bluuebunny/crossref_metadata_2025 huggingface dataset:
Japanese Feminism in East-Asian Networking
Authors: Kitagawa Sakiko
Published: January 2012

Japanese feminist philosophy has in the last 15 years focused on the theme of‘ sexual slavery’, especially on the issue of ‘comfort women’. The issue of ‘comfort women’ was not only a highly charged social and political issue, but also the turning point in conceptualizing the category of ‘the other’ from the viewpoint of East Asian feminist philosophy. It enabled Asian women philosophers to rethink the feminine solidarity and also to create a new forum for a transnational feminist philosophy in East Asia. For this purpose of feminist philosophy in networking, a group of East Asian women philosopher is working together on the task of Asian philosophy of gender as well as on a new line in the philosophy of ‘the other’.

In my paper, I would like to describe the conceptual framework of this feminist philosophy in networking and want to try to redefine the concept of gender from East Asian feminist philosophy.
From Philosophy of the Feminine to Clinical Philosophy
Authors: Kanai Yoshiko
Published: January 2012

By focusing on the concept of “clinical philosophy”, this paper develops a Narrative/Trauma approach to deal with the philosophical problematic of oppression and violence. It establishes a link to a “philosophy of the feminine” and brings it together with clinical wisdom to describe a “sphere of intimacy without violence”. The ideology of motherhood so deeply embedded in Japanese society makes unavoidable for feminist philosophy in Japan to question femininity from the standpoint of the double nature of female self as woman and mother. Confronting the motherhood that regulates core Japanese culture and mentality requires a critique of the practice of matri-archy in the intimate sphere. Historically, post-war Japanese family appears in continuity with the matriarchal nature of the imperial and military regime in pre-war Japan. To be fully effective, feminism should therefore transform itself from a gender category to a philosophy, and create a concept of feminine that would be the core notion of feminism as a philosophy.
Does the Word Exhaust Meaning?
Authors: Nakajima Takahiro
Published: January 2012

In order to control language Chinese philosophy discovered methods other than the ‘rectification of names’. On one hand there is the total annihilation of language, and on the other a greater clarification of language than the one performed by the ‘rectification of language’. To understand this situation better it is necessary to go backwards in the genealogy from the controversy over the theory that ‘language exhausts meaning’ and the one that maintains ‘language does not exhaust meaning’, which took place in the period of the six dynasties (second half of the third century of the Christian era). We shall look at the controversy between the argument of Ouyang Jian and that of Xun Can. Then we reach the theory of Wang Bi, who synthesizes the controversy and invents another idea about language. This idea is a ‘forgotten language’ that tries to annihilate completely the alterity of language. What is aimed at in the annihilation of language is a world of pure meaning which increases profit, which is governed magnificently: it is a world where everything is reduced to the One.
The Acetyltransferase CLOCK Is Dispensable for Circadian Aftereffects in Mice
Authors: Beaulé Christian , Cheng Hai-Ying M.
Published: January 2012

Recent demonstration of the histone acetyltransferase activity of the Clock gene greatly expanded the regulatory role of circadian clocks in gene transcription. Clock and its partner Bmal1 are responsible for the generation of circadian oscillations that are synchronized (entrained) to the external light cycle. Entraining light often produces long-lasting changes in the endogenous period called aftereffects. Aftereffects are light-dependent alterations in the speed of free-running rhythms that persist for several weeks upon termination of light exposure. How light causes such long-lasting changes is unknown. However, the persistent nature of circadian aftereffects in conjunction with the long-term effects of epigenetic modifications on development and various aspects of brain physiology prompted us to hypothesize that the histone acetyltransferase CLOCK was required for circadian aftereffects. The authors exposed Clock knockout mice to 25-hour light cycles and report that these mice retain the ability to display circadian aftereffects, indicating that Clock is dispensable for this form of circadian plasticity.
Light Affects the Branching Pattern of Peptidergic Circadian Pacemaker Neurons in the Brain of the Cockroach Leucophaea maderae
Authors: Wei Hongying , Stengl Monika
Published: January 2012

Pigment-dispersing factor–immunoreactive neurons anterior to the accessory medulla (aPDFMes) in the optic lobes of insects are circadian pacemaker neurons in cockroaches and fruit flies. The authors examined whether any of the aPDFMes of the cockroach Leucophaea maderae are sensitive to changes in period and photoperiod of light/dark (LD) cycles as a prerequisite to adapt to changes in external rhythms. Cockroaches were raised in LD cycles of 11:11, 13:13, 12:12, 6:18, or 18:6 h, and the brains of the adults were examined with immunocytochemistry employing antisera against PDF and orcokinin. Indeed, in 11:11 LD cycles, only the number of medium-sized aPDFMes specifically decreased, while it increased in 13:13. In addition, 18:6 LD cycles increased the number of large- and medium-sized aPDFMes, as well as the posterior pPDFMes, while 6:18 LD cycles only decreased the number of medium-sized aPDFMes. Furthermore, PDF-immunoreactive fibers in the anterior optic commissure and orcokinin-immunoreactive fibers in both the anterior and posterior optic commissures were affected by different lengths of light cycles. Thus, apparently different groups of the PDFMes, most of all the medium-sized aPDFMes, which colocalize orcokinin, respond to changes in period and photoperiod and could possibly allow for the adjustment to different photoperiods.
Seasonal Changes in Cell Proliferation in the Adult Sheep Brain and Pars Tuberalis
Authors: Migaud Martine , Batailler Martine , Pillon Delphine , Franceschini Isabelle , Malpaux Benoît
Published: January 2012

