bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of the representativeness of a sentinel surveillance site for campylobacteriosis
Authors: BOLWELL C. F. , GILPIN B. J. , CAMPBELL D. , FRENCH N. P.
Published: November 2014

It is important to assess the suitability of sentinel sites for human disease; however, there have been few publications documenting the process of formal evaluation. We describe an approach to examining the representativeness of a single sentinel site employed for campylobacteriosis surveillance and source attribution, utilizing a selection of data sources and statistical comparisons of demographic, epidemiological and pathogen genotyping data across selected regions of New Zealand. Our findings showed that while this region captured the national variability in many variables, for example by containing sizable urban and rural populations, the relative frequency of these features did vary from other regions of New Zealand. We discuss the value of choosing a sentinel site that represents the national distribution of key variables, compared to a site that captures the broad features of the wider population, but provides greater power for the monitoring of sub-populations.
Complete paroxysmal atrioventricular block in a 2-year-old girl
Authors: Holst Line M. , Dixen Ulrik , Jeppesen Dorthe L.
Published: November 2014

We present a case of atypical syncope in a 2-year-old, otherwise healthy girl. The patient presented with three episodes of syncope without any precipitating factors and no family history of sudden unexpected death. Holter monitoring revealed 24 events of complete atrioventricular block lasting up to 6 seconds. A normal 12-lead electrocardiogram does not necessarily exclude cardiac disease, and Holter monitoring is warranted in children with atypical syncope.
Adolescent coarctation of aorta treated with subclavian-descending aorta bypass grafting
Authors: Benomrane Skander , Soumer Khedija , Khayati Adel
Published: November 2014

Background

Aortic coarctation in older children most frequently represents cases of re-coarctation following previous transcatheter or surgical therapy or missed cases of native coarctation.

Methods

We describe three cases of adolescents – two girls and one boy – with aortic coarctation, operated between January, 2012 and December, 2013. Computed tomography angiography was performed as an essential diagnostic procedure.

Results

Hypertension was detected, and weaker arterial pulses in the lower limbs were noted in all cases. All operations were performed via left posterolateral thoracotomy. Aortic coarctation was treated surgically, with left subclavian-lower descending thoracic aorta bypass grafting. Postoperative course was uneventful in all cases. No residual brachial-ankle pressure gradient was observed, and all patients have remained in good condition after the operation.

Conclusions

Surgical treatment of aortic coarctation in adolescent patients can be achieved by resection with end-to-end anastomosis, interposition of a graft or bypass graft across the area of coarctation when the distance to be bridged is too long for end-to-end repair.

The extra-anatomic subclavian-descending aortic bypass grafting provides good results in adolescent patients, particularly in those with complex coarctation.
Impairment of both languages in late bilinguals with dementia of the Alzheimer type
Authors: MANCHON MÉLANIE , BUETLER KARIN , COLOMBO FRANÇOISE , SPIERER LUCAS , ASSAL FRÉDÉRIC , ANNONI JEAN-MARIE
Published: November 2014

Neuropsychological theories raise the question if in late bilinguals with dementia of the Alzheimer type (DAT), the second language (L2) may be more impaired than the first (L1). We compared language performance in different tasks of oral comprehension (semantic and syntactic) and production (naming, repetition and fluency) in L1 and L2 in a group of 13 late proficient bilinguals wit DAT immersion, and a matched control group of 12 healthy late bilinguals. Two-way mixed repeated-measure ANOVAs with factors Language and Group revealed main effects of Group (p < .05) indicating that DAT affects all aspects of language. There was no Group × Language interaction, suggesting that DAT affects both languages similarly. Our study thus shows that neurodegenerative diseases affect L1 and L2 in a parallel manner, particularly at the levels of semantic, lexical and syntactic processing. These results speak in favour of a shared L1 and L2 network in late bilinguals.
Bilingualism and cognition: A focus on mechanisms
Authors: VALIAN VIRGINIA
Published: November 2014

The goal of my keynote article, “Bilingualism and Cognition” (Valian, 2014), was to resolve the inconsistencies in effects of bilingualism on executive functions, whether the individuals were children, young adults, or old people. To summarize (and sharpen) my argument:

1.

Especially in children and young adults, benefits of bilingualism for executive functions are not reliable. In old people, there are benefits for executive functions but contradictory results on delay of cognitive impairment, depending on whether studies are retrospective or prospective.

2.

All experiences that have benefits for executive functions and aging – and there are many – yield inconsistent effects. Bilingualism is not alone.

3.

Three reasons for inconsistencies in bilingualism and other experiences are:

a.

Executive function and cognitive reserve are broad cover terms for a variety of mechanisms, most of which are ill-understood. Because we mean different things by ‘executive function’ from one experiment to the next, we can both think we don't have an effect when we do and think we have an effect when we don’t.

b.

Tasks are impure: apparently similar tasks measure different aspects of executive function and measure other aspects of cognition as well. Because we lack a good analysis of tasks, we too often do not know what we are measuring. I encourage readers to examine the demos in the supplementary materials of the keynote article to see for themselves what the tasks are like.

c.

Individuals engage in many different activities that may be on a par with bilingualism in their benefits.

4.

Different types of bilingual experience are unlikely to explain the variability of findings, given the inconsistencies in extant data on varieties of bilingualism.

5.

