bluuebunny/crossref_metadata_2025 huggingface dataset:
DNA prime‐protein boost vaccine encoding HLA‐A2, HLA‐A24 and HLA‐DR1 restricted epitopes of CaNA2 against visceral leishmaniasis
Authors: He Jinlei , Huang Fan , Zhang Jianhui , Chen Han , Chen Qiwei , Zhang Junrong , Li Jiao , Zheng Zhiwan , Chen Dali , Chen Jianping
Published: October 2018

Visceral leishmaniasis is a tropical and neglected disease with an estimated 200 000–400 000 cases and 60 000 deaths worldwide each year. Currently, no clinically valid vaccine is available for this disease. In this study, we formulated DNA and protein vaccines encoding HLA‐A2, HLA‐A24 and HLA‐DR1 restricted epitopes of CaNA2 against visceral leishmaniasis. We predicted the secondary and tertiary structures, surface properties, subcellular localization, potential binding sites and HLA‐A2, HLA‐A24 and HLA‐DR1 restricted epitopes of CaNA2. The best candidate CpG ODN (2395, M362, D‐SL03 or 685) was screened out as a DNA vaccine adjuvant. We also prepared Kmp‐11 and Kmp‐11/CaNA2 DNA and protein vaccines, respectively, for comparison. BALB/c mice were immunized with a DNA prime‐protein boost immunization strategy and challenged with a newly isolated Leishmania strain from an individual with visceral leishmaniasis. The IgG antibody titers showed that our vaccine had strong immunogenicity with a long duration, especially cellular immunity. The spleen parasite burden of each group demonstrated that the CaNA2 vaccine had a certain immune protective effect on visceral leishmaniasis in BALB/c mice, and the amastigote reduction rate reached 76%. Preliminary safety tests confirmed the safety of the vaccine. Our work demonstrates that the HLA‐A2, HLA‐A24 and HLA‐DR1 restricted epitope CaNA2 DNA prime‐protein boost vaccine may be a safe and effective epitope vaccine candidate against visceral leishmaniasis.
Defending the Data
Authors: Jacobsen Jonny
Published: October 2018

When sick miners sued Britain's National Coal Board in the 1990s, they did so on the basis of research that linked coal dust exposure to lung disease. But that research was soon under attack in court. Jonny Jacobsen reports on his father's role justifying decades of work on coal miners’ lung disease during landmark litigation
Divergent melanism strategies in Andean butterfly communities structure diversity patterns and climate responses
Authors: Dufour Pauline C. , Willmott Keith R. , Padrón Pablo S. , Xing Shuang , Bonebrake Timothy C. , Scheffers Brett R.
Published: October 2018

Aim

Geographic distributions are driven by a combination of species sensitivity and exposure to climate. We quantified colour lightness, a trait that mediates the interaction between sensitivity and exposure, of diverse butterfly communities to test whether colour lightness is associated with community assembly across climate‐elevation gradients.

Location

Ecuadorian Andes.

Methods

We used a long‐term dataset of museum specimens for two of the most species‐rich genera of Pieridae butterflies in Ecuador, Catasticta and Leptophobia. Within a phylogenetic framework, we examined how communities assemble based on four traits across elevation: colour lightness, species‐specific heating rate, maximum temperature (under experimental solar exposure), and elevation breadth.

Results

We found that colour lightness in both genera was related to elevation, but the two genera exhibited opposite patterns; Catasticta are darker and Leptophobia are lighter with increasing elevation. The two genera have opposite configurations of body and body + wings colour lightness but achieve comparable thermoregulation, assessed via their rates of heating under experimental solar exposure. Additionally, we found that the phylogenetic signal for colour lightness was strong, and that patterns between traits and elevation held after correction for phylogeny in Catasticta but not in Leptophobia.

Main conclusions

The two genera exhibit divergent relationships between elevational and colour lightness patterns, with evidence that these relationships evolved multiple times in Catasticta. Communities from these two genera have likely been shaped by selection on different traits, with Catasticta colour lightness more responsive to temperature than Leptophobia. The observed geographic patterns of colour lightness in both body + wings (Catasticta) and body (Leptophobia) correspond strikingly with the distribution of montane cloud forests. Habitat fragmentation and cloud lifting from climate change documented across the Andes may therefore significantly impact communities through increased exposure to solar radiation, highlighting the complexity of conserving these diverse montane communities.
Characteristics of non‐melanoma skin cancers of the cutaneous perioral and vermilion lip treated by Mohs micrographic surgery
Authors: Queen D. , Knackstedt T. , Polacco M.A. , Collins L.K. , Lee K. , Samie F.H.
Published: October 2018

Background

The lip and surrounding perioral region are susceptible to non‐melanoma skin cancer, but the distribution of basal cell and squamous cell carcinoma on the cutaneous and vermilion lips has not been fully elucidated.

Objective

To investigate the distribution of cutaneous and vermilion lip non‐melanoma skin cancer and to better describe risk factors, anatomic location, treatment characteristics and oncologic outcomes.

Methods

A retrospective comparative case series of patients undergoing Mohs micrographic surgery (MMS) at a single academic centre for lip and perioral basal cell and squamous cell carcinoma was performed over a 5‐year period. Demographics, medical comorbidities, surgical characteristics and recurrence status were extracted.