To adapt to seasonal variations in the environment, most mammalian species exhibit seasonal cycles in their physiology and behavior. Seasonal plasticity in the structure and function of the central nervous system contributes to the adaptation of this physiology in seasonal mammals. As part of these plasticity mechanisms, seasonal variations in proliferation rate and neuron production have been extensively studied in songbirds. In this report, we investigated whether this type of brain plasticity also occurs in sheep, a seasonal species, by assessing variations in cell proliferation in the sheep diencephalon. We administered the cell birth marker 5′-bromodeoxyuridine (BrdU) to adult female sheep in July and December, during long and short photoperiod, respectively. The BrdU incorporation was analyzed and quantified in the hypothalamus, a key center for neuroendocrine regulations, as well as in other structures involved in relaying neuroendocrine and sensory information, including the median eminence, the pars tuberalis of the pituitary gland, and the thalamus. In December, 2-fold and 6-fold increases in the number of BrdU+ nuclei were observed in the hypothalamus and thalamus, respectively, when compared with July. This variation is independent of the influence of peripheral gonadal estradiol variations. An inverse seasonal regulation of cell proliferation was observed in the pars tuberalis. In contrast, no seasonal variation in cell proliferation was seen in the subventricular zone of the lateral ventricle. Many of the newborn cells in the adult ovine hypothalamus and thalamus differentiate into neurons and glial cells, as assessed by the expression of neuronal (DCX, NeuN) and glial (GFAP, S100B) fate markers. In summary, we show that the estimated cell proliferation rates in the sheep hypothalamus, thalamus, and pars tuberalis are different between seasons. These variations are independent of the seasonal fluctuations of peripheral estradiol levels, unlike the results described in the brain nuclei involved in song control of avian species.
Functional Conservation of Clock Output Signaling between Flies and Intertidal Crabs
Authors: Beckwith Esteban J. , Lelito Katherine R. , Hsu Yun-Wei A. , Medina Billie M. , Shafer Orie , Ceriani M. Fernanda , de la Iglesia Horacio O.
Published: January 2012

Intertidal species have both circadian and circatidal clocks. Although the behavioral evidence for these oscillators is more than 5 decades old, virtually nothing is known about their molecular clockwork. Pigment-dispersing hormones (PDHs) were originally described in crustaceans. Their insect homologs, pigment-dispersing factors (PDFs), have a prominent role as clock output and synchronizing signals released from clock neurons. We show that gene duplication in crabs has led to two PDH genes (β -pdh-I and β -pdh-II). Phylogenetically, β -pdh-I is more closely related to insect pdf than to β -pdh-II, and we hypothesized that β-PDH-I may represent a canonical clock output signal. Accordingly, β-PDH-I expression in the brain of the intertidal crab Cancer productus is similar to that of PDF in Drosophila melanogaster, and neurons that express PDH-I also show CYCLE-like immunoreactivity. Using D. melanogaster pdf-null mutants ( pdf01) as a heterologous system, we show that β -pdh-I is indistinguishable from pdf in its ability to rescue the mutant arrhythmic phenotype, but β -pdh-II fails to restore the wild-type phenotype. Application of the three peptides to explanted brains shows that PDF and β-PDH-I are equally effective in inducing the signal transduction cascade of the PDF receptor, but β-PDH-II fails to induce a normal cascade. Our results represent the first functional characterization of a putative molecular clock output in an intertidal species and may provide a critical step towards the characterization of molecular components of biological clocks in intertidal organisms.
Daily Rhythms in Olfactory Discrimination Depend on Clock Genes but Not the Suprachiasmatic Nucleus
Authors: Granados-Fuentes Daniel , Ben-Josef Gal , Perry Gavin , Wilson Donald A. , Sullivan-Wilson Alexander , Herzog Erik D.
Published: January 2012

The suprachiasmatic nucleus (SCN) regulates a wide range of daily behaviors and has been described as the master circadian pacemaker. The role of daily rhythmicity in other tissues, however, is unknown. We hypothesized that circadian changes in olfactory discrimination depend on a genetic circadian oscillator outside the SCN. We developed an automated assay to monitor olfactory discrimination in individual mice throughout the day. We found olfactory sensitivity increased approximately 6-fold from a minimum during the day to a peak in the early night. This circadian rhythm was maintained in SCN-lesioned mice and mice deficient for the Npas2 gene but was lost in mice lacking Bmal1 or both Per1 and Per2 genes. We conclude that daily rhythms in olfactory sensitivity depend on the expression of canonical clock genes. Olfaction is, thus, the first circadian behavior that is not based on locomotor activity and does not require the SCN.
Hypothesis
Authors: Hazlerigg David G. , Lincoln Gerald A.
Published: January 2012

