bluuebunny/crossref_metadata_2025 huggingface dataset:
Management of choanal atresia in the newborn
Authors: Weseman Chester M.
Published: September 2006

Bilateral congenital choanal atresia carries a high risk of brain damage due to hypoxia. Proper management requires early diagnosis, preferably in the delivery room, where temporary measures such as inserting an oral airway or a gavage tube are usually sufficient to establish satisfactory respiration. Careful observation is essential in the nursery during the period of local and general diagnostic evaluation to prevent repeated, even brief, spells of apnea. If satisfactory ventilation cannot be maintained, and particularly if there are associated serious anomalies, tracheotomy is indicated, rather than an immediate attempt to establish choanal patency.

Definitive transnasal surgical correction can be accomplished during the neonatal period. Relatively non‐traumatic perforation of the obstruction with a probe or trocar, as reported by Hough in 1955, is followed by dilatation with appropriate metal sounds, and emplacement of non‐reactive plastic tubing.

Excessive cicatrization, which is responsible for many failures of transnasal surgical methods, is further discouraged by the use of anti‐microbial agents to control infection in the choanal area. This can be expected to succeed in most cases if the tubing is maintained until healing is accomplished.
Massive surgery for palliation in malignancy of the head and neck
Authors: Tucker Harvey M. , Rabuzzi Daniel D. , Reed George F.
Published: September 2006

Since World War II, major advances in surgical management and life support have made possible operative procedures that could not have been undertaken previously. As a result of these encouraging developments, it has become apparent that the possibilities for palliative surgery now demand our attention and should be considered along with radiotherapy, chemotherapy, cryosurgery, and immunotherapy as suitable management of the patient with advanced malignancy.

It should be possible, on the basis of all available information, to excise the primary lesion and all metastases without leaving known tumor. This concept differs from that of “curability” in that it includes lesions which can be removed, but which are statistically not likely to be cured. The surgeon must be reasonably certain that the patient can be reconstructed sufficiently well and that his quality of survival will be superior to the disabilities that would be expected if the local tumor were left uncontrolled. The patient being considered for massive palliative surgery must, of course, be a sufficiently good surgical risk to tolerate the planned procedures.

This criterion is not intended to be taken in the medicolegal sense, but rather implies that the patient and his family must fully understand the massive nature of the surgery planned. More important, all concerned must have a realistic expectation as to what can be accomplished.

In applying these criteria to carefully selected cases, we have been encouraged to find that most patients are willing to undertake procedures that offer virtually no chance for cure in an effort to obtain the best possible quality of survival for as long as useful life can be prolonged. Morbidity as a result of these palliative attempts has been acceptably low and patient acceptance of these concepts very high.
Pediatric head and neck tumors: A study of 178 cases
Authors: Jaffe Burton F.
Published: September 2006

This report is based on 178 pediatric patients diagnosed with head and neck tumors in a 10‐year period at the Children's Hospital Medical Center in Boston, Mass. A statistical comparison was made with two other publications limited to pediatric head and neck tumors, and the similarity in rank‐order was clearly noted except in a few isolated instances.

Malignant tumors of the neck occurred in 104 children. From newborn to six years, the most common neck tumors were neuroblastoma, lymphosarcoma, and rhabdomyosarcoma. From ages seven to 13 the most common neck tumors were Hodgkin's disease, lymphosarcoma, and thyroid tumors. From ages 14‐21 the most common neck tumors were Hodgkin's disease, lymphosarcoma, and squamous cell carcinoma.

Malignant tumors of the head occurred in 74 children. Each anatomic site of the head was analyzed to determine what tumor cell was present when a mass lesion occurred. These data may help the physician to make more accurate clinical diagnoses.

A general discussion of the methods of treatment are also presented, including surgery, radiation therapy, chemotherapy and a new modality, cryosurgery.
Lymphatics in middle ear effusion
Authors: Galich Richard
Published: September 2006

Serous middle ear effusions frequently fail to resolve, long after the causative inflammatory‐obstructive process of the tympanum and eustachian tube have cleared. A disruption of the normal subepithelial connective tissue and lymphatic function is postulated. An animal experiment is described which demonstrates an ability of particles, in the size range of transudate proteins, to cross the tympanic mucosa and be cleared by a healthy functioning lymphatic system.
A high placed jugular bulb in the middle ear: A clinical and temporal bone study
Authors: Overton Stephen B. , Ritter Frank N.
Published: September 2006

Anatomically, the superior boundary of the jugular bulb lies below the floor of the hypotympanum of the middle ear space. In a rare instance, it can extend upward, elevate the floor of the hypotympanum and present in the middle ear. This elevation is an anomaly well known but rarely witnessed or documented in the literature. This may result in serious hemorrhage at the time of surgery if unrecognized by the surgeon and if it is injured during temporal bone surgery.

