bluuebunny/crossref_metadata_2025 huggingface dataset:
Making Sense of Skin Color in Clinical Care
Authors: Everett Janine S. , Budescu Mia , Sommers Marilyn S.
Published: May 2012

The background of this article is that assessment and quantification of skin color is important to health care; color is one indicator of overall health and is linked to oxygenation, tissue perfusion, nutritional status, and injury. The purpose is to describe how skin color varies across racial/ethnic groups so that the information can be applied to clinical practice. The method used is cross-sectional, descriptive design ( n = 257). We recorded self-defined race/ethnicity and used a spectrophotometer to measure skin color at two anatomic sites. Skin color variables included L* (light/dark), a* (red/green), and b* (yellow/blue). As regards results, we found significant differences in L*, a*, and b* values by site and race/ethnicity in White, Asian, and Biracial participants. L*: F(3, 233) = 139.04, p < .01 and F(3, 233) = 118.47, p < .01. Black participants had significantly lower mean L* values and wider ranges of L*, a*, and b* as compared with other groups. In regard to application, these findings suggest that clinicians and researchers should plan and provide care based on skin color, rather than race/ethnicity.
The Patient-Centered Medical Home
Authors: Hoff Timothy , Weller Wendy , DePuccio Matthew
Published: May 2012

The patient-centered medical home is an important innovation in health care delivery. There is a need to assess the scope and substance of published research on medical homes. This article reviews published evaluations of medical home care for the period 2007 to 2010. Chief findings from these evaluations as a whole include associations between the provision of medical home care and improved quality, in addition to decreased utilization associated with medical home care in high-cost areas such as emergency department use. However, fewer associations were found across evaluations between medical home care and enhanced patient or family experiences. The early medical home research appears to reflect both the wide variation in how medical homes are being designed and implemented in practice and in how researchers are choosing to evaluate patient-centered medical home design and implementation. While some aspects of medical home care show promise, continued evolution of medical home evaluative research is needed.
What is Known About the Effectiveness of Police Practices in Reducing Crime and Disorder?
Authors: Telep Cody W. , Weisburd David
Published: May 2012

We build upon previous reviews of the police effectiveness literature to categorize strategies and tactics based on what police should and should not be doing. We also provide relevant information on what police agencies should be doing to implement effective strategies. We argue police should be focusing on hot spots policing, problem-oriented policing (POP), focused deterrence approaches, directed patrol to reduce gun crime, and using DNA in property cases. Police should also recognize the importance of efforts to enhance legitimacy. In contrast, police should be avoiding standard policing tactics such as random preventive patrol, second responder programs, and Drug Abuse Resistance Education (D.A.R.E.). We discuss how well current policing practices match up with effective approaches, describe general implications for policing, and conclude by noting policing strategies which we know too little about to make informed recommendations.
Reinventing global democracy
Authors: Scholte Jan Aart
Published: May 2012

How can democracy be suitably formulated in face of the more global character of contemporary society? Modern ideas and practices of ‘people’s rule’ (whether in a statist or a cosmopolitan mode) fall short as frameworks for global democracy. Statist approaches to global democracy have a host of behavioural, institutional, historical and cultural problems. Modern cosmopolitan approaches do better in addressing contemporary social changes, but are deficient in terms of their globalist tendencies, often oversimplified notions of political identity, limited cultural reflexivity, usually tame responses to resource inequalities and anthropocentrism. To address these shortcomings one might explore an alternative of ‘postmodern global democracies’ built around principles of transscalarity, plural solidarities, transculturality, egalitarian distribution and more ecologically framed ideas of political rights and duties.
Left ventricle remodeling in men with moderate to severe volume-dependent hypertension
Authors: Indra Tomáš , Holaj Robert , Zelinka Tomáš , Petrák Ondřej , Štrauch Branislav , Rosa Ján , Šomlóová Zuzana , Malík Jan , Janota Tomáš , Hradec Jaromír , Widimský Jiří
Published: May 2012

We evaluated the influence of increased intravascular volume on the heart anatomy in salt-sensitive types of hypertension, represented by primary aldosteronism (PA) and low-renin essential hypertension (LREH). Echocardiography was performed in 128 males with moderate to severe or resistant hypertension: 44 patients had PA, 40 patients had LREH and 44 patients had normal-renin essential hypertension (NREH). Groups were comparable in demographic characteristics, blood pressure, duration of hypertension and previous antihypertensive treatment. Patients with PA and LREH, in comparison with NREH patients, showed both greater end-systolic (37.6±5.4 and 35.6±4.5 vs 32.6±4.4 mm, p<0.001 and p<0.05) and end-diastolic (56.1±4.5 and 54.0±4.8 vs 50.4±5.1 mm; p<0.001 and p<0.01) left ventricle (LV) diameter. There were no significant differences either in LV wall thicknesses or LV mass, although a higher percentage of patients with PA and LREH met the criteria of eccentric hypertrophy ( p<0.001 and p<0.05 respectively). Aldosterone concentration was positively related to LV cavity dimensions, whether wall thicknesses were rather associated with blood pressure levels. In conclusion, plasma volume overload was identified as an important factor influencing LV remodeling in PA and LREH, whether due to excessive aldosterone levels in PA or other pathophysiological mechanisms.
Characterisation of force–displacement curve in self-pierce riveting
Authors: Haque R , Beynon J H , Durandet Y
Published: May 2012

