bluuebunny/crossref_metadata_2025 huggingface dataset:
Workplace Practices for Retaining Older Hospital Nurses: Implications From a Study of Nurses With Eldercare Responsibilities
Authors: Rosenfeld Peri
Published: July 2007

Attempts to address the nursing shortage must consider the aging nursing supply and the decreased labor participation among nurses at age 55 and older. Efforts to retain older, experienced nurses have been meager, and little attention is paid to the role of eldercare in decisions to leave the profession. This pilot study examines current workplace practices that may contribute to early withdrawal of older nurses from the hospital workforce. Interviews with 28 elder caregiving registered nurses and assistive nursing personnel at a New York hospital were conducted. Respondents reported that successful management of their dual roles rests on identifying units and shifts that suit their needs, erecting clear boundaries between home and work, and their love of nursing. “Caregiver-friendly” practices such as creative, flexible scheduling; access to social workers; financial and legal services; and increased awareness among managers about caregiver strains were recommended.
Work Attitudes of Older RNs
Authors: Kovner Christine T. , Brewer Carol S. , Ying Cheng  , Djukic Maja
Published: July 2007

Using data collected from 1,906 RNs from Metropolitan Statistical Areas in 29 states, the purpose of this study was to examine the characteristics and work attitudes of older RNs compared to RNs less than age 50 at two time periods, and compare among the older RNs those who are working in nursing, working outside nursing, and not working. Older RNs reported more distributive justice (fairness of rewards), work group cohesion, and supervisory support and less organizational constraint, and quantitative workload than younger RNs. Overall, older RNs were more satisfied, had greater organizational commitment, and had less desire to quit than younger RNs. There were no significant differences between older and younger RNs for autonomy, mentor support, or variety. Strategic efforts by employers and government could be used to retain older workers, attract RNs working in nonnursing settings back into nursing, and recruit retired RNs into the nursing workforce.
Characterization and expression patterns of let-7 microRNA in the silkworm (Bombyx mori)
Authors: Liu Shiping , Xia Qingyou , Zhao Ping , Cheng Tingcai , Hong Kaili , Xiang Zhonghuai
Published: July 2007

Background

lin-4 and let-7, the two founding members of heterochronic microRNA genes, are firstly confirmed in Caenorhabditis elegans to control the proper timing of developmental programs in a heterochronic pathway. let-7 has been thought to trigger the onset of adulthood across animal phyla. Ecdysone and Broad-Complex are required for the temporal expression of let-7 in Drosophila melanogaster. For a better understanding of the conservation and functions of let-7, we seek to explore how it is expressed in the silkworm (Bombyx mori).

Results

One member of let-7 family has been identified in silkworm computationally and experimentally. All known members of this family share the same nucleotides at ten positions within the mature sequences. Sequence logo and phylogenetic tree show that they are not only conserved but diversify to some extent among some species. The bmo-let-7 was very lowly expressed in ova harvested from newborn unmated female adult and in individuals from the first molt to the early third instar, highly expressed after the third molt, and the most abundant expression was observed after mounting, particularly after pupation. The expression levels were higher at the end of each instar and at the beginning of each molt than at other periods, coinciding with the pulse of ecdysone and BR-C as a whole. Using cultured ovary cell line, BmN-SWU1, we examined the effect of altered ecdysone levels on bmo-let-7 expression. The expression was also detected in various tissues of day 3 of the fifth instar and of from day 7 of the fifth to pupa, suggesting a wide distributing pattern with various signal intensities.

Conclusion

bmo-let-7 is stage- and tissue-specifically expressed in the silkworm. Although no signals were detected during embryonic development and first larval instar stages, the expression of bmo-let-7 was observed from the first molt, suggesting that it might also function at early larval stage of the silkworm. The detailed expression profiles in the whole life cycle and cultured cell line of silkworm showed a clear association with ecdysone pulse and a variety of biological processes.
TrED: the Trichophyton rubrum Expression Database
Authors: Yang Jian , Chen Lihong , Wang Lingling , Zhang Wenliang , Liu Tao , Jin Qi
Published: July 2007

Background

Trichophyton rubrumis the most common dermatophyte species and the most frequent cause of fungal skin infections in humans worldwide. It's a major concern because feet and nail infections caused by this organism is extremely difficult to cure. A large set of expression data including expressed sequence tags (ESTs) and transcriptional profiles of this important fungal pathogen are now available. Careful analysis of these data can give valuable information about potential virulence factors, antigens and novel metabolic pathways. We intend to create an integrated database TrED to facilitate the study of dermatophytes, and enhance the development of effective diagnostic and treatment strategies.

Description

All publicly available ESTs and expression profiles ofT. rubrumduring conidial germination in time-course experiments and challenged with antifungal agents are deposited in the database. In addition, comparative genomics hybridization results of 22 dermatophytic fungi strains from three genera,Trichophyton,MicrosporumandEpidermophyton, are also included. ESTs are clustered and assembled to elongate the sequence length and abate redundancy. TrED provides functional analysis based on GenBank, Pfam, and KOG databases, along with KEGG pathway and GO vocabulary. It is integrated with a suite of custom web-based tools that facilitate querying and retrieving various EST properties, visualization and comparison of transcriptional profiles, and sequence-similarity searching by BLAST.

