bluuebunny/crossref_metadata_2025 huggingface dataset:
Cells expressing Desiccate are essential for morphogenesis of labial sensilla in Drosophila melanogaster adults
Authors: KAWANO Takeshi , MATSUMOTO Hitoshi , MAEKAWA Emi , NAKANO Fumihiro , KANUKA Hirotaka , TSUZUKI Seiji , HAYAKAWA Yoichi
Published: March 2011

We recently discovered a new gene, Desiccate (Desi), that is expressed in the epidermis and protects larvae from desiccation stress in Drosophila melanogaster. In the present study, we found that taste organs express more Desi than the epidermis both in larvae and adults. Green fluorescent protein (GFP) expression in larvae under the direction of a Desi promoter‐Gal4 line containing the 1,010‐bp 5′ flanking region of Desi produced no signal in the epidermis but strong signals in cells of the larval gustatory sense organs, indicating that this driver works specifically in the gustatory organs. In adults, GFP expression was also observed in basal cells of sensilla on labella, tarsi and wings. More precise morphological analysis of GFP expression located its expression in the outer accessory cells rather than neurons of the labial sensilla. Although Desi knockdown or induction of cell death in Desi‐expressing cells did not change the morphological or physiological characters of the larvae, larvae lacking Desi‐expressing cells failed to metamorphose normally, and all of them died inside puparia. Dying pharate adults were found to lack all labial sensilla. The proneural genes Achaete and Scute, which are involved in the development of the adult central and peripheral nervous system, were normally expressed in the pupae lacking Desi‐expressing cells. These results suggested that the lack of Desi‐expressing cells makes it impossible to produce outer accessory cells for development of the sensilla, thereby signifying that cells expressing Desi are essential for normal morphogenesis of the labial sensilla in Drosophila adults.
Reproductive biology of the microtype tachinid fly Zenillia dolosa (Meigen) (Diptera: Tachinidae)
Authors: HO Giang T. T. , ICHIKI Ryoko T. , NAKAMURA Satoshi
Published: March 2011

Reproductive biology including mating, adult longevity, fecundity and development of the tachinid fly Zenillia dolosa was investigated for optimizing rearing procedures using Mythimna separata as a host in the laboratory. Females lay microtype eggs containing a first instar larva on food plants of the host and then the eggs must be ingested by the host for parasitization. Mating success was 58.5% with mating duration of 80.7 min. Mating was most successful when day 0–1 females were kept with day 2–4 male flies. Female body size was positively correlated with its fecundity but not with longevity. However, females that survived longer produced more eggs during their lifetime. Parasitoids successfully developed in 4th to 6th instar host larvae. Host instars at the time of parasitoid egg ingestion significantly influenced development time of the immature parasitoid, but did not affect body size of the emerging parasitoid. We suggest that pairing newly emerged females with day 2–4 males should result in higher mating success and using the last instar hosts for parasitization should minimize development time of the parasitoid for rearing.
Hybrid Follicular Cyst (Pilomatrical and Infundibular) Arising Within a Sebaceous Nevus
Authors: Rodins Karl , Baillie Laura
Published: March 2011

Abstract:  A 7‐year‐old girl presented with a 3‐month history of a small blue–brown papule arising within a large sebaceous nevus on her temporal scalp. A punch excision was performed that demonstrated a hybrid follicular cyst. The majority of the cyst wall displayed pilomatrical differentiation consisting of basaloid matrical‐type cells with luminal shadow cell keratinization. The matrical epithelium displayed strong membranous, cytoplasmic, and nuclear staining for β‐catenin. Only a small component of the wall displayed infundibular differentiation. These findings were consistent with a hybrid follicular cyst predominantly displaying pilomatrical differentiation with only a small component of infundibular lining. The most common tumors arising within sebaceous nevi are the syringocystadenoma papilliferum and trichoblastoma. Follicular cysts with infundibular (sebaceous cyst) and trichilemmal (pilar cyst) differentiation are exceedingly common, although their development within sebaceous nevi appears to be rare. We report a rare case of a hybrid follicular cyst with matrical differentiation occurring within a sebaceous nevus.
Effect of Exercise on Cognitive Performance in Community‐Dwelling Older Adults: Review of Intervention Trials and Recommendations for Public Health Practice and Research
Authors: Snowden Mark , Steinman Lesley , Mochan Kara , Grodstein Francine , Prohaska Thomas R. , Thurman David J. , Brown David R. , Laditka James N. , Soares Jesus , Zweiback Damita J. , Little Deborah , Anderson Lynda A.
Published: March 2011

There is evidence from observational studies that increasing physical activity may reduce the risk of cognitive decline in older adults. Exercise intervention trials have found conflicting results. A systematic review of physical activity and exercise intervention trials on cognition in older adults was conducted. Six scientific databases and reference lists of previous reviews were searched. Thirty studies were eligible for inclusion. Articles were grouped into intervention–outcome pairings. Interventions were grouped as cardiorespiratory, strength, and multicomponent exercises. Cognitive outcomes were general cognition, executive function, memory, reaction time, attention, cognitive processing, visuospatial, and language. An eight‐member multidisciplinary panel rated the quality and effectiveness of each pairing. Although there were some positive studies, the panel did not find sufficient evidence that physical activity or exercise improved cognition in older adults. Future research should report exercise adherence, use longer study durations, and determine the clinical relevance of measures used.
Do Vaccination Strategies Implemented by Nursing Homes Narrow the Racial Gap in Receipt of Influenza Vaccination in the United States?
Authors: Bardenheier Barbara , Shefer Abigail , Ahmed Faruque , Remsburg Robin , Rowland Hogue Carol J. , Gravenstein Stefan
Published: March 2011

OBJECTIVES: To determine whether the racial inequity between African Americans and Caucasians in receipt of influenza vaccine is narrower in residents of nursing homes with facility‐wide vaccination strategies than in residents of facilities without vaccination strategies.

