Low dose β blockade in acute stroke (“BEST” trial): an evaluation

The β blocker stroke (“BEST”) trial was designed to see if the apparent protective effect of propranolol on cerebral function in patients with subarachnoid haemorrhage applied also to patients suffering from acute stroke. Three hundred and two conscious patients with clinically diagnosed hemispheric strokes sustained within the past 48 hours were randomly assigned to receive atenolol, propranolol, or matching placebo capsules for three weeks. More early deaths occurred among the patients allocated to receive β blockers, but this was largely explained by differences in the initial characteristics of the patients among the different treatment groups. By contrast, the outcome in a further 60 patients, who had been taking β blockers at the time of their stroke but were otherwise similar to the patients in the trial, was considerably better, suggesting that prior treatment with β blockers might be protective.The search for an effective medical treatment for acute stroke must continue. The approach used here, in which neurological outcome was assessed in a modest number of patients with a view to proceeding subsequently to a full scale trial of functional outcome, allows practical benefits of a treatment to be evaluated under realistic conditions and an ineffective treatment to be eliminated without undue cost.     

Engineering an ultra-thermostable β(1)-adrenoceptor

Conformational thermostabilisation of G-protein-coupled receptors is a successful strategy for their structure determination. The thermostable mutants tolerate short-chain detergents, such as octylglucoside and nonylglucoside, which are ideal for crystallography, and in addition, the receptors are preferentially in a single conformational state. The first thermostabilised receptor to have its structure determined was the β₁-adrenoceptor mutant β₁AR-m23 bound to the antagonist cyanopindolol, and recently, additional structures have been determined with agonist bound. Here, we describe further stabilisation of β₁AR-m23 by the addition of three thermostabilising mutations (I129V, D322K, and Y343L) to make a mutant receptor that is 31 °C more thermostable than the wild-type receptor in dodecylmaltoside and is 13 °C more thermostable than β₁AR-m23 in nonylglucoside. Although a number of thermostabilisation methods were tried, including rational design of disulfide bonds and engineered zinc bridges, the two most successful strategies to improve the thermostability of β₁AR-m23 were an engineered salt bridge and leucine scanning mutagenesis. The three additional thermostabilising mutations did not significantly affect the pharmacological properties of β₁AR-m23, but the new mutant receptor was significantly more stable in short-chain detergents such as heptylthioglucoside and denaturing detergents such as SDS.     

A survey of a familial transmission of an anomalous autosome in group 13–15

A male child hospitalized due to undescended testes (cryptorchism) was found to possess an abnormal autosome with an unusually elongated short arm in group 13–15. A familial chromosome investigation undertaken in 14 persons related to the propositus in his paternal line and in his mother revealed that his clinically normal father, grandfather, 2 aunts and a female cousin carried the same aberrant autosome. It is evident that a carrier of the abnormal chromosome is the grandfather, that the anomalous element was transmitted, irrespective of sex, from the parents either one of whom carried the aberrant one, and that the particular autosomal abnormality is not always associated with specific phenotypic anomaly. A possible origin of the aberrant autosome is discussed.Contribution no. 733 from the Zoological Institute, Faculty of Science, Hokkaido University, Sapporo.The senior author (S. M.) wishes to dedicate this paper to Dr. Jakob Seiler on the occasion of his 80th birthday, May 16, 1966.     

Ashkenazi levites’ “Y modal haplotype” (LMH) – an artificially created phenomenon?

The article on the Y chromosomes of Ashkenazi Levites (Behar et al., 2003. Am. J. Hum. Genet. 73, 768-779) is the fourth in a series on the Y chromosomes of the three Jewish male castes: Cohanim (priests), Levites (priests' helpers) and Israelites (lay people). It became apparent that there is a problem with omission of samples when the second article "Origins of Old Testament priests" (Thomas et al., 1998. Nature 394, 138-140) was published. In the fourth article a remarkable 55% of the Ashkenazi Levite samples from the earlier 1998 study are not included. This causes the "Levite modal haplotype" to double its frequency from 21% of the Ashkenazi Levite sample in 1998 to 42% of the Ashkenazi Levite sample in 2003. The authors offer three main explanations: The explanations offered to the problem of omitting samples from subsequent studies after their haplotypes or partial haplotypes are known, are not convincing. Consequently their sample sets cannot be considered random and non-biased. At the least, these laboratories have bad practices of sample handling and many typing errors, which are enough to invalidate their studies.     