Two hundred fifty‐seven histologically prepared temporal bones were examined microscopically for anomalous positions of the jugular bulb. This survey represents 189 patients. Thirteen temporal bones were found in which the jugular bulb extended into the middle ear space above the inferior rim of the bony annulus. Although this anatomical variation occurs infrequently in the general population, a 6 percent incidence of high placed jugular bulb in the middle ear was found in the temporal bones studied in this series.
Electronystagmographic comparison of acute idiopathic and herpes zoster facial paralysis
Authors: Adour Kedar K. , Doty Howard E.
Published: September 2006

Electronystagmographic findings in idiopathic facial paralysis have been adduced by some as evidence for a vascular etiology; others, on clinical grounds, hold that it is a viral disease. Electronystagmographic abnormalities appeared in 43 percent of 28 patients with idiopathic, and 42 percent of 19, with herpes zoster facial paralysis. The only observed difference between the two types of facial paralysis was evidence for more widespread neural involvement and a greatly heightened percentage (56 percent versus 8 percent) of denervation, in the herpes zoster group. The clinical findings indicate that idiopathic facial paralysis is a polyneuropathy involving the Vth and VIIIth cranial nerves. Its protean manifestations and clinical similarity to a disease known to be viral in origin, appear to support the hypothesis that it is also a viral disorder.
Mucocele of the sphenoid sinus with sudden blindness
Authors: Blum Mitchell E. , Larson Alvin
Published: September 2006

Mucocele of the sphenoid sinus is a rare condition that usually presents with frontal and retroorbital headache of a constant unrelenting nature. Ophthalmoplegia that is progressive and blindness that is usually gradual in onset, but may be sudden, may complicate the illness. Chronic inflammation or congenital goblet cell cysts are the suspected etiologies. Diagnosis is made by X‐ray evidence of a sphenoid sinus mass that may destroy the floor of the sella turcica. The most important X‐ray studies are the AP and lateral tomograms. Our case represents the first case of sudden blindness reported with this condition and also presents a relatively new surgical approach to the sphenoid sinus. Other surgical approaches are also discussed.
Surgical management of combined cervical tracheo‐esophageal defects
Authors: Pearson Bruce W. , Harrison D. F. N.
Published: September 2006

Three rather complicated cervical tracheo‐esophageal problems and their appropriate management, are described. In each case, a tracheal defect required repair. In one case, fascia lata was used to close a defect in the posterior tracheal wall. In another, this type of repair was unsuccessful in one‐stage closure of a large tracheo‐esophageal fistula. A 7 cm defect of esophagus in heavily irradiated tissues was successfully reconstituted with transposed colon. The co‐existing postirradiation tracheo‐esophageal fistula was repaired at an earlier stage to ensure that the patient's recovery from the laparotomy would not be complicated by aspiration pneumonitis. Thoracotomy was not required, but resection of the clavicular head and mobilization of the origin of the sternomastoid were used to improve the transcervical exposure of the superior mediastinum.

In the second case, a tracheal defect that involved the tracheal cartilage was repaired by sleeve resection and end‐to‐end anastomosis. In revision surgery of chronic cervical tracheal and subglottic stenosis, one can anticipate massive local scar formation. The densely fibrosed common wall between the trachea and the esophagus should be left completely with the esophagus and only the lateral and anterior remnants of the trachea excised to avoid iatrogenic recurrent nerve paralysis or inadvertent perforation into a traction diverticulum of the esophagus. One should anticipate the use of the laryngeal drop procedure to make up the tracheal defect. The suprathyroid tissues will be virgin, whereas the previous tracheal procedures will have reduced the length attainable below from tracheal remobilization. Suturing the chin toward the chest is an effective and well‐tolerated prophylactic measure that prevents both extension of the neck after the operation and undue tension on the tracheal anastomosis.

In the third case, closure of a vertical tracheal‐esophageal fistula and repair of a tracheal defect were undertaken simultaneously. The procedure involved mobilizing the larynx from its hyoid attachments, dropping the larynx, and bringing the margins of the esophageal defect together transversely, as in a pyloroplasty. This application of the laryngeal drop procedure, not previously described, was effective.
Ethmoid sinus surgery
Authors: Kidder Thomas M. , Toohill Robert J. , Unger June D. , Lehman Roger H.
Published: September 2006

The literature on ethmoiditis was reviewed emphasizing the diagnostic and therapeutic aspects of the disease.

The records of 47 patients with chronic inflammatory nasoethmoid disease, treated by polypectomy and intranasal ethmoidectomy, were reviewed to determine the effectiveness of the operative procedure.

There has been follow‐up of two years or more on 26 patients. The records were analyzed with attention to etiologic factors, diagnostic criteria, surgical procedure and results.

We have found that the preoperative sinus roentgenograms frequently do not reveal the extent and severity of the disease noted at the time of surgery.

Our review supports the intranasal ethmoidectomy as an effective procedure for chronic nasoethmoid inflammatory disease, especially with recent emphasis on total resection of the middle turbinate.
Labyrinthectomy: Indications, technique and results
Authors: Pulec Jack L.
Published: September 2006

The patient with unilateral useless hearing and persistent symptoms of labyrinthine vertigo, aural tinnitus, pressure, distortion of sound or efferent involvement of hearing in the opposite normal ear, can benefit from destructive labyrinthectomy. Three techniques to accomplish this end are transcanal labyrinthectomy, postauricular labyrinthectomy and translabyrinthine section of the VIIIth cranial nerve.