A systematic study of the force–displacement curve of the self-piercing riveting (SPR) process and associated sample characterisation have been carried out in this work. Carbon steel sheet with three different thicknesses and steel rivets with three different hardness levels have been used to examine their impact on the force–displacement characteristic curve. The force–displacement curve is segmented into four different stages, which give the signature of the quality of the joint depending on different process variables. This study shows that the force–displacement curve can be used to monitor the quality of the joint within the same process parameters (rivet length and hardness, total stack thickness and die geometry).
TCL1: a shared tumor-associated antigen for immunotherapy against B-cell lymphomas
Authors: Weng Jinsheng , Rawal Seema , Chu Fuliang , Park Hyun Jun , Sharma Rakesh , Delgado David A. , Fayad Luis , Fanale Michelle , Romaguera Jorge , Luong Amber , Kwak Larry W. , Neelapu Sattva S.
Published: May 2012

Immunotherapy with therapeutic idiotype vaccines offers promise for treatment of B-cell malignancies. However, identification of novel immunogenic lymphoma-associated antigens that are universally expressed is necessary to overcome the barriers of patient-specific idiotype vaccines. Here, we determined whether T-cell leukemia/lymphoma 1 (TCL1) oncoprotein encoded by the TCL1 gene could be a target for immunotherapy of B-cell malignancies. We show that TCL1 mRNA and protein are selectively expressed in normal B cells but markedly hyperexpressed in multiple human B-cell lymphomas, including follicular lymphoma, chronic lymphocytic leukemia, mantle cell lymphoma, diffuse large B-cell lymphoma, and splenic marginal zone B-cell lymphoma. We demonstrated that TCL1-specific CD8+ T cells can be generated from HLA-A*0201 (HLA-A2)+ normal donors and identified TCL171-78 (LLPIMWQL) as the minimal epitope recognized by these T cells. More importantly, TCL171-78 peptide-specific T cells were present in the peripheral blood and tumor-infiltrating lymphocytes of lymphoma patients, could be expanded in vitro, and lysed autologous tumor cells but not normal B cells in an HLA-A2–restricted manner. Our results suggest that TCL1 is naturally processed and presented on the surface of lymphoma cells for recognition by cytotoxic T cells and can serve as a novel target for development of immunotherapeutic strategies against common B-cell lymphomas.
A Prospective Study of Bisphosphonate Use and Risk of Colorectal Cancer
Authors: Khalili Hamed , Huang Edward S. , Ogino Shuji , Fuchs Charles S. , Chan Andrew T.
Published: May 2012

Purpose

Bisphosphonates are used for the treatment of bone metastases and have been associated with a lower risk of breast cancer. A recent case-control study showed an inverse association between bisphosphonate use and colorectal cancer. Data from prospective cohorts are lacking.

Patients and Methods

We prospectively examined the relationship between bisphosphonate use and risk of colorectal cancer among 86,277 women enrolled onto the Nurses Health Study (NHS). Since 1998, participants have returned biennial questionnaires in which they were specifically queried about the regular use of bisphosphonates. We used Cox proportional hazards models to calculate hazard ratios (HRs) and 95% CIs for risk of colorectal cancer.

Results

Through 2008, we documented 801 cases of colorectal cancer over 814,406 person-years of follow-up. The age-adjusted HR for women who regularly used bisphosphonates was 0.92 (95% CI, 0.73 to 1.14) and was further attenuated after adjustment for other risk factors (multivariate HR, 1.04; 95% CI, 0.82 to 1.33). The risk was not influenced by duration of use (Ptrend = 0.79). Compared with nonusers, the multivariate-adjusted HRs of colorectal cancer were 1.24 (95% CI, 0.94 to 1.64) for women with 1 to 2 years of use, 1.16 (95% CI, 0.79 to 1.69) for 3 to 4 years of use, and 0.97 (95% CI, 0.60 to 1.56) for ≥ 5 years of use. There was no association between bisphosphonate use and colorectal cancer within strata of other risk factors.

Conclusion

In a large prospective cohort, we did not observe an association between long-term use of bisphosphonates and risk of colorectal cancer.
Long-Term Results of CCG 5942: A Randomized Comparison of Chemotherapy With and Without Radiotherapy for Children With Hodgkin's Lymphoma—A Report From the Children's Oncology Group
Authors: Wolden Suzanne L. , Chen Lu , Kelly Kara M. , Herzog Philip , Gilchrist Gerald S. , Thomson John , Sposto Richard , Kadin Marshall E. , Hutchinson Raymond J. , Nachman James
Published: May 2012

Purpose

In 1995, the Children's Cancer Group (CCG) opened a trial for patients with Hodgkin's lymphoma evaluating whether low-dose involved-field radiation therapy (IFRT) improved event-free survival (EFS) for patients achieving a complete response after chemotherapy. We present the long-term study outcome using final data through March 2007.

Patients and Methods

Between January 1995 and December 1998, 826 eligible patients were enrolled onto CCG 5942. Four hundred ninety-eight patients achieving an initial complete response to chemotherapy were randomly assigned to receive IFRT or no further therapy. EFS and overall survival (OS) were assessed from the date of study entry or random assignment, as appropriate.

Results

Ten-year EFS and OS rates for the entire cohort were 83.5% and 92.5%, respectively. In an as-treated analysis for randomly assigned patients, the 10-year EFS and OS rates were 91.2% and 97.1%, respectively, for IFRT and 82.9% and 95.9%, respectively, for no further therapy. For EFS and OS comparisons, P = .004 and P = .50, respectively. Bulk disease, “B” symptoms, and nodular sclerosis histology were risk factors for inferior EFS.