Cytologische untersuchungen an einem pentaploiden Rosenbastard (Rosa hybr. “315”) und seiner Nachkommenschaft

Zusammenfassung In Übereinstimmung mit der morphologischen Analyse ergab die cytologische Untersuchung für einen alsR. pomifera subsp.pomifera × pendulina gedeuteten, hier alsR. hybr. 315 bezeichneten Rosenbastard die somatische Chromosomenzahl 2n=35 und die meiotische Paarung zu 14 Bivalenten und 7 Univalenten.Abgesehen von dem veränderten Mengenverhältnis zwischen Bi-und Univalenten lief die Meiosis in den Pollenmutterzellen nach dem Caninaeschema ab.Die Univalenten wurden teils in der 1., teils in der 2. Anaphase eliminiert und meistens sehr schnell im Plasma gelöst. Bildung zusätzlicher Kerne aus ihnen trat nur selten auf, so daß die Meiosis in der Regel mit der Entstehung von 4 Kernen abschloß. Diese enthielten fast ausschließlich 14 — in einem Fall 12 — Chromosomen.In der anschließenden Cytokinese entstanden überwiegend regelmäßige Tetraden. Die Pollenfertilität lag mit 83% morphologisch guten Pollens außerordentlich hoch.Die Tetraploidie der BastardeR. hybr. Schweizer Gruß × 315 bewies in Ergänzung der direkten cytologischen Beobachtungen an der Mikrosporogenese, daß der funktionsfähige Pollen vonR. hybr. 315 14-chromosomig ist.Bei freiem Abblühen entwickelten sich aus allen Blüten Hagebutten, die 5–12 in Wasser untersinkende Nüßchen enthielten.Von vier der bei freiem Abblühen gebildeten Sämlinge waren einer pentaploid (2n=35), zwei tetraploid (2n=28) und einer triploid (2n=21). Unter der Voraussetzung, daß auch die Makrosporogenese derR. hybr. 315 dem Caninaeschema folgt und wahrscheinlich zu 21-chromosomigen Eikernen führt, sind der pentaploide mit Selbstbefruchtung und die tetraploiden Sämlinge mit Fremdbefruchtung durch 7-chromosomige Pollenkörner zu erklären. Die Triploidie des 4. Sämlings macht die zu überprüfenden Annahmen einer inversen Verteilung aller Univalenten bei der Makrosporogenese oder einer Gonenkonkurrenz erforderlich.Mit 4 Textabbildungen in 26 Einzeldarstellungen.     

Lipoprotein(a): still an enigma?

PURPOSE OF REVIEW: Lipoprotein(a) belongs to the class of the most atherogenic lipoproteins. Despite intensive research - in the last year more than 80 papers have been published on this topic - information is still lacking on the physiological function of lipoprotein(a) and the site of its catabolism. Important advances have been made in the knowledge of these points, which may have some therapeutic implications. RECENT FINDINGS: The association of high lipoprotein(a) values with an increase in risk for coronary events has been documented in further prospective studies. This increased risk may relate to recent findings that apolipoprotein(a) is produced in situ within the vessel wall. In addition, lipoprotein(a) binds and inactivates the tissue factor pathway inhibitor and induces plasminogen activator inhibitor type 2 expression in monocytes. A new antisense oligonucleotide strategy has been proposed which efficiently inhibits apolipoprotein(a) expression in vitro and in vivo. Apolipoprotein(a), however, suppresses angiogenesis and thus may interfere with the infiltration of tumor cells. Finally, the enzymatic activity leading to the formation of apolipoprotein(a) fragments in plasma and their catabolism have been further elucidated. SUMMARY: We are still far away from understanding the pathways involved in lipoprotein(a) catabolism, and the physiological function of this lipoprotein. Recent findings, however, provide new insight into pathomechanisms in patients with increased lipoprotein(a) related to hemostasis, which may serve as a basis for designing new treatment strategies.     

Cinematographic observation of an “activation wave” (AW) on the locally inseminated egg ofXenopus laevis

Summary Shortly after local artificial insemination, but well before egg rotation,Xenopus eggs show a wave-like propagation of dark-light-dark zones from the site of sperm entrance. This presumably reflects the movement of the front of cortical granule breakdown.     

Empirical modelling using dummy atoms (EMUDA): an alternative approach for studying “auxetic” structures

Auxetics (materials or structures) are systems with a negative Poisson's ratio, a property that arises from the way various geometric features in the structure (or internal structure in the case of materials) deform when subjected to uniaxial loads. Such systems are normally studied by examining the behaviour of idealised representations of structures, which deform in a controlled fashion (e.g. deforming solely through hinging or stretching). Methods used for the analysis typically involve construction of real physical macro-models and/or derivation of analytical expressions for the mechanical properties. This paper proposes an alternative method for analysing such structures whereby idealised “hinging” or “stretching” structures are constructed within a molecular modelling environment using dummy atoms and examined using standard molecular mechanics techniques. We will show that this methodology of “empirical modelling using dummy atoms” (EMUDA) successfully reproduces the known properties of 2D conventional and auxetic hexagonal honeycombs hence confirming the suitability of this technique for studying auxetic structures.     