DESIGN: Secondary data analysis using the National Nursing Home Survey 2004, a nationally representative survey.

SETTING: One thousand one hundred seventy‐four participating nursing homes sampled systematically with probability proportional to bed size.

PARTICIPANTS: Thirteen thousand five hundred seven randomly sampled residents of nursing homes between August and December 2004.

MEASUREMENTS: Receipt of influenza vaccine within the last year. Logistic regression was used to examine the relationship between facility‐level influenza immunization strategy and racial inequity in receipt of vaccination, adjusted for characteristics at the resident, facility, state, and regional levels.

RESULTS: Overall in the Untied States, vaccination coverage was higher for Caucasian and African‐American residents; the racial vaccination gaps were smaller (<6 percentage points) and nonsignificant in residents of homes with standing orders for influenza vaccinations (P=.14), verbal consent allowed for vaccinations(P=.39), and routine review of facility‐wide vaccination rates (P=.61) than for residents of homes without these strategies. The racial vaccination gap in residents of homes without these strategies were two to three times as high (P=.009, P=.002, and P=.002, respectively).

CONCLUSION: The presence of several immunization strategies in nursing homes is associated with higher vaccination coverage for Caucasian and African‐American residents, narrowing the national vaccination racial gap.
Resilience and Self‐Perceived Oral Health: A Hierarchical Approach
Authors: Martins Aline Blaya , dos Santos Camila Mello , Hilgert Juliana Balbinot , de Marchi Renato José , Hugo Fernando Neves , Pereira Padilha Dalva Maria
Published: March 2011

OBJECTIVES: To determine whether positive self‐perceived oral health is associated with sociodemographic health variables, with an emphasis on resilience, in community‐dwelling older adults in southern Brazil.

DESIGN: Cross‐sectional study nested within a cohort study.

SETTING: Carlos Barbosa in southern Brazil.

PARTICIPANTS: Four hundred ninety‐six community‐dwelling adults aged 64 and older.

MEASUREMENTS: Sociodemographic information, a health history, and health perceptions were assessed using a structured questionnaire. Resilience was assessed using a resilience scale. For each participant, a brief oral examination was performed to assess number of teeth. Positive self‐perceived oral health was the outcome of interest.

RESULTS: A final, fully adjusted Poisson regression model showed that high resilience potential (prevalence ratio (PR)=1.18, 95% confidence interval (CI)=1.06–1.32), income (PR=1.18, 95% CI=1.07–1.30), and no reported change in diet because of dental problems (PR=1.34, 95% CI=1.13–1.60) were associated with positive self‐perceived oral health. Participants living in rural areas were less likely to report positive self‐perceived oral health (PR=0.83, 95% CI=0.75–0.93).

CONCLUSION: Using a hierarchical approach, positive self‐perceived oral health was found to be associated with several variables included in the conceptual framework of oral health outcomes, such as resilience. Resilience may act as a potentiating agent in the positive adaptation to tooth loss.
19. Carpal Tunnel Syndrome
Authors: Patijn Jacob , Vallejo Ricardo , Janssen Markus , Huygen Frank , Lataster Arno , van Kleef Maarten , Mekhail Nagy
Published: March 2011

Abstract:  Carpal tunnel syndrome (CTS) is a common disorder. In the majority of cases, patients with CTS can be diagnosed by means of appropriate history taking. Nerve conduction examination of the nervus medianus is the most important additional diagnostic test and is the best predictor of symptom severity and functional status in idiopathic CTS. Treatment option depends on the severity of the symptoms and the degree of functional daily limitations. If few limitations are present, splinting or corticosteroid injections are preferred. Surgical interventions are reserved for the more severe conditions resulting in significant disability.

Interventional pain treatment such as pulsed radiofrequency could be an addition to the future treatment options for CTS.
Diagnostic Pacing Maneuvers for Supraventricular Tachycardia: Part 1
Authors: VEENHUYZEN GEORGE D. , QUINN F. RUSSELL , WILTON STEPHEN B. , CLEGG ROBIN , MITCHELL L. BRENT
Published: March 2011

This two‐part manuscript reviews diagnostic pacing maneuvers for supraventricular tachycardia (SVT). Part one will involve a detailed consideration of ventricular overdrive pacing (VOP), since this pacing maneuver provides the diagnosis in the majority of cases. This will include a review of the post‐VOP response, fusion during entrainment, the importance of the VOP site, quantitative results of entrainment such as the postpacing interval, differential entrainment, and new criteria derived from features found at the beginning of the VOP train. There is a considerable literature on this topic, and this review is by no means meant to be all‐encompassing. Rather, we hope to clearly explain and illustrate the physiology, strengths, and weaknesses of what we consider to be the most important and commonly employed diagnostic pacing maneuvers, that is, those that trainees in cardiac electrophysiology should be well familiar with at a minimum. (PACE 2011; 767–782)
Comparison of Hemodynamic versus Dyssynchrony Assessment for Interventricular Delay Optimization with Echocardiography in Cardiac Resynchronization Therapy
Authors: DOLTRA ADELINA , VIDAL BÀRBARA , SILVA ETELVINO , MONT LLUÍS , TAMBORERO DAVID , CASTEL MARÍA ÁNGELES , TOLOSANA JOSÉ MARÍA , BERRUEZO ANTONIO , BRUGADA JOSEP , SITGES MARTA
Published: March 2011

Background: Best practice for cardiac resynchronization therapy (CRT) device optimization is not established. This study compared Tissue Doppler Imaging (TDI) to study left ventricular (LV) synchrony and left ventricular outflow tract velocity‐time integral (LVOT VTI) to assess hemodynamic performance.