Conclusion

TrED is built upon a relational database, with a web interface offering analytic functions, to provide integrated access to various expression data ofT. rubrumand comparative results of dermatophytes. It is devoted to be a comprehensive resource and platform to assist functional genomic studies in dermatophytes. TrED is available from URL:http://www.mgc.ac.cn/TrED/.
Genomic organization of duplicated major histocompatibility complex class I regions in Atlantic salmon (Salmo salar)
Authors: Lukacs Morten F , Harstad Håvard , Grimholt Unni , Beetz-Sargent Marianne , Cooper Glenn A , Reid Linda , Bakke Hege G , Phillips Ruth B , Miller Kristina M , Davidson William S , Koop Ben F
Published: July 2007

Background

We have previously identified associations between major histocompatibility complex (MHC) class I and resistance towards bacterial and viral pathogens in Atlantic salmon. To evaluate if only MHC or also closely linked genes contributed to the observed resistance we ventured into sequencing of the duplicated MHC class I regions of Atlantic salmon.

Results

Nine BACs covering more than 500 kb of the two duplicated MHC class I regions of Atlantic salmon were sequenced and the gene organizations characterized. Both regions contained the proteasome components PSMB8, PSMB9, PSMB9-like and PSMB10 in addition to the transporter for antigen processing TAP2, as well as genes for KIFC1, ZBTB22, DAXX, TAPBP, BRD2, COL11A2, RXRB and SLC39A7. The IA region contained the recently reported MHC class ISasa-ULAlocus residing approximately 50 kb upstream of the majorSasa-UBAlocus. The duplicated class IB region contained an MHC class I locus resembling the rainbow troutUCAlocus, but although transcribed it was a pseudogene. No other MHC class I-like genes were detected in the two duplicated regions. Two allelic BACs spanning theUBAlocus had 99.2% identity over 125 kb, while the IA region showed 82.5% identity over 136 kb to the IB region. The Atlantic salmon IB region had an insert of 220 kb in comparison to the IA region containing three chitin synthase genes.

Conclusion

We have characterized the gene organization of more than 500 kb of the two duplicated MHC class I regions in Atlantic salmon. Although Atlantic salmon and rainbow trout are closely related, the gene organization of their IB region has undergone extensive gene rearrangements. The Atlantic salmon has only one class IUCApseudogene in the IB region while trout contains the four MHCUCA,UDA,UEAandUFAclass I loci. The large differences in gene content and most likely function of the salmon and trout class IB region clearly argues that sequencing of salmon will not necessarily provide information relevant for trout and vice versa.
Favorable prognostic value of SOCS2 and IGF-I in breast cancer
Authors: Haffner Michael C , Petridou Barbara , Peyrat Jean Phillipe , Révillion Françoise , Müller-Holzner Elisabeth , Daxenbichler Günter , Marth Christian , Doppler Wolfgang
Published: July 2007

Background

Suppressor of cytokine signaling (SOCS) proteins comprise a protein family, which has initially been described as STAT induced inhibitors of the Jak/Stat pathway. Recent in vivo and in vitro studies suggest that SOCS proteins are also implicated in cancer. The STAT5 induced IGF-I acts as an endocrine and para/autocrine growth and differentiation factor in mammary gland development. Whereas high levels of circulating IGF-I have been associated with increased cancer risk, the role of autocrine acting IGF-I is less clear. The present study is aimed to elucidate the clinicopathological features associated with SOCS1, SOCS2, SOCS3, CIS and IGF-I expression in breast cancer.

Methods

We determined the mRNA expression levels of SOCS1, SOCS2, SOCS3, CIS and IGF-I in 89 primary breast cancers by reverse transcriptase PCR. SOCS2 protein expression was further evaluated by immuno-blot and immunohistochemistry.

Results

SOCS2 expression inversely correlated with histopathological grade and ER positive tumors exhibited higher SOCS2 levels. Patients with high SOCS2 expression lived significantly longer (108.7 vs. 77.7 months; P = 0.015) and high SOCS2 expression proved to be an independent predictor for good prognosis (HR = 0.45, 95% CI 0.23 – 0.91, P = 0.026). In analogy to SOCS2, high IGF-I expression was an independent predictor for good prognosis in the entire patient cohort. In the subgroup of patients with lymph-node negative disease, high IGF-I was a strong predictor for favorable outcome in terms of overall survival and relapse free survival (HR = 0.075, 95% CI 0.014 – 0.388, P = 0.002).

Conclusion

This is the first report on the favorable prognostic value of high SOCS2 expression in primary mammary carcinomas. Furthermore a strong association of high IGF-I expression levels with good prognosis was observed especially in lymph-node negative patients. Our results suggest that high expression of the STAT5 target genes SOCS2 and IGF-I is a feature of differentiated and less malignant tumors.
PI3K activation is associated with intracellular sodium/iodide symporter protein expression in breast cancer
Authors: Knostman Katherine AB , McCubrey James A , Morrison Carl D , Zhang Zhaoxia , Capen Charles C , Jhiang Sissy M
Published: July 2007

Background

The sodium/iodide symporter (NIS) is a membrane glycoprotein mediating active iodide uptake in the thyroid gland and is the molecular basis for radioiodide imaging and therapeutic ablation of thyroid carcinomas. NIS is expressed in the lactating mammary gland and in many human breast tumors, raising interest in similar use for diagnosis and treatment. However, few human breast tumors have clinically evident iodide uptake ability. We previously identified PI3K signaling as important in NIS upregulation in transgenic mouse models of breast cancer, and the PI3K pathway is commonly activated in human breast cancer.