Results

Forty‐five vermilion and 116 cutaneous lip cancers were identified. Basal cell carcinoma (BCC) was more common in the cutaneous perioral region, while squamous cell carcinoma (SCC) was more common on the vermilion lip (P < 0.001). BCCs were more common on the upper vermilion lip and SCCs were more common on the lower vermilion lip (P < 0.001). Within the cutaneous perioral region, both BCCs and SCCs were more common on the upper perioral surface (P = 0.002). Male gender was associated with lower lip SCC (P = 0.015). Smoking, immunosuppression, anticoagulant use and hydrochlorothiazide use were not associated with cancer type or location. Recurrences were rare, but more common in vermilion lip cancers (6.6%) compared to perioral cutaneous cancers (0.8%). Outcomes for all groups were similar; BCCs of the vermilion lip had significantly greater mean MMS stages (P < 0.001) as did SCCs (P = 0.05).

Conclusion

Basal cell carcinoma is more commonly encountered on the cutaneous lip, whereas SCC is more common on the vermilion lip. Within the vermilion lip, BCC favours the upper lip, while SCC favours the lower lip. Within the cutaneous perioral region, both BCC and SCC favour the upper cutaneous tissue. Early stage lip cancers are curable by Mohs micrographic surgery with rare recurrences.
New Species of Closely Related Endosymbiotic Dinoflagellates in the Greater Caribbean have Niches Corresponding to Host Coral Phylogeny
Authors: Lewis Allison M. , Chan Andrea N. , LaJeunesse Todd C.
Published: October 2018

Symbiotic dinoflagellates in the genusBreviolum(formerlySymbiodiniumClade B) dominate coral communities in shallow waters across the Greater Caribbean. While some formally described species exist, mounting genetic, and ecological evidence indicate that numerous more comprise this genus, many of which are closely related. To test this, colonies of common reef‐building corals were sampled across a large geographical range. Phylogenetic and population genetic markers then used to examine evolutionary divergence and delineate boundaries of genetic recombination. Three new candidate species were distinguished by fixed differences in nucleotide sequences from nuclear and chloroplast DNA. Population connectivity was evident within each lineage over thousands of kilometers, however, substantial genetic structure persisted between lineages co‐occurring within sampling locations, signifying reproductive isolation. While geographically widespread with overlapping distributions, each species is ecologically distinct, exhibiting specific mutualisms with phylogenetically distinct coral hosts. Moreover, significant differences in mean cell sizes provide some morphological evidence substantiating formal species distinctions. In providing evidence that satisfies the biological, phylogenetic, ecological, and morphological species concepts, we classify and formally nameBreviolum faviinorumn. sp., primarily associated with Caribbean corals belonging to the Caribbean subfamily Faviinae;B. meandriniumn. sp., associated with corals belonging to the family Meandrinidae; andB. dendrogyrumn. sp., a symbiont harbored exclusively by the threatened coralDendrogyra cylindrus. These findings support the primary importance of niche diversification (i.e. host habitat) in the speciation of symbiotic dinoflagellates.
Catch‐related and genetic outcome of adult northern pike Esox lucius stocking in a large river system
Authors: Guillerault Nicolas , Loot Géraldine , Blanchet Simon , Santoul Frederic
Published: October 2018

Genetic introgression from stocked adult northern pike Esox lucius to a wild self‐recruiting population was detected in a large river system and some stocked E. lucius survived up to two spawning seasons and dispersed over several kilometres in the river. Moreover, the catch rate of stocked E. lucius by anglers was low (9.6%), hence suggesting that the efficiency of stocking activity is questionable.
Seasonal impact and daily intake assessment of mycotoxins in flour, bread, and nixtamalized maize
Authors: Kanwal Rukhsana , Mehmood Asim , Saleem Shahzad , Randhawa Muhammad Atif , Ihsan Awais , Amir Rai Muhammad , Nadeem Muhammad , Sajid Muhammad Wasim
Published: October 2018

The temperature and conditions of moisture after harvesting have the most important impact on fungal growth and mycotoxin production. The present study was designed to assess the presence of different mycotoxins in grains of spring and autumn varieties of maize collected from Sahiwal, district Pakistan. A total of 234 samples of maize flour, bread, and nixtamalized flour were analyzed. All samples were found to be contaminated with aflatoxin and zearalenone while ochratoxin was not detected in any sample. Bread showed the reduction in mycotoxins level for autumn and spring season as (55 and 51%) for aflatoxins (AFs) and (84 and 63% for zearalenone (ZEA) for autumn and spring season's samples. Nixtamalization also showed the reduction in mycotoxins level for autumn and spring (73 and 60%) for AFs and (72.9 and 52%) for ZEA for autumn and spring seasons sample. The probable daily intake values for aflatoxin and zearalenone in autumn and spring seasons were in the range between 0.035–0.049 and 0.350–0.336 μg/kg b.w./day.

