bluuebunny/crossref_metadata_2025 huggingface dataset:
Late Development of a Lower Third Molar—A Case Report
Authors: Barnett D. P.
Published: December 2014

A case is reported of the late development of a lower third molar at 15 years 3 months. This extends the range of variation a little further and suggests caution in stating that third molars are unlikely to develop after the fourteenth year.
Directional Forces
Authors: Berman Maurice
Published: December 2014

Cervical traction is being superseded by occipital traction. Headcaps are linked to a face bow, or through cheekwires, direct to the archwire. The direction of this force is controlled and specific and in line with the aims of treatment. Various types are described and the indications for their use discussed.
Simplified Extraoral Radiography
Authors: Moskowitz Elliott M. , Moskowitz Hyman
Published: December 2014

A simple extraoral radiographic technique is presented. This method is both practical and useful for obtaining accurate radiographs which are important in orthodontic and pedodontic diagnosis.
Direct Bonding of Orthodontic Brackets—a Comparative Study of Adhesives
Authors: Reynolds I. R. , von Fraunhofer J. A.
Published: December 2014

Various materials are currently available to orthodontists for use as adhesives in the direct bonding of orthodontic brackets to teeth.

In this comparative study three factors have been examined, namely the tensile bond strength of suitable adhesives in orthodontic bracket—adhesive—human enamel combinations, the effect of water immersion on the bond strength and the effect of the acid etchant on the bond strength. This work should give the practitioner an indication of the clinical merits of some of these materials.
Clinical Evaluation of Direct Bonding
Authors: Cavina R. A.
Published: December 2014

The results of direct bonding of orthodontic brackets to the teeth in 160 cases were investigated. The direct bonding system and its failure rate using different types of bracket was evaluated. Various causes of failure of direct bonding were investigated and discussed; these included the position of the tooth, occlusal factors and the length of treatment.
A Cephalometric Appraisal of a Group of Children with Surgically Repaired Unilateral Cleft Lip and Palate
Authors: Mowbray John B.
Published: December 2014

This study investigated the effect of a standard surgical technique for the repair of unilateral cleft lip and palate by one surgeon. Limitations were set by the numbers available for investigation, however comparison was made between a small group of such treated cases and a group of normal children.

The method of assessment was based on a cephalometric analysis with extrapolation to the integumental profile. A number of different points were proposed for attributes of the soft tissue profile.

The base reference line used was Sella-Nasion, points A and B and the extrapolations to the overlying soft tissue. Facial convexity was proposed as an angle subtended at the tip of the nose by the chin point and soft tissue nasion. Facial height was measured as a ratio between upper and lower facial dimensions. Lip tissue thickness was a direct measurement.

The result of this study supported some findings in other studies. The point of most interest was the small amount of difference between the experimental group and the group used for comparison. Both maxillary and mandibular retrusion was noted and there appeared slight flattening of the soft tissue profile. However, no differences were noted in lip thickness and facial height.
Direct Bonding in Orthodontics: A Comparison of Attachments
Authors: Reynolds I. R. , von Fraunhofer J. A.
Published: December 2014

The tensile bond strengths to human enamel of metallic and non-metallic direct bonding attachments used with their recommended adhesives are reported. The results obtained are compared and contrasted and the findings are discussed in relation to clinical practice.
A Lower Fixed Lingual Tongue Crib and Lip Toning Exercises: Report of an Unusual Case
Authors: Cooke Michael S.
Published: December 2014

A lower fixed ‘tongue crib’ was used diagnostically in a case of bimaxillary protrusion. The anterior open bite and lower incisor spacing resolved under the influence of soft tissue action. Lip exercises were instituted to create a new muscle balance and thus maintain the new incisor positions. The literature is reviewed in relation to tongue cribs, lower incisor position and lip tone. The fundamental interest in the case presented is the support it provides for the ‘balance’ theory of lower incisor position.
The Design of Buccal Canine Retraction Springs for Removable Orthodontic Appliances
Authors: Houston W. J. B. , Waters N. W.
Published: December 2014

The Characteristics of three types of buccal canine retraction springs are investigated. In general, these springs are unduly stiff and so excessive forces can be applied by even small activations. Additionally, they can be unstable vertically. By careful attention to geometry, it is possible to design a spring with acceptable clinical properties.
Factors Influencing the Primary Inclination of Lower Third Molar Crypts
Authors: Tait R. V. , Williams M.
Published: December 2014

A significant correlation is demonstrated in children of ages 10·6 to 11·7 years between the tilt of unerupted lower third molars and deficiency of space in the dental arch. It is also shown that the mesiodistal axis of the lower third molar crypt at an early stage of growth lies closely parallel to the bone surface in which the crypt develops. Some clinical implications are discussed.
A Method of Superimposing Serial Lateral Cephalometric Films for the Purpose of Comparison: A Preliminary Report
Authors: Kerr W. J. S.
Published: December 2014

A method is described for superimposing and comparing serial lateral cephalometric films using de Coster's line, the Adams Blink Comparator and correction for vertical movements of Nasion due to growth. Using the method no significant change (P < 0·05) was recorded in Cranial Base Angle for a group of 85 subjects between 5 and 15 years. It is suggested that the method may remove inaccuracies due to vertical movements of Nasion.
Calculation of the Position of the Axis of Rotation when Single-rooted Teeth are Orthodontically Tipped
Authors: Steyn C. L. , Verwoerd W. S. , van der Merwe E. J. , Fourie O. L.
Published: December 2014

A formula based on certain simplifying assumptions is presented by means of which the axis of rotation of any single-rooted tooth can be calculated using the minimum of data. The only information that is necessary is the length of the root and the distance between the cervix and the point on the crown at which the tipping force is applied. In this case the direction of force application is perpendicular to the long axis of the tooth. A table is provided from which this information can directly be taken.
A Comparison of Xeroradiographs with Conventional Lateral Skull Radiographs
Authors: Erskine R. B.
Published: December 2014

Forty xeroradiographs were compared with forty conventional lateral skull radiographs, using a digitizer.