Methods

NIS expression, subcellular localization, and function were analyzed in MCF-7 human breast cancer cells and MCF-7 cells stably or transiently expressing PI3K p110alpha subunit using Western blot of whole cell lysate, cell surface biotinylation Western blot and immunofluorescence, and radioiodide uptake assay, respectively. NIS localization was determined in a human breast cancer tissue microarray using immunohistochemical staining (IHC) and was correlated with pre-existing pAkt IHC data. Statistical analysis consisted of Student's t-test (in vitro studies) or Fisher's Exact Test (in vivo correlational studies).

Results

In this study, we demonstrate that PI3K activation in MCF-7 human mammary carcinoma cells leads to expression of underglycosylated NIS lacking cell surface trafficking necessary for iodide uptake ability. PI3K activation also appears to interfere with cell surface trafficking of exogenous NIS as well as all-trans retinoic acid-induced endogenous NIS. A correlation between NIS expression and upregulation of PI3K signaling was found in a human breast cancer tissue microarray.

Conclusion

Thus, the PI3K pathway likely plays a major role in the discordance between NIS expression and iodide uptake in breast cancer patients. Further study is warranted to realize the application of NIS-mediated radioiodide ablation in breast cancer.
Prevalence and determinants of adolescent tobacco smoking in Addis Ababa, Ethiopia
Authors: Rudatsikira Emmanuel , Abdo Abdurahman , Muula Adamson S
Published: July 2007

Background

Tobacco smoking is a growing public health problem in the developing world. There is paucity of data on smoking and predictors of smoking among school-going adolescents in most of sub-Saharan Africa. Hence, the aim of this study is to estimate the prevalence of smoking and its associations among school-going adolescents in Addis Ababa, Ethiopia.

Methods

Data from the Global Youth Tobacco Survey (GYTS) 2003 were used to determine smoking prevalence, determinants, attitudes to, and exposure to tobacco advertisements among adolescents.

Results

Of the 1868 respondents, 4.5% males and 1% females reported being current smokers (p < 0.01). Having smoking friends was strongly associated with smoking after controlling for age, gender, parental smoking status, and perception of risks of smoking (OR = 33; 95% CI [11.6, 95.6]). Male gender and having one or both smoking parents were associated with smoking. Perception that smoking is harmful was negatively associated with being a smoker (odds ratio 0.3; 95% confidence interval, 0.2–0.5)

Conclusion

Prevalence of smoking among adolescents in Ethiopia is lower than in many other African countries. There is however need to strengthen anti-tobacco messages especially among adolescents.
A systematic review of tests of empathy in medicine
Authors: Hemmerdinger Joanne M , Stoddart Samuel DR , Lilford Richard J
Published: July 2007

Background

Empathy is frequently cited as an important attribute in physicians and some groups have expressed a desire to measure empathy either at selection for medical school or during medical (or postgraduate) training. In order to do this, a reliable and valid test of empathy is required. The purpose of this systematic review is to determine the reliability and validity of existing tests for the assessment of medical empathy.

Methods

A systematic review of research papers relating to the reliability and validity of tests of empathy in medical students and doctors. Journal databases (Medline, EMBASE, and PsycINFO) were searched for English-language articles relating to the assessment of empathy and related constructs in applicants to medical school, medical students, and doctors.

Results

From 1147 citations, we identified 50 relevant papers describing 36 different instruments of empathy measurement. As some papers assessed more than one instrument, there were 59 instrument assessments. 20 of these involved only medical students, 30 involved only practising clinicians, and three involved only medical school applicants. Four assessments involved both medical students and practising clinicians, and two studies involved both medical school applicants and students.

Eight instruments demonstrated evidence of reliability, internal consistency, and validity. Of these, six were self-rated measures, one was a patient-rated measure, and one was an observer-rated measure.

Conclusion

A number of empathy measures available have been psychometrically assessed for research use among medical students and practising medical doctors. No empathy measures were found with sufficient evidence of predictive validity for use as selection measures for medical school. However, measures with a sufficient evidential base to support their use as tools for investigating the role of empathy in medical training and clinical care are available.
A qualitative study of referral to community mental health teams in the UK: exploring the rhetoric and the reality
Authors: Chew-Graham Carolyn , Slade Mike , Montana Carolyn , Stewart Mairi , Gask Linda
Published: July 2007

Background

Generic community mental health teams (CMHTs) currently deliver specialist mental health care in England. Policy dictates that CMHTs focus on those patients with greatest need but it has proved difficult to establish consistent referral criteria. The aim of this study was to explore the referral process from the perspectives of both the referrers and the CMHTs.

Methods

Qualitative study nested in a randomised controlled trial. Interviews with general practitioner (GP) referrers, CMHT Consultant Psychiatrists and team leaders. Taping of referral allocation meetings.

Results

There was a superficial agreement between the referrers and the referred to on the function of the CMHT, but how this was operationalised in practice resulted in a lack of clarity over the referral process, with tensions apparent between the views of the referrers (GPs) and the CMHT team leaders, and between team members. The process of decision-making within the team was inconsistent with little discussion of, or reflection on, the needs of the referred patient.

Conclusion

CMHTs describe struggling to deal with GPs who are perceived as having variable expertise in managing patients with mental health problems. CMHT rhetoric about defined referral criteria is interpreted flexibly with CMHT managers and Psychiatrists concentrating on their own capacity, roles and responsibilities with limited consideration of the primary care perspective or the needs of the referred patient.

