bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Evolution of Two Mutations During Clonal Expansion
Authors: Haeno Hiroshi , Iwasa Yoh , Michor Franziska 
Published: December 2007

Abstract
Knudson's two-hit hypothesis proposes that two genetic changes in the RB1 gene are the rate-limiting steps of retinoblastoma. In the inherited form of this childhood eye cancer, only one mutation emerges during somatic cell divisions while in sporadic cases, both alleles of RB1 are inactivated in the growing retina. Sporadic retinoblastoma serves as an example of a situation in which two mutations are accumulated during clonal expansion of a cell population. Other examples include evolution of resistance against anticancer combination therapy and inactivation of both alleles of a metastasis-suppressor gene during tumor growth. In this article, we consider an exponentially growing population of cells that must evolve two mutations to (i) evade treatment, (ii) make a step toward (invasive) cancer, or (iii) display a disease phenotype. We calculate the probability that the population has evolved both mutations before it reaches a certain size. This probability depends on the rates at which the two mutations arise; the growth and death rates of cells carrying none, one, or both mutations; and the size the cell population reaches. Further, we develop a formula for the expected number of cells carrying both mutations when the final population size is reached. Our theory establishes an understanding of the dynamics of two mutations during clonal expansion.
Differential Nuclear Localization Does Not Determine the Silencing Status ofSaccharomyces cerevisiaeTelomeres
Authors: Mondoux Michelle A , Scaife Jillian G , Zakian Virginia A 
Published: December 2007

AbstractIn Saccharomyces cerevisiae, genes near telomeres are transcriptionally repressed, a phenomenon termed telomere position effect (TPE). Yeast telomeres cluster near the nuclear periphery, as do foci of proteins essential for TPE: Rap1p, Sir2-4p, and yKu70p/yKu80p. However, it is not clear if localization of telomeres to the periphery actually contributes to TPE. We examined the localization patterns of two telomeres with different levels of TPE: truncated VII-L and native VI-R. For both telomeres, localization to the nuclear periphery or to the silencing foci was neither necessary nor sufficient for TPE. Moreover, there was no correlation between TPE levels and the extent of localization. Tethering the truncated VII-L telomere to the nuclear periphery resulted in a modest increase in TPE. However, tethering did not bypass the roles of yKu70p, Sir4p, or Esc1p in TPE. Using mutations in RIF genes that bypass the role of Ku in TPE, a correlation between the level of silencing and the number of Rap1p foci present in the nucleus was observed, suggesting that Sir protein levels at telomeres determine both the level of TPE and the number of foci.
The Tetrad-Pollen Model Fails to Explain the Bias in Mendel's Pea (Pisum sativum) Experiments
Authors: Fairbanks Daniel J , Schaalje G Bruce 
Published: December 2007

AbstractFor &gt;40 years, geneticists and science historians have appealed to the tetrad-pollen model as an explanation of the bias toward expectation in Mendel's data, albeit without experimental support. Our experiments demonstrate that pollen sampling during self-pollination in pea conforms to the binomial distribution with no evidence of a tetrad-pollen effect.
Mapping Quantitative Trait Loci Affecting Susceptibility to Marek's Disease Virus in a Backcross Population of Layer Chickens
Authors: Heifetz E M , Fulton J E , O'Sullivan N P , Arthur J A , Wang J , Dekkers J C M , Soller M 
Published: December 2007

Abstract
Marek's disease (MD), caused by the oncogenic MD avian herpes virus (MDV), is a major source of economic losses to the poultry industry. A reciprocal backcross (BC) population (total 2052 individuals) was generated by crossing two partially inbred commercial Leghorn layer lines known to differ in MDV resistance, measured as survival time after challenge with a (vv+) MDV. QTL affecting resistance were identified by selective DNA pooling using a panel of 198 microsatellite markers covering two-thirds of the chicken genome. Data for each BC were analyzed separately, and as a combined data set. Markers showing significant association with resistance generally appeared in blocks of two or three, separated by blocks of nonsignificant markers. Defined this way, 15 chromosomal regions (QTLR) affecting MDV resistance, distributed among 10 chromosomes (GGA 1, 2, 3, 4, 5, 7, 8, 9, 15, and Z), were identified. The identified QTLR include one gene and three QTL associated with resistance in previous studies of other lines, and three additional QTL associated with resistance in previous studies of the present lines. These QTL could be used in marker-assisted selection (MAS) programs for MDV resistance and as a platform for high-resolution mapping and positional cloning of the resistance genes.
Synthetic Lethal Interactions Identify Phenotypic “Interologs” of the Spindle Assembly Checkpoint Components
Authors: Tarailo Maja , Tarailo Sanja , Rose Ann M 
Published: December 2007