A double plotting method was used by one observer and the variation between plots was calculated. Xeroradiographs appeared to give better agreement between observations for most, but not all, of the landmarks.
Long-term Occlusal Stability after Labial Segmental Osteotomy
Authors: Shepherd J. P.
Published: December 2014

Changes in the occlusion following labial alveolar osteotomy in 11 patients are described. Alterations in overbite, overjet and inter-canine width which occurred up to 9 years after operation are recorded. Relapse of more than 1 mm was not seen, except in two cases where a complete overbite was not achieved. Relapse in these cases was limited to the first year after operation.
Cephalometric Parameters in Hypopituitary Patients
Authors: Edler R. J.
Published: December 2014

The lateral cephalograms of 20 hypopituitary patients were analysed. The cases were untreated at the time, and covered an age range of 6–15 years. The linear and angular measurements were compared with those of growth study controls, and were tested for significance. The results confirm the facial immaturity of Patients with a deficiency of growth hormone and indicate that, whilst all linear parameters are reduced, maxillary length is less retarded than the others. There were differences amongst the angular comparisons, the gonial angle being particularly increased.
A Loopformer for Archwires
Authors: Davis H. D.
Published: December 2014

A calibrated loop-forming jig is described, which can be used to bend standard sized loops and stops at known intervals along an archwire. A variety of loops may be constructed, using rectangular or round wire.
The Expansion ‘W’ and its Modification in Orthodontic Treatment
Authors: Sandham J. A.
Published: December 2014

A quad helix expansion device is described and modifications shown which increase its range of action.
Spontaneous Changes in the Incisor Relationship following Extraction of Lower First Permanent Molars
Authors: Richardson Andrew
Published: December 2014

The spontaneous changes in overbite, overjet and incisor inclinations during the first year following extraction of both lower first permanent molars were investigated in 43 (19M, 24F) patients whose ages ranged from 8–14 years at the time of extraction. The changes were measured on 90° left lateral cephalometric radiographs taken before extraction and approximately 12 months later.

On average, there was a tendency for the overbite and overjet to increase with associated retroclination of lower and proclination of upper incisors. The range of the changes was relatively large.

When the overbite showed an appreciable increase during the period of observation, pre-existing proclination of upper or lower incisors and an increased overbite or overjet were the most frequent findings. Remarkably, a previously increased overjet seemed to be a better indicator of an overbite that would increase than was the Previous overbite itself. In most cases showing a previously normal overbite or overjet, the overjet after extraction remained stable. Correlation of the overbite and overjet together against the changes in overbite proved disappointing from the prognostic standpoint except that previously incomplete overbites almost invariably increased.
Upper Torque/Intrusion Mechanics in Deep Bite Cases Using the Upper Utility Wire and Directional Headgear
Authors: Cooke Michael S. , Wreakes Glyn
Published: December 2014

The problems of correcting deep bites are outlined and the advantages and usage of the upper utility wire are described with special reference to some case reports. High pull headgear direct to the arch Wire allows an orthopaedic force to be added if required, in addition to opposing the extrusive force vector applied by the torqueing mechanics. Treatment may be commenced with only two molars and four incisors banded and the edgewise system allows the incisor roots to be kept away from palatal and buccal plates during intrusion. This prevents the root resorption described recently when incisors roots have been allowed to contact the cortical plates of bone during movement. Use of Cobalt—Nickel—Chrome* wire and pre-torqued brackets allows the application of a light physiological force acting over a long period and this reduces patient visits. Overbite correction is achieved by true incisor intrusion and not by molar extrusion.
Auto Transplant Replacement of a Geminated Incisor by a Supplemental Incisor
Authors: Taylor G. S.
Published: December 2014

This case demonstrates that surplus tooth material from within a patient's mouth may be transplanted to replace a missing or malformed tooth. The usual precaution of immobilization is necessary and if root development is incomplete at the time of operation, it will proceed as before. Apparent vitality can be restored as evidenced by a positive response to electric pulp stimulation.
Enamel Loss on Bond Removal
Authors: Jones M.
Published: December 2014

A case is reported of loss of enamel when a patient attempted to remove her fixed appliance.
A Functional Approach to Orofacial Orthopaedics
Authors: Fränkel Rolf
Published: December 2014

In general orthopaedics, the clinical relevance of muscular functions has been long recognised. It is suggested that in the development of skeletal deformities a faulty postural performance pattern may play an important causative role. Therefore the primary therapeutic problem in functional orthopaedics is to overcome these functional disorders. From the excellent results achieved by these methods the question arises, are we not obliged to follow the example set by general orthopaedists?

