Plasma Biomarkers Discriminate Clinical Forms of Multiple Sclerosis

Multiple sclerosis, the most common cause of neurological disability in young population after trauma, represents a significant public health burden. Current challenges associated with management of multiple sclerosis (MS) patients stem from the lack of biomarkers that might enable stratification of the different clinical forms of MS and thus prompt treatment for those patients with progressive MS, for whom there is currently no therapy available. In the present work we analyzed a set of thirty different plasma cytokines, chemokines and growth factors present in circulation of 129 MS patients with different clinical forms (relapsing remitting, secondary progressive and primary progressive MS) and 53 healthy controls, across two independent cohorts. The set of plasma analytes was quantified with Luminex xMAP technology and their predictive power regarding clinical outcome was evaluated both individually using ROC curves and in combination using logistic regression analysis. Our results from two independent cohorts of MS patients demonstrate that the divergent clinical and histology-based MS forms are associated with distinct profiles of circulating plasma protein biomarkers, with distinct signatures being composed of chemokines and growth/angiogenic factors. With this work, we propose that an evaluation of a set of 4 circulating biomarkers (HGF, Eotaxin/CCL11, EGF and MIP-1β/CCL4) in MS patients might serve as an effective tool in the diagnosis and more personalized therapeutic targeting of MS patients.     

Protein binding and stability of norepinephrine in human blood plasma. Involvement of prealbumin, alpha 1-acid glycoprotein and albumin

The binding of norepinephrine (NE) to plasma proteins of fresh human blood obtained from healthy volunteers was studied by ultrafiltration at different NE concentrations and incubation times at 37 degrees C. At 1.7 nM L-[3H]-NE binding was approximately 25%. The binding was rapid and was not influenced by the incubation time. [3H]-NE could be dissociated from its binding sites by acid precipitation and, after HPLC, showed to be unchanged NE. No difference in NE binding was found between plasma collected in EGTA-GSH or heparin solution. There was no degradation of NE when incubated in plasma at 37 degrees C for 10 h, even without the addition of antioxidants. Therefore, in the present study, binding represented interaction of unchanged NE with plasma proteins. The whole plasma binding was saturable over the range of 0.66 nM to 0.59 mM of NE. Scatchard plot of specific binding revealed high-affinity sites with a Kd of 5.4 nM and a Bmax of 3.9 fmoles.mg-1 protein, and low-affinity sites with a Kd of 2.7 microM and a Bmax of 3.3 pmoles.mg-1 protein. Electrophoretic characterization of NE-binding proteins showed that about 60% of bound NE was associated to albumin, and 20% to prealbumin. NE binding to pure human plasma proteins was also studied using ultrafiltration. Scatchard analyses revealed a single class of very high-affinity binding sites for prealbumin (Kd 4.9 nM), a single class of binding sites for alpha 1-acid glycoprotein (Kd 54 microM) and two classes of binding sites for albumin with high (Kd 1.7 microM) and low (Kd 0.8 mM) affinities respectively. The main results obtained in this study - a) reversibility of NE binding, b) stability of free and bound NE in plasma, c) involvement of the prealbumin as a specific binding protein - point out to a specific transport for NE in human blood plasma.     

Effect of fertilizers on Cd accumulation and subcellular distribution of two cosmos species (Cosmos sulphureus and Cosmos bipinnata)

Addition of fertilizer amendments is regarded as an ideal approach to enhancing phytoextraction. However, there is little information available on the influence of common fertilizers on Cd accumulation of two newly reported Cd accumulators, Cosmos sulphureus and Cosmos bipinnata (C. sulphureus and C. bipinnata). The effects of N (CO(NH₂)₂), NP (CO(NH₂)₂ + Ca(H₂PO₄)₂), and NPK (CO(NH₂)₂ + Ca(H₂PO₄)₂ + KCl) fertilizers on Cd accumulation and subcellular distribution of C. sulphureus and C. bipinnata were studied in a 70-d pot experiment. The results showed that Cd uptake of C. sulphureus and C. bipinnata with NPK fertilizer was significantly higher than control, N, and NP fertilizers, especially 3.8- and 4.7-fold higher than control (p < 0.05). Compared with C. bipinnata, C. sulphureus achieved higher biomass and Cd uptake in aboveground parts under fertilizer treatments, especially NPK fertilizer. The Cd subcellular distribution revealed that segregation of Cd to Cd-rich granules (MRG) might play an important role in Cd detoxification in both species. C. sulphureus is more likely than C. bipinnata to separate the Cd in MRG and reduce the partition in the heat-denatured protein fraction, especially with NPK fertilizer. Therefore, C. sulphureus combined with NPK fertilizers could be an effective method to remediate Cd-polluted farmland soils in China.     

