bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel G6PC3 gene mutation in severe congenital neutropenia: pancytopenia and variable bone marrow phenotype can also be part of this syndrome
Authors: Arikoglu Tugba , Kuyucu Necdet , Germeshausen Manuela , Kuyucu Semanur
Published: April 2014

Glucose‐6‐phosphatase catalytic subunit 3 (G6PC3) deficiency is a newly described syndrome characterized by severe congenital neutropenia associated with multiple organ abnormalities including cardiac and urogenital malformations. The underlying pathophysiology of increased apoptosis of myeloid cells and of neutrophil dysfunction in G6PC3 deficiency involves disturbed glucose metabolism, increased endoplasmic reticulum stress and deficient protein folding. Here, we report a new case of G6PC3 deficiency caused by a novel homozygous G6PC3 gene mutation p.Trp59Arg. The patient showed pancytopenia and a variable bone marrow phenotype with maturation arrest and vacuolization in myeloid lineage cells and a normocellular marrow, respectively. She also showed persistent lymphopenia with low CD4 T‐ and CD19 B‐cell counts. Lymphopenia and even pancytopenia as well as a variable bone marrow phenotype can be part of this syndrome. These clinical findings in a patient with chronic neutropenia should alert the clinician to consider a diagnosis of G6PC3 deficiency.
Role of lateral hypothalamus in two aspects of attention in associative learning
Authors: Wheeler Daniel S. , Wan Sandy , Miller Alexandra , Angeli Nicole , Adileh Bayan , Hu Weidong , Holland Peter C.
Published: April 2014

Orexin (hypocretin) and melanin‐concentrating hormone (MCH) neurons are unique to the lateral hypothalamic (LH) region, but project throughout the brain. These cell groups have been implicated in a variety of functions, including reward learning, responses to stimulants, and the modulation of attention, arousal and the sleep/wakefulness cycle. Here, we examined roles for LH in two aspects of attention in associative learning shown previously to depend on intact function in major targets of orexin and MCH neurons. In experiments 1 and 2, unilateral orexin‐saporin lesions of LH impaired the acquisition of conditioned orienting responses (ORs) and bilaterally suppressed FOS expression in the amygdala central nucleus (CeA) normally observed in response to food cues that provoke conditioned ORs. Those cues also induced greater FOS expression than control cues in LH orexin neurons, but not in MCH neurons. In experiment 3, unilateral orexin‐saporin lesions of LH eliminated the cue associability enhancements normally produced by the surprising omission of an expected event. The magnitude of that impairment was positively correlated with the amount of LH damage and with the loss of orexin neurons in particular, but not with the loss of MCH neurons. We suggest that the effects of the LH orexin‐saporin lesions were mediated by their effect on information processing in the CeA, known to be critical to both behavioral phenomena examined here. The results imply close relations between LH motivational amplification functions and attention, and may inform our understanding of disorders in which motivational and attentional impairments co‐occur.
A diagnostic evaluation of real‐time PCR, fluorescent antibody and microscopic agglutination tests in cases of equine leptospiral abortion
Authors: Erol E. , Jackson C. B. , Steinman M. , Meares K. , Donahoe J. , Kelly N. , Locke S. , Smith J. L. , Carter C. N.
Published: April 2014

Reasons for performing study

A comprehensive evaluation of the real‐time PCR assay for leptospirosis in comparison with other diagnostic assays on a large‐scale basis is fundamental in validating the assay and determining the causes of equine abortions.

Objectives

To compare and evaluate the diagnostic value of real‐time PCR assay for leptospirosis with traditional methods in equine leptospiral abortions.

Study design

Cross‐sectional observational study.

Methods

A Leptospira spp. fluorescent antibody test (FAT), microscopic agglutination test (MAT) and real‐time PCR (targeting the LipL32 gene) were compared and evaluated in equine fetal necropsy specimens (placenta, kidney, liver and heart blood) and maternal serum (when available) in 339 equine fetuses.

Results

From a total of 339 equine fetuses necropsied, 21 cases (6.19%) were diagnosed as leptospiral abortion. The majority of leptospiral abortions occurred in January (8 cases) and February (5 cases). Real‐time PCR detected 21 of 21 cases, whereas MAT and FAT detected 19 and 18 (including 2 suspicious cases) cases, respectively. Comparing tissues, placenta yielded somewhat similar cycle of threshold values by real‐time PCR compared with kidney, whereas kidney was the best specimen for the diagnosis of leptospirosis by the FAT test. In all MAT positive cases, the predominant titre in fetal heart blood was to serovar Pomona (ranging 1:100 to 1:204,800) with little or no cross‐reaction to serovar Grippotyphosa.