The acoustic end‐organ is extremely resistant to surgical assault. Residual function following incomplete destruction often subjects the patient to persistent, unpleasant symptoms. The technique to accomplish effectively each of the three procedures is described and the results of 93 operations are reviewed to demonstrate their effectiveness.
Fungal derivatives as antigenic excitants of episodic vertigo
Authors: Wilson William H.
Published: September 2006

Thirty cases of episodic vertigo of labyrinthine origin with the common denominator of a history of hypersensitivity to fungal derivatives are grouped for study. Verification of the history of specific intolerances to fungal ingestants was accomplished by performing provocative intracutaneous or challenge feeding tests for hypersensitivity to yeast. A positive test response was obtained in each instance. Sixteen of the 30 patients gave a history of hypersensitivity to penicillin and 21 reported an intolerance to ingested, fermented alcohol. An antigenic cross‐reactivity between penicillin, yeast and other fungi is suggested.

Ten of the 30 cases qualified as classic Ménière's disease and 14 as vestibular Ménière's disease without auditory involvement. Six fell into the category of benign, positional vertigo.

Therapy entailed correction of proven metabolic and endocrine dysfunctions, when present and complete elimination from the diet of all proven allergenic offenders. Hyposensitization therapy for inhalant allergens supplemented the program when indicated.

Therapeutic results are classified according to the criteria set forth by the Subcommittee on Equilibrium and Its Management of the American Academy of Ophthalmology and Otolaryngology. Two of the 10 cases of classic Ménière's disease fell into the Class A category with absence of definitive spells of vertigo for the prescribed “10 times the average interval of spells before treatment” plus an improvement in hearing. Three cases fell into the Class B group, experiencing no definitive spells of vertigo but failing to show auditory improvement. Definitive spells persisted in the remaining 5 cases.

Allergic management of the vestibular Méniére's group of 14 cases allowed for the classification of 7 as meeting the prescribed requirement of 10 times the average pretreatment interval between definitive attacks. Seven cases of vestibular Ménière's disease failed to obtain relief from definitive spells.

Only 1 of 6 cases of benign positional vertigo experienced relief with allergic management. The high failure rate suggests other etiologic factors in this group.

It is conceivable that the initial hypersensitization of the patient to penicillin in some instances may be responsible for the eventual antigenic excitation of a perverse labyrinthine response by commonly ingested fungi.

Antigenic stimuli may excite episodic vertigo of labyrinthine origin. An acute episode of vertigo may be precipitated by the intracutaneous injection of a predetermined dilution and volume of a specific food antigen or by its ingestion, if the patient is hypersensitive to that food and the labyrinth is in a state of readiness to react.
Nasopharyngeal angiofibroma in the elderly: Report of a case
Authors: Pradillo Juan Andrade , Rodriguez Hector A. , Arroyo Juan Fajardo
Published: September 2006

Although nasopharyngeal angiofibromas usually occur during puberty and adolescence, thus being considered as juvenile, very rare documented reports describe this condition in old persons. The case of a 62‐year‐old man with a nasopharyngeal angiofibroma successfully resected is presented. It was the only lesion found in an old individual among 283 cases seen during a 20‐year period in a large city hospital.
Panel discussion on glottic tumors. VI. Laryngeal carcinomas
Authors: Ennuyer A. , Bataini P.
Published: September 2006

This study is based upon 214 cases of laryngeal carcinoma treated at the Foundation Curie, Paris, France, from January, 1958, to 1968. The results in terms of five‐year survival have been

By radiocobalt teletherapy 74/134

By surgery and postoperative radiation therapy 29/ 37

By surgery alone 32/ 43

A statistical study of these results was made by Professor Daudel and demonstrated the absence of significant difference for the groups of tumors classed T1 and in Stage I and II treated either by radiocobalt or by surgery, whether followed or not by radiotherapy. By contrast there was a clearly significant difference in favor of surgery for the group of tumors classified as T2, T3, T4, or in Stage III.

This significant difference in favor of primary surgery disappeared if we excluded the patients who died of intercurrent illnesses or of a second cancer not involving the larynx, and when we took into account those cures obtained by surgery in the event of failure of radiation and inversely, of those cures having been obtained by radiation therapy in the event of failure of surgery.
Panel discussion on glottic tumors. VII. The management of glottic carcinoma by primary irradiation with surgery in reserve
Authors: Stewart J. G. , Brown J. R. , Palmer M. K. , Cooper A.
Published: September 2006

Four hundred nineteen cases of carcinoma of the larynx (1962–1965, Christie Hospital) treated primarily by radiation with surgery in reserve for cases where radiation failed, are reviewed. Two hundred ninety‐one of these cases were glottic carcinomas and cure rates, and contribution from subsequent surgery is indicated in detail. Finally the overall results are compared with a larger series of 605 cases (1955–1961). Five‐year cure rate in early cases is consistent at 89 percent; likewise in the latest cases at 30 percent, the intermediate group appear to have improved by some 8 percent over the period outlined. The overall cure rate is 70 percent.
Evaluation of nasal tip surgery
Authors: Friedma William H. , Oliver Mae , Biller Hugh F.
Published: September 2006

Nasal tip surgery has been evaluated with respect to correction of the lower lateral cartilages. Indications, techniques, results, and complications related to three generic approaches to the lower lateral cartilages are described.