Methods: LVOT VTI and LV synchrony were tested in 50 patients at three interventricular (VV) delays (LV preactivation at −30 ms, simultaneous biventricular pacing, and right ventricular preactivation at +30 ms), selecting the highest VTI and the greatest degree of superposition of the displacement curves, respectively, as the optimum VV delay.

Results: In 39 patients (81%), both techniques agreed (Kappa = 0.65, p < 0.0001) on the optimum VV delay. LV preactivation (VV − 30) was the interval most frequently chosen.

Conclusions: Both TDI and LVOT VTI are useful CRT programming methods for VV optimization. The best hemodynamic response correlates with the best synchrony. In most patients, the optimum VV interval is LV preactivation. (PACE 2011; 34:984–990)
Getting the Goods on Social Capital1
Authors: Wall Ellen , Ferrazzi Gabriele , Schryer Frans
Published: March 2011

Abstract This article presents an overview of the origins, development, rapid diffusion, and current usage of the concept of social capital in both the academic (research‐oriented) and more applied (social policy) literature. Following a short quantitative survey of the appearance of the term in both theses and journals, various meanings of social capital are examined in the light of classical and contemporary sociological theory. Three main research approaches, which are based on the operationalization of social capital or its application as a heuristic device, are critically examined. These approaches are associated with the work ofJames Coleman, Pierre Bourdieu, and Robert Putnam, but there are also some references to the work of economists. The authors contend that, while social capital has value and appeal as a new term, basic theory needs greater development. In particular, attention should be paid to acknowledging the specific perspective on social capital that underlies its usage, the scale or level of analysis employed, and the value of a qualitative use of social capital.
Plastic Deformation of 〈001〉 Single‐Crystal SrTiO3 by Compression at Room Temperature
Authors: Yang Kai‐Hsun , Ho New‐Jin , Lu Hong‐Yang
Published: March 2011

The plastic deformation of (001) single‐crystal SrTiO3 is investigated using compression along [001] at room temperature. A total plastic strain of ∼19% ± 2% is consistently obtained. The stress–strain curve exhibiting four work‐hardening stages are describable using the stage 0 of axis rotation, the stage I “easy glide,” the stage II multiple slip and the wall‐and‐cell structure, and the stage III work softening and dynamic recovery before sample fracture takes place. It is revealed by analyzing the microstructure for each work‐hardening stage that the plastic deformation of single‐crystal SrTiO3 closely resembles that of metals. The primary slip systems of [011]

and

(011) predominate in stage I where plastic deformation occurs by the migration of kink pairs in collinear partial dislocations. The activation of multiple slips including [101]

and

(101), and [011]

and

(011) in stage II produces the cell‐and‐wall structure which is also characteristic of plastically deformed metals. In stage III with decreasing work‐hardening rate, the bow‐out dislocation interaction from opposite walls results in annihilation. The reaction between dislocations from adjacent walls produces the resultant dislocations with

parallel to the load axis [001]. These dislocations are sessile, which eventually leads to sample fracture.
Secretion of annexin A3 from ovarian cancer cells and its association with platinum resistance in ovarian cancer patients
Authors: Yin Jie , Yan Xuedong , Yao Xin , Zhang Yongli , Shan Ying , Mao Ning , Yang Yili , Pan Lingya
Published: March 2011

Early detection of resistance to platinum‐based therapy is critical for improving the treatment of ovarian cancers. We have previously found that increased expression of annexin A3 is a mechanism for platinum resistance in ovarian cancer cells. Here we demonstrate that annexin A3 can be detected in the culture medium of ovarian cancer cells, particularly these cells that express high levels of annexin A3. Levels of annexin A3 were then determined in sera from ovarian cancer patients using an enzyme‐linked immunosorbent assay. Compared with those from normal donors, sera from ovarian cancer patients contain significantly higher levels of annexin A3. Furthermore, serum levels of annexin A3 were significantly higher in platinum‐resistant patients than in platinum‐sensitive patients. To gain insight into the mechanism of secretion, the ovarian cancer cell lines were examined using both transmission electron microscopy and immunoelectron microscopy. Compared with parent cells, there are significantly more vesicles in the cytoplasm of ovarian cancer cells that express high levels of annexin A3, and at least some vesicles are annexin A3‐positive. Moreover, some vesicles appear to be fused with the cell membrane, suggesting that annexin A3 secretion may be associated with exocytosis and the release of exosomes. This is supported by our observation that ovarian cancer cells expressing higher levels of annexin A3 released increased numbers of exosomes. Furthermore, annexin A3 can be detected in exosomes released from cisplatin‐resistant cells (SKOV3/Cis) by immunoblotting and immunoelectron microscopy.
Methamphetamine alters occludin expression via NADPH oxidase‐induced oxidative insult and intact caveolae
Authors: Park Minseon , Hennig Bernhard , Toborek Michal
Published: March 2011