Conclusions

The results indicate that real‐time PCR is an effective method for the diagnosis of leptospiral abortion in horses. However, MAT should continue to be used in clinical cases for serovar determination.
Cannabinoid 1 receptors in keratinocytes attenuate fluorescein isothiocyanate‐induced mouse atopic‐like dermatitis
Authors: Gaffal Evelyn , Glodde Nicole , Jakobs Mira , Bald Tobias , Tüting Thomas
Published: April 2014

Atopic dermatitis is a chronic inflammatory disease characterized by an impaired epidermal barrier function combined with a chronic Th2‐type inflammatory response and an intense pruritus. Here, we used an experimental mouse model for Th2‐type contact hypersensitivity (CHS) to fluorescein isothiocyanate (FITC) to investigate the potential role of cannabinoid 1 receptors (CB1) in the pathophysiology of mouse atopic‐like dermatitis. Mice lacking CB1 receptors globally (Cnr1−/−) or specifically in keratinocytes (KC‐Cnr1−/−) as well as wild‐type (WT) control mice were sensitized and challenged with FITC. We examined ear swelling responses, transepidermal water loss, Th2‐type skin inflammatory responses and serum IgE levels. Both Cnr1−/− and KC‐Cnr1−/− showed enhanced CHS responses to FITC and a delayed epidermal barrier repair when compared with WT mice. mRNA levels for IL‐4, thymic stromal lymphopoietin (TSLP) and CCL8, as well as eosinophil activity, were significantly increased in inflamed ear tissue of FITC‐challenged Cnr1−/− and KC‐Cnr1−/− mice. Importantly, CB1 receptor‐deficient keratinocytes secreted increased levels of TSLP, a proinflammatory mediator that drives Th2‐type skin inflammation in atopic dermatitis, under basal and Th2‐type inflammatory conditions. Taken together, our results demonstrate that CB1 receptors in keratinocytes help to maintain epidermal barrier homoeostasis and attenuate Th2‐type allergic inflammatory responses. Based on our work, we propose that enhanced epidermal allergen penetrance cooperates with increased production of TSLP and CCL8 by epidermal keratinocytes for the induction of type 2 CD4+ T helper cells. Our results place keratinocytes at the cross‐roads of outside‐in and inside‐out pathophysiologic mechanisms of atopic dermatitis.
Distinct protein expression and activity of transglutaminases found in different epidermal tumors
Authors: Karashima Tadashi , Furumura Minao , Ishii Norito , Ohyama Bungo , Saruta Hiroshi , Natsuaki Yohei , Nakama Takekuni , Ohata Chika , Tsuruta Daisuke , Hitomi Kiyotaka , Hashimoto Takashi
Published: April 2014

We investigated protein expression and in situ activity of transglutaminases (TGs) in normal skin and various epidermal neoplasms. In normal skin, TG1 protein expression and TG activity were found at keratinocyte cell membranes in upper epidermis and granular layer, respectively. In seborrhoeic keratosis, TG1 protein was expressed evenly throughout tumors, while TG activity increased in gradient fashion from lower tumor area to cornified layer. In squamous cell carcinoma, TG1 protein was expressed at inner side of cell membranes, whereas TG activity was found in cytoplasm predominantly at horn pearls. In basal cell carcinoma, weak TG activity was found in cytoplasm of all tumor cells without the presence of TG1 protein. Immunoblotting and in situ activity assays using specific substrate peptides confirmed that TG2, but not TG1, contributed to the TG activity. These results suggested that different expression and activation of TGs may contribute to characteristics of the skin tumors.
Planning for Children and Resolving Custodial Disputes: A Comment on the Think Tank Report
Authors: Scott Elizabeth S.
Published: April 2014

This comment praises the report from the AFCC Think Tank on Research, Policy, Practice, and Shared Parenting for its support for separating parents' active role in custody planning, its emphasis on both parents' involvement in postdissolution parenting when cooperation is possible and also its recognition of the destructive impact on children of interparental conflict. The comment also commends the report's highlighting the importance of social science research in informing policy in the area, while recognizing that research has little utility in resolving individual cases and is often subject to misuse both in courts and in the policy arena. My primary criticism of the report is its endorsement of the best interest of the child standard as the basis of individualized decisions by judges when parents fail to agree on custody plans. I argue that the application of the best interest standard is in tension with the goals and values of the report, promoting conflict between parents by inviting them to offer evidence of each other's deficiencies, undermining their future cooperation, and encouraging judges to rely inappropriately on mental health professionals who have little expertise to offer in this setting. Instead, I argue that the American Law Institute's (ALI) approximation standard, which allocates parents' future time sharing on the basis of their past roles, is more compatible with the report's goals. The ALI standard promotes parental involvement and cooperation, reduces conflict, and deters the inappropriate use of expert testimony and of weak social science research evidence.

Key Points for the Family Court Community:

Parental cooperation and shared involvement in parenting postdissolution promotes children's welfare.

Parental planning and decision making about their children's custody usually furthers this goal.

For parents who cannot agree on custody, the application of the best interest of the child standard is likely to undermine future cooperation.

The American Law Institute's approximation standard is more likely than the best interest standard to further the goals of the Think Tank report.
Supervised Visitation and Family Financial Well‐Being: Broadening Access to Community Services for Low‐Income Parents in the Court System
Authors: Oehme Karen , Stern Mark Joseph
Published: April 2014

This article describes a federally funded pilot program designed to connect low‐income families at supervised visitation (SV) programs to other community resources to improve their economic well‐being. The pilot program established additional community connections for families in both urban and rural communities. We describe outcomes that suggest that many SV clients can benefit when SV programs are engaged with multiple community service partnerships. We also recommend that judges refer families primarily to those supervised visitation programs that can connect low‐income families to additional resources to help address their problems and improve their economic self‐sufficiency.