Conclusion

With a median follow-up of 7.7 years, IFRT produced a statistically significant improvement in EFS but no improvement in OS. For individual patients, the relative risks of relapse versus late effects of IFRT must be considered. Patient and disease characteristics and early response assessment will aid in deciding which patients are most likely to benefit from IFRT.
Narrative and Noncausal Bargaining
Authors: Flesch William
Published: May 2012

Most philosophical accounts of the puzzle of emotional engagement with characters we know to be fictional treat our emotion as static. This essay argues that it's part of the way humans interact with each other as a social species that a highly dynamic form of noncausal willing and noncausal bargaining enters into all our cooperative relationships with each other. Such bargaining can be illuminated by game theory and, in particular, by the version of prisoner's dilemma known as “Newcomb's problem.” Newcomb's problem models some of our most important relationships with each other and also some of the most central aspects of our relationship with narratives whose outcomes we care intensely about even though our caring cannot affect those outcomes. Fictional characters are especially immune to the exercise of a reader's or audience's will, so Newcomb's problem is particularly relevant to the noncausal nature of the bargaining that readers engage in.
Plastic Reading
Authors: Galloway Alexander R.
Published: May 2012

In her book Plasticity at the Dusk of Writing, philosopher Catherine Malabou tells a story about the historical end of reading and writing and their reinvention in a new form. The new mode is seen most vividly, suggests Malabou, in the cerebral plasticity of the brain, but also holds sway in philosophy and literature. The concept of the plastic—which she defines, using the image of plastic explosive, as the capacity to give form and the capacity to take form—refers to mutability, change, exchange, morphing, metamorphosis, and transformation. Plastic reading is a structural approach that aims to document the “structure of philosophy” that remains after a text has been subjected to certain analyses. This essay describes Malabou's vision of plastic reading as a living relation to texts in which metamorphosis regulates the metabolism between stasis and aleatory change.
A History of Absences: The Problem of Reference in Monique Truong's The Book of Salt
Authors: Fung Catherine
Published: May 2012

Monique Truong's 2003 novel The Book of Salt is a fictionalized story of a gay Vietnamese chef who, while working in the household of Gertrude Stein and Alice B. Toklas, briefly meets Paul Robeson and Ho Chi Minh. Rather than assume that the inclusion of historical persons constitutes markers of a story that can be categorized as historical fiction, this essay reads Truong's treatment of these figures as the vehicle through which she problematizes the act of giving a particular experience or subject historical presence. The essay explores how Truong uses Stein's modernist experimentation with referentiality toward her own critique of how events get represented, arguing that The Book of Salt plays with Steinian aesthetics in order to offer a critique of the structures of power that grant the racialized subject visibility. Paul Robeson and Ho Chi Minh become subjects of history not through presence but, contradictorily, through how they are made into “absent referents.”
Synthesis and Properties of Anthrylene-Substituted Phenyleneethynylene Dyes Having Amino/Cyano Group(s) and Their Application to Dye-Sensitized Solar Cells
Authors: Yang Xin , Kajiyama Shingo , Fang Jing-Kun , Xu Feng , Uemura Yu , Koumura Nagatoshi , Hara Kohjiro , Orita Akihiro , Otera Junzo
Published: May 2012

A series of anthrylene-substituted phenyleneethynylene dyes having amino/cyano group(s) were prepared by repeating Sonogashira coupling between aryl halides and terminal acetylenes. In UV–vis absorption spectra, the 9,10-anthrylene-substituted dyes showed a strong absorption band of which λmax was located from 502 to 521 nm and ε was more than 5.2 × 104 L mol−1 cm−1 indicating a highly expanded π-system in comparison with 1,5-anthrylene dye (λmax = 431 nm, ε = 2.6 × 104 L mol−1 cm−1). Lippert–Mataga plots demonstrated that the amino- and cyano-substituted dyes underwent larger charge separation in the excited states. These acetylenic dyes served as sensitizers of dye-sensitized solar cell to achieve 5.0% of photo-to-current energy conversion efficiency.
Synthesis of Peptide-Based Cyclophane Oligomers Having Multivalently Enhanced Guest-Binding Affinity
Authors: Hayashida Osamu , Nakashima Tomomi
Published: May 2012

Water-soluble cyclophane dimer, trimer, tetramer, and pentamer were prepared by aminolysis of succinimidyl ester derivative of tetraaza[6.1.6.1]paracyclophane with lysine and the corresponding lysine peptide as a scaffold, followed by removal of the protecting groups. The present cyclophane oligomers showed enhanced guest-binding affinities toward fluorescent guests such as 6-p-toluidinonaphthalene-2-sulfonate, in comparison with those of monocyclic cyclophane, reflecting multivalency effects in macrocycles. The effects of multivalent macrocycles on the guest-binding of the present cyclophane oligomers were also confirmed by surface plasmon resonance (SPR) measurements.
Decisions
Authors: Devakumar Delan
Published: May 2012

The decision about whether to have a termination of pregnancy, particularly in light of a potentially unwell child, is a very difficult one. The following represents two separate accounts of the same event giving the individual thoughts of both parents confronted with this dilemma. They can be read simultaneously or consecutively or a mixture of the two.
A retained menstrual cup
Authors: Day S
Published: May 2012

A 20-year-old woman attended a genitourinary clinic with a retained vaginal Mooncup that she had inserted the night before. A Mooncup is one type of menstrual cup. On speculum examination the device was visualized high in the vagina and the cervix appeared firmly lodged within it. The physician experienced difficulty in retrieving the cup despite following product instructions. This case highlights a new adverse event with an increasingly used sanitation product. It is important that clinicians are familiar with the cup, its removal process and are able to counsel patients with retained devices on future correct placement.
Impact of antiretroviral dosing frequency and pill burden on adherence among newly diagnosed, antiretroviral-naïve HIV patients
Authors: Buscher A , Hartman C , Kallen M A , Giordano T P
Published: May 2012