Methamphetamine (METH) is a drug of abuse with neurotoxic and vascular effects that may be mediated by reactive oxygen species (ROS). However, potential sources of METH‐induced generation of ROS are not fully understood. This study is focused on the role of NAD(P)H oxidase (NOX) in METH‐induced dysfunction of brain endothelial cells. Treatment with METH induced a time‐dependent increase in phosphorylation of NOX subunit p47, followed by its binding with gp91 and p22, and the formation of an active NOX complex. An increase in NOX activity was associated with elevated production of ROS, alterations of occludin levels and increased transendothelial migration of monocytes. Inhibition of NOX by NSC 23766 attenuated METH‐induced ROS generation, changes in occludin protein levels and monocyte migration. Because an active NOX complex is localized to caveolae, we next evaluated the role of caveolae in METH‐mediated toxicity to brain endothelial cells. Treatment with METH induced phosphorylation of ERK1/2 and caveolin‐1 protein. Inhibition of ERK1/2 activity or caveolin‐1 silencing protected against METH‐induced alterations of occludin levels. These findings indicate an important role of NOX and functional caveolae in METH‐induced oxidative stress in brain endothelial cells that contribute to the subsequent alterations of occludin levels and transendothelial migration of inflammatory cells.
Nursing caries, linear hypoplasia, and nursing and weaning habits in Tanzanian infants
Authors: Matee Mecky , van't Hof Martin , Maselle Sam , Mikx Frans , Helderman Wim van Palenstein
Published: March 2011

Abstract— A cross‐sectional survey on the prevalence of rampant caries in infants and a case‐control study were executed to determine the prevalence of rampant caries and its etiology. A total of 2192 infants aged between 1 and 4.0 yr from nine regions of Tanzania comprised the sample of the prevalence survey. The overall prevalence of rampant caries resembling nursing canes was 6.8%. The prevalence varied considerably between 1.5% and 12.8% in the different regions and was closely associated with the varying prevalence of linear hypoplasia but not with fluoride content in drinking water. The relative risk of developing rampant caries in the presence of linear hypoplasia was 14.5. The case‐control study comprised 116 cases, infants with rampant caries and 243 controls, without the disorder. Risk factors such as breast feeding frequency and duration during day and night, bottle feeding and weaning habits were assessed through a structured interview with the mother. Bottlefeeding was performed in only a minority of the infants for a short period (1.1 months) and in a low exposure frequency (0.4 daily) and was not associated with rampant caries. The frequency of sugar moments in the supplementary diet was on average 1.5 times per day and was not associated with rampant caries. The duration and frequency of breast feeding during the day was also not associated. The habit of allowing infants to sleep with the breast nipple in their mouths and the presence of linear hypoplasia were strongly associated with rampant caries. Odds ratios for these variables were 17.8 and 15.6 respectively. Based on these associations it is concluded that rampant caries in this sample was caused by the habit of allowing infants to sleep with the breast nipple in their mouths, whereas linear hypoplasia is considered to be a predisposing factor.
Relationship of gingival calculus and bleeding on probing in CPITN Code 2 sextants
Authors: Dong Yuan‐Jang , Lee May Meei‐Shyuan , Pai Lu , Peng Tzi‐Kang
Published: March 2011

Abstract— The aims of this study were twofold: firstly, to evaluate the relationship of supra‐ or subgingival calculus and bleeding on probing (BOP) in sextants coded 2 in the Community Periodontal Index of Treatment Needs (CPITN); and secondly, to compare the differences in four investigations in Taiwan, Hong Kong, Japan and Norway. In a national survey, a total of 2658 Chinese dentate adults were examined by using modified CPITN in the Taiwan area from 1985 to 1987. Sextants given Code 2 were divided into four subclassifications: supragingival calculus with bleeding (I +), supragingival calculus without bleeding (I‐), subgingival calculus with bleeding (II +) and subgingival calculus without bleeding (II‐). The results showed that of the 9394 sextants given Code 2, the highest percentage (70%) were characterized by the presence of subgingival calculus with bleeding and the lowest percentage (4%) by supragingival calculus with bleeding. The ratio of sextants coded 2 with only supragingival calculus versus subgingival was 1:6.2. The bleeding to nonbleeding ratio of sextants coded 2 in this study was similar to the Hong Kong study. However, differences among Taiwan, Japan and Norway were found. The results indicated that sextants with subgingival calculus had a higher tendency to BOP, with a ratio of 4:1. Those with supragingival calculus had a ratio of 3:7. We conclude therefore, that it is essential to scale teeth to remove subgingival calculus for determination of the necessity of periodontal treatment.
Lifestyle, dental caries and number of teeth
Authors: Sakki Tero K. , Knuuttila Matti L. E. , Vimpari Sirpa S. , Kivelä Sirkka‐Liisa
Published: March 2011

Abstract— All 55‐yr‐old citizens (n = 1012) of Oulu (a middle‐sized Finnish town) were invited to a clinical examination; 780 agreed to participate. The associations of lifestyle with decayed tooth surfaces and the number of teeth were studied in the 533 dentate subjects. Measures of lifestyle included dietary habits, a smoking habit, alcohol consumption and physical activity. When the associations of dental caries with lifestyle, sex, dental health behavior, social class and number of teeth were studied by logistic regression analysis, lifestyle was shown to have an independent association with dental caries. Further analysis of the data showed that dental caries increased with a more negative lifestyle in every social class, but most significantly in the lowest. Number of teeth was not associated with lifestyle, but subjects with lower social status had fewer teeth than those with higher social status. The association of lifestyle with dental caries supports the idea that behavior in a broader sense should be taken into consideration in caries prevention.
Role of health beliefs in patient compliance with preventive dental advice
Authors: Barker Teresa
Published: March 2011