Key Points for the Family Court Community:

practical advice about connecting low‐income clients in the court system to community resources,

information for supervised visitation and other social service programs on how to effectively connect families to additional services that can assist with economic well‐being,

steps for making the natural connection between single parents and the local child support enforcement offices,

strategies for connecting families to financial literacy resources, and

ideas and strategies for social service providers to begin the shift of services to a holistic partnership approach that can benefit all families who seek support through community programs.
Closing the Crossover Gap: Amending Fostering Connections to Provide Independent Living Services for Foster Youth Who Crossover to the Justice System
Authors: Wylie Lauren
Published: April 2014

In the last three decades, Congress has enacted a series of amendments to the Social Security Act to address the growing number of youth who “age out” of the foster care system. The most recent and, arguably, the most notable of these programs was The Fostering Connections to Success and Increasing Adoptions Act of 2008 (“Fostering Connections”). Fostering Connections provides funding for states to extend federally supported foster care services to youth beyond their eighteenth birthdays. The Act also requires state agencies to work with each emancipating youth to write a personalized and comprehensive plan for his or her transition to independent living. While this is a huge achievement for the aging‐out population, the language of legislation excludes many foster youth who are arrested and committed to a detention facility. Current legislation dose not ensure that independent living services and opportunities for support under Fostering Connections are extended to foster youth who crossover to the justice system. This Note proposes that the Fostering Connections to Success Act be amended to require that states provide for continuous and coordinated independent living services when a youth in foster care enters the justice system. These services must include ongoing access to contact with child welfare professionals, family members, and mentors who may help the youth to draft a detailed independent living plan.

Key Points for the Family Court Community:

Foster youth who commit crimes and transition to the justice system are at risk of losing access to independent living planning opportunities and support services that are available for their peers in foster care.

A substantial body of research has demonstrated that there is a very strong connection between child maltreatment and delinquency, yet few jurisdictions have taken the steps to remedy information sharing and communication gaps between child welfare systems and juvenile delinquency systems.

The Fostering Connections to Success and Increasing Adoptions Act of 2008 provides many benefits for foster youth who emancipate from the welfare system, yet older foster youth who crossover to the juvenile justice system may be excluded from the receipt of these benefits. While Fostering Connections funding is available for foster youth who live in a variety of settings, the language of the statute excludes youth placed in facilities operated for juvenile delinquents. This may prohibit many former foster youth from accessing opportunities that are specifically designed to assist them with the difficult transition to adulthood.
Ending Reparative Therapy in Minors: An Appropriate Legislative Response
Authors: Moss Ian
Published: April 2014

Reparative Therapy is a controversial Psychological practice designed to “cure” subjects, many of whom are minors, of their homo/bisexuality. These attempts to alter sexual orientation are not only generally met with failure, but also frequently involve the use of therapy methods that provide no medical benefit and carry a great risk of harm. Most troubling about this practice though is that for years, there have been persistent reports of Lesbian, Gay, and Bisexual (LGB) minors being forcibly subjected to this therapy by their parents. It is known that providers of Reparative Therapy, who maintain that homosexuality is a treatable mental disorder, often mislead parents about the risks of the treatment and the therapy's likelihood of success. This Note proposes a state ban on Reparative Therapy, which would prohibit Reparative Therapy Practitioners from using psychological methodologies to attempt to alter the sexual orientation of minors. Modeled off the statutes of New Jersey and California, this ban would protect LGB minors from ineffective and harmful therapies, and do so in a way that does not violate patients, parents, or practitioners' rights under the 1st and 14th Amendments.

Key Points for the Family Court Community:

Therapeutic attempts to “cure” homosexuality, collectively referred to as “Reparative Therapy,” are widely condemned by most mental health organizations as dangerous and ineffective.

There have been many problematic reports of LGB minors being forced into Reparative Therapy, often by parents who have been misled or left unaware of the numerous potential harms that have been associated with the practice like depression, self‐harm, and suicide.

State Bans on Reparative Therapy as applied to minors, as seen in New Jersey and California, are an efficient way to protect minors from being subjected to this practice without penalizing parents, who in most cases are acting in good faith.
Response of deep‐sea biodiversity to abrupt deglacial and Holocene climate changes in the North Atlantic Ocean
Authors: Yasuhara Moriaki , Okahashi Hisayo , Cronin Thomas M. , Rasmussen Tine L. , Hunt Gene
Published: April 2014

Aim

Little is known about how marine biodiversity responds to oceanographic and climatic changes over the decadal to centennial time‐scales which are most relevant for predicted climate changes due to greenhouse gas forcing. This paper aims to reveal decadal–centennial scale deep‐sea biodiversity dynamics for the last 20,000 years and then explore potential environmental drivers.

Location

The North Atlantic Ocean.

Methods

We investigated deep‐sea benthic microfossil records to reveal biodiversity dynamics and subsequently applied comprehensive ecological modelling to test possible environmental factors (i.e. surface productivity, seasonality of productivity or deepwater circulation related to bottom‐water temperature) that may have influenced deep‐sea biodiversity over these time‐scales.

Results

Deep‐sea biodiversity changed synchronously with stadial–interstadial climate changes over the last 20,000 years across a large area of the North Atlantic in both ostracod crustaceans and foraminiferan protozoa (in spite of their different dispersal abilities). Species diversity rapidly increased during abrupt stadial events during the last deglacial and the Holocene interglacial periods. These include the well‐known Heinrich 1, the Younger Dryas and the 8.2 ka events when the strength of Atlantic Meridional Overturning Circulation (AMOC) decreased. There is also evidence for quasi‐cyclic changes in biodiversity at a c. 1500‐year periodicity, consistent with the well‐known ‘1500‐year climatic cycle’. Statistical analyses revealed that AMOC variability (probably specifically the variability in AMOC‐driven bottom‐water temperature) is correlated with deep‐sea biodiversity.

