bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic allergen modification in the development of novel approaches to specific immunotherapy
Authors: Mutschlechner S. , Deifl S. , Bohle B.
Published: July 2009

In the recent past, multiple allergens from relevant allergen sources have been cloned, sequenced and produced as recombinant proteins. The availability of recombinant allergens with immunological characteristics similar to their natural counterparts has improved the diagnosis of allergic disorders and increased our knowledge of the biochemical, structural and immunological characteristics of proteins with allergenic potential. Moreover, the use of defined recombinant proteins as vaccines substituting currently used total protein extracts from allergen sources may improve specific immunotherapy (SIT) of Type I allergy. In addition to producing well‐defined batches of wild‐type allergens, the recombinant technology offers the possibility to easily and selectively modify their properties or functions. Diverse modifications of allergens can be genetically engineered, e.g. variants with reduced IgE‐binding capacity, multi‐mers of single allergens or hybrids consisting of different allergens. Furthermore, allergens can be genetically fused with proteins that promote immune responses, which counterregulate the disease‐eliciting T‐helper type 2‐dominated immune response in allergic individuals and may therefore, improve the efficacy of SIT. This review will introduce different concepts of allergen modification using genetic engineering to improve vaccines for SIT of Type I allergy.
Is CSF cytology a useful diagnostic procedure in staging paediatric CNS tumours?
Authors: Cohen N. R. , Phipps K. , Harding B. , Jacques T. S.
Published: July 2009

Objectives:  To evaluate whether there are any factors that predict malignant cells being found in paediatric cerebrospinal fluid (CSF) samples. To determine whether CSF provides useful staging information not provided by magnetic resonance imaging (MRI) in paediatric patients with primary central nervous system (CNS) malignancy.

Methods:  We compared the CSF cytology and spinal MRI staging results in paediatric patients with primary CNS malignancy at a UK tertiary referral centre, over a decade.

Results:  Of 159 CSF samples, 72 samples were from 72 patients with primary CNS malignancy with spinal MRI available for comparison. Eight of these 72 had positive cytology (seven malignant and one suspicious). All had a high clinical suspicion of tumour at the time of sampling. Of the 72 patients, only two had evidence of CSF spread on MRI spinal staging and CSF cytology; ten had MRI without cytological evidence and six had cytological without MRI evidence.

Conclusions:  In paediatric patients with primary CNS tumours, CSF cytology provides useful staging information. Spinal MRI alone may miss some patients with CSF spread who would be identified with CSF cytology.
The BSCC Code of Practice – exfoliative cytopathology (excluding gynaecological cytopathology)
Authors: Chandra A. , Cross P. , Denton K. , Giles T. , Hemming D. , Payne C. , Wilson A. , Wilson P.
Published: July 2009

Exfoliative cytopathology (often referred to as non‐gynaecological cytology) is an important part of the workload of all diagnostic pathology departments. It clearly has a role in the diagnosis of neoplastic disease but its role in establishing non‐neoplastic diagnoses should also be recognised. Ancillary tests may be required to establish a definitive diagnosis. Clinical and scientific teamwork is essential to establish an effective cytology service and staffing levels should be sufficient to support preparation, prescreening, on‐site adequacy assessment and reporting of samples as appropriate. Routine clinical audit and histology/cytology correlation should be in place as quality control of a cytology service. Cytology staff should be involved in multidisciplinary meetings and appropriate professional networks. Laboratories should have an effective quality management system conforming to the requirements of a recognised accreditation scheme such as Clinical Pathology Accreditation (UK) Ltd. Consultant pathologists should sign out the majority of exfoliative cytology cases. Where specimens are reported by experienced biomedical scientists (BMS), referred to as cytotechnologists outside the UK, this must only be when adequate training has been given and be defined in agreed written local protocols. An educational basis for formalising the role of the BMS in exfoliative cytopathology is provided by the Diploma of Expert Practice in Non‐gynaecological Cytology offered by the Institute of Biomedical Science (IBMS). The reliability of cytological diagnoses is dependent on the quality of the specimen provided and the quality of the preparations produced. The laboratory should provide feedback and written guidance on specimen procurement. Specimen processing should be by appropriately trained, competent staff with appropriate quality control. Microscopic examination of preparations by BMS should be encouraged wherever possible. Specific guidance is provided on the clinical role, specimen procurement, preparation and suitable staining techniques for urine, sputum, semen, serous cavity effusion, cerebrospinal fluid, synovial fluid, cyst aspirates, endoscopic specimens, and skin and mucosal scrapes.
Obesity and metabolic syndrome in histone demethylase JHDM2a‐deficient mice
Authors: Inagaki Takeshi , Tachibana Makoto , Magoori Kenta , Kudo Hiromi , Tanaka Toshiya , Okamura Masashi , Naito Makoto , Kodama Tatsuhiko , Shinkai Yoichi , Sakai Juro
Published: July 2009