“Unwarranted survivals” and “anomalous deaths” from coronary heart disease: prospective survey of general population

ObjectivesTo assess survival in people who are at apparent high risk who do not develop coronary heart disease (“unwarranted survivals”) and mortality in people at low risk who die from the disease (“anomalous deaths”) and the extent to which these outcomes are explained by other, less visible, risk factors.DesignProspective general population survey.SettingRenfrew and Paisley, Scotland.Participants6068 men aged 45-64 years at screening in 1972-6, allocated to “visible” risk groups on the basis of body mass index and smoking.ResultsVisible risk was a good predictor of mortality: 13% (45) of men at low risk and 45% (86) of men at high risk had died by age 70 years. Of these deaths, 12 (4%) and 44 (23%), respectively, were from coronary heart disease. In the group at low visible risk other less visible risk factors accounted for increased risk in 83% (10/12) of men who died from coronary heart disease and 29% (84/292) of men who survived. In the high risk group 81/107 who survived (76%) and 19/44 (43%) who died from coronary heart disease had lower risk after other factors were considered. Different risk factors modified risk (beyond smoking and body mass index) in the two groups. Among men at low visible risk, poor respiratory function, diabetes, previous coronary heart disease, and socioeconomic deprivation modified risk. Among men at high visible risk, height and cholesterol concentration modified risk.ConclusionsDifferences in survival between these extreme risk groups are dramatic. Health promotion messages would be more credible if they discussed anomalies and the limits of prediction of coronary disease at an individual level.

What is already known on this topic

People pay attention to visible risk factors, such as smoking and weight, in explaining or predicting coronary events but are aware that these behavioural risk factors fail to explain some early deaths from coronary heart disease (in those with “low risk” lifestyles) and long survival (in those with “high risk” lifestyles)Such violations to notions of coronary candidacy undermine people''s belief in the worth of modifying behavioural risk factors for coronary heart disease

What this study adds

Visible risk status was a good marker for other coronary risk factors at the extremes of the risk distributionMost men at low visible risk (slim, never smoked) who died prematurely from coronary heart disease had poorer risk profiles on other less visible risk factors; similarly, men at high visible risk (obese, heavy smokers) who survived often had more favourable profiles on other risk factors     

„Kragen” an Atrypiden aus Schillen des Unteren Plattenkalkes (Givet) von Bergisch Gladbach (Rheinisches Schiefergebirge)

In the Lower Plattenkalk of Bergisch Gladbach occur, besides the well known?Hians”-beds, polymictic accumulations of shell material. Together with the valves ofMartinia inflata (Schnur),Uncinulus parallelepipedus (Br.) andIsopoma brachyptyctum (Schnur) are great numbers ofSpinatrypa tubaecostata (Paeck.) andAtrypa prisca gladbachensis n. subsp. In spite of the fact that the host rock was deposited as shell debris, in particular the rhynchonellids and atrypids are easily separated from it in a well preserved state. Atrypa (Desquamatia) prisca gladbachensis n. subsp. is commonly found with its alations intact. This subspecies, which is here described in some detail, fluorisched on a marly ooze bottom. The expanded valves increased the food gathering field, while the alations, surrounding the shell margin almost like a flange, functioned as effective particle filters. Because of this, the free valves floated under wave attack and became fossilized almost undamaged. The brachiopod shells and the organoplastic debris were washed on to discontinuity surfaces which probably had already been lithified by algal growth.     

“膈”与“隔”、“栅(zhà)”与“栅(shān)”辨析

在生物课的学习过程中,常见有许多同学乃至个别教师在作业、试卷、读书当中,将“膈膜”写作“隔膜”,将“栅（zha）栏组织”读作“栅（shan）栏组织”。笔者在此提出异议与各位同学及同仁商榷。“膈”,也叫“横隔膜”,是人和哺乳动物的胸腔和腹腔之间的肌膜结构,它是一块骨路肌,属于名词。而“隔”是“分开”、“间隔”的意思,属于动词。因此,人和哺乳动物胸腔和腹腔的特有结构应是“隔”,而不是“隔”。关于“栅”,在《现代汉语词典》中,有两种读音、两种解释：（l）栅（Zhd）：［栅栏」：用铁条或木条做成的类似篱笆而较坚固…     

Cyprinotus incongruens (Ostracoda): an ancient asexual?