Main conclusions

Our finding of a significant AMOC–diversity relationship may indicate pervasive control of the diversity of deep‐sea benthic species by rapidly changing climate, specifically bottom‐water temperature, over decadal to centennial time‐scales. Our results, based on highly resolved fossil records, may portend pervasive, synchronous and sudden ecosystem responses to human‐induced changes to climate and ocean circulation in this century.
Global change community ecology beyond species‐sorting: a quantitative framework based on mediterranean‐biome examples
Authors: Guerin Greg R. , Martín‐Forés Irene , Biffin Ed , Baruch Zdravko , Breed Martin F. , Christmas Matthew J. , Cross Hugh B. , Lowe Andrew J.
Published: April 2014

Aim

Species‐sorting predicts the influences of the environment on ecosystem composition across heterogeneous landscapes. It assumes that extinction and adaptation are negligible at ecological scales. Meanwhile, shifts associated with global change have been observed in metacommunity composition (species pools affected by extinctions and introductions) and in phenotypes. This suggests that predictions of future composition must move beyond re‐sorting present‐day species with fixed traits. We extend plant species‐sorting concepts to consider biogeography and demography. We give an empirical context, highlighting the influences of biogeography, species‐sorting and adaptation on community composition.

Location

Global; case studies focus on the terrestrial mediterranean biome.

Methods

We review case studies of empirical approaches that have examined community composition at various scales. We develop a mathematical model based on community mechanics that incorporates species‐sorting with shifting phenotypes and species pools.

Results

As illustrated by real examples, community composition is influenced by factors such as history, modern extinction risk, species‐sorting, biotic interactions, adaptation and ecological drift. There is ample evidence that species pools and phenotypes are not constant at ecological scales in the context of global change. Any implicit assumption in community analysis that they are constant should therefore be revisited. Our model breaks down shifting community constraints into intraspecific components – including genotype sorting, selection and plasticity – and interspecific components, including changes in relative abundance and species replacement from a shifting metacommunity.

Main conclusions

Predictions of community composition could benefit from extending species‐sorting, to allow species pools and species traits to shift through time, as dealt with explicitly in our framework. The model predicts that responses to a shifting community constraint can be more diverse than deterministic species re‐sorting. Consequently, the rate of species replacement depends on factors such as species adaptive capacity, competition, physical disturbance and habitat fragmentation.
First Detected Helicobacter pylori Infection in Infancy Modifies the Association Between Diarrheal Disease and Childhood Growth in Peru
Authors: Jaganath Devan , Saito Mayuko , Gilman Robert H. , Queiroz Dulciene M.M. , Rocha Gifone A. , Cama Vitaliano , Cabrera Lilia , Kelleher Dermot , Windle Henry J. , Crabtree Jean E. , Checkley William
Published: April 2014

Background

In endemic settings, Helicobacter pylori infection can occur shortly after birth and may be associated with a reduction in childhood growth.

Materials and Methods

This study investigated what factors promote earlier age of first H. pylori infection and evaluated the role of H. pylori infection in infancy (6–11 months) versus early childhood (12–23 months) on height. We included 183 children near birth from a peri‐urban shanty town outside of Lima, Peru. Field‐workers collected data on socioeconomic status (SES), daily diarrheal and breast‐feeding history, antibiotic use, anthropometrics, and H. pylori status via carbon 13‐labeled urea breath test up to 24 months after birth. We used a proportional hazards model to assess risk factors for earlier age at first detected infection and linear mixed‐effects models to evaluate the association of first detected H. pylori infection during infancy on attained height.

Results

One hundred and forty (77%) were infected before 12 months of age. Lower SES was associated with earlier age at first detected H. pylori infection (low vs middle‐to‐high SES Hazard ratio (HR) 1.59, 95% CI 1.16, 2.19; p = .004), and greater exclusive breast‐feeding was associated with reduced likelihood (HR 0.63, 95% CI 0.40, 0.98, p = .04). H. pylori infection in infancy was not independently associated with growth deficits (p = .58). However, children who had their first detected H. pylori infection in infancy (6–11 months) versus early childhood (12–23 months) and who had an average number of diarrhea episodes per year (3.4) were significantly shorter at 24 months (−0.37 cm, 95% CI, −0.60, −0.15 cm; p = .001).

Discussion

Lower SES was associated with a higher risk of first detected H. pylori infection during infancy, which in turn augmented the adverse association of diarrheal disease on linear growth.
Anti‐M3 muscarinic acetylcholine receptor antibodies in patients with primary biliary cirrhosis
Authors: Tsuboi Hiroto , Ohira Hiromasa , Asashima Hiromitsu , Tsuzuki Sayaka , Iizuka Mana , Matsuo Naomi , Kondo Yuya , Matsumoto Isao , Sumida Takayuki
Published: April 2014

Aim

M3 muscarinic acetylcholine receptor (M3R) is expressed in biliary tracts as well as in exocrine glands. It is reported that some patients with primary biliary cirrhosis (PBC) carry autoantibodies against M3R. The aim of this study is to clarify the presence, potential use as diagnostic marker and clinical roles of anti‐M3R antibodies in PBC.