Abstract— Lack of patient compliance with health recommendations is a well known fact. What is less well understood are the reasons why. This study used the Health Belief Model (HBM) to investigate the role of patients' health beliefs in Patient compliance with preventive dental advice. A questionnaire was constructed to explore the four beliefs of “seriousness”, “susceptibility”, “benefits” and “self‐efficacy” and this was administered to 43 adult patients attending the conservation department of a large teaching hospital for routine examination. Patients were seen twice, 1 month apart. At visit one, plaque was disclosed and plaque and bleeding scores were recorded. Patients were taught the modified Bass technique of plaque removal. Plaque and bleeding scores were repeated on visit two. 1 month later. Compliance was defined as any reduction in these scores at visit two. The health belief of “benefits” taken as a single variable showed a significant correlation with compliance and the combined beliefs of “susceptibility” and “benefits” were also found to be significantly related to compliance.
In vivo reflectance confocal microscopy imaging of vitiligo, nevus depigmentosus and nevus anemicus
Authors: Lai Lai‐gui , Xu Ai‐e
Published: March 2011

Background/purpose: Hypopigmentary skin disorders such as vitiligo, nevus depigmentosus and nevus anemicus are common diseases in clinic. The lesions of these diseases could be similar to some extent, although each of them has its own characteristic clinical appearance and histological features. Clinically, the atypical lesions are often difficult to be differentiated. In vivo reflectance confocal microscopy (RCM) is a non‐invasive, repetitive imaging tool that provides real‐time images at a nearly cellular histological resolution. Our aim was to investigate the RCM features of vitiligo, nevus depigmentosus and nevus anemicus.

Subjects and Methods: A total of 135 patients with a clinical diagnosis of the aforementioned diseases were included in this study. The RCM images from depigmented skin, border of the white macules, adjacent normal‐appearing skin and distant normal skin for all patients at the dermo‐epidermal junction (DEJ) level were investigated.

Results: In the active phase of vitiligo (AVP), the RCM demonstrated a complete loss of melanin in lesional skin in eight (53; 15.1%) patients. In 45 patients (53; 84.9%) of the AVP, part of the bright dermal papillary rings normally seen at the DEJ level disappeared or part of the rings lost their integrity and the content of melanin decreased obviously. In 20 patients (53; 37.7%) of the AVP, highly refractile inflammatory cells could be seen within the papillary dermis in the lesional and adjacent normal‐appearing skin, which may indicate the lesion progresses. In addition, part of the dermal papillary rings showed lack of integrity or their brightness decreased in adjacent normal‐appearing skin in all the patients of the AVP. It is important to know that the RCM demonstrated an ill‐defined border. In the stable phase of vitiligo (SPV), the RCM demonstrates a complete loss of melanin in lesional skin and a clear border in 31 (41; 75.6%) patients; the content of melanin and dermal papillary rings in adjacent normal‐appearing skin show no changes. In 10 (41; 24.4%) patients, the dendritic and highly refractile melanocytes arose in the recovery phase of vitiligo, which may indicate the repigmentation of vitiligo. There are three kinds of repigmentation patterns under RCM: marginal, perifollicular and diffuse. Distant normal skin showed no difference from controls in both the active and the SPV. In all the patients with nevus depigmentosus, the content of melanin decreases obviously but the dermal papillary rings are intact. The dermal papillary rings show no differences between lesional skin and adjacent normal‐appearing skin of nevus anemicus.

Conclusion: Considering our results, RCM may be useful to non‐invasively discriminate vitiligo, nevus depigmentosus and nevus anemicus in vivo.
Mitotic Moonlighting Functions for Membrane Trafficking Proteins
Authors: Royle Stephen J.
Published: March 2011

In recent years, cell biologists have uncovered a number of new functions for proteins that were previously thought to operate solely in membrane trafficking. These alternative roles, termed moonlighting functions, can occur at distinct intracellular sites or at different stages of the cell cycle. Here, I evaluate the evidence for mitotic moonlighting functions of proteins that have membrane trafficking roles during interphase. The aim is to identify key issues facing the field and to outline important questions for future work.
Forward Targeting of Toxoplasma gondii Proproteins to the Micronemes Involves Conserved Aliphatic Amino Acids
Authors: Gaji Rajshekhar Y. , Flammer Halley P. , Carruthers Vern B.
Published: March 2011

Like other apicomplexan parasites, Toxoplasma gondii actively invades host cells using a combination of secretory proteins and an acto‐myosin motor system. Micronemes are the first set of proteins secreted during invasion that play an essential role in host cell entry. Many microneme proteins (MICs) function in protein complexes, and each complex contains at least one protein that displays a cleavable propeptide. Although MIC propeptides have been implicated in forward targeting to micronemes, the specific amino acids involved have not been identified. It was also not known if the propeptide has a general function in MICs trafficking in T. gondii and other apicomplexans. Here we show that propeptide domains are extensively interchangeable between T. gondii MICs and also with that of Eimeria tenella MIC5 (EtMIC5), suggesting a common mechanism of function. We also performed N‐terminal deletion and mutational analysis of M2AP and MIC5 propeptides to show that a valine at position +3 (relative to signal peptidase cleavage) of proM2AP and a leucine at position +1 of proMIC5 are crucial for targeting to micronemes. Valine and leucine are closely related amino acids with similar side chains, implying a similar mode of function, a notion that was confirmed by correct trafficking of TgM2AP‐V/L and TgMIC5‐L/V substitution mutants. Propeptides of AMA1, MIC3 and EtMIC5 have valine or leucine at or near the N‐termini and mutagenesis of these conserved residues validated their role in microneme trafficking. Collectively, our findings suggest that discrete, aliphatic residues at the extreme N‐termini of proMICs facilitate trafficking to the micronemes.
Syntaxin7 Is Required for Lytic Granule Release from Cytotoxic T Lymphocytes
Authors: Pattu Varsha , Qu Bin , Marshall Misty , Becherer Ute , Junker Christian , Matti Ulf , Schwarz Eva C. , Krause Elmar , Hoth Markus , Rettig Jens
Published: March 2011