There are few data on the impact of antiretroviral therapy (ART) regimen factors on adherence in ART-naïve HIV patients on contemporary once- or twice-daily regimens. Ninety-nine newly diagnosed patients in a prospective observational cohort study completed a visual analogue scale to assess their ART adherence. Adherence by type of ART and dosing frequency were compared by Brown–Mood median tests. Participants taking once-daily regimens had higher adherence ( n = 70, 99.5%) compared with participants taking twice-daily regimens ( n = 29, 94%; P = 0.01). Adherence of participants taking the fixed dose combination efavirenz–emtricitabine–tenofovir ( n = 34, 100%) compared with those taking once-daily regimens of two or more pills was no different ( n = 36, 99.3%; P = 0.34). Among a cohort of newly diagnosed ART-naïve patients, once-daily dosing of ART resulted in higher adherence than twice-daily dosing. Pill burden among once-daily regimens did not predict adherence, suggesting that factors other than pill burden should drive regimen selection.
Rare case of combined factor V and factor X deficiency in pregnancy: presenting as secondary postpartum haemorrhage in first pregnancy and successful outcome in second pregnancy
Authors: Kakade Aniket , Panchanadikar Tushar , Kulkarni Yashwant
Published: May 2012

Isolated factor V and factor X deficiency is a very rare condition affecting 1 in 500,000–1,000,000 persons worldwide. We present a rare first reported case of combined deficiency of factor V and factor X where the patient developed secondary postpartum haemorrhage in first pregnancy, after which she was diagnosed to have this rare disorder and her subsequent pregnancy was then successfully managed.
Questionnaires: the bane of our lives?
Authors: Williams Norman
Published: May 2012

One of my particular bugbears, and I suspect I am not alone, is receiving a request via email to fill out a questionnaire (except College questionnaires, of course!). The number of such requests has increased exponentially as email has become the key means of communication. These requests are always accompanied by a message to say that this particular questionnaire will take no more than five minutes to complete – usually an underestimate in my experience. My natural inclination is to delete the request unless I really think it is an important topic and that my participation might change thinking. I would therefore like to thank all those individuals who completed the College's questionnaire regarding concerns related to the Health and Social Care Act. The results of the questionnaire can be found at www.rcseng.ac.uk/policy/publicaffairs and you will see that the principle concern of respondents is the impact of the changes on education and training.
On Computation of Exact van der Waerden Numbers
Authors: Ahmed Tanbir
Published: May 2012

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On the Complexity of Chooser–Picker Positional Games
Authors: Csernenszky András , Martin Ryan R. , Pluhár András
Published: May 2012

Two new versions of the so-called Maker–Breaker Positional Games are defined by József Beck. He defines two players, Picker and Chooser. In each round, Picker takes a pair of elements not already selected and Chooser keeps one and returns the other to Picker. In the Picker–Chooser version Picker plays as Maker and Chooser plays as Breaker, while the roles are swapped in the Chooser–Picker version. The outcome of these games is sometimes very similar to that of the traditional Maker–Breaker games. Here we show that both Picker–Chooser and Chooser–Picker games are NP-hard, which gives support to the paradigm that the games behave similarly while being quite different in definition. We also investigate the pairing strategies for Maker–Breaker games, and apply these results to the game called “Snaky”.
Altered Distribution of Juxtaparanodal Kv1.2 Subunits Mediates Peripheral Nerve Hyperexcitability in Type 2 Diabetes Mellitus
Authors: Zenker Jennifer , Poirot Olivier , de Preux Charles Anne-Sophie , Arnaud Estelle , Médard Jean-Jacques , Lacroix Catherine , Kuntzer Thierry , Chrast Roman
Published: May 2012

Peripheral nerve hyperexcitability (PNH) is one of the distal peripheral neuropathy phenotypes often present in patients affected by type 2 diabetes mellitus (T2DM). Throughin vivoandex vivoelectrophysiological recordings in db/db mice, a model of T2DM, we observed that, in addition to reduced nerve conduction velocity, db/db mice also develop PNH. By using pharmacological inhibitors, we demonstrated that the PNH is mediated by the decreased activity of Kv1-channels. In agreement with these data, we observed that the diabetic condition led to a reduced presence of the Kv1.2-subunits in juxtaparanodal regions of peripheral nerves in db/db mice and in nerve biopsies from T2DM patients. Together, these observations indicate that the T2DM condition leads to potassium channel-mediated PNH, thus identifying them as a potential drug target to treat some of the DPN related symptoms.
Fgf-Dependent Glial Cell Bridges Facilitate Spinal Cord Regeneration in Zebrafish
Authors: Goldshmit Yona , Sztal Tamar E. , Jusuf Patricia R. , Hall Thomas E. , Nguyen-Chi Mai , Currie Peter D.
Published: May 2012

Adult zebrafish show a remarkable capacity to regenerate their spinal column after injury, an ability that stands in stark contrast to the limited repair that occurs within the mammalian CNS post-injury. The reasons for this interspecies difference in regenerative capacity remain unclear. Here we demonstrate a novel role for Fgf signaling during glial cell morphogenesis in promoting axonal regeneration after spinal cord injury. Zebrafish glia are induced by Fgf signaling, to form an elongated bipolar morphology that forms a bridge between the two sides of the resected spinal cord, over which regenerating axons actively migrate. Loss of Fgf function inhibits formation of this “glial bridge” and prevents axon regeneration. Despite the poor potential for mammalian axonal regeneration, primate astrocytes activated by Fgf signaling adopt a similar morphology to that induced in zebrafish glia. This suggests that differential Fgf regulation, rather than intrinsic cell differences, underlie the distinct responses of mammalian and zebrafish glia to injury.
Soluble Adenylyl Cyclase Activity Is Necessary for Retinal Ganglion Cell Survival and Axon Growth
Authors: Corredor Raul G. , Trakhtenberg Ephraim F. , Pita-Thomas Wolfgang , Jin Xiaolu , Hu Ying , Goldberg Jeffrey L.
Published: May 2012

