bluuebunny/crossref_metadata_2025 huggingface dataset:
Even Highly Correlated Measures Can Add Incrementally to Predicting Recidivism Among Sex Offenders
Authors: Babchishin Kelly M. , Hanson R. Karl , Helmus Leslie
Published: September 2012

Criterion-referenced measures, such as those used in the assessment of crime and violence, prioritize predictive accuracy (discrimination) at the expense of construct validity. In this article, we compared the discrimination and incremental validity of three commonly used criterion-referenced measures for sex offenders (Rapid Risk Assessment for Sex Offence Recidivism [RRASOR], Static-99R, and Static-2002R). In a meta-analysis of 20 samples ( n = 7,491), Static-99R and Static-2002R provided similar discrimination but outperformed the RRASOR in the prediction of sexual, violent, and any recidivism. Remarkably, despite large correlations between them ( rs ranging from .70 to .92), these risk scales consistently added incremental validity to one another. The direction of the incremental effects, however, was not consistently positive. When controlling for the other measures, high scores on the RRASOR were associated with lower risk for violent and any recidivism. We also examined different methods of combining risk scales and found that the averaging approach produced better discrimination than choosing the highest score and produced better calibration than either choosing the lowest or highest risk score. The findings reinforce the importance of understanding the psychological content of criterion-referenced measures, even when the sole purpose is to predict a particular outcome and provide some direction concerning the best methods for combining risk scales.
The International Union for Health Promotion and Education (IUHPE) Student and Early Career Network (ISECN): a case illustrating three strategies for maximizing synergy in professional collaboration
Authors: Corbin J. Hope , Fisher Emily A. , Bull Torill
Published: September 2012

The International Union for Health Promotion and Education (IUHPE) Student and Early Career Network (ISECN) was constructed upon a foundation of research, using the Bergen Model of Collaborative Functioning (BMCF) as a blueprint to inform its leadership, communication, structure, and culture. The BMCF consists of inputs (partners, mission, and financial resources), throughputs (operational processes), and outputs (synergy and antagony). In this commentary, we use the BMCF to describe the ISECN work, highlighting opportunities, successes, and challenges. We also put forward three strategies derived from the BMCF that have been purposefully employed by ISECN to maximize its production of synergy from the voluntary contributions of its members.
Effect of Cr addition on microstructures and nanohardness of rapidly solidified Ti–48Al alloy
Authors: Zhu D D , Wang H W , Qi J Q , Zou C M , Wei Z J
Published: September 2012

In this present work, the microstructure and nanohardness of rapidly solidified Ti–48 at-Al alloy with various Cr additions were experimentally investigated using the single roller melt spinning technique. Ti–48Al alloy with various Cr additions were prepared by arc melting for comparison. In the arc melted alloy, the volume fraction of the interdendritic γ phase decreases, and the lamellar structure and the B2 phase increase with the increase in Cr addition. After rapid solidification, the Ti–48Al alloy consists of the γ phase and α2 the phase, with the γ phase as the matrix. The α2 phase exists as particles or in lamellar structure, which embed in the matrix. With 2 at-Cr addition, the alloy ribbons mainly consist of equiaxial α2 grains and small particles of the B2 phase, with few lamellar structures occasionally found at the triple grain boundary. Increasing Cr content to 4 at-, the grain size of the B2 phase increases, and lamellar structures disappear. The change in nanohardness was discussed based on the microstructural observations. It shows a certain increase in the nanohardness as Cr content increases to 4 at-. This can be attributed to the changes in the microstructures.
Random homomorphisms and random derivations in random normed algebras via fixed point method
Authors: Park Choonkil , Eshaghi Gordji Madjid , Saadati Reza
Published: September 2012

Using the fixed point method, we prove the Hyers-Ulam stability of the Cauchy additive functional inequality and of the Cauchy-Jensen additive functional inequality in random normed spaces.

MSC:47H10, 39B52, 37H10, 60H25, 17B40, 39B72, 47B47, 54E70.
ReQON: a Bioconductor package for recalibrating quality scores from next-generation sequencing data
Authors: Cabanski Christopher R , Cavin Keary , Bizon Chris , Wilkerson Matthew D , Parker Joel S , Wilhelmsen Kirk C , Perou Charles M , Marron JS , Hayes D Neil
Published: September 2012

Background

Next-generation sequencing technologies have become important tools for genome-wide studies. However, the quality scores that are assigned to each base have been shown to be inaccurate. If the quality scores are used in downstream analyses, these inaccuracies can have a significant impact on the results.

Results

Here we present ReQON, a tool that recalibrates the base quality scores from an input BAM file of aligned sequencing data using logistic regression. ReQON also generates diagnostic plots showing the effectiveness of the recalibration. We show that ReQON produces quality scores that are both more accurate, in the sense that they more closely correspond to the probability of a sequencing error, and do a better job of discriminating between sequencing errors and non-errors than the original quality scores. We also compare ReQON to other available recalibration tools and show that ReQON is less biased and performs favorably in terms of quality score accuracy.