It is the purpose of this article to demonstrate that this can be realised, provided that faulty postural performances are seen in a close functional inter-relationship with spatial disorders in the oro-naso-pharyngeal spaces.
Technique of Rapid Expansion in Patients with Cleft Lip and Palate
Authors: Townend P. I.
Published: December 2014

A new device for rapid expansion of the maxillary arch in cleft palate patients, is described. Its main advantages are that it is designed to prevent uncontrolled relapse while the expansion screw is changed and while a retaining arch is fabricated. The buccal retaining arch leaves the alveolus and cleft accessible for surgery.
Nicknames, Teasing, Harassment and the Salience of Dental Features among School Children
Authors: Shaw W. C. , Meek S. C. , Jones D. S.
Published: December 2014

The aim of the study was to explore the extent to which deviant dental features may expose children to ridicule and embarrassment. In the first part of the study, 531 school children were interviewed about their experience of nicknaming, teasing and harassment and it appeared that for teasing in particular, dental features could provide a significant target for abuse. The findings were also related to a teacher's brief assessment of the child's personality.

In the second part of the investigation, the salience of dental features to children was examined by asking 82 children to respond to a cine film showing 12 children's faces and it appeared that in general, the more deviant the dental arrangement, the more salient will it be. In discussion however, it is considered that many other characteristics of an individual child will influence not only the abuse which he may attract but also the nature of his response.
Hypo-hyperodontia—Report of a Rare Case
Authors: Moore R.
Published: December 2014

This report records a condition of absent maxillary canines but with an erupted supernumerary incisor in the same labial segment.
Retraction of Canines with Axial Control Using Extra-oral Traction
Authors: Davis H. D. , Usiskin L. A.
Published: December 2014

Retraction of canines with control of tooth inclination is described, using the direct application of extra-oral traction. The technique requires a modified facebow to be inserted into buccal tubes on canine bands; no archwires or springs are involved. In the upper arch the facebow is connected to a standard variable pull headgear, while a supported cervical strap is required for the lower canines. Preliminary investigations are outlined and the procedure is illustrated by some clinical cases from a pilot feasibility study.
Holographic Investigation of Bone Response to Small Forces
Authors: Hewitt A. B.
Published: December 2014

The small forces used in orthodontic treatment when applied to a tooth, teeth or dental arches, generate stress which affects bone not only adjacent to the tooth but bone remote from the site of application of force. A technique employing holography has been devised to study quantitatively and qualitatively the observed stress pattern.
Developmental Mechanisms in Normal and Abnormal Palate Formation with Particular Reference to the Aetiology, Pathogenesis and Prevention of Cleft Palate
Authors: Ferguson Mark W. J.
Published: December 2014

Palatal development was studied macroscopically, microscopically and ultrastructurally in foetuses of inbred Wistar rats and Alligator mississippiensis. In the rat, elevation of the palatal shelves from a vertical position lateral to the tongue to a horizontal position above the tongue, occurs very rapidly. This reorientation is postulated to be caused by an intrinsic turgor shelf force generated by the hydration of mesenchymal mucopolysaccharides (predominantly hyaluronic acid). Cleft palate was induced in rat foetuses using 5-fluoro-2-desoxyuridine and was associated with greatly decreased mucopolysaccharide synthesis. The alligator is the only animal which develops in an external egg and which possesses a true mammal-like secondary palate: it is therefore a useful animal model system because longitudinal studies and direct surgical and pharmacological manipulations can be performed. The palatal shelves of alligators grow horizontally above the dorsum of the tongue from their first appearance. This de novo horizontal shelf growth is associated with an increased amount of space in the alligator oronasal cavity due to the small, fatty, alligator tongue. It is postulated that the evolution of the large muscular mammalian tongue constrains the palatal shelves to grow vertically until sufficient space can be created to form the common nasal passage simultaneous with shelf elevation.
Dento-Facial Orthopaedics in the Correction of Class II Malocclusion
Authors: Bass N. M.
Published: December 2014

An orthopaedic appliance system has been developed with the specific therapeutic intention of removing those factors responsible for the initiation or maintenance of the skeletal Class II malocclusion. This is accomplished by means of restraint and redirection of forward maxillary growth and induction of mandibular growth. Concurrently, adverse soft tissue influences are eliminated or ameliorated.

Clinical and experimental evidence gives support to this concept and case histories show the clinical mode of use of the appliance system. An initial 10–12 month orthopaedic phase is followed by a second phase of similar duration, utilizing full Edgewise therapy to perfect the occlusion. The second phase is much reduced in complexity and is generally confined to alignment and final detailing as the essential corrections have been achieved in the orthopaedic phase.