In 673 consecutive rhinoplasties the commonest type of nasal tip surgery was excisional, utilizing either a marginal or cartilage splitting technique. These techniques were utilized: 1. to accomplish debulking, and 2. to accomplish the installation of facets. The excisional technique found its greatest utility in primary rhinoplasties.

The version technique, utilizing a change of direction of the thrust of the lower lateral cartilages was utilized in a variety of situations, particularly for the correction of moderately congenitally hypoplastic tip cartilages. It also found great utility in surgery of the Negro or cleft palate nose, increasing tip projection, correcting unacceptable bifidity, and in revision rhinoplasty.

Augmentation rhinoplasty, utilizing conchal cartilage as an elastic strut was particularly useful for severe hypoplastic cartilage deficits, the Negro nose, columellar retraction, and alar rim deficits.

The overall complication rate of lower lateral rhinoplasty was 17.4 percent. The rate of unacceptable complications related to lower lateral rhinoplasty was 2.7 percent.
Human auditory nerve responses: A comparison of three commonly used recording sites
Authors: Simmons F. Blair
Published: September 2006

The computer‐averaged N1 response from humans to click stimuli was compared at three recording sites — dermal and subdermal electrodes in the ear canal, and a transtympanic electrode on the promontory. A total of 26 subjects, some of whom were measured at all three sites, participated in 47 experiments. The promontory electrodes were consistently more sensitive and yielded cleaner N1 waveforms than did the ear canal sites. In considering the clinical use of N1 averaging, the advantages of the trans‐tympanic method outweigh the risks. While a few persons yield reasonably good ear canal potentials, the reliability of this method in general application is inadequate and unpredictable.
Anesthetic management for carbon dioxide laser surgery of the larynx
Authors: Shaker Mohamed H. , Konchigeri Halappa N. , Andrews Albert H. , Holinger Paul H.
Published: September 2006

Fifty‐one patients underwent 71 carbon dioxide laser procedures under general anesthesia for various intralaryngeal pathology. Anesthesia was induced with thiopental sodium followed by succinylcholine to facilitate endotracheal intubation. For maintenance of anesthesia, 70 percent nitrous oxide was supplemented with halothane, enflurane or small doses of fentanyl. Succinylcholine, d‐tubocurare or pancuronium were used to maintain muscular relaxation of jaw, pharyngeal and laryngeal muscles for a smooth lasing procedure. Small diameter (16–22 Fr.), red rubber, cuffed endotracheal tubes provided maximum working space, facilitated the controlled ventilation and reduced the explosion hazard of the anesthetic gases. Safely eyeglasses were used by all the personnel in the operating room against accidental injury to the cornea by the laser beam. Anesthetic management provided excellent operative conditions with maximum safety to the patient and the personnel in the operating room.
Cricopharyngeal myotomy in amyotrophic lateral sclerosis
Authors: Lebo Charles P. , Sangü Kwei , Norris Forbes H.
Published: September 2006

Reported herein is the experience of the authors with 38 amyotrophic lateral sclerosis (ALS) patients for whom cricopharyngeal myotomy was performed. The major surgical objectives were facilitation of swallowing and amelioration of the tendency of these patients to aspirate ingestants and secretions. In the group of these patients in which the follow‐up information has been adequate, 64 percent were improved and 36 percent experienced no significant benefits. The authors' surgical indications, methods of anesthesia, surgical technique, and postoperative care are described.
Examination of the vestibular system by short‐time accelerations
Authors: Bodó GyÖRgy
Published: September 2006

Short accelerations, lasting for the split part of a second can be produced by the chair rotating with uniform speed in such a way that the chair will change its direction after each turn of 360°. The accelerations of alternating directions produce ampullopetal flows in the right and the left labyrinth alternately. The nystagmus elicited will be finished during the rotation of the chair with uniform speed, thus during the stimulus‐free period.

The short acceleration rates render possible the multiple dosage of identical stimuli as well as the gradual increase of the intensity of the stimulus. Since the stimulus produces ampullopetal flow in the right and the left labyrinth alternately the central vestibular equilibrium will not be changed. The author applied acceleration stimuli of 20, 30, 40 and 50°/sec2 doses to 20 healthy male subjects and studied the manifestations of the nystagmus elicited.
Executive Motivation: From the Front Lines to the Boardroom?
Authors: Murphy Steven A.
Published: September 2006

This study examines the motivation of rank-and-file police officers to become executives in a large Canadian police force, and the efficacy of the succession management system for the strategic priority of developing the next generation of leaders. The timing of the study is crucial, as police agencies face a looming challenge of managing the retirement of a large number of baby boomers, potentially leaving gaping holes across organisations. The study found that police officers' primary driver for entering the executive ranks is to enhance their own financial security (pension enhancement). Of secondary concern was what police officers could do as executives. Concerns over conflicts with child-rearing and elder care responsibilities, the negative perceptions of executives, workloads, lack of mentoring and the loss of paid overtime were the major negative influences on a decision to become an executive. Important gender differences and cultural issues are discussed to help explain the findings.
Algorithmic and Abstraction-Based Design of Discrete Controllers for Hybrid Automata (Algorithmischer und abstraktionsbasierter Entwurf diskreter Steuerungen für hybride Automaten)
Authors: Stursberg Olaf , Tran Thanh Ha
Published: September 2006