Methods

We synthesized peptides encoding the extracellular domains of human‐M3R, including the N‐terminal region, the first, second and third extracellular loops. Antibodies against these regions were examined by peptide‐based enzyme‐linked immunoassay in sera of 90 patients with PBC and 40 with chronic hepatitis C (CHC), 21 with non‐alcoholic steatohepatitis (NASH), 10 with primary sclerosing cholangitis (PSC), 14 with obstructive jaundice, 10 with drug‐induced liver injury and 42 healthy controls.

Results

Antibodies to the N‐terminal, first, second and third loop were detected in 90.0% (81/90), 73.3% (66/90), 76.7% (69/90) and 66.7% (60/90) of PBC, in 67.5% (27/40), 10.0% (4/40), 67.5% (27/40) and 27.5% (11/40) of CHC, in 85.7% (18/21), 9.5% (2/21), 4.8% (1/21) and 57.1% (12/21) of NASH, in 60.0% (6/10), 20.0% (2/10), 60.0% (6/10) and 60.0% (6/10) of PSC, in 100.0% (14/14), 0% (0/14), 64.3% (9/14) and 78.6% (11/14) of obstructive jaundice, in 100.0% (10/10), 0% (0/10), 30.0% (3/10) and 10.0% (1/10) of drug‐induced liver injury, and in 4.8% (2/42), 7.1% (3/42), 2.4% (1/42) and 2.4% (1/42) of the controls, respectively.

Conclusion

A high frequency of PBC carried anti‐M3R antibodies. Anti‐M3R antibodies against the first loop of M3R are a potentially useful diagnostic marker for PBC.
Association of chemokine receptor gene variants with HIV‐1 genotype predicted tropism
Authors: Parczewski M , Urbańska A , Maciejewska K , Clark J , Leszczyszyn‐Pynka M
Published: April 2014

Objectives

As a switch from chemokine (C‐C motif) receptor 5 [CCR5 (R5)] to chemokine (C‐X‐C motif) receptor 4 [CXCR4 (X4)] HIV‐1 tropism is associated with symptomatic and AIDS stages of infection, while chemokine receptor gene variants modify the tempo of HIV disease progression, we aimed to analyse the association between pretreatment HIV‐1 tropism and chemokine polymorphisms known to restrict disease progression.

Methods

V3 genotype tropism prediction was performed in a group of 221 treatment‐naïve patients, with subsequent CCR5 Δ32 (rs333), CCR2 V64I (rs1799864), CCR5 promoter (−627 C/T; rs1799988) and CX3CR1 V249I (rs3732378) genotyping performed in 206 patients. Alleles with a protective effect were assigned positive values while risk alleles were assigned negative values to calculate genetic scores. χ2 tests, Mann−Whitney U‐tests and logistic and linear regression models were used for statistical analyses.

Results

R5 tropism was found in 85.5% of patients (n = 189) using a false positive rate (FPR) of 5.75% and in 72.8% of patients (n = 161) using an FPR of 10%. A higher frequency of the 5.75% FPR predicted R5 tropism was associated with the CX3CR1 A allele (P = 0.027). Lower additive genetic scores were associated with an increased frequency of 5.75% FPR predicted R5 tropism (P = 0.0059), with the trend confirmed by logistic regression [odds ratio (OR) 0.5819; 95% confidence interval (CI) 0.3457–0.9795; P = 0.0416]. Viral load tended to increase with decreasing genetic score in the logistic regression analysis (slope = −0.127 ± 0.076; P = 0.095; r2 = 0.161).

Conclusions

The CX3CR1 A allele and lower genetic scores may restrict the switch of HIV‐1 tropism from R5 to X4. This effect may be associated with the amount of co‐receptor on the cell surface. Chemokine receptor gene polymorphisms influence both disease progression and tropism variability.
Antigen 43/Fcε3 chimeric protein expressed by a novel bacterial surface expression system as an effective asthma vaccine
Authors: Huang Feng‐Ying , Wang Cai‐Chun , Huang Yong‐Hao , Zhao Huan‐Ge , Guo Jun‐Li , Zhou Song‐Lin , Wang Hua , Lin Ying‐Ying , Tan Guang‐Hong
Published: April 2014

The IgE Fcε3 domain is an active immunotherapeutic target for asthma and other allergic diseases. However, previous methods for preparing IgE fusion protein vaccines are complex. Antigen 43 (Ag43) is a surface protein found in Escherichia coli that contains α and β subunits (the α subunit contains multiple T epitopes). Here we constructed a novel Ag43 surface display system (Ag43 system) to express Ag43 chimeric proteins to disrupt immune tolerance against IgE. The Ag43 system was constructed from the E. coli strain Tan109, in which the Ag43 gene was deleted and a recombinant plasmid (pETAg43) expressing a partial Ag43 gene was introduced. The Fcε3 domain of the IgE gene was then subcloned into plasmid pETAg43, resulting in a recombinant plasmid pETAg43/Fcε3, which was used to transform Tan109 for Ag43/Fcε3 surface expression. Thereafter, Ag43/Fcε3 was investigated as an asthma vaccine in a mouse model. Ag43/Fcε3 was expressed on and could be separated from the bacterial surface by heating to 60° while retaining activity. Ag43/Fcε3, as a protein vaccine, produced neutralizing autoantibodies to murine IgE, induced significant anti‐asthma effects, and regulated IgE and T helper cytokines in a murine asthma model. Data show that Ag43/Fcε3 chimeric protein is a potential model vaccine for asthma treatment, and that the Ag43 system may be an effective tool for novel vaccine preparation to break immune tolerance to other self‐molecules.
A multiobjective optimization approach for location‐allocation of clinics
Authors: Beheshtifar Sara , Alimoahmmadi Abbas
Published: April 2014