Conclusion

ReQON is an open source software package, written in R and available through Bioconductor, for recalibrating base quality scores for next-generation sequencing data. ReQON produces a new BAM file with more accurate quality scores, which can improve the results of downstream analysis, and produces several diagnostic plots showing the effectiveness of the recalibration.
Using BAC transgenesis in zebrafish to identify regulatory sequences of the amyloid precursor protein gene in humans
Authors: Shakes Leighcraft A , Du Hansen , Wolf Hope M , Hatcher Charles , Norford Derek C , Precht Patricia , Sen Ranjan , Chatterjee Pradeep K
Published: September 2012

Background

Non-coding DNA in and around the human Amyloid Precursor Protein (APP) gene that is central to Alzheimer’s disease (AD) shares little sequence similarity with that of appb in zebrafish. Identifying DNA domains regulating expression of the gene in such situations becomes a challenge. Taking advantage of the zebrafish system that allows rapid functional analyses of gene regulatory sequences, we previously showed that two discontinuous DNA domains in zebrafish appb are important for expression of the gene in neurons: an enhancer in intron 1 and sequences 28–31 kb upstream of the gene. Here we identify the putative transcription factor binding sites responsible for this distal cis-acting regulation, and use that information to identify a regulatory region of the human APP gene.

Results

Functional analyses of intron 1 enhancer mutations in enhancer-trap BACs expressed as transgenes in zebrafish identified putative binding sites of two known transcription factor proteins, E4BP4/ NFIL3 and Forkhead, to be required for expression of appb. A cluster of three E4BP4 sites at −31 kb is also shown to be essential for neuron-specific expression, suggesting that the dependence of expression on upstream sequences is mediated by these E4BP4 sites. E4BP4/ NFIL3 and XFD1 sites in the intron enhancer and E4BP4/ NFIL3 sites at −31 kb specifically and efficiently bind the corresponding zebrafish proteins in vitro. These sites are statistically over-represented in both the zebrafish appb and the human APP genes, although their locations are different. Remarkably, a cluster of four E4BP4 sites in intron 4 of human APP exists in actively transcribing chromatin in a human neuroblastoma cell-line, SHSY5Y, expressing APP as shown using chromatin immunoprecipitation (ChIP) experiments. Thus although the two genes share little sequence conservation, they appear to share the same regulatory logic and are regulated by a similar set of transcription factors.

Conclusion

The results suggest that the clock-regulated and immune system modulator transcription factor E4BP4/ NFIL3 likely regulates the expression of both appb in zebrafish and APP in humans. It suggests potential human APP gene regulatory pathways, not on the basis of comparing DNA primary sequences with zebrafish appb but on the model of conservation of transcription factors.
Emergence of serogroup C meningococcal disease associated with a high mortality rate in Hefei, China
Authors: Xu Xi-Hai , Ye Ying , Hu Li-Fen , Jin Yu-Hui , Jiang Qin-Qin , Li Jia-Bin
Published: September 2012

Background

Neisseria meningitidis serogroup C has emerged as a cause of epidemic disease in Hefei. The establishment of serogroup C as the predominant cause of endemic disease has not been described.

Methods

We conducted national laboratory-based surveillance for invasive meningococcal disease during 2000–2010. Isolates were characterized by pulsed-field gel electrophoresis and multilocus sequence typing.

Results

A total of 845 cases of invasive meningococcal disease were reported. The incidence increased from 1.25 cases per 100,000 population in 2000 to 3.14 cases per 100,000 in 2003 (p < 0.001), and peaked at 8.43 cases per 100,000 in 2005. The increase was mainly the result of an increase in the incidence of serogroup C disease. Serogroup C disease increased from 2/23 (9%) meningococcal cases and 0.11 cases per 100,000 in 2000 to 33/58 (57%) cases and 1.76 cases per 100,000 in 2003 (p < 0.01). Patients infected with serogroup C had serious complications more frequently than those infected with other serogroups. Specifically, 161/493 (32.7%) cases infected with serogroup C had at least one complication. The case-fatality rate of serogroup C meningitis was 11.4%, significantly higher than for serogroup A meningitis (5.3%, p = 0.021). Among patients with meningococcal disease, factors associated with death in univariate analysis were age of 15–24 years, infection with serogroup C, and meningococcemia.

Conclusions

The incidence of meningococcal disease has substantially increased and serogroup C has become endemic in Hefei. The serogroup C strain has caused more severe disease than the previously predominant serogroup A strain.
Effect of routine probiotic, Lactobacillus reuteri DSM 17938, use on rates of necrotizing enterocolitis in neonates with birthweight < 1000 grams: a sequential analysis
Authors: Hunter Chelsea , Dimaguila Mary Ann VT , Gal Peter , Wimmer John E , Ransom James Laurence , Carlos Rita Q , Smith McCrae , Davanzo Christie C
Published: September 2012

Background

Necrotizing enterocolitis (NEC) is a disease in neonates, often resulting in death or serious medical or neurodevelopmental complications. The rate of NEC is highest in the smallest babies and many efforts have been tried to reduce the rate of NEC. In neonates born below 1500 grams, the rate of NEC has been significantly reduced with the use of various probiotics. This study examines the impact of routine use of a probiotic, Lactobacillus reuteri DSM 17938 (BioGaia®), on the rate of NEC in neonates at highest risk for developing NEC, those with birth weight ≤1000 grams.

Methods

This is a retrospective cohort study comparing the rates of NEC in neonates with birth weight ≤ 1000 grams. The groups are separated into those neonates born from January 2004 to June 30, 2009, before introduction of L. reuteri , and neonates born July 2009 through April 2011 who received routine L. reuteri prophylaxis. The chart review study was approved by our institutional review board and exempted from informed consent.