Abstract
Here, we report genetic interactions with mdf-1(gk2)/MAD1 in Caenorhabditis elegans. Nine are evolutionarily conserved or phenotypic “interologs” and two are novel enhancers, hcp-1 and bub-3. We show that HCP-1 and HCP-2, the two CENP-F-related proteins, recently implicated in the spindle assembly checkpoint (SAC) function, do not have identical functions, since hcp-1(RNAi), but not hcp-2(RNAi), enhances the lethality of the SAC mutants.
A Measurable Increase in Oxidative Damage Due to Reduction in Superoxide Detoxification Fails to Shorten the Life Span of Long-Lived Mitochondrial Mutants of Caenorhabditis elegans
Authors: Yang Wen , Li Jingjing , Hekimi Siegfried 
Published: December 2007

Abstract
SOD-1 and SOD-2 detoxify superoxide in the cytoplasm and mitochondria. We find that, although several long-lived mutants of Caenorhabditis elegans have increased SOD levels, this phenomenon does not correlate with life span or growth rate. Furthermore, although disruption of sod-1 or -2 expression produces numerous phenotypes, including increased sensitivity to paraquat and increased oxidative damage to proteins (except in daf-2 mutants), this fails to shorten the life span of these long-lived mutants. In fact, sod-1(RNAi) increases the life span of daf-2 mutants and sod-2(RNAi) that of clk-1 mutants. Our results suggest that increased superoxide detoxification and low oxidative damage are not crucial for the longevity of the mutants examined, with the possible exception of daf-2, where our results are inconclusive. These results are surprising because several of the long-lived mutants that we examined specifically affect mitochondrial electron transport, a process whose involvement in life-span determination is believed to be related to superoxide generation. We discuss the significance of our findings in light of the oxidative stress theory of aging.
Investigating the Genetic Circuitry of Mastermind in Drosophila, a Notch Signal Effector
Authors: Kankel Mark W , Hurlbut Gregory D , Upadhyay Geeta , Yajnik Vijay , Yedvobnick Barry , Artavanis-Tsakonas Spyros 
Published: December 2007

AbstractNotch signaling regulates multiple developmental processes and is implicated in various human diseases. Through use of the Notch transcriptional co-activator mastermind, we conducted a screen for Notch signal modifiers using the Exelixis collection of insertional mutations, which affects ∼50% of the Drosophila genome, recovering 160 genes never before associated with Notch, extending the previous roster of genes that interact functionally with the Notch pathway and mastermind. As the molecular identity for most recovered genes is known, gene ontology (GO) analysis was applied, grouping genes according to functional classifications. We identify novel Notch-associated GO categories, uncover nodes of integration between Notch and other signaling pathways, and unveil groups of modifiers that suggest the existence of Notch-independent mastermind functions, including a conserved ability to regulate Wnt signaling.
Deletion-Mutant mtDNA Increases in Somatic Tissues but Decreases in Female Germ Cells With Age
Authors: Sato Akitsugu , Nakada Kazuto , Shitara Hiroshi , Kasahara Atsuko , Yonekawa Hiromichi , Hayashi Jun-Ichi 
Published: December 2007

Abstract
The proportions of mutant and wild-type mtDNA are crucial in determining the severity of mitochondrial diseases. It has been generally considered that deletion-mutant mtDNA has replication advantages and accumulates with time. Here, we examine the tissue-by-tissue proportions of mutant mtDNA with a 4696-bp deletion (ΔmtDNA) and wild-type mtDNA in mitochondrial disease model mice (mito-mice). Comparison of the proportions of ΔmtDNA in each tissue at various ages showed that the rate of accumulation of ΔmtDNA differed among tissues. The heart, skeletal muscles, kidney, liver, testis, and ovary showed increases in the proportion of ΔmtDNA with age, but the pancreas, spleen, brain, and blood showed only a slight or no increase in proportion. In contrast to the somatic tissues, however, the germ cells of female mito-mice and resultant offspring showed a strong decrease in ΔmtDNA with maternal age. The decrease was so acute that some offspring showed complete disappearance of ΔmtDNA, even though their elder brothers and sisters had high proportions of ΔmtDNA. Female germ cells have a machinery that prevents the inheritence of defective mtDNA to the following generation since germ cells are kept for a long time until they are ovulated.
Multiple Functions and Dynamic Activation of MPK-1 Extracellular Signal-Regulated Kinase Signaling inCaenorhabditis elegansGermline Development
Authors: Lee Min-Ho , Ohmachi Mitsue , Arur Swathi , Nayak Sudhir , Francis Ross , Church Diane , Lambie Eric , Schedl Tim 
Published: December 2007

