Human alpha-fetoprotein binds to primary macrophages

We have previously reported that alpha-fetoprotein (AFP) inhibits infection of human monocyte-derived macrophages (MDM) by R5-HIV-1 strains and that a peptide mimicking the clade B HIV-1 gp120 consensus V3 domain (V3Cs) binds to CCR5. We demonstrate here that AFP binds high- and low-affinity binding sites of MDM, characterized, respectively, by 5.15 and 100nM K(d) values. Heat denaturation or neuraminidase treatment of AFP inhibits this binding, suggesting the involvement of protein-protein and lectin-carbohydrate interactions. Moreover, AFP displaces V3Cs binding to MDM. In addition, MIP-1beta, the most specific CCR5 ligand, displaces AFP binding to MDM (IC(50)=4.3nM). Finally, we demonstrate that AFP binds to a ligand of HIV-gp120 V3Cs domain, CCR5, expressed by MDM and by HeLa cells expressing CCR5. Such binding is not observed in the presence of HeLa cells lacking CCR5. The present results provide strong evidence that AFP directly binds to CCR5 expressed by human primary macrophages and by transfected CCR5+ HeLa cells.     

Isolation,identification and localization of a second beetle antidiuretic peptide

We isolated from head extracts of Tenebrio molitor a peptide that inhibits fluid secretion by the Malpighian tubules of this insect. This second antidiuretic factor, ADFb, like the previously published ADFa, works through cyclic GMP as a second messenger. It has primary structure Tyr-Asp-Asp-Gly-Ser-Tyr-Lys-Pro-His-Ile-Tyr-Gly-Phe-OH with an EC(50) of approximately 240 pM in a fluid secretion assay. This peptide is now the second sequenced endogenous insect ADF which inhibits Malpighian tubule fluid secretion. Immunohistochemical techniques show that the peptide is localized in the brain; it appears to be produced mainly in two pairs of bilaterally symmetrical cells in the protocerebrum.     

Synthesis and antimalarial activity of 2-methoxyprop-2-yl peroxides derivatives

2-Methoxyprop-2-yl peroxides were synthesized and evaluated in vitro against Plasmodium falciparum. These acyclic artemisinin-related peroxides revealed moderate to good activity but were devoid of alkylating property towards the synthetic model of heme Mn(II)-TPP.     

RFLP-based analysis of three RbcS subfamilies in diploid and polyploid species of wheat

The RbcS multigene family of hexaploid (bread) wheat, Triticum aestivum (genome BBAADD), which encodes the small subunit of Rubisco, comprises at least 22 genes. Based on their 3′ non-coding sequences, these genes have been classified into four subfamilies (SFs), of which three (SF-2, SF-3 and SF-4) are located on chromosomes of homoeologous group 2 and one (SF-1) on homoeologous group 5. In the present study we hybridized three RbcS subfamily-specific probes (for SF-1, SF-2 and SF-3) to total DNA digested with four restriction enzymes and analyzed the RFLP patterns of these subfamilies in eight diploid species of Aegilops and Triticum, and in two tetraploid and one hexaploid species of wheat (the diploid species are the putative progenitors of the polyploid wheats). The three subfamilies varied in their level of polymorphism, with SF-2 being the most polymorphic in all species. In the diploids, the order of polymorphism was SF-2 > SF-3 > SF-1, and in the polyploids SF-2 > SF-1 > SF-3. The RbcS genes of the conserved SF-1 were previously reported to have the highest expression levels in all the wheat tissues studied, indicating a negative correlation between polymorphism and gene expression. Among the diploids, the species with the D and the S genomes were the most polymorphic and the A-genome species were the least polymorphic. The polyploids were less polymorphic than the diploids. Within the polyploids, the A genome was somewhat more polymorphic than the B genome, while the D genome was the most conserved. Among the diploid species with the A genome, the RFLP pattern of T. urartu was closer to that of the A genome of the common wheat cultivar Chinese Spring (CS) than to that of T. monococcum. The pattern in Ae. tauschii was similar to that of the D genome of CS. Only partial resemblance was found between the RFLP patterns of the species with the S genome and the B genome of CS. Received: 10 February 2000 / Accepted: 21 February 2000     

Synthesis and biological activity of N-aroyl-tetrahydro-γ-carbolines

Research on dual inhibitors of both 5-LOX and COXs gained interest due to the overexpressions of these enzymes during the malignant state of the evolution of prostate cancer. In order to take part in this research, new N-aroyl-tetrahydro-γ-carbolines issued from the modification of Indomethacin have been synthesised. As for the NSAIDs, the compounds have been tested for their activity against COX₁, COX₂ plus against 5-LOX and against the proliferation of malignant prostate cancer. Interesting cytotoxic activities and selectivities of some tetrahydro-γ-carboline derivatives have been obtained.     

Bioactive peptides,networks and systems biology

Bioactive peptides are a group of diverse intercellular signalling molecules. Almost half a century of research on this topic has resulted in an enormous amount of data. In this essay, a general perspective to interpret all these data will be given. In classical endocrinology, neuropeptides were thought of as simple signalling molecules that each elicit one response. However, the fact that the total bioactive peptide signal is far from simple puts this view under pressure. Cells and tissues express many different bioactive peptides and they are also able to respond to many different bioactive peptides, indicating that multiple receptors and signal transduction pathways are present in a single cell. Therefore, the authors suggest that the bioactive peptide signalling system should be regarded in the context of network and systems biology. Bioactive peptides can best be viewed as an extension of the protein interaction network that allows regulating and fine‐tuning the metabolism of the different cells and tissues in the body. The cell thus responds to the ‘peptidome’ instead of to a single peptide. The intracellular part of this signalling network consists of the various signalling transduction cascades. Recently, new systems biology approaches have emerged for the modelling of cell signalling. The network and systems biology approach is also able to shed new light on the evolution of intercellular signalling.     

The Effect of Two Speed Endurance Training Regimes on Performance of Soccer Players

In order to better understand the specificity of training adaptations, we compared the effects of two different anaerobic training regimes on various types of soccer-related exercise performances. During the last 3 weeks of the competitive season, thirteen young male professional soccer players (age 18.5±1 yr, height 179.5±6.5 cm, body mass 74.3±6.5 kg) reduced the training volume by ~20% and replaced their habitual fitness conditioning work with either speed endurance production (SEP; n = 6) or speed endurance maintenance (SEM; n = 7) training, three times per wk. SEP training consisted of 6–8 reps of 20-s all-out running bouts followed by 2 min of passive recovery, whereas SEM training was characterized by 6–8 x 20-s all-out efforts interspersed with 40 s of passive recovery. SEP training reduced (p<0.01) the total time in a repeated sprint ability test (RSA_t) by 2.5%. SEM training improved the 200-m sprint performance