Trial Registration number

ISRCTN86197914
Association of dopamine receptor polymorphisms with schizophrenia and antipsychotic response in a South Indian population
Authors: Vijayan Neetha N. , Bhaskaran Sujatha , Koshy Linda V. , Natarajan Chandrasekhar , Srinivas Lekshmy , Nair Chandrasekharan M. , Allencherry Priya M. , Banerjee Moinak
Published: July 2007

Background

Alterations in the dopamine transmission and receptor density are hypothesized in the pathophysiology of schizophrenia but ethnic disparities are reported to exist in disease association and therapeutic response to psychotropic medication. Antipsychotics have higher binding affinity to D2 subtype of dopamine receptor. DRD2 Cys311, TaqIB1 and TaqIA1 variants are considered to have either reduced affinity for dopamine and hypo-dopaminergic activity.

Methods

We examined the role of Taq1B, Taq1D, S311C, H313H and Taq1A polymorphisms of DRD2 gene in schizophrenia and antipsychotic treatment response in 213 patients and 196 controls from a homogenous South Indian population. A more detailed genotype phenotype association analysis was carried out to understand the disease in terms of its socio-cultural factors.

Results

H313HTT genotype was found to be associated with schizophrenia (P = 0.004) while TaqIB1B1 genotype was significantly associated with higher psychopathology score. When treatment response was considered H313HCC, TaqIA2A2 and Taq1D1D1 had higher mean improvement scores. TaqID1D1 and H313HTT genotype were found to be significantly higher in responders than in nonresponder group. Distinct shift in the LD patterns of responder and non-responder group was observed. Certain symptoms were characteristic of our patient population. Following medication the scores and presentation of these symptoms tend to vary in the responder and non-responder groups.

Conclusion

Based on genotype phenotype correlations it can be suggested that certain polymorphisms can be defined for their critical functions in disease and their role in treatment response in South Indian population. The present study suggests that in addition to ethnic bias, socio-cultural factors should also be considered while evaluating genotype phenotype correlations, in association and treatment response to complex disorders like schizophrenia.
Co-localization of CENP-C and CENP-H to discontinuous domains of CENP-A chromatin at human neocentromeres
Authors: Alonso Alicia , Fritz Björn , Hasson Dan , Abrusan György , Cheung Fanny , Yoda Kinya , Radlwimmer Bernhard , Ladurner Andreas G , Warburton Peter E
Published: July 2007

Background

Mammalian centromere formation is dependent on chromatin that contains centromere protein (CENP)-A, which is the centromere-specific histone H3 variant. Human neocentromeres have acquired CENP-A chromatin epigenetically in ectopic chromosomal locations on low-copy complex DNA. Neocentromeres permit detailed investigation of centromeric chromatin organization that is not possible in the highly repetitive alpha satellite DNA present at endogenous centromeres.

Results

We have examined the distribution of CENP-A, as well as two additional centromeric chromatin-associated proteins (CENP-C and CENP-H), across neocentromeric DNA using chromatin immunoprecipitation (ChIP) on CHIP assays on custom genomic microarrays at three different resolutions. Analysis of two neocentromeres using a contiguous bacterial artificial chromosome (BAC) microarray spanning bands 13q31.3 to 13q33.1 shows that both CENP-C and CENP-H co-localize to the CENP-A chromatin domain. Using a higher resolution polymerase chain reaction (PCR)-amplicon microarray spanning the neocentromere, we find that the CENP-A chromatin is discontinuous, consisting of a major domain of about 87.8 kilobases (kb) and a minor domain of about 13.2 kb, separated by an approximately 158 kb region devoid of CENPs. Both CENP-A domains exhibit co-localization of CENP-C and CENP-H, defining a distinct inner kinetochore chromatin structure that is consistent with higher order chromatin looping models at centromeres. The PCR microarray data suggested varying density of CENP-A nucleosomes across the major domain, which was confirmed using a higher resolution oligo-based microarray.

Conclusion

Centromeric chromatin consists of several CENP-A subdomains with highly discontinuous CENP-A chromatin at both the level of individual nucleosomes and at higher order chromatin levels, raising questions regarding the overall structure of centromeric chromatin.
Impact of Acute and Chronic Low-Dose Glucocorticoids on Protein Metabolism
Authors: Burt Morton G. , Johannsson Gudmundur , Umpleby A. Margot , Chisholm Donald J. , Ho Ken K. Y.
Published: July 2007

Context: High-dose glucocorticoids cause acute protein loss by increasing protein breakdown and oxidation. Whether lower glucocorticoid doses, typical of therapeutic use, induce sustained catabolism has not been studied.

Objective: Our objective was to assess the effect of acute and chronic therapeutic glucocorticoid doses on protein metabolism.

Design and Setting: We conducted an open longitudinal and a cross-sectional study at a clinical research facility.

Patients and Intervention: Ten healthy subjects were studied before and after a short course of prednisolone (5 and 10 mg/d sequentially for 7 d each). Twelve subjects with inactive polymyalgia rheumatica receiving chronic (>12 months) prednisone (mean = 5.0 ± 0.8 mg/d) were compared with 12 age- and gender-matched normal subjects.

Main Outcome Measure: Whole-body protein metabolism was assessed using a 3-h primed constant infusion of 1-[13C]leucine, from which rates of leucine appearance (leucine Ra, an index of protein breakdown), leucine oxidation (Lox, index of protein oxidation) and leucine incorporation into protein (LIP, index of protein synthesis) were estimated.