AbstractThe raison d'etre of the germline is to produce oocytes and sperm that pass genetic material and cytoplasmic constituents to the next generation. To achieve this goal, many developmental processes must be executed and coordinated. ERK, the terminal MAP kinase of a number of signaling pathways, controls many aspects of development. Here we present a comprehensive analysis of MPK-1 ERK in Caenorhabditis elegans germline development. MPK-1 functions in four developmental switches: progression through pachytene, oocyte meiotic maturation/ovulation, male germ cell fate specification, and a nonessential function of promoting the proliferative fate. MPK-1 also regulates multiple aspects of cell biology during oogenesis, including membrane organization and morphogenesis: organization of pachytene cells on the surface of the gonadal tube, oocyte organization and differentiation, oocyte growth control, and oocyte nuclear migration. MPK-1 activation is temporally/spatially dynamic and most processes appear to be controlled through sustained activation. MPK-1 thus may act not only in the control of individual processes but also in the coordination of contemporaneous processes and the integration of sequential processes. Knowledge of the dynamic activation and diverse functions of MPK-1 provides the foundation for identification of upstream signaling cascades responsible for region-specific activation and the downstream substrates that mediate the various processes.
Cell Cycle Arrest of Stamen Initials in Maize Sex Determination
Authors: Kim Jong Cheol , Laparra Hélène , Calderón-Urrea Alejandro , Mottinger John P , Moreno Maria A , Dellaporta Stephen L 
Published: December 2007

Abstract
The maize sex determination pathway results in the arrest of stamen in ear spikelets and the abortion of pistils in both the tassel spikelets and in the secondary florets of ear spikelets. Arrested stamen cells showed no signs of DNA fragmentation, an absence of CYCLIN B expression, and an accumulation of the negative cell cycle regulator WEE1 RNA.
Changes in Vitamin Status of Indian Antarctic Expeditioners During a One-Month Stay in Austral Summer
Authors: Vats Praveen , Singh Som N. , Singh Vijay K. , Shyam Radhey , Upadhyay Tribhuvan N. , Singh Shashi B. , Banerjee Pratul K. 
Published: December 2007

Objective Antarctic expeditioners face extremes of environmental conditions along with isolation which affect normal human activity at a polar station. Diets of polar expeditioners consist of products that have been kept in storage for more than a year. Processing and preservation adversely affect the nutritive value of the food products, especially water-soluble vitamins. This study was conducted to determine water-soluble vitamin status of Antarctic expeditioners consuming processed canned food. Methods Twenty-two healthy male volunteers age 26 to 56 years (39.5 ± 8.5, mean ± SD) participated in the study. The study was conducted in 3 phases: at Goa, India (phase I), 48 hours after arriving in Antarctica (phase II) and after 1 month in Antarctica (phase III). Water-soluble vitamin status in erythrocytes was assessed at each phase with evaluation of riboflavin, thiamine, and pyridoxine status. Urinary N-methyl nicotinamide and methylmalonic acid (MMA) levels were measured to assess niacin and vitamin B12 status. Blood plasma assays were used to assess ascorbic acid status. Results No significant changes in riboflavin, thiamine, and pyridoxine status in erythrocytes and urinary excretion levels were observed after 1 month in Antarctica. Vitamin C levels decreased significantly ( P < .001) after 1 month in Antarctica compared with basal values (1.31 ± 0.076 mg/dL during phase I to 0.81 ± 0.063 mg/dL during phase III). However, these levels were still within the normal reference range. Conclusion This study found no water-soluble vitamin deficiencies in participants consuming processed and canned food after 1 month in Antarctica.
Ginkgo biloba Decreases Acute Mountain Sickness in People Ascending to High Altitude at Ollagüe (3696 m) in Northern Chile
Authors: Moraga Fernando A. , Flores Alejandro , Serra Jordi , Esnaola Carla , Barriento Corina 
Published: December 2007

