用混合模型定位一个复杂家猪家系13号染色体QTL的研究

用混合模型方法 ,分析了一个复杂家猪家系 13号染色体上微卫星座位与数量性状间的相关性 ,结果发现 ,该家系猪 13号染色体上存在一个显著影响屠宰重和日均屠宰重的QTL。区间定位将该QTL定位到SW1898～SW398标记内 ,相对位置估计为 ρ =0 .5 2± 0 .36 ,在遗传连锁图上的平均位置为 75 .19cM。该QTL对于屠宰重的加性和显性效应分别为 1.31± 0 .5 5kg和 1.95± 0 .80kg ,对于日均屠宰重的加性和显性效应分别为 0 .0 18± 0 .0 0 7kg d和 0 .0 12± 0 .0 0 7kg d。估计的屠宰重和日均屠宰重QTL方差分别 0 .90 37和 0 .0 0 10。该区域实际上是测夹PIT1基因的区域 ,PIT1基因是生长激素、催乳激素、促甲状腺激素 β亚基的一个重要的转录调节因子 ,为PIT1基因作为重要的生长QTL提供了一个有利的旁证。由此推论 ,PIT1对于生长的影响不只是早期的 ,可能延续至个体生长发育的全过程。此外 ,13号染色体上可能存在一个背膘厚QTL ,相距屠宰重QTL约 2 8.3～ 6 3.4cM ,不确定因素是标记 -性状相关在世代间存在差异。     

Distributive Models of Culture: A Sapirian Alternative to Essentialism

The Boasian conception of culture has been roundly criticized in recent years for its essentialist, or even racist, implications. Yet an alternative model that avoids these implications was proposed in the 1930s by Boas student Edward Sapir. Having long survived on the margins of anthropological theory, Sapir's "distributive" concept of culture is now entering the theoretical mainstream through recent developments in both psychological and "postmodernist" anthropology.
By emphasizing the full range of variation within any so-called culture, anthropologists have begun to apply the same style of population thinking that helped launch the Darwinian revolution in biology.     

A Consideration of Alternative Models for the Initiation of Translation in Eukaryotes

Abstract

Although recent biochemical and genetic investigations have produced some insights into the mechanism of initiation of translation in eukaryotic cells, two aspects of the initiation process remain controversial. One unsettled issue concerns a variety of functions that have been proposed for mRNA binding proteins, including some initiation factors. The need to distinguish between specific and nonspecific binding of proteins to mRNA is discussed herein. The possibility that certain initiation factors might act as RNA helicases is evaluated along with other ideas about the functions of mRNA- and ATP-binding factors. A second controversial issue concerns the universality of the scanning mechanism for initiation of translation. According to the conventional scanning model, the initial contact between eukaryotic ribosomes and mRNA occurs exclusively at the 5' terminus of the message, which is usually capped. The existence of uncapped mRNAs among a few plant and animal viruses has prompted a vigorous search for other modes of initiation. An “internal initiation” mechanism, first proposed for picornaviruses, has received considerable attention. Although a large body of evidence has been adduced in support of such a mechanism, many of the experiments appear flawed or inconclusive. Some suggestions are given for improving experiments designed to test the internal initiation hypothesis.     

A Sorrow Shared is a Sorrow Halved: The Search for Empathetic Understanding of Family Members of a Person with Early-Onset Dementia

In this article, I explore how family members of a person with early-onset dementia in the Netherlands attempt to achieve empathetic understanding from significant others, and the barriers they encounter in the process. Based on qualitative interviews, I show that the type of relationship shapes the choices people have to communicate their suffering and their expectations regarding the reactions of others. This article builds on theoretical work on empathy and problematises the notion of shared experiences. It focuses on empathy between family members and significant others, arguing that empathetic understanding between these people is a field of study thus far insufficiently explored.     