Histone H3 lysine 9 (H3K9) methylation is a crucial epigenetic mark of heterochromatin formation and transcriptional silencing. Recent studies demonstrated that most covalent histone lysine modifications are reversible and the jumonji C (JmjC)‐domain‐containing proteins have been shown to possess such demethylase activities. However, there is little information available on the biological roles of histone lysine demethylation in intact animal model systems. JHDM2A (JmjC‐domain‐containing histone demethylase 2A, also known as JMJD1A) catalyses removal of H3K9 mono‐ and dimethylation through iron and α‐ketoglutarate dependent oxidative reactions. Here, we demonstrate that JHDM2a also regulates metabolic genes related to energy homeostasis including anti‐adipogenesis, regulation of fat storage, glucose transport and type 2 diabetes. Mice deficient in JHDM2a (JHDM2a−/−) develop adult onset obesity, hypertriglyceridemia, hypercholesterolemia, hyperinsulinemia and hyperleptinemia, which are hallmarks of metabolic syndrome. JHDM2a−/− mice furthermore exhibit fasted induced hypothermia indicating reduced energy expenditure and also have a higher respiratory quotient indicating less fat utilization for energy production. These observations may explain the obesity phenotype in these mice. Thus, H3K9 demethylase JHDM2a is a crucial regulator of genes involved in energy expenditure and fat storage, which suggests it is a previously unrecognized key regulator of obesity and metabolic syndrome.
Sexual division of antibacterial resource defence in breeding burying beetles, Nicrophorus vespilloides
Authors: Cotter Sheena C. , Kilner Rebecca M.
Published: July 2009

1. A key component of parental care involves defending resources destined for offspring from a diverse array of potential interspecific competitors, such as social parasites, fungi and bacteria.

2. Just as with other aspects of parental care, such as offspring provisioning or brood defence, sexual conflict between parents may arise over how to share the costs of this form of care. There has been little previous work, however, to investigate how this particular burden might be shared.

3. Here, we describe a hitherto uncharacterized form of parental care in burying beetles Nicrophorus vespilloides, a species which prepares carrion for its young and faces competition from microbes for this resource. We found that parents defend the carcass with antibacterial anal exudates, and that the antibacterial activity of these exudates is only upregulated following the discovery of a corpse. At the same time, phenoloxidase activity in the anal exudates is downregulated, indicating parallels with the internal insect immune system.

4. In unmanipulated breeding pairs, females had higher antibacterial activity in their anal exudates than males, suggesting sex‐specific roles in this aspect of parental care.

5. When we experimentally widowed males, we found that they increased levels of antibacterial activity in their anal exudates. Experimentally widowing females, however, led them to decrease levels of antibacterial activity in their anal exudates. Widowed beetles of each sex thus produced anal exudates of comparable antibacterial activity. We suggest that this flexible division of antibacterial activity may be coordinated by Juvenile Hormone.
Effects of atorvastatin on circulating CD34+/CD133+/ CD45− progenitor cells and indices of angiogenesis (vascular endothelial growth factor and the angiopoietins 1 and 2) in atherosclerotic vascular disease and diabetes mellitus
Authors: Jaumdally R. J. , Goon P. K. Y. , Varma C. , Blann A. D. , Lip G. Y. H.
Published: July 2009

Abstract.  Jaumdally RJ, Goon PKY, Varma C, Blann AD, Lip GYH (City Hospital, Birmingham, United Kingdom). Effects of atorvastatin on circulating CD34+/CD133+/CD45− progenitor cells and indices of angiogenesis (vascular endothelial growth factor and the angiopoietins 1 and 2) in atherosclerotic vascular disease and diabetes mellitus. J Intern Med 2010; 267: 385–393.

Background.  Cardiovascular disease (CVD) remains a major cause of morbidity and mortality, especially in the presence of diabetes, possibly because of endothelial damage. Increased circulating progenitor cells (CPCs) and increased plasma markers of angiogenesis [vascular endothelial growth factor (VEGF) and the angiopoietins (Ang‐1 and ‐2)] may be evidence of this damage. Treatment with hydroxy‐methyl‐glutaryl (HMG‐CoA) reductase inhibitors (‘statins’) improves outcomes in patients with vascular disease, including diabetic patients. We hypothesized that 80 mg per day atorvastatin influences CPC counts of VEGF and the angiopoietins in patients with atherosclerotic CVD with or without diabetes mellitus.

Methods.  Cardiovascular disease patients with diabetes mellitus (Group A, n = 14) and nondiabetic patients with CVD only (Group B, n = 10) took atorvastatin 80 mg per day for a period of 8–10 weeks. CPCs (CD34+/CD133+/CD45−) were defined by flow cytometry, plasma levels VEGF and Ang‐1 and Ang‐2 by ELISA).

Results.  Circulating progenitor cell counts increased (P < 0.001) in Group A compared with a nonsignificant change in Group B (P = 0.37). VEGF levels fell significantly in Group A (P = 0.04) but no significant change was seen in Group B (P = 0.16). Whilst Ang‐1 remained unchanged (P = 0.41), Ang‐2 levels increased markedly in both groups (P < 0.05). These effects were independent of LDL and total cholesterol changes but were associated with HDL changes

Conclusion.  High‐dose atorvastatin increased circulating CPCs, reduced VEGF and increased Ang‐2 in patients with diabetes and CVD, providing another possible pathophysiological mechanism for the beneficial effects of statins in CVD.
Two methods of random seed generation to avoid over‐segmentation with stochastic watershed: application to nuclear fuel micrographs
Authors: TOLOSA S. CATIVA , BLACHER S. , DENIS A. , MARAJOFSKY A. , PIRARD J.‐P. , GOMMES C.J.
Published: July 2009

