Influence of systemic fluoroquinolone administration on the presence of <Emphasis Type="Italic">Pasteurella multocida</Emphasis> in the upper respiratory tract of clinically healthy calves

The influence of enrofloxacin administration (5 mg/kg) for five consecutive days on the occurrence of Pasteurella multocida in the upper respiratory tract of two healthy calves was monitored over a 10-day period. From nasal swabs of two additional healthy control calves, which received a placebo saline administration, P. multocida was isolated throughout the study period. In the enrofloxacin treated calves, P. multocida was not demonstrated in the nasopharynx from 48 h after the first injection until two days after the last administration, when P. multocida reappeared and proved to be clonal in nature to the original isolates. During the experiment, no change in minimal inhibitory concentration for enrofloxacin of the P. multocida isolates was detected (MIC ≤ 0.015 μg/mL). Enrofloxacin concentrations were determined in the plasma by a high-performance liquid chromatography method with fluorescence detection. The PK/PD indices AUC/MIC and C_max/MIC ratio were calculated and found to be 1157.7 and 129.8, respectively. Remarkably, the respiratory pathogen Arcanobacterium pyogenes became the predominant recovered organism in the nasopharynx of one animal following enrofloxacin therapy throughout the remaining of the experiment.     

Treatment-associated polymorphisms in protease are significantly associated with higher viral load and lower CD4 count in newly diagnosed drug-naive HIV-1 infected patients

Background

Bone marrow stromal cell antigen 2 (BST-2) is a cellular factor that restricts the egress of viruses such as human immunodeficiency virus (HIV-1) from the surface of infected cells, preventing infection of new cells. BST-2 is variably expressed in most cell types, and its expression is enhanced by cytokines such as type I interferon alpha (IFN-??). In this present study, we used the beta-retrovirus, mouse mammary tumor virus (MMTV) as a model to examine the role of mouse BST-2 in host infection in vivo.

Results

By using RNA interference, we show that loss of BST-2 enhances MMTV replication in cultured mammary tumor cells and in vivo. In cultured cells, BST-2 inhibits virus accumulation in the culture medium, and co-localizes at the cell surface with virus structural proteins. Furthermore, both scanning electron micrograph (SEM) and transmission electron micrograph (TEM) show that MMTV accumulates on the surface of IFN??-stimulated cells.

Conclusions

Our data provide evidence that BST-2 restricts MMTV release from naturally infected cells and that BST-2 is an antiviral factor in vivo.     

Experimental nasal dermatitis in the Mongolian gerbil: effect of bilateral harderian gland adenectomy on development of facial lesions

Two groups of adult Mongolian gerbils (Meriones unguiculatus) of mixed ages and sex were used to study the effect of bilateral Harderian gland adenectomy on development of nasal dermatitis. One group of gerbils underwent bilateral Harderian gland adenectomies, while the other group underwent sham surgeries, leaving the Harderian gland intact. All animals in both groups were fitted with Elizabethian collars to prevent self-grooming, allowing a buildup of nasolacrimal or Harderian gland secretions near the medial canthus of the eye and at the external nares. Twenty-six of 27 animals with intact Harderian glands developed nasal and facial lesions within 20 days. None of the 27 Harderian gland adenectomized animals developed nasal or facial lesions. Apparently, accumulation of Harderian gland secretions is involved in the pathogenesis of nasal dermatitis in the Mongolian gerbil.     

Ensemble attribute profile clustering: discovering and characterizing groups of genes with similar patterns of biological features

Background  

Ensemble attribute profile clustering is a novel, text-based strategy for analyzing a user-defined list of genes and/or proteins. The strategy exploits annotation data present in gene-centered corpora and utilizes ideas from statistical information retrieval to discover and characterize properties shared by subsets of the list. The practical utility of this method is demonstrated by employing it in a retrospective study of two non-overlapping sets of genes defined by a published investigation as markers for normal human breast luminal epithelial cells and myoepithelial cells.     

