Unemotional traits predict early processing deficit for fearful expressions in young violent offenders: an investigation using continuous flash suppression.

BACKGROUND: Research evidence suggests that cognitive and neural mechanisms involved in social information processing may underlie the key aspects associated with the emergence of aggression and psychopathy. Despite extensive research in this field, it is unclear whether this deficit relates to general attentional problems or affects early stages of information processing. Therefore, the aim was to explore the link between aggression, psychopathic traits, and the early processing deficits in young antisocial violent offenders (YAVOs) and healthy controls (CTLs). METHOD: Participants were presented with rapidly changing Mondrian-like images in one eye, while a neutral or emotional (happy, angry, fearful, disgusted, surprised, sad) face was slowly introduced to the other eye. Participants indicated the location in which the face had appeared on the screen, reflecting the time when they became aware of the stimulus. The relative processing advantage was obtained by subtracting mean reaction times for emotional from neutral faces. RESULTS: The results indicated that individuals with higher levels of unemotional traits tended to exhibit an extensive early processing disadvantage for fearful facial expressions; this relationship was only evident in the YAVO as opposed to the CTL sample. CONCLUSIONS: These findings indicate that an emotion processing deficit in antisocial individuals is present even at the most basic levels of processing and closely related to certain psychopathic traits. Furthermore, this early processing deficit appears to be highly specific to fearful expressions, which is consistent with predictions made by influential models of psychopathy. The clinical significance and potential implications of the results are discussed.

[Preoperative and postoperative imaging in patients with transposition of the great arteries]. / Prä- und Postoperative Bildgebung bei Patienten mit Transposition der großen Gefäße.

Transposition of the great arteries (TGA) is a rare disease representing not more than 3-5% of all congenital heart diseases. TGA is a cardiac anomaly in which the aorta arises entirely or largely from the morphological right ventricle and the pulmonary artery from the morphological left ventricle. This is called a ventriculo-arterial discordant connection and when accompanied by an atrio-ventricular concordant connection it is called a complete or D-transposition (D-TGA). The terms congenitally corrected TGA (ccTGA) or L-TGA describe an atrio-ventricular discordant connection. In D-TGA survival can only be achieved if additional shunting is simultaneously present, which possibly has to be created post-natal by the so-called Rashkind maneuver.Nowadays, an early anatomic correction using the arterial switch operation is the treatment of choice. Up to the 1980s, an atrial switch operation according to Senning/Mustard was performed. Apart from echocardiography the imaging modality of choice is usually MRI to assess the complex postoperative anatomy, viability of the myocardium and to perform a volumetric and functional assessment, including MR flow measurements. Multidetector computed tomography (MDCT) is used if there are contraindications to MRI or if an assessment of cardiac and especially coronary anatomy is the main interest.

Elucidation of the function of two glycosyltransferase genes (lanGT1 and lanGT4) involved in landomycin biosynthesis and generation of new oligosaccharide antibiotics.

BACKGROUND: The genetic engineering of antibiotic-producing Streptomyces strains is an approach that became a successful methodology in developing new natural polyketide derivatives. Glycosyltransferases are important biosynthetic enzymes that link sugar moieties to aglycones, which often derive from polyketides. Biological activity is frequently generated along with this process. Here we report the use of glycosyltransferase genes isolated from the landomycin biosynthetic gene cluster to create hybrid landomycin/urdamycin oligosaccharide antibiotics. RESULTS: Production of several novel urdamycin derivatives by a mutant of Streptomyces fradiae Tü2717 has been achieved in a combinatorial biosynthetic approach using glycosyltransferase genes from the landomycin producer Streptomyces cyanogenus S136. For the generation of gene cassettes useful for combinatorial biosynthesis experiments new vectors named pMUNI, pMUNII and pMUNIII were constructed. These vectors facilitate the construction of gene combinations taking advantage of the compatible MunI and EcoRI restriction sites. CONCLUSIONS: The high-yielding production of novel oligosaccharide antibiotics using glycosyltransferase gene cassettes generated in a very convenient way proves that glycosyltransferases can be flexible towards the alcohol substrate. In addition, our results indicate that LanGT1 from S. cyanogenus S136 is a D-olivosyltransferase, whereas LanGT4 is a L-rhodinosyltransferase.