It is considered that this combined approach to Skeletal II treatment is more physiologic than conventional treatment and results in a better harmony of dental and facial features.
Bilateral Transmigration of Mandibular Canines
Authors: Joshi M. R. , Daruwala N. R. , Ahuja H. C.
Published: December 2014

A case is reported in which both mandibular canines have migrated towards each other across the midline.
An Investigation into Factors Influencing the Amount of Orthodontic Treatment Attempted by the Recent Graduates of Two Dental Schools
Authors: Brown I. D. , Stephens C. D. , Usiskin L. A.
Published: December 2014

A questionnaire was sent to Bristol and Guy's Dental Graduates who had been qualified for between 3 and 5 years. This showed that three-quarters of those who were currently in general dental practice had treated six or more orthodontic patients since qualification. A fifth claimed to have treated more than 45. An important factor in determining whether a practitioner carries out orthodontic treatment himself, or refers Patients to a specialist, is the confidence he has in his own ability to adjust and monitor orthodontic appliances. The convenience of alternative orthodontic services would appear to have no influence in such decisions.
Some Thoughts on Undergraduate Orthodontic Training Viewed by a Regional Consultant
Authors: Webb W. G.
Published: December 2014

The emphasis in the undergraduate orthodontic curriculum should be on understanding the principles of removable appliance therapy. The student must be able to design and adjust these appliances and to realise their limitations. The effect of extractions with or without appliance therapy should be stressed. Some theoretical background is needed on the development of normal occlusion and its variations, and on diagnosis and treatment planning but the emphasis should be on the practical aspects of treatment. This means that the practitioner will then be in a position to treat the more simple cases to a consultant prescription. Obviously this knowledge can be expanded on short post-graduate courses for general practitioners and ideally with clinical attachments in a Regional orthodontic department for the most interested.
The Orthodontic Treatment of Malocclusion in Patients with Previous Periodontal Disease
Authors: Williams Stephen , Melsen Birte , Agerbaek Nine , Asboe Vibeke
Published: December 2014

The loss of osseous support resulting from periodontal disease is an aetiological factor in the development of secondary malocclusions. Correction of these malocclusions demands advanced techniques and an understanding of the biological situation present in the adult patient with periodontal disease. Judicious interdisciplinary treatment planning, in particular with respect to the size and direction of the forces applied, can lead to satisfactory results obtained over relatively short periods.
Bilateral Calcified Choroid Plexus: A Case Report
Authors: Brocklebank Laetitia M.
Published: December 2014

This report presents a case of bilateral calcified choroid plexus in a 13 year old girl. The diagnosis and possible pathological causes are discussed.
Isolated middle cerebral artery dissection: a systematic review
Authors: Asaithambi Ganesh , Saravanapavan Pradeepan , Rastogi Vaibhav , Khan Sheema , Bidari Sharatchandra , Khanna Anna Y , Ganti Latha , Qureshi Adnan I , Hedna Vishnumurthy Shushrutha
Published: December 2014

Acute stroke can be missed in the emergency department, particularly in younger patients and in those with more vague symptoms such as headache or dizziness. Cervicocephalic dissections are one group of etiologies for acute stroke in the young. While cervicocephalic dissections are not uncommon in clinical practice, isolated middle cerebral artery dissection (MCAD) has been rarely reported as a cause for stroke. We sought to review the clinical implications and pathophysiology of an isolated MCAD. We searched the medical literature for isolated MCAD in clinical stroke patients using MEDLINE, HighWire, and Google Scholar databases from 1966 to 2013 using the keywords ‘middle cerebral artery dissection,’ ‘intracerebral artery dissection,’ and ‘middle cerebral artery dissection stroke.’ We reviewed cases to learn various characteristics of isolated MCAD. A total of 61 cases (62.3% male, mean age 44.16 ± 19.17 years) were reviewed from 54 publications. Most cases were reported from Asian countries (78.7%). Ischemic strokes were more common than hemorrhagic strokes (68.9%). Digital subtraction angiography was the most common imaging modality used to diagnose isolated MCAD (75.4%). Surgery was the preferred form of therapeutic intervention (39.3%). Males (n = 27/48, p = 0.0008) and those who presented with only ischemic syndromes (n = 22/48, p = 0.0009) had significantly higher rates of favorable outcome. Isolated MCAD is a rare disease that can contribute to the stroke burden of young patients. Further studies are needed to better characterize optimal treatment strategies and define outcomes for this rare condition.
Genomes of the rice pest brown planthopper and its endosymbionts reveal complex complementary contributions for host adaptation
Authors: Xue Jian , Zhou Xin , Zhang Chuan-Xi , Yu Li-Li , Fan Hai-Wei , Wang Zhuo , Xu Hai-Jun , Xi Yu , Zhu Zeng-Rong , Zhou Wen-Wu , Pan Peng-Lu , Li Bao-Ling , Colbourne John K , Noda Hiroaki , Suetsugu Yoshitaka , Kobayashi Tetsuya , Zheng Yuan , Liu Shanlin , Zhang Rui , Liu Yang , Luo Ya-Dan , Fang Dong-Ming , Chen Yan , Zhan Dong-Liang , Lv Xiao-Dan , Cai Yue , Wang Zhao-Bao , Huang Hai-Jian , Cheng Ruo-Lin , Zhang Xue-Chao , Lou Yi-Han , Yu Bing , Zhuo Ji-Chong , Ye Yu-Xuan , Zhang Wen-Qing , Shen Zhi-Cheng , Yang Huan-Ming , Wang Jian , Wang Jun , Bao Yan-Yuan , Cheng Jia-An
Published: December 2014

Background

The brown planthopper, Nilaparvata lugens, the most destructive pest of rice, is a typical monophagous herbivore that feeds exclusively on rice sap, which migrates over long distances. Outbreaks of it have re-occurred approximately every three years in Asia. It has also been used as a model system for ecological studies and for developing effective pest management. To better understand how a monophagous sap-sucking arthropod herbivore has adapted to its exclusive host selection and to provide insights to improve pest control, we analyzed the genomes of the brown planthopper and its two endosymbionts.

