Neglected markers: altered serum proteome in murine models of disease

More than a decade ago our groups pioneered the analysis of serum proteins of laboratory animals with up-to-date proteomic techniques. We were, and still are, convinced that conforming animal procedures to the minimally invasive approaches typical of clinical biochemistry focuses attention on the actual conditions under which any finding arrived at on animal models of disease may eventually be applied to human patients for screening/diagnosis. We are also convinced that, besides the proteins present in trace level as a result of tissue leakage during disorders affecting specific peripheral organs, changes in the concentration of some of the major serum proteins as part of an acute-phase response may be taken as biological end-points during a number of experimental procedures. When reviewing literature data about proteomic investigations on plasma or serum of mice, we realized that not much work has been done in the direction we favor. In addition, we noticed that sometimes information about serum proteome has been coarsely treated and in a few cases even misunderstood/misused. In the following, we present current findings on serum/plasma proteome of the laboratory mouse not only under control conditions and during an experimentally induced acute-phase reaction, but also in a number of models of disease, mainly related to cancer and to metabolic disorders.     

Identification of serum proteomic biomarkers for early porcine reproductive and respiratory syndrome (PRRS) infection

ABSTRACT: BACKGROUND: Porcine reproductive and respiratory syndrome (PRRS) is one of the most significant swine diseases worldwide. Despite its relevance, serum biomarkers associated with early-onset viral infection, when clinical signs are not detectable and the disease is characterized by a weak anti-viral response and persistent infection, have not yet been identified. Surface-enhanced laser desorption ionization time of flight mass spectrometry (SELDI-TOF MS) is a reproducible, accurate, and simple method for the identification of biomarker proteins related to disease in serum. This work describes the SELDI-TOF MS analyses of sera of 60 PRRSV-positive and 60 PRRSV-negative, as measured by PCR, asymptomatic Large White piglets at weaning. Sera with comparable and low content of hemoglobin (< 4.52 ug/mL) were fractionated in 6 different fractions by anion-exchange chromatography and protein profiles in the mass range 1-200 kDa were obtained with the CM10, IMAC30, and H50 surfaces. RESULTS: A total of 200 significant peaks (p < 0.05) were identified in the initial discovery phase of the study and 47 of them were confirmed in the validation phase. The majority of peaks (42) were up-regulated in PRRSV-positive piglets, while 5 were down-regulated. A panel of 14 discriminatory peaks identified in fraction 1 (pH=9), on the surface CM10, and acquired at low focus mass provided a serum protein profile diagnostic pattern that enabled to discriminate between PRRSV-positive and -negative piglets with a sensitivity and specificity of 77% and 73%, respectively. CONCLUSIONS: SELDI-TOF MS profiling of sera from PRRSV-positive and PRRSV-negative asymptomatic piglets provided a proteomic signature with large scale diagnostic potential for early identification of PRRSV infection in weaning piglets. Furthermore, SELDI-TOF protein markers represent a refined phenotype of PRRSV infection that might be useful for whole genome association studies.     

The Right Time to Happen: Play Developmental Divergence in the Two Pan Species

Bonobos, compared to chimpanzees, are highly motivated to play as adults. Therefore, it is interesting to compare the two species at earlier developmental stages to determine how and when these differences arise. We measured and compared some play parameters between the two species including frequency, number of partners (solitary, dyadic, and polyadic play), session length, and escalation into overt aggression. Since solitary play has a role in developing cognitive and physical skills, it is not surprising that chimpanzees and bonobos share similar developmental trajectories in the motivation to engage in this activity. The striking divergence in play developmental pathways emerged for social play. Infants of the two species showed comparable social play levels, which began to diverge during the juvenile period, a ‘timing hotspot’ for play development. Compared to chimpanzees, social play sessions in juvenile bonobos escalated less frequently into overt aggression, lasted longer, and frequently involved more than two partners concurrently (polyadic play). In this view, play fighting in juvenile bonobos seems to maintain a cooperative mood, whereas in juvenile chimpanzees it acquires more competitive elements. The retention of juvenile traits into adulthood typical of bonobos can be due to a developmental delay in social inhibition. Our findings show that the divergence of play ontogenetic pathways between the two Pan species and the relative emergence of play neotenic traits in bonobos can be detected before individuals reach sexual maturity. The high play motivation showed by adult bonobos compared to chimpanzees is probably the result of a long developmental process, rooted in the delicate transitional phase, which leads subjects from infancy to juvenility.     