In order to establish new healthcare facilities, their optimal number and locations should be determined. Unsuitable locations for these facilities may result in substandard customer services and increased expenses. To solve this location‐allocation problem, this study applied a multiobjective model that combined geographical information system (GIS) analysis with a multiobjective genetic algorithm. Optimum sites for new clinics were determined by considering four objectives: minimizing total travel cost, minimizing inequity in access to clinics, minimizing the land‐use incompatibility in the study area, and minimizing the costs of land acquisition and facility establishment. Chromosomes of varying lengths were used in the multiobjective optimization process. An important advantage of this is that multiple optimal solutions with different numbers of healthcare facilities can be compared directly. An a posteriori preference method was used in this study. TOPSIS (Technique for Order Preference by Similarity to an Ideal Solution) was applied to assess and compare the Pareto‐optimal solutions and to select the best solution according to different weight vectors. Visualization of the best solution according to each weight vector and compromising among different objectives provided valuable possibilities for selection of the best alternative to decision makers.
Phase Evolution of Ga2O3 Produced from Morphology‐Controllable α‐GaOOH Nanocrystals
Authors: Shi Lihui , Zhang Jian , Wu Si , Li Yingai , Jiang Lina , Cui Qiliang
Published: April 2014

Fine powders of GaOOH nanocrystals are synthesized via a facile hydrolysis process through the solution–solution interface reactions of anhydrous GaCl3 and distilled water followed by subsequent solvothermal treatment at mild conditions. Well‐faceted α‐GaOOH hexagonal prism‐like nanorods are prepared through solvothermal treatment at 180°C with CTAB as the morphology controlling surfactant. Ga2O3 nanocrystals are fabricated via the pyrolysis of α‐GaOOH hexagonal prism‐like nanostructures at temperatures above 410°C. A peculiar back‐transformation from β‐Ga2O3 to α‐Ga2O3 has been observed to occur between about 557°C and 719°C, which is considered to be responsible for the coexistence of the two phases. The phase transformation mechanisms of Ga2O3 at elevated temperatures, as well as the possible transformation route, have been postulated from a thermodynamic point of view.
Genomic predictions across Nordic Holstein and Nordic Red using the genomic best linear unbiased prediction model with different genomic relationship matrices
Authors: Zhou L. , Lund M.S. , Wang Y. , Su G.
Published: April 2014

This study investigated genomic predictions across Nordic Holstein and Nordic Red using various genomic relationship matrices. Different sources of information, such as consistencies of linkage disequilibrium (LD) phase and marker effects, were used to construct the genomic relationship matrices (G‐matrices) across these two breeds. Single‐trait genomic best linear unbiased prediction (GBLUP) model and two‐trait GBLUP model were used for single‐breed and two‐breed genomic predictions. The data included 5215 Nordic Holstein bulls and 4361 Nordic Red bulls, which was composed of three populations: Danish Red, Swedish Red and Finnish Ayrshire. The bulls were genotyped with 50 000 SNP chip. Using the two‐breed predictions with a joint Nordic Holstein and Nordic Red reference population, accuracies increased slightly for all traits in Nordic Red, but only for some traits in Nordic Holstein. Among the three subpopulations of Nordic Red, accuracies increased more for Danish Red than for Swedish Red and Finnish Ayrshire. This is because closer genetic relationships exist between Danish Red and Nordic Holstein. Among Danish Red, individuals with higher genomic relationship coefficients with Nordic Holstein showed more increased accuracies in the two‐breed predictions. Weighting the two‐breed G‐matrices by LD phase consistencies, marker effects or both did not further improve accuracies of the two‐breed predictions.
Modulation of sphingosine‐1‐phosphate and apolipoprotein M levels in the plasma, liver and kidneys in streptozotocin‐induced diabetic mice
Authors: Nojiri Takahiro , Kurano Makoto , Tokuhara Yasunori , Ohkubo Shigeo , Hara Masumi , Ikeda Hitoshi , Tsukamoto Kazuhisa , Yatomi Yutaka
Published: April 2014

Aims/Introduction

Sphingosine‐1‐phosphate (S1P), a multifunctional bioactive lipid mediator, is involved in various diseases. Apolipoprotein M (ApoM) carries S1P on high‐density lipoprotein and modulates S1P metabolism to increase the total S1P mass in the body. Both S1P and ApoM are involved in diabetes.

Materials and Methods

The present study examined the modulation of S1P and ApoM levels in the plasma, liver and kidneys in streptozotocin‐induced diabetes (STZ) mice, and the effects of insulin on the S1P and ApoM levels in the plasma and liver in STZ mice and normal mice. We also examined the effects of insulin and glucose on the ApoM levels in HepG2 cells.

Results

In STZ mice, both the plasma S1P and ApoM levels were higher than those in control mice. The hepatic S1P and ApoM contents were also elevated. The hepatic S1P and ApoM contents were reduced by insulin treatment, whereas high‐dose insulin decreased the plasma S1P and ApoM levels. In mice without streptozotocin treatment, the administration of insulin decreased the plasma S1P and ApoM levels, and the hepatic content of ApoM, whereas the hepatic level of S1P was not altered. Treatment with insulin and incubation under a low glucose level decreased the ApoM levels in HepG2 cells. Regarding the kidney, the renal levels of S1P and ApoM were increased in STZ mice, and insulin treatment partially restored this increment.