There is a benefit of bilingualism, but bilingualism competes with other sources of benefits. Especially for children and young adults, whose daily lives are full of cognitively enriching and challenging experiences, we should expect variability in effects of being bilingual.

6.

The way forward is to focus on underlying mechanisms.
Bilingualism, cognition, and aging
Authors: ABUTALEBI JUBIN , CLAHSEN HARALD
Published: November 2014

Topics in psycholinguistics and the neurocognition of language rarely attract the attention of journalists or the general public. One topic that has done so, however, is the potential benefits of bilingualism for general cognitive functioning and development, and as a precaution against cognitive decline in old age. Sensational claims have been made in the public domain, mostly by journalists and politicians. Recently (September 4, 2014) The Guardian reported that “learning a foreign language can increase the size of your brain”, and Michael Gove, the UK's previous Education Secretary, noted in an interview with The Guardian (September 30, 2011) that “learning languages makes you smarter”. The present issue of BLC addresses these topics by providing a state-of-the-art overview of theoretical and experimental research on the role of bilingualism for cognition in children and adults.
The impact of the 2008 financial crisis on food security and food expenditures in Mexico: a disproportionate effect on the vulnerable
Authors: Vilar-Compte Mireya , Sandoval-Olascoaga Sebastian , Bernal-Stuart Ana , Shimoga Sandhya , Vargas-Bustamante Arturo
Published: November 2014

Objective

The present paper investigated the impact of the 2008 financial crisis on food security in Mexico and how it disproportionally affected vulnerable households.

Design

A generalized ordered logistic regression was estimated to assess the impact of the crisis on households’ food security status. An ordinary least squares and a quantile regression were estimated to evaluate the effect of the financial crisis on a continuous proxy measure of food security defined as the share of a household’s current income devoted to food expenditures.

Setting

Both analyses were performed using pooled cross-sectional data from the Mexican National Household Income and Expenditure Survey 2008 and 2010.

Subjects

The analytical sample included 29 468 households in 2008 and 27 654 in 2010.

Results

The generalized ordered logistic model showed that the financial crisis significantly (P<0·05) decreased the probability of being food secure, mildly or moderately food insecure, compared with being severely food insecure (OR=0·74). A similar but smaller effect was found when comparing severely and moderately food-insecure households with mildly food-insecure and food-secure households (OR=0·81). The ordinary least squares model showed that the crisis significantly (P<0·05) increased the share of total income spent on food (β coefficient of 0·02). The quantile regression confirmed the findings suggested by the generalized ordered logistic model, showing that the effects of the crisis were more profound among poorer households.

Conclusions

The results suggest that households that were more vulnerable before the financial crisis saw a worsened effect in terms of food insecurity with the crisis. Findings were consistent with both measures of food security – one based on self-reported experience and the other based on food spending.
Stunting at birth: recognition of early-life linear growth failure in the western highlands of Guatemala
Authors: Solomons Noel W , Vossenaar Marieke , Chomat Anne-Marie , Doak Colleen M , Koski Kristine G , Scott Marilyn E
Published: November 2014

Objective

Measurements of length at birth, or in the neonatal period, are challenging to obtain and often discounted for lack of validity. Hence, classical ‘under-5’ stunting rates have been derived from surveys on children from 6 to 59 months of age. Guatemala has a high prevalence of stunting (49·8 %), but the age of onset of growth failure is not clearly defined. The objective of the study was to assess length-for-age within the first 1·5 months of life among Guatemalan infants.

Design

As part of a cross-sectional observational study, supine length was measured in young infants. Mothers’ height was measured. Length-for-ageZ-scores (HAZ) were generated and stunting was defined as HAZ <−2 using WHO growth standards.

Setting

Eight rural, indigenous Mam-Mayan villages (n200, 100 % of Mayan indigenous origin) and an urban clinic of Quetzaltenango (n106, 27 % of Mayan indigenous origin), Guatemala.

Subjects

Three hundred and six newborns with a median age of 19 d.

Results

The median rural HAZ was −1·56 and prevalence of stunting was 38 %; the respective urban values were −1·41 and 25 %. Linear regression revealed no relationship between infant age and HAZ (r=0·101,r2=0·010,P=0·077). Maternal height explained 3 % of the variability in HAZ (r=0·171,r2=0·029,P=0·003).

Conclusions

Stunting must be carried over fromin uterogrowth retardation in short-stature Guatemalan mothers. As linear growth failure in this setting beginsin utero, its prevention must be linked to maternal care strategies during gestation, or even before. A focus on maternal nutrition and health in an intergenerational dimension is needed to reduce its prevalence.
PRO CDH-DESCENT FOR CYCLIC HOMOLOGY AND -THEORY
Authors: Morrow Matthew
Published: November 2014

In this paper, we prove that cyclic homology, topological cyclic homology, and algebraic $K$-theory satisfy a pro Mayer–Vietoris property with respect to abstract blow-up squares of varieties, in both zero and finite characteristic. This may be interpreted as the well-definedness of $K$-theory with compact support.
Effect of Fertility on Secondary Sex Ratio and Twinning Rate in Sweden, 1749–1870
Authors: Fellman Johan , Eriksson Aldur W.
Published: November 2014

