Localization of glyoxylic acid-induced histofluorescence in surgically isolated medial basal hypothalamus of the rat

Summary Examination of glyoxylic acid-induced catecholamine histofluorescence in the hypothalamic median eminence of adult male rats revealed a linear pattern of fine varicosities coursing through the ependymal and fibrous zones, suggestive of juxtaposition to tanycytes. In order to determine the origin of these terminals, adult rats were subjected to complete isolation of the medial basal hypothalamus, using a small Halasz-Pupp knife. As rapidly as 24h after this deafferentation degenerative axon profiles were observed dorsal, as well as anterior and lateral, to the knife track. Occasionally at three days postoperatively, and routinely by seven days after surgery, fine-sized new fibres were seen passing through the knife wound. The linear profiles of varicosities observed in the normal median eminence remained traceable in the experimental preparations; the site of origin for these terminals therefore appears to be neurons of the arcuate (A12) and rostral periventricular (A14) regions. The results also indicate that fibres innervating the isolated area are capable of morphologically demonstrable new growth. The observations bear functional implications in assessing endocrine regulation following MBH isolation of the type used in this study.This study was supported by USPHS Postdoctoral Fellowship 5-F₂2-HD00630 (CT) and USPHS Grant NS-11642 (JRS). The authors wish to express their appreciation to Yvonne Cheung and Patricia Walker for technical assistance     

Hypothalamic and hormonal control of photoperiodically induced vernal functions in the white-crowned sparrow,Zonotrichia leucophrys gambelii

Summary The effects of implantation of testosterone propionate (TP) in various sites in the hypothalamus on the photoperiodically induced vernal premigratory functions in the White-crowned Sparrows were investigated in order to assess the role of the hypothalamo-hypophysial-testicular axis in the induction of these responses.Implantation of glass capillary tubes containing TP in the basal infundibular nucleus (IN), in the median eminence, or in the pars distalis inhibited the photoperiodically induced increase in plasma levels of luteinizing hormone (LH), as measured by radioimmunoassay, and testicular growth. The effective implants significantly lowered the levels of LH in birds held on nonstimulatory short days. These TP implants apparently inhibited release from the pars distalis of both LH and follicle-stimulating hormone (FSH). It is concluded that the site of sensitivity in the negative feedback by testosterone is either the basal IN or the pars distalis, or both. The implants of TP that inhibited the increase in plasma LH and testicular growth completely did not prevent the birds from fattening.These investigations were supported, in part, by research grants from the National Institutes of Health (HD-6527) and National Science Foundation (BMS 79-13933) to Professor Donald S. Farner. This paper is based on a dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy from the University of WashingtonThe author is grateful to Professor Donald S. Farner for his guidance throughout the course of these investigations. The assistance of Mr. Philip W. Mattocks, Jr. in performing radioimmunoassays is sincerely appreciated     

Likelihood-based experimental design for estimation of ED50

In selecting the best dosage choice for the estimation of ED50, it is natural to try to minimize the length of the confidence intervals. In this presentation, the dose allocation that minimizes the length of the likelihood-based confidence intervals is presented and compared with alternative allocations that have been proposed based on the length of different types of confidence intervals, such as those based on the asymptotic variance or on Fieller's Theorem. Effective strategies to deal with the parameter dependence of these allocations are explored. A series of experiments to evaluate the effect of small doses per fraction on the radiation tolerance of the rat cervical spinal cord provide the motivation and an illustration for the proposed procedures.     

Reduced sensitivity to hidden bias at upper quantiles in observational studies with dilated treatment effects

When a treatment has a dilated effect, with larger effects when responses are higher, there can be much less sensitivity to bias at upper quantiles than at lower quantiles; i.e., small, plausible hidden biases might explain the ostensible effect of the treatment for many subjects, and yet only quite large hidden biases could explain the effect on a few subjects having dramatically elevated responses. An example concerning kidney function of cadmium workers is discussed in detail. In that example, the treatment effect is far from additive: It is plausibly zero at the lower quartile of responses to control, and it is large and fairly insensitive to bias at the upper quartile.     

High levels of Paleolithic Y-chromosome lineages characterize Serbia

Whether present-day European genetic variation and its distribution patterns can be attributed primarily to the initial peopling of Europe by anatomically modern humans during the Paleolithic, or to latter Near Eastern Neolithic input is still the subject of debate. Southeastern Europe has been a crossroads for several cultures since Paleolithic times and the Balkans, specifically, would have been part of the route used by Neolithic farmers to enter Europe. Given its geographic location in the heart of the Balkan Peninsula at the intersection of Central and Southeastern Europe, Serbia represents a key geographical location that may provide insight to elucidate the interactions between indigenous Paleolithic people and agricultural colonists from the Fertile Crescent. In this study, we examine, for the first time, the Y-chromosome constitution of the general Serbian population. A total of 103 individuals were sampled and their DNA analyzed for 104 Y-chromosome bi-allelic markers and 17 associated STR loci. Our results indicate that approximately 58% of Serbian Y-chromosomes (I1-M253, I2a-P37.2 and R1a1a-M198) belong to lineages believed to be pre-Neolithic. On the other hand, the signature of putative Near Eastern Neolithic lineages, including E1b1b1a1-M78, G2a-P15, J1-M267, J2-M172 and R1b1a2-M269 accounts for 39% of the Y-chromosome. Haplogroup frequency distributions in Western and Eastern Europe reveal a spotted landscape of paleolithic Y chromosomes, undermining continental-wide generalizations. Furthermore, an examination of the distribution of Y-chromosome filiations in Europe indicates extreme levels of Paleolithic lineages in a region encompassing Serbia, Bosnia-Herzegovina and Croatia, possibly the result of Neolithic migrations encroaching on Paleolithic populations against the Adriatic Sea.     