Results

We describe the 1.14 gigabase planthopper draft genome and the genomes of two microbial endosymbionts that permit the planthopper to forage exclusively on rice fields. Only 40.8% of the 27,571 identified Nilaparvata protein coding genes have detectable shared homology with the proteomes of the other 14 arthropods included in this study, reflecting large-scale gene losses including in evolutionarily conserved gene families and biochemical pathways. These unique genomic features are functionally associated with the animal’s exclusive plant host selection. Genes missing from the insect in conserved biochemical pathways that are essential for its survival on the nutritionally imbalanced sap diet are present in the genomes of its microbial endosymbionts, which have evolved to complement the mutualistic nutritional needs of the host.

Conclusions

Our study reveals a series of complex adaptations of the brown planthopper involving a variety of biological processes, that result in its highly destructive impact on the exclusive host rice. All these findings highlight potential directions for effective pest control of the planthopper.
Determining the quality and complexity of next-generation sequencing data without a reference genome
Authors: Anvar Seyed Yahya , Khachatryan Lusine , Vermaat Martijn , van Galen Michiel , Pulyakhina Irina , Ariyurek Yavuz , Kraaijeveld Ken , den Dunnen Johan T , de Knijff Peter , ’t Hoen Peter AC , Laros Jeroen FJ
Published: December 2014

We describe an open-source kPAL package that facilitates an alignment-free assessment of the quality and comparability of sequencing datasets by analyzing k-mer frequencies. We show that kPAL can detect technical artefacts such as high duplication rates, library chimeras, contamination and differences in library preparation protocols. kPAL also successfully captures the complexity and diversity of microbiomes and provides a powerful means to study changes in microbial communities. Together, these features make kPAL an attractive and broadly applicable tool to determine the quality and comparability of sequence libraries even in the absence of a reference sequence. kPAL is freely available at https://github.com/LUMC/kPAL.
A multi-gene signature predicts outcome in patients with pancreatic ductal adenocarcinoma
Authors: Haider Syed , Wang Jun , Nagano Ai , Desai Ami , Arumugam Prabhu , Dumartin Laurent , Fitzgibbon Jude , Hagemann Thorsten , Marshall John F , Kocher Hemant M , Crnogorac-Jurcevic Tatjana , Scarpa Aldo , Lemoine Nicholas R , Chelala Claude
Published: December 2014

Background

Improved usage of the repertoires of pancreatic ductal adenocarcinoma (PDAC) profiles is crucially needed to guide the development of predictive and prognostic tools that could inform the selection of treatment options.

Methods

Using publicly available mRNA abundance datasets, we performed a large retrospective meta-analysis on 466 PDAC patients to discover prognostic gene signatures. These signatures were trained on two clinical cohorts (n = 70), and validated on four independent clinical cohorts (n = 246). Further validation of the identified gene signature was performed using quantitative real-time RT-PCR.

Results

We identified 225 candidate prognostic genes. Using these, a 36-gene signature was discovered and validated on fully independent clinical cohorts (hazard ratio (HR) = 2.06, 95% confidence interval (CI) = 1.51 to 2.81, P = 3.62 × 10−6, n = 246). This signature serves as a good alternative prognostic stratification marker compared to tumour grade (HR = 2.05, 95% CI = 1.45 to 2.88, P = 3.18 × 10−5) and tumour node metastasis (TNM) stage (HR = 1.13, 95% CI = 0.66 to 1.94, P = 0.67). Upon multivariate analysis with adjustment for TNM stage and tumour grade, the 36-gene signature remained an independent prognostic predictor of clinical outcome (HR = 2.21, 95% CI = 1.17 to 4.16, P = 0.01). Univariate assessment revealed higher expression of ITGA5, SEMA3A, KIF4A, IL20RB, SLC20A1, CDC45, PXN, SSX3 and TMEM26 was correlated with shorter survival while B3GNT1, NOSTRIN and CADPS down-regulation was associated with poor outcome.

Conclusions

Our 36-gene classifier is able to prognosticate PDAC independent of patient cohort and microarray platforms. Further work on the functional roles, downstream events and interactions of the signature genes is likely to reveal true molecular candidates for PDAC therapeutics.
The emerging need for family-centric initiatives for obtaining consent in personal genome research
Authors: Minari Jusaku , Teare Harriet , Mitchell Colin , Kaye Jane , Kato Kazuto
Published: December 2014

Editorial summary

The use of information and communication technology can offer a novel way to promote family-centric initiatives for informed consent, and can address associated ethical challenges in personal genome research.
Formal sector subcontracting and informal sector employment in Indian manufacturing
Authors: Moreno-Monroy Ana I , Pieters Janneke , Erumban Abdul A
Published: December 2014

Using nationally representative survey data of Indian manufacturing enterprises spanning the period 1995–2006, we analyze the link between formal sector subcontracting and informal sector employment. A novelty in our analysis is that this relationship is allowed to differ between modern and traditional segments of the informal sector. We show that formal sector subcontracting is positively related to employment growth only in the most modern segments of the informal sector. Increased subcontracting cannot explain the persistently high employment in traditional informal manufacturing activities in India. Instead, subcontracting can contribute to job creation in relatively modern segments of the informal sector.