A stochastic version of the watershed algorithm is obtained by choosing randomly in the image the seeds from which the watershed regions are grown. The output of the procedure is a probability density function corresponding to the probability that each pixel belongs to a boundary. In the present paper, two stochastic seed‐generation processes are explored to avoid over‐segmentation. The first is a non‐uniform Poisson process, the density of which is optimized on the basis of opening granulometry. The second process positions the seeds randomly within disks centred on the maxima of a distance map. The two methods are applied to characterize the grain structure of nuclear fuel pellets. Estimators are proposed for the total edge length and grain number per unit area, LA and NA, which take advantage of the probabilistic nature of the probability density function and do not require segmentation.
Assessment scale of the oral motor performance of children and adolescents with neurological damages
Authors: DE OLIVEIRA LIRA ORTEGA A. , CIAMPONI A. L. , MENDES F. M. , SANTOS M. T. B. R.
Published: July 2009

Summary  Among the conditions that classify individuals as special needs patients are those resulting from neurological sequelae, particularly cerebral palsy (CP), which is a disorder of high prevalence. Innumerable alterations can be found in individuals with CP but the inability to control striated muscles, due to damages suffered by the central nervous system, should be emphasized. Changes in tonus, speed and strength of oral muscles, reduction of mandibular mobility amplitude and difficulty to passively seal the lips are characteristics observed in such individuals. Categorization of the individual’s mastication pattern is important in order to establish diagnosis and treatment protocols and prognosis. The aim of this study was to develop an Oral Motor Assessment Scale (OMAS) and evaluate its performance in terms of construct validity and reliability in a cohort of 53 children and individuals with CP. Two dentists examined the same patients on two different occasions. Good interexaminer (kappa > 0·85) and intra‐examiner (kappa > 0·90) agreement was obtained for the majority of the OMAS items. This study shows that the OMAS is an accurate and valid method of assessment of oral motor skills in children and adolescents with neurological damages.
Resilience: resistance factor for depressive symptom
Authors: SMITH P. R.
Published: July 2009

Accessible summary

Resilience is the ability of an individual or group to carry on and solve problems so that survival of hard times is more likely. Resilience protects individuals from depression and includes behaviours that can be taught to persons who are vulnerable to hardships including physical illness, psychosocial isolation and aloneness, and mental illness.

Older adults who rated their overall health as relatively good were also more willing to talk with health providers about depressive symptoms if it was affecting their social activities, making them feel useless to others, or affecting how well they could think or concentrate.

New research needs to occur to learn more about how to build resilience in older adults with symptoms of depression in hopes of encouraging them to talk about depressive symptoms with the health provider. The goal is to prevent symptoms from progressing to a diagnosable disorder.

The more resilience a person demonstrates, the more likely that person is to talk with health professionals about depressive symptoms and seek care to relieve those symptoms. New research is also needed to learn which factors other than resilience and depressive symptoms have an influence on how willing older African Americans are to seek mental health care for those symptoms.

The purpose was to explore influence of resilience on the willingness of African Americans aged 65 and over to seek mental health care for depressive symptoms. Specifically, the study examined relationships between personal resilience and willingness of undiagnosed, community dwelling older adults to seek mental health care for depressive symptoms. A cross‐sectional, correlational, causal modelling design was used to study older African Americans (N= 158; 121 women and 37 men) recruited from churches, retirement organizations and senior nutrition centres. Participants completed study instruments to measure depressive symptoms, resilience, willingness to seek mental health care, and general demographics information. Descriptive statistics and multiple regression analyses were preformed. Depressive symptoms and resilience accounted for 15.4% of the willingness to seek mental health care variance; extraction of resilience lowered variance to 0.9%. A direct, predictive relationship between resilience and willingness to seek mental health care was documented. Understanding resilience and willingness to seek mental health care supports future research for interventions that bolster resilience in older adults. Identifying the influence of resilience on such willingness may provide direction for developing interventions for older African Americans and may be applicable to vulnerable, marginalized and minority older adults worldwide.
Special observations in forensic psychiatric practice: gender issues of the watchers and the watched
Authors: MASON T. , MASON‐WHITEHEAD E. , THOMAS M.
Published: July 2009

Accessible summary

Special observations in mental health nursing involve staff watching patients who may be at risk.

These observations may need to take place in close proximity to the patients.

The closeness of the proximity may cause embarrassment for both the nurses and the patient.

A risk assessment should address these issues.

Special observations in psychiatric practice may create tensions for both the patient under surveillance and the staff undertaking the procedure. This study reports on special observations undertaken in forensic settings focusing specifically on the gender‐sensitive issues. The aim of the study was to investigate the specific gender issues relating to special observations in relation to those under the procedure and those engaged in observing. Three medium secure units in the UK formed the sampling frame, and the population studied was eight female and seven male clinical Registered nurses. Semi‐structured interviews were conducted, audio‐tape‐recorded and transcribed for analysis. The analysis involved a Grounded Theory approach to explicate categories and formulate two overarching themes: (1) the psychosocial fusion; and (2) the private as spectacle. There are implications for practice in relation to policy formulation and the implementation of special observations following risk assessment and individual skill identification. It is concluded that gender issues are extremely important for all concerned in this intrusive practice.
Pharaonic necrostratigraphy: a review of geological and archaeological studies in the Theban Necropolis, Luxor, West Bank, Egypt
Authors: Aubry Marie‐Pierre , Berggren William A. , Dupuis Christian , Ghaly Holeil , Ward David , King Chris , Knox Robert W. O'B. , Ouda Khaled , Youssef Moustafa , Galal Wael Fathi
Published: July 2009