cAMP is a critical second messenger mediating activity-dependent neuronal survival and neurite growth. We investigated the expression and function of the soluble adenylyl cyclase (sAC, ADCY10) in CNS retinal ganglion cells (RGCs). We found sAC protein expressed in multiple RGC compartments including the nucleus, cytoplasm and axons. sAC activation increased cAMP above the level seen with transmembrane adenylate cyclase (tmAC) activation. Electrical activity and bicarbonate, both physiologic sAC activators, significantly increased survival and axon growth, whereas pharmacologic or siRNA-mediated sAC inhibition dramatically decreased RGC survival and axon growthin vitro, and survivalin vivo. Conversely, RGC survival and axon growth were unaltered in RGCs from AC1/AC8 double knock-out mice or after specifically inhibiting tmACs. These data identify a novel sAC-mediated cAMP signaling pathway regulating RGC survival and axon growth, and suggest new neuroprotective or regenerative strategies based on sAC modulation.
Optimal Deployment of Attentional Gain during Fine Discriminations
Authors: Scolari Miranda , Byers Anna , Serences John T.
Published: May 2012

Most models assume that top-down attention enhances the gain of sensory neurons tuned to behaviorally relevant stimuli (on-target gain). However, theoretical work suggests that when targets and distracters are highly similar, attention should enhance the gain of neurons that are tuned away from the target, because these neurons better discriminate neighboring features (off-target gain). While it is established that off-target neurons support difficult fine discriminations, it is unclear if top-down attentional gain can be optimally applied to informative off-target sensory neurons or if gain is always applied to on-target neurons, regardless of task demands. To test the optimality of attentional gain in human visual cortex, we used functional magnetic resonance imaging and an encoding model to estimate the response profile across a set of hypothetical orientation-selective channels during a difficult discrimination task. The results suggest that top-down attention can adaptively modulate off-target neural populations, but only when the discriminanda are precisely specified in advance. Furthermore, logistic regression revealed that activation levels in off-target orientation channels predicted behavioral accuracy on a trial-by-trial basis. Overall, these data suggest that attention does not only increase the gain of sensory-evoked responses, but may bias population response profiles in an optimal manner that respects both the tuning properties of sensory neurons and the physical characteristics of the stimulus array.
Disrupted Autophagy Leads to Dopaminergic Axon and Dendrite Degeneration and Promotes Presynaptic Accumulation of α-Synuclein and LRRK2 in the Brain
Authors: Friedman Lauren G. , Lachenmayer M. Lenard , Wang Jing , He Liqiang , Poulose Shibu M. , Komatsu Masaaki , Holstein Gay R. , Yue Zhenyu
Published: May 2012

Parkinson's disease (PD) is characterized pathologically by the formation of ubiquitin and α-synuclein (α-syn)-containing inclusions (Lewy bodies), dystrophic dopamine (DA) terminals, and degeneration of midbrain DA neurons. The precise molecular mechanisms underlying these pathological features remain elusive. Accumulating evidence has implicated dysfunctional autophagy, the cell self-digestion and neuroprotective pathway, as one of the pathogenic systems contributing to the development of idiopathic PD. Here we characterize autophagy-deficient mouse models and providein vivoevidence for the potential role that impaired autophagy plays in pathogenesis associated with PD. Cell-specific deletion of essential autophagy geneAtg7in midbrain DA neurons causes delayed neurodegeneration, accompanied by late-onset locomotor deficits. In contrast,Atg7-deficient DA neurons in the midbrain exhibit early dendritic and axonal dystrophy, reduced striatal dopamine content, and the formation of somatic and dendritic ubiquitinated inclusions in DA neurons. Furthermore, whole-brain-specific loss ofAtg7leads to presynaptic accumulation of α-syn and LRRK2 proteins, which are encoded by two autosomal dominantly inherited PD-related genes. Our results suggest that disrupted autophagy may be associated with enhanced levels of endogenous α-syn and LRRK2 proteinsin vivo. Our findings implicate dysfunctional autophagy as one of the failing cellular mechanisms involved in the pathogenesis of idiopathic PD.
Surprise and Error: Common Neuronal Architecture for the Processing of Errors and Novelty
Authors: Wessel Jan R. , Danielmeier Claudia , Morton J. Bruce , Ullsperger Markus
Published: May 2012

According to recent accounts, the processing of errors and generally infrequent, surprising (novel) events share a common neuroanatomical substrate. Direct empirical evidence for this common processing network in humans is, however, scarce. To test this hypothesis, we administered a hybrid error-monitoring/novelty-oddball task in which the frequency of novel, surprising trials was dynamically matched to the frequency of errors. Using scalp electroencephalographic recordings and event-related functional magnetic resonance imaging (fMRI), we compared neural responses to errors with neural responses to novel events. In Experiment 1, independent component analysis of scalp ERP data revealed a common neural generator implicated in the generation of both the error-related negativity (ERN) and the novelty-related frontocentral N2. In Experiment 2, this pattern was confirmed by a conjunction analysis of event-related fMRI, which showed significantly elevated BOLD activity following both types of trials in the posterior medial frontal cortex, including the anterior midcingulate cortex (aMCC), the neuronal generator of the ERN. Together, these findings provide direct evidence of a common neural system underlying the processing of errors and novel events. This appears to be at odds with prominent theories of the ERN and aMCC. In particular, the reinforcement learning theory of the ERN may need to be modified because it may not suffice as a fully integrative model of aMCC function. Whenever course and outcome of an action violates expectancies (not necessarily related to reward), the aMCC seems to be engaged in evaluating the necessity of behavioral adaptation.
Short-term effects of GH treatment on coagulation, fibrinolysis, inflammation biomarkers, and insulin resistance status in prepubertal children with GH deficiency
Authors: Cañete Ramón , Valle Miguel , Martos Rosario , Sánchez-Carrión Adela , Cañete María Dolores , van Donkelaar Eva L
Published: May 2012

Objective

The aims of this study was to determine whether prepubertal GH deficiency (GHD) children showed any impairment in coagulation- and fibrinolysis-related parameters and in inflammatory and insulin resistance markers and to evaluate the effect of short-term GH therapy on these parameters.