Lingual tuberculosis: a rare disease in Western countries

Here we report on two consecutive cases of tuberculosis in immunocompetent HIV-negative patients with lingual lesions. In both patients diagnosis was delayed. Disease progressed involving the lungs, lymph nodes and also the brain. Both patients are disease-free at 30 and 22 month follow-up respectively. Isolated Mycobacterium tuberculosis from these patients was multi-susceptible. Tuberculosis lesions of the oral cavity and brain are infrequently diagnosed in immunocompetent subjects from Western countries. Clinicians must take into greater consideration tuberculosis as a possible diagnosis when diagnosing chronic and/or recurrent lingual lesions even in the absence of pulmonary lesions.     

An in vitro evaluation of the effect of probiotics and prebiotics on the metabolic profile of human microbiota

In the current study, batch culture fermentations on fecal samples of 3 healthy individuals were performed to assess the effect of the addition of prebiotics (FOS), probiotics (Bifidobacterium longum Bar33 and Lactobacillus helveticus Bar13) and synbiotics (B. longum Bar33 + L. helveticus Bar13 + FOS) on the fecal metabolic profiles. A total of 84 different metabolites belonging to the families of sulfur compounds, nitrogen compounds, aldehydes, ketones, esters, alcohols, phenols, organic acids, and hydrocarbons were detected by GC-MS/SPME analysis. The highest number of metabolites varied in concentration in the models with added FOS and synbiotics, where several metabolic signatures were found in common. The increase of butyrate represented the greatest variation registered after the addition of FOS alone. Following the B. longum Bar33 addition, 2-methyl butyrate underwent the most evident variation. In the batch fermentation with added L. helveticus Bar13, the decrease of pyridine and butandiene was observed together with the increase of 2-methyl-5-ethyl-pyrazine, 2-butanone and butyrate. The modification of the fecal metabolic profiles induced by the simultaneous addition of B. longum Bar33 and L. helveticus Bar13 was very similar to that observed after the supplementation with L. helveticus Bar13, regarding mainly the decrease of pyridine and the increase of butyrate.     

[35S]GTPγS binding studies of amphiphilic drugs-activated Gi proteins: A caveat

This paper documents a serious problem met during the testing of Gi protein-activating properties of a new series of synthetic compounds by measuring the induced binding of [³⁵S]GTPγS to different subtypes of Gi protein. The problem arose from the strong affinity between [³⁵S]GTPγS and the tested compounds, that are characterized by several (2–4) positive charges and high lipophilicity. Apparently, such affinity yields insoluble, labelled complexes that, also in the absence of Gi protein, are retained on the filters and give rise to false positive results.     

Calcareous nannofossil changes during the late Callovian–early Oxfordian cooling phase

Calcareous nannofossil quantitative and biostratigraphic analyses integrated with carbon and oxygen stable isotopes were carried out on the core ANDRA (Agence Nationale pour la gestion des Déchets Radio-Actifs—FRANCE) HTM 102 across the Callovian/Oxfordian boundary drilled at Cirfontaines-en-Ornois, Départment de Haute-Marne, eastern France. Calcareous nannofossil assemblages at the Callovian–Oxfordian transition are dominated by the genus Watznaueria. An increase in abundance of Biscutum spp. and A-group, which consists of Axopodorhabdus spp. (A. atavus, A. rahla, and A. cylindratus), Podorhabdus grassei, Octopodorhabdus decussatus, Hexapodorhabdus cuvillieri (family Axopodorhabdaceae), and Triscutum spp., correlates with a significant positive excursion in δ¹⁸O suggesting that these groups were probably adapted to cooler surface waters. A positive increase in δ¹³C values is coupled with high abundances of eutrophic taxa such as Zeughrabdotus erectus, Biscutum spp., and small-sized Watznaueria britannica, and a decrease in abundance of the big and oligotrophic taxa Schizosphaerella punctulata and Watznaueria manivitae. Climate cooling across the Callovian/Oxfordian boundary probably triggered a breakdown in stratification of surface waters leading to more intense nutrient recycling and higher primary productivity that favoured the shift in abundance of small-sized eutrophic taxa in the East Paris Basin.     

Evidence for l-fucose (6-deoxy-l-galactopyranose)-mediated adherence of Campylobacter spp. to epithelial cells

Abstract 14 strains of Campylobacter isolated from humans and birds were tested for adhesion on intestine cell line. All the strains showed quick adhesion which was inhibited by l -fucose (6-deoxy- l -galactopyranose), among the sugars and lectins used in the adhesion inhibition assay. Inhibition was a function of l -fucose concentration and was not complete, suggesting that beside l -fucose other receptors—or nonspecific interactions—may cooperate in the cell binding by Campylobacter .