We present a review of archaeological and geological studies on the West Bank as a basis for discussing the geological setting of the tombs and geologically related problems with a view to providing archaeologists with a framework in which to conduct their investigations on the restoration, preservation and management of the antique monuments. Whereas the geology of the Upper Nile Valley appears to be deceptively simple, the lithological succession is vertically variable, and we have recognized and defined several new lithological units within the upper Esna Shale Formation. We have been able to delineate lithological (shale/limestone) contacts in several tombs and observed that the main chambers in some were excavated below the Esna Shale in the Tarawan Chalk Formation. We have been able to document changing dip in the strata (warping) in several tombs, and to delineate two major orientations of fractures in the field. Investigations behind the Temple of Hatshepsut, in the Valley of the Kings and around Deir El Medina have revealed four broad regional structures. We confirm that the hills located near the Nile Valley, such as Sheik Abdel Qurna, do not belong to the tabular structure of the Theban Mountain, but are discrete displaced blocks including the Thebes Limestone, as supported by Google Earth photographs.
Global hydrocarbon seep‐carbonate precipitation correlates with deep‐water temperatures and eustatic sea‐level fluctuations since the Late Jurassic
Authors: Kiel Steffen
Published: July 2009

The anaerobic oxidation of methane (AOM) in marine sediments, most obviously at cold seeps, is a major sink for this important greenhouse gas and is associated with the precipitation of carbonates. The geological record of seep carbonates provides insights into the long‐term dynamics of this process. Since the Late Jurassic, rates of seep‐carbonate precipitation have been high during times of low sea levels and cold deep‐water temperatures, and vice versa. One possibility is that sea‐level fall decreases the thickness of the methane hydrate stability zone in the sediment so that gas hydrates decompose in deeper sediments, thereby increasing seepage and carbonate precipitation. Alternatively, low deep‐water temperature facilitates gas hydrate formation on continental slopes and may thereby increase methane availability for AOM‐performing consortia and associated carbonate precipitation. These correlations and their potential causes may be of interest for the modelling of global carbon budgets and of past and future climates.
Post‐rift volcanism and high heat‐flow at the ocean‐continent transition of the eastern Gulf of Aden
Authors: Lucazeau Francis , Leroy Sylvie , Autin Julia , Bonneville Alain , Goutorbe Bruno , Watremez Louise , D’Acremont Elia , Düsünur Doga , Rolandone Frédérique , Huchon Philippe , Bellahsen Nicolas , Tuchais Patrick
Published: July 2009

A high heat‐flow (∼900 mW m−2) has been observed over a volcanic structure at the Ocean‐Continent Transition in the Eastern Gulf of Aden (Oman margin). The anomaly is superposed to a progressive increase of heat‐flow across the margin and can be interpreted either by (1) heat refraction, (2) fluid discharge or (3) cooling magma. The two first explanations cannot be ruled out definitely by modelling analysis, but require unlikely thermal conductivity or permeability values. The third one implies that the latest activity of the volcano was about 100 000 years old and therefore continued c. 18 Ma after the break‐up of Africa and Arabia. This potential mechanism is consistent with other lines of evidence of post‐rifting activity in the Gulf of Aden and could invalidate the conventional assumption that rifted‐margins become passive after the break‐up of continents.
Southern African topography and erosion history: plumes or plate tectonics?
Authors: Moore Andy , Blenkinsop Tom , Cotterill Fenton (Woody)
Published: July 2009

The physiography of southern Africa comprises a narrow coastal plain, separated from an inland plateau by a horseshoe‐shaped escarpment. The interior of the inland plateau is a sedimentary basin. The drainage network of southern Africa is characterized by three river divides, broadly parallel to the coastline. These features contrast strongly with the broad dome and radial drainage patterns predicted by models which ascribe the physiography of southern Africa to uplift over a deep mantle plume. The drainage divides are interpreted as axes of epeirogenic uplift. The ages of these axes, which young from the margin to the interior, correlate closely with major reorganizations of spreading regimes in the oceanic ridges surrounding southern Africa, suggesting an origin from stresses related to plate motion. Successive epeirogenic uplifts of southern Africa on the axes, forming the major river divides, initiated cyclic episodes of denudation, which are coeval with erosion surfaces recognized elsewhere across Africa.
Copy number variations in three children with sudden infant death
Authors: Toruner GA , Kurvathi R , Sugalski R , Shulman L , Twersky S , Pearson PG , Tozzi R , Schwalb MN , Wallerstein R
Published: July 2009

Sudden death of an infant is a devastating event that needs an explanation. When an explanation cannot be found, the case is labeled as sudden infant death syndrome or unclassified sudden infant death. The influence of genetic factors has been recognized for sudden infant death, but copy number variations (CNVs) as potential risk factors have not been evaluated yet. Twenty‐seven families were enrolled in this study. The tissue specimens from deceased children were obtained and array‐based comparative genomic hybridization (array‐CGH) experiments were performed on the genomic DNA isolated from these specimens using Agilent Technologies Custom 4 × 44K arrays. Quantitative polymerase chain reaction experiments were performed to confirm the overlapping duplication and deletion region in two different cases. A de novo CNV is detected in 3 of 27 cases (11%). In case 1, an ∼3‐Mb (chr 8: 143,211,215‐qter) duplication on 8q24.3‐qter and a 4.4‐Mb deletion on the 22q13.3‐qter (chr 22: 45,047,068‐qter) were detected. Subtelomeric chromosome analysis of the father and the surviving sibling of case 1 showed a balanced reciprocal translocation, 46,XY,t(8;22)(q24.3;q13.3). A 240‐kb (chr 6: 26,139,810‐26,380,787) duplication and a 1.9‐Mb deletion (chr 6: 26,085,971‐27,966,150) at chromosome 6p22 were found in cases 2 and 3, respectively. Array‐CGH and conventional cytogenetic studies did not reveal the observed CNVs in the parents and the siblings of cases 2 and 3. The detected CNVs in cases 2 and 3 encompassed several genes including the major histone cluster genes. Array‐CGH analysis may be beneficial during the investigations after sudden infant death.
Molecular analysis of the GNPTAB and GNPTG genes in 13 patients with mucolipidosis type II or type III – identification of eight novel mutations
Authors: Encarnação M , Lacerda L , Costa R , Prata MJ , Coutinho MF , Ribeiro H , Lopes L , Pineda M , Ignatius J , Galvez H , Mustonen A , Vieira P , Lima MR , Alves S
Published: July 2009