Design

This was a 6-month, prospective, observational, case–control study (36 prepubertal children with GHD and 38 healthy prepubertal children with no differences in BMI). Comparison of study parameter values in GHD and control groups at baseline and after 6 months of GH treatment in the GHD group. The following were analyzed: glucose, insulin, fibrinogen, absolute plasminogen activator inhibitor type 1 (aPAI-1), von Willebrand factor (vWF), homeostasis model assessment for insulin resistance (HOMA-IR) index, C-reactive protein (CRP), and interleukin 6 (IL6) levels.

Results

Children with GHD showed higher baseline levels of aPAI-1 and fibrinogen and lower levels of glucose, insulin, and HOMA-IR index than healthy controls. No intergroup differences were found for vWF. After 6 months of treatment, aPAI-1 levels were lower but no changes were observed in fibrinogen or vWF levels, which were similar to those of controls. Glucose levels increased, though not significantly, while insulin levels and HOMA-IR index rose to normal levels. A positive correlation was found between changes in insulin status/HOMA-IR index and levels of aPAI-1, fibrinogen, vWF, CRP, and IL6.

Conclusions

At early ages, GH therapy appears to exert beneficial effects on the amount of aPAI-1. At the same time, it increases the state of insulin resistance (HOMA-IR index) without modifying the levels of fibrinogen, vWF, CRP, and IL6.
Expression of guanylyl cyclase-B (GC-B/NPR2) receptors in normal human fetal pituitaries and human pituitary adenomas implicates a role for C-type natriuretic peptide
Authors: Thompson Iain R , Chand Annisa N , King Peter J , Ansorge Olaf , Karavitaki Niki , Jones Ceri Alexander , Rahmutula Dolkun , Gardner David G , Zivkovic Vladimir , Wheeler-Jones Caroline P , McGonnell Imelda M , Korbonits Márta , Anderson Richard A , Wass John A H , McNeilly Alan S , Fowkes Robert C
Published: May 2012

C-type natriuretic peptide (CNP/Nppc) is expressed at high levels in the anterior pituitary of rats and mice and activates guanylyl cyclase B receptors (GC-B/Npr2) to regulate hormone secretion. Mutations in NPR2/Npr2 can cause achondroplasia, GH deficiency, and female infertility, yet the normal expression profile within the anterior pituitary remains to be established in humans. The current study examined the expression profile and transcriptional regulation of NPR2 and GC-B protein in normal human fetal pituitaries, normal adult pituitaries, and human pituitary adenomas using RT-PCR and immunohistochemistry. Transcriptional regulation of human NPR2 promoter constructs was characterized in anterior pituitary cell lines of gonadotroph, somatolactotroph, and corticotroph origin. NPR2 was detected in all human fetal and adult pituitary samples regardless of age or sex, as well as in all adenoma samples examined regardless of tumor origin. GC-B immunoreactivity was variable in normal pituitary, gonadotrophinomas, and somatotrophinomas. Maximal transcriptional regulation of the NPR2 promoter mapped to a region within −214 bp upstream of the start site in all anterior pituitary cell lines examined. Electrophoretic mobility shift assays revealed that this region contains Sp1/Sp3 response elements. These data are the first to show NPR2 expression in normal human fetal and adult pituitaries and adenomatous pituitary tissue and suggest a role for these receptors in both pituitary development and oncogenesis, introducing a new target to manipulate these processes in pituitary adenomas.
Involvement of AMP-activated protein kinase in thrombin-stimulated interleukin 6 synthesis in osteoblasts
Authors: Tokuda H , Kato K , Natsume H , Kondo A , Kuroyanagi G , Matsushima-Nishiwaki R , Ito Y , Otsuka T , Kozawa O
Published: May 2012

We previously demonstrated that thrombin stimulates synthesis of interleukin 6 (IL6), a potent bone resorptive agent, in part via p44/p42 MAP kinase and p38 MAP kinase but not through stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) among the MAP kinase superfamily in osteoblast-like MC3T3-E1 cells. In this study, we investigated the involvement of AMP-activated protein kinase (AMPK), a regulator of energy metabolism, in thrombin-stimulated IL6 synthesis in MC3T3-E1 cells. The phosphorylation of p44/p42 MAP kinase, p38 MAP kinase, SAPK/JNK, or AMPK was determined by western blot analysis. The release of IL6 was determined by the measurement of IL6 concentration in the conditioned medium using an ELISA kit. The expression ofIL6mRNA was determined by RT-PCR. Thrombin time dependently induced the phosphorylation of AMPK α-subunit (Thr-172). Compound C, an inhibitor of AMPK, dose-dependently suppressed the thrombin-stimulated IL6 release in the range between 0.3 and 10 μM. Compound C reduced thrombin-induced acetyl-CoA carboxylase phosphorylation. TheIL6mRNA expression induced by thrombin was markedly reduced by compound C. Downregulation of AMPK by siRNA suppressed the thrombin-stimulated IL6 release. The thrombin-induced phosphorylation of p44/p42 MAP kinase and p38 MAP kinase was inhibited by compound C, which failed to affect SAPK/JNK phosphorylation. These results strongly suggest that AMPK regulates thrombin-stimulated IL6 synthesis via p44/p42 MAP kinase and p38 MAP kinase in osteoblasts.
The expression of translocator protein in human thyroid cancer and its role in the response of thyroid cancer cells to oxidative stress
Authors: Klubo-Gwiezdzinska Joanna , Jensen Kirk , Bauer Andrew , Patel Aneeta , Costello John , Burman Kenneth D , Wartofsky Leonard , Hardwick Matthew J , Vasko Vasyl V
Published: May 2012