Fatigue of the plantar intrinsic foot muscles increases navicular drop

Our purpose was to assess the effect of foot intrinsic muscle fatigue on pronation, as assessed with navicular drop, during static stance. Twenty-one healthy young adults participated. Navicular drop was measured before and after fatiguing exercise of the plantar foot intrinsic muscles. Surface electromyography of the abductor hallucis muscle was recorded during maximum voluntary isometric contractions (MVIC) in order to find the baseline median frequency (MedF). Subjects then performed sets of 75 repetitions of isotonic flexion contractions of the intrinsic foot muscles against a 4.55 kg weight on a custom pulley system. After each set an MVIC was performed to track shifts in MedF. After a MedF shift of at least 10%, navicular drop measurements were repeated. Subjects exhibited 10.0 ± 3.8 mm of navicular drop at baseline and 11.8 ± 3.8 mm after fatigue (p < 0.0005). The change in navicular drop was significantly correlated with change in MedF (r = .47, p = .03). The intrinsic foot muscles play a role in support of the medial longitudinal arch in static stance. Disrupting the function of these muscles through fatigue resulted in an increase in pronation as assessed by navicular drop.     

Median Tests for Censored Survival Data; a Contingency Table Approach

Summary The median failure time is often utilized to summarize survival data because it has a more straightforward interpretation for investigators in practice than the popular hazard function. However, existing methods for comparing median failure times for censored survival data either require estimation of the probability density function or involve complicated formulas to calculate the variance of the estimates. In this article, we modify a K ‐sample median test for censored survival data ( Brookmeyer and Crowley, 1982 , Journal of the American Statistical Association 77, 433–440) through a simple contingency table approach where each cell counts the number of observations in each sample that are greater than the pooled median or vice versa. Under censoring, this approach would generate noninteger entries for the cells in the contingency table. We propose to construct a weighted asymptotic test statistic that aggregates dependent χ² ‐statistics formed at the nearest integer points to the original noninteger entries. We show that this statistic follows approximately a χ² ‐distribution with k? 1 degrees of freedom. For a small sample case, we propose a test statistic based on combined p ‐values from Fisher’s exact tests, which follows a χ² ‐distribution with 2 degrees of freedom. Simulation studies are performed to show that the proposed method provides reasonable type I error probabilities and powers. The proposed method is illustrated with two real datasets from phase III breast cancer clinical trials.     

中国甜菜夜蛾地理种群的遗传分化与基因流

【目的】为了明确我国甜菜夜蛾Spodoptera exigua地理种群间的遗传分化及基因流,阐明该种害虫在我国的种群历史动态。【方法】本研究对采自我国20个地理种群的529头甜菜夜蛾样品进行线粒体COI基因序列测定与分析,利用DnaSP 5.0和Arlequin 3.11软件分析种群间遗传多样性、遗传分化、基因流水平及分子变异,构建了单倍型系统发育树与单倍型网络图。【结果】在所分析的所有529个序列样本中,共检测出10个单倍型,其中Hap_1为所有种群所共享。总群体遗传多样性较低（Hd=0.257±0.025,Pi=0.0007±0.0001,Kxy=0.323）,群体间遗传分化较小（F_ST=0.211）,基因流水平较高（N_m=1.870）。AMOVA分析表明,甜菜夜蛾遗传变异主要来自种群内,种群间变异水平较低。各种群间遗传分化程度与地理距离无显著相关性（R²=0.005,P>0.05）。各单倍型相互散布在不同种群中,未形成明显系统地理结构。中性检验（Tajima’s D=-2.177, P<0.05; Fu’s F_S=-8.629, P<0.05)与错配分布分析表明,我国甜菜夜蛾种群曾经历种群近期扩张。【结论】研究结果揭示,甜菜夜蛾各种群间的基因交流并未受到地理距离的影响,验证了甜菜夜蛾具有高度的迁飞能力。     

The hypophyseal pars tuberalis is enriched with distinct phosphotyrosine-containing proteins not detected in other areas of the brain and pituitary

The regulation of cell activity, growth and metabolism by a number of growth factor receptors and proto-oncogene products involves tyrosine kinase activity resulting in autophosphorylation of the receptors and production of phosphorylated tyrosine-containing protein substrates. The identification and precise localization of phosphotyrosine (PY)-containing proteins are first steps in elucidating the functional role of tyrosine kinases in the modulation of the central nervous system and related areas. In the present report, we describe PY-containing proteins in the median eminence and adjacent pars tuberalis of the rat adenohypophysis by immunocytochemistry using light and electron microscopy, and by Western blotting analysis. PY-immunoreactivity was found to be most intense throughout the cytoplasm of a population of epithelial pars tuberalis cells. Polyacrylamide gel electrophoresis and Western blotting of tissue extracts from various brain and pituitary regions demonstrated a general pattern of 4 major bands of PY-proteins, with an additional dense band representing a 44 kDa protein that was highly phosphorylated on tyrosines and that was exclusively found in the pars tuberalis. Additional investigation for the presence of insulin receptors, a tyrosine kinase previously correlated with the distribution of PY-proteins, demonstrated a receptor localization in axons and nerve terminals in the external and internal zone of the median eminence. However, the large amount of different PY-proteins present in the secretory cell population of the pars tuberalis could not be attributed to the insulin receptor. Our findings demonstrate that there is a large amount of cell-specific tyrosine kinase activity in the median eminence and contacting the pars tuberalis; these may play a significant role for transduction of biological signals or metabolic regulation in the neuroendocrine region.This paper is dedicated to Professor Dr. Leonhardt on the occasion of his 75th birthday