Circannual rhythms are innately timed long-term (tau ≈ 12 months) cycles of physiology and behavior, crucial for life in habitats ranging from the equator to the Poles. Here the authors propose that circannual rhythm generation depends on tissue-autonomous, reiterated cycles of cell division, functional differentiation, and cell death. They see the feedback control influencing localized stem cell niches as crucial to this cyclical histogenesis hypothesis. Analogous to multi-oscillator circadian organization, circannual rhythm generation occurs in multiple tissues with hypothalamic and pituitary sites serving as central pacemakers. Signals including day length, nutrition, and social factors can synchronize circannual rhythms through hormonal influences, notably via the thyroid and glucocorticoid axes, which have profound effects on histogenesis. The authors offer 4 arguments in support of this hypothesis: (1) Cyclical histogenesis is a prevalent process in seasonal remodeling of physiology. It operates over long time domains and exhibits tissue autonomy in its regulation. (2) Experiments in which selected peripheral endocrine signals are held constant indicate that circannual rhythms are not primarily the product of interacting hormonal feedback loops. (3) Hormones known to control cell proliferation, differentiation, and organogenesis profoundly affect circannual rhythm expression. (4) The convergence point between photoperiodic input pathways and circannual rhythm expression occurs in histogenic regions of the hypothalamus and pituitary. In this review, the authors discuss how testing this hypothesis will depend on the use of cellular/molecular tools and animal models borrowed from developmental biology and neural stem cell research.
Addressing Alcohol Abuse in Gay Men
Authors: Blackwell Christopher W.
Published: January 2012

Research indicates gay men have higher rates of alcohol abuse compared to their heterosexual counterparts, suggesting this is a serious health concern for this patient population. Clinicians need to have a comprehensive understanding of this clinical problem and need to have an applicable understanding of strategies they can use to address this issue. This article presents a brief overview of alcohol abuse by gay men and highlights an approach clinicians can employ to effectively screen and treat these men for this problem. In conclusion, recommendations for future research are also discussed. Clinicians need to present with a non-judgmental and unbiased attitude towards their gay patients to best meet their health needs, including issues related to mental health and substance abuse.
Association between genetic variant on chromosome 12p13 and stroke survival and recurrence: a one year prospective study in Taiwan
Authors: Hsieh Yi-Chen , Seshadri Sudha , Chung Wen-Ting , Hsieh Fang-I , Hsu Yi-Hsiang , Lin Huey-Juan , Tseng Hung-Pin , Lien Li-Ming , Bai Chyi-Huey , Hu Chaur-Jong , Jeng Jiann-Shing , Tang Sung-Chun , Chen Chin-I , Yu Chia-Chen , Chiou Hung-Yi ,   the Formosa Stroke Genetic Consortium (FSGC)
Published: January 2012

Background

The association between ischemic stroke and 2 single nucleotide polymorphisms (SNPs) on chromosome 12p13, rs12425791 and rs11833579 appears inconsistent across different samples. These SNPs are close to the ninjurin2 gene which may alter the risk of stroke by affecting brain response to ischemic injury. The purpose of this study was to investigate the association between these two SNPs and ischemic stroke risk, as well as prognostic outcomes in a Taiwanese sample.

Methods

We examined the relations of these two SNPs to the odds of new-onset ischemic stroke, ischemic stroke subtypes, and to the one year risk of stroke-related death or recurrent stroke following initial stroke in a case-control study. A total of 765 consecutive patients who had first-ever ischemic stroke were compared to 977 stroke-free, age-matched controls. SNPs were genotyped by Taqman fluorescent allelic discrimination assay. The association between ischemic stroke and SNPs were analyzed by multivariate logistic regression. Cox proportional hazard model was used to assess the effect of individual SNPs on stroke-related mortality or recurrent stroke.

Results

There was no significant association between SNP rs12425791 and rs11833579 and ischemic stroke after multiple testing corrections. However, the marginal significant association was observed between SNP rs12425791 and large artery atherosclerosis under recessive model (OR, 2.30; 95%CI, 1.22-4.34; q-value = 0.062). Among the 765 ischemic stroke patients, 59 died or developed a recurrent stroke. After adjustment for age, sex, vascular risk factors and baseline stroke severity, Cox proportional hazard analysis indicated that the hazard ratios were 2.76 (95%CI, 1.34-5.68; q-value, 0.02) and 2.15 (95%CI, 1.15-4.02; q-value, 0.03) for individuals with homozygous variant allele of rs12425791 and rs11833579, respectively.

Conclusions

This is a precedent study that found genetic variants of rs12425791 and rs11833579 on chromosome 12p13 are independent predictors of stroke-related mortality or stroke recurrence in patients with incident ischemic stroke in Taiwan. Further study is needed to explore the details of the physiological function and the molecular mechanisms underlying the association of this genetic locus with ischemic stroke.
siRNA against presenilin 1 (PS1) down regulates amyloid β42 production in IMR-32 cells
Authors: Kandimalla Ramesh JL , Wani Willayat Yousuf , BK Binukumar , Gill Kiran Dip
Published: January 2012

Background

One of the pathological hallmarks of Alzheimer's disease (AD) is the deposition of the ~4 kDa amyloid β protein (Aβ) within lesions known as senile plaques. Aβ is also deposited in the walls of cerebral blood vessels in many cases of AD. A substantial proportion of the Aβ that accumulates in the AD brain is deposited as Amyloid, which is highly insoluble, proteinaceous material with a β-pleated-sheet conformation and deposited extracellularly in the form of 5-10 nm wide straight fibrils. As γ-secretase catalyzes the final cleavage that releases the Aβ42 or 40 from amyloid β -protein precursor (APP), therefore, it is a potential therapeutic target for the treatment of AD. γ-Secretase cleavage is performed by a high molecular weight protein complex containing presenilins (PSs), nicastrin, Aph-1 and Pen-2. Previous studies have demonstrated that the presenilins (PS1 and PS2) are critical components of a large enzyme complex that performs γ-secretase cleavage.