SNARE proteins are essential fusion mediators for many intracellular trafficking events. Here, we investigate the role of Syntaxin7 (Stx7) in the release of lytic granules from cytotoxic T lymphocytes (CTLs). We show that Stx7 is expressed in CTLs and is preferentially localized to the region of lytic granule release, the immunological synapse (IS). Interference of Stx7 function by expression of a dominant‐negative Stx7 construct or by small interfering RNA leads to a dramatic reduction of CTL‐mediated killing of target cells. Real‐time visualization of individual lytic granules at the IS by evanescent wave microscopy reveals that lytic granules in Stx7‐deprived CTLs not only fail to fuse with the plasma membrane but even fail to accumulate at the IS. Surprisingly, the accumulation defect is not caused by an overall reduction in lytic granule number, but by a defect in the trafficking of T cell receptors (TCRs) through endosomes. Subsequent high‐resolution nanoscopy shows that Stx7 colocalizes with Rab7 on late endosomes. We conclude from these data that the accumulation of recycling TCRs at the IS is a SNARE‐dependent process and that Stx7‐mediated processing of recycling TCRs through endosomes is a prerequisite for the cytolytic function of CTLs.
Influence of brain-derived neurotrophic factor and apolipoprotein E genetic variants on hemispheric and lateral ventricular volume of young healthy adults
Authors: Sidiropoulos Christos , Jafari-Khouzani Kourosh , Soltanian-Zadeh Hamid , Mitsias Panayiotis , Alexopoulos Panagiotis , Richter-Schmidinger Tanja , Reichel Martin , Lewczuk Piotr , Doerfler Arnd , Kornhuber Johannes
Published: March 2011

Objective: Brain-derived neurotrophic factor (BDNF) and apolipoprotein E (ApoE) are thought to be implicated in a variety of neuronal processes, including cell growth, resilience to noxious stimuli and synaptic plasticity. A Val to Met substitution at codon 66 in the BDNF protein has been associated with a variety of neuropsychiatric conditions. The ApoE4 allele is considered a risk factor for late-onset Alzheimer's disease, but its effects on young adults are less clear. We sought to investigate the effects of those two polymorphisms on hemispheric and lateral ventricular volumes of young healthy adults.

Methods: Hemispheric and lateral ventricular volumes of 144 healthy individuals, aged 19–35 years, were measured using high resolution magnetic resonance imaging and data were correlated with BDNF and ApoE genotypes.

Results: There were no correlations between BDNF or ApoE genotype and hemispheric or lateral ventricular volumes.

Conclusion: These findings indicate that it is unlikely that either the BDNF Val66Met or ApoE polymorphisms exert any significant effect on hemispheric or lateral ventricular volume. However, confounding epistatic genetic effects as well as relative insensitivity of the volumetric methods used cannot be ruled out. Further imaging analyses are warranted to better define any genetic influence of the BDNF Val6Met and ApoE polymorphism on brain structure of young healthy adults.
The Teratogenic Potencies of Valproic Acid Derivatives and Their Effects on Biological End‐points are Related to Changes in Histone Deacetylase and Erk1/2 Activities
Authors: Gotfryd Kamil , Hansen Maria , Kawa Anna , Ellerbeck Ursula , Nau Heinz , Berezin Vladimir , Bock Elisabeth , Walmod Peter S.
Published: March 2011

Abstract:  Valproic acid (VPA) is a known teratogen. In the present study, the effects of VPA and seven VPA derivatives with different teratogenic potencies (isobutyl‐, 5‐methyl‐, ethyl‐, propyl‐, butyl‐, pentyl‐ and hexyl‐4‐yn‐VPA) were investigated in L929 cells in vitro. Evaluated end‐points included changes in cell proliferation, growth, cell cycle distribution, morphology, speed, glycogen synthase kinase‐3β (GSK‐3β) and Erk1/2 phosphorylation, and histone H3 acetylation. Changes in proliferation, growth, speed, Erk1/2 and GSK‐3β‐Tyr216 phosphorylation, and H3 acetylation were significantly associated with the teratogenic potencies of the VPA derivatives. However, in contrast to changes in Erk1/2 phosphorylation and H3 acetylation, significant changes in GSK‐3β phosphorylation could only be obtained in response to prolonged incubation at high drug concentration. There was an association between changes in H3 acetylation and GSK‐3β‐Tyr216 phosphorylation, whereas none of these end‐points were associated with changes in Erk1/2 phosphorylation. These results suggest that the teratogenic potencies of VPA and VPA derivatives are related to effects on both Erk1/2 and histone deacetylase activities, whereas changes in GSK‐3β activity are possibly a secondary effect.
Update on T‐cell immunity: Implications for tumor immunology
Authors: McCLUSKEY James
Published: March 2011

The association between the immune system and malignancy is at the forefront of research aimed at identifying and developing effective immunotherapies to treat and suppress cancer. Understanding the mechanisms underlying the biology, differentiation and effector functions of key immune cells in the tumor microenvironment is central to this process. The stimulation of T cells results in their activation, triggering the release of cellular mediators, including cytokines and chemokines. The interplay between these components determines the polarization of T cells into phenotypically‐, functionally‐ and transcriptionally‐distinct subsets (e.g. T‐helper [Th] 1, Th2, Th17 and T‐regulatory cells). Given that antigen recognition, costimulation and the cytokine milieu are critical signals in T‐cell activation and differentiation, they represent potential and important therapeutic targets for modulating immune responses in disease. The aim of this article is to review the role of T cells in immune protection and pathogenesis, and to discuss the key pathways involved in these processes.
Developing cancer immunotherapies
Authors: DAVIS Ian D , CEBON Jonathan S.
Published: March 2011