We analyzed the effect of total fertility rate (TFR) and crude birth rate (CBR) on the number of males per 100 females at birth, also called the secondary sex ratio (SR), and on the twinning rate (TWR). Earlier studies have noted regional variations in TWR and racial differences in the SR. Statistical analyses have shown that comparisons between SRs demand large data sets because random fluctuations in moderate data are marked. Consequently, reliable results presuppose national birth data. Here, we analyzed historical demographic data and their regional variations between counties in Sweden. We built spatial models for the TFR in 1860 and the CBR in 1751–1870, and as regressors we used geographical coordinates for the provincial capitals of the counties. For both variables, we obtained significant spatial variations, albeit of different patterns and power. The SR among the live-born in 1749–1869 and the TWR in 1751–1860 showed slight spatial variations. The influence of CBR and TFR on the SR and TWR was examined and statistical significant effects were found.
The elimination of miR-23a in heat-stressed cells promotes NOXA-induced cell death and is prevented by HSP70
Authors: Roufayel R , Johnston D S , Mosser D D
Published: November 2014

Protein-damaging stress stimulates cell destruction through apoptosis; however, non-lethal proteotoxic stress induces an adaptive response leading to the increased synthesis of heat shock proteins, which inhibit apoptosis. In this study, we sought to determine the mechanism responsible for the accumulation of the BH3-only protein NOXA in heat-stressed cells and its prevention by the heat shock protein HSP70. Analysis of transcript levels by RT-qPCR revealed that miR-23a levels decreased in heat-stressed cells and that this was correlated with an increased abundance of NOXA mRNA, which contains a miR-23a binding site in its 3′ untranslated region. Cells overexpressing HSP70 had higher levels of miR-23a, maintained these levels after heat shock and accumulated lower levels of NOXA mRNA and protein. The enhanced abundance of mir-23a in these HSP70-expressing cells is primarily due to its increased stability although higher levels of pri/pre-miR-23a expression, nuclear export and maturation were also contributing factors. Stable overexpression of miR-23a in the acute lymphoblastic T-cell line PEER resulted in reduced basal and heat-induced levels of NOXA mRNA and significantly inhibited heat-induced apoptosis. Additionally, stable overexpression of an shRNA targeting miR-23a in U937 lymphoma cells produced stable knockdown of miR-23a and resulted in increased NOXA mRNA and an increased sensitivity to heat-induced apoptosis. These results demonstrate the novel finding that hyperthermia affects the abundance of a microRNA that targets the expression of a pro-apoptotic protein and that HSP70 protects cells from heat-induced apoptosis by regulating the abundance of this microRNA. We speculate that the inhibition of miRNA transcription in heat-stressed cells could represent a general mechanism for apoptosis induction that is regulated by the molecular chaperone protein HSP70. Furthermore, we propose that HSP70 could be beneficial to tumor cells by helping to maintain the expression of oncogenic miRNAs under conditions of cellular stress.
SAP97-mediated ADAM10 trafficking from Golgi outposts depends on PKC phosphorylation
Authors: Saraceno C , Marcello E , Di Marino D , Borroni B , Claeysen S , Perroy J , Padovani A , Tramontano A , Gardoni F , Di Luca M
Published: November 2014

A disintegrin and metalloproteinase 10 (ADAM10) is the major α-secretase that catalyzes the amyloid precursor protein (APP) ectodomain shedding in the brain and prevents amyloid formation. Its activity depends on correct intracellular trafficking and on synaptic membrane insertion. Here, we describe that in hippocampal neurons the synapse-associated protein-97 (SAP97), an excitatory synapse scaffolding element, governs ADAM10 trafficking from dendritic Golgi outposts to synaptic membranes. This process is mediated by a previously uncharacterized protein kinase C phosphosite in SAP97 SRC homology 3 domain that modulates SAP97 association with ADAM10. Such mechanism is essential for ADAM10 trafficking from the Golgi outposts to the synapse, but does not affect ADAM10 transport from the endoplasmic reticulum. Notably, this process is altered in Alzheimer's disease brains. These results help in understanding the mechanism responsible for the modulation of ADAM10 intracellular path, and can constitute an innovative therapeutic strategy to finely tune ADAM10 shedding activity towards APP.
TRPM2 channel deficiency prevents delayed cytosolic Zn2+ accumulation and CA1 pyramidal neuronal death after transient global ischemia
Authors: Ye M , Yang W , Ainscough J F , Hu X-P , Li X , Sedo A , Zhang X-H , Zhang X , Chen Z , Li X-M , Beech D J , Sivaprasadarao A , Luo J-H , Jiang L-H
Published: November 2014

Transient ischemia is a leading cause of cognitive dysfunction. Postischemic ROS generation and an increase in the cytosolic Zn2+ level ([Zn2+]c) are critical in delayed CA1 pyramidal neuronal death, but the underlying mechanisms are not fully understood. Here we investigated the role of ROS-sensitive TRPM2 (transient receptor potential melastatin-related 2) channel. Using in vivo and in vitro models of ischemia–reperfusion, we showed that genetic knockout of TRPM2 strongly prohibited the delayed increase in the [Zn2+]c, ROS generation, CA1 pyramidal neuronal death and postischemic memory impairment. Time-lapse imaging revealed that TRPM2 deficiency had no effect on the ischemia-induced increase in the [Zn2+]c but abolished the cytosolic Zn2+ accumulation during reperfusion as well as ROS-elicited increases in the [Zn2+]c. These results provide the first evidence to show a critical role for TRPM2 channel activation during reperfusion in the delayed increase in the [Zn2+]c and CA1 pyramidal neuronal death and identify TRPM2 as a key molecule signaling ROS generation to postischemic brain injury.
Combination therapy targeting ectopic ATP synthase and 26S proteasome induces ER stress in breast cancer cells
Authors: Chang H-Y , Huang T-C , Chen N-N , Huang H-C , Juan H-F
Published: November 2014

