. To begin evaluating whether Cluap1 has an evolutionarily conserved role in cilia in mammalian systems and to explore the association of Cluap1 with disease pathogenesis and developmental abnormalities, we generated Cluap1 mutant mice.

Methods

Cluap1 mutant embryos were generated and examined for gross morphological and anatomical defects using light microscopy. Reverse transcription PCR, β-galactosidase staining assays, and immunofluorescence analysis were used to determine the expression of the gene and localization of the protein in vivo and in cultured cell lines. We also used immunofluorescence analysis and qRT-PCR to examine defects in the Sonic hedgehog signaling pathway in mutant embryos.

Results

Cluap1 mutant embryos die in mid-gestation, indicating that it is necessary for proper development. Mutant phenotypes include a failure of embryonic turning, an enlarged pericardial sac, and defects in neural tube development. Consistent with the diverse phenotypes, Cluap1 is widely expressed. Furthermore, the Cluap1 protein localizes to primary cilia, and mutant embryos were found to lack cilia at embryonic day 9.5. The phenotypes observed in Cluap1 mutant mice are indicative of defects in Sonic hedgehog signaling. This was confirmed by analyzing hedgehog signaling activity in Cluap1 mutants, which revealed that the pathway is repressed.

Conclusions
These data indicate that the function of Cluap1 is evolutionarily conserved with regard to ciliogenesis. Further, the results implicate mammalian Cluap1 as a key regulator of hedgehog signaling and as an intraflagellar transport B complex protein. Future studies on mammalian Cluap1 utilizing this mouse model may provide insights into the role for Cluap1 in intraflagellar transport and the association with colon cancer and cystic kidney disorders.
Association between water related factors and active trachoma in Hai district, Northern Tanzania
Authors: Mahande Michael J , Mazigo Humphrey D , Kweka Eliningaya J 
Published: November 2012

Abstract

Background
Trachoma is widely distributed in sub-Saharan Africa and is mainly associated with poor water accessibility. However, these associations have never been demonstrated in some of the communities, especially in northern Tanzania. To cover that gap, the present case control study was conducted to assess the association of water related factors, general hygiene and active trachoma among preschool and school age children in Hai district, northern Tanzania.

Results
Families reported to use > 60 litres of water per day were less likely to have active disease (OR= 0.4, 95% CI: 0.1 - 0.3; P<0.001) compared to households collecting ≤ 60 litres. The risk of having trachoma increased with increase in distance to the water point (OR= 6.5, 95% CI; 1.8 - 16.7; P= 0.003). Households members who reported to use < 2 liters of water for face washing were more likely to be trachomatous (OR= 5.12, 95% CI: 1.87-14.6, P = 0.001). Increased number of preschool children in the household was also associated with increased risk of active trachoma by 2.46 folds.

Conclusions
Improving water supply near the households and providing public health education focusing on improving households socio-economic status and individual hygiene especially in pre-school children in part will help to reduce the prevalence of the disease. In addition, integrating public health education with other interventions such as medical interventions remains important.
A sensitive method for rapid detection of alkyl halides and dehalogenase activity using a multistep enzyme assay
Authors: Fabritz Sebastian , Maaß Franziska , Avrutina Olga , Heiseler Tim , Steinmann Björn , Kolmar Harald 
Published: November 2012

Abstract
A method for the detection of haloalkane conversion to the corresponding alcohols by haloalkane dehalogenases is described. It is based on a multistage enzyme reaction which allows for the analysis of alkyl halides in buffered systems. Irreversible hydrolytic dehalogenation catalyzed by haloalkane dehalogenase DhaA from Rhodococcus erythropolis transfers an alkyl halide into a corresponding alcohol that is further oxidized by alcohol oxidase AOX from Pichia pastoris yielding a respective aldehyde and hydrogen peroxide easily detectable via the horseradish peroxidase catalyzed oxidation of chromogenic molecules. Due to its high sensitivity (0.025 mM, 0.43 ppm for 1,3-dibromopropane), low expenditure and the ability of handling a large number of samples in parallel, this method is an attractive alternative to existing procedures for the monitoring of both haloalkanes and dehalogenases.
Acute exercise exacerbates ischemia-induced diastolic rigor in hypertensive myocardium
Authors: Reger Patricia O , Kolwicz Stephen C , Libonati Joseph R 
Published: November 2012