Practical applications

The potential presence of mycotoxins in maize is a major health concern for the producers as well as consumers. Mycotoxins presence in food supply chain is result of poor storage condition favoring growth of mold. The mold produces secondary metabolites, mycotoxins. Mycotoxins once become part of maize will be carried out with supply chain. Therefore, monitoring of mycotoxins is necessary to assess their concentration so that food can be made safe for the consumer. Other than quantification of mycotoxins, analysis of mycotoxins behavior toward processing or heat have significant importance for the maize processing industry. This study provides quantification and fate of mycotoxins during processing of maize and nixtamalization. Mycotoxins behavior toward processing will provide relation to their presence and possible reduction.
Effect of Site‐Neutral Payment Policy on Long‐Term Acute Care Hospital Use
Authors: Makam Anil N. , Nguyen Oanh Kieu , Kirby Benjamin , Miller Michael E. , Xuan Lei , Halm Ethan A.
Published: October 2018

Objective

To assess the projected effect of the Centers for Medicare and Medicaid Services new site‐neutral payment policy, which aims to decrease unnecessary long‐term acute care hospital (LTACH) admissions by reducing reimbursements for less‐ill individuals by 2020.

Design

Observational.

Setting

National 5% Medicare data (2011–12).

Measurements

We examined the proportion of site‐neutral LTACH admissions. Regional LTACH market supply was defined as LTACH beds per 100,000 residents, categorized according to tertile. We conducted a hospital‐level analysis to compare the projected effect of site‐neutral payment on “propensity score” matched high‐ and low‐LTACH‐use hospitals.

Results

Forty‐one percent of LTACH admissions would be subjected to site‐neutral payment. The proportion of site‐neutral admissions was large, varied considerably according to LTACH (median 40%, interquartile range 22–60%), and was only modestly greater with greater market supply (Pearson correlation coefficient=0.23, p<.001; coefficient of determination=0.10). The site‐neutral payment policy would affect 47% of admissions from the highest‐supply regions, versus 30% from the lowest‐supply regions (p<.001); and 43% from high‐use hospitals versus 36% from propensity score‐matched low‐use hospitals (p<.001).

Conclusion

A considerable proportion of LTACH admissions will be subjected to lower site‐neutral payments. Although the policy will disproportionately affect high‐use regions and hospitals, it will also affect nearly one‐third of the current LTACH population from low‐use hospitals and regions. As such, the site‐neutral payment policy may limit LTACH access in existing LTAC‐scarce markets, with potential adverse implications for recovery of hospitalized older adults. J Am Geriatr Soc 66:2104–2111, 2018.
Atrial Fibrillation: Possible Influences of Rate and Rhythm Control Strategy on Cognitive Performance
Authors: Damanti Sarah , Pasina Luca , Cortesi Laura , Rossi Paolo D. , Cesari Matteo
Published: October 2018

Objectives

To determine whether rate or rhythm control strategy may affect cognition in older adults with atrial fibrillation (AF).

Design

Retrospective analysis of the REgistro POliterapie SIMI database.

Setting

Italian internal medicine and geriatric wards.

Participants

Individuals aged 65 and older (N=1,082, mean age 80.6 ± 7; 50% male) with AF before hospital admission (for any cause).

Measurements

Evaluation of cognitive performance using the Short Blessed Test (SBT) according to rhythm and rate control strategy, anticoagulant and antiplatelet therapy, age, education, and comorbidities.

Results

Two hundred seventy‐two participants (25%) received rhythm control therapy, 331 (30.6%) rate control therapy, and 479 (44.3%) no therapy of interest. Four hundred thirty‐six (40.3%) in the total sample and in the different rhythm and rate control strategy groups were treated with an oral anticoagulant. Cognitive performance (mean SBT score) was found to be higher in the rhythm control group (7.5 ± 6.6) than in the no therapy (9.9 ± 7.9) and rate control (10.6 ± 8.3) (p<.001) groups. Logistic regression models adjusted for age, sex, education, anticoagulant and antiplatelet therapy, and comorbidities found that the rhythm control strategy (adjusted odds ratio (aOR)=0.56, 95% confidence interval (CI)=0.40–0.79, p=.001) and education (aOR 0.50, 95% CI=0.35–0.62; p<.001) were associated with less likelihood of cognitive impairment

Conclusion

In the absence of anticoagulation, rhythm control of AF may protect against cognitive decline. J Am Geriatr Soc 66:2178–2182, 2018.
Nicotinamide nucleotide transhydrogenase is required for brain mitochondrial redox balance under hampered energy substrate metabolism and high‐fat diet
Authors: Francisco Annelise , Ronchi Juliana A. , Navarro Claudia D. C. , Figueira Tiago R. , Castilho Roger F.
Published: October 2018

Among mitochondrial NADP‐reducing enzymes, nicotinamide nucleotide transhydrogenase (NNT) establishes an elevated matrix NADPH/NADP+ by catalyzing the reduction of NADP+ at the expense of NADH oxidation coupled to inward proton translocation across the inner mitochondrial membrane. Here, we characterize NNT activity and mitochondrial redox balance in the brain using a congenic mouse model carrying the mutated Nnt gene from the C57BL/6J strain. The absence of NNT activity resulted in lower total NADPH sources activity in the brain mitochondria of young mice, an effect that was partially compensated in aged mice. Nonsynaptic mitochondria showed higher NNT activity than synaptic mitochondria. In the absence of NNT, an increased release of H2O2 from mitochondria was observed when the metabolism of respiratory substrates occurred with restricted flux through relevant mitochondrial NADPH sources or when respiratory complex I was inhibited. In accordance, mitochondria from Nnt‐/‐ brains were unable to sustain NADP in its reduced state when energized in the absence of carbon substrates, an effect aggravated after H2O2 bolus metabolism. These data indicate that the lack of NNT in brain mitochondria impairs peroxide detoxification, but peroxide detoxification can be partially counterbalanced by concurrent NADPH sources depending on substrate availability. Notably, only brain mitochondria from Nnt−/− mice chronically fed a high‐fat diet exhibited lower activity of the redox‐sensitive aconitase, suggesting that brain mitochondrial redox balance requires NNT under the metabolic stress of a high‐fat diet. Overall, the role of NNT in the brain mitochondria redox balance especially comes into play under mitochondrial respiratory defects or high‐fat diet.