Mental Health: The Search for a Definition

Various attempts to define the concept of “mental health” are examined. Value judgments permeate much mental health literature. Their use militates against obtaining an objective definition, capable of universal application. The acceptance of a definition including a value judgment implies taking an attitude toward a particular society and its social ideals.Present limits of competence only allow us to describe “mental health” conceptually. Such “untechnical” proposals are liable to be confused with “technical” (“scientific”) propositions. Multiple criteria are likely to be helpful in improving our concept of “mental health”.The intrusion of morals into the world of health is discussed as part of the contemporary intellectual dilemma of determined human behaviour versus human responsibility and the reality of moral values.It is suggested that “mental health” might consist simply of an individual''s possession of insight into his own personality, combined with an honest recognition and acceptance of his condition.     

The Search for New Screening Models of Pharmacoresistant Epilepsy: Is Induction of Acute Seizures in Epileptic Rodents a Suitable Approach?

Epilepsy, a prevalent neurological disease characterized by spontaneous recurrent seizures (SRS), is often refractory to treatment with anti-seizure drugs (ASDs), so that more effective ASDs are urgently needed. For this purpose, it would be important to develop, validate, and implement new animal models of pharmacoresistant epilepsy into drug discovery. Several chronic animal models with difficult-to-treat SRS do exist; however, most of these models are not suited for drug screening, because drug testing on SRS necessitates laborious video-EEG seizure monitoring. More recently, it was proposed that, instead of monitoring SRS, chemical or electrical induction of acute seizures in epileptic rodents may be used as a surrogate for testing the efficacy of novel ASDs against refractory SRS. Indeed, several ASDs were shown to lose their efficacy on acute seizures, when such seizures were induced by pentylenetetrazole (PTZ) in epileptic rather than nonepileptic rats, whereas this was not observed when using the maximal electroshock seizure test. Subsequent studies confirmed the loss of anti-seizure efficacy of valproate against PTZ-induced seizures in epileptic mice, but several other ASDs were more potent against PTZ in epileptic than nonepileptic mice. This was also observed when using the 6-Hz model of partial seizures in epileptic mice, in which the potency of levetiracetam, in particular, was markedly increased compared to nonepileptic animals. Overall, these observations suggest that performing acute seizure tests in epileptic rodents provides valuable information on the pharmacological profile of ASDs, in particular those with mechanisms inherent to disease-induced brain alterations. However, it appears that further work is needed to define optimal approaches for acute seizure induction and generation of epileptic/drug refractory animals that would permit reliable screening of new ASDs with improved potential to provide seizure control in patients with pharmacoresistant epilepsy.     

A Rhodobacter capsulatus Member of a Universal Permease Family Imports Molybdate and Other Oxyanions