F1Fo ATP synthase is present in all organisms and is predominantly located on the inner membrane of mitochondria in eukaryotic cells. The present study demonstrated that ATP synthase and electron transport chain complexes were ectopically expressed on the surface of breast cancer cells and could serve as a potent anticancer target. We investigated the anticancer effects of the ATP synthase inhibitor citreoviridin on breast cancer cells through proteomic approaches and revealed that differentially expressed proteins in cell cycle regulation and in the unfolded protein response were functionally enriched. We showed that citreoviridin triggered PERK-mediated eIF2α phosphorylation, which in turn attenuated general protein synthesis and led to cell cycle arrest in the G0/G1 phase. We further showed that the combination of citreoviridin and the 26S proteasome inhibitor bortezomib could improve the anticancer activity by enhancing ER stress, by ameliorating citreoviridin-caused cyclin D3 compensation, and by contributing to CDK1 deactivation and PCNA downregulation. More interestingly, the combined treatment triggered lethality through unusual non-apoptotic caspase- and autophagy-independent cell death with a cytoplasmic vacuolization phenotype. The results imply that by boosting ER stress, the combination of ATP synthase inhibitor citreoviridin and 26S proteasome inhibitor bortezomib could potentially be an effective therapeutic strategy against breast cancer.
Evolution of dominance mechanisms at a butterfly mimicry supergene
Authors: Le Poul Yann , Whibley Annabel , Chouteau Mathieu , Prunier Florence , Llaurens Violaine , Joron Mathieu
Published: November 2014

Genetic dominance in polymorphic loci may respond to selection; however, the evolution of dominance in complex traits remains a puzzle. We analyse dominance at a wing-patterning supergene controlling local mimicry polymorphism in the butterfly Heliconius numata. Supergene alleles are associated with chromosomal inversion polymorphism, defining ancestral versus derived alleles. Using controlled crosses and the new procedure, Colour Pattern Modelling, allowing whole-wing pattern comparisons, we estimate dominance coefficients between alleles. Here we show strict dominance in sympatry favouring mimicry and inconsistent dominance throughout the wing between alleles from distant populations. Furthermore, dominance among derived alleles is uncoordinated across wing-pattern elements, producing mosaic heterozygous patterns determined by a hierarchy in colour expression. By contrast, heterozygotes with an ancestral allele show complete, coordinated dominance of the derived allele, independently of colours. Therefore, distinct dominance mechanisms have evolved in association with supergene inversions, in response to strong selection on mimicry polymorphism.
Direct evidence of milk consumption from ancient human dental calculus
Authors: Warinner C. , Hendy J. , Speller C. , Cappellini E. , Fischer R. , Trachsel C. , Arneborg J. , Lynnerup N. , Craig O. E. , Swallow D. M. , Fotakis A. , Christensen R. J. , Olsen J. V. , Liebert A. , Montalva N. , Fiddyment S. , Charlton S. , Mackie M. , Canci A. , Bouwman A. , Rühli F. , Gilbert M. T. P. , Collins M. J.
Published: November 2014

Milk is a major food of global economic importance and its consumption is regarded as a classic example of gene-culture evolution. Humans have exploited animal milk as a food resource for at least 8500 years, but the origins, spread and scale of dairying remain poorly understood. Indirect lines of evidence, such as lipid isotopic ratios of pottery residues, faunal mortality profiles and lactase persistence allele frequencies, provide a partial picture of this process; however, in order to understand how, where and when humans consumed milk products, it is necessary to link evidence of consumption directly to individuals and their dairy livestock. Here we report the first direct evidence of milk consumption, the whey protein β-lactoglobulin (BLG), preserved in human dental calculus from the Bronze Age (ca. 3000 BCE) to the present day. Using protein tandem mass spectrometry, we demonstrate that BLG is a species-specific biomarker of dairy consumption and we identify individuals consuming cattle, sheep and goat milk products in the archaeological record. We then apply this method to human dental calculus from Greenland's medieval Norse colonies and report a decline of this biomarker leading up to the abandonment of the Norse Greenland colonies in the 15th century CE.
IMP-1 encoded by a novel Tn402-like class 1 integron in clinical Achromobacter xylosoxidans, China
Authors: Chen Zhenhong , Fang Haihong , Wang Li , Sun Fengjun , Wang Yong , Yin Zhe , Yang Huiying , Yang Wenhui , Wang Jie , Xia Peiyuan , Zhou Dongsheng , Liu Changting
Published: November 2014

Achromobacter xylosoxidans strain A22732 is isolated from a pneumonia patient in China and produces carbapenemases OXA-114e and IMP-1, which are encoded by chromosome and plasmid, respectively and confer resistance to multiple ß-lactam antibiotics including carbapenems. The blaIMP-1 gene together with aacA7 and orfE is captured by a novel Tn402-like class 1 integron in a conjugative IncP-1ß plasmid. In addition to the intrinsic integron promoter PcW, there is still a blaIMP-1 gene cassette-specific promoter. This is the first report of carbapenemase-encoding IncP-1ß plasmid in clinical bacterial isolate.
Anthrapyrazolone analogues intercept inflammatory JNK signals to moderate endotoxin induced septic shock
Authors: Prasad Karothu Durga , Trinath Jamma , Biswas Ansuman , Sekar Kanagaraj , Balaji Kithiganahalli N. , Guru Row Tayur N.
Published: November 2014