Neonates were excluded if they died or were transferred within the first week of life. The remainder were categorized as having no NEC, medical NEC, surgical NEC, or NEC associated death. Since no major changes occurred in our NICU practice in recent years, and the introduction of L. reuteri as routine prophylaxis was abrupt, we attributed the post-probiotic changes to the introduction of this new therapy. Rates of NEC were compared using Chi square analysis with Fisher exact t-test.

Results

Medical records for 311 neonates were reviewed, 232 before- and 79 after-introduction of L. reuteri prophylaxis. The incidence of NEC was significantly lower in the neonates who received L. reuteri (2 of 79 neonates [2.5%] versus 35 of 232 untreated neonates [15.1%]). Rates of late-onset gram-negative or fungal infections (22.8 versus 31%) were not statistically different between treated and untreated groups. No adverse events related to use of L reuteri were noted.

Conclusions

Prophylactic initiation of L. reuteri as a probiotic for prevention of necrotizing enterocolitis resulted in a statistically significant benefit, with avoidance of 1 NEC case for every 8 patients given prophylaxis.
The potential impact of plain packaging of cigarette products among Brazilian young women: an experimental study
Authors: White Christine M , Hammond David , Thrasher James F , Fong Geoffrey T
Published: September 2012

Background

Tobacco use is responsible for 5.4 million deaths every year worldwide and is a leading cause of preventable death. The burden of these deaths is rapidly shifting to low and middle-income countries, such as Brazil. Brazil has prohibited most forms of tobacco advertising; however, the cigarette pack remains a primary source of marketing. The current study examined how tobacco packaging influences brand appeal and perceptions of health risk among young women in Brazil.

Methods

A between-subjects experiment was conducted in which 640 Brazilian women aged 16–26 participated in an online survey. Participants were randomized to view 10 cigarette packages according to one of three experimental conditions: standard branded packages, the same packs without brand imagery (“plain packaging”), or the same packs without brand imagery or descriptors (e.g., flavors). Participants rated packages on perceived appeal, taste, health risk, smoothness, and smoker attributes. Finally, participants were shown a range of branded and plain packs from which they could select one as a free gift, which constituted a behavioral measure of appeal.

Results

Branded packs were rated as significantly more appealing, better tasting, and smoother on the throat than plain packs. Branded packs were also associated with a greater number of positive smoker attributes including style and sophistication, and were perceived as more likely to be smoked by females than the plain packs. Removing descriptors from the plain packs further decreased the ratings of appeal, taste and smoothness, and also reduced associations with positive attributes. In the pack offer, participants were three times more likely to select branded packs than plain packs.

Conclusions

Plain packaging and removal of descriptors may reduce the appeal of smoking for youth and young adults, and consequently reduce smoking susceptibility. Overall, the findings provide support for plain packaging regulations, such as those in Australia.
Tenascin-W is a better cancer biomarker than tenascin-C for most human solid tumors
Authors: Brellier Florence , Martina Enrico , Degen Martin , Heuzé-Vourc’h Nathalie , Petit Agnès , Kryza Thomas , Courty Yves , Terracciano Luigi , Ruiz Christian , Chiquet-Ehrismann Ruth
Published: September 2012

Background

Tenascins are large glycoproteins found in the extracellular matrix of many embryonic and adult tissues. Tenascin-C is a well-studied biomarker known for its high overexpression in the stroma of most solid cancers. Tenascin-W, the least studied member of the family, is highly expressed in the stroma of colon and breast tumors and in gliomas, but not in the corresponding normal tissues. Other solid tumors have not been analyzed. The present study was undertaken to determine whether tenascin-W could serve as a cancer-specific extracellular matrix protein in a broad range of solid tumors.

Methods

We analyzed the expression of tenascin-W and tenascin-C by immunoblotting and by immunohistochemistry on multiple frozen tissue microarrays of carcinomas of the pancreas, kidney and lung as well as melanomas and compared them to healthy tissues.

Results

From all healthy adult organs tested, only liver and spleen showed detectable levels of tenascin-W, suggesting that tenascin-W is absent from most human adult organs under normal, non-pathological conditions. In contrast, tenascin-W was detectable in the majority of melanomas and their metastases, as well as in pancreas, kidney, and lung carcinomas. Comparing lung tumor samples and matching control tissues for each patient revealed a clear overexpression of tenascin-W in tumor tissues. Although the number of samples examined is too small to draw statistically significant conclusions, there seems to be a tendency for increased tenascin-W expression in higher grade tumors. Interestingly, in most tumor types, tenascin-W is also expressed in close proximity to blood vessels, as shown by CD31 co-staining of the samples.

Conclusions

The present study extends the tumor biomarker potential of tenascin-W to a broad range of solid tumors and shows its accessibility from the blood stream for potential therapeutic strategies.
Agonistic effect of polyunsaturated fatty acids (PUFAs) and its metabolites on brain-derived neurotrophic factor (BDNF) through molecular docking simulation
Authors: Vetrivel Umashankar , Ravichandran Sathya Baarathi , Kuppan Kaviarasan , Mohanlal Jithu , Das Undurti Narasimha , Narayanasamy Angayarkanni
Published: September 2012

Background

Brain-derived neurotrophic factor (BDNF) is a potent neurotrophic factor that is implicated in the regulation of food intake and body weight. Polyunsaturated fatty acids (PUFAs) localised in cell membranes have been shown to alter the levels of BDNF in the brain, suggesting that PUFAs and BDNF could have physical interaction with each other. To decipher the molecular mechanism through which PUFAs modulates BDNF’s activity, molecular docking was performed for BDNF with PUFAs and its metabolites, with 4-Methyl Catechol as a control.