Objective To determine the prophylactic effect of Ginkgo biloba (doses 80 mg/12 h, 24 h before high-altitude ascension and with continued treatment) in preventing acute mountain sickness (AMS) at 3696 m in participants without high-altitude experience. Methods Thirty-six participants who reside at sea level were transported to an altitude of 3696 m (Ollagüe). The participants were divided into 3 groups and received G biloba ( n = 12) 80 mg/12 h, acetazolamide ( n = 12) 250 mg/12 h, or placebo ( n = 12) 24 hours before ascending and during their 3-day stay at high altitude. The Lake Louise Questionnaire constituted the primary outcome measurement at sea level and at 3696 m. A Lake Louise Self-Report Score greater than 3 was indicative of AMS. Oxygen saturation, heart rate, and arterial pressure were taken with each evaluation for AMS. Results A significant reduction in AMS was observed in the group that received G biloba (0%, P < .05) comparison with the groups receiving acetazolamide (36%, P < .05) or placebo (54%). No difference was observed in arterial oxygen saturation in the G biloba (92 ± 2) vs the acetazolamide (89 ± 2) groups. However, a marked increased saturation in arterial oxygen was seen in comparison with the placebo group (84 ± 3, P < .05). No statistically significant differences were observed in mean arterial pressure or heart rate. Conclusions This study provides evidence supporting the use of G biloba in the prevention of AMS, demonstrating that 24 hours of pretreatment with G biloba and subsequent maintenance during exposure to high altitude are sufficient to reduce the incidence of AMS in participants with no previous high-altitude experience.
Snakebite Injuries Treated in United States Emergency Departments, 2001–2004
Authors: O’Neil Mary Elizabeth , Mack Karin A. , Gilchrist Julie , Wozniak Edward J. 
Published: December 2007

Objective Venomous and nonvenomous snakes are found throughout most of the United States. While the literature on treatment is robust, there is not a current national epidemiologic profile of snakebite injuries in the United States. National estimates of such injuries treated in emergency departments (EDs) are presented along with characteristics of the affected population. Methods Data on snakebite injuries were abstracted from the National Electronic Injury Surveillance System–All Injury Program (2001–04). Variables included age, gender, body part affected, cause, disposition, and treatment date. When available, location, intentionality of the interaction, and snake species were coded based on narrative comments. Estimates were weighted and analyzed with SPSS Complex Samples. Results An estimated 9873 snakebites were treated in US EDs each year between 2001 and 2004. Males were more frequently seen in the ED for snakebites than were females (males: 72.0% [95% confidence interval (CI), 68.0–75.7]; females: 28.0% [95% CI, 24.3–32.0]). Approximately 32% of patients were known to be bitten by venomous species. Overall, more than one quarter of patients were hospitalized (27.9% [95% CI, 15.9–44.2]), although 58.9% of patients with known venomous bites were hospitalized (95% CI, 41.5–74.3). Conclusions While they are rare events, snakebites cause nearly 10 000 visits to EDs for treatment every year. Epidemiologic data regarding snakebites provide practicing physicians with an understanding of the population affected and can help guide public health practitioners in their prevention efforts.
Animal-Caused Fatalities in New Mexico, 1993–2004
Authors: Lathrop Sarah L. 
Published: December 2007

Objective To evaluate animal-caused fatalities in New Mexico using data collected during medicolegal death investigations, including toxicology, survival interval, and circumstances. Methods A retrospective review of the computerized database and hard copies of files from a centralized, statewide medical examiner's office, excluding deaths due to zoonotic diseases and motor vehicle collisions involving animals. Results Between 1993 and 2004, 63 deaths caused by animals were reported in New Mexico. The majority of decedents were male (46/63, 73%) and non-Hispanic white (33/63, 52%). Horses were the most commonly implicated animals, with 43 (68%) deaths due to a person being thrown from, crushed, dragged, or kicked by a horse. Cattle caused 9 deaths (14%), dogs caused 3 (5%), and venomous animals caused 3, whereas a bear was responsible for 1 death. Ten decedents (16%) had alcohol present at the time of death, and 8 would have been over the legal blood alcohol concentration for driving (0.08%). Ten deaths (16%) were work-related and included deaths of jockeys and ranch workers. The majority of deaths (42/63, 67%) occurred in remote locations, potentially delaying access to treatment. Survival intervals ranged from 1 day to 33 years. Conclusions Whereas both human and animal behavior can be difficult to predict, a review of animal-caused fatalities investigated by a medical examiner revealed that in many cases, deaths could have been prevented by either the use of protective gear or alterations in human behavior.
Medical Incidents and Evacuations on Wilderness Expeditions
Authors: McIntosh Scott E. , Leemon Drew , Visitacion Joshua , Schimelpfenig Tod , Fosnocht David 
Published: December 2007