JEL codes:J21, O14, O17
Publication rate of abstracts presented at the Canadian society of otolaryngology- head and neck surgery annual meetings: A five year study 2006–2010
Authors: Ogilvie Lauren N , Pauwels Julie , Chadha Neil K , Kozak Frederick K
Published: December 2014

Background

To determine the rate of publication in a peer-reviewed journal for all oral presentations made at the Canadian Society for Otolaryngology- Head and Neck Surgery's Annual Meetings from 2006–2010.

Methods

All abstracts were searched by keywords and authors’ names in Medline via PubMed and Google Scholar. Authors of presented abstracts not found to be published were contacted directly for further information.

Results

50.5% of presented abstracts (n = 198) were subsequently published with an average time to publication of 21 months. For those abstracts found not to be published 74.6% (n = 167) of authors responded with further information about their research, 66% (n = 89) of abstracts with author response that were not published were never submitted for publication. Authors’ main reasons for not publishing were that the research was still in process (34%, n = 21) or that a resident or fellow working on the project “had moved on” (26%, n = 16).

Conclusion

The publication rate for the Canadian Society for Otolaryngology- Head and Neck Surgery's Annual Meetings from 2006–2010 is within the range reported by other conferences and specifically other Canadian conferences in different specialties; however, roughly half of presentations went on to be published. The main barrier to publication was bringing projects to the submission stage and not rejection by journals. Resources such as more time for research or personnel to coordinate projects may result in a greater rate of project completion.
Impact of incorrect tissue classification in Dixon-based MR-AC: fat-water tissue inversion
Authors: Ladefoged Claes Nøhr , Hansen Adam Espe , Keller Sune Høgild , Holm Søren , Law Ian , Beyer Thomas , Højgaard Liselotte , Kjær Andreas , Andersen Flemming Littrup
Published: December 2014

Background

The current MR-based attenuation correction (AC) used in combined PET/MR systems computes a Dixon attenuation map (MR-ACDixon) based on fat and water images derived from in- and opposed-phase MRI. We observed an occasional fat/water inversion in MR-ACDixon. The aim of our study was to estimate the prevalence of this phenomenon in a large patient cohort and assess the possible bias on PET data.

Methods

PET/MRI was performed on a Siemens Biograph mMR (Siemens AG, Erlangen, Germany). We visually inspected attenuation maps of 283 brain or head/neck (H/N) patients, classified them as non-inverted or inverted, and calculated the fat/water tissue fraction. We selected ten FDG-PET brain patients with non-inverted attenuation maps for further analysis. Tissue inversion was simulated, and PET images were reconstructed using both original and inverted attenuation maps. The FDG-PET images of the ten brain patients were analyzed using 11 concentric annulus regions of 5 mm width placed over a central transaxial image plane traversing PETDixon.

Results

Out of the 283 patients, a fat/water inversion in 23 patients (8.1%) was observed. The average fraction of fat in the correct MR-ACDixon was 13% for brain and 17% for H/N patients. In the inverted cases, we found an average fat fraction of 56% for the brain patients and 41% for the H/N patients. The effect of the simulated tissue inversion in the brain studies was clearly seen on AC-PET images. The percent-difference image revealed a radial error where the largest difference was at the ventricles (30% ± 3%) and smallest at the cortical region (10% ± 2%).

Conclusions

Tissue inversion in Dixon MRI is well known and can occur when there is an error in the off-resonance correction method. Tissue inversion needs to be considered if, based on Dixon-AC, the construction of normal PET databases is performed or any quantitative physiological parameters are fitted. Visual inspection is needed if Dixon-AC is to be used in clinical routine.
Positive Feedback Regulation Between Adiponectin and T-Cadherin Impacts Adiponectin Levels in Tissue and Plasma of Male Mice
Authors: Matsuda Keisuke , Fujishima Yuya , Maeda Norikazu , Mori Takuya , Hirata Ayumu , Sekimoto Ryohei , Tsushima Yu , Masuda Shigeki , Yamaoka Masaya , Inoue Kana , Nishizawa Hitoshi , Kita Shunbun , Ranscht Barbara , Funahashi Tohru , Shimomura Iichiro
Published: December 2014

Adiponectin (Adipo), a multimeric adipocyte-secreted protein abundant in the circulation, is implicated in cardiovascular protective functions. Recent work documented that Adipo locally associates with responsive tissues through interactions with T-cadherin (Tcad), an atypical, glycosylphosphatidylinositol (GPI)-anchored cadherin cell surface glycoprotein. Mice deficient for Tcad lack tissue-associated Adipo, accumulate Adipo in the circulation, and mimic the Adipo knockout (KO) cardiovascular phenotype. In reverse, Tcad protein is visibly reduced from cardiac tissue in Adipo-KO mice, suggesting interdependent regulation of the 2 proteins. Here, we evaluate the effect of Adipo on Tcad protein expression. Adipo and Tcad proteins were colocalized in aorta, heart, and skeletal muscle. Adipo positively regulated levels of Tcad protein in vivo and in endothelial cell (EC) cultures. In Tcad-KO mice, binding of endogenous and exogenously administered Adipo to cardiovascular tissues was dramatically reduced. Consistently, knockdown of Tcad in cultured murine vascular ECs significantly diminished Adipo binding. In search for a possible mechanism, we found that enzymatic cleavage of Tcad with phosphatidylinositol-specific phospholipase C increases plasma Adipo while decreasing tissue-bound levels. Similarly, pretreatment of cultured ECs with serum containing Adipo attenuated phosphatidylinositol-specific phospholipase C-mediated Tcad cleavage. In vivo administration of adenovirus producing Adipo suppressed plasma levels of GPI phospholipase D, the endogenous cleavage enzyme for GPI-anchored proteins. In conclusion, our data show that both circulating and tissue-bound Adipo levels are dependent on Tcad and, in reverse, regulate tissue Tcad levels through a positive feedback loop that operates by suppressing phospholipase-mediated Tcad release from the cell surface.
Gestational Diabetes Alters Offspring DNA Methylation Profiles in Human and Rat: Identification of Key Pathways Involved in Endocrine System Disorders, Insulin Signaling, Diabetes Signaling, and ILK Signaling
Authors: Petropoulos Sophie , Guillemin Claire , Ergaz Zivanit , Dimov Sergiy , Suderman Matthew , Weinstein-Fudim Liza , Ornoy Asher , Szyf Moshe
Published: December 2014

