Identification of dynamic structural motifs involved in peptidoglycan glycosyltransfer

We have determined the structure of a new form of the bifunctional peptidoglycan glycosyltransferase (GT)/transpeptidase penicillin-binding protein 2 from the pathogen Staphylococcus aureus. We observe several previously unstructured regions of the GT substrate-binding pockets, including a π-bulge in the outer helix that may be responsible for the conformational flexibility of active-site motifs required for transfer of product to the donor binding site during processive rounds of peptidoglycan polymerization. The identification of a β-hairpin in the usually unstructured region of the fold shares local structural homology to that of an exomuramidase, heightening comparisons between this biosynthetic enzyme and lytic peptidoglycan transglycosylases. This new form also shows remarkable interdomain flexibility, causing the linker region of the fold to project into the GT active site. This self-interaction may have significant consequences for the regulation of polymerization activity. The derived information is used to build a catalytic model of both donor and acceptor glycolipid substrates.     

Clinical and pathological aspects of filarial lymphedema and its management

Lymphatic filariasis, transmitted by mosquitoes is the commonest cause of lymphedema in endemic countries. Among 120 million infected people in 83 countries, up to 16 million have lymphedema. Microfilariae ingested by mosquitoes grow into infective larvae. These larvae entering humans after infected mosquito bites grow in the lymphatics to adult worms that cause damage to lymphatics resulting in dilatation of lymph vessels. This earliest pathology is demonstrated in adults as well as in children, by ultrasonography, lymphoscintigraphy and histopathology studies. Once established, this damage was thought to be irreversible. This lymphatic damage predisposes to bacterial infection that causes recurrent acute attacks of dermato-lymphangio-adenitis in the affected limbs. Bacteria, mainly streptococci gain entry into the lymphatics through 'entry lesions' in skin, like interdigital fungal infections, injuries, eczema or similar causes that disrupt integrity of skin. Attacks of dermato-lymphangio-adenitis aggravates lymphatic damage causing lymphedema, which gets worse with repeated acute attacks. Elephantiasis is a late manifestation of lymphatic filariasis, which apart from limbs may involve genitalia or breasts. Lymphedema management includes use of antifilarial drugs in early stages, treatment and prevention of acute attacks through 'limb-hygiene', antibiotics and antifungals where indicated, and physical measures to reduce the swelling. In selected cases surgery is helpful.     

Trypanosoma cruzi in non-human primates with a history of stillbirths: a retrospective study (Papio hamadryas spp.) and case report (Macaca fascicularis)

Background Congenital transmission of Trypanosoma cruzi has been described in humans and experimental work has been conducted with mice, but not with non‐human primates (NHPs). Methods We conducted a retrospective study of female baboons (Papio hamadryas spp.) naturally seropositive or seronegative for T. cruzi with history of fetal loss, and we report a stillbirth in a cynomolgus macaque (Macaca fascicularis) with placental T. cruzi amastigotes. Results There were no differences in menstrual cycle parameters and the number of fetal losses between seropositive and seronegative baboons with history of fetal loss. The amount of parasite DNA detected using quantitative polymerase chain reaction (Q‐PCR) in M. fascicularis placenta was within the range detected in infected baboon tissues. Conclusions There is no evidence that chronic maternal T. cruzi infection causes fetal loss in baboons. Q‐PCR is a useful diagnostic tool to study archived NHP placentas.     

Dental wear and oral pathology: possible evidence and consequences of habitual use of teeth in a Swedish Neolithic sample

Atypical wear and oral lesions were studied in the dental remains from the Middle Neolithic Pitted Ware Culture site Ajvide on the island of Gotland in the Baltic Sea. Teeth (n = 764) from 17 males and 11 females were examined microscopically to document unusual wear, assess wear patterns and oral lesions as evidence of habitual behavior, and determine their effect on the oral health of this population. Five atypical wear types were observed: occlusal facets, occlusal excessive load, labial vertical striae, labial horizontal striae, and interproximal striae. Three oral lesions were recorded: chipping, periapical lesions, and dental tilting. Results indicate that teeth were used in a habitual manner at Ajvide, based on the morphology and regularity of the patterns of atypical wear. Differences were observed between the sexes, indicating gender-related differences in the habitual use of teeth. Some wear categories showed a significant correlation with age, signifying increased or accumulated wear with age. Statistically significant positive correlations were found in the molars between occlusal excessive load wear and periapical lesions as well as tilting. Other apparent links were also observed between chipping and vertical striae as well as excessive load, although these were not significant. This suggests a relationship between dental wear and dental pathologies at this site, suggesting that habitual use of teeth indirectly affected the general oral health at the site. Wear patterns, furthermore, seem to mirror both frequent activities as well as single events.     