Severe sepsis or septic shock is one of the rising causes for mortality worldwide representing nearly 10% of intensive care unit admissions. Susceptibility to sepsis is identified to be mediated by innate pattern recognition receptors and responsive signaling pathways of the host. Thec-Jun N-terminal Kinase (JNK)-mediated signaling events play critical role in bacterial infection triggered multi-organ failure, cardiac dysfunction and mortality. In the context of kinase specificities, an extensive library of anthrapyrazolone analogues has been investigated for the selective inhibition of c-JNK and thereby to gain control over the inflammation associated risks. In our comprehensive biochemical characterization, it is observed that alkyl and halogen substitution on the periphery of anthrapyrazolone increases the binding potency of the inhibitors specifically towards JNK. Further, it is demonstrated that hydrophobic and hydrophilic interactions generated by these small molecules effectively block endotoxin-induced inflammatory genes expression inin vitroand septic shockin vivo, in a mouse model, with remarkable efficacies. Altogether, the obtained results rationalize the significance of the diversity oriented synthesis of small molecules for selective inhibition of JNK and their potential in the treatment of severe sepsis.
Theoretical study on the role of dynamics on the unusual magnetic properties in MnBi
Authors: Shanavas K. V. , Parker David , Singh David J.
Published: November 2014

We study the electronic structure and lattice dynamics in the ferromagnet MnBi using first-principles calculations and a tight-binding model. The band structure around the Fermi level is dominated by Bi-p states which are the primary contributors to the magnetic anisotropy energy in the low temperature structure. A tight-binding model consisting of Mn-d and Bi-p states is developed and the parameters are determined from first-principles calculations. Phonon dispersions and elastic moduli exhibit several interesting features. The results imply that the magnetic interaction with the crystal lattice in MnBi is considerably more complex than previously thought and in particular that there is a rich interplay between phonons and magnetism involving both magnetoelastic and magnetostrictive coupling.
Net ammonium and nitrate fluxes in wheat roots under different environmental conditions as assessed by scanning ion-selective electrode technique
Authors: Zhong Yangquanwei , Yan Weiming , Chen Juan , Shangguan Zhouping
Published: November 2014

Wheat is one of the most important food crops in the world, its availability affects global food security. In this study, we investigated variations in NH4+ and NO3- fluxes in the fine roots of wheat using a scanning ion-selective electrode technique in the presence of different nitrogen (N) forms, N concentrations and pH levels as well as under water stress. Our results show that the fine roots of wheat demonstrated maximum NH4+ and NO3− influxes at 20 mm and 25 mm from the root tip, respectively. The maximal net NH4+ and NO3− influxes were observed at pH 6.2 in the presence of a 1/4 N solution. We observed N efflux in two different cultivars following the exposure of roots to a 10% PEG-6000 solution. Furthermore, the drought-tolerant cultivar generally performed better than the drought-intolerant cultivar. Net NH4+ and NO3− fluxes may be determined by plant growth status, but environmental conditions can also affect the magnitude and direction of N flux. Interestingly, we found that NO3− was more sensitive to environmental changes than NH4+. Our results may be used to guide future hydroponic experiments in wheat as well as to aid in the development of effective fertilisation protocols for this crop.
Supercooled water escaping from metastability
Authors: Aliotta Francesco , Giaquinta Paolo V. , Ponterio Rosina C. , Prestipino Santi , Saija Franz , Salvato Gabriele , Vasi Cirino
Published: November 2014

The return of supercooled water to a stable equilibrium condition is an irreversible process which, in large enough samples, takes place adiabatically. We investigated this phenomenon in water by fast imaging techniques. As water freezes, large energy and density fluctuations promote the spatial coexistence of solid and liquid phases at different temperatures. Upon synchronously monitoring the time evolution of the local temperature, we observed a sharp dynamic transition between a fast and a slow decay regime at about 266.6 K. We construe the observed phenomenon in terms of the temperature dependence of heat transfers from solid and liquid volumes already at their bulk coexistence temperature towards adjacent still supercooled liquid regions. These findings can be justified by observing that convective motions induced by thermal gradients in a supercooled liquid near coexistence are rapidly suppressed as the nucleated solid fraction overcomes, at low enough temperatures, a characteristic percolation threshold.
Nutritional Requirements for Manganese
Authors: Freeland-Graves Jeanne H. , Mousa Tamara Y. , Sanjeevi Namrata
Published: November 2014