Abstract
Previous studies have shown that acute exercise preconditions the myocardium from ischemic injury. The purpose of this study was to test whether acute exercise protects the hypertensive myocardium from ischemia-induced diastolic rigor, and to compare the response between normotensive and uncompensated hypertensive hearts. Hearts harvested from female Wistar-Kyoto (WKY; n = 24) and spontaneously hypertensive rats (SHR; n = 27) (age:10–12 weeks) were exposed to ischemia (Langendorff isovolumic preparation; 22 minutes of no flow ischemia and studied following prior conditions of: 1) no exercise (WKY-CON, n=8; SHR-CON, n=8); 2) ischemia initiated one hour post-acute exercise (WKY-1HR, n = 8; SHR-1HR, n = 11); and 3) ischemia initiated 24 hours post-acute exercise (WKY-24HR; n = 8; SHR-24HR, n = 8). Acute exercise consisted of one bout of treadmill running at 25 m/min for 60 minutes. Heart weight was similar between WKY and SHR despite elevated in vivo resting systolic blood pressure and rate pressure product in SHR (P<0.05). During normoxic perfusion, left ventricular (LV) Langendorff performance was similar between WKY and SHR over the post-exercise time course. However, during ischemia, LV diastolic rigor was less in WKY vs. SHR (P<0.05). Acute exercise augmented ischemia-induced LV dysfunction one hour post-exercise in SHR (P<0.05), with gradual recovery by 24 hours post-exercise. These data suggest that acute exercise promotes ischemic diastolic rigor in SHR, even prior to the development of cardiac hypertrophy.
Deletion of interferon-γ delays onset and severity of dacryoadenitis in CD25KO mice
Authors: Pelegrino Flavia SA , Volpe Eugene A , Gandhi Niral B , Li De-Quan , Pflugfelder Stephen C , de Paiva Cintia S 
Published: November 2012

Abstract
Introduction
To investigate the role of interferon-gamma (IFN-γ) in the onset and severity of dacryoadenitis in the CD25 knockout (KO) mouse model of Sjögren Syndrome.

Methods
CD25/IFN-γ double KO (γDKO) mice were created by crossbreeding CD25KO and IFN-γKO mice. Mice were used at 8, 12, and 16 weeks. Lacrimal gland (LG) infiltrating lymphocytes were characterized with flow cytometry. Tear epidermal growth factor (EGF) concentration was measured with enzyme-linked immunosorbent assay (ELISA). Quantitative polymerase chain reaction (PCR) evaluated T-cell-related cytokines in LGs. Serum autoantibodies against M3R in LG lysates were detected with Western blot.

Results
γDKO LG showed lower lymphocytic infiltration at 8 weeks than in the CD25KO parental strain (˜20% versus ˜60%, respectively), which increased to CD25KO levels at 16 weeks. Flow-cytometry analysis showed an increase in CD4+ and CD8+ T cells with aging in γDKO LG, similar to that in CD25KO. γDKO had lower levels of interleukin (IL)-17A, transforming growth-factor (TGF)-β1, IL-21, and CCL20, and higher IL-1β and IL-13 mRNA transcripts in the LG than in the parental CD25KO strain. Autoantibodies to M3R were observed in both strains and significantly increased with aging in both strains. CD25KO mice had very low tear EGF concentrations at all ages, whereas the ear EGF concentration in γDKO mice significantly decreased with aging and inversely correlated with the presence of M3R autoantibodies and the degree of LG CD4 and CD8+ T-cell infiltration.