Anti-Angiogenic/Vascular Effects of the mTOR Inhibitor Everolimus Are Not Detectable by FDG/FLT-PET

Noninvasive functional imaging of tumors can provide valuable early-response biomarkers, in particular, for targeted chemotherapy. Using various experimental tumor models, we have investigated the ability of positron emission tomography (PET) measurements of 2-deoxy-2-[¹⁸F]fluoro-glucose (FDG) and 3′-deoxy-3′-[¹⁸F]fluorothymidine (FLT) to detect response to the allosteric mammalian target of rapamycin (mTOR) inhibitor everolimus. Tumor models were declared sensitive (murine melanoma B16/BL6 and human lung H596) or relatively insensitive (human colon HCT116 and cervical KB31), according to the IC₅₀ values (concentration inhibiting cell growth by 50%) for inhibition of proliferation in vitro (<10 nM and >1 µM, respectively). Everolimus strongly inhibited growth of the sensitive models in vivo but also significantly inhibited growth of the insensitive models, an effect attributable to its known anti-angiogenic/vascular properties. However, although tumor FDG and FLT uptake was significantly reduced in the sensitive models, it was not affected in the insensitive models, suggesting that endothelial-directed effects could not be detected by these PET tracers. Consistent with this hypothesis, in a well-vascularized orthotopic rat mammary tumor model, other antiangiogenic agents also failed to affect FDG uptake, despite inhibiting tumor growth. In contrast, the cytotoxic patupilone, a microtubule stabilizer, blocked tumor growth, and markedly reduced FDG uptake. These results suggest that FDG/FLT-PET may not be a suitable method for early markers of response to antiangiogenic agents and mTOR inhibitors in which anti-angiogenic/vascular effects predominate because the method could provide false-negative responses. These conclusions warrant clinical testing.     

饲喂黄曲霉毒素B_1大鼠肝中AFB_1-DNA加合物的免疫组织化学研究

应用免疫组织化学ＳＰ法对４例饲喂黄曲霉毒素Ｂ１的Ｗｉｓｔａｒ大鼠肝组织中ＡＦＢ１－ＤＮＡ加合物的染色及常规ＨＥ染色发现,４例肝细胞核均出现异型性,但未见肝细胞坏死、增生灶及肝细胞癌;免疫组化揭示部分肝细胞核出现棕黄色、不均质状的ＡＦＢ１－ＤＮＡ加合物,阳性细胞数占１０～８５％。结果提示免疫组织化学方法可作为一种ＡＦＢ１的定位方法,ＡＦＢ１在动物致癌过程中ＡＦＢ１－ＤＮＡ加合物可能具有启动作用     

Ancient large-scale genome duplications: phylogenetic and linkage analyses shed light on chordate genome evolution

Paralogous genes from several families were found in four human chromosome regions (4p16, 5q33-35, 8p12-21, and 10q24-26), suggesting that their common ancestral region underwent several rounds of large- scale duplication. Searches in the EMBL databases, followed by phylogenetic analyses, showed that cognates (orthologs) of human duplicated genes can be found in other vertebrates, including bony fishes. In contrast, within each family, only one gene showing the same high degree of similarity with all the duplicated mammalian genes was found in nonvertebrates (echinoderms, insects, nematodes). This indicates that large-scale duplications occurred after the echinoderms/chordates split and before the bony vertebrate radiation. It has been suggested that two rounds of gene duplication occurred in the vertebrate lineage after the separation of Amphioxus and craniate (vertebrates + Myxini) ancestors. Before these duplications, the genes that have led to the families of paralogous genes in vertebrates must have been physically linked in the craniate ancestor. Linkage of some of these genes can be found in the Drosophila melanogaster and Caenorhabditis elegans genomes, suggesting that they were linked in the triploblast Metazoa ancestor.      