Manganese (Mn) is a ubiquitous trace mineral that is essential for living organisms. This mineral is a cofactor of enzymes such as superoxide dismutase and arginase. It assumes a significant role in the metabolism of carbohydrates, amino acids and cholesterol, the formation of bone, digestion, and development. Food sources include whole grains, cereals, green leafy vegetables, nuts, and tea. Approaches to assess Mn requirements include metabolic balance, blood levels, and response of biomarkers. In the United States, the adequate intake (AI) of Mn is 1.8 and 2.3 mg day−1 for women and men, respectively. Negative balance has been reported in numerous studies, where Mn intake was greater than the AI; thus, the adequacy of current dietary recommendations is unclear. Factors that influence Mn requirements include life stage and gender, bioavailability (fiber, phytates, mineral interactions, polyphenolic compounds), and international considerations. Deficiency of Mn has been associated with adverse health conditions including dermatitis, osteoporosis, dyslipidemia, diabetes, metabolic syndrome, hypertension, epilepsy, cancer, asthma, problems with cognitive function, and poor birth outcomes. Toxicity of Mn may be a potential problem with contaminated drinking water, parenteral nutrition, individuals with hepatic dysfunction, and soy formula-fed infants. An understanding of Mn nutrient requirements is important for achievement of optimal health.
Manganese Superoxide Dismutase
Authors: Kiningham Kinsley K.
Published: November 2014

Highly reactive oxygen species (ROS) such as superoxide anion, O2•−, are formed in various locations within a cell and their generation can alter a variety of signaling cascades and impact numerous cellular processes such as proliferation, respiration and survival. The primary antioxidant, manganese-containing superoxide dismutase (MnSOD), is critical for mitochondrial dismutation of O2•−, with subsequent generation of hydrogen peroxide (H2O2) and modulation of cellular redox status. Genetically modified animals have identified MnSOD as essential for aerobic life and current experimental Cre-loxP strategies are furthering our knowledge of tissue specific contributions of the enzyme. Current knowledge about the transcriptional and post-translational regulation of MnSOD as well as recent studies of how these changes influence specific disease states are reviewed. For over 30 years the role of MnSOD in cancer has been extensively studied. First thought to act as a tumor suppressor, studies were aimed at overexpression in both in vitro and in vivo carcinogenesis models. Recent studies suggest oncogenic potential of the enzyme in a variety of tumors and discussions of this recently discovered paradox, as well as future experiments for improving prognosis, are reviewed.
Manganese Transport Across the Pulmonary Epithelium
Authors: Thompson Khristy J. , Kim Jonghan , Wessling-Resnick Marianne
Published: November 2014

Our lungs represent a significant exposure site to airborne metals. Manganese and other metals enter the bloodstream from a variety of airborne sources across the pulmonary epithelium. Once absorbed, manganese can be taken up by other organ systems like the brain, where it is known to exert neurotoxic effects. Models of pulmonary manganese absorption have been developed based on known pathways of uptake across the intestinal epithelium, which are regulated by iron status. The sum of evidence suggests that additional and perhaps unique transport pathways are available to manganese in order to transit the pulmonary epithelium. Both in vitro and in vivo models have been established to characterize not only the transport but also toxicity of manganese on pulmonary epithelial cells. Handling of manganese by the lungs plays an important role in the inflammatory response, and has a strong influence on lung infection. These issues and emerging new questions are discussed in this chapter.
Effect of Manganese on Signaling Pathways
Authors: Peres Tanara V. , Cordova Fabiano M. , Lopes Mark W. , Costa Ana Paula , Leal Rodrigo Bainy
Published: November 2014

A complex intercellular and intracellular signaling network modulates the main neural functions. Regulation of protein kinases and protein phosphatases activities modify the phosphorylation state of target proteins that direct a diversity of cell fates, including gene expression, neural cell migration, differentiation or proliferation, cell survival or death, and synaptic plasticity. Regardless of all these aspects, modulation of intracellular signaling pathways by toxicants has only recently become part of the molecular toxicology research. Manganese (Mn) exposure causes a neurological syndrome, manganism, which resembles Parkinson's disease. The mechanisms of Mn neurotoxicity are not completely clear but may involve mitochondrial dysfunctions, induction of oxidative stress, and alterations in dopaminergic system, especially in the basal ganglia. The modulation of intracellular cell signaling elements by Mn and the cell fates of these effects is an issue that requires attention. In this chapter, we will present cell signaling pathways dependent of protein kinases (e.g. PKA, PKC, MAPKs, AKT, and GSK3β) and protein phosphatases (e.g. PP1 and PP2A) that have been reported to be altered in response to Mn exposure. Since only a few studies have addressed these aspects in vivo, a series of data obtained in vitro from cell cultures exposed to Mn will also be presented, aiming to help us identify the possible sites of Mn action in cell signaling networks involved in the patophysiology of Mn neurotoxicity.
Manganese and Oxidative Stress
Authors: Ávila Daiana Silva , Farina Marcelo , Teixeira da Rocha João Batista , Aschner Michael
Published: November 2014

Although reactive oxygen species (ROS) are known to play crucial roles in maintaining cellular homeostasis, either an excessive increase in their production or a decrease of their detoxification causes oxidative stress, which is characterized as a disturbance in the pro-oxidant/antioxidant balance in favor of the former, leading to cellular damage. This chapter delves into the relationship between manganese (Mn) toxicity and oxidative stress. Although Mn has central physiological roles as cofactor of several enzymes, including antioxidant enzymes (i.e. Mn-superoxide dismutase), this chapter focuses on the pro-oxidative properties of Mn, presenting and discussing literature data concerning its effects on mitochondrial functioning, dopamine oxidation, and antioxidant defenses. The potential use of antioxidant approaches to mitigate Mn-induced toxicity is also presented.
Mechanism of Manganese-Induced Impairment of Astrocytic Glutamate Transporters
Authors: Karki Pratap , Smith Keisha , Aschner Michael , Lee Eunsook
Published: November 2014