Methods

In this study we used RNA interference (RNAi) technology to examine the effects of small-interfering RNA (siRNA) against PS1 on expression levels of PS1 and Aβ42 in IMR-32 Cells using RTPCR, western blotting and immunofluorescence techniques.

Results

The results of the present study showed down regulation of PS1 and Aβ42 in IMR32 cells transfected with siRNA against PS1.

Conclusion

Our results substantiate the concept that PS1 is involved in γ-secretase activity and provides the rationale for therapeutic strategies aimed at influencing Aβ42 production.
GuiTope: an application for mapping random-sequence peptides to protein sequences
Authors: Halperin Rebecca F , Stafford Phillip , Emery Jack S , Navalkar Krupa Arun , Johnston Stephen Albert
Published: January 2012

Background

Random-sequence peptide libraries are a commonly used tool to identify novel ligands for binding antibodies, other proteins, and small molecules. It is often of interest to compare the selected peptide sequences to the natural protein binding partners to infer the exact binding site or the importance of particular residues. The ability to search a set of sequences for similarity to a set of peptides may sometimes enable the prediction of an antibody epitope or a novel binding partner. We have developed a software application designed specifically for this task.

Results

GuiTope provides a graphical user interface for aligning peptide sequences to protein sequences. All alignment parameters are accessible to the user including the ability to specify the amino acid frequency in the peptide library; these frequencies often differ significantly from those assumed by popular alignment programs. It also includes a novel feature to align di-peptide inversions, which we have found improves the accuracy of antibody epitope prediction from peptide microarray data and shows utility in analyzing phage display datasets. Finally, GuiTope can randomly select peptides from a given library to estimate a null distribution of scores and calculate statistical significance.

Conclusions

GuiTope provides a convenient method for comparing selected peptide sequences to protein sequences, including flexible alignment parameters, novel alignment features, ability to search a database, and statistical significance of results. The software is available as an executable (for PC) at http://www.immunosignature.com/software and ongoing updates and source code will be available at sourceforge.net.
Yeast-based assay identifies novel Shh/Gli target genes in vertebrate development
Authors: Milla Luis A , Cortés Claudio R , Hodar Q Christian , Oñate Maritza G , Cambiazo Veronica , Burgess Shawn M , Palma Verónica
Published: January 2012

Background

The increasing number of developmental events and molecular mechanisms associated with the Hedgehog (Hh) pathway from Drosophila to vertebrates, suggest that gene regulation is crucial for diverse cellular responses, including target genes not yet described. Although several high-throughput, genome-wide approaches have yielded information at the genomic, transcriptional and proteomic levels, the specificity of Gli binding sites related to direct target gene activation still remain elusive. This study aims to identify novel putative targets of Gli transcription factors through a protein-DNA binding assay using yeast, and validating a subset of targets both in-vitro and in-vivo. Testing in different Hh/Gli gain- and loss-of-function scenarios we here identified known (e.g., ptc1) and novel Hh-regulated genes in zebrafish embryos.

Results

The combined yeast-based screening and MEME/MAST analysis were able to predict Gli transcription factor binding sites, and position mapping of these sequences upstream or in the first intron of promoters served to identify new putative target genes of Gli regulation. These candidates were validated by qPCR in combination with either the pharmacological Hh/Gli antagonist cyc or the agonist pur in Hh-responsive C3H10T1/2 cells. We also used small-hairpin RNAs against Gli proteins to evaluate targets and confirm specific Gli regulation their expression. Taking advantage of mutants that have been identified affecting different components of the Hh/Gli signaling system in the zebrafish model, we further analyzed specific novel candidates. Studying Hh function with pharmacological inhibition or activation complemented these genetic loss-of-function approaches. We provide evidence that in zebrafish embryos, Hh signaling regulates sfrp2, neo1, and c-myc expression in-vivo.

Conclusion

A recently described yeast-based screening allowed us to identify new Hh/Gli target genes, functionally important in different contexts of vertebrate embryonic development.
Analysis of human immune responses in quasi-experimental settings: tutorial in biostatistics
Authors: Sarkar Rajiv , Ajjampur Sitara S , Ward Honorine D , Kang Gagandeep , Naumova Elena N
Published: January 2012

Background

Human immunology is a growing field of research in which experimental, clinical, and analytical methods of many life science disciplines are utilized. Classic epidemiological study designs, including observational longitudinal birth cohort studies, offer strong potential for gaining new knowledge and insights into immune response to pathogens in humans. However, rigorous discussion of methodological issues related to designs and statistical analysis that are appropriate for longitudinal studies is lacking.