Mucolipidosis II (ML II) and mucolipidosis III (ML III) are diseases in which the activity of the uridine diphosphate (UDP)‐N‐acetylglucosamine:lysosomal enzyme N‐acetylglucosamine‐1‐phosphotransferase (GlcNAc‐phosphotransferase) is absent or reduced, respectively. In the absence of mannose phosphorylation, trafficking of lysosomal hydrolases to the lysosome is impaired. In these diseases, mistargeted lysosomal hydrolases are secreted into the blood, resulting in lysosomal deficiency of many hydrolases and a storage‐disease phenotype. GlcNAc‐phosphotransferase is a multimeric transmembrane enzyme composed of three subunits (α, β and γ) encoded by two genes –GNPTAB and GNPTG. Defects in GNPTAB result in ML II and III whereas mutations in GNPTG were only found in ML III patients. We have performed a molecular analysis of the GNPTAB and GNPTG genes in 13 mucolipidosis II and III patients (10 Portuguese, one Finnish, one Spanish of Arab origin and one Indian). Mutations were identified by the study of both cDNA and gDNA. The GNPTAB and GNPTG mRNA expressions were determined by quantitative reverse transcriptase polymerase chain reaction (qRT‐PCR). The study led to the identification of 11 different mutations. Eight of these mutations are novel, six in the GNPTAB gene [c.121delG (V41FfsX42), c.440delC (A147AfsX5), c.2249_50insA (N750KfsX8), c.242G>T (W81L), c.1208T>C (I403T) and c.1999G>T (p.E667X)] and two in the GNPTG gene [c.610‐1G>T and c.639delT (F213LfsX7)]. With regard to the mRNA expression studies, the values obtained by qRT‐PCR indicate the possible existence of feedback regulation mechanisms between α/β and the γ subunits.
A child cohort study from southern Italy enlarges the genetic spectrum of hypertrophic cardiomyopathy
Authors: Frisso G , Limongelli G , Pacileo G , Del Giudice A , Forgione L , Calabrò P , Iacomino M , Detta N , Di Fonzo LM , Maddaloni V , Calabrò R , Salvatore F
Published: July 2009

Hypertrophic cardiomyopathy (HCM) is the most frequent genetic cardiovascular disorder worldwide. It is the leading cause of sudden cardiac‐related death in young people and a major cause of cardiac failure and death in elderly people. However, HCM frequently goes undiagnosed until the appearance of overt signs and symptoms, thereby delaying prophylactic and therapeutic measures. We screened patients for sarcomeric genes associated with HCM to obtain information that could be useful for an early diagnosis and so limit the severe consequences of silent HCM. We recruited 39 families with HCM from southern Italy and found mutations in 41% of families (12 with familial HCM and 4 with sporadic HCM). The remaining 23 families (59%) were negative for myofilament gene mutations. Of the 12 mutations identified, 8 were novel. Screening of the other family members available revealed that 27 had mutations; 11 of these individuals had no signs or symptoms suggestive of HCM. This study, besides characterizing the spectrum of mutations in another childhood population, and revealing an even greater genetic heterogeneity than formerly recognized, may increase genotype‐phenotype correlations, and thus may help to identify asymptomatic candidates for early preventive or therapeutic measures.
Review of the Lynch syndrome: history, molecular genetics, screening, differential diagnosis, and medicolegal ramifications
Authors: Lynch HT , Lynch PM , Lanspa SJ , Snyder CL , Lynch JF , Boland CR
Published: July 2009

More than one million patients will manifest colorectal cancer (CRC) this year of which, conservatively, approximately 3% (∼30,700 cases) will have Lynch syndrome (LS), the most common hereditary CRC predisposing syndrome. Each case belongs to a family with clinical needs that require genetic counseling, DNA testing for mismatch repair genes (most frequently MLH1 or MSH2) and screening for CRC. Colonoscopy is mandated, given CRC's proximal occurrence (70–80% proximal to the splenic flexure). Due to its early age of onset (average 45 years of age), colonoscopy needs to start by age 25, and because of its accelerated carcinogenesis, it should be repeated every 1 to 2 years through age 40 and then annually thereafter. Should CRC occur, subtotal colectomy may be necessary, given the marked frequency of synchronous and metachronous CRC. Because 40–60% of female patients will manifest endometrial cancer, tailored management is essential. Additional extracolonic cancers include ovary, stomach, small bowel, pancreas, hepatobiliary tract, upper uroepithelial tract, brain (Turcot variant) and sebaceous adenomas/carcinomas (Muir‐Torre variant). LS explains only 10–25% of familial CRC.
Dynactin mutations and promises for neurodegenerative pathology
Authors: Stein RA
Published: July 2009

DCTN1 mutations in Perry syndrome

Farrer et al. (2009)