Conclusions
The deletion of IFN-γ in the CD25KO mice strain delays glandular destruction and preserves glandular function. M3R autoantibodies increased with aging in both the γDKO and the CD25KO strains. The decrease in LG function in γDKO correlated with the degree of T-cell infiltration and the presence of M3R autoantibodies.
Y27, a novel derivative of 4-hydroxyquinoline-3-formamide, prevents the development of murine systemic lupus erythematosus-like diseases in MRL/lpr autoimmune mice and BDF1 hybrid mice
Authors: Xiao Zhi-Yong , Chen Shao-Hui , Cheng Jun-Ping , Zhou Wen-Xia , Zhang Yong-Xiang , Yang Ri-Fang , Yun Liu-Hong 
Published: November 2012

Abstract
Introduction
Naturally occurring CD4+CD25+ regulatory T (Treg) cells are central to the maintenance of peripheral tolerance. Impaired activity and/or a lower frequency of these cells lead to systemic lupus erythematosus (SLE). Manipulating the number or activity of Treg cells is to be a promising strategy in treating it and other autoimmune diseases. We have examined the effects of Y27, a novel derivative of 4-hydroxyquinoline-3-formamide, on SLE-like symptoms in MRL/lpr autoimmune mice and BDF1 hybrid mice. Whether the beneficial effect of Y27 involves modulation of CD4+CD25+ Treg cells has also been investigated.

Methods
Female MRL/lpr mice that spontaneously develop lupus were treated orally by gavage with Y27 for 10 weeks, starting at 10 weeks of age. BDF1 mice developed a chronic graft-versus-host disease (GVHD) by two weekly intravenous injections of parental female DBA/2 splenic lymphocytes, characterized by immunocomplex-mediated glomerulonephritis resembling SLE. Y27 was administered to chronic GVHD mice for 12 weeks. Nephritic symptoms were monitored and the percentage of CD4+CD25+FoxP3+ Treg peripheral blood leukocyte was detected with mouse regulatory T cell staining kit by flowcytometry. Purified CD4+CD25+ Tregs were assessed for immune suppressive activity using the mixed lymphocyte reaction.

Results
The life-span of MRL/lpr mice treated with Y27 for 10 weeks was significantly prolonged, proteinuria and renal lesion severity were ameliorated, and blood urea nitrogen, triglyceride and serum anti-double-stranded DNA antibodies were decreased. Similar results were found in chronic GVHD mice. Administration of Y27 had little impact on percentage of the peripheral blood lymphocyte CD4+CD25+Foxp3+ Treg cells in both groups of mice. In contrast, the suppressive capacity of CD4+CD25+ Treg cells in splenocytes was markedly augmented in Y27-treated mice ex vivo.

Conclusions
Experimental evidence of the protect effects of Y27 against autoimmune nephritis has been shown. The mechanism may involve enhancement of the suppressive capacity of CD4+CD25+ Treg cells.
Systems analysis of primary Sjögren's syndrome pathogenesis in salivary glands identifies shared pathways in human and a mouse model
Authors: Horvath Steve , Nazmul-Hossain Abu NM , Pollard Rodney PE , Kroese Frans GM , Vissink Arjan , Kallenberg Cees GM , Spijkervet Fred KL , Bootsma Hendrika , Michie Sara A , Gorr Sven U , Peck Ammon B , Cai Chaochao , Zhou Hui , Wong David TW 
Published: November 2012

Abstract
Introduction
Primary Sjögren's syndrome (pSS) is a chronic autoimmune disease with complex etiopathogenesis. Despite extensive studies to understand the disease process utilizing human and mouse models, the intersection between these species remains elusive. To address this gap, we utilized a novel systems biology approach to identify disease-related gene modules and signaling pathways that overlap between humans and mice.

Methods
Parotid gland tissues were harvested from 24 pSS and 16 non-pSS sicca patients and 25 controls. For mouse studies, salivary glands were harvested from C57BL/6.NOD-Aec1Aec2 mice at various times during development of pSS-like disease. RNA was analyzed with Affymetrix HG U133+2.0 arrays for human samples and with MOE430+2.0 arrays for mouse samples. The images were processed with Affymetrix software. Weighted-gene co-expression network analysis was used to identify disease-related and functional pathways.