The translocator protein (TSPO), formerly known as a peripheral benzodiazepine receptor, exerts pro-apoptotic function via regulation of mitochondrial membrane potential. We examined TSPO expression in human thyroid tumors (25 follicular adenomas (FA), 15 follicular cancers (FC), and 70 papillary cancers (PC)). The role of TSPO in the regulation of cell growth, migration, and apoptosis was examined in thyroid cancer cell lines after TSPO knockdown with siRNA and after treatment with TSPO antagonist (PK11195). Compared with normal thyroid, the level of TSPO expression was increased in FA, FC, and PC in 24, 26.6, and 55.7% of cases respectively. Thyroid cancer cell lines demonstrated variable levels of TSPO expression, without specific association with thyroid oncogene mutations. Treatment with inhibitors of PI3K/AKT or MEK/ERK signaling was not associated with changes in TSPO expression. Treatment with histone deacetylase inhibitor (valproic acid) increased TSPO expression in TSPO-deficient cell lines (FTC236 cells). TSPO gene silencing or treatment with PK11195 did not affect thyroid cancer cell growth and migration but prevented depolarization of mitochondrial membranes induced by oxidative stress. Induction of TSPO expression by valproic acid was associated with increased sensitivity of FTC236 to oxidative stress-inducible apoptosis. Overall, we showed that TSPO expression is frequently increased in PC. In vitro data suggested the role of epigenetic mechanism(s) in the regulation of TSPO in thyroid cells. Implication of TSPO in the thyroid cancer cell response to oxidative stress suggested its potential role in the regulation of thyroid cancer cell response to treatment with radioiodine and warrants further investigation.
Upregulation of Calprotectin and Downregulation of Retinol Binding Protein in the Serum of Workers with Trichloroethylene‐induced Hypersensitivity Dermatitis
Authors: Huang Zhenlie , Yue Fei , Yang Xingfen , Xia Lihua , Chen Cishan , Qiu Xinxiang , Huang Jianxun , Li Laiyu , Kamijima Michihiro , Nakajima Tamie , Huang Hanlin
Published: May 2012

Upregulation of Calprotectin and Down‐regulation of Retinol Binding Protein in the Serum of Workers with Trichloroethylene‐induced Hyper‐sensitivity Dermatitis: Zhenlie HUANG, et al. Guangdong Prevention and Treatment Center for Occupational Diseases, China—

Objectives

The aim of this study was to explore the involved pathophysiological processes and develop biomarkers of trichloroethylene‐induced hypersensitivity dermatitis (THD).

Methods

We examined the impact of THD on the serum proteome in 8 male patients by comparing the serum samples between acute and healed stages. Sample pooling and immunodepletion were applied for sample preparation. Two‐dimensional gel electrophoresis coupled with matrix‐assisted laser‐desorption ionization time‐of‐flight mass spectrometry (MALDI‐TOF‐TOF/MS) was utilized to identify and quantitate differentially expressed proteins. Changes in selected proteins were further confirmed by an ELISA assay.

Results

A total of 41 spots were quantitated with significant alteration (p<0.05; fold‐change≥± 3.0) in the serum between the acute and healed stages. Of these proteins, 26 proteins were identified by MALDI‐TOF‐TOF/MS. The identified proteins could be categorized into diverse functional classes, e.g., immunity and defense response, vitamin and lipid transport, fatty acid biosynthesis, actin binding, proteolysis and glycolysis. The ELISA assay confirmed the relative upregulation of calprotectin (S100A8/A9) and downregulation of retinol binding protein (RBP4) in the serum of the acute stage. The alteration of calprotectin and RBP4 was found to be specific to THD rather than trichloroethylene exposure.

Conclusions

The pathophysiological processes underlying THD may involve elevated inflammatory responses and oxidative stress, inhibition of vitamin transport, depression of fatty acid biosynthesis, loss of extracellular actin scavenger, increase in oxygen transport, dysfunction in lipid transport, proteolysis and glycolysis. The combination of higher calprotectin and lower RBP4 levels in the serum could be used as potential biomarkers of THD.
U-Pb dating by zircon dissolution method using chemical abrasion
Authors: Takehara Lucy , Chemale Júnior Farid , Hartmann Léo A. , Dussin Ivo A. , Kawashita Koji
Published: May 2012