The NDP-sugar co-substrate concentration and the enzyme expression level influence the substrate specificity of glycosyltransferases: cloning and characterization of deoxysugar biosynthetic genes of the urdamycin biosynthetic gene cluster.

BACKGROUND: Streptomyces fradiae is the principal producer of urdamycin A. The antibiotic consists of a polyketide-derived aglycone, which is glycosylated with four sugar components, 2x D-olivose (first and last sugar of a C-glycosidically bound trisaccharide chain at the 9-position), and 2x L-rhodinose (in the middle of the trisaccharide chain and at the 12b-position). Limited information is available about both the biosynthesis of D-olivose and L-rhodinose and the influence of the concentration of both sugars on urdamycin biosynthesis. RESULTS: To further investigate urdamycin biosynthesis, a 5.4 kb section of the urdamycin biosynthetic gene cluster was sequenced. Five new open reading frames (ORFs) (urdZ3, urdQ, urdR, urdS, urdT) could be identified each one showing significant homology to deoxysugar biosynthetic genes. We inactivated four of these newly allocated ORFs (urdZ3, urdQ, urdR, urdS) as well as urdZ1, a previously found putative deoxysugar biosynthetic gene. Inactivation of urdZ3, urdQ and urdZ1 prevented the mutant strains from producing L-rhodinose resulting in the accumulation of mainly urdamycinone B. Inactivation of urdR led to the formation of the novel urdamycin M, which carries a C-glycosidically attached D-rhodinose at the 9-position. The novel urdamycins N and O were detected after overexpression of urdGT1c in two different chromosomal urdGT1c deletion mutants. The mutants lacking urdS and urdQ accumulated various known diketopiperazines. CONCLUSIONS: Analysis of deoxysugar biosynthetic genes of the urdamycin biosynthetic gene cluster revealed a widely common biosynthetic pathway leading to D-olivose and L-rhodinose. Several enzymes responsible for specific steps of this pathway could be assigned. The pathway had to be modified compared to earlier suggestions. Two glycosyltransferases normally involved in the C-glycosyltransfer of D-olivose at the 9-position (UrdGT2) and in conversion of 100-2 to urdamycin G (UrdGT1c) show relaxed substrate specificity for their activated deoxysugar co-substrate and their alcohol substrate, respectively. They can transfer activated D-rhodinose (instead of D-olivose) to the 9-position, and attach L-rhodinose to the 4A-position normally occupied by a D-olivose unit, respectively.

Function of glycosyltransferase genes involved in urdamycin A biosynthesis.

BACKGROUND: Urdamycin A, the principle product of Streptomyces fradiae Tü2717, is an angucycline-type antibiotic. The polyketide-derived aglycone moiety is glycosylated at two positions, but only limited information is available about glycosyltransferases involved in urdamycin biosynthesis. RESULTS: To determine the function of three glycosyltransferase genes in the urdamycin biosynthetic gene cluster, we have carried out gene inactivation and expression experiments. Inactivation of urdGT1a resulted in the predominant accumulation of urdamycin B. A mutant lacking urdGT1b and urdGT1c mainly produced compound 100-2. When urdGT1c was expressed in the urdGT1b/urdGT1c double mutant, urdamycin G and urdamycin A were detected. The mutant lacking all three genes mainly accumulated aquayamycin and urdamycinone B. Expression of urdGT1c in the triple mutant led to the formation of compound 100-1, whereas expression of urdGT1a resulted in the formation of compound 100-2. Co-expression of urdGT1b and urdGT1c resulted in the production of 12b-derhodinosyl-urdamycin A, and co-expression of urdGT1a, urdGT1b and urdGT1c resulted in the formation of urdamycin A. CONCLUSIONS: Analysis of glycosyltransferase genes of the urdamycin biosynthetic gene cluster led to an unambiguous assignment of each glycosyltransferase to a certain biosynthetic saccharide attachment step.

Prevalence and Associated Risk Factors for Obesity During Pregnancy Over Time.