image
FINANCIAL FRAUD: A LITERATURE REVIEW
Authors: Reurink Arjan
Published: October 2018

This paper describes the empirical universe of financial fraud as it has been documented in the academic literature. Specifically, it describes the different forms of fraudulent behaviour in the context of financial market activities, the prevalence and consequences of such behaviour as identified by previous research, and the economic and market structures that scholars believe facilitate it. To structure the discussion, a conceptual distinction is made between three types of financial fraud: false financial disclosures, financial scams, and financial mis‐selling. The findings of the literature review highlight a number of recent developments that scholars think have facilitated the occurrence of financial fraud, including (1) the development of new fundamental conflicts of interest and perverse incentive structures in the financial industry; (2) an influx of unsophisticated, gullible participants in the financial marketplace; (3) the increasing complexity involved in financial market transactions as a result of rapid technological, legal, and financial innovation and an ever‐widening menu of financial products; (4) an increase in the use of justified secrecy in the form of a mystification of trading models adopted by fund managers.
Caregiving and Union Instability in Middle and Later Life
Authors: Penning Margaret J. , Wu Zheng
Published: October 2018

Objective:This study addressed the implications of informal caregiving for subsequent union instability in middle and later life, focusing on associations between gender and union type (marital, cohabiting) and the risk of separation or divorce within heterosexual unions.

Background:Although caregiving is widely reported to be stressful and to have negative implications for the health and well‐being of individual caregivers, its implications for union stability are less clear. This is particularly evident with regard to middle‐aged and older adults in both marital and cohabiting unions. Yet caregiving may increase separation or divorce risk by operating as a stressor on the marital or union relationship, leading to lower union quality and subsequent dissolution.

Method:Using retrospective data on union histories for a national population‐based cohort of married or cohabiting Canadian men and women aged 45 years and older (N= 17,194), Cox proportional hazard models were used to examine the main and interactive effects of caregiving history, union type, and gender on union dissolution from age 45 to the time of the survey.

Results:Caregiving was more destabilizing when it involved cohabiting rather than marital unions and female rather than male caregivers.

Conclusion:These findings suggest that caregiving is associated with union dissolution but that the type of union and gender need to be considered.
Orofacial pain and its potential oral causes in older people with mild cognitive impairment or dementia
Authors: Delwel Suzanne , Scherder Erik J. A. , de Baat Cees , Binnekade Tarik T. , van der Wouden Johannes C. , Hertogh Cees M. P. M. , Maier Andrea B. , Perez Roberto S. G. M. , Lobbezoo Frank
Published: October 2018

Background

The number of people with dementia and natural dentition is growing. As dementia progresses, the degree of self‐care decreases and the risk of oral health problems and orofacial pain increases.

Objectives

To examine and compare the presence of orofacial pain and its potential causes in older people with Mild Cognitive Impairment (MCI) or dementia.

Methods

In this cross‐sectional observational study, the presence of orofacial pain and its potential causes was studied in 348 participants with MCI or dementia with all levels of cognitive impairment in two outpatient memory clinics and ten nursing homes.

Results

Orofacial pain was reported by 25.7% of the 179 participants who were considered to present a reliable pain self‐report (Mini‐Mental State Examination score ≥14 points), while it could not be determined in people with more severe cognitive impairment. The oral health examination of the 348 participants indicated that potential painful conditions, such as coronal caries, root caries, tooth root remnants or ulcers were present in 50.3%. There was a significant correlation between the level of cognitive impairment and the number of teeth, r = 0.185, P = 0.003, teeth with coronal caries, r = −0.238, P < 0.001, and the number of tooth root remnants, r = −0.229, P = 0.004, after adjusting for age.

Conclusions

This study indicated that orofacial pain and its potential causes were frequently present in participants with MCI or dementia. Therefore, a regular oral examination by (oral) healthcare providers in people with MCI or dementia remains imperative, even if no pain is reported.
Clinical Comparative Evaluation of Nd:YAG Laser and a New Varnish Containing Casein Phosphopeptides‐Amorphous Calcium Phosphate for the Treatment of Dentin Hypersensitivity: A Prospective Study
Authors: Bou Chebel Fady , Zogheib Carina Mehanna , Baba Nadim Z. , Corbani Karim A.
Published: October 2018

Purpose

The aim of this study was to compare the effect of Nd:YAG laser to that of a new varnish: MI Varnish with RECALDENT (GC), for the treatment of dentin hypersensitivity, with a follow‐up of 6 months. Dentinal hypersensitivity was evaluated using a new thermal test never before used on dental tissue.