Nature Genetics 41(2):163–165
A new TBX gene linked to human disease
Authors: Stein RA
Published: July 2009

TBX15 mutations cause craniofacial dysmorphism, hypoplasia of scapula and pelvis, and short stature in Cousin syndrome

Lausch et al. (2009)

American Journal of Human Genetics 83(5): 649–655
New tools to monitor the impact of viral infection on the alloreactive T‐cell repertoire
Authors: D'Orsogna L. J. , Amir A. L. , Zoet Y. M. , Van Der Meer‐Prins P. M. W. , Van Der Slik A. R. , Kester M. G. D. , Heemskerk M. H. M. , Doxiadis I. I. N. , Roelen D. L. , Claas F. H. J.
Published: July 2009

Accumulating evidence suggests that alloreactive memory T‐cells may be generated as a result of viral infection. So far, a suitable tool to define the individual human leukocyte antigen (HLA) cross‐reactivity of virus‐specific memory T‐cells is not available. We therefore aimed to develop a novel system for the detection of cross‐reactive alloresponses using single HLA antigen expressing cell lines (SALs) as stimulator. Herein, we generated Epstein‐Barr Virus (EBV) EBNA3A specific CD8 memory T‐cell clones (HLA‐B*0801/FLRGRAYGL peptide restricted) and assayed for alloreactivity against a panel of SALs using interferon‐γ Elispot as readout. Generation of the T‐cell clones was performed by single cell sorting based on staining with viral peptide/major histocompatibility complex‐specific tetramer. Monoclonality of the T‐cell clones was confirmed by T‐cell receptor (TCR) polymerase chain reaction analysis. First, we confirmed the previously described alloreactivity of the EBV EBNA3A‐specific T‐cell clones against SAL‐expressing HLA‐B*4402. Further screening against the entire panel of SALs also showed additional cross‐reactivity against SAL‐expressing HLA‐B*5501. Functionality of the cross‐reactive T‐cell clones was confirmed by chromium release assay using phytohemagglutinin blasts as targets. SALs are an effective tool to detect cross‐reactivity of viral‐specific CD8 memory T‐cell clones against individual class I HLA molecules. This technique may have important implications for donor selection and monitoring of transplant recipients.
A novel HLA‐B*44 allele, B*4466, discovered in a potential donor for a hematopoietic stem cell transplant
Authors: Redman H. , Marcus N. , Marlowe M. , Endres R. O.
Published: July 2009

This report describes the discovery and characterization of the human leukocyte antigen‐B*4466 allele.
A novel HLA‐DRB1 allele, DRB1*1219, was identified by sequence‐based typing in a Chinese leukaemia family
Authors: Nie X.‐M. , Fang Y.‐H. , Zhang Y. , He W.‐D. , Zhu C.‐F.
Published: July 2009

A novel human leukocyte antigen DRB1 allele, DRB1*1219, has been identified in a Chinese leukaemia patient and his family by polymerase chain reaction sequence‐based typing, which has one nucleotide change at position 341 (C→T) in exon 2 from the closest matching allele DRB1*120201, resulting in an amino acid substitution from Ala→Val at codon 85.
Actinomyces naeslundii genospecies 1 and 2 express different binding specificities to N‐acetyl‐β‐D‐galactosamine, whereas Actinomyces odontolyticus expresses a different binding specificity in colonizing the human mouth
Authors: Hallberg K. , Hammarström K.‐J. , Falsen E. , Dahlén G. , Gibbons R. J. , Hay D. I. , Strömberg N.
Published: July 2009

A total of 102 strains of Actinomyces were isolated from teeth, buccal mucosa and tongue in eight individuals. The isolates were characterized by multivariate statistical analyses of phenotypic characteristics, serotyping and binding to β‐linked galactosamine (N‐acetyl‐β‐D‐galactosamine) and acidic proline‐rich protein structures. Based on these characteristics, isolates were classified into three major groups: (i) Isolates of Actinomyces naeslundii genospecies 2 were the dominant species on teeth and buccal mucosa and bound commonly to Nacetyl‐β‐D‐galactosamine (63 of 63 isolates) and acidic proline‐rich proteins (63 of 63 isolates), regardless of tissue origin. They all exhibited a N‐acetyl‐β‐D‐galactosamine binding specificity signified by N‐acetyl‐β‐D‐galactosamine‐inhibitable coaggregation with the streptococcal strains LVG1. GVE1, 24892 and MPB1; (ii) Isolates of A. naeslundii genospecies 1 were prevalent on teeth in certain individuals and bound commonly to N‐acetyl‐β‐D‐galactosamine (20 of 20 isolates), but less commonly to acidic proline‐rich proteins (5 of 20 isolates). They all possessed another N‐acetyl‐β‐D‐galactosamine specificity, i.e. N‐acetyl‐β‐D‐galactosamine‐in‐hibitable coaggregation with the same streptococcal strains except for strain MPB1; (iii) Isolates of Actinomyces odontolyticus, the dominant species on the tongue (17 of 19 isolates), bound commonly to unknown structures on streptococci (17 of 19 isolates) but rarely to N‐acetyl‐β‐D‐galactosamine (2 of 19 isolates) or acidic proline‐rich proteins (3 of 19 isolates). In conclusion, A. naeslundii genospecies 1 and 2 exhibit different patterns of N‐acetyl‐β‐D‐galactosamine and acidic proline‐rich protein specificities to colonize dental and buccal mucosa surfaces, whereas A. odontolyticus utilizes another specificity to colonize the tongue.
Actinomyces serovar WVA963 coaggregation‐defective mutant strain PK2407 secretes lactosesensitive adhesin that binds to coaggregation partner Streptococcus oralis 34
Authors: Klier C. M. , Roble A. G. , Kolenbrander P. E.
Published: July 2009