Molybdenum (Mo) is an important trace element that is toxic at high concentrations. To resolve the mechanisms underlying Mo toxicity, Rhodobacter capsulatus mutants tolerant to high Mo concentrations were isolated by random transposon Tn5 mutagenesis. The insertion sites of six independent isolates mapped within the same gene predicted to code for a permease of unknown function located in the cytoplasmic membrane. During growth under Mo-replete conditions, the wild-type strain accumulated considerably more Mo than the permease mutant. For mutants defective for the permease, the high-affinity molybdate importer ModABC, or both transporters, in vivo Mo-dependent nitrogenase (Mo-nitrogenase) activities at different Mo concentrations suggested that ModABC and the permease import molybdate in nanomolar and micromolar ranges, respectively. Like the permease mutants, a mutant defective for ATP sulfurylase tolerated high Mo concentrations, suggesting that ATP sulfurylase is the main target of Mo inhibition in R. capsulatus. Sulfate-dependent growth of a double mutant defective for the permease and the high-affinity sulfate importer CysTWA was reduced compared to those of the single mutants, implying that the permease plays an important role in sulfate uptake. In addition, permease mutants tolerated higher tungstate and vanadate concentrations than the wild type, suggesting that the permease acts as a general oxyanion importer. We propose to call this permease PerO (for oxyanion permease). It is the first reported bacterial molybdate transporter outside the ABC transporter family.Molybdenum (Mo) is utilized by many bacteria, archaea, and eukaryotes as a cofactor of redox enzymes catalyzing key reactions in the nitrogen, sulfur, and carbon cycles (62). Nitrogenase, which catalyzes the reduction of dinitrogen to ammonia, carries the unique iron-molybdenum cofactor FeMoco. In contrast to nitrogenase, all other molybdoenzymes harbor the molybdenum cofactor Moco, which transfers either an oxo group or two electrons to or from the substrate in a wide variety of transformations at nitrogen, sulfur, and carbon atoms (47).The phototrophic alphaproteobacterium Rhodobacter capsulatus serves as a model organism to study Mo metabolism because it synthesizes several molybdoenzymes, including dimethyl sulfoxide reductase, xanthine dehydrogenase, and nitrogenase (29, 30, 46). In addition to Mo-dependent nitrogenase (Mo-nitrogenase), R. capsulatus uses an alternative, Mo-free nitrogenase when Mo is limiting (55, 57). Two related Mo-responsive regulators, MopA and MopB, control expression of the alternative nitrogenase and molybdate uptake genes (22, 57, 58).Mo is available for living cells in its oxyanion form, molybdate. The vast majority of Mo-utilizing bacteria is known or predicted to possess ModABC-type high-affinity molybdate uptake systems (62, 63). These importers belong to the family of ATP-binding cassette (ABC) transporters, which couple ATP hydrolysis to substrate translocation across biological membranes (13, 15). ModABC transporters typically consist of a periplasmic molybdate-binding protein (ModA), a membrane-spanning channel protein (ModB), and a cytoplasmic ATP-binding protein (ModC), which specifically interacts with ModB and, upon ATP hydrolysis, energizes the uptake system.ModABC transporters enable bacteria to actively take up molybdate against a concentration gradient and synthesize active molybdoenzymes at nanomolar Mo concentrations in the environment (37, 49). Accordingly, modABC mutants are not able to make use of molybdoenzymes under Mo-limiting conditions, as shown for several bacteria, including Escherichia coli, Anabaena variabilis, Azotobacter vinelandii, and R. capsulatus (16, 33, 55, 61). High Mo concentrations, however, support synthesis of active molybdoenzymes in modABC mutants, indicating the presence of low-affinity molybdate uptake systems in these bacteria. Low-affinity molybdate uptake in E. coli and several other bacteria is mediated (at least in part) by the sulfate-repressed high-affinity sulfate transporter CysTWA (37, 43, 61).In the present study, we describe the identification and characterization of a permease mediating molybdate uptake at micromolar concentrations in R. capsulatus. The permease belongs to the widely distributed family of ArsB/NhaD permeases (27). Several members of this family have been shown to transport various anorganic and organic anions across biological membranes, but molybdate uptake is a previously unrecognized novel function of these permeases. In addition to molybdate, other oxyanions, like sulfate, tungstate, and vanadate, are likely to be imported by the R. capsulatus permease.     

A BAP1 Mutation in a Danish Family Predisposes to Uveal Melanoma and Other Cancers

Truncating germline mutations in the tumor suppressor gene BRCA-1 associated protein-1 (BAP1) have been reported in families predisposed to developing a wide range of different cancer types including uveal melanoma and cutaneous melanoma. There has also been an association between amelanotic tumor development and germline BAP1 mutation suggesting a possible phenotypic characteristic of BAP1 mutation carriers. Though there have been many types of cancer associated with germline BAP1 mutation, the full spectrum of disease association is yet to be ascertained. Here we describe a Danish family with predominantly uveal melanoma but also a range of other tumor types including lung, neuroendocrine, stomach, and breast cancer; as well as pigmented skin lesions. Whole-exome sequencing identified a BAP1 splice mutation located at c.581-2A>G, which leads to a premature truncation of BAP1 in an individual with uveal melanoma. This mutation was carried by several other family members with melanoma or various cancers. The finding expands on the growing profile of BAP1 as an important uveal and cutaneous melanoma tumor suppressor gene and implicates its involvement in the development of lung, and stomach cancer.