Stretching the boundaries of elastin function

Elastin is an essential determinant of arterial morphogenesisLi, D.Y. et al. (1998)Nature 393, 276–280An elastin gene mutation producing abnormal tropoelastin and abnormal elastic fibres in a patient with autosomal dominant cutis laxaTassabehji, M. et al. (1998)Hum. Mol. Genet. 7, 1021–1028     

Making an impression on X-linked mental retardation

Oligophrenin-1 encodes a rhoGAP protein involved in X-linked mental retardationBilluart, P. (1998)Nature 392, 923–926PAK3 mutation in nonsyndromic X-linked mental retardationAllen, K.M. et al. (1998)Nat. Genet. 20, 25–30Mutations in GDI1 are responsible for X-linked non-specific mental retardationD'Adamo, P. et al. (1998)Nat. Genet. 19, 134–139Non-specific X-linked semidominant mental retardation by mutations in a Rab GDP-dissociation inhibitorBienvenu, T. et al. (1998)Hum. Mol. Genet. 7, 1311–1315     

Giving it all away: altruism and answers to the Wason selection task

The Wason selection task, a standard test of conditional reasoning, has featured prominently in experimental studies of cognitive adaptations for cooperation. The most prominent of these is Cosmides' investigations of cheater detection on social contract versions of the Wason selection task [Cognition 31 (1989) 187–276]. Subsequent to Cosmides' initial investigations, several researchers [Evol Hum Behav 21 (200) 25–37; Manage Decis Econ 19 (1998) 467–480; J Genet Psychol 163 (2002) 425–444; Evol Hum Behav 27 (2006) 366–380] have argued that people also are competent at detecting altruism on the Wason selection task, suggesting that there is nothing privileged about the detection of cheaters. However, an analysis of the selection tasks on which these claims are based suggests that participants may have solved these altruism-detection tasks correctly because the scenarios explicitly or implicitly provide the answer to the task in the scenario [Evol Hum Behav 21 (200) 25–37; Manage Decis Econ 19 (1998) 467–480; J Genet Psychol 163 (2002) 425–444], or due to confounds in the cheater-detection tasks leading to the (misleading) appearance of enhanced altruist-detection performance [Evol Hum Behav 27 (2006) 366–380]. We tested our conjecture by giving participants selection tasks with and without the answer embedded in the scenario. Performance dropped significantly on the altruism-detection tasks when the embedded answers were removed, whereas performance on cheater-detection versions was unaffected by the manipulation. A reanalysis of the findings of Oda et al. suggested that participants performed significantly worse on their altruism-detection problems than their cheater-detection problems — a finding that we replicate after removing confounds from the cheater-detection tasks of Oda et al. The results reaffirm the specificity of cheater-detection.     

Close encounters of the type III secretion kind

Protein translocation into host epithelial cells by infecting enteropathogenic Escherichia coliWolff, C. et al. (1998)Mol. Microbiol. 28, 143–155The complete sequence of the locus of enterocyte effacement (LEE) from enteropathogenic Escherichia coli E2348/69Elliott, S.J. et al. (1998)Mol. Microbiol. 28, 1–4     

Therapy for CAG-repeat diseases?

Suppression of aggregate formation and apoptosis by transglutaminase inhibitors in cells expressing truncated DRPLA protein with an expanded polyglutamine stretchIgarashi, S. et al. (1998)Nat. Genet. 18, 111–117     

Genome-wide meta-analysis for rheumatoid arthritis

Meta-analysis is being increasingly used as a tool for integrating data from different studies of complex phenotypes, because the power of any one study to identify causal loci is limited. We applied a novel meta-analytical approach (Loesgen et al. in Genet Epidemiol 21(Suppl 1):S142–S147, 2001) in compiling results from four studies of rheumatoid arthritis in Caucasians including two studies from NARAC (Jawaheer et al. in Am J Hum Genet 68:927–936, 2001; Jawaheer et al. in Arthritis Rheum 48:906–916, 2003), one study from the UK (MacKay et al. in Arthritis Rheum 46:632–639, 2001) and one from France (Cornelis et al. in Proc Natl Acad Sci USA 95:10746–10750, 1998). For each study, we obtained NPL scores by performing interval mapping (2 cM intervals) using GeneHunter2 (Kruglyak et al. in Am J Hum Genet 58:1347–1363, 1996; Markianos et al. in Am J Hum Genet 68:963–977, 2001). The marker maps differed among the three consortium groups, therefore, the marker maps were aligned after the interval mapping was completed and the NPL scores that were within 1 cM of each other were combined using the method of Loesgen et al. (Genet Epidemiol 21(Suppl 1):S142–S147, 2001) by calculating the weighted average of the NPL score. This approach avoids some problems in analysis encountered by using GeneHunter2 when some markers in the sample are not genotyped. This procedure provided marginal evidence (P<0.05) of linkage on chromosome 1, 2, 5 and 18, strong evidence (P<0.01) on chromosomes 8 and 16, and overwhelming evidence in the HLA region of chromosome 6.     