Actinomyces serovar WVA963 strain PK1259 mediates intergeneric coaggregation with several oral streptococci. These lactose‐inhibitable coaggregations appear to involve a 95‐kDa putative actinomyces adhesin in complex with type 2 fimbriae. A coaggregation‐defective strain PK2407 lacking type 2 fimbriae synthesizes the putative adhesin but appears unable to present it properly on its surface. Antiserum was raised against surface sonicates of PK2407 and was absorbed with a different coaggregation‐defective mutant PK3092 that synthesizes type 2 fimbriae but no adhesin. This absorbed antiserum specifically blocked lactose‐inhibitable coaggregation of wild‐type strain PK1259 and Streptococcus oralis 34 and identified a 95‐kDa protein in ammonium sulfate precipitates of culture supernatant of the coaggregation‐defective mutant PK2407. The 95‐kDa secreted protein was bound to the streptococcal partner cells and to lactose‐agarose affinity beads and was released by lactose from both the affinity beads and partner, indicating that the secreted and precipitated protein is biochemically active and may mediate coaggregation with streptococci.
Epithelial cell invasion by Actinobacillus actinomycetemcomitans strains from restriction fragment‐length polymorphism groups associated with juvenile periodontitis or carrier status
Authors: Lépine G. , Caudry S. , DiRienzo J. M. , Ellen R. P.
Published: July 2009

The epithelial cell invasiveness of Actinobacillus actinomycetemcomitans strains of different restriction fragment‐length polymorphism (RFLP) groups associated with disease conversion and asymptomatic carrier status in localized juvenile periodontitis was examined. Twenty clinical isolates were studied for their ability to invade KB monolayers, using the quantitative gentamicin killing assay. Five isolates were found to be invasive; five were not invasive; and the other 10 did not invade better than an invasion negative control Haemophilus aphrophilus strain ATCC 19415. Using probe‐specific DNA fingerprinting, 11 strains were assigned to RFLP group II (disease‐associated); 4 to RFLP type XIII (carrier status‐associated); and the others to groups III, IV, V and VII. Eight isolates, all RFLP group II, were leukotoxin producers as determined by PCR amplification of the Ikt promoter region. No correlation was found between invasiveness and RFLP group. Leukotoxin production was more associated with noninvasive than invasive strains.
Antigen‐specific T‐cell receptor Vβ expression in Porphyromonas gingivalis–specific T‐cell lines
Authors: Gemmell E. , Grieco D. A. , Cullinan M. P. , Westerman B. , Seymour G. J.
Published: July 2009

FACS analysis was used to determine the expression of 15 T‐cell receptor Vβ families on CD4 and CD8 cells in Porphyromonas gingivalis—specific T‐cell lines established from eight P. gingivalis—positive. adult periodontitis and seven P. gingivalis—positive healthy or gingivitis subjects. All 15 T‐cell receptor Vβ families were expressed by the T‐cell lines, although a significantly higher proportion of the CD4 cells expressed the 5.2‐3 Vβ region compared with the other 14 families, including the 5.3 region, suggesting that it is the 5.2 family which is overexpressed. This was also true for the CD8 cells, with the exception of the 3.1 region in adult periodontitis T‐cell lines and the 3.1, 13.1/13.3 and 21.3 regions in healthy or gingivitis lines. Between the two clinical groups, a significantly lower percentage of 13.1/13.3‐positive CD8 cells was noted in the adult periodontitis lines compared with the healthy or gingivitis lines. There was a significant reduction in DNA synthesis by the lines in the presence of P. gingivalis outer membrane antigens and fixed irradiated lymphoblastoid cell lines compared with cultures containing untreated irradiated lymphoblastoid cell lines and in cultures containing anti‐class II major histocompatibility complex antibody in comparison with all other cultures. The results of this study have shown that P. gingivalis preferentially induces the T‐cell receptor Vβ5.2 family on CD4 and CD8 cells in P. gingivalis‐specific T‐cell lines and that activation of T cells by P. gingivalis outer membrane antigens may be by antigen‐specific rather than superantigen activity.
Pathogenicity of facultative and obligate anaerobic bacteria in monoculture and combined with either Prevotella intermedia or Prevotella nigrescens
Authors: Siqueira J. F. , Magalhães F. A. C. , Lima K. C. , de Uzeda M.
Published: July 2009

The pathogenicity of obligate and facultative anaerobic bacteria commonly found in endodontic infections was tested using a mouse model. The capacity of inducing abscesses was evaluated seven days after subcutaneous injection of the bacteria in pure culture and in combinations with either Prevotella intermedia or Prevotella nigrescens. Nine of the fifteen bacterial strains tested were pathogenic in pure culture. No statistically significant differences were detected between these strains in pure culture and in mixtures with either P. intermedia or P. nigrescens. Synergism beetween the bacterial strains was only apparent when associating Porphyromonas endodontalis with P. intermedia or P. nigrescens. Histopathological examination of tissue sections from induced abscesses revealed an acute inflammatory reaction, dominated by polymorphonuclear leukocytes. Sections from the control group using sterile medium showed no evidence of inflammatory reaction.
Virulence of a polymicrobic complex, Treponema denticola and Porphyromonas gingivalis, in a murine model
Authors: Kesavalu L. , Holt S. C. , Ebersole J. L.
Published: July 2009

