A region of human chromosome 9p required for testis development contains two genes related to known sexual regulators.

Deletion of the distal short arm of chromosome 9 (9p) has been reported in a number of cases to be associated with gonadal dysgenesis and XY sex reversal, suggesting that this region contains one or more genes required in two copies for normal testis development. Recent studies have greatly narrowed the interval containing this putative autosomal testis-determining gene(s) to the distal portion of 9p24.3. We previously identified DMRT1, a human gene with sequence similarity to genes that regulate the sexual development of nematodes and insects. These genes contain a novel DNA-binding domain, which we named the DM domain. DMRT1 maps to 9p24. 3 and in adults is expressed specifically in the testis. We have investigated the possible role of DM domain genes in 9p sex reversal. We identified a second DM domain gene, DMRT2, which also maps to 9p24.3. We found that point mutations in the coding region of DMRT1 and the DM domain of DMRT2 are not frequent in XY females. We showed by fluorescence in situ hybridization analysis that both genes are deleted in the smallest reported sex-reversing 9p deletion, suggesting that gonadal dysgenesis in 9p-deleted individuals might be due to combined hemizygosity of DMRT1 and DMRT2.     

Endogenous nitric oxide acts as a natural antithrombotic agent in vivo by inhibiting platelet aggregation in the pulmonary vasculature.

Nitric oxide (NO) is a powerful vasodilator and an inhibitor of platelet aggregation in vitro. While the ability of NO to modulate vascular tone in vivo has been proven, only a few studies have assessed its platelet inhibitory activity in vivo. We have employed two complementary animal models of pulmonary platelet thromboembolism to assess the antithrombotic activity of endogenous NO in vivo. The inhibition of nitric oxide synthase (NOS) by L-NAME significantly potentiated while the administration of the NOS substrate L-arginine significantly reduced the accumulation of 111In-labelled platelets in the pulmonary vasculature of rabbits induced by intravenous collagen plus epinephrine. L-NAME or L-arginine did not, however, modify 111In-labelled erythrocyte distribution in lungs and phenylephrine had no effect on platelet accumulation following collagen + adrenaline, suggesting that the effects of L-NAME were not due to vasoconstriction but rather to a direct modification of platelet function. In mice, L-NAME significantly reduced the dose of collagen + adrenaline required to induce thromboembolic mortality, increased the fall in circulating platelets and increased the % of pulmonary vessels occluded by platelet thrombi. The effects of L-NAME were reversed by L-arginine but not by a dose of nicardipine exerting maximal vasodilatation. Phenylephrine did not potentiate collagen + adrenaline-induced mortality. In the pulmonary vasculature in vivo, endogenous NO inhibits collagen + adrenaline-induced aggregation and enhances platelet disaggregation. This natural modulator function of NO is exerted via a direct effect on platelets and not as a result of haemodynamic changes.     

Naturally occurring growth factors in porcine wounds treated with autologous keratinocytes in a liquid environment

A step toward an improved understanding of the complex mechanisms of growth factor interactions may lie in the detection of endogenous growth factors during normal wound healing. The findings of this study on standardized full thickness wounds in swine, provide direct evidence that growth factors were present in the wound fluid in the picogram range (highest concentrations ranging from 1273 pg/ml for transforming growth factor-beta (TGFβ) to 85.6 pg/ml for platelet-derived growth factor-AB (PDGF-AB ) during healing. The presence of transplanted autologous keratinocyte suspensions and cultured epithelial sheet graft had no significant effect upon the observed growth factor levels, although transplanted keratinocyte cell suspensions (KCS) and cultured epidermal autografts (CEA) did accelerate healing in comparison to control wounds in our model (KCS treated wounds healed in 13.2±0.9 days, CEA in 13.7 days±0.8 and control wounds in 14.7 days±0.3). The variable occurrence of growth factors during normal wound healing may suggest possible mechanisms of growth factor interaction which could have an impact on the future design of their therapeutic use. Received: 28 September 1998 / Accepted: 16 November 1998     