Methods

In this communication we address key questions of quality and validity of traditional and recently developed statistical tools applied to measures of immune responses. For this purpose we use data on humoral immune response (IR) associated with the first cryptosporidial diarrhea in a birth cohort of children residing in an urban slum in south India. The main objective is to detect the difference and derive inferences for a change in IR measured at two time points, before (pre) and after (post) an event of interest. We illustrate the use and interpretation of analytical and data visualization techniques including generalized linear and additive models, data-driven smoothing, and combinations of box-, scatter-, and needle-plots.

Results

We provide step-by-step instructions for conducting a thorough and relatively simple analytical investigation, describe the challenges and pitfalls, and offer practical solutions for comprehensive examination of data. We illustrate how the assumption of time irrelevance can be handled in a study with a pre-post design. We demonstrate how one can study the dynamics of IR in humans by considering the timing of response following an event of interest and seasonal fluctuation of exposure by proper alignment of time of measurements. This alignment of calendar time of measurements and a child's age at the event of interest allows us to explore interactions between IR, seasonal exposures and age at first infection.

Conclusions

The use of traditional statistical techniques to analyze immunological data derived from observational human studies can result in loss of important information. Detailed analysis using well-tailored techniques allows the depiction of new features of immune response to a pathogen in longitudinal studies in humans. The proposed staged approach has prominent implications for future study designs and analyses.
Association of polymorphisms in survivin gene with the risk of hepatocellular carcinoma in Chinese han population: a case control study
Authors: Li Yuhua , Wang Jiaofeng , Jiang Feng , Lin Wenyao , Meng Wei
Published: January 2012

Background

Survivin, one of the strongest apoptosis inhibitors, plays a critical role in the development and progression of hepatocellular carcinoma (HCC). By comparison, relatively little is known about the effect of survivin gene polymorphisms on HCC susceptibility. Our study aimed to investigate the association of survivin gene polymorphisms with the risk of HCC in Chinese han population.

Methods

A case-control study was conducted in Chinese han population consisting of 178 HCC cases and 196 cancer-free controls. Information on demographic data and related risk factors was collected for all subjects. Polymorphisms of the survivin gene, including three loci of rs8073069, rs9904341 and rs1042489, were selected and genotyped by a polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) technique. Association analysis of genotypes/alleles and haplotypes from these loci with the risk of HCC was conducted under different genetic models.

Results

Using univariate analysis of rs8073069, rs9904341 and rs1042489 under different genetic models, no statistically significant difference was found in genotype or allele distribution of HCC cases relative to the controls (P > 0.05). Linkage disequilibrium (LD) analysis showed that these loci were in LD. Multivariate logistic regression indicated that with no G-C-T haplotype as reference, the haplotype of G-C-T from these loci was associated with a lower risk for HCC under the recessive model (OR = 0.46, 95% confidence interval (CI): 0.24~0.90, P = 0.023). Both HBsAg+ and the medical history of viral hepatitis type B were risk factors for HCC. However, no statistically significant haplotype-environment interaction existed.

Conclusions

No association between rs8073069, rs9904341 or rs1042489 in survivin gene and the risk of HCC is found in Chinese han population, but rs8073069G-rs9904341C- rs1042489T is perhaps a protective haplotype for HCC.
Accounts of severe acute obstetric complications in Rural Bangladesh
Authors: Sikder Shegufta S , Labrique Alain B , Ullah Barkat , Ali Hasmot , Rashid Mahbubur , Mehra Sucheta , Jahan Nusrat , Shamim Abu A , West Keith P , Christian Parul
Published: January 2012

Background

As maternal deaths have decreased worldwide, increasing attention has been placed on the study of severe obstetric complications, such as hemorrhage, eclampsia, and obstructed labor, to identify where improvements can be made in maternal health. Though access to medical care is considered to be life-saving during obstetric emergencies, data on the factors associated with health care decision-making during obstetric emergencies are lacking. We aim to describe the health care decision-making process during severe acute obstetric complications among women and their families in rural Bangladesh.

Methods

Using the pregnancy surveillance infrastructure from a large community trial in northwest rural Bangladesh, we nested a qualitative study to document barriers to timely receipt of medical care for severe obstetric complications. We conducted 40 semi-structured, in-depth interviews with women reporting severe acute obstetric complications and purposively selected for conditions representing the top five most common obstetric complications. The interviews were transcribed and coded to highlight common themes and to develop an overall conceptual model.

Results

Women attributed their life-threatening experiences to societal and socioeconomic factors that led to delays in seeking timely medical care by decision makers, usually husbands or other male relatives. Despite the dominance of male relatives and husbands in the decision-making process, women who underwent induced abortions made their own decisions about their health care and relied on female relatives for advice. The study shows that non-certified providers such as village doctors and untrained birth attendants were the first-line providers for women in all categories of severe complications. Coordination of transportation and finances was often arranged through mobile phones, and referrals were likely to be provided by village doctors.

Conclusions

Strategies to increase timely and appropriate care seeking for severe obstetric complications may consider targeting of non-certified providers for strengthening of referral linkages between patients and certified facility-based providers. Future research may characterize the treatments and appropriateness of emergency care provided by ubiquitous village doctors and other non-certified treatment providers in rural South Asian settings. In addition, future studies may explore the use of mobile phones in decreasing delays to certified medical care during obstetric emergencies.
Internal construct validity of the Shirom-Melamed Burnout Questionnaire (SMBQ)
Authors: Lundgren-Nilsson Åsa , Jonsdottir Ingibjörg H , Pallant Julie , Ahlborg Gunnar
Published: January 2012

Background

Burnout is a mental condition defined as a result of continuous and long-term stress exposure, particularly related to psychosocial factors at work. This paper seeks to examine the psychometric properties of the Shirom-Melamed Burnout Questionnaire (SMBQ) for validation of use in a clinical setting.