Results
Nineteen co-expression modules were identified in human parotid tissue, of which four were significantly upregulated and three were downregulated in pSS patients compared with non-pSS sicca patients and controls. Notably, one of the human disease-related modules was highly preserved in the mouse model, and was enriched with genes involved in immune and inflammatory responses. Further comparison between these two species led to the identification of genes associated with leukocyte recruitment and germinal center formation.

Conclusion
Our systems biology analysis of genome-wide expression data from salivary gland tissue of pSS patients and from a pSS mouse model identified common dysregulated biological pathways and molecular targets underlying critical molecular alterations in pSS pathogenesis.
Triple-negative breast cancer and PTEN (phosphatase and tensin homologue)loss are predictors of BRCA1 germline mutations in women with early-onset and familial breast cancer, but not in women with isolated late-onset breast cancer
Authors: Phuah Sze-Yee , Looi Lai-Meng , Hassan Norhashimah , Rhodes Anthony , Dean Sarah , Taib Nur Aishah Mohd , Yip Cheng-Har , Teo Soo-Hwang 
Published: November 2012

Abstract
Introduction
Given that breast cancers in germline BRCA1 carriers are predominantly estrogen-negative and triple-negative, it has been suggested that women diagnosed with triple-negative breast cancer (TNBC) younger than 50 years should be offered BRCA1 testing, regardless of family cancer characteristics. However, the predictive value of triple-negative breast cancer, when taken in the context of personal and family cancer characteristics, is unknown. The aim of this study was to determine whether TNBC is a predictor of germline BRCA1 mutations, in the context of multiple predictive factors.

Methods
Germline mutations in BRCA1 and BRCA2 were analyzed by Sanger sequencing and multiple ligation-dependent probe amplification (MLPA) analysis in 431 women from the Malaysian Breast Cancer Genetic Study, including 110 women with TNBC. Logistic regression was used to identify and to estimate the predictive strength of major determinants. Estrogen receptor (ER) and phosphatase and tensin homologue (PTEN) status were assessed and included in a modified Manchester scoring method.

Results
Our study in an Asian series of TNBC patients demonstrated that 27 (24.5%) of 110 patients have germline mutations in BRCA1 (23 of 110) and BRCA2 (four of 110). We found that among women diagnosed with breast cancer aged 36 to 50 years but with no family history of breast or ovarian cancer, the prevalence of BRCA1 and BRCA2 mutations was similar in TNBC (8.5%) and non-TNBC patients (6.7%). By contrast, in women diagnosed with breast cancer, younger than 35 years, with no family history of these cancers, and in women with a family history of breast cancer, the prevalence of mutations was higher in TNBC compared with non-TNBC (28.0% and 9.9%; P = 0.045; and 42.1% and 14.2%; P < 0.0001, respectively]. Finally, we found that incorporation of estrogen-receptor and TNBC status improves the sensitivity of the Manchester Scoring method (42.9% to 64.3%), and furthermore, incorporation of PTEN status further improves sensitivity (42.9% to 85.7%).

Conclusions
We found that TNBC is an important criterion for highlighting women who may benefit from genetic testing, but that this may be most useful for women with early-onset breast cancer (35 years or younger) or with a family history of cancers. Furthermore, addition of TNBC and PTEN status improves the sensitivity of the Manchester scoring method and may be particularly important in the Asian context, where risk-assessment models underestimate the number of mutation carriers.
Good (or bad) vibrations: clinical intuition in violence risk assessment
Authors: Carroll Andrew 
Published: November 2012

SummaryAssessment and management of the risk of violence in psychiatry inevitably and appropriately draws on emotionally laden ‘intuitive’ modes of thought, as well as deliberative analytic thinking. This article discusses the concept of ‘intuition’ and proposes a brief set of guidelines, derived from work by the cognitive psychologist Robin Hogarth, by which intuitive thinking may be applied by clinicians when undertaking risk assessment work. The guidelines are: consider the learning structure relevant to the risk assessment task; use your own emotions as a source of data; impose ‘circuit breakers' such as cost–benefit analyses and validated structured risk assessment tools; and use a narrative approach to develop formulations. The guidelines are intended to provide a framework for ongoing reflective practice in assessing and managing risk.
Patient experience and psychiatric discourse
Authors: Jacob K. S. 
Published: November 2012