Gestational diabetes is associated with risk for metabolic disease later in life. Using a cross-species approach in rat and humans, we examined the hypothesis that gestational diabetes during pregnancy triggers changes in the methylome of the offspring that might be mediating these risks. We show in a gestation diabetes rat model, the Cohen diabetic rat, that gestational diabetes triggers wide alterations in DNA methylation in the placenta in both candidate diabetes genes and genome-wide promoters, thus providing evidence for a causal relationship between diabetes during pregnancy and DNA methylation alterations. There is a significant overlap between differentially methylated genes in the placenta and the liver of the rat offspring. Several genes differentially methylated in rat placenta exposed to maternal diabetes are also differentially methylated in the human placenta of offspring exposed to gestational diabetes in utero. DNA methylation changes inversely correlate with changes in expression. The changes in DNA methylation affect known functional gene pathways involved in endocrine function, metabolism, and insulin responses. These data provide support to the hypothesis that early-life exposures and their effects on metabolic disease are mediated by DNA methylation changes. This has important diagnostic and therapeutic implications.
New NOBOX Mutations Identified in a Large Cohort of Women With Primary Ovarian Insufficiency Decrease KIT-L Expression
Authors: Bouilly Justine , Roucher-Boulez Florence , Gompel Anne , Bry-Gauillard Hélène , Azibi Kemal , Beldjord Cherif , Dodé Catherine , Bouligand Jérôme , Mantel Anne Guiochon , Hécart Annie-Claude , Delemer Brigitte , Young Jacques , Binart Nadine
Published: December 2014

Context:

Primary ovarian insufficiency (POI) is a major cause of anovulation and infertility in women. This disease affects 1% of women before 40 years, and several genetic causes have been reported.

Objective:

The aim of the study was to evaluate the prevalence of NOBOX mutations in a new large cohort of women with POI and to characterize these variants and identify a NOBOX novel target gene.

Patients and Methods:

A total of 213 unrelated patients with POI were screened for NOBOX mutations, and luciferase reporter assays were performed for the mutations identified.

Results:

We reported 3 novel and 2 recurrent heterozygous missense NOBOX rare variants found in 12 patients but not in 724 alleles from ethnic-matched individual women with occurrence of menopause at a normal age. Their functional impact had been tested on the classic growth differentiation factor-9 (GDF9) promoter and on KIT-L, a new NOBOX target gene. The p.Gly91Thr, p.Gly111Arg, p.Arg117Trp, p.Lys371Thr, and p.Pro619Leu mutations were deleterious for protein function.

Conclusions:

In our series, 5.6% of the patients with POI displayed heterozygous NOBOX mutations. We demonstrate that KIT-L could be now a direct NOBOX target. These findings replicate the high prevalence of the association between the NOBOX rare variants and POI.
Nesprins anchor kinesin-1 motors to the nucleus to drive nuclear distribution in muscle cells
Authors: Wilson Meredith H. , Holzbaur Erika L. F.
Published: December 2014

During skeletal muscle development, nuclei move dynamically through myotubes in a microtubule-dependent manner, driven by the microtubule motor protein kinesin-1. Loss of kinesin-1 leads to improperly positioned nuclei in culture and in vivo. Two models have been proposed to explain how kinesin-1 functions to move nuclei in myotubes. In the cargo model, kinesin-1 acts directly from the surface of the nucleus, whereas in an alternative model, kinesin-1 moves nuclei indirectly by sliding anti-parallel microtubules. Here, we test the hypothesis that an ensemble of Kif5B motors acts from the nuclear envelope to distribute nuclei throughout the length of syncytial myotubes. First, using an inducible dimerization system, we show that controlled recruitment of truncated, constitutively active kinesin-1 motors to the nuclear envelope is sufficient to prevent the nuclear aggregation resulting from depletion of endogenous kinesin-1. Second, we identify a conserved kinesin light chain (KLC)-binding motif in the nuclear envelope proteins nesprin-1 and nesprin-2, and show that recruitment of the motor complex to the nucleus via this LEWD motif is essential for nuclear distribution. Together, our findings demonstrate that the nucleus is a kinesin-1 cargo in myotubes and that nesprins function as nuclear cargo adaptors. The importance of achieving and maintaining proper nuclear position is not restricted to muscle fibers, suggesting that the nesprin-dependent recruitment of kinesin-1 to the nuclear envelope through the interaction of a conserved LEWD motif with kinesin light chain might be a general mechanism for cell-type-specific nuclear positioning during development.
Myocardin-related transcription factors control the motility of epicardium-derived cells and the maturation of coronary vessels
Authors: Trembley Michael A. , Velasquez Lissette S. , de Mesy Bentley Karen L. , Small Eric M.
Published: December 2014