Presenilin Transmembrane Domain 8 Conserved AXXXAXXXG Motifs Are Required for the Activity of the γ-Secretase Complex

Understanding the molecular mechanisms controlling the physiological and pathological activity of γ-secretase represents a challenging task in Alzheimer disease research. The assembly and proteolytic activity of this enzyme require the correct interaction of the 19 transmembrane domains (TMDs) present in its four subunits, including presenilin (PS1 or PS2), the γ-secretase catalytic core. GXXXG and GXXXG-like motifs are critical for TMDs interactions as well as for protein folding and assembly. The GXXXG motifs on γ-secretase subunits (e.g. APH-1) or on γ-secretase substrates (e.g. APP) are known to be involved in γ-secretase assembly and in Aβ peptide production, respectively. We identified on PS1 and PS2 TMD8 two highly conserved AXXXAXXXG motifs. The presence of a mutation causing an inherited form of Alzheimer disease (familial Alzheimer disease) in the PS1 motif suggested their involvement in the physiopathological configuration of the γ-secretase complex. In this study, we targeted the role of these motifs on TMD8 of PSs, focusing on their role in PS assembly and catalytic activity. Each motif was mutated, and the impact on complex assembly, activity, and substrate docking was monitored. Different amino acid substitutions on the same motif resulted in opposite effects on γ-secretase activity, without affecting the assembly or significantly impairing the maturation of the complex. Our data suggest that AXXXAXXXG motifs in PS TMD8 are key determinants for the conformation of the mature γ-secretase complex, participating in the switch between the physiological and pathological functional conformations of the γ-secretase.     

Encounter with New Resources Causes Polarized Growth of the Cord-Forming Basidiomycete Phanerochaete velutina on Soil

Abstract The development and physiology of cord-forming saprotrophic basidiomycetes, which form extensive and persistent mycelial networks in woodland ecosystems, can be conveniently studied on non-sterile soil in laboratory microcosms mimicking field conditions. Morphological responses of Phanerochaete velutina mycelial systems to resource encounters, and decay partitioning following encounters, varied according to whether simulated woody litter was unsterile or autoclaved and on whether encounter took place at the mycelial foraging front or behind the margin (simulating litter fall onto established systems in the field). Results show that encounter of discrete resources by P. velutina is rapidly communicated to the entire mycelial system; that resource capture takes high priority at the expense of continued system extension and decay-derived carbon reallocation; and that polarized growth toward newly encountered resources, previously considered to occur infrequently with this species, may be readily detected using image analysis techniques. Potential advantages of polarized development of P. velutina are discussed.     

The consequences of metabolic changes in high-yielding dairy cows on oocyte and embryo quality

Unsatisfactory reproductive performance in dairy cows, such as reduced conception rates, in addition to an increased incidence of early embryonic mortality, is reported worldwide and has been associated with a period of negative energy balance (NEB) early post partum. Typically, NEB is associated with biochemical changes such as high non-esterified fatty acid (NEFA), high β-hydroxybutyrate (β-OHB) and low glucose concentrations. The concentrations of these and other metabolites in the follicular fluid (FF) of high-yielding dairy cows during NEB were determined and extensively analyzed, and then were replicated in in vitro maturation models to investigate their effect on oocyte quality. The results showed that typical metabolic changes during NEB are well reflected in the FF of the dominant follicle. However, the oocyte seems to be relatively isolated from extremely elevated NEFA or very low glucose concentrations in the blood. Nevertheless, the in vitro maturation models revealed that NEB-associated high NEFA and low glucose levels in the FF are indeed toxic to the oocyte, resulting in deficient oocyte maturation and developmental competence. Induced apoptosis and necrosis in the cumulus cells was particularly obvious. Furthermore, maturation in saturated free fatty acid-rich media had a carry-over effect on embryo quality, leading to reduced cryotolerance of day 7 embryos. Only β-OHB showed an additive toxic effect in moderately hypoglycemic maturation conditions. These in vitro maturation models, based on in vivo observations, suggest that a period of NEB may hamper the fertility of high-yielding dairy cows through increased NEFA and decreased glucose concentrations in the FF directly affecting oocyte quality. In addition to oocyte quality, these results also demonstrate that embryo quality is reduced following an NEB episode. This important observation may be linked to the typical diet provided to stimulate milk yield, or to physiological adaptations sustaining the high milk production. Research into this phenomenon is ongoing.