Objective: The increasing prevalence of obesity is having an impact on morbidity worldwide. Since young mature women are equally affected by the general increase in weight, the aim of the study was to evaluate the prevalence of obesity together with associated maternal risk factors, complications during pregnancy, and fetal outcomes in a local cohort for the years 2006 and 2011. Study Design: Maternal and fetal records of women who delivered at the University of Würzburg, with a 5-year interval (2006 and 2011) between investigations, were retrospectively analyzed. Descriptive statistics included prevalence of obesity, maternal weight gain, as well as several complications during pregnancy and fetal characteristics. The association between maternal or fetal complications and extent of maternal obesity was analyzed. Results: Our analysis included 2838 mothers with singleton pregnancies who delivered in 2006 (n = 1293) or 2011 (n = 1545) in our department. We found that neither pre-pregnancy body mass index (23.77 ± 4.85 vs. 24.09 ± 5.10 kg/m2, p = 0.25) nor weight gain (14.41 ± 5.77 vs. 14.78 ± 5.65 kg; p = 0.09) increased significantly over time. But the majority of all overweight (71 %) or obese (60.4 %) mothers gained more weight than generally recommended. The prevalence of gestational diabetes, gestational hypertension, and preeclampsia increased significantly and was associated with high pre-pregnancy body mass index, as was delivery by cesarean section. However, obesity was not associated with prolonged pregnancy and did not seem to negatively affect fetal outcome. Conclusion: There is a trend to increasing weight gain during pregnancy, and the majority of mothers, especially those with a high pre-pregnancy body mass index, exceeded the weight gain recommendations. Associated risk factors such as gestational diabetes, hypertension, and delivery by cesarean section are increasing.

The fine structure of the boundary tissue of the seminiferous tubule of the camel (Camelus dromedarius).

An ultrastructural study of the boundary tissue of the seminiferous tubule of the camel reveals that it consists of three lamellae; inner fibrous, inner cellular and outer cellular. The inner lamella is subdivided into two homogeneous layers enclosing a third one that contains collagenous fibres and fine filaments. The inner cellular lamella consists of several layers of myoid cells; each layer is separated from the adjacent layer by homogeneous material and varying amounts of collagen. The outer cellular lamella consists predominantly of fibrocytes together with some fibroblasts and scattered collagen.

Classification of a collection of malformed human hearts: practical experience in the use of sequential segmental analysis.

The inauguration of Sequential Segmental Analysis (SSA) a few decades ago provides basic conditions to establish a universally applicable classification system for cardiac malformations. To gain practical experience, we used this method to classify a collection of 292 congenitally malformed human hearts. Our aims were to determine advantages and problems of the SSA and to make recommendations for a better practical usability and documentation. SSA is an appropriate instrument for the description of complex cardiac malformations because it is a logical step-by-step approach based on the heart morphology. The method optimizes the diagnosis of different malformed hearts. However, there are some disadvantages of SSA concerning terminology, localization of simple septal defects and exact topographic description of heart structures. For these reasons, we recommend a graphic description of the malformed heart using symbols based on the SSA. The most important prerequisite for an interdisciplinary acceptable classification system of cardiac malformations is to include morphological as well as functional aspects of the hearts.

Fresh meniscal allograft transplantation and autologous ACL/PCL reconstruction in a patient with complex knee trauma following knee dislocation--a case report.

Instability of the knee joint, particularly in combination with the loss of one meniscus, regularly leads to the early development of arthritis. This paper describes the case of a 19-year-old male with ruptures of the anterior (ACL) and posterior cruciate ligament (PCL) along with the loss of the medial meniscus due to knee dislocation. Combined, time-delayed reconstruction of both the ACL and PCL and the allogenic fresh meniscal transplantation of the medial meniscus without bone plugs were performed. The control arthroscopy performed 6 months post-transplantation revealed good vitality and integration of the grafts as assessed both macroscopically and histologically. A small portion of the posterior horn had to be refixated, and the anterior horn was atrophic. At 24 months after trauma and 13 months following meniscal transplantation, the patient achieved a Lysholm score of 88 points and clinical examination indicated a stable knee. Fresh meniscal allograft transplantation, in combination with autologous ACL and PCL reconstruction, constitutes--in specialized centers--an alternative treatment option for complex trauma of the knee joint with loss of a meniscus.

The structure of mithramycin reinvestigated.

A reinvestigation of the structure of mithramycin, the principal product of Streptomyces argillaceus ATCC 12956, is reported. The structure elucidation was carried out with mithramycin decaacetate (4) using 2D NMR methods, including TOCSY, HMBC, and HSQC experiments. The work resulted in structure 3being confirmed for mithramycin.

The mtmVUC genes of the mithramycin gene cluster in Streptomyces argillaceus are involved in the biosynthesis of the sugar moieties.