Effects of larval competition on survival and growth in Mediterranean fruit flies

1. Larval success was compared when one, two, or three egg clutches were laid in kumquat fruits (≈ 10 ml in volume) either successively on the same day or at the rate of one clutch per day. 2. Increased clutch density was associated with a significant decrease in larval survival rate and non‐significant decreases in larval growth rate and pupal mass. 3. Larval and pupal parameters showed significantly larger variance when clutches were laid on successive days than on the same day, suggesting a competitive advantage for older larvae over younger larvae. 4. The results suggest that, in small fruit, reduced fitness due to larval competition may act against possible fitness benefits due to social facilitation among adult females, hence reducing the likelihood of non‐linear population dynamics caused by processes such as the Allee effect.     

A Microarray-Based Analysis Reveals that a Short Photoperiod Promotes Hair Growth in the Arbas Cashmere Goat

Many animals exhibit different behaviors in different seasons. The photoperiod can have effects on migration, breeding, fur growth, and other processes. The cyclic growth of the fur and feathers of some species of mammals and birds, respectively, is stimulated by the photoperiod as a result of hormone-dependent regulation of the nervous system. To further examine this phenomenon, we evaluated the Arbas Cashmere goat (Capra hircus), a species that is often used in this type of research. The goats were exposed to an experimentally controlled short photoperiod to study the regulation of cyclic cashmere growth. Exposure to a short photoperiod extended the anagen phase of the Cashmere goat hair follicle to increase cashmere production. Assessments of tissue sections indicated that the short photoperiod significantly induced cashmere growth. This conclusion was supported by a comparison of the differences in gene expression between the short photoperiod and natural conditions using gene chip technology. Using the gene chip data, we identified genes that showed altered expression under the short photoperiod compared to natural conditions, and these genes were found to be involved in the biological processes of hair follicle growth, structural composition of the hair follicle, and the morphogenesis of the surrounding skin appendages. Knowledge about differences in the expression of these genes as well as their functions and periodic regulation patterns increases our understanding of Cashmere goat hair follicle growth. This study also provides preliminary data that may be useful for the development of an artificial method to improve cashmere production by controlling the light cycle, which has practical significance for livestock breeding.     

Stereospecific reactivation of human brain and erythrocyte acetylcholinesterase inhibited by 1,2,2-trimethylpropyl methylphosphonofluoridate (soman)

Human erythrocyte and brain acetylcholinesterase are preferentially inhibited by the P(-)-isomers of C(+/-)P(+/-)-soman. The enzymes inhibited by the P(-)-isomers behave similarly with respect to oxime-induced reactivation and aging. HI-6 is the best reactivator for C(+)P(-)-soman-inhibited acetylcholinesterases. Oxime-induced reactivation of the C(-)P(-)-soman-inhibited acetylcholinesterases is much more difficult to achieve.     

Comparative study of the microtriches of adult Cestodes (Proteocephalidea: Monticelliidae), and some comments on their systematic value

The surface of the tegument of the scolex and the immature proglottides of Monticellia belavistensis, M. ventrei, Nomimoscolex chubbi, and N. lopesi is described using scanning electron microscopy. Only blade-like spiniform microtriches and filiform microtriches were observed in the species studied. The types, size and density of microtriches on the apical region surface of the scolex, central cavity surface of suckers, marginal ring surface of suckers, non-adherent surface of suckers, proliferation zone surface, and immature proglottis surface were compared among these species. The distribution pattern of the microtriches was not a reliable feature to discriminate among the genera considered in this study. It varied in each of the species of Monticellia examined, and did not permit to split the heterogeneous genus Nomimoscolex. However, the microthrix pattern can be regarded as an additional diagnostic feature to distinguish among species of proteocephalideans. Further comparative research involving other species of proteocephalid taxa is needed to elucidate the systematic value of the tegumental morphology.     

Paracoccidioides brasiliensis Interferes on Dendritic Cells Maturation by Inhibiting PGE2 Production

Paracoccidioidomycosis (PCM) is a systemic mycosis, endemic in most Latin American countries, especially in Brazil, whose etiologic agent is the thermodimorphic fungus of the genus Paracoccidioides, comprising cryptic species of Paracoccidioides brasiliensis, S1, PS2, PS3 and Paracoccidioides lutzii. The mechanisms involved in the initial interaction of the fungus with cells of the innate immune response, as dendritic cells (DCs), deserve to be studied. Prostaglandins (PGs) are eicosanoids that play an important role in modulating functions of immune cells including DCs. Here we found that human immature DCs derived from the differentiation of monocytes cultured with GM-CSF and IL-4 release substantial concentrations of PGE₂, which, however, were significantly inhibited after challenge with P. brasiliensis. In vitro blocking of pattern recognition receptors (PRRs) by monoclonal antibodies showed the involvement of mannose receptor (MR) in PGE₂ inhibition by the fungus. In addition, phenotyping assays showed that after challenge with the fungus, DCs do not change their phenotype of immature cells to mature ones, as well as do not produce IL-12 p70 or adequate concentrations of TNF-α. Assays using exogenous PGE₂ confirmed an association between PGE₂ inhibition and failure of cells to phenotypically mature in response to P. brasiliensis. We conclude that a P. brasiliensis evasion mechanism exists associated to a dysregulation on DC maturation. These findings may provide novel information for the understanding of the complex interplay between the host and this fungus.