Objective Expedition activities such as mountaineering, rock climbing, river running, sea kayaking, and canoeing all involve an element of risk. Organizations that provide group wilderness and adventure experiences are responsible for managing the risk of their courses. The leaders and medical providers of these trips must therefore be prepared to anticipate and manage medical problems that may arise. The aim of this study is to provide the medical community with a better understanding of the specific injuries and illnesses that occur on wilderness expeditions. Methods A retrospective descriptive study was done examining the medical incidents that occurred on wilderness-based courses during the 3-year period from September 1, 2002, through August 31, 2005. Participants and staff of the National Outdoor Leadership School (NOLS) served as the study population. Results Injuries occurred at a rate of 1.18 per 1000 program days, and illnesses at a rate of 1.08 per 1000 program days. There were no fatalities during the time period. Athletic injuries (sprains, strains) and gastrointestinal illnesses were the most common medical incidents. Hypothermia, seizures, appendicitis, heat stroke, and pregnancy occurred but with low frequency. Fractures, dental emergencies, tick fever, athletic injuries, and nonspecific body pains were the conditions most frequently requiring evacuation. Conclusions The rate of medical incidents on NOLS courses declined during the 1990s and has remained relatively steady apart from a slight increase in 2004 and 2005. Athletic injuries continue to be a difficulty, as they frequently result in evacuation even though their ultimate outcome is usually benign. Evacuation decisions should be made considering both the potential severity of the medical condition as well as patient comfort. Wilderness medical personnel must be familiar with a diverse range of medical conditions in order to provide optimal care.
Pulmonary Artery Pressure in Healthy Subjects at 4250 m Measured by Doppler Echocardiography
Authors: Dubowitz Gerald , Peacock Andrew J. 
Published: December 2007

Objective Acute hypoxia causes vasoconstriction in the pulmonary arteries. This hypoxic pulmonary vasoconstriction (HPV) has been reported to be common in subjects exposed to high altitude. In the past, it has been difficult to directly measure this HPV because of the invasive nature of tests, but the recent availability of portable color flow Doppler ultrasound has enabled measurements of pulmonary artery systolic pressure (PASP) in the field. We set out to study the feasibility of this method to detect changes related to HPV at 4250 m. We hypothesized that significant changes in the cardiopulmonary circulation are seen at high altitude and are detectable with Doppler echocardiography. In addition, we hypothesized that detected changes are related to the syndrome of acute mountain sickness (AMS) and could be reversed using 100% oxygen. Methods Over a 10-week period in the spring of 1998, 56 healthy lowlanders not normally residing at altitude were studied while visiting 4250 m in Nepal having walked from 2774 m. This was a cross-sectional observational study conducted by a single experienced observer at high altitude, using transthoracic color flow continuous wave Doppler echocardiography. Subjects were initially assessed for significant tricuspid regurgitation (TR) to measure PASP. After estimating PASP under ambient conditions at altitude, oxygen was delivered and PASP remeasured. Results Of 56 subjects, 36 had Doppler signals appropriate for estimation of pulmonary artery systolic pressure. In these 36, a wide range of PASP was observed (mean 25 mm Hg, range 18–36 mm Hg), but none fell outside of the normal range. After oxygen administration, PASP was reduced (from mean 25 mm Hg to mean 18 mm Hg, P < .0001) suggesting that a degree of hypoxic pulmonary vasoconstriction was present. No subjects in the study group reported clinical AMS. Conclusions We found PASP at 4250 m to be within the normal range but higher than would be expected at sea level; however, unlike previous reports, we found such increases to be mild and reversible with oxygen. In addition, the observed incidence of AMS was low when compared with earlier studies, perhaps related to adequate acclimatization.