Effective antitumor responses require communication between antigen‐presenting cells, T‐cell subsets, B cells and natural killer cells. However, tumors have developed a number of mechanisms to avoid detection and elimination by the immune system. This results in a microenvironment that can contribute to the failure of the immune response to the tumor or the prevention of effective immune‐mediated killing. Understanding the barriers to effective tumor immunity allows for the rational design of targeted immunotherapies. The characterization of tumor antigens has led to the development of promising vaccine candidates. Our work has concentrated on the cancer/testis antigen NY‐ESO‐1, which has been an important focus in the development of vaccine‐based therapies against melanoma. Immune responses against NY‐ESO‐1 can occur spontaneously or be induced by vaccination in patients with resected disease. In contrast, the use of NY‐ESO‐1 vaccines in the advanced melanoma setting has been disappointing, with reduced clinical and immunological efficacy. This lack of response is observed in other disease settings with other antigens, and might in part be explained by the recruitment of increased numbers of T‐regulatory cells and a strong immunosuppressive environment. The benefits of cancer immunotherapy might be enhanced if it were possible to identify characteristics that distinguish patients who are more likely to respond.
CTLA‐4 to overcome immunological tolerance to melanoma
Authors: HODI F Stephen
Published: March 2011

There has been much recent attention on immunotherapy for cancer due to the promising results of several randomized phase‐III trials. The management of metastatic melanoma in particular is a significant clinical challenge, and it has long been a desired target of immunotherapies due to evidence of the importance of host immune responses. Cytotoxic T‐lymphocyte‐associated antigen‐4 (CTLA‐4) serves as a negative regulator of immunity. Recent trials administering fully‐human anti‐CTLA‐4 monoclonal antibodies to patients with melanoma have demonstrated survival benefits. However, treatment with anti‐CTLA‐4 antibodies is not without potential toxicities. Autoimmune side‐effects, such as diarrhea, bowel inflammation and dermatitis, were the most commonly reported. To build upon the activity seen with anti‐CTLA‐4 antibodies, both in toxicity and efficacy profiles, there has been significant interest in investigating combinations with vaccination strategies. In recent trials, patients who were vaccinated with autologous tumor cells engineered to secrete granulocyte–macrophage colony‐stimulating factor, and were then infused with anti‐CTLA‐4 antibodies, demonstrated clinically‐significant antitumor immunity without grade‐3 or ‐4 toxicity in most patients. These data demonstrate how manipulation of immune regulation has produced patient benefits, and this area is a rich avenue for future investigation.
Regulation by litigation
Authors: Yandle Bruce , Dorchak Andrew , Morriss Andrew P.
Published: March 2011

We believe that careful application of the logic of economics and public choice shines important light on regulation through litigation and can explain at least partly why regulators choose the litigation route, when they choose it, and how the choice may or may not achieve broad goals of efficiency and fairness. We present three case studies: heavy‐duty diesel engines, silica and asbestos, and the tobacco industry's Master Settlement Agreement (MSA).
Metabolic surgery for type 2 diabetes
Authors: Ahn Soo Min , Pomp Alfons , Rubino Francesco
Published: March 2011

Conventional bariatric operations, including Roux‐en‐Y gastric bypass (RYGB), laparoscopic adjustable gastric banding, and biliopancreatic diversion (BPD) appear to be a safe and effective treatment for many severely obese patients with type 2 diabetes mellitus (T2DM). These operations improve glucose homeostasis through a variety of mechanisms, however, not only due to reduced food intake and body weight. Research to elucidate the weight‐independent antidiabetic mechanisms of gastrointestinal (GI) surgery and to clarify the molecular mechanisms responsible for the benefits of GI surgery on glucose homeostasis is a compelling research objective. We review the existing knowledge regarding the clinical outcomes and of the mechanisms of GI surgery to treat T2DM.
Chemopreventive effect of epigallocatechin‐3‐gallate (EGCG) and folic acid on the N‐methyl‐N′‐nitro‐N‐nitrosoguanidine (MNNG)‐induced gastrointestinal cancer in rat model
Authors: XU Qi , YANG Chuan Hua , LIU Qiang , JIN Xi Feng , XU Xi Tao , TONG Jin Lu , XIAO Shu Dong , RAN Zhi Hua
Published: March 2011

OBJECTIVE:  To investigate the chemopreventive effect and mechanisms of epigallocatechin‐3‐gallate (EGCG) and folic acid on N‐methyl‐N′‐nitro‐N‐nitrosoguanidine (MNNG)‐induced gastrointestinal cancer in rats, and to investigate and compare the combinatorial effects of EGCG and folic acid on the chemoprevention of gastrointestinal carcinogenesis.

METHODS:  A total of 159 healthy male Wistar rats were randomly divided into seven groups to have the MNNG in drink (group M), MNNG in drink and EGCG in the feed (group ME), MNNG in drink and folic acid in the feed (group MF), MNNG in drink and EGCG + folic acid in the feed (group MEF), EGCG in the feed (group E), folic acid in the feed (group F) or normal feed (group C), respectively. At 44 weeks, all the rats were killed and assessed for the presence of gastrointestinal tumor. The occurrence of cancer was evaluated by histology. Ki‐67 in cancerous tissues and in situ apoptosis were determined by immunohistochemical staining or terminal deoxyribonucleotide transferase‐mediated nick‐end labeling (TUNEL) assay, respectively.