Mithramycin is a glycosylated aromatic polyketide produced by Streptomyces argillaceus, and is used as an antitumor drug. Three genes (mtmV, mtmU and mtmC) from the mithramycin gene cluster have been cloned, and characterized by DNA sequencing and by analysis of the products that accumulate in nonproducing mutants, which were generated by insertional inactivation of these genes. The mtm V gene codes for a 2,3-dehydratase that catalyzes early and common steps in the biosynthesis of the three sugars found in mithramycin (D-olivose, D-oliose and D-mycarose); its inactivation caused the accumulation of the nonglycosylated intermediate premithramycinone. The mtmU gene codes for a 4-ketoreductase involved in D-oliose biosynthesis, and its inactivation resulted in the accumulation of premithramycinone and premithramycin A , the first glycosylated intermediate which contains a D-olivose unit. The third gene, mtmC, is involved in D-mycarose biosynthesis and codes for a C-methyltransferase. Two mutants with lesions in the mtmC gene accumulated mithramycin intermediates lacking the D-mycarose moiety but containing D-olivose units attached to C-12a in which the 4-keto group is unreduced. This suggests that mtmC could code for a second enzyme activity, probably a D-olivose 4-ketoreductase, and that the glycosyltransferase responsible for the incorporation of D-olivose (MtmGIV) shows some degree of flexibility with respect to its sugar co-substrate, since the 4-ketoanalog is also transferred. A pathway is proposed for the biosynthesis of the three sugar moieties in mithramycin.

Two new tailoring enzymes, a glycosyltransferase and an oxygenase, involved in biosynthesis of the angucycline antibiotic urdamycin A in Streptomyces fradiae Tü2717.

Urdamycin A, the principal product of Streptomyces fradiae Tu2717, is an angucycline-type antibiotic and anticancer agent containing C-glycosidically linked D-olivose. To extend knowledge of the biosynthesis of urdamycin A the authors have cloned further parts of the urdamycin biosynthetic gene cluster. Three new ORFs (urdK, urdJ and urdO) were identified on a 3.35 kb fragment, and seven new ORFs (urdL, urdM, urdJ2, urdZl, urdGT2, urdG and urdH) on an 8.05 kb fragment. The deduced products of these genes show similarities to transporters (urdJ and urdJ2), regulatory genes (urdK), reductases (urdO), cyclases (urdL) and deoxysugar biosynthetic genes (urdG, urdH and urdZ1). The product of urdM shows striking sequence similarity to oxygenases (N-terminal sequence) as well as reductases (C-terminal sequence), and the deduced amino acid sequence of urdGT2 resembles those of glycosyltransferases. To determine the function of urdM and urdGT2, targeted gene inactivation experiments were performed. The resulting urdM deletion mutant strains accumulated predominantly rabelomycin, indicating that UrdM is involved in oxygenation at position 12b of urdamycin A. A mutant in which urdGT2 had been deleted produced urdamycin I, urdamycin J and urdamycin K instead of urdamycin A. Urdamycins I, J and K are tetracyclic angucyclinones lacking a C-C connected deoxysugar moiety. Therefore UrdGT2 must catalyse the earliest glycosyltransfer step in the urdamycin biosynthetic pathway, the C-glycosyltransfer of one NDP-D-olivose.

Characterization of two glycosyltransferases involved in early glycosylation steps during biosynthesis of the antitumor polyketide mithramycin by Streptomyces argillaceus.

A 2,580-bp region of the chromosome of Streptomyces argillaceus, the producer of the antitumor polyketide mithramycin, was sequenced. Analysis of the nucleotide sequence revealed the presence of two genes (mtmGIII and mtmGIV) encoding proteins that showed a high degree of similarity to glycosyltransferases involved in the biosynthesis of various antibiotics and antitumor drugs. Independent insertional inactivation of both genes produced mutants that did not synthesize mithramycin but accumulated several mithramycin intermediates. Both mutants accumulated premithramycinone, a non-glycosylated intermediate in mithramycin biosynthesis. The mutant affected in the mtmGIII gene also accumulated premithramycin A1, which contains premithramycinone as the aglycon unit and a D-olivose attached at C-12a-O. These experiments demonstrate that the glycosyltransferases MtmGIV and MtmGIII catalyze the first two glycosylation steps in mithramycin biosynthesis. A model is proposed for the glycosylation steps in mithramycin biosynthesis.