Results: Prednisolone induced an acute significant increase in Lox (P = 0.008) and a fall in LIP (P = 0.08) but did not affect leucine Ra. There was no significant difference between the effects of the 5- and 10-mg prednisolone doses on leucine metabolism. In subjects receiving chronic prednisone therapy, leucine Ra, Lox, and LIP were not significantly different from normal subjects.

Conclusion: Glucocorticoids stimulate protein oxidation after acute but not chronic administration. This time-related change suggests that glucocorticoid-induced stimulation of protein oxidation does not persist but that a metabolic adaptation occurs to limit protein loss.
Intact Kinase Homology Domain of Natriuretic Peptide Receptor-B Is Essential for Skeletal Development
Authors: Hachiya Rumi , Ohashi Yuko , Kamei Yasutomi , Suganami Takayoshi , Mochizuki Hiroshi , Mitsui Norimasa , Saitoh Masaaki , Sakuragi Masako , Nishimura Gen , Ohashi Hirofumi , Hasegawa Tomonobu , Ogawa Yoshihiro
Published: July 2007

Context: Natriuretic peptide receptor-B (NPR-B, GC-B in rodents; gene name NPR2) is a guanylyl cyclase-coupled receptor that mediates the effect of C-type natriuretic peptide. Homozygous mutations in human NPR-B cause acromesomelic dysplasia, type Maroteaux (OMIM 602875), an autosomal recessive skeletal dysplasia. NPR-B has an intracellular kinase homology domain (KHD), which has no kinase activity, and its functional significance in vivo is currently unknown.

Objective: We examined the functional significance of a novel NPR-B KHD mutation in humans.

Patients and Methods: A 28-yr-old Japanese male presented with marked short stature (118.5 cm, −9.3 sd). His limbs showed marked shortening in the middle and distal segments. His parents had relatively short stature with height z-scores of −2.75 and −0.98 (his father and mother, respectively). Direct sequencing of coding region of the NPR2 gene of the family was performed. The mutant receptor activity was investigated by saturation binding assay and cGMP measurement. Additionally, interaction between the mutant and wild type allele was investigated by the titration experiments.

Results: We identified a novel missense mutation L658F in KHD of NPR-B in homozygous and heterozygous states in the patient and his parents, respectively. The mutation conferred normal binding affinity for C-type natriuretic peptide but no discernible ligand-induced cGMP production. Furthermore, L658F mutant impaired wild-type NPR-B-mediated cGMP production in a dose-dependent manner, suggesting that short stature found in L658F heterozygote can be caused by its dominant-negative effect.

Conclusions: This study provides the first evidence that intact KHD of NPR-B is essential for skeletal development.
Genetic Removal of Smad3 from Inhibin-Null Mice Attenuates Tumor Progression by Uncoupling Extracellular Mitogenic Signals from the Cell Cycle Machinery
Authors: Looyenga Brendan D. , Hammer Gary D.
Published: July 2007

Inhibin and activin are members of the TGFβ family that perform mutually antagonistic signaling roles in the anterior pituitary, gonads, and adrenal gland. Unopposed activin signaling in inhibin-null (Inha−/−) mice causes the formation of granulosa cell tumors in the gonads and adrenal cortex, which depend upon FSH for efficient growth and progression. In this study, we demonstrate that Smad3, a key effector of activin signaling, is expressed at high levels and is constitutively activated in tumors from these mice. Removal of Smad3 from Inha−/− mice by a genetic cross to Smad3-null (Madh3−/−) mice leads to a significant decrease in cyclinD2 expression and a significant attenuation of tumor progression in the gonads and adrenal. The decrease in cyclinD2 levels in compound knockout mice is related to a reduction in mitogenic signaling through the phosphoinositide-3-kinase (PI3-kinase)/Akt pathway, which is required for normal cell cycle progression in tumor cells. Loss of PI3-kinase/Akt signaling cannot be attributed to alterations in IGF expression, suggesting instead that signaling through the FSH receptor is attenuated. Gene expression profiling in the ovaries of Madh3−/− and Inha−/−:Madh3−/− compound knockout mice supports this hypothesis and further suggests that Smad3 is specifically required for FSH to activate PI3-kinase/Akt, but not protein kinase A. Together these observations imply that activin/Smad3 signaling is necessary for efficient signaling by FSH in Inha−/− tumor cells and that interruption of this pathway uncouples FSH from its intracellular mitogenic effectors.
Osteopenia, decreased bone formation and impaired osteoblast development inSox4heterozygous mice
Authors: Nissen-Meyer Lise Sofie Haug , Jemtland Rune , Gautvik Vigdis T. , Pedersen Mona E. , Paro Rita , Fortunati Dario , Pierroz Dominique D. , Stadelmann Vincent A. , Reppe Sjur , Reinholt Finn P. , Del Fattore Andrea , Rucci Nadia , Teti Anna , Ferrari Serge , Gautvik Kaare M.
Published: July 2007