Conclusions

In STZ mice, the levels of S1P and ApoM in the plasma, liver, and kidneys were increased. Insulin treatment somehow reversed this modulation in STZ mice.
Role of obesity on the thickness of primary cutaneous melanoma
Authors: Skowron F. , Bérard F. , Balme B. , Maucort‐Boulch D.
Published: April 2014

Background

Thick primary cutaneous melanoma (PCM) is associated with older age, male sex, being single, a low educational level, self‐detection and general practice detection, nodular melanoma (NM) and acral lentiginous melanoma (ALM) types; and are found in the head–neck and lower limb locations. Obesity plays a direct role on melanoma tumour growth, as it has been shown in animal models, but its role in the thickness of PCM remains unknown.

Objectives

We investigated the impact of obesity on the thickness of invasive PCM.

Methods

A cross‐sectional study was performed in a prospective cohort for which we collected several clinical and histological data already known to be associated with thick PCM and the Body Mass Index from new cases of invasive PCM which were referred to the dermatology department in Valence.

Results

Four hundred and twenty‐seven patients were studied. In an univariate analysis, thick PCM was associated with low educational level, obesity, identification by the patient or the general practitioner (GP), location on the cephalic extremity, in a non‐visible area of the body, the NM and ALM type, and an ulceration. In a multivariate analysis, NM, ulceration, topography of the melanoma and identification of the melanoma by the patient or GP were significantly associated with thick melanoma. When including only clinical features in the model, low educational level, mode of melanoma identification and obesity were significantly associated with a risk of thick melanoma.

Conclusions

Obesity is a clinical independent risk factor of thick PCM. For health policies, governments should pay greater attention to detect melanoma in obese patients. Our results encourage the basic research on tumoural growth mechanisms due to obesity in melanoma.
Epicardial adipose tissue and coronary artery calcification in psoriasis patients
Authors: Torres T. , Bettencourt N. , Mendonça D. , Vasconcelos C. , Gama V. , Silva B.M. , Selores M.
Published: April 2014

Background

Psoriasis is a chronic, immune‐mediated disease associated with several cardio‐metabolic comorbidities, accelerated atherosclerosis and cardiovascular disease (CVD). Other causes beyond systemic inflammation and traditional cardiovascular risk factors (CVRF) may be implicated in the increased risk of CVD observed in these patients. Epicardial adipose tissue (EAT), a type of visceral adipose tissue surrounding the heart and coronary vessels has been implicated in the development of coronary artery disease, by endocrine mechanisms, but particularly by local inflammation.

Objective

To compare EAT volumes in psoriasis patients and controls using multidetector computed tomography (MDCT) and to analyse if eventual differences were independent from abdominal visceral adiposity; to determine, within psoriasis patients, its relation with subclinical atherosclerosis and other markers of cardiometabolic risk.

Methods

One hundred patients with severe psoriasis, without CVD underwent MDCT, with EAT and abdominal visceral fat (AVF) assessment and coronary artery calcification (CAC) quantification and were compared with 202 control patients.

Results

EAT volume was increased in psoriasis patients compared to control subjects, independently from age, sex and AVF, being, on average, 15.2 ± 4.41 mL higher (95% CI: 6.5–26.0, P = 0.001) than in controls. Moreover, psoriasis patients had a statistically significant higher risk of having subclinical atherosclerosis (OR 2.52, 95% CI: 1.23–5.16) than controls, after adjusting for traditional CVRF. Within psoriasis patients EAT volume was associated with subclinical atherosclerosis, independently of age, sex, psoriasis duration, classical CVRF and AVF.

Conclusion

This study showed that psoriasis was associated with increased EAT volume independently of visceral abdominal fat and with subclinical atherosclerosis. Within psoriasis patients EAT volume was independently associated with CAC. EAT may be another important contributor to the higher cardiovascular risk observed in psoriasis.
The serum proteome of nonalcoholic fatty liver disease: A multimodal approach to discovery of biomarkers of nonalcoholic steatohepatitis
Authors: Miller Michael H , Walsh Shaun V , Atrih Abdel , Huang Jeffrey T‐J , Ferguson Michael A J. , Dillon John F
Published: April 2014

Background and Aim

Nonalcoholic fatty liver disease (NAFLD) is a common condition affecting up to 25% of the developed world. It is a progressive disease, leading in some to the development of liver cirrhosis. Currently, accurate diagnosis and staging of this condition is only possible with histological examination of a liver biopsy. This gold standard test is neither suitable nor practical for large‐scale use as is necessary for a condition as common as NAFLD. The aim of this study is to describe the proteome of human NAFLD using two distinct shotgun proteomic methods, translating the findings into potential biomarkers of NAFLD.

Methods

Two distinct shotgun proteomic techniques (iTRAQ and label free) were used to describe the proteome of NAFLD. Thereafter, candidate biomarkers were selected for validation by ELISA.

Results

Over 550 protein identifications were made in the description of the NAFLD proteome. Several proteins were found to be significantly up/downregulated in nonalcoholic steatohepatitis compared with control, including apolipoprotein E (fold ratio of 1.67), insulin‐like growth factor‐binding protein 3 (IGFBP3, fold ratio of 1.642), Vitamin D‐binding protein (fold ratio of 4.587), and lymphocyte cytosolic protein1 (LCP1, fold ratio of 4.356). ELISA validation of a subset of these proteins confirms the validity of the proteomic studies and suggests possible new biomarkers of NAFLD.