A rigorous modeling of discretely controlled processes requires to account for the abrupt change of dynamics when a process event (typically a limit switch) triggers a discrete control action. Using hybrid automata as a suitable means to model such discrete-continuous interactions, this contribution describes an algorithmic procedure to generate discrete controllers. For hybrid automata with linear continuous dynamics and additive uncertainties, a computational scheme is proposed which ensures that the controlled system meets specifications for safety and goal attainment. The key idea of the scheme is that discrete abstractions of the hybrid automaton are used to determine a feasible control strategy with relatively low computational effort.
Inter- and Intramolecular Association in Differently Substituted 2-(X-Pyridyl-)Ethan-1-ols
Authors: Kolbe Alfred , Kolbe Adelheid , Plass Monika
Published: September 2006

The homoassociative behaviour in molecules carrying dominant hydrogen bond donor and strong hydrogen bond acceptor functionalities has been investigated on the example of differently substituted 2-(X-pyridyl-)ethan-1-ols withXequals to 4, 3, and 2, abbreviated in this paper as I, II, and III, respectively. The associative behaviour is rather similar for the different substances. Only monomers and cyclic dimers have been found in the solutions of I and II. Compound III behaves differently due to the occurrence of intramolecular hydrogen bonds. The assumption of the existence of open dimers possessing one free OH group per associate does not fit the experimental results. The ring sizes of the cyclic associates decrease from 16 to 14 to 12 members, in compounds I, II, III, respectively, depending on the site of substitution in the pyridyl ring. The values of the association enthalpy ΔHof intermolecular hydrogen bonding have been calculated asca.−14 kJ/mol per two hydrogen bonds for all substances in CH2Cl2solutions, but the intramolecular hydrogen bond is characterized by a ΔHof −4.5 kJ/mol. The equilibrium constants of associationKand entropy changes −ΔSdiffer characteristically depending on the substance. Experiments and results are described and discussed.
Ni2+ Diffusion Through Microemulsion-Based Organo-Gels
Authors: Atay Naz Zeynep , Kornfilt Jak , Erkahraman Ayşegül
Published: September 2006

The transport of Ni2+ through an AOT-stabilised microemulsion-based organo-gel (MBG), located in between two aqueous regions A and B, has been studied. Using a mathematical model, the effective diffusion coefficient, D
eff, of Ni2+ ion was estimated to be in the range 5–7×10−7 cm2 s−1.
Dielectric Relaxation Studies of Primary Alcohols and Alkyl Methacrylates
Authors: Dharmalingam K. , Ramachandran K. , Sivagurunathan P. , Kalamse G. M.
Published: September 2006

Dielectric relaxation studies of alkyl (methyl, ethyl, and butyl) methacrylates with primary alcohols (1-propanol, 1-pentanol, 1-heptanol, and 1-octanol) at 9.84 GHz have been studied in benzene at 298 K. The results show that the most likely association between alcohol and ester is 1 : 1 complex through the free hydroxyl group of the alcohol and the carbonyl group of ester and the alkyl chain-length of both the alcohols and esters plays an important role in the determination of the strength of hydrogen bond (O–H:O=C) formed. Comparative study of free energy of activation for the dielectric relaxation and viscous flow suggest the fact that the process of viscous flow involves greater interference by neighbors than does dielectric relaxation, as the latter takes place by rotation only whereas the viscous flow involves both the rotational and translational forms of motion.
Evolution of the Human Immunodeficiency Virus Envelope Gene Is Dominated by Purifying Selection
Authors: Edwards C T T , Holmes E C , Pybus O G , Wilson D J , Viscidi R P , Abrams E J , Phillips R E , Drummond A J
Published: September 2006

The evolution of the human immunodeficiency virus (HIV-1) during chronic infection involves the rapid, continuous turnover of genetic diversity. However, the role of natural selection, relative to random genetic drift, in governing this process is unclear. We tested a stochastic model of genetic drift using partial envelope sequences sampled longitudinally in 28 infected children. In each case the Bayesian posterior (empirical) distribution of coalescent genealogies was estimated using Markov chain Monte Carlo methods. Posterior predictive simulation was then used to generate a null distribution of genealogies assuming neutrality, with the null and empirical distributions compared using four genealogy-based summary statistics sensitive to nonneutral evolution. Because both null and empirical distributions were generated within a coalescent framework, we were able to explicitly account for the confounding influence of demography. From the distribution of corrected P-values across patients, we conclude that empirical genealogies are more asymmetric than expected if evolution is driven by mutation and genetic drift only, with an excess of low-frequency polymorphisms in the population. This indicates that although drift may still play an important role, natural selection has a strong influence on the evolution of HIV-1 envelope. A negative relationship between effective population size and substitution rate indicates that as the efficacy of selection increases, a smaller proportion of mutations approach fixation in the population. This suggests the presence of deleterious mutations. We therefore conclude that intrahost HIV-1 evolution in envelope is dominated by purifying selection against low-frequency deleterious mutations that do not reach fixation.
Isochores Exhibit Evidence of Genes Interacting With the Large-Scale Genomic Environment
Authors: Press William H , Robins Harlan
Published: September 2006