The effect of a polymierobic infection employing Treponema denticola and Porphyromonas gingivalis in the murine lesion model was used to determine the synergistic virulence of these two periodontopathic bacteria. At high doses of P. gingivalis W50, addition of T. denticola in the infection mixture had no effect on the formation and size of the spreading lesion caused by this microorganism. However, at low P. gingivalis challenge doses, T. denticola significantly enhanced the virulence of P. gingivalis compared with monoinfection of this microorganism. A potential role of the trypsin‐like protease enzyme activity of P. gingivalis in this synergistic virulence was tested using P. gingivalis mutants deficient (i.e., BEI) or devoid (i.e., NG4B19) of this protease activity. These findings demonstrated that T. denticola—P. gingivalis complexes exhibit enhanced virulence in this model and that even using a polymicrobic challenge infection, the trypsin‐like protease activity was important to P. gingivalis virulence expression.
Combined inhibitory effect of bovine immune whey and peroxidase‐generated hypothiocyanite against glucose uptake by Streptococcus mutans
Authors: Loimaranta V. , Tenovuo J. , Korhonen H.
Published: July 2009

Immune whey product was obtained from Streptococcus mutans‐ and Streptococcus sobrinus‐immunized cows. Hypothiocyanite (HOSCN/OSCN‐) was generated in VMG‐buffer, pH 5.5 or 6.5, by bovine milk lactoperoxidase, KSCN and hydrogen peroxide. The glucose incorporation by late‐log cells of S. mutans 10449, serotype c, was followed by measuring the uptake of 14C‐glucose at 37°C. At pH 5.5 and 6.5 both immune whey product and HOSCN/OSCTST‐ dosedependently inhibited glucose uptake. The inhibition by their combination was additive if bacterial cells were treated with HOSCN/OSCN‐ before exposed to immune whey product. In contrast to immune whey product, the control product from sham‐immunized cows increased the glucose uptake even when added simultaneously with HOSCN/OSCN‐. However, when bacterial cells were pretreated with HOSCN/OSCN‐ an enhanced inhibitory effect was observed also with control product. The results indicate that colostral proteins from S. mutans‐ or S. sobrinus‐immunized cows inhibit glucose uptake and that the effect is enhanced by pretreatment with lactoperoxidase‐generated HOSCN/OSCN‐.
Purification and properties of a bacteriocin of Staphylococcus epidermidis isolated from dental plaque
Authors: Nakamura T. , Hirai K. , Shibata Y. , Fujimura S.
Published: July 2009

An extracellular bacteriocin of Staphylococcus epidermidis isolated from dental plaque was purified and characterized. Its molecular mass was 3500 Da and pI was 10.5. This bacteriocin inhibited the growth of Staphylococcus aureus, Streptococcus salivarius, and Streptococcus mitis, but Streptococcus mutans, Streptococcus sanguis and other oral indigenous bacterial species examined were not inhibited. The mode of inhibition was found to be bacteriostatic.
Pollination ecology of Isoglossa woodii, a long‐lived, synchronously monocarpic herb from coastal forests in South Africa
Authors: Griffiths M. E. , Tsvuura Z. , Franklin D. C. , Lawes M. J.
Published: July 2009

Synchronous monocarpy in long‐lived plants is often associated with pollination by wind, in part because infrequent mass flowering may satiate pollinators. Selfing in synchronous monocarps may provide reproductive assurance but conflict with the benefits of outcrossing, a key evolutionary driver of synchrony. We predicted that animal‐pollinated species with synchronous flowering would have unspecialised flowers and attract abundant generalised pollinators, but predictions for selfing and outcrossing frequencies were not obvious. We examined the pollination biology of Isoglossa woodii (Acanthaceae), an insect‐pollinated, monocarpic herb that flowers synchronously at 4–7‐year intervals. The most frequent visitor to I. woodii flowers was the African honeybee, Apis mellifera adansonii. Hand‐pollination failed to enhance seed production, indicating that the pollinators were not saturated. No seed was set in the absence of pollinators. Seed set was similar among selfed and outcrossed flowers, demonstrating a geitonogamous mixed‐mating strategy with no direct evidence of preferential outcrossing. Flowers contained four ovules, but most fruits only developed one seed, raising the possibility that preferential outcrossing occurs by post‐pollination processes. We argue that a number of the theoretical concerns about geitonogamous selfing as a form of reproductive assurance do not apply to a long‐lived synchronous monocarp such as I. woodii.
Genetic screening of the canine zinc finger protein multitype 2 (cZFPM2) gene in dogs with tetralogy of Fallot (TOF)
Authors: Lee J.‐S. , Hyun C.
Published: July 2009

A recent genetic study in humans where the ZFPM2 gene was screened for mutations revealed a heterozygous mutation that was found to contribute to several sporadic cases of tetralogy of Fallot (TOF). We hypothesized that this would also hold true for a study group of dogs with TOF. We isolated the full‐length cDNA of the canine ZFPM2 and aligned the deduced amino acid sequence against sequences from other species. Our analysis indicated that the canine ZFPM2 was phylogenetically much closer to the human ZFPM2 compared with the mouse or rat sequences. Further gene expression analysis also failed to identify differential gene expression between affected and unaffected dogs. We screened the cZFPM2 for mutations in a group of dogs with TOF but found no significant base changes in either the splice sites or the coding regions.