Results

Inferring from molecular docking studies, lipoxin A4 (LXA4), and a known anti-inflammatory bioactive metabolite derived from PUFAs, with a binding energy of −3.98 Kcal/mol and dissociation constant of 1.2mM showed highest binding affinity for BDNF in comparison to other PUFAs and metabolites considered in the study. Further, the residues Lys 18, Thr 20, Ala 21, Val 22, Phe 46, Glu 48, Lys 50, Lys 58, Thr 75, Gln 77, Arg 97 and Ile 98 form hot point motif, which on interaction enhances BDNF’s function.

Conclusion

These results suggest that PUFAs and their metabolites especially, LXA4, modulate insulin resistance by establishing a physical interaction with BDNF. Similar interaction(s) was noted between BDNF and resolvins and protectins but were of lesser intensity compared to LXA4.
Sentinel site community surveillance of mortality and nutritional status in southwestern Central African Republic, 2010
Authors: Caleo Grazia M , Sy Aly Penda , Balandine Serge , Polonsky Jonathan , Palma Pedro Pablo , Grais Rebecca Freeman , Checchi Francesco
Published: September 2012

Background

During 2010, a community-based, sentinel site prospective surveillance system measured mortality, acute malnutrition prevalence, and the coverage of a Médecins Sans Frontières (MSF) intervention in four sous-préfectures of Lobaye prefecture in southwestern Central African Republic. We describe this surveillance system and its evaluation.

Methods

Within 24 randomly selected sentinel sites, home visitors performed a census, weekly demographic surveillance of births, deaths, and in- or out-migration, and weekly anthropometry on a sample of children. We evaluated the system through various methods including capture-recapture analysis and repeat census.

Results

The system included 18,081 people at baseline. Over 32 weeks, the crude death rate was 1.0 (95% confidence interval [CI]: 0.8-1.2) deaths per 10,000 person-days (35 deaths per 1,000 person-years), with higher values during the rainy season. The under-5 death rate was approximately double. The prevalence of severe acute malnutrition (SAM) was 3.0% (95% CI: 2.3-4.0), almost half featuring kwashiorkor signs. The coverage of SAM treatment was 29.1%. The system detected >90% of deaths, and >90% of death reports appeared valid. However, demographic surveillance yielded discrepancies with the census and an implausible rate of population growth, while the predictive value of SAM classification was around 60%.

Discussion

We found evidence of a chronic health crisis in this remote region. MSF's intervention coverage improved progressively. Mortality data appeared valid, but inaccuracies in population denominators and anthropometric measurements were noted. Similar systems could be implemented in other remote settings and acute emergencies, but with certain technical improvements.
Magnonic band structure investigation of one-dimensional bi-component magnonic crystal waveguides
Authors: Ma Fu Sheng , Lim Hock Siah , Zhang Vanessa Li , Ng Ser Choon , Kuok Meng Hau
Published: September 2012

The magnonic band structures for exchange spin waves propagating in one-dimensional magnonic crystal waveguides of different material combinations are investigated using micromagnetic simulations. The waveguides are periodic arrays of alternating nanostripes of different ferromagnetic materials. Our results show that the widths and center frequencies of the bandgaps are controllable by the component materials, the stripe widths, and the orientation of the applied magnetic field. One salient feature of the bandgap frequency plot against stripe width is that there are n-1 zero-width gaps for the n th bandgap for both transversely and longitudinally magnetized waveguides. Additionally, the largest bandgap widths are primarily dependent on the exchange constant contrast between the component materials of the nanostructured waveguides.
Difference-differential operators for basic adaptive discretizations and their central function systems
Authors: Birk Lucia , Roßkopf Sophia , Ruffing Andreas
Published: September 2012

The concept of inherited orthogonality is motivated and an optimality statement for it is derived. Basic adaptive discretizations are introduced. Various properties of difference operators which are directly related to basic adaptive discretizations are looked at. A Lie-algebraic concept for obtaining basic adaptive discretizations is explored. Some of the underlying moment problems of basic difference equations are investigated in greater detail.
Proximal junctional vertebral fracture-subluxation after adult spine deformity surgery. Does vertebral augmentation avoid this complication? A case report
Authors: Fernández-Baíllo Nicomedes , Sánchez Márquez José Miguel , Sánchez Pérez-Grueso Francisco Javier , García Fernández Alfredo
Published: September 2012

Background

To report to the orthopedic community a case of vertebral fracture and adjacent vertebral subluxation through the upper instrumented vertebra after thoracolumbar fusion with augmentation of the cranial level.

Methods

This report reviewed the patient`s medical record, her imaging studies and related literature. The possible factors contributing to this fracture are hypothesized.

Results

A 70-year-old woman underwent decompressive surgery and posterolateral fusion for adult lumbar scoliosis. We used pedicular screws from T10 to S1 and iliac screw at the right side, augmented with cement at T10, T11, L1, L5 and S1; and prophylactic vertebroplasty at T9 to avoid the "topping-off syndrome".