Methods

Data from both a clinical (319) and general population (319) samples of health care and social insurance workers were included in the study. Data were analysed using both classical and modern test theory approaches, including Confirmatory Factor Analysis (CFA) and Rasch analysis.

Results

Of the 638 people recruited into the study 416 (65%) persons were working full or part time. Data from the SMBQ failed a CFA, and initially failed to satisfy Rasch model expectations. After the removal of 4 of the original items measuring tension, and accommodating local dependency in the data, model expectations were met. As such, the total score from the revised scale is a sufficient statistic for ascertaining burnout and an interval scale transformation is available. The scale as a whole was perfectly targeted to the joint sample. A cut point of 4.4 for severe burnout was chosen at the intersection of the distributions of the clinical and general population.

Conclusion

A revised 18 item version of the SMBQ satisfies modern measurement standards. Using its cut point it offers the opportunity to identify potential clinical cases of burnout.
Actinoplanes teichomyceticus ATCC 31121 as a cell factory for producing teicoplanin
Authors: Taurino Carlo , Frattini Luca , Marcone Giorgia Letizia , Gastaldo Luciano , Marinelli Flavia
Published: January 2012

Background

Teicoplanin is a glycopeptide antibiotic used clinically in Europe and in Japan for the treatment of multi-resistant Gram-positive infections. It is produced by fermenting Actinoplanes teichomyceticus. The pharmaceutically active principle is teicoplanin A2, a complex of compounds designated T-A2-1-A2-5 differing in the length and branching of the fatty acid moiety linked to the glucosamine residue on the heptapeptide scaffold. According to European and Japanese Pharmacopoeia, components of the drug must be reproduced in fixed amounts to be authorized for clinical use.

Results

We report our studies on optimizing the fermentation process to produce teicoplanin A2 in A. teichomyceticus ATCC 31121. Robustness of the process was assessed on scales from a miniaturized deep-well microtiter system to flasks and 3-L bioreactor fermenters. The production of individual factors T-A2-1-A2-5 was modulated by adding suitable precursors to the cultivation medium. Specific production of T-A2-1, characterized by a linear C10:1 acyl moiety, is enhanced by adding methyl linoleate, trilinoleate, and crude oils such as corn and cottonseed oils. Accumulation of T-A2-3, characterized by a linear C10:0 acyl chain, is stimulated by adding methyl oleate, trioleate, and oils such as olive and lard oils. Percentages of T-A2-2, T-A2-4, and, T-A2-5 bearing the iso-C10:0, anteiso-C11:0, and iso-C11:0 acyl moieties, respectively, are significantly increased by adding precursor amino acids L-valine, L-isoleucine, and L-leucine. Along with the stimulatory effect on specific complex components, fatty acid esters, oils, and amino acids (with the exception of L-valine) inhibit total antibiotic productivity overall. By adding industrial oils to medium containing L-valine the total production is comparable, giving unusual complex compositions.

Conclusions

Since the cost and the quality of teicoplanin production depend mainly on the fermentation process, we developed a robust and scalable fermentation process by using an industrial medium in which a complex composition can be modulated by the combined addition of suitable precursors. This work was performed in the wild-type strain ATCC 31121, which has a clear genetic background. This is important for starting a rational improvement program and also helps to better control teicoplanin production during process and strain development.
Laboratory evolution of copper tolerant yeast strains
Authors: Adamo Giusy Manuela , Brocca Stefania , Passolunghi Simone , Salvato Benedetto , Lotti Marina
Published: January 2012

Background

Yeast strains endowed with robustness towards copper and/or enriched in intracellular Cu might find application in biotechnology processes, among others in the production of functional foods. Moreover, they can contribute to the study of human diseases related to impairments of copper metabolism. In this study, we investigated the molecular and physiological factors that confer copper tolerance to strains of baker's yeasts.

Results

We characterized the effects elicited in natural strains of Candida humilis and Saccharomyces cerevisiae by the exposure to copper in the culture broth. We observed that, whereas the growth of Saccharomyces cells was inhibited already at low Cu concentration, C. humilis was naturally robust and tolerated up to 1 g · L-1 CuSO4 in the medium. This resistant strain accumulated over 7 mg of Cu per gram of biomass and escaped severe oxidative stress thanks to high constitutive levels of superoxide dismutase and catalase. Both yeasts were then "evolved" to obtain hyper-resistant cells able to proliferate in high copper medium. While in S. cerevisiae the evolution of robustness towards Cu was paralleled by the increase of antioxidative enzymes, these same activities decreased in evolved hyper-resistant Candida cells. We also characterized in some detail changes in the profile of copper binding proteins, that appeared to be modified by evolution but, again, in a different way in the two yeasts.