Conclusion

Serum markers are able to distinguish between the stages of disease in NAFLD as well as detect the grade of fibrosis. Ultimately, noninvasive serum markers may replace liver biopsy in the investigation of patients with suspected NAFLD.
Uma cultura atrasada: The Luso‐Baroque Manezinha, Hyper‐Whiteness, and the Modern Middle Classes in Florianópolis, Brazil
Authors: Turner Jimmy
Published: April 2014

O presente artigo investiga as opinões da classe média branca em Florianópolis sobre seus vizinhos descendentes da diáspora açoreana, conhecidos em Florianópolis como “manezinhos”. Este último grupo enfrenta preconceitos baseados na sua imagem de pessoas simples, atrasadas e presas na tradição. São rotulados como Luso‐Barrocos – sobras da época colonial, uma lembrança embaraçosa da colonização portuguesa. Pessoas da classe média se auto‐diferenciam dos “manezinhos”, pois estes são vistos como um anacronismo que passou ignorado pela época da democracia racial, e eu sugero que são visto como brancos e europeus demais para serem brasileiros. O artigo também apresenta uma análise de gênero ao investigar a construção das “manezinhas” pelas mulheres de classe média, uma construção que confere às manezinhas o papel de vítimas de sua cultura tradicional. É contra as “manezinhas” que a classe média busca construir uma modernidade brasileira pós‐colonial que melhora sua própria branquitude.
Amphetamine‐induced release of dopamine in primate prefrontal cortex and striatum: striking differences in magnitude and timecourse
Authors: Jedema Hank P. , Narendran Rajesh , Bradberry Charles W.
Published: April 2014

The psychostimulant amphetamine (AMPH) is frequently used to increase catecholamine levels in attention disorders and positron emission tomography imaging studies. Despite the fact that most radiotracers for positron emission tomography studies are characterized in non‐human primates (NHPs), data on regional differences of the effect of AMPH in NHPs are very limited. This study examined the impact of AMPH on extracellular dopamine (DA) levels in the medial prefrontal cortex and the caudate of NHPs using microdialysis. In addition to differences in magnitude, we observed striking differences in the temporal profile of extracellular DA levels between these regions that can likely be attributed to differences in the regulation of dopamine uptake and biosynthesis. The present data suggest that cortical DA levels may remain elevated longer than in the caudate which may contribute to the clinical profile of the actions of AMPH.

image

Using microdialysis probes implanted in the cortex and caudate region of non‐human primate brains, we observed in vivo differences in the magnitude and temporal profile of extracellular dopamine levels in response to intravenous amphetamine administration.
Transcutaneous electrical nerve stimulation for the relief of post‐partum uterine contraction pain during breast‐feeding: A randomized clinical trial
Authors: de Sousa Ligia , Gomes‐Sponholz Flávia A. , Nakano Ana Márcia S.
Published: April 2014

Aim

To evaluate transcutaneous electrical nerve stimulation (TENS) used to relieve uterine contraction pain during breast‐feeding in multiparous women.

Methods

A controlled and randomized clinical trial was performed with 32 post‐partum multiparous women who were breast‐feeding. The participants were randomized into an experimental (EG, n = 16) and a control group (CG, n = 16). Pain was assessed using the Numerical Rating Scale and the descriptors of the Present Pain Intensity (PPI – McGill) during two sequential feeds. In the first assessment, the post‐partum women in the EG and CG were monitored while breast‐feeding and questioned regarding the degree of uterine contraction pain. In the second assessment, which was performed at the next feed, the EG used TENS while the CG was monitored, with pain being reassessed following. In the EG, the TENS electrodes were placed between T10–L1 and S2–S4, with a frequency of 100 Hz, a pulse duration of 75 μs and amplitude adjusted to produce a strong and tolerable sensation for 40 min. A descriptive analysis of the data and comparative intra‐ and intergroup analyses were performed by means of a non‐parametrical test, with a significance level P ≤ 0.05.

Results

The level of basal pain was 5.56 in the EG and 5.50 in the CG. In the intragroup analysis, the EG (P < 0.0001) and CG (P = 0.04) presented significant pain reduction. In the intergroup analysis, the EG had significant pain reduction (P < 0.01) in comparison to the CG. In the PPI analysis, a non‐significant decrease in pain intensity was observed in the EG.

Conclusion

TENS was found to be effective in reducing post‐partum uterine contraction pain during breast‐feeding.
Management of squamous cell vulvar cancer: A review
Authors: Deppe Gunter , Mert Ismail , Winer Ira S.
Published: April 2014

Squamous cell vulvar cancer is a rare gynecologic malignancy. Standard treatment for early stage disease consists of wide radical excision of the primary tumor with inguinal–femoral lymphadenectomy or sentinel lymph node mapping/biopsy. Because of the general paucity of patients with advanced vulvar cancer, there is no standard therapy for advanced disease and therefore treatment should be individualized. Intergroup trials are needed to clarify the value of chemoradiation, neoadjuvant chemotherapy and targeted therapy in patients with advanced squamous cell cancer of the vulva to identify modalities with the best therapeutic index and lowest morbidity.