Thirty days after discharge, without recognizable inciting trauma, the patient complained of pain in the lower thoracic area. The exam revealed overall neurological deficit below the level of fracture.

CT scan and MRI demonstrated a T10 vertebral collapse and T9 vertebral subluxation with morphologic features of flexion-distraction fracture through the upper edge of the screw.

At this point, the authors performed posterior decompression at T9 to T10 and extended posterolateral arthrodesis from T2 to T10.

To our knowledge, this is an unreported fracture.

Conclusions

Augmentation of the cranial level in a long thoracolumbar fusion has been developed to avoid the junctional kyphosis and compression fractures at that level. We alert the orthopedic community that this augmentation may lead to further and more severe fractures, although this opinion requires investigation for confirmation.
Evolutionary principles and synthetic biology: avoiding a molecular tragedy of the commons with an engineered phage
Authors: Gladstone Eric G , Molineux Ian J , Bull James J
Published: September 2012

Background

In prior work, adding a gene to phage T7 that degraded the host K1 capsule facilitated growth when plated on capsulated hosts. However, the transgenic protein (an endosialidase) is expressed as an exoenzyme, released from the cell at lysis but unattached to the phage particle. There is thus the possibility that the gene will be subject to a tragedy of the commons and be selected against, if the enzyme benefits other genomes.

Results

This evolutionary perspective was supported in short term experiments. The genome carrying the endosialidase gene was favored on a capsulated host if grown in physical isolation of control genomes (lacking the gene) but was selected against otherwise.

Conclusions

These results challenge efforts to engineer phages with exoenzymes that degrade biofilm polymers. If biofilms do not facilitate spatially structured phage growth, the transgenic enzymes may be rapidly eliminated from the phage population after release in the environment, even if the transgene benefits overall phage growth on the biofilm.
Differentiating Entamoeba histolytica, Entamoeba dispar and Entamoeba moshkovskii using nested polymerase chain reaction (PCR) in rural communities in Malaysia
Authors: Ngui Romano , Angal Lorainne , Fakhrurrazi Siti Aminah , Lian Yvonne Lim Ai , Ling Lau Yee , Ibrahim Jamaiah , Mahmud Rohela
Published: September 2012

Background

In this study, a total of 426 human faecal samples were examined for the presence of Entamoeba histolytica, Entamoeba dispar, Entamoeba moshkovskii infection via a combination of microscopic examination and nested polymerase chain reaction (PCR) targeting 16S ribosomal RNA of Entamoeba species.

Methods

Faecal sample were collected from 426 participants in five rural villages in Peninsular Malaysia. The faecal samples were processed by direct wet smear and formalin ethyl acetate concentration technique followed by iodine staining and examined via microscopy for the presence of Entamoeba species and other intestinal parasites. Microscopically positive samples for Entamoeba species cysts were further characterized using a Nested Polymerase Chain Reaction (Nested-PCR) targeting 16S-like ribosomal RNA gene. The data entry and analysis was carried out using the SPSS software (Statistical Package for the Social Sciences) program for Windows version 17 (SPSS, Chicago, IL, USA).

Results

Based on single faecal examination, overall prevalence of Entamoeba infection was 17.6% (75/426). Females (19.1%) were more commonly infected compared to males (15.9%). Comparison by age groups showed that adults (23.9%) had higher infection rates than children (15.3%). The PCR results showed that 52 out of 75 microscopy positive samples successfully generated species-specific amplicons. The infection with E. histolytica (75.0%; 39/52) was the most common, followed by E. dispar (30.8%; 18/52) and E. moshkovskii (5.8%; 3/52). Of these, 33 (63.5%) were shown to contain only E. histolytica, 10 (19.2%) contained E. dispar and 3 (5.8%) contained only E. moshkovskii. Mixed infection with E. histolytica and E. dispar was found in 6 (11.5%) samples.

Conclusions

The present study essentially emphasized the benefit of molecular techniques in discriminating the pathogenic Entamoeba species from the non-pathogenic for accurate diagnosis and better management of amoebiasis. The presence of E. moshkovskii is of great public health concern as it was the first time it has been reported in Malaysia.
Skeletal muscle volume following dehydration induced by exercise in heat
Authors: Hackney Kyle J , Cook Summer B , Fairchild Timothy J , Ploutz-Snyder Lori L
Published: September 2012

Background

Intracellular skeletal muscle water is redistributed into the extracellular compartment during periods of dehydration, suggesting an associated decline in muscle volume. The purpose of this study was to evaluate skeletal muscle volume in active (knee extensors (KE)) and less active (biceps/triceps brachii, deltoid) musculature following dehydration induced by exercise in heat.

Methods

Twelve participants (seven men, five women) cycled in the heat under two conditions: (1) dehydration (DHYD) resulting in 3% and 5% losses of estimated total body water (ETBW), which was assessed by changes in body mass, and (2) fluid replacement (FR) where 3% and 5% losses of ETBW were counteracted by intermittent (20 to 30 min) fluid ingestion via a carbohydrate-electrolyte beverage. During both conditions, serum osmolality and skeletal muscle volume (assessed by magnetic resonance imaging) were measured at baseline and at the 3% and 5% ETBW loss measurement points.