Conclusions

Following evolution, both Candida and Saccharomyces cells were able to proliferate up to 2.5 g · L-1 CuSO4 and to accumulate high amounts of intracellular copper. The comparison of yeasts differing in their robustness, allowed highlighting physiological and molecular determinants of natural and acquired copper tolerance. We observed that different mechanisms contribute to confer metal tolerance: the control of copper uptake, changes in the levels of enzymes involved in oxidative stress response and changes in the copper-binding proteome. However, copper elicits different physiological and molecular reactions in yeasts with different backgrounds.
Detailed interrogation of trypanosome cell biology via differential organelle staining and automated image analysis
Authors: Wheeler Richard J , Gull Keith , Gluenz Eva
Published: January 2012

Background

Many trypanosomatid protozoa are important human or animal pathogens. The well defined morphology and precisely choreographed division of trypanosomatid cells makes morphological analysis a powerful tool for analyzing the effect of mutations, chemical insults and changes between lifecycle stages. High-throughput image analysis of micrographs has the potential to accelerate collection of quantitative morphological data. Trypanosomatid cells have two large DNA-containing organelles, the kinetoplast (mitochondrial DNA) and nucleus, which provide useful markers for morphometric analysis; however they need to be accurately identified and often lie in close proximity. This presents a technical challenge. Accurate identification and quantitation of the DNA content of these organelles is a central requirement of any automated analysis method.

Results

We have developed a technique based on double staining of the DNA with a minor groove binding (4'', 6-diamidino-2-phenylindole (DAPI)) and a base pair intercalating (propidium iodide (PI) or SYBR green) fluorescent stain and color deconvolution. This allows the identification of kinetoplast and nuclear DNA in the micrograph based on whether the organelle has DNA with a more A-T or G-C rich composition. Following unambiguous identification of the kinetoplasts and nuclei the resulting images are amenable to quantitative automated analysis of kinetoplast and nucleus number and DNA content. On this foundation we have developed a demonstrative analysis tool capable of measuring kinetoplast and nucleus DNA content, size and position and cell body shape, length and width automatically.

Conclusions

Our approach to DNA staining and automated quantitative analysis of trypanosomatid morphology accelerated analysis of trypanosomatid protozoa. We have validated this approach using Leishmania mexicana, Crithidia fasciculata and wild-type and mutant Trypanosoma brucei. Automated analysis of T. brucei morphology was of comparable quality to manual analysis while being faster and less susceptible to experimentalist bias. The complete data set from each cell and all analysis parameters used can be recorded ensuring repeatability and allowing complete data archiving and reanalysis.
Alveolar adenoma of the lung: unusual diagnosis of a lesion positive on PET scan. A case report
Authors: Nosotti Mario , Mendogni Paolo , Rosso Lorenzo , Tosi Davide , Palleschi Alessandro , Basciu Maria , Santambrogio Luigi , Ferrero Stefano
Published: January 2012

The authors report a clinical case of alveolar adenoma presenting as a solitary pulmonary nodule which was positive to PET and deeply located in the lung. Few cases of alveolar adenomas have been reported in literature; these lesions are considered pulmonary neoplasms with benign behaviour, usually presenting as a peripheral or subpleural coin lesion; the PET activities of such neoplasms were unknown.

The present clinical case was singular for the deep location of the nodule and its tight adhesion to left inferior pulmonary vein requiring a lobectomy. In addition, alveolar adenoma PET behaviour has been reported as light positivity.
SimReg1 is a master switch for biosynthesis and export of simocyclinone D8 and its precursors
Authors: Horbal Liliya , Rebets Yuriy , Rabyk Mariya , Makitrynskyy Roman , Luzhetskyy Andriy , Fedorenko Victor , Bechthold Andreas
Published: January 2012

Analysis of the simocyclinone biosynthesis (sim) gene cluster of Streptomyces antibioticus Tü6040 led to the identification of a putative pathway specific regulatory gene simReg1. In silico analysis places the SimReg1 protein in the OmpR-PhoB subfamily of response regulators. Gene replacement of simReg1 from the S. antibioticus chromosome completely abolishes simocyclinone production indicating that SimReg1 is a key regulator of simocyclinone biosynthesis. Results of the DNA-shift assays and reporter gene expression analysis are consistent with the idea that SimReg1 activates transcription of simocyclinone biosynthesis, transporter genes, regulatory gene simReg3 and his own transcription. The presence of extracts (simocyclinone) from S. antibioticus Tü6040 × pSSimR1-1 could dissociate SimReg1 from promoter regions. A preliminary model for regulation of simocyclinone biosynthesis and export is discussed.
Immobilization of anode-attached microbes in a microbial fuel cell
Authors: Wagner Rachel C , Porter-Gill Sikandar , Logan Bruce E
Published: January 2012