Vaccine evasion by pneumococci: as easy as changing a cassette

Recombinational exchanges at the capsular polysaccharide biosynthetic locus lead to frequent serotype changes among natural isolates of Streptococcus pneumoniaeCoffey, T.J. et al. (1998)Mol. Microbiol. 27, 73–83     

The synaptonemal complex and meiotic recombination in humans: new approaches to old questions

Meiotic prophase serves as an arena for the interplay of two important cellular activities, meiotic recombination and synapsis of homologous chromosomes. Synapsis is mediated by the synaptonemal complex (SC), originally characterized as a structure linked to pairing of meiotic chromosomes (Moses (1958) J Biophys Biochem Cytol 4:633–638). In 1975, the first electron micrographs of human pachytene stage SCs were presented (Moses et al. (1975) Science 187:363–365) and over the next 15 years the importance of the SC to normal meiotic progression in human males and females was established (Jhanwar and Chaganti (1980) Hum Genet 54:405–408; Pathak and Elder (1980) Hum Genet 54:171–175; Solari (1980) Chromosoma 81:315–337; Speed (1984) Hum Genet 66:176–180; Wallace and Hulten (1985) Ann Hum Genet 49(Pt 3):215–226). Further, these studies made it clear that abnormalities in the assembly or maintenance of the SC were an important contributor to human infertility (Chaganti et al. (1980) Am J Hum Genet 32:833–848; Vidal et al. (1982) Hum Genet 60:301–304; Bojko (1983) Carlsberg Res Commun 48:285–305; Bojko (1985) Carlsberg Res Commun 50:43–72; Templado et al. (1984) Hum Genet 67:162–165; Navarro et al. (1986) Hum Reprod 1:523–527; Garcia et al. (1989) Hum Genet 2:147–53). However, the utility of these early studies was limited by lack of information on the structural composition of the SC and the identity of other SC-associated proteins. Fortunately, studies of the past 15 years have gone a long way toward remedying this problem. In this minireview, we highlight the most important of these advances as they pertain to human meiosis, focusing on temporal aspects of SC assembly, the relationship between the SC and meiotic recombination, and the contribution of SC abnormalities to human infertility.The synaptonemal complex–50 years     

A new type of tumour suppressor gene: a serine/threonine kinase joins the list

Peutz–Jeghers syndrome is caused by mutations in a novel serine threonine kinaseJenne, D.E. et al. (1998)Nat. Genet. 18, 38–43A serine/threonine kinase gene defective in Peutz–Jeghers syndromeHemminki, A. et al. (1998)Nature 391, 184–187     

Non-viral gene transfer: liposomes and nanospheres promise to deliver the goods

Effective treatment of early endobronchial cancer with regional administration of liposome–p53 complexesZou, Y. et al. (1998)J. Natl. Cancer Inst. 90, 1130–1137Controlled gene delivery by DNA–gelatin nanospheresTruong-Le, V.L. et al. (1998)Hum. Gene Ther. 9, 1709–1717     

A stress sensitive ER membrane-association domain in Huntingtin protein defines a potential role for Huntingtin in the regulation of autophagy

We have recently published the precise definition of an amino-terminal membrane association domain in huntingtin, capable of targeting to the endoplasmic reticulum and late endosomes as well as autophagic vesicles. In response to ER stress induced by several pathways, huntingtin releases from membranes and rapidly translocates into the nucleus. Huntingtin is then capable of nuclear export and re-association with the ER in the absence of stress. This release is inhibited when huntingtin contains the polyglutamine expansion seen in Huntington's disease. As a result, mutant huntingtin expressing cells have a perturbed ER and an increase in autophagic vesicles. Here, we discuss the potential function of the huntingtin protein as an ER sentinel, potentially regulating autophagy in response to ER stress. We compare these recent findings to the well characterized mammalian target of rapamycin, mTor, a protein described over a decade ago as related to huntingtin structurally by leucine–rich, repetitive HEAT sequences. Since then, the described functional similarities between huntingtin and mTor are striking, and this new information about huntingtin’s direct association with autophagic vesicles indicates that this structural similarity may extend to functional similarities having an impact upon ER functionality and autophagy.

Addendum to: Atwal RS, Xia J, Pinchev D, Taylor J, Epand RM, Truant R. Huntingtin has a membrane association signal that can modulate huntingtin aggregation, nuclear entry and toxicity. Hum Mol Genet 2007; 16:2600-15.     