The transcription factor Sox4 is vital for fetal development, as Sox4–/– homozygotes die in utero. Sox4 mRNA is expressed in the early embryonic growth plate and is regulated by parathyroid hormone, but its function in bone modeling/remodeling is unknown. We report that Sox4+/– mice exhibit significantly lower bone mass (by dual-energy X-ray absorptiometry) from an early age, and fail to obtain the peak bone mass of wild-type (WT) animals. Microcomputed tomography (μCT), histomorphometry and biomechanical testing of Sox4+/– bones show reduced trabecular and cortical thickness, growth plate width, ultimate force and stiffness compared with WT. Bone formation rate (BFR) in 3-month-old Sox4+/– mice is 64% lower than in WT. Primary calvarial osteoblasts from Sox4+/– mice demonstrate markedly inhibited proliferation, differentiation and mineralization. In these cultures, osterix (Osx) and osteocalcin (OCN) mRNA expression was reduced, whereas Runx2 mRNA was unaffected. No functional defects were found in osteoclasts. Silencing of Sox4 by siRNA in WT osteoblasts replicated the defects observed in Sox4+/– cells. We demonstrate inhibited formation and altered microarchitecture of bone in Sox4+/– mice versus WT, without apparent defects in bone resorption. Our results implicate the transcription factor Sox4 in regulation of bone formation, by acting upstream of Osx and independent of Runx2.
Rapid effects of acute anoxia on spindle kinetochore interactions activate the mitotic spindle checkpoint
Authors: Pandey Rahul , Heeger Sebastian , Lehner Christian F.
Published: July 2007

The dramatic chromosome instability in certain tumors might reflect a synergy of spindle checkpoint defects with hypoxic conditions. In Caenorhabditis elegans and Drosophila melanogaster, spindle checkpoint activation has been implicated in the response to acute anoxia. The activation mechanism is unknown. Our analyses in D. melanogaster demonstrate that oxygen deprivation affects microtubule organization within minutes. The rapid effects of anoxia are identical in wild-type and spindle checkpoint-deficient Mps1 mutant embryos. Therefore, the anoxia effects on the mitotic spindle are not a secondary consequence of spindle checkpoint activation. Some motor, centrosome and kinetochore proteins (dynein, Kin-8, Cnn, TACC, Cenp-C, Nuf2) are rapidly relocalized after oxygen deprivation. Kinetochores congress inefficiently into the metaphase plate and do not experience normal pulling forces. Spindle checkpoint proteins accumulate mainly within the spindle midzone and inhibit anaphase onset. In checkpoint-deficient embryos, mitosis is still completed after oxygen deprivation, although accompanied by massive chromosome missegregation. Inhibitors of oxidative phosphorylation mimic anoxia effects. We conclude that oxygen deprivation impairs the chromosome segregation machinery more rapidly than spindle checkpoint function. Although involving adenosine triphosphate (ATP)-consuming kinases, the spindle checkpoint can therefore be activated by spindle damage in response to acute anoxia and protect against aneuploidies.
The exon-junction-complex-component metastatic lymph node 51 functions in stress-granule assembly
Authors: Baguet Aurélie , Degot Sébastien , Cougot Nicolas , Bertrand Edouard , Chenard Marie-Pierre , Wendling Corinne , Kessler Pascal , Le Hir Hervé , Rio Marie-Christine , Tomasetto Catherine
Published: July 2007

Metastatic lymph node 51 [MLN51 (also known as CASC3)] is a component of the exon junction complex (EJC), which is assembled on spliced mRNAs and plays important roles in post-splicing events. The four proteins of the EJC core, MLN51, MAGOH, Y14 and EIF4AIII shuttle between the cytoplasm and the nucleus. However, unlike the last three, MLN51 is mainly detected in the cytoplasm, suggesting that it plays an additional function in this compartment. In the present study, we show that MLN51 is recruited into cytoplasmic aggregates known as stress granules (SGs) together with the SG-resident proteins, fragile X mental retardation protein (FMRP), poly(A) binding protein (PABP) and poly(A)+ RNA. MLN51 specifically associates with SGs via its C-terminal region, which is dispensable for its incorporation in the EJC. MLN51 does not promote SG formation but its silencing, or the overexpression of a mutant lacking its C-terminal region, alters SG assembly. Finally, in human breast carcinomas, MLN51 is sometimes present in cytoplasmic foci also positive for FMRP and PABP, suggesting that SGs formation occurs in malignant tumours.
The influence of the first-mating age of rats on the number of pups born, their weights and their mortality
Authors: Rosen M. , Kahan E. , Derazne E.
Published: July 2007

Widely differing ranges for the preferred first-mating age for rats have been reported by different investigators. As well as being of physiological interest this information is important for optimum utilization of animal resources. Previously published results, however, do not provide sufficient information on mortality and the numbers of pups born and weaned. We studied 1623 pups born to 36 female Wistar rats. Dams were first mated at the age of 35 days or 70 days or 105 days. The results show that reproduction and weaning weights increase with an increased first-mating age of dams, although the pup mortality rate also increases. This study can be used when a programme for the production and supply of Wistar rats is planned.
Observations on soft tissue calcification in DBA/2NCrj mice in comparison with CRJ:CD-1 mice
Authors: Yamate J. , Tajima M. , Maruyama Y. , Kudow S.
Published: July 2007

Male and female DBA/2NCrj (DBA/2) mice 3, 4, 5 and 10 weeks old were examined biochemically and pathologically and the results obtained were compared with those for CRJ:CD-1 (ICR) mice of the same age. The plasma levels of glucose, triglyceride and total cholesterol tended to be lower in DBA/2 mice than in ICR mice but the levels of non-esterified fatty acid, calcium and inorganic phosphorus were almost the same in the two strains. The mean body weight of DBA/2 mice was significantly lower than that of ICR mice at each examination, and the relative weights of the hearts of male and female DBA/2 mice were significantly greater than those of male and female ICR mice. Cardiac calcinosis, tongue calcification and corneal degeneration occurred exclusively in DBA/2 mice with incidences of 30%-100%. The incidence and severity of these lesions increased with age but no sex differences were seen. It was difficult to relate differences in biochemical features of the two strains with pathological findings obtained in the DBA/2 mice. The numbers of cells secreting adrenocorticotropic hormone in the pituitary glands were significantly greater in male and female DBA/2 mice than in ICR mice, suggesting a higher secretion of corticosteroids in the former strain.
A method for culturing the nasopharyngeal area of rabbits
Authors: Holmes H. T. , Matsumoto M. , Patton N. M. , Harris D. J.
Published: July 2007