Recombinational Repair in Schizosaccharomyces pombe: A Role in Maintaining Genome Integrity

Recombinational DNA repair was first detected in budding yeast Saccharomyces cerevisiaeand was also studied in fission yeast Schizosaccharomyces pombeover the recent decade. The discovery of Sch. pombehomologs of the S. cerevisiae RAD52genes made it possible not only to identify and to clone their vertebrate counterparts, but also to study in detail the role of DNA recombination in certain cell processes. For instance, recombinational repair was shown to play a greater role in maintaining genome integrity in fission yeast and in vertebrates compared with S. cerevisiae. The present state of the problem of recombinational double-strand break repair in fission yeast is considered in this review with a focus on comparisons between Sch. pombeand higher eukaryotes. The role of double-strand break repair in maintaining genome stability is discussed.     

Ultrastructure of Necrotic Lesions in Nicotiana glutinosa Leaves Locally Infected with a Variant of Cucumber mosaic virus

CMV(Y/GM2)tr is a variant of Cucumber mosaic virus strain Y [CMV(Y)] which infects Nicotiana species, including N. glutinosa, to induce necrotic local lesions (NLLs) in inoculated leaves, although all other CMV strains including CMV(Y) systemically infect Nicotiana species. To investigate the morphological features of this unique host response in N. glutinosa leaves infected with CMV(Y/GM2)tr, the ultrastructure of cells surrounding completely collapsed NLLs in virus‐inoculated N. glutinosa leaves was compared with that of normal cells of mock‐inoculated N. glutinosa leaves. The changes, which have been reported in other several virus–host plant systems showing the hypersensitive response (HR), were frequently observed in cells surrounding the NLLs. Furthermore, clumping of the nuclear matrix within the nuclei, which is a feature of programmed cell death, also occurred in these cells. These results indicated that the HR‐like host response occurred at the fine structural level in the cells of N. glutinosa plants infected with CMV(Y/GM2)tr.     

Ultrastructure du tissu apical testiculaire du doryphore Leptinotarsa decemlineata Say (Coléoptère: Chrysomélidé): étude autoradiographique et cytochimique / Ultrastructure of the apical testicular tissue of the doryphore Leptinotarsa decemlineata Say (Coleopterae: Chrysomelidae): an autoradiographic and cytochemical study

Summary

The somatic ‘apical tissue’ is present in the testes of the Colorado potato beetle from the embryonic stage until the end of the reproductive life. In the vicinity of this tissue, cyst cells and primary gonia are often pycnotic. Incorporation of labelled amino acids in vivo and treatment with pronase indicate that apical cells are sites of protein synthesis. Secretions are glycosylated in the Golgi apparatus where they are also concentrated in granules. Some of them display a positive reaction to the acid phosphatase test. They are extruded by exocytosis into the intercellular spaces which they distend. We conclude that the apical secretions have a lytic activity: gonia and cyst cells are reduced to cellular residues which are accumulated in the intercellular spaces.     

Observations of an extreme form of late eccentric lytic fission in Schizosaccharomyces pombe

Abstract Late eccentric lytic fission was initially observed in Schizosaccharomyces pombe in 1967 (Johnson, B.F. (1967) J. Bacteriol. 94, 192–195). We report here an extreme form of this morphology and have studied the incidence of severity with respect to glucose concentration of the growth media. Alterations to the composition of the growth medium were made to allow cells to reach a density of 1 × 10⁸ cells ml⁻¹ before lysis occurred.     

Progressive formation of DNA lesions during treatment with anti-metabolites without incorporation of the drugs into DNA

Anti-metabolites, such as methotrexate, 5-fluoropyrimidines or hydroxyurea, induced progressive formation of DNA lesions. 5-Fluoropyrimidines induce DNA lesions either by incorporation of the drug into DNA or by a mechanism not involving incorporation. The second mechanism, not involving incorporation, is also seen with methotrexate and hydroxyurea. The three anti-metabolites have in common their ability to reduce intracellular levels of nucleotides, resulting in reduced efficiency of repair of DNA lesions. The lesions probably appear spontaneously, independently of the drug treatment.