Manganese (Mn) is an essential trace element, playing a vital role in numerous biochemical and cellular reactions; however, chronic exposure to high Mn levels from environmental and occupational sources causes a neurological disorder with shared features of Parkinson's disease (PD), referred to as manganism. Despite well-established pathological signs, the molecular mechanism(s) by which Mn induces these neurological disorders still remain to be established. In addition to oxidative stress and impairment of mitochondria, Mn dysregulates astrocytic glutamate transporters (GLAST [glutamate aspartate transporter] and GLT-1 [glutamate transporter 1]) by decreasing their promoter activity, mRNA, and protein levels as well as astrocytic glutamate uptake. The Mn-induced impairment in glutamate transporters is directly associated with excitotoxic neuronal death because the astrocytic glutamate transporters, GLAST and GLT-1, are mainly responsible for maintaining optimal glutamate levels in the synaptic clefts, thereby preventing glutamate-induced neuronal excitotoxicity. It is widely recognized that reduced expression and function of astrocytic glutamate transporters, in particular GLT-1, are associated with various neurodegenerative diseases, including PD and amyotrophic lateral sclerosis (ALS). Therefore, Mn-induced impairment of astrocytic glutamate transporters might be a critical mechanism for Mn neurotoxicity. Our latest studies have uncovered a novel mechanism of Mn-induced repression of GLT-1 at the transcriptional level. It appears that the transcription factor yin yang 1 (YY1) plays a critical role in Mn-induced repression of GLT-1 promoter activity and expression. Herein, we will discuss the cellular and molecular mechanisms by which Mn induces neurotoxicity, such as oxidative stress, mitochondrial impairment, inflammation, and dysregulation of glutamate transporters.
Modeling Manganese Kinetics for Human Health Risk Assessment
Authors: Yoon Miyoung , Taylor Michael D. , Clewell Harvey J. , Andersen Melvin E.
Published: November 2014

Manganese (Mn) is an essential element that is also toxic under conditions where body burden becomes sufficient to saturate homeostatic processes regulating excretion. The primary health concern regarding Mn overexposure is neurotoxicity, often expressed by varying degrees of motor or cognitive deficits. Target tissue concentration is the critical determinant for Mn toxicity, regardless of exposure route. Physiologically based pharmacokinetic (PBPK) models provide a means to predict the internal dose at the target tissue and extrapolate across subpopulations and/or exposure conditions. Recently a variety of PBPK models have been developed for Mn (e.g. adult, pregnant, lactating, and neonatal rats; non-human primates; and adult, pregnant, lactating, and neonatal humans). These models can predict exposure conditions that would lead to toxicologically significant increases in tissue Mn concentrations compared with those associated with normal dietary intake. This is done by incorporating uptake both from normal daily ingestion and additional exposure and homeostatic regulation of tissue levels that may lead to adaptive changes or tissue level excursions when it is overwhelmed. A review of Mn pharmacokinetic data used for model development, the PBPK modeling process incorporating Mn homeostasis in various exposure conditions and subpopulations, and the application of the models to Mn risk assessment is provided in this chapter.
Significance and Usefulness of Biomarkers of Exposure to Manganese
Authors: Hoet Perrine , Roels Harry A.
Published: November 2014

Manganese (Mn) accomplishes functions essential to maintaining human health, but at the same time this trace element can be toxic at low levels of exposure and accurate estimation of internal exposure is needed. A biomarker of exposure to Mn is meaningful only if there is sufficient knowledge of the toxicokinetics determining its presence in a biological medium (e.g. whole blood, plasma, urine, hair, nail). Moreover, biological monitoring of exposure to Mn is useful only when the biomarker is sufficiently specific and sensitive to distinguish exposed from non-exposed subjects, when it is dose-related to the external exposure (current, recent, or time-integrated), and when it displays reasonable dose–effect/response relationships with the occurrence of adverse effects on the central nervous system, the critical target for Mn exposure. Human investigations in which biomarkers of Mn exposure meet all these criteria are hard to locate. Overall, the available studies report poor or no associations on an individual basis between external (Mn in air or drinking water) and internal (Mn in blood, urine, hair, or nail) Mn exposure indices. This may be to some extent explained by features inherent of the Mn metabolism (homeostatic control), the Mn biomarker's half-life with respect to the exposure window, and the variable nature of external exposure scenarios. Studies particularly dealing with Mn inhalation exposure, different or poorly described methodological approaches, or air sampling strategies may render direct comparison and interpretation of results a tedious task. Nevertheless, several studies report significant dose–effect associations between biomarkers of Mn exposure and subclinical deficits of psychomotor or neuropsychological test performances. Because directly associated with the site of toxic action and providing the magnetic resonance imaging is done no later than three months after Mn exposure ceased, the Mn T1 relaxation time is potentially the better biomarker of Mn exposure in a clinical context (e.g. after long-term parenteral nutrition, chronic liver failure, methcathinone drug abuse). Magnetic resonance imaging is, however, unpractical as a tool for biological monitoring of exposure to Mn in the occupational setting (inhalation) and in the general population (air, drinking water). In conclusion, it would be inappropriate to recommend, on the basis of the currently available evidence, a reliable well-validated biomarker of exposure to Mn, or to establish a health-based threshold value for subclinical neurotoxic effects.
Developmental Effects of Manganese
Authors: Langevin Scott M. , Haynes Erin N.
Published: November 2014