A method for obtaining antemortem nasopharyngeal cultures is described. Its usefulness for detecting the carrier state of Pasteurella multocida in clinically normal, apparently healthy nasal-culture-negative rabbits is also discussed.
Diagnosis and monitoring of pregnancy in mice: correlations between maternal weight, fetal and placental mass and the maternal serum levels of progesterone, pregnancy-associated murine protein-2 and α-fetoprotein
Authors: Hau J. , Jensen H.-J. Skovgaard
Published: July 2007

Outbred Bom:NMRI mice were weighed daily for 18 days from observation of a vaginal plug. In a separate experiment, fetuses and placentae were weighed on each day of pregnancy. Pregnancy can be determined with 99% certainty on day 12 of gestation by the maternal body weight increase from day 1. The pregnancy-specific proteins α-fetoprotein (m-AFP) and pregnancy-associated murine protein-2 (PAMP-2), of fetal and placental origin respectively, were detectable on days 8 and 10 in the maternal circulation. Significant correlations were observed between m-AFP and fetal weight and PAMP-2 and placental weight. These markers may therefore be useful in the monitoring of fetal growth and placental growth respectively.
The association between spontaneous pyelonephritis and maturity-onset diabetes mellitus in male MM mice
Authors: Taylor D. M. , Neal D. L. , McBride P. A.
Published: July 2007

Blood glucose and glucose tolerance tests demonstrated that many male MM mice are diabetic. Serial urine sampling showed that the diabetes occurred only in mature MM males and consisted of a single self-limiting episode. Histological examination of the pancreas, together with measurements of body weight, glycosylated haemoglobin and plasma insulin, revealed that the diabetes was of the maturity-onset insulin-resistant type. Bacteriological examination of the urine samples showed that urinary tract infection, a known feature of male MM mice, occurred in the diabetics but only after the onset of hyperglucosuria. It was concluded that the high urinary glucose levels of diabetic MM males are of prime importance in the aetiology of the renal infection which occurs rarely in non-diabetic MM males or in other strains in the colony. An infectious aetiology for the diabetes per se was excluded by the existence of diabetes in germfree MM males.
Sequential study of vasculitis in MRL mice
Authors: Hewicker M. , Trautwein G.
Published: July 2007

The frequency, age of onset and organ distribution of spontaneously occurring vasculitis was examined in a sequential study with 170 MRL mice of both substrains. Necrotizing vasculitis was seen in 55·8% of MRL/Mp-lpr/lpr mice studied, beginning at the age of 3 months. The kidney and urinary bladder were most frequently involved. In MRL/Mp-+/+ mice necrotizing vasculitis was much less frequently present (7·6%), beginning at the age of 18 months, and was seen only in the kidney, stomach and testes. In both substrains mononuclear infiltration of pulmonary vessel walls preceded the occurrence of necrotizing arteritis in other organs. The immunofluorescence study revealed the presence of immune complex components (immunoglobulin G, C3, murine leukaemia virus antigen gp71) in the vessel walls of the renal arteries of six out of 36 lpr/lpr mice with necrotizing arteritis.
Distinct ribonucleoprotein reservoirs for microRNA and siRNA populations in C. elegans
Authors: Gu Sam G. , Pak Julia , Barberan-Soler Sergio , Ali Mustapha , Fire Andrew , Zahler Alan M.
Published: July 2007

MicroRNAs (miRNAs) are regulatory molecules that share both biosynthetic derivation (cleavage from short hairpin precursor RNAs) and functional roles (downregulation of specific mRNAs through targeted degradation and/or translational inhibition). A distinct family of small RNAs, termed siRNAs, have some common characteristics but exhibit distinct modes of biosynthesis and function. In this study, we report procedures for purification of a predominant species of miRNA-containing ribonucleoprotein complexes from Caenorhabditis elegans and demonstrate that this population is distinct from the predominant pool of siRNA-containing ribonucleoprotein complexes. An observed miRNP-associated RNA population consisting predominantly (>95%) of miRNAs supported the unique identity of miRNPs as biological effectors within the cell, provided clean material for analysis of changes in miRNA spectra during development, and provided strong evidence of miRNA character for a number of novel small RNAs. Likewise, the RNA spectrum derived from partial siRNP purification was useful in defining functional characteristics of this more diverse population of small RNAs.
The Hsp40 chaperone Jjj1 is required for the nucleo-cytoplasmic recycling of preribosomal factors in Saccharomyces cerevisiae
Authors: Demoinet Emilie , Jacquier Alain , Lutfalla Georges , Fromont-Racine Micheline
Published: July 2007