Results

In DHYD, serum osmolality increased at 3% (p = 0.005) and 5% (p < 0.001) ETBW losses, while FR decreased serum osmolality at the 5% loss of ETBW time point (p = 0.009). In DHYD, KE muscle volume declined from 1,464 ± 446 ml to 1,406 ± 425 ml (3.9%, p < 0.001) at 3% ETBW loss and to 1,378 ± 421 ml (5.9%, p < 0.001) at 5% ETBW loss. The largest decline in KE volume in DYHD occurred in the mid-belly (31 ml, p = 0.001) and proximal (24 ml, p = 0.001) regions of the grouped vasti muscles. There were no changes in volume for the biceps/triceps (p = 0.35) or deltoid (p = 0.92) during DHYD. FR prevented the loss of KE muscle volume at 3% (1,430 ± 435 ml, p = 0.074) and 5% (1,431 ± 439 ml, p = 0.156) ETBW loss time points compared to baseline (1,445 ± 436 ml).

Conclusions

Following exercise in the heat, the actively contracting muscles lost volume, while replacing lost fluids intermittently during exercise in heat prevented this decline. These results support the use of muscle volume as a marker of water loss.
What Are They Thinking? Automated Analysis of Student Writing about Acid–Base Chemistry in Introductory Biology
Authors: Haudek Kevin C. , Prevost Luanna B. , Moscarella Rosa A. , Merrill John , Urban-Lurain Mark
Published: September 2012

Students’ writing can provide better insight into their thinking than can multiple-choice questions. However, resource constraints often prevent faculty from using writing assessments in large undergraduate science courses. We investigated the use of computer software to analyze student writing and to uncover student ideas about chemistry in an introductory biology course. Students were asked to predict acid–base behavior of biological functional groups and to explain their answers. Student explanations were rated by two independent raters. Responses were also analyzed using SPSS Text Analysis for Surveys and a custom library of science-related terms and lexical categories relevant to the assessment item. These analyses revealed conceptual connections made by students, student difficulties explaining these topics, and the heterogeneity of student ideas. We validated the lexical analysis by correlating student interviews with the lexical analysis. We used discriminant analysis to create classification functions that identified seven key lexical categories that predict expert scoring (interrater reliability with experts = 0.899). This study suggests that computerized lexical analysis may be useful for automatically categorizing large numbers of student open-ended responses. Lexical analysis provides instructors unique insights into student thinking and a whole-class perspective that are difficult to obtain from multiple-choice questions or reading individual responses.
Student Learning Outcomes and Attitudes When Biotechnology Lab Partners Are of Different Academic Levels
Authors: Miller Heather B. , Witherow D. Scott , Carson Susan
Published: September 2012

The North Carolina State University Biotechnology Program offers laboratory-intensive courses to both undergraduate and graduate students. In “Manipulation and Expression of Recombinant DNA,” students are separated into undergraduate and graduate sections for the laboratory, but not the lecture, component. Evidence has shown that students prefer pairing with someone of the same academic level. However, retention of main ideas in peer learning environments has been shown to be greater when partners have dissimilar abilities. Therefore, we tested the hypothesis that there will be enhanced student learning when lab partners are of different academic levels. We found that learning outcomes were met by both levels of student, regardless of pairing. Average undergraduate grades on every assessment method increased when undergraduates were paired with graduate students. Many of the average graduate student grades also increased modestly when graduate students were paired with undergraduates. Attitudes toward working with partners dramatically shifted toward favoring working with students of different academic levels. This work suggests that offering dual-level courses in which different-level partnerships are created does not inhibit learning by students of different academic levels. This format is useful for institutions that wish to offer “boutique” courses in which student enrollment may be low, but specialized equipment and faculty expertise are needed.
Biology Undergraduates’ Misconceptions about Genetic Drift
Authors: Andrews T. M. , Price R. M. , Mead L. S. , McElhinny T. L. , Thanukos A. , Perez K. E. , Herreid C. F. , Terry D. R. , Lemons P. P.
Published: September 2012

This study explores biology undergraduates’ misconceptions about genetic drift. We use qualitative and quantitative methods to describe students’ definitions, identify common misconceptions, and examine differences before and after instruction on genetic drift. We identify and describe five overarching categories that include 16 distinct misconceptions about genetic drift. The accuracy of students’ conceptions ranges considerably, from responses indicating only superficial, if any, knowledge of any aspect of evolution to responses indicating knowledge of genetic drift but confusion about the nuances of genetic drift. After instruction, a significantly greater number of responses indicate some knowledge of genetic drift (p = 0.005), but 74.6% of responses still contain at least one misconception. We conclude by presenting a framework that organizes how students’ conceptions of genetic drift change with instruction. We also articulate three hypotheses regarding undergraduates’ conceptions of evolution in general and genetic drift in particular. We propose that: 1) students begin with undeveloped conceptions of evolution that do not recognize different mechanisms of change; 2) students develop more complex, but still inaccurate, conceptual frameworks that reflect experience with vocabulary but still lack deep understanding; and 3) some new misconceptions about genetic drift emerge as students comprehend more about evolution.
Epithelial-mesenchymal transitions: insights from development
Authors: Lim Jormay , Thiery Jean Paul
Published: September 2012

