Haploid selection within a single ejaculate increases offspring fitness

Diploid organisms produce haploid gametes for sexual reproduction, resulting in a biphasic life cycle. Although selection during the diploid phase is well understood, selection during the haploid gametic stage and its consequences are largely ignored despite its potential importance for fundamental evolutionary processes, including the rate of adaptation and inbreeding depression, as well as for applied research into fertilization technology. A current dogma assumes that in animals selection on the haploid gametic genotype is minimal. We examined the importance of haploid selection in the zebrafish and found strong fitness consequences of selection on sperm phenotype in the resulting offspring. Genomic data support the idea that these effects may well be the consequence of selection on the haploid sperm genotype

Different forms of informal coercion in psychiatry: a qualitative study.

OBJECTIVES: The objective of the study was to investigate how mental health professionals describe and reflect upon different forms of informal coercion. RESULTS: In a deductive qualitative content analysis of focus group interviews, several examples of persuasion, interpersonal leverage, inducements, and threats were found. Persuasion was sometimes described as being more like a negotiation. Some participants worried about that the use of interpersonal leverage and inducements risked to pass into blackmail in some situations. In a following inductive analysis, three more categories of informal coercion was found: cheating, using a disciplinary style and referring to rules and routines. Participants also described situations of coercion from other stakeholders: relatives and other authorities than psychiatry. The results indicate that informal coercion includes forms that are not obviously arranged in a hierarchy, and that its use is complex with a variety of pathways between different forms before treatment is accepted by the patient or compulsion is imposed

Mutating a Conserved Proline Residue within the Trimerization Domain Modifies Na+ Binding to Excitatory Amino Acid Transporters and Associated Conformational Changes

Excitatory amino acid transporters (EAATs) are crucial for glutamate homeostasis in the mammalian central nervous system. They are not only secondary active glutamate transporters but also function as anion channels, and different EAATs vary considerably in glutamate transport rates and associated anion current amplitudes. A naturally occurring mutation, which was identified in a patient with episodic ataxia type 6 and that predicts the substitution of a highly conserved proline at position 290 by arginine (P290R), was recently shown to reduce glutamate uptake and to increase anion conduction by hEAAT1. We here used voltage clamp fluorometry to define how the homologous P259R mutation modifies the functional properties of hEAAT3. P259R inverts the voltage dependence, changes the sodium dependence, and alters the time dependence of hEAAT3 fluorescence signals. Kinetic analysis of fluorescence signals indicate that P259R decelerates a conformational change associated with sodium binding to the glutamate-free mutant transporters. This alteration in the glutamate uptake cycle accounts for the experimentally observed changes in glutamate transport and anion conduction by P259R hEAAT3

Hereditary spastic paraplegia caused by compound heterozygous mutations outside the motor domain of the <em>KIF1A</em> gene.

Background and purpose: Hereditary spastic paraplegia is a clinically and genetically heterogeneous group of rare, inherited disorders causing an upper motor neuron syndrome with (complex) or without (pure) additional neurological symptoms. Mutations in the KIF1A gene have already been associated with recessive and dominant forms of hereditary spastic paraplegia (SPG30) in a few cases. Methods: All family members included in the study were examined neurologically. Whole-exome sequencing was used in affected individuals to identify the responsible candidate gene. Conventional Sanger sequencing was conducted to validate familial segregation. Results: A family of Macedonian origin with two affected siblings, one with slowly progressive and the other one with a more complex and rapidly progressing hereditary spastic paraplegia is reported. In both affected individuals, two novel pathogenic mutations outside the motor domain of the KIF1A gene were found (NM_001244008.1:c.2909G&gt;A, p.Arg970His and c.1214dup, p.Asn405Lysfs*40) that segregate with the disease within the family establishing the diagnosis of autosomal recessive SPG30. Conclusions: This report provides the first evidence that mutations outside the motor domain of the gene can cause (recessive) SPG30 and extends the genotype-phenotype association for KIF1A-related diseases

Idiopathic generalized epilepsy phenotypes associated with different EFHC1 mutations.

We sequenced 61 patients with various idiopathic generalized epilepsy (IGE) syndromes for mutations in the EFHC1 gene. We detected three novel heterozygous missense mutations (I174V, C259Y, A394S) and one possibly pathogenic variant in the 3&#39; UTR (2014t&gt;c). The mutation I174V was also detected in 1 of 372 screened patients with temporal lobe epilepsy. We conclude that mutations in the EFHC1 gene may underlie different types of epilepsy syndromes

Mutations in the CLCN2 gene are a rare cause of idiopathic generalized epilepsy syndromes.

Mutations in the chloride channel gene CLCN2 have been reported in families with generalized and focal epilepsy syndromes. To evaluate the contribution of mutations in the CLCN2 gene to the etiology of epilepsies in our population, we screened 96 patients with different epilepsy syndromes and a putative genetic background. No definite mutations were found in our study population. We conclude that mutations in the CLCN2 gene are only a rare cause of idiopathic generalized epilepsy. &copy; Springer-Verlag 2006