Ribosome biogenesis is a major conserved cellular pathway that requires both ribosomal proteins and many preribosomal factors. Most of the pre-60S factors are recycled into the nucleus; some of them shuttle between the nucleus and the cytoplasm while a few others, like Rei1, are strictly cytoplasmic and are mostly involved in the dissociation/recycling of the pre-60S shuttling factors. Here, we investigated the role of the Jjj1 Hsp40 chaperone in ribosome biogenesis. The absence of Jjj1 leads to a cold sensitive phenotype, a defect in the relative amount of the large ribosomal subunit with the appearance of halfmers, and to cytoplasmic accumulation of shuttling factors such as Arx1 and Alb1, which stay bound to the pre-60S particles. Jjj1 is, thus, a novel pre-60S factor involved in the last cytoplasmic steps of the large ribosomal subunit biogenesis. We report the biochemical association of Jjj1 and Rei1 to similar pre-60S complexes, their two-hybrid interactions, and their functional links. Altogether, these results indicate that Rei1 and Jjj1 share many common features. However, while the functions of Jjj1 and Rei1 partially overlap, we could distinguish specific role of the two proteins in Arx1/Alb1 and Tif6 recycling. We propose that Jjj1 is preferentially required for the release of Arx1 and Alb1 shuttling factors from the cytoplasmic pre-60S particles while Rei1 is preferentially involved in their recycling.
Ty1 reverse transcriptase does not read through the proposed 2′,5′-branched retrotransposition intermediate in vitro
Authors: Pratico Elizabeth D. , Silverman Scott K.
Published: July 2007

2′,5′-Branched RNA was recently proposed as a key Ty1 retrotransposition intermediate, for which cleavage by lariat debranching enzyme (Dbr1p) enables reverse transcription to continue synthesizing the complete Ty1 cDNA. Because dbr1 cells can produce substantial Ty1 cDNA despite lacking Dbr1p, the obligatory intermediacy of branched RNA would require that Ty1 reverse transcriptase (RT) can read through the proposed branch site with considerable efficiency. Here we have used deoxyribozyme-synthesized 2′,5′-branched RNA corresponding exactly to the proposed Ty1 branch site for a direct test of this read-through ability. Using an in vitro assay that incorporates all components known to be required for Ty1 cDNA synthesis (including the TyA chaperone protein), Ty1 RT can elongate up to the branch site. Strand transfer from the 2′-arm to the 3′-arm of the branch is observed when the Ty1 RT is RNase H+ (i.e., wild-type) but not when the Ty1 RT is RNase H−. When elongating from either the 2′-arm or the 3′-arm, Ty1 RT reads through the branch site with ≤0.3% efficiency. This is at least 60-fold lower than would be necessary to explain in vivo Ty1 cDNA synthesis in dbr1 cells, because others have reported 18% cDNA synthesis relative to wild-type cells. Our finding that Ty1 RT cannot efficiently read through the proposed Ty1 branch site is inconsistent with the hypothesis that branched RNA is an obligatory Ty1 retrotransposition intermediate. This suggests that Dbr1p acts as other than a 2′,5′-phosphodiesterase during Ty1 retrotransposition.
MicroRNA regulation of human protein–protein interaction network
Authors: Liang Han , Li Wen-Hsiung
Published: July 2007

Since the functional state of a protein–protein interaction network depends on gene expression, a fundamental question is what relationships exist between protein interaction network and gene regulation. In particular, microRNAs have recently emerged as a major class of post-transcriptional regulators that influences a large proportion of genes in higher eukaryotes. Here we show that protein connectivity in the human protein–protein interaction network is positively correlated with the number of microRNA target-site types in the 3′ untranslated regions of the gene encoding the protein and that interacting proteins tend to share more microRNA target-site types than random pairs. Moreover, our results demonstrate that microRNA targeting propensity for genes in different biological processes can be largely explained by their protein connectivity. Finally, we show that for hub proteins, microRNA regulation complexity is negatively correlated with clustering coefficient, suggesting that microRNA regulation is more important to inter-modular hubs than to intramodular ones. Taken together, our study provides the first evidence for global correlation between microRNA repression and protein–protein interactions.
Dosing Considerations in the Use of Sodium Phosphate Bowel Preparations for Colonoscopy
Authors: Rex Douglas K
Published: July 2007

Objective:

To review dosing considerations and other treatment recommendations to maximize the efficacy, tolerability, and safety of sodium phosphate (NaP) preparations.

Data Sources:

Literature was accessed through PubMed (1990–May 2007) and abstracts from scientific meetings.

Study Selection and Data Extraction:

English-language publications including clinical trials and case reports were evaluated. Recent reports assessing newer bowel preparations containing reduced doses of NaP were reviewed to evaluate efficacy, tolerability, and safety.

Data Synthesis:

Among commonly administered bowel preparations for colonoscopy, NaP preparations are generally more effective and better tolerated compared with polyethylene glycol electrolyte lavage solution regimens. However, NaP preparations are contraindicated in specific patient populations, and clinicians must use effective screening mechanisms to select proper patients to receive NaP preparation for colonoscopy. Recently, cases of renal failure in patients with previously normal renal function have been reported after NaP preparation for colonoscopy, heightening concerns about the safety of these agents. Newer products contain reduced doses of NaP and may improve the safety and tolerability of NaP purgatives without compromising efficacy of colon cleansing. In addition, accumulating clinical data and/or rationale support split dosing of NaP products, wide intervals between doses, and aggressive hydration before and during bowel preparation and after the colonoscopy procedure.

Conclusions:

Safe administration of NaP products requires rigorous attention to dosing considerations and other treatment recommendations, including administration of minimally effective doses of NaP, split-dosing schedules, and aggressive hydration.