Epithelial-mesenchymal transition (EMT) is a crucial, evolutionarily conserved process that occurs during development and is essential for shaping embryos. Also implicated in cancer, this morphological transition is executed through multiple mechanisms in different contexts, and studies suggest that the molecular programs governing EMT, albeit still enigmatic, are embedded within developmental programs that regulate specification and differentiation. As we review here, knowledge garnered from studies of EMT during gastrulation, neural crest delamination and heart formation have furthered our understanding of tumor progression and metastasis.
Promoter DNA methylation couples genome-defence mechanisms to epigenetic reprogramming in the mouse germline
Authors: Hackett Jamie A. , Reddington James P. , Nestor Colm E. , Dunican Donncha S. , Branco Miguel R. , Reichmann Judith , Reik Wolf , Surani M. Azim , Adams Ian R. , Meehan Richard R.
Published: September 2012

Mouse primordial germ cells (PGCs) erase global DNA methylation (5mC) as part of the comprehensive epigenetic reprogramming that occurs during PGC development. 5mC plays an important role in maintaining stable gene silencing and repression of transposable elements (TE) but it is not clear how the extensive loss of DNA methylation impacts on gene expression and TE repression in developing PGCs. Using a novel epigenetic disruption and recovery screen and genetic analyses, we identified a core set of germline-specific genes that are dependent exclusively on promoter DNA methylation for initiation and maintenance of developmental silencing. These gene promoters appear to possess a specialised chromatin environment that does not acquire any of the repressive H3K27me3, H3K9me2, H3K9me3 or H4K20me3 histone modifications when silenced by DNA methylation. Intriguingly, this methylation-dependent subset is highly enriched in genes with roles in suppressing TE activity in germ cells. We show that the mechanism for developmental regulation of the germline genome-defence genes involves DNMT3B-dependent de novo DNA methylation. These genes are then activated by lineage-specific promoter demethylation during distinct global epigenetic reprogramming events in migratory (∼E8.5) and post-migratory (E10.5-11.5) PGCs. We propose that genes involved in genome defence are developmentally regulated primarily by promoter DNA methylation as a sensory mechanism that is coupled to the potential for TE activation during global 5mC erasure, thereby acting as a failsafe to ensure TE suppression and maintain genomic integrity in the germline.
Cingulin is dispensable for epithelial barrier function and tight junction structure, and plays a role in the control of claudin-2 expression and response to duodenal mucosa injury
Authors: Guillemot Laurent , Schneider Yann , Brun Paola , Castagliuolo Ignazio , Pizzuti Daniela , Martines Diego , Jond Lionel , Bongiovanni Massimo , Citi Sandra
Published: September 2012

Cingulin (CGN) is a Mr 140 kDa protein, which is localized in the cytoplasmic region of vertebrate tight junctions (TJ), and regulates gene expression and RhoA signalling in cultured cells. To investigate the function of CGN at the organism level, we generated CGN knockout (CGN−/−) mice by homologous recombination. CGN−/− mice are viable and fertile, and are born at the expected mendelian ratios. Immunohistochemistry, immunofluorescence, electron microscopy, and permeability assays of epithelial tissues of CGN−/− mice show no cingulin labelling at junctions, normal localization of TJ proteins, and normal TJ structure and barrier function. Microarray analysis of intestinal cells does not show significant changes in gene expression between CGN−/− and CGN+/+ mice, whereas immunoblotting analysis shows a 2-fold increase in the levels of claudin-2 protein in the duodenum and the kidney of CGN−/− mice, compared to CGN+/+ littermates. Furthermore, CGN−/− mice show an exacerbated response to the ulcerogenic action of cysteamine, whereas acute injury of the colon by dextran sodium sulphate elicits undistinguishable responses in CGN−/− and CGN+/+ mice. We conclude that at the organism level cingulin is dispensable for the structure and barrier function of TJ, and it is embedded in signalling networks that control the expression of claudin-2, and the mucosal response to acute injury in the duodenum.
Autocrine regulation of TGF-β1-induced cell migration by exocytosis of ATP and activation of P2 receptors in human lung cancer cells
Authors: Takai Erina , Tsukimoto Mitsutoshi , Harada Hitoshi , Sawada Keisuke , Moriyama Yoshinori , Kojima Shuji
Published: September 2012

TGF-β1 plays a key role in cancer progression through induction of various biological effects, including cell migration. Extracellular nucleotides released from cells, such as ATP, play a role in signaling via activation of P2 receptors. We show here that exocytosis of ATP followed by activation of P2 receptors play a key role in TGF-β1-induced actin remodeling associated with cell migration. Treatment with TGF-β1 facilitated migration of human lung cancer A549 cells, which was blocked by pretreatment with ecto-nucleotidase and P2 receptor antagonists. ATP and P2 agonists facilitated cell migration. TGF-β1-induced actin remodeling, which contributes to cell migration, was also suppressed by pretreatment with ecto-nucleotidase and P2 receptor antagonists. Knockdown of P2X7 receptor suppressed TGF-β1-induced migration and actin remodeling. These results indicate the involvement of TGF-β1-induced ATP release in cell migration, at least in part, via activation of P2X7 receptors. TGF-β1 caused release of ATP from A549 cells within 10 min. Both ATP-enriched vesicles and expression of a vesicular nucleotide transporter (VNUT) SLC17A9, which is responsible for exocytosis of ATP, were found in cytosol of A549 cells. TGF-β1 failed to induce release of ATP from SLC17A9-knockdown cells. TGF-β1-induced cell migration and actin remodeling were also decreased in SLC17A9-knockdown cells. These results suggest the importance of exocytosis of ATP in cell migration. We conclude that autocrine signaling through exocytosis of ATP and activation of P2 receptors is required for the amplification of TGF-β1-induced migration of lung cancer cells.
Microdomains of muscarinic acetylcholine and InsP3 receptors create InsP3 junctions and sites of Ca2+ wave initiation in smooth muscle
Authors: Olson Marnie L. , Sandison Mairi E. , Chalmers Susan , McCarron John G.
Published: September 2012

