Three-dimensional structure of RTD-1, a cyclic antimicrobial defensin from rhesus macaque leukocytes

Most mammalian defensins are cationic peptides of 29-42 amino acids long, stabilized by three disulfide bonds. However, recently Tang et al. (1999, Science 286, 498-502) reported the isolation of a new defensin type found in the leukocytes of rhesus macaques. In contrast to all the other defensins found so far, rhesus theta defensin-1 (RTD-1) is composed of just 18 amino acids with the backbone cyclized through peptide bonds. Antibacterial activities of both the native cyclic peptide and a linear form were examined, showing that the cyclic form was 3-fold more active than the open chain analogue [Tang et al. (1999) Science 286, 498-502]. To elucidate the three-dimensional structure of RTD-1 and its open chain analogue, both peptides were synthesized using solid-phase peptide synthesis and tert-butyloxycarbonyl chemistry. The structures of both peptides in aqueous solution were determined from two-dimensional H-1 NMR data recorded at 500 and 750 MHz. Structural constraints consisting of interproton distances and dihedral angles were used as input for simulated-annealing calculations and water refinement with the program CNS. RTD-1 and its open chain analogue oRTD-1 adopt very similar structures in water. Both comprise an extended beta -hairpin structure with turns at one or both ends. The turns are well defined within themselves and seem to be flexible with respect to the extended regions of the molecules. Although the two strands of the beta -sheet are connected by three disulfide bonds, this region displays a degree of flexibility. The structural similarity of RTD-1 and its open chain analogue oRTD-1, as well as their comparable degree of flexibility, support the theory that the additional charges at the termini of the open chain analogue rather than overall differences in structure or flexibility are the cause for oRTD-1's lower antimicrobial activity. In contrast to numerous other antimicrobial peptides, RTD-1 does not display any amphiphilic character, even though surface models of RTD-1 exhibit a certain clustering of positive charges. Some amide protons of RTD-1 that should be solvent-exposed in monomeric beta -sheet structures show low-temperature coefficients, suggesting the possible presence of weak intermolecular hydrogen bonds.

The calculation of accident risks in fitness for work assessments: diseases that can cause sudden incapacity

Risk equations have been developed to assist in determining fitness for work of people with diseases that may cause rapid loss of control. The four equations calculate the frequency of fatal injury to the person with the disease, the frequency of fatal injury to colleagues in the workplace, and the cost of fatal injury and property damage to the employer, it is suggested that the additional risk of fatal injury to the person with the disease should not exceed the fatal injury rate in high-risk industries such as forestry, fishing and mining. it is also suggested that the additional risk of fatal injury to each colleague should be no more than one-tenth of the fatal injury rate due to motor vehicle accidents in the community. Two hypothetical case examples are given, demonstrating the use of the equations. The equations highlight the need to examine the risks associated with individuals, their specific jobs and their workplaces. They also highlight significant uncertainties in the determination of fitness, which perhaps have been underestimated in the past. Wherever possible, redundant defences should be utilized to prevent accidents in the event of sudden incapacity.

Parasite infection rather than tactile stimulation is the proximate cause of cleaning behaviour in reef fish

Cleaning behavior is a popular example of non-kin cooperation. However, quantitative support for this is generally sparse and the alternative, that cleaners are parasitic: has also been proposed. Although the behaviour involves some of the most complex and highly developed interspecific communication signals known, the proximate causal factors for why clients Seek cleaners are controversial. However, this information is essential to understanding the evolution of cleaning. I tested whether clients seek cleaners in response to parasite infection or whether clients seek cleaners for tactile stimulation regardless of parasite load. Parasite loads oil client fish were manipulated and clients exposed to cleaner fish and control fish hehind glass. I found that parasitized client fish spent more time than unparasitized fish next to a cleaner fish. In addition; parasitized clients spent more rime next to cleaners than next to control fish whereas unparasitized fish were not attracted to cleaners. This study shows, I believe for the first time, which is somewhat surprising, that parasite infection alone causes clients to seek cleaning by cleaners and provides insight into how this behaviour evolved.

Mutations in the human ortholog of Aristaless cause X-linked mental retardation and epilepsy

Mental retardation and epilepsy often occur together. They are both heterogeneous conditions with acquired and genetic causes. Where causes are primarily genetic, major advances have been made in unraveling their molecular basis. The human X chromosome alone is estimated to harbor more than 100 genes that, when mutated, cause mental retardation(1). At least eight autosomal genes involved in idiopathic epilepsy have been identified(2), and many more have been implicated in conditions where epilepsy is a feature. We have identified mutations in an X chromosome-linked, Aristaless-related, homeobox gene (ARX), in nine families with mental retardation (syndromic and nonspecific), various forms of epilepsy, including infantile spasms and myoclonic seizures, and dystonia. Two recurrent mutations, present in seven families, result in expansion of polyalanine tracts of the ARX protein. These probably cause protein aggregation, similar to other polyalanine(3) and polyglutamine(4) disorders. In addition, we have identified a missense mutation within the ARX homeodomain and a truncation mutation. Thus, it would seem that mutation of ARX is a major contributor to X-linked mental retardation and epilepsy.

Rumors and stable-cause attribution in prediction and behavior

Two stock-market simulation experiments investigated the notion that rumors that invoke stable-cause attributions spawn illusory associations and less regressive predictions and behavior. In Study 1, illusory perceptions of association and stable causation (rumors caused price changes on the day after they appeared) existed despite rigorous conditions of nonassociation (price changes were unrelated to rumors). Predictions (recent price trends will continue) and trading behavior (departures from a strong buy-low-sell-high strategy) were both anti-regressive. In Study 2, stability of attribution was manipulated via a computerized tutorial. Participants taught to view price-changes as caused by stable forces predicted less regressively and departed more from buy-low-sell-high trading patterns than those taught to perceive changes as caused by unstable forces. Results inform a social cognitive and decision theoretic understanding of rumor by integrating it with causal attribution, covariation detection, and prediction theory. (C) 2002 Elsevier Science (USA). All rights reserved.

Taking Darwin seriously: More than telling just so stories

No Abstract

Sertoli-Leydig Cell Tumor of the Ovary, a Rare Cause of Precocious Puberty in a 12-Month-Old Infant

We report a 12-month-old infant who presented with a 4-month history of isosexual precocious puberty secondary to an estrogenizing Sertoli-Leydig cell tumor of the ovary. Total serum immunoreactive inhibin and subunits A and B were markedly elevated before surgical resection and subsequently decreased 7 wk later into the normal prepubertal range. Twenty weeks following surgical removal, the patient presented again with central precocious puberty; inhibin B levels were raised on this occasion, a luteinizing releasing hormone stimulation test confirmed central precocious puberty. This is the youngest reported occurrence of this rare sex cord stromal neoplasm. The prognosis of this extremely rare tumor presenting at this early juvenile stage is uncertain. This report illustrates the usefulness of serum inhibin as a tumor marker during therapeutic suppression with leuprorelin acetate for central precocious puberty. Analysis of genomic and tumor DNA revealed a normal nucleotide sequence for the LH receptor and the G{alpha}s gene. To understand the molecular pathogenesis of this tumor we analyzed mRNA levels for the inhibin A and B subunits, FSH receptor, LH receptor aromatase, steroidogenic factor-1 and the ER ß genes. Molecular characterization reveals the presence of genes specific for granulosa and Leydig cells; the relative expression of these genes, in addition to its histologic characteristics, suggests that this tumor may result from a dysdifferentiation of a primordial follicle.

Preventing drug misuse by young people: we need to do more than 'just say no'

No Abstract