Meiosis in Holocentric Chromosomes: Orientation and Segregation of an Autosome and Sex Chromosomes in Triatoma infestans (Heteroptera)

The meiotic behaviour of the X chromosome and one autosomal pair of the heteropteran Triatoma infestans was analysed by means of C-banding plus DAPI staining. At first metaphase, the X univalent is oriented with its long axis parallel to the equatorial plate, which suggests a holocentric interaction with the spindle fibres. After this initial orientation, kinetic activity is restricted to one of both chromatid ends. The election of the active chromatid end is random and it is independent of the end selected in the sister chromatid. At second metaphase, the X and Y chromatids associate side by side forming a pseudobivalent. After that, the kinetic activity is again restricted to either of both chromosomal ends in a random fashion. At first metaphase, the fourth autosomal bivalent shows two alternative random orientations depending on the chromosome end showing kinetic activity (DAPI positive or opposite). At second metaphase, half bivalents are oriented with their long axis parallel to the equatorial plate. Three different segregation patterns are observed. The kinetic activity can be localised: (i) in the end with the DAPI signal (46.9%), (ii) in the opposite end (44.6%) or (iii) in one DAPI-positive end in one chromatid and in the opposite end in the other one (8.5%). The existence of the last pattern indicates that the same end can show kinetic activity during both meiotic divisions. Our results provide new information on the comparative meiotic behaviour of autosomes and sex chromosomes in holocentric systems.     

Proteomics: a major new technology for the drug discovery process

Proteomics is a new enabling technology that is being integrated into the drug discovery process. This will facilitate the systematic analysis of proteins across any biological system or disease, forwarding new targets and information on mode of action, toxicology and surrogate markers. Proteomics is highly complementary to genomic approaches in the drug discovery process and, for the first time, offers scientists the ability to integrate information from the genome, expressed mRNAs, their respective proteins and subcellular localization. It is expected that this will lead to important new insights into disease mechanisms and improved drug discovery strategies to produce novel therapeutics.     

Patel S,Turner PR,Stubberfield C,Barry E,Rohlff CR,Stamps A,McKenzie E,Young K,Tyson K,Terrett J,Box G,Eccles S,Page MJ. Hyaluronidase gene profiling and role of HYAL‐1 overexpression in an orthotopic model of prostate cancer. International Journal of Cancer 2002;97(4): 416–424.

The original article to which this Erratum refers was published in International Journal of Cancer; 2002; 97(4) 416–422.     

Variability of the obturator vessels

The obturator artery and vein are usually described as branches or tributaries of the internal iliac vessels although variations with connections to the external iliac or inferior epigastric vessels have been reported. Because these anomalous vessels are at risk in groin or pelvic surgeries that require dissection or suturing along the pelvic rim, we measured the frequency of these variations in 105 pelvic walls (45 in the United States and 60 in China). Our data show that 70–82% of pelvic halves and 83–90% of whole pelves had an artery, vein, or both in the variant position. Arteries were most often found in the normal position only but normal and anomalous veins were most frequently found together. These data show that it is far more common to find a vessel coursing over the pelvic rim at this site than not and have implications for both pelvic surgeons and anatomists. Clin. Anat. 10:328–332, 1997. © 1997 Wiley-Liss, Inc.     

The emergence and perils of polarization

We provide commentaries on the papers included in the Dynamics of Political Polarization Special Feature. Baldassarri reads the contribution of the papers in light of the theoretical distinction between ideological partisanship, which is generally rooted in sociodemographic and political cleavages, and affective partisanship, which is, instead, mostly fueled by emotional attachment and repulsion, rather than ideology and material interests. The latter, she argues, is likely to lead to a runaway process and threaten the pluralistic bases of contemporary democracy. Page sees the contribution of the many distinct models in the ensemble as potentially contributing more than the parts. Individual papers identify distinct causes of polarization as well as potential solutions. Viewed collectively, the papers suggest that the multiple causes of polarization may self-reinforce, which suggests that successful interventions would require a variety of efforts. Understanding how to construct such interventions may require larger models with greater realism.