Current-generating (exoelectrogenic) bacteria in bioelectrochemical systems (BESs) may not be culturable using standard in vitro agar-plating techniques, making isolation of new microbes a challenge. More in vivo like conditions are needed where bacteria can be grown and directly isolated on an electrode. While colonies can be developed from single cells on an electrode, the cells must be immobilized after being placed on the surface. Here we present a proof-of-concept immobilization approach that allows exoelectrogenic activity of cells on an electrode based on applying a layer of latex to hold bacteria on surfaces. The effectiveness of this procedure to immobilize particles was first demonstrated using fluorescent microspheres as bacterial analogs. The latex coating was then shown to not substantially affect the exoelectrogenic activity of well-developed anode biofilms in two different systems. A single layer of airbrushed coating did not reduce the voltage produced by a biofilm in a microbial fuel cell (MFC), and more easily applied dip-and-blot coating reduced voltage by only 11% in a microbial electrolysis cell (MEC). This latex immobilization procedure will enable future testing of single cells for exoelectrogenic activity on electrodes in BESs.
Extravascular lung water index improves the diagnostic accuracy of lung injury in patients with shock
Authors: Chew Michelle S , Ihrman Lilian , During Joachim , Bergenzaun Lill , Ersson Anders , Undén Johan , Ryden Jörgen , Åkerman Eva , Larsson Marina
Published: January 2012

Introduction

The diagnosis of acute lung injury (ALI) may be more robust if more accurate physiological markers can be identified. Extravascular lung water (EVLW) is one possible marker, and it has been shown to correlate with respiratory function and mortality in patients with sepsis. Whether EVLW confers diagnostic value in a general population with shock, as well as which index performs best, is unclear. We investigated the diagnostic accuracy of various EVLW indices in patients with shock.

Methods

We studied a prospective, observational cohort of 51 patients with shock admitted to a tertiary ICU. EVLW was measured within 6 hours of ICU admission and indexed to actual body weight (EVLW/ABW), predicted body weight (EVLW/PBW) and pulmonary blood volume (EVLW/PBV). The relationship of these indices to the diagnosis and severity of lung injury and ICU mortality were studied. Positive and negative likelihood ratios, pre- and posttest odds for diagnosis of lung injury and mortality were calculated.

Results

All EVLW indices were higher among patients with lung injury and significantly correlated with respiratory parameters. Furthermore, all EVLW indices were significantly higher in nonsurvivors. The use of EVLW improves the posttest OR for the diagnosis of ALI, acute respiratory distress syndrome (ARDS) and severe lung injury (sLI) by up to eightfold. Combining increased EVLW and a diagnosis of ALI, ARDS or sLI increases the posttest odds of ICU mortality. EVLW/ABW and EVLW/PBV demonstrated the best diagnostic performance in this population.

Conclusions

EVLW was associated with degree of lung injury and mortality, regardless of the index used, confirming that it may be used as a bedside indicator of disease severity. The use of EVLW as a bedside test conferred added diagnostic value for the identification of patients with lung injury.
Editorial: Semaphorins: a further chemotropic family expressed in the thymus
Authors: Orciari Silvia , Catalano Alfonso
Published: January 2012

Discussion on Garcia and coworkers suggesting that Sema3A, in collaboration with SDF1/CXCL12, plays a role in thymocyte trafficking.
Editorial: Molecular eavesdropping: phagocytic cells spy on bacterial communication
Authors: Hänsch Gertrud M
Published: January 2012

Discussion on Karlsson et al. and the use of a bacterial signaling molecule by neutrophils and implication for the host defense.
Estimation of formation shear and borehole-fluid slownesses using sonic dispersion data in well-bonded cased boreholes
Authors: Yang Jiaqi , Sinha Bikash K. , Habashy Tarek M.
Published: January 2012

New inversion algorithms have been developed for estimating the formation shear and borehole-fluid slownesses, using either the borehole Stoneley or dipole flexural dispersion in well-bonded cased boreholes surrounded by a fast or slow isotropic and purely elastic formation. Two inversion algorithms have been developed for each type of formation. The first algorithm inverts either the measured borehole Stoneley or flexural dispersion at select frequencies for the formation shear slowness when all other model parameters are known. The second algorithm inverts either the borehole Stoneley or flexural dispersion for both the formation shear and borehole-fluid compressional slownesses. Optimal bandwidths for the inversion of the Stoneley and dipole flexural dispersions for the formation shear slowness range from about 5 to 8 kHz. The well-bonded cased borehole dispersion sensitivity to formation shear slowness becomes larger at these higher frequencies than in an open-hole. Moreover, the Stoneley dispersion sensitivity to the borehole-fluid compressional slowness is so large that it becomes necessary to input an extremely accurate estimate of fluid compressional slowness in the inversion algorithm. Inverted formation shear slowness from the Stoneley data in a fast formation exhibits an uncertainty of about 3%, whereas the input borehole-fluid slowness has an uncertainty of 0.5%. Given a certain amount of uncertainty in the borehole-fluid slowness, one can then estimate possible variances in the inverted formation shear slowness. In contrast, inversion of the flexural dispersion for formation shear slowness is less sensitive to the input borehole-fluid compressional slowness in the preferred frequency band of 5 to 8 kHz. Inverted formation shear slownesses in slow formations that use either the Stoneley or flexural dispersion are also far less sensitive to uncertainties in the borehole-fluid compressional slowness.
Further rare and unusual dementias
Authors: Gupta Susham , Fiertag Olivia , Thanulingam Thanakumar , Ros Elena , Strange Bryan , Warner James
Published: January 2012

In the second of two articles on rare causes of dementia, the authors describe toxic, iatrogenic, nutritional, traumatic, metabolic, neoplastic and autoimmune causes of dementia. Disorders are graded according to their prevalence, to give an idea of the likelihood of their presentation. Guidance is given on the investigation of uncommon cognitive impairment and dementia, especially in early-onset illness.