Inositol 1,4,5-trisphosphate (InsP3)-mediated increases in cytosolic Ca2+ concentration ([Ca2+]c) regulate activities which include division, contraction and cell death. InsP3-evoked Ca2+ release often begins in a single site then regeneratively propagates through the cell as a Ca2+ wave. The Ca2+ wave consistently begins at the same site on successive activations. We addressed the mechanisms that determine the Ca2+ wave initiation site in intestinal smooth muscle cells. Neither an increased sensitivity of InsP3 receptors (InsP3R) to InsP3 nor regional clustering of muscarinic receptors (mAChR3) or InsP3R1 explained the initiation site. However, examination of the overlap of mAChR3 and InsP3R1 by centre of mass analysis revealed a small percentage (∼10%) of sites which showed colocalisation. Indeed, the extent of colocalisation was greatest at Ca2+ wave initiation site. The initiation site may arise from a selective delivery of InsP3 from mAChR3 activity to particular InsP3R to generate faster local [Ca2+]c increases at sites of co-localization. In support, a localized subthreshold ‘priming’ InsP3 concentration applied rapidly but at regions distant from the initiation site shifted the wave to the site of priming InsP3 release. Conversely, when the Ca2+ rise at the initiation site was rapidly and selectively attenuated the Ca2+ wave again shifted and initiated at a new site. These results indicate that Ca2+ waves initiate where there is a structural and functional coupling of mAChR3 and InsP3R1 which generates junctions in which InsP3 acts as a highly localized signal by being rapidly and selectively delivered to InsP3R.
Focal adhesion disassembly is regulated by a RIAM to MEK-1 pathway
Authors: Coló Georgina P. , Hernández-Varas Pablo , Lock John , Bartolomé Rubén A. , Arellano-Sánchez Nohemí , Strömblad Staffan , Teixidó Joaquin
Published: September 2012

Cell migration and invasion require regulated turnover of integrin-dependent adhesion complexes. RIAM is an adaptor protein mediating talin recruitment to the cell membrane, whose depletion leads to defective melanoma cell migration and invasion. Here we investigated the potential involvement of RIAM in focal adhesion (FA) dynamics. RIAM-depleted melanoma and breast carcinoma cells displayed an increased number, size and stability of FAs, which accumulated centrally located at the ventral cell surface, a phenotype caused by defective FA disassembly. Impairment in FA disassembly due to RIAM knocking down correlated with deficient integrin-dependent MEK-Erk1/2 activation, and importantly, overexpression of constitutively active MEK resulted in rescue of FA disassembly and recovery of cell invasion. Furthermore, RIAM-promoted RhoA activation following integrin engagement was needed for subsequent Erk1/2 activation, and RhoA overexpression partially rescued the FA phenotype in RIAM-depleted cells, suggesting a functional role also for RhoA downstream of RIAM, but upstream of Erk1/2. In addition, RIAM knock down led to enhanced phosphorylation of paxillin Tyr118 and Tyr31. However, expression of phosphomimetic and non-phosphorylatable mutants at these paxillin residues indicated that paxillin hyper-phosphorylation is a subsequent consequence of the blockade of FA disassembly, but does not cause the FA phenotype. RIAM depletion also weakened association between FA proteins, suggesting that it may play important adaptor roles for the correct assembly of adhesion complexes. Our data indicate that integrin-triggered, RIAM-dependent MEK activation may represent a key feed-back event required for efficient FA disassembly, which may contribute to explain the role of RIAM in cell migration and invasion.
Arsenite interferes with protein folding and triggers formation of protein aggregates in yeast
Authors: Jacobson Therese , Navarrete Clara , Sharma Sandeep K. , Sideri Theodora C. , Ibstedt Sebastian , Priya Smriti , Grant Chris M. , Christen Philipp , Goloubinoff Pierre , Tamás Markus J.
Published: September 2012

Several metals and metalloids profoundly affect biological systems, but their impact on the proteome and mechanisms of toxicity are not fully understood. Here, we demonstrate that arsenite causes protein aggregation in Saccharomyces cerevisiae. Various molecular chaperones were found to be associated with arsenite-induced aggregates indicating that this metalloid promotes protein misfolding. Using in vivo and in vitro assays, we show that proteins in the process of synthesis/folding are particularly sensitive to arsenite-induced aggregation, that arsenite interferes with protein folding by acting on unfolded polypeptides, and that arsenite directly inhibits chaperone activity. Thus, folding inhibition contributes to arsenite toxicity in two ways: by aggregate formation and by chaperone inhibition. Importantly, arsenite-induced protein aggregates can act as seeds committing other, labile proteins to misfold and aggregate. Our findings describe a novel mechanism of toxicity that may explain the suggested role of this metalloid in the etiology and pathogenesis of protein folding disorders associated with arsenic poisoning.