The impact of manganese on human development is paradoxical, as it is both an essential nutrient and a toxicant. Current evidence indicates that manganese toxicity follows an inverted U-shaped curve where both low and high biological levels are associated with negative health consequences. Such adverse effects may be most severe in children at the earliest developmental stages, owing to their immature capacity for homeostatic control and underdeveloped blood–brain barrier, particularly in terms of neurodevelopment, bone development and growth, and possibly sexual maturation. This chapter summarizes the current body of literature surrounding these developmental effects.
The Effects of Manganese on Female Pubertal Development
Authors: Dees William L. , Hiney Jill K. , Srivastava Vinod K.
Published: November 2014

Manganese (Mn) is a naturally occurring essential trace element required for normal physiological processes. Both excesses and deficiencies of Mn are known to affect brain functions and are associated with health-related problems. For years it has been recognized that laboratory animals which are deficient in Mn show signs of impaired growth and reproduction. Because this element can cross the blood–brain barrier more efficiently in the young than in adult animals, and since it can accumulate in the hypothalamus, we have assessed the effects of low level Mn exposure on the onset of pubertal development. The age at which normal puberty occurs depends on a complex series of events within the hypothalamus that culminate in the increased synthesis and release of gonadotropin-releasing hormone (GnRH). This chapter will describe the action of prepubertal Mn exposure in inducing precocious puberty. Additionally, we will discuss the physiological and molecular mechanisms by which Mn can activate specific upstream puberty-related genes regulating hypothalamic GnRH synthesis and release. Our results are discussed in terms of how low level Mn exposure, resulting in a modest accumulation of the element within the hypothalamus too early in life, may cause a potential risk for developing precocious puberty.
Epidemiological Studies of Parkinsonism in Welders
Authors: Checkoway Harvey , Nielsen Susan Searles , Racette Brad A.
Published: November 2014

Welders have been the focus of numerous epidemiological studies addressing possible etiologic relations between manganese (Mn) and Parkinson disease (PD). These include investigations of defined cohorts of welders, which we regard as most informative, general population surveys of welding occupations, and population-based case-control studies. With a few notable exceptions among the studies of defined cohorts of welders, there is little evidence that welders are at increased risk of PD. However, most prior research has suffered from severe limitations due to incomplete ascertainment of incident cases, questionable diagnostic accuracy, and non-specific Mn exposure assessment that precludes quantitative dose–response estimation. A potential etiologic relation between environmental Mn exposure and PD continues to be an important scientific and public health topic, given the ubiquitous nature of Mn exposure. Investigations of welders, who experience some of the highest Mn doses in the population, should remain a priority. Recommended future epidemiological research should involve longitudinal assessments of risk, severity, and progression of clinically diagnosed PD among well-characterized cohorts of welders, whose exposures to Mn and potential confounders can be assessed quantitatively.
Manganese and Huntington Disease
Authors: Tidball Andrew M. , Bichell Terry Jo , Bowman Aaron B.
Published: November 2014

Huntington's disease (HD) is a devastating neurodegenerative disease presenting with impaired movement, psychological and behavioral disturbances, and cognitive decline. The most pronounced symptoms are motor impairments caused by degeneration of the medium spiny neurons of the caudate and putamen. Heavy metals are closely linked with both function and dysfunction in these basal ganglia nuclei, and are, therefore, likely candidates to be the environmental modifiers for age of onset in HD. HD patient cortices and mouse in vitro and in vivo models of HD have shown decreases in accumulation of manganese (Mn2+). Manganese is a necessary cofactor for several enzymes vital to proper cellular functioning, including arginase, manganese superoxide dismutase, glutamine synthetase, and pyruvate carboxylase. Additionally, manganese has also been shown to alter cellular signaling, particularly in the IGF–AKT and ATM–p53 pathways. Manganese deficiency can result in many dysfunctional manifestations similar to Huntington's disease, including urea cycle dysfunction, altered glutamate regulation, increased oxidative stress, and metabolic disturbances, in which these enzymatic functions are crucial. In this chapter, we elaborate on the potential influence of manganese and other metals in Huntington's disease; we also investigate the potential role of manganese-dependent enzymes in HD pathophysiology.
DNA Damage Induced by Manganese
Authors: Bornhorst Julia , Schwerdtle Tanja
Published: November 2014

This chapter summarizes the current studies on the genotoxic potential of manganese (Mn) and is thereby points out that the knowledge gained up to now is quite equivocal. Besides reviewing the current literature on Mn-induced DNA damage on a chromosomal as well as a DNA level, possible underlying mechanisms, including disturbances of DNA replication/DNA polymerases as well as DNA damage response pathways, are discussed. Finally, this chapter gives a brief overview of the possible consequences of DNA damage induced by manganese.
Amperometric hydrogen peroxide and glucose biosensor based on NiFe2/ordered mesoporous carbon nanocomposites
Authors: Xiang Dong , Yin Longwei , Ma Jingyun , Guo Enyan , Li Qun , Li Zhaoqiang , Liu Kegao
Published: November 2014

Well-dispersed NiFe2 nanoparticles homogeneously embedded in OMC display high electrochemical biosensing performance for the amperometric detection of H2O2 and glucose.