RESULTS:  The experiment was completed in 157 rats (98.74%). As compared with group M, the tumor incidence of group MEF decreased significantly (P = 0.011). Ki‐67 expression in cancerous tissues of group ME and MEF also decreased significantly (P = 0.038, P = 0.009), while apoptosis of group ME, MF and MEF increased significantly (P = 0.000, P = 0.003, P = 0.000).

CONCLUSION:  EGCG combined with folic acid has an obvious chemopreventive effect on gastrointestinal carcinogenesis induced by MNNG in rats.
Inferred Indium Resources of the Bolivian Tin‐Polymetallic Deposits
Authors: ISHIHARA Shunso , MURAKAMI Hiroyasu , MARQUEZ‐ZAVALIA Maria Florencia
Published: March 2011

Tin‐polymetallic base metal deposits of Miocene age in the Eastern Cordillera in Bolivia were studied by ICP/MS and EPMA for major and minor elements, paying an attention to indium concentration of the ore deposits. The highest indium content and 1000 In/Zn ratio of individual ore deposits are 5,740 ppm and 22.2 for the Potosi deposits, 2,730 ppm and 7.4 for Bolivar deposit, 2,510 ppm and 17.5 for Siete Suyos–Animas deposits, and 1,290 ppm and 3.3 for San Vicente deposit.

The same content and ratio of composite samples of the studied deposits are up to 292 ppm and 4.0 for Potosi deposits, 3,080 ppm and 11.3 for Huari Huari deposit, 100 ppm and 0.3 for Tuntoco deposit, 152 ppm and 1.8 for Porco deposit, 103 ppm and 59.2 for Animas deposit, and 1,160 ppm and 3.7 for Pirquitas deposit. Those of zinc concentrates are as follows: 1,080 ppm and 2.1 at San Lorenzo; 584 ppm and 1.7 at Bolivar; 499 ppm and 1.23 at Porco; 449 ppm and 1.21 at Reserva, and 213 ppm and 0.61 at Colquiri deposit. Indium occurs mostly in dark colored sphalerite and that of the Potosi deposit was found to have one of the highest concentrations, containing up to 1.27 wt% In. Petrukite was discovered in the Potosi deposit, and indium minerals are expected to occur in the Huari Huari deposit and others with the high 1000 In/Zn ratios.

The indium contents of the zinc concentrates and composite samples were applied to the produced and remaining ores, then the total amounts of indium in the Bolivian tin‐polymetallic base metal deposits are speculated to be more than 12,000 tons In, which is bigger than that of South China (11,000 tons) and the Japanese Islands (9,000 tons). Sphalerites of the Potosi deposit have one of the highest ranges of indium, similarly to those of the San Vicente deposit. Both the San Vicente and Potosi deposits are rich in silver, implying significance of both silver‐polymetallic and tin‐polymetallic environments for the concentration of trace amounts of indium.
Hydrothermal alteration and K–Ar ages of Neogene‐Quaternary magmatic‐hydrothermal systems at Toyoha‐Muine area in southwest Hokkaido, Japan
Authors: SHIMIZU Toru , AOKI Masahiro
Published: March 2011

This paper presents a review of hydrothermal alteration and K–Ar age data from the Toyoha‐Muine area (TMA), where the Toyoha polymetallic (Ag–Pb–Zn–Cu–In) deposit is located near the Pliocene andesitic volcano that formed Mt Muine. Systematic prospect‐scale mapping, sampling, X‐ray analysis and microscopic observation show that hydrothermal alteration is divided into two groups: acid‐pH and neutral‐pH alteration types. The former is further divided into mineral assemblages I, II and III, while the latter into mineral assemblages IV and V. Different mineralogical features in five mineral assemblages are summarized as follows: (I) Quartz (silicified rock); (II) Pyrophyllite or dickite; (III) Kaolinite or halloysite ± alunite; (IV) Sericite or K‐feldspar; and (V) Interstratified minerals (illite/smectite and chlorite/smectite) and/or smectite.

K–Ar radiometric ages determined on twenty‐eight K‐bearing samples (whole volcanic rocks and separated hydrothermal minerals) mainly fall into one of three periods: Early Miocene (24.6–21.4 Ma), Middle–Late Miocene (12.5–8.4 Ma) and Pliocene–Pleistocene (3.2–0 Ma). These three periods are characterized as follows. Early Miocene: A minor hydrothermal activity, which might be genetically related to the intermediate or felsic magmatic activities, formed mineral assemblage IV at 24.6 Ma in the northern part of the TMA. Middle to Late Miocene: The basaltic intrusion, andesitic eruption, and granodiorite intrusions induced hydrothermal activities between 12.5 and 8.4 Ma, resulting in the formation of a mineral assemblage IV with some base metal mineralization. Pliocene–Pleistocene: An andesitic eruption formed Mt Muine between 3.2 and 2.9 Ma. The andesitic activity was associated with acid‐pH mineral assemblages I, II and III locally around the volcano. Latent magmatic intrusions subsequent to the andesitic eruption generated hydrothermal activities that formed mineral assemblages IV and V between 1.9 and 0 Ma in the southern and southeastern parts of Toyoha deposit at depth, overprinting the Middle to Late Miocene alteration. The hydrothermal activities also formed mineral assemblages I, II and III along the Yunosawa fault (east of the Toyoha deposit) and assemblage III in the south and southeast of the Toyoha deposit near the surface.