Materials and Methods

A split‐mouth design was used where teeth on one side received the same type of treatment. Twelve patients suffering from dentin hypersensitivity were chosen. Fifty‐four teeth were divided into 27 pairs. Twenty‐seven teeth received the Nd:YAG laser treatment, and the 27 contralateral teeth received MI Varnish application. Five parameters were measured, and the measurements were taken before treatment at baseline (T0), after 1 week (T1), 1 month (T2), 3 months (T3), and 6 months (T4) of the application. Air stimulation to obtain the Schiff air score, the score of discomfort according to the visual analog scale (VAS), the tactile score, and the thermal test that determines the minimum cold‐stimulating temperature and the maximum heat‐stimulating temperature were all used to assess sensitivity. Statistical analyses of the data were performed, and the significance level was set at p ≤ 0.05. Exact Fisher tests and Chi‐Square tests were conducted to compare percentages.

Results

There was a clear decrease in dentin hypersensitivity for both treatments (Nd:YAG laser and MI Varnish) especially between baseline and 1 week, with maintenance of this state through the 6‐month follow‐up period. The difference between the two treatments was not significant, comparing, over time, the Schiff air score, the thermal test, and the VAS; however, the tactile score was significantly improved 6 months after the application of MI Varnish compared to the laser (p = 0.05).

Conclusion

There was no significant difference between the two treatments, Nd:YAG laser and MI Varnish. Both treatments were effective and reduced dentin hypersensitivity immediately after treatment up to 6 months.
Income inequality, perceived competitiveness, and approach‐avoidance motivation
Authors: Sommet Nicolas , Elliot Andrew J. , Jamieson Jeremy P. , Butera Fabrizio
Published: October 2018

Objective

Scholars disagree on whether income inequality has incentive or disincentive effects. In the present research, we move beyond such debate and focus on the motivational processes that income inequality predicts. First, income inequality makes economic stratification salient; therefore, it should promote perceived competitiveness. Second, competitiveness can be appraised as both a challenge and a threat; therefore, it should promote both approach and avoidance motivation.

Method

In three studies (N = 2,543), U.S. residents from various ZIP codes reported the extent to which they perceived competitiveness in their town/city (Studies 1–3), as well as their economic achievement goals, achievement motives, and self‐regulatory foci (Studies 2–3).

Results

Level of local income inequality was found to be a positive predictor—via increased perceived competitiveness—of other‐approach economic goals, need for achievement, and promotion focus, as well as other‐avoidance economic goals, fear of failure (specifically, the shame/embarrassment component), and prevention focus. Furthermore, actual and perceived income inequality were positively correlated.

Conclusions

The conceptual and empirical work herein is the first to show how the economic environment predicts individuals’ perceptions of competitiveness, influencing personal goals, motives, and orientations. It provides a more nuanced perspective on the implications of income inequality than perspectives currently available.
A genome‐wide association study identifies an association between variants in EFCAB4B gene and periodontal disease in an Italian isolated population
Authors: Bevilacqua Lorenzo , Navarra Chiara O. , Pirastu Nicola , Lenarda Roberto Di , Gasparini Paolo , Robino Antonietta
Published: October 2018

Background and Objective

Periodontitis in one of the most prevalent dental diseases. Despite numerous studies have investigated its aetiopathogenetic factors, few works have focused on its genetic predisposition and most of them took into account only candidate genes. Therefore, we conducted a Genome Wide Association Study in an Italian isolated population aimed at uncovering genetic variants that predispose to this disorder.

Methods

Diagnosis of chronic periodontitis was made following the criteria of the American Academy of Periodontology. Patients with chronic periodontitis were grouped into different categories: slight, severe, localized and generalized. A control group composed by people without signs of periodontitis or gingivitis was defined. DNA was genotyped using 370k Illumina chips. Linear mixed model regression was used to test the association between each single nucleotide polymorphism (SNP) (independent variable) and the periodontitis status (dependent variable), controlling for confounders sex, age and smoking. The genomic kinship matrix was also used as random effect.

Results

Four SNPs on the gene EFCAB4B resulted significantly associated to localized periodontitis (P < 5 × 10−8), with the best hit on the rs242016 SNP (P = 1.5 × 10−8).

Conclusion

We have identified a novel significant association between the EFCAB4B gene and localized periodontitis. These results open a new perspective in the understanding of genetic factors contributing to this common disorder.
Association of LTA gene haploblock with periodontal disease in Italian adults
Authors: Zupin Luisa , Moura Rodrigues Ronald , Navarra Chiara Ottavia , Bevilacqua Lorenzo , Catamo Eulalia , Di Lenarda Roberto , Gasparini Paolo , Crovella Sergio , Robino Antonietta
Published: October 2018

Background

Periodontitis is a common oral disease caused by host inflammatory response towards bacteria biofilm. The chronic activation of immune response leads to destruction of teeth supporting tissue, bone loss and tooth detachment. Different factors could be involved in the development and severity of the disease; among them the host genetic background should be considered.

Objectives

In our study, we analysed haploblocks in a genomic region within major histocompatibility complex (MHC) locus aimed at disclosing a possible correlation with the risk of periodontal disease in 602 adult subjects from North‐East Italy.

Results

The CTTAC haploblock (formed by LTA‐rs2857709, LTA‐rs2844484, LTA‐ rs2229094, LTA‐rs2229092 and LTA‐rs1041981 polymorphisms) correlated with protection towards periodontitis condition, after regression analysis including age and smoking status as covariates (P‐value = 0.015).