Although unisexual ostracods are common, their evolutionary history is now known only from inferences gained through examination of the fossil record. Here we use mtDNA, allozyme and genome size analyses to investigate the origins of unisexuality, polyploidy and clonal diversity in the freshwater ostracod Cyprinotus incongruens . Our genetic evidence suggests that transitions to polyploidy have been common in this taxon and may sometimes involve internal genome-fusion events, in contrast to the usual origin of animal polyploids through interspecific hybridization. Both the extent and congruent patterns of allozyme and mtDNA divergence amongst clones of C. incongruens are consistent with its persistence as an asexual taxon for approximately 5 million years. However, the detected patterns of genetic variation might also reflect the origins of this ostracod through a series of independent transitions to asexuality by several closely related ancestral taxa. The results make it clear that efforts to demonstrate the antiquity of asexual taxa, solely from surveys of the extent of genetic divergence among their component lineages, will ordinarily be ambiguous, requiring confirmation through investigations which search the genome for the genetic consequences of long abandoned recombination.     

“客家人”的习俗(二)

美丽的“笠披”与弯襟衣经过上千年的发展、变化,闽西南客家人的着装与当地人相差无几,只是妇女的服装头帕别具风采。客家女至今仍穿着弯襟布扣的衣裳。这种衣裳用黑或蓝色粗布,手工裁剪而成。它的前襟开口由右边向腋下弯曲(与旗袍式样略同),用布打结成扣子和扣眼,一件衣服一般由7或9个布扣连在一起。布扣的形状、式     

“客家人”的习俗(一)

据史料载,从晋朝至清末的千余年间,黄河中下游一带由于战乱、饥荒等原因,汉族人先后出现五次大规模南迁,辗转来到赣、闽、粵和台湾等地。“先居是主,后来是客”,他们被当地人称为“客家”。目前,客家人散居在全世界的几十个国家和地区,总人口约4700万;我国约有客家人口3500万以上,他们的衣食起居、精神风貌无不体现古代中原的文化传统。这里记述的是居住在闽西南山区的客家人保留至今的独特风俗。     

“溴”结构域(bromo-domain)简介

“溴”结构域是近 10年来发现的广泛存在于多种真核生物中的保守结构域 ,由 6 0～ 110个高度保守的氨基酸残基组成 ,有形成双性α螺旋的潜能 .常见的“溴”结构域含 6 0或 110个氨基酸残基 .“溴”结构域蛋白一般有 1～5个“溴”结构域拷贝 ,这类蛋白质“溴”基序所在位置变异颇多 ,已经登录的“溴”结构域蛋白有 5 0余种 .“溴”结构域的空间结构相似 .含 6 0或 110个氨基酸残基的“溴”结构域可分别形成两个或四个反向平行的α螺旋 .Ｐ/ＣＡＦ“溴”结构域的空间构型为左手旋转反向平行的上下四螺旋束状结构 ,由αＺ、αＡ、αＢ和αＣ四…     

Über Untersuchungen an Zuchtmaterial von cumarinarmem („süßem”) Steinklee(Melilotus)

Zusammenfassung Eine Zusammenstellung von Ergebnissen zeigt, daß es weitestgehend gelungen ist, einen cumarinarmen Steinklee zu züchten. Es wird die Untersuchungsmethodik in qualitativer und quantitativer Hinsicht beschrieben und auf das Auftreten von Wechseltypen innerhalb des süßen Zuchtmaterials hingewiesen, denen besondere Beachtung im Rahmen der Züchtung geschenkt werden muß.Was die Untersuchungen des Blatt- und Stengel-anteils der verschiedenen Arten betrifft, so tragen diese Ergebnisse einen vorläufigen Charakter.Mit 13 Abbildungen     

“Veils” Against Predators: Modified Web Structure of a Host Spider Induced by an Ichneumonid Parasitoid, Brachyzapus nikkoensis (Uchida) (Hymenoptera)

When the larva of Brachyzapus nikkoensis, a koinobiont ectoparasitoid of Agelena limbata forming a funnel web, is a penultimate instar, “veils” of very fine and dense threads covering the spider and parasitoid larva were observed in the tunnel of funnel web. As the veils are not formed until the parasitoid became penultimate instar and the parasitoid larvae are on active hosts at this stage, the veils are considered to be formed by the spider under the manipulation of the parasitoid larva. Removal of the veil indicated that penultimate larvae and pupae were more likely to fail to emerge in manipulated webs compared to the controls. The modified web seems resistant against predators and scavengers such as ants. This is the first record of web modification demonstrating its resistance to predators.