The genomes of mammals and birds can be partitioned into megabase-long regions, termed isochores, with consistently high, or low, average C + G content. Isochores with high CG contain a mixture of CG-rich and AT-rich genes, while high-AT isochores contain predominantly AT-rich genes. The two gene populations in the high-CG isochores are functionally distinguishable by statistical analysis of their gene ontology categories. However, the aggregate of the two populations in CG isochores is not statistically distinct from AT-rich genes in AT isochores. Genes tend to be located at local extrema of composition within the isochores, indicating that the CG-enriching mechanism acted differently when near to genes. On the other hand, maximum-likelihood reconstruction of molecular phylogenetic trees shows that branch lengths (evolutionary distances) for third codon positions in CG-rich genes are not substantially larger than those for AT-rich genes. In the context of neutral mutation theory this argues against any strong positive selection. Disparate features of isochores might be explained by a model in which about half of all genes functionally require AT richness, while, in warm-blooded organisms, about half the genome (in large coherent blocks) acquired a strong bias for mutations to CG. Using mutations in CG-rich genes as convenient indicators, we show that ≈20% of amino acids in proteins are broadly substitutable, without regard to chemical similarity.
Assignment of Rainbow Trout Linkage Groups to Specific Chromosomes
Authors: Phillips Ruth B , Nichols Krista M , DeKoning Jenefer J , Morasch Matthew R , Keatley Kimberly A , Rexroad Caird , Gahr Scott A , Danzmann Roy G , Drew Robert E , Thorgaard Gary H
Published: September 2006

The rainbow trout genetic linkage groups have been assigned to specific chromosomes in the OSU (2N = 60) strain using fluorescence in situ hybridization (FISH) with BAC probes containing genes mapped to each linkage group. There was a rough correlation between chromosome size and size of the genetic linkage map in centimorgans for the genetic maps based on recombination from the female parent. Chromosome size and structure have a major impact on the female:male recombination ratio, which is much higher (up to 10:1 near the centromeres) on the larger metacentric chromosomes compared to smaller acrocentric chromosomes. Eighty percent of the BAC clones containing duplicate genes mapped to a single chromosomal location, suggesting that diploidization resulted in substantial divergence of intergenic regions. The BAC clones that hybridized to both duplicate loci were usually located in the distal portion of the chromosome. Duplicate genes were almost always found at a similar location on the chromosome arm of two different chromosome pairs, suggesting that most of the chromosome rearrangements following tetraploidization were centric fusions and did not involve homeologous chromosomes. The set of BACs compiled for this research will be especially useful in construction of genome maps and identification of QTL for important traits in other salmonid fishes.
Natural Isolates of Saccharomyces cerevisiae Display Complex Genetic Variation in Sporulation Efficiency
Authors: Gerke Justin P , Chen Christina T L , Cohen Barak A
Published: September 2006

Sporulation is a well-studied process executed with varying efficiency by diverse yeast strains. We developed a high-throughput method to quantify yeast sporulation efficiency and used this technique to analyze a line cross between a high-efficiency oak tree isolate and a low-efficiency wine strain. We find that natural variation in sporulation efficiency mirrors natural variation in higher eukaryotes: it shows divergence between isolated populations, arises from loci of major effect, and exhibits epistasis. We show that the lower sporulation efficiency of the wine strain results from a failure to initiate sporulation, rather than from slower kinetics of meiosis and spore formation. The two strains differentially regulate many genes involved in aerobic respiration, an essential pathway for sporulation, such that the oak tree strain appears better poised to generate energy from this pathway. We also report that a polymorphism in RME1 that affects sporulation efficiency in laboratory strains also cosegregates with significant phenotypic differences in our cross of natural isolates. These results lay the groundwork for the study of variation in sporulation efficiency among natural isolates of yeast.
Identifying the Environmental Factors That Determine the Genetic Structure of Populations
Authors: Foll Matthieu , Gaggiotti Oscar
Published: September 2006

The study of population genetic structure is a fundamental problem in population biology because it helps us obtain a deeper understanding of the evolutionary process. One of the issues most assiduously studied in this context is the assessment of the relative importance of environmental factors (geographic distance, language, temperature, altitude, etc.) on the genetic structure of populations. The most widely used method to address this question is the multivariate Mantel test, a nonparametric method that calculates a correlation coefficient between a dependent matrix of pairwise population genetic distances and one or more independent matrices of environmental differences. Here we present a hierarchical Bayesian method that estimates FST values for each local population and relates them to environmental factors using a generalized linear model. The method is demonstrated by applying it to two data sets, a data set for a population of the argan tree and a human data set comprising 51 populations distributed worldwide. We also carry out a simulation study to investigate the performance of the method and find that it can correctly identify the factors that play a role in the structuring of genetic diversity under a wide range of scenarios.
A Polymorphism in the 5′-Untranslated Region of the Porcine Cholecystokinin Type A Receptor Gene Affects Feed Intake and Growth
Authors: Houston R D , Haley C S , Archibald A L , Cameron N D , Plastow G S , Rance K A
Published: September 2006