SummaryLanguage, concepts and frameworks employed by psychiatrists contrast starkly to those held by patients. Despite the fact that the battle to understand patient experience was won long ago, current biomedical approaches and the DSM culture prevent such understanding. Positioning patient narratives in the foreground will help translate experience, provide legitimate frameworks, create common language and interface for communication, offer powerful insights, influence clinical practice and have an impact on psychiatric theory.
The Health and Social Care Act 2012: what will it mean for mental health services in England?
Authors: Holloway Frank 
Published: November 2012

SummaryThe Health and Social Care Act 2012 brings in profound changes to the organisation of healthcare in England. These changes are briefly described and their implications for mental health services are explored. They occur as the National Health Service (NHS) and social care are experiencing significant financial cuts, the payment by results regime is being introduced for mental health and the NHS is pursuing the personalisation agenda. Psychiatrists have an opportunity to influence the commissioning of mental health services if they understand the organisational changes and work within the new commissioning structures.
Corticotropin-Releasing Factor Receptor Binding in the Amygdala Changes Across Puberty in a Sex-Specific Manner
Authors: Weathington Jill M. , Cooke Bradley M. 
Published: November 2012

Abstract
Corticotropin-releasing factor receptors type 1 (CRF1) and type 2 (CRF2) have complementary roles in controlling the hypothalamic-pituitary-adrenal (HPA) axis. Because CRF receptors are expressed in sex steroid-sensitive areas of the forebrain, they may contribute to sex-specific patterns of stress sensitivity and susceptibility to stress-related mood disorders, which are more frequent in women. To determine whether CRF receptors vary as a function of age and/or sex, we measured receptor binding in the amygdala of male and female, prepubertal and adult rats. Both receptor subtypes demonstrated age- and sex-specific binding patterns. In the basolateral amygdala and posteroventral medial amygdala, CRF1 binding decreased in males and increased in females after puberty, there, CRF2 binding increased in males and was unchanged in females. In the posterodorsal medial amygdala, CRF1 binding was unchanged across puberty, whereas CRF2 binding increased across puberty far more in males than in females. Binding was lowest overall in the central amygdala; there, CRF1 was unchanged while CRF2 binding increased across puberty only in males. Thus, in all four examined areas across prepuberty to adulthood, CRF2 binding increased far more in males than in females and resulted in significantly more binding in adult males than in adult females. These sex-specific developmental patterns are consistent with sex differences in hypothalamic-pituitary-adrenal responsiveness and may thus contribute to sex differences in mood disorder susceptibility.
Social status-dependent modulation of LG-flip habituation in the crayfish
Authors: Araki Makoto , Hasegawa Takuya , Komatsuda Shohei , Nagayama Toshiki 
Published: November 2012

SummaryStrong stimuli applied to tailfan of the crayfish Procambarus clarkii (Girard) evoked lateral giant (LG) mediated tailflips. When the sensory stimulus was applied repeatedly, the response of LG habituated until it failed to give rise to a spike. We found that this LG-flip habituation was dependent on social-status. With a short interstimulus interval of 5 s, the rate of habituation of the LG in both socially dominant and subordinate crayfish was less than in socially isolated animals. By contrast, with a long interstimulus interval of 60 s, the rate of habituation of subordinate animals was less than both socially isolated and dominant animals. The excitability of the LGs following habituation was also dependent on social status. Following habituation the spike response of LGs recovered within several minutes, however they showed significant depression with a decrease in excitability. With a 5 s or 60 s interstimulus interval, subordinate animals showed longer delays of depression compared to dominant animals. A decrease in the rate of habituation and a delay of depression in subordinate crayfish would be advantageous to maintain an active escape response to evade repeated attacks of dominant animals and a reduced learning ability to adapt to social status.