Conclusion

Our results suggest that a haplotype within LTA gene (encoding for lymphotoxin alpha) is involved in the susceptibility towards chronic periodontitis.
Using Single‐Case Research Designs to Examine the Effects of Interventions in Special Education
Authors: Maggin Daniel M. , Cook Bryan G. , Cook Lysandra
Published: October 2018

Single‐case research methods provide the basis for evaluating effective instructional approaches in special education. The purpose of this article is to provide special educators an overview of single‐case research methods, with an emphasis on how these designs are used to establish whether an instructional practice relates to improved learner outcomes. Specifically, we describe (1) core principles of single‐case design (SCD) research, (2) two frequently used SCDs—withdrawal and multiple‐baseline designs, (3) how visual analysis of graphed data is used to examine functional relations in SCDs, (4) limitations to the generalizability of findings from individual SCD studies, and (5) two studies in the special education literature that use SCDs. Our take‐home message is that SCDs can be used to determine whether an instructional intervention causes improved outcomes for students, but caution is warranted when generalizing results from individual SCD studies.
Primary feldspar in the Semarkona LL3.00 chondrite: Constraints on chondrule formation and secondary alteration
Authors: Lewis Jonathan A. , Jones Rhian H.
Published: October 2018

Feldspar in ordinary chondrites (OCs) is often associated with thermal metamorphism, as a secondary mineral that forms from the crystallization of matrix and chondrule mesostasis. However, studies of feldspar in equilibrated OCs show that there is a range of plagioclase compositions within chondrules, some of which may be primary products of chondrule crystallization. It is important to recognize primary feldspar within chondrules because it can be used to help understand the secondary effects of thermal metamorphism and aqueous alteration. The presence of primary feldspar also provides important petrologic constraints on chondrule formation time scales. We undertook a careful study of Semarkona (LL3.00) and observed feldspar in 18% of chondrules. The feldspar is plagioclase covering a wide range of compositions (An2–An99) with little K‐feldspar component (<Or3). We show that plagioclase is a primary igneous phase, based on grain morphology and compositions consistent with growth from a melt having the bulk compositions of the host chondrules. Based on experimental studies, the presence of plagioclase suggests chondrules cooled slowly at temperatures close to the solidus. We also observed several secondary features consistent with the aqueous alteration. These features include zoning of Na and Ca in plagioclase, heterogeneity in plagioclase compositions in altered chondrules, development of porosity from the dissolution of chondrule glass, and alteration of glass to phyllosilicates. Alteration of major Al‐bearing phases, like plagioclase and glass, has important implications for interpretations of ages derived from Al‐Mg dating of chondrules, if they have been affected by secondary processes.
Independent homoploid hybrid speciation events in the Macaronesian endemic genusArgyranthemum
Authors: White Oliver W. , Reyes‐Betancort Alfredo , Chapman Mark A. , Carine Mark A.
Published: October 2018

Well‐characterized examples of homoploid hybrid speciation (HHS) are rare in nature, yet they offer the potential to study a number of evolutionary processes. In this study, we investigate putative homoploid hybrid species in the genusArgyranthemum(Asteraceae), a group of plants endemic to the Macaronesian archipelagos of the North Atlantic Ocean. We specifically address a number of knowledge gaps surrounding the origin(s) ofA. sundingiiandA. lemsii, which are thought to be derived from the same parental cross. Comparisons of leaf morphology suggest thatA. sundingiiandA. lemsiiare distinct from their parental progenitors and distinguishable from each other based on leaf area. Ecological niche modelling (ENM) demonstrated that the homoploid hybrid species occupy novel habitats that are intermediate relative to the parental species. Nuclear simple sequence repeat markers (SSRs) and single nucleotide polymorphism (SNP) data indicate that the homoploid hybrid species are distinct from the parental taxa, while population‐level sampling of chloroplastSSRs and approximate Bayesian computation show thatA. sundingiiandA. lemsiiare independently derived from the same parental cross. As such,Argyranthemumrepresents an example of independent homoploid hybrid speciation events with evidence of divergence in leaf morphology and adaptation to novel intermediate habitats. On oceanic islands, which are often typified by steep ecological gradients and inhabited by recently derived species with weak reproductive barriers, multipleHHSevents from the same parental cross are not only possible but also likely to have played a more important role in oceanic island radiations than we currently think.
Sphingosine‐1‐phosphate protects against brain microvascular endothelial junctional protein disorganization and barrier dysfunction caused by alcohol
Authors: Alves Natascha G. , Yuan Sarah Y. , Breslin Jerome W.
Published: October 2018

Objective

S1P has known endothelial barrier‐protective properties, but whether this extends to the BBB is unclear. We hypothesized that alcohol‐induced disruption of brain microvascular endothelial barrier function and junctional protein organization can be ameliorated by S1P treatment.

Methods

Cultured primary HBMEC monolayers were used to characterize endothelial‐specific mechanisms of BBB regulation. TER and apparent permeability coefficients for albumin, dextran‐4 kDa, and sodium fluorescein were used as indices of barrier function. Junctional localization of Claudin‐5, VE‐cadherin, and β‐catenin was determined by immunofluorescence confocal microscopy. S1P was applied following treatment with alcohol.