The location and utilization of quantitative trait loci (QTL) and candidate genes with significant effects on economically important traits are becoming increasingly important in livestock breeding programs. The porcine cholecystokinin type A receptor (CCKAR) is a candidate gene for performance traits, due to its known role in the physiological control of feed intake, satiety, and obesity. We investigated the association of CCKAR polymorphisms with feeding, growth, and efficiency traits in an F2 population derived from a cross between Meishan and Large White founder animals and in lines of Large White pigs that had been divergently selected on the basis of lean growth efficiency traits. In the F2 population, CCKAR genotype was significantly associated with daily feed intake and average daily gain. The effects of the polymorphisms were then assessed in a larger-scale analysis of segregating commercial lines. A newly discovered single-nucleotide polymorphism (SNP) within the 5′-untranslated region (5′-UTR) had highly significant effects on feed intake, average daily gain, and days to 110 kg, which were not seen for a previously reported SNP within the CCKAR gene. Furthermore, we provide evidence that the novel SNP disrupts the binding of the YY1 transcription factor, which raises the possibility that it is the causal variant. The 5′-UTR SNP could be utilized as a molecular genetic test for increased feed intake, faster lean growth, and reduced days to market weight in segregating commercial lines.
Complex Genetic Architecture Revealed by Analysis of High-Density Lipoprotein Cholesterol in Chromosome Substitution Strains and F2 Crosses
Authors: Stylianou Ioannis M , Tsaih Shirng-Wern , DiPetrillo Keith , Ishimori Naoki , Li Renhua , Paigen Beverly , Churchill Gary
Published: September 2006

Intercrosses between inbred lines provide a traditional approach to analysis of polygenic inheritance in model organisms. Chromosome substitution strains (CSSs) have been developed as an alternative to accelerate the pace of gene identification in quantitative trait mapping. We compared a classical intercross and three CSS intercrosses to examine the genetic architecture underlying plasma high-density lipoprotein cholesterol (HDL) levels in the C57BL/6J (B) and A/J (A) mouse strains. The B × A intercross revealed significant quantitative trait loci (QTL) for HDL on chromosomes 1, 4, 8, 15, 17, 18, and 19. A CSS survey revealed that many have significantly different HDL levels compared to the background strain B, including chromosomes with no significant QTL in the intercross and, in some cases (CSS-1, CSS-17), effects that are opposite to those observed in the B × A intercross population. Intercrosses between B and three CSSs (CSS-3, CSS-11, and CSS-8) revealed significant QTL but with some unexpected differences from the B × A intercross. Our inability to predict the results of CSS intercrosses suggests that additional complexity will be revealed by further crosses and that the CSS mapping strategy should be viewed as a complement to, rather than a replacement for, classical intercross mapping.
Chromatin-Modifiying Enzymes Are Essential When the Saccharomyces cerevisiae Morphogenesis Checkpoint Is Constitutively Activated
Authors: Ruault Myriam , Pillus Lorraine
Published: September 2006

Hsl7p plays a central role in the morphogenesis checkpoint triggered when yeast bud formation is impaired and is proposed to function as an arginine methyltransferase. HSL7 is also essential in the absence of the N-terminal tails of histones H3 or H4. The requirement for H3 and H4 tails may indicate a need for their post-translational modification to bypass the morphogenesis checkpoint. In support of this, the absence of the acetyltransferases Gcn5p or Esa1p, the deacetylase Rpd3p, or the lysine-methyltransferase Set1p resulted in death or extreme sickness in hslΔ mutants. These synthetic interactions involved both the activity of the chromatin-modifying enzymes and the complexes through which they act. Newly reported silencing phenotypes of hsl7Δ mirror those previously reported for gcn5Δ and rpd3Δ, thereby strengthening their functional links. In addition, synthetic interactions and silencing phenotypes were suppressed by inactivation of the morphogenesis checkpoint, either by SWE1 deletion or by preventing Cdc28p phosphorylation. A catalytically dead Hsl7p retained wild-type interactions, implying that modification of histone H3 or H4 N termini by Gcn5p, Esa1p, Rpd3p, and Set1p, but not by Hsl7p, was needed to bypass the morphogenesis checkpoint.
Unique Classes of Mutations in the Saccharomyces cerevisiae G-Protein Translation Elongation Factor 1A Suppress the Requirement for Guanine Nucleotide Exchange
Authors: Ozturk Sedide B , Vishnu Melanie R , Olarewaju Olubunmi , Starita Lea M , Masison Daniel C , Kinzy Terri Goss
Published: September 2006