Chemical abrasion was carried out on zircons grains of the Temora II standard for U-Pb dating prior to analyses using in situ Laser Ablation-MultiCollector Ion Coupled Plasma Mass Spectrometer (LA-ICPMS) followed by the Isotope Dissolution Thermal Ionization Mass Spectrometer (ID-TIMS) method. The proposed methodology was herein applied in order to reduce primarily the effects of secondary Pb loss, the presence of common lead and/or silicate impurities. Nine Temora II zircon grains were analyzed by the laser ablation method yielding an age of 418.3±4.3 Ma. Zircon grains of a same population were separated for chemical abrasion before dissolution and mass spectrometry analyses. Six fractions of them were separated for isotope dissolution using 235U-205Pb mixed spike after we have checked and assured the laboratory conditions of low blank values for total Pb of less than 2 pg/g. The obtained U-Pb zircon age by the ID-TIMS method was 415.7±1.8 Ma (error 0.43 %) based on four successful determinations. The results are consistent with the published ages for the Temora diorite (Temora I â€“ 416.75±1.3 Ma; Temora II â€“ 416.78±0.33 Ma) and established as 416±0.33 Ma. The technique is thus recommended for high precision U-Pb zircon analyses (error < 1 %), mainly for high resolution stratigraphic studies of Phanerozoic sequences.
Purification, characterization and structural determination of chitinases produced by Moniliophthora perniciosa
Authors: Galante Rafaela S. , Taranto Alex G. , Koblitz Maria G.B. , Góes-Neto Aristóteles , Pirovani Carlos P. , Cascardo Júlio C.M. , Cruz Sandra H. , Pereira Gonçalo A.G. , Assis Sandra A. de
Published: May 2012

The enzyme chitinase from Moniliophthora perniciosa the causative agent of the witches' broom disease in Theobroma cacao, was partially purified with ammonium sulfate and filtration by Sephacryl S-200 using sodium phosphate as an extraction buffer. Response surface methodology (RSM) was used to determine the optimum pH and temperature conditions. Four different isoenzymes were obtained: ChitMp I, ChitMp II, ChitMp III and ChitMp IV. ChitMp I had an optimum temperature at 44-73ºC and an optimum pH at 7.0-8.4. ChitMp II had an optimum temperature at 45-73ºC and an optimum pH at 7.0-8.4. ChitMp III had an optimum temperature at 54-67ºC and an optimum pH at 7.3-8.8. ChitMp IV had an optimum temperature at 60ºC and an optimum pH at 7.0. For the computational biology, the primary sequence was determined in silico from the database of the Genome/Proteome Project of M. perniciosa, yielding a sequence with 564 bp and 188 amino acids that was used for the three-dimensional design in a comparative modeling methodology. The generated models were submitted to validation using Procheck 3.0 and ANOLEA. The model proposed for the chitinase was subjected to a dynamic analysis over a 1 ns interval, resulting in a model with 91.7% of the residues occupying favorable places on the Ramachandran plot and an RMS of 2.68.
Influence of the nycthemeral cycle on the roosting behaviour of the Orange-winged Amazon
Authors: Moura Leiliany N. de , Silva Maria Luisa da , Vielliard Jacques M.E.
Published: May 2012

Environmental stimuli exert important effects on the expression of the endogenous rhythms. Daily movements of groups of parrots in response to the light/dark cycle have been studied by several researchers. However, the factors modifying the intrinsic rhythmicity of this behaviour remain little known. This study describes how the nychthemeral/circadian periodicity of roost daily movements of the Orange-winged Amazon Amazona amazonica is modified by weather factors. Numbers of parrots arriving or leaving the roosting site Ilha dos Papagaios were determined on a minute by minute basis. More parrots have significantly arrived at the roost after sunset than before, while more parrots have significantly left the roost before sunrise than after. The peak exodus of parrots occurred at 23 ± 5.24 minutes before sunrise, when the average light intensity was 1 lux. The peak influx of parrots occurred at 6 ± 6.1 minutes after sunset, when the average light intensity was 50 lux. By altering ambient light intensity, weather conditions have significantly influenced the arrival and departure times, with parrots leaving later and arriving earlier when conditions were overcast at the roost site.
TL, OSL and C-14 dating results of the sediments and bricks from mummified nuns' grave
Authors: Tudela Diego R.G. , Tatumi Sonia H. , Yee Márcio , Brito Silvio L.M. , Morais José L. , Morais Daisy de , Piedade Silvia C. , Munita Casimiro S.P. , Hazenfratz Roberto
Published: May 2012

This paper presents the results of TL and OSL dating of soil and fragments of bricks from a grave, which was occupied by two mummified nuns, found at "Luz" Monastery, located in the state of São Paulo, Brazil. The TL and OSL ages were compared to C-14 dating ones obtained from bone collagens of the mummies. The majority of the ages is related to the eighteenth century. The gamma-ray spectroscopy was used to evaluate natural radioisotope concentrations in the samples, and by using these concentrations the annual dose rates, from 3.0 to 5.3 Gy/kyr, were obtained. Neutron activation analysis was performed and the radioisotope contents results are in agreement with those obtained by gamma-ray spectroscopy. The contents of U, Th and Ce elements were higher than those found in usual sediments.
Influência varietal e do solo no estado nutricional na cana-de-açúcar (Saccharum spp) pela análise foliar
Authors: Haag Henrique Paulo , Orlando Filho José
Published: May 2012

Com o objetivo de se estudar o comportamento varietal e do solo na concentração de macronutrientes nas folhas de cana-de--açúcar e, ao mesmo tempo, executar o levantamento do estado nutricional das variedades através da análise foliar, instalaram-se ensaios em quatro Grandes Grupos de Solos cultivando 16 plantadas sob idênticas condições de clima, adubação, tratos culturais, idade, estado de sanidade e procedência de mudas. O delineamento estatístico foi o de blocos ao acaso com 16 tratamentos (variedades) e 4 repetições. Realizou-se a amostragem foliar aos 4 meses de idade, tomando-se os 20 cm centrais da folha +3 (20 por parcela), desprezando-se a nervura principal. Determinaram-se os macronutrientes (nitrogênio, fósforo, potássio, cálcio, magnésio e enxofre) os quais foram expressos em percentagem de matéria seca. Os ensaios foram colhidos aos 18 meses de idade, sendo que para cada um deles determinou-se as produtividades em toneladas por pol/ha.