Results

Alcohol significantly impaired HBMEC TER. Application of S1P after alcohol treatment resulted in a hastened recovery to the baseline HBMEC TER. Alcohol‐treated HBMEC had a significantly higher mean permeability than control that was reversed by S1P. Alcohol caused the formation of gaps between cells. Treatment with S1P (after alcohol) increased junctional localization of VE‐Cadherin, Claudin‐5, and β‐catenin.

Conclusions

Alcohol impairs the barrier function and junctional organization of HBMEC monolayers. S1P enhanced barrier function and restored junctions in the presence of alcohol, and thus may be useful for restoring BBB function during alcohol intoxication.
Cryptic protein interactions regulate DNA replication initiation
Authors: Matthews Lindsay A. , Simmons Lyle A.
Published: October 2018

DNA replication is a fundamental biological process that is tightly regulated in all cells. In bacteria, DnaA controls when and where replication begins by building a step‐wise complex that loads the replicative helicase onto chromosomal DNA. In many low‐GC Gram‐positive species, DnaA recruits the DnaD and DnaB proteins to function as adaptors to assist in helicase loading. How DnaA, its adaptors and the helicase form a complex at the origin is unclear. We addressed this question using the bacterial two‐hybrid assay to determine how the initiation proteins from Bacillus subtilis interact with each other. We show that cryptic interaction sites play a key role in this process and we map these regions for the entire pathway. In addition, we found that the SirA regulator that blocks initiation in sporulating cells binds to a surface on DnaA that overlaps with DnaD. The interaction between DnaA and DnaD was also mapped to the same DnaA surface in the human pathogen Staphylococcus aureus, demonstrating the broad conservation of this surface. Therefore, our study has unveiled key protein interactions essential for initiation and our approach is widely applicable for mapping interactions in other signaling pathways that are governed by cryptic binding surfaces.
Chronic stress and intestinal permeability: Lubiprostone regulates glucocorticoid receptor‐mediated changes in colon epithelial tight junction proteins, barrier function, and visceral pain in the rodent and human
Authors: Zong Ye , Zhu Shengtao , Zhang Shutian , Zheng Gen , Wiley John W , Hong Shuangsong
Published: October 2018

Background

Chronic psychological stress is associated with increased intestinal epithelial permeability and visceral hyperalgesia. Lubiprostone, an agonist for chloride channel‐2, promotes secretion and accelerates restoration of injury‐induced epithelial barrier dysfunction. The mechanisms underlying how lubiprostone regulates colon epithelial barrier function and visceral hyperalgesia in chronic stress remain unknown.

Methods

Male rats were subjected to water avoidance stress for 10 consecutive days. Lubiprostone was administered daily during the stress phase. Visceromotor response to colorectal distension was measured. Human colon crypts and cell lines were treated with cortisol and lubiprostone. The transepithelial electrical resistance and FITC‐dextran permeability were assayed. Chromatin immunoprecipitation was conducted to assess glucocorticoid receptor binding at tight junction gene promoters.

Key Results

Lubiprostone significantly decreased chronic stress‐induced visceral hyperalgesia in the rat (P < 0.05; n = 6). WA stress decreased occludin and claudin‐1 and increased claudin‐2 in rat colon crypts, which was prevented by lubiprostone. Cortisol treatment induced similar alterations of tight junction protein expression in Caco‐2/BBE cells (P < 0.05) and significantly changed paracellular permeability in monolayers (P < 0.01). These changes were blocked by lubiprostone. Glucocorticoid receptor and its binding at occludin promoter region were decreased in cortisol‐treated cells and human colon crypts, which was largely reversed by lubiprostone. In rat colonic cells, glucocorticoid receptor and its co‐chaperone proteins were down‐regulated after corticosterone treatment and lubiprostone reversed these changes.

Conclusions & Inferences

Lubiprostone preferentially prevents chronic stress‐induced alterations of intestinal epithelial tight junctions, barrier function, and visceral hyperalgesia that was associated with modulation of glucocorticoid receptor expression and function.
Genome‐wide association study reveals new loci involved in Arabidopsis thaliana and Turnip mosaic virus (TuMV) interactions in the field
Authors: Rubio Bernadette , Cosson Patrick , Caballero Mélodie , Revers Frédéric , Bergelson Joy , Roux Fabrice , Schurdi‐Levraud Valérie
Published: October 2018

The genetic architecture of plant response to viruses has often been studied in model nonnatural pathosystems under controlled conditions. There is an urgent need to elucidate the genetic architecture of the response to viruses in a natural setting.

A field experiment was performed in each of two years. In total, 317 Arabidopsis thaliana accessions were inoculated with its natural Turnip mosaic virus (TuMV). The accessions were phenotyped for viral accumulation, frequency of infected plants, stem length and symptoms. Genome‐wide association mapping was performed.

Arabidopsis thaliana exhibits extensive natural variation in its response to TuMV in the field. The underlying genetic architecture reveals a more quantitative picture than in controlled conditions. Ten genomic regions were consistently identified across the two years. RTM3 (Restricted TEV Movement 3) is a major candidate for the response to TuMV in the field. New candidate genes include Dead box helicase 1, a Tim Barrel domain protein and the eukaryotic translation initiation factor eIF3b.