Unusual imprinting defects with low recurrence risks

Sporadic imprinting defects in Prader–Willi syndrome and Angelman syndrome: implications for imprint-switch models, genetic counselling, and prenatal diagnosisBuiting, K. et al. (1998)Am. J. Hum. Genet. 63, 170–180     

Attraction and the single cell

Selective expression of the eotaxin receptor CCR3 by human T helper 2 cellsSallusto, F. et al. (1997)Science 277, 2005–2007Functional expression of the eotaxin receptor CCR3 in T lymphocytes co-localising with eosinophilsGerber, B.O. et al. (1997)Curr. Biol. 7, 836–843Differential expression of chemokine receptors and chemotactic responsiveness of type 1 T helper cells (Th1s) and Th2sBonecchi, R. et al. (1998)J. Exp. Med. 187, 129–134CCR5 is characteristic of Th1 lymphocytesLoetscher, M. et al. (1998)Nature 391, 344–345     

Expression of human salivary protein genes

Human proline-rich proteins (PRPs) are polymorphic, homologous in sequence, and linked in a cluster called the human salivary protein complex (SPC). Recently this complex was localized to human chromosome band 12p13.2 (Mamulaet al., Cytogenet. Cell Genet. 39:279, 1985). We have isolated a PRP cDNA, EO27, from a human parotid gland library, identified it by DNA sequencing, and used it to study the molecular and cellular biology of PRP production. Cell-free translation and mRNA characterization with EO27 indicate that the numerous PRPs seen in saliva are produced from relatively few, large precursors, probably by posttranslational cleavage. This supports an hypothesis originally proposed by Friedman and Karn in 1977 (Am. J. Hum. Genet. 29:44A;Biochem. Genet. 15:549) and later supported by biochemical studies (Karnet al., Biochem Genet. 17:1061, 1979) and molecular studies (Mamulaet al., Fed. Proc. 43:1522, 1984; Maedaet al., J. Biol. Chem. 260:1123, 1985). EO27 was also used in this study to localize PRP mRNA production to the acinar cells of the parotid gland byin situ hybridization.     

Morphology and dynamics of chromosome territories in living cells

Chromosome territories formed by fluorescence-labeled sub-chromosomal foci were analyzed in time-lapse series of 3D confocal data sets of living HeLa and human neuroblastoma cells. The quantitative analysis of the chromosome territory morphology confirmed previous results obtained by visual observation [Zink et al., Hum. Genet. 102 (1998) 241–251] that chromosome territories persisted as stable entities over an observation time >4 h. The changes in morphology with time of single chromosome territories were found to be less pronounced than differences in morphology of different chromosome territories in fixed cells. The analysis of the individual motion of chromosome territories recently showed ‘Brownian’ diffusion-like motion at very slow rates [Bornfleth et al., Biophys. J. 77 (1999) 2871–2886]. Here, we show that the mutual motion of different chromosome territories was independent and also ‘Brownian’ diffusion-like.     

Comments on the entropy-based transmission/disequilibrium test

It has recently been claimed in this journal (Zhao et al. in Hum Genet 121:357–367, 2007) that a so-called “entropy-based” TDT test has improved power over the standard TDT test of Spielman et al. (Am J Hum Genet 52:506–516, 1993). We show that this claim is contradicted by standard statistical theory as well as by our simulation results. We show that the incorrect claim arises because of inappropriate assumptions, and also show that the entropy-based statistic has various undesirable properties.     

A candidate gene for schizophrenia and bipolar disorder

Isolation of a novel potassium channel gene hSKCa3 containing a polymorphic CAG repeat: a candidate for schizophrenia and bipolar disorder?Chandy, K.G. et al. (1998)Mol. Psychiatr. 3, 32–37     

Winning the war against antibiotic resistance

Antibiotic sensitization using biphenyl tetrazoles as potent inhibitors of Bacteroides fragilis metallo-β-lactamaseToney, J.H. et al. (1998)Chem. Biol. 5, 185–196Autoinducer of virulence as a target for vaccine and therapy against Staphylococcus aureusBalaban, N. et al. (1998)Science 280, 438–440     

Adenoviral gene transfer to committed hematopoietic progenitors

High-efficiency gene transfer into ex vivo expanded human hematopoietic progenitors and precursor cells by adenovirus vectorsFrey, B.M. et al. (1998)Blood 91, 2781–2792     

New evidence for neuroprotection by estrogen

Estrogen reduces neuronal generation of Alzheimer β-amyloid peptidesXu, H. et al. (1998)Nat. Med. 4, 447–451Nuclear estrogen receptor-independent neuroprotection by estratrienes: a novel interaction with glutathioneGreen, P.S. et al. (1998)Neuroscience 84, 7–10