G-proteins play critical roles in many cellular processes and are regulated by accessory proteins that modulate the nucleotide-bound state. Such proteins, including eukaryotic translation elongation factor 1A (eEF1A), are frequently reactivated by guanine nucleotide exchange factors (GEFs). In the yeast Saccharomyces cerevisiae, only the catalytic subunit of the GEF complex, eEF1Bα, is essential for viability. The requirement for the TEF5 gene encoding eEF1Bα can be suppressed by the presence of excess substrate, eEF1A. These cells, however, have defects in growth and translation. Two independent unbiased screens performed to dissect the cause of these phenotypes yielded dominant suppressors that bypass the requirement for extra eEF1A. Surprisingly, all mutations are in the G-protein eEF1A and cluster in its GTP-binding domain. Five mutants were used to construct novel strains expressing only the eEF1A mutant at normal levels. These strains show no growth defects and little to no decreases in total translation, which raises questions as to the evolutionary expression of GEF complexity and other potential functions of this complex. The location of the mutations on the eEF1A-eEF1Bα structure suggests that their mechanism of suppression may depend on effects on the conserved G-protein elements: the P-loop and NKXD nucleotide-binding element.
Precise Centromere Mapping Using a Combination of Repeat Junction Markers and Chromatin Immunoprecipitation–Polymerase Chain Reaction
Authors: Luce Amy C , Sharma Anupma , Mollere Oliver S B , Wolfgruber Thomas K , Nagaki Kiyotaka , Jiang Jiming , Presting Gernot G , Dawe R Kelly
Published: September 2006

Centromeres are difficult to map even in species where genetic resolution is excellent. Here we show that junctions between repeats provide reliable single-copy markers for recombinant inbred mapping within centromeres and pericentromeric heterochromatin. Repeat junction mapping was combined with anti-CENH3-mediated ChIP to provide a definitive map position for maize centromere 8.
A Chip off the Old Block: A Model for the Evolution of Genomic Imprinting via Selection for Parental Similarity
Authors: Spencer Hamish G , Clark Andrew G
Published: September 2006

A consequence of genomic imprinting is that offspring are more similar to one parent than to the other, depending on which parent's genes are inactivated in those offspring. We hypothesize that genomic imprinting may have evolved at some loci because of selection to be similar to the parent of one sex or the other. We construct and analyze an evolutionary-genetic model of a two-locus two-deme system, in which one locus codes for a character under local selection and the second locus is a potential cis-acting modifier of imprinting. A proportion of males only migrate between demes every generation, and prebreeding males are less fit, on average, than females. We examine the conditions in which an imprinting modifier allele can invade a population fixed for a nonimprinting modifier allele and vice versa. We find that the conditions under which the imprinting modifier invades are biologically restrictive (high migration rates and high values of recombination between the two loci) and thus this hypothesis is unlikely to explain the evolution of imprinting. Our modeling also shows that, as with several other hypotheses, polymorphism of imprinting status may evolve under certain circumstances, a feature not predicted by verbal accounts.
Misregulation of Sex-Lethal and Disruption of Male-Specific Lethal Complex Localization in Drosophila Species Hybrids
Authors: Pal Bhadra Manika , Bhadra Utpal , Birchler James A
Published: September 2006

A major model system for the study of evolutionary divergence between closely related species has been the unisexual lethality resulting from reciprocal crosses of Drosophila melanogaster and D. simulans. Sex-lethal (Sxl), a critical gene for sex determination, is misregulated in these hybrids. In hybrid males from D. melanogaster mothers, there is an abnormal expression of Sxl and a failure of localization of the male-specific lethal (MSL) complex to the X chromosome, which causes changes in gene expression. Introduction of a Sxl mutation into this hybrid genotype will allow expression of the MSL complex but there is no sequestration to the X chromosome. Lethal hybrid rescue (Lhr), which allows hybrid males from this cross to survive, corrects the SXL and MSL defects. The reciprocal cross of D. simulans mothers by D. melanogaster males exhibits underexpression of Sxl in embryos.
Perfect Simulation From Nonneutral Population Genetic Models: Variable Population Size and Population Subdivision
Authors: Fearnhead Paul
Published: September 2006

We show how the idea of monotone coupling from the past can produce simple algorithms for simulating samples at a nonneutral locus under a range of demographic models. We specifically consider a biallelic locus and either a general variable population size mode or a general migration model for population subdivision. We investigate the effect of demography on the efficacy of selection and the effect of selection on genetic divergence between populations.
Using Dominance Relationship Coefficients Based on Linkage Disequilibrium and Linkage With a General Complex Pedigree to Increase Mapping Resolution
Authors: Lee S H , Van der Werf J H J
Published: September 2006

Dominance (intralocus allelic interactions) plays often an important role in quantitative trait variation. However, few studies about dominance in QTL mapping have been reported in outbred animal or human populations. This is because common dominance effects can be predicted mainly for many full sibs, which do not often occur in outbred or natural populations with a general pedigree. Moreover, incomplete genotypes for such a pedigree make it infeasible to estimate dominance relationship coefficients between individuals. In this study, identity-by-descent (IBD) coefficients are estimated on the basis of populationwide linkage disequilibrium (LD), which makes it possible to track dominance relationships between unrelated founders. Therefore, it is possible to use dominance effects in QTL mapping without full sibs. Incomplete genotypes with a complex pedigree and many markers can be efficiently dealt with by a Markov chain Monte Carlo method for estimating IBD and dominance relationship matrices ($\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(D_{\mathrm{RM}}\) \end{document}$). It is shown by simulation that the use of $\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(D_{\mathrm{RM}}\) \end{document}$ increases the likelihood ratio at the true QTL position and the mapping accuracy and power with complete dominance, overdominance, and recessive inheritance modes when using 200 genotyped and phenotyped individuals.