To our knowledge, this study is the first to report the genetic architecture of quantitative response of A. thaliana to a naturally occurring virus in a field environment, thereby highlighting relevant candidate genes involved in plant virus interactions in nature.
Functional trait divergence and trait plasticity confer polyploid advantage in heterogeneous environments
Authors: Wei Na , Cronn Richard , Liston Aaron , Ashman Tia‐Lynn
Published: October 2018

Polyploidy, or whole‐genome duplication often with hybridization, is common in eukaryotes and is thought to drive ecological and evolutionary success, especially in plants. The mechanisms of polyploid success in ecologically relevant contexts, however, remain largely unknown.

We conducted an extensive test of functional trait divergence and plasticity in conferring polyploid fitness advantage in heterogeneous environments, by growing clonal replicates of a worldwide genotype collection of six allopolyploid and five diploid wild strawberry (Fragaria) taxa in three climatically different common gardens.

Among leaf functional traits, we detected divergence in trait means but not plasticities between polyploids and diploids, suggesting that increased genomic redundancy in polyploids does not necessarily translate into greater trait plasticity in response to environmental change. Across the heterogeneous garden environments, however, polyploids exhibited fitness advantage, which was conferred by both trait means and adaptive trait plasticities, supporting a ‘jack‐and‐master’ hypothesis for polyploids.

Our findings elucidate essential ecological mechanisms underlying polyploid adaptation to heterogeneous environments, and provide an important insight into the prevalence and persistence of polyploid plants.
Cold sensitivity of mitochondrial ATP synthase restricts oxidative phosphorylation in Arabidopsis thaliana
Authors: Kerbler Sandra M. , Taylor Nicolas L. , Millar A. Harvey
Published: October 2018

The combined action of the electron transport chain (ETC) and ATP synthase is essential in determining energy efficiency in plants, and so is important for cellular biosynthesis, growth and development. Owing to the sessile nature of plants, mitochondria must operate over a wide temperature range in the environment, necessitating a broad temperature tolerance of their biochemical reactions.

We investigated the temperature response of mitochondrial respiratory processes in isolated mitochondria and intact plants of Arabidopsis thaliana and considered the effect of instantaneous responses to temperature and acclimation responses to low temperatures.

We show that at 4°C the plant mitochondrial ATP synthase is differentially inhibited compared with other elements of the respiratory pathway, leading to decreased ADP : oxygen ratios and a limitation to the rate of ATP synthesis. This effect persists in vivo and cannot be overcome by cold‐temperature acclimation of plants.

This mechanism adds a new element to the respiratory acclimation model and provides a direct means of temperature perception by plant mitochondria. This also provides an alternative explanation for non‐phosphorylating ETC bypass mechanisms, like the alternative oxidase to maintain respiratory rates, albeit at lower ATP synthesis efficiency, in response to the sensitivity of ATP synthase to the prevailing temperature.
Inhibition of isoprenylation synergizes with MAPK blockade to prevent growth in treatment‐resistant melanoma, colorectal, and lung cancer
Authors: Theodosakis Nicholas , Langdon Casey G. , Micevic Goran , Krykbaeva Irina , Means Robert E. , Stern David F. , Bosenberg Marcus W.
Published: October 2018

This study evaluates the use of HMG‐CoA reductase inhibitors, or statins, as an adjunctive to BRAF and MEK inhibition as a treatment in melanomas and other tumors with driver mutations in the MAPK pathway. Experiments used simvastatin in conjunction with vemurafenib and selumetinib in vitro and simvastatin with vemurafenib in vivo to demonstrate additional growth abrogation beyond MAPK blockade alone. Additional studies demonstrated that statin anti‐tumor effects appeared to depend on inhibition of isoprenoid synthesis given rescue with add‐back of downstream metabolites. Ultimately, we concluded that statins represent a possible useful adjunctive therapy in MAPK‐driven tumors when given with current approved targeted therapy.
Dermatophytosis of the diaper area: Case report and literature review
Authors: Morales‐Conde Macarena , Feito‐Rodríguez Marta , de Lucas‐Laguna Raúl
Published: October 2018

Dermatophytosis in infants is rare, especially dermatophytosis of the diaper area. This case report and literature review provides keys to establishing the above diagnosis and discusses the current controversies concerning the use of antifungal drugs in this age group.
Methods of Assessment of the Corneas of the Eyes Laboratory Rabbits Exposed to Solar Ultraviolet‐B Radiation
Authors: Doughty Michael J.
Published: October 2018

The goal of this review was to identify and discuss the specialized methods that have been used to assess the corneas of the eyes of living rabbits exposed to the damaging effects of ultraviolet‐B (UV‐B). From publications reviewed between 1916 and 2018, both albino and pigmented rabbits were used, usually being young adults weighing between 2 and 2.5 kg, and with many recent studies carried out under sedation. Older assessments were generally based on the use of in vivo slitlamp examinations, sometimes with the use of fluorescein or rose bengal to identify damaged cells, supported by light microscopy (histology) of excised corneas. In later years (after 1960), these structural studies have included in vivo and ex vivo specular microscopy, transmission and scanning electron microscopy as well as impression cytology. Early studies included measurements of the thickness of excised corneal specimens but in vivo pachymetry methods were widely used from the 1980s. Other assessments have included measurement of light transmission spectra of excised corneas, measures of metabolites in isolated corneas or staining corneal specimens for enzyme activities. While a wide range of specialized methods have been used, most of them have provided only descriptions of the effects of UV‐B.