An important pool of cardiovascular progenitor cells arises from the epicardium, a single layer of mesothelium lining the heart. Epicardium-derived progenitor cell (EPDC) formation requires epithelial-to-mesenchymal transition (EMT) and the subsequent migration of these cells into the sub-epicardial space. Although some of the physiological signals that promote EMT are understood, the functional mediators of EPDC motility and differentiation are not known. Here, we identify a novel regulatory mechanism of EPDC mobilization. Myocardin-related transcription factor (MRTF)-A and MRTF-B (MKL1 and MKL2, respectively) are enriched in the perinuclear space of epicardial cells during development. Transforming growth factor (TGF)-β signaling and disassembly of cell contacts leads to nuclear accumulation of MRTFs and the activation of the motile gene expression program. Conditional ablation of Mrtfa and Mrtfb specifically in the epicardium disrupts cell migration and leads to sub-epicardial hemorrhage, partially stemming from the depletion of coronary pericytes. Using lineage-tracing analyses, we demonstrate that sub-epicardial pericytes arise from EPDCs in a process that requires the MRTF-dependent motile gene expression program. These findings provide novel mechanisms linking EPDC motility and differentiation, shed light on the transcriptional control of coronary microvascular maturation and suggest novel therapeutic strategies to manipulate epicardium-derived progenitor cells for cardiac repair.
From naïve pluripotency to chimeras: a new ethical challenge?
Authors: Hyun Insoo
Published: December 2014

In recent years, there has been much interest in the prospect of generating and using human stem cells that exhibit a state of naïve pluripotency. Such a pluripotent state might be functionally confirmed by assessing the chimeric contribution of these cells to non-human blastocysts. Furthermore, the generation of naïve human pluripotent stem cells in vitro could lead to the creation of chimeric animal models that can facilitate the study of human development and disease. However, these lines of research raise thorny ethical concerns about the moral status of such chimeric animals. Here, I call attention to these ethical barbs and suggest a way in which to proceed cautiously.
Looking inwards: opening a window onto human development
Authors: Pourquié Olivier , Bruneau Benoit , Keller Gordon , Smith Austin
Published: December 2014

Summary: Development Editors announce a new focus on human developmental biology and discuss how they hope to support this expanding field.
Role of tautomerism in RNA biochemistry
Authors: Singh Vipender , Fedeles Bogdan I. , Essigmann John M.
Published: December 2014

Heterocyclic nucleic acid bases and their analogs can adopt multiple tautomeric forms due to the presence of multiple solvent-exchangeable protons. In DNA, spontaneous formation of minor tautomers has been speculated to contribute to mutagenic mispairings during DNA replication, whereas in RNA, minor tautomeric forms have been proposed to enhance the structural and functional diversity of RNA enzymes and aptamers. This review summarizes the role of tautomerism in RNA biochemistry, specifically focusing on the role of tautomerism in catalysis of small self-cleaving ribozymes and recognition of ligand analogs by riboswitches. Considering that the presence of multiple tautomers of nucleic acid bases is a rare occurrence, and that tautomers typically interconvert on a fast time scale, methods for studying rapid tautomerism in the context of nucleic acids under biologically relevant aqueous conditions are also discussed.
Life without post-transcriptional addition of G−1: two alternatives for tRNAHis identity in Eukarya
Authors: Rao Bhalchandra S. , Jackman Jane E.
Published: December 2014

The identity of tRNAHis is strongly associated with the presence of an additional 5′-guanosine residue (G−1) in all three domains of life. The critical nature of the G−1 residue is underscored by the fact that two entirely distinct mechanisms for its acquisition are observed, with cotranscriptional incorporation observed in Bacteria, while post-transcriptional addition of G−1 occurs in Eukarya. Here, through our investigation of eukaryotes that lack obvious homologs of the post-transcriptional G−1-addition enzyme Thg1, we identify alternative pathways to tRNAHis identity that controvert these well-established rules. We demonstrate that Trypanosoma brucei, like Acanthamoeba castellanii, lacks the G−1 identity element on tRNAHis and utilizes a noncanonical G−1-independent histidyl-tRNA synthetase (HisRS). Purified HisRS enzymes from A. castellanii and T. brucei exhibit a mechanism of tRNAHis recognition that is distinct from canonical G−1-dependent synthetases. Moreover, noncanonical HisRS enzymes genetically complement the loss of THG1 in Saccharomyces cerevisiae, demonstrating the biological relevance of the G−1-independent aminoacylation activity. In contrast, in Caenorhabditis elegans, which is another Thg1-independent eukaryote, the G−1 residue is maintained, but here its acquisition is noncanonical. In this case, the G−1 is encoded and apparently retained after 5′ end processing, which has so far only been observed in Bacteria and organelles. Collectively, these observations unearth a widespread and previously unappreciated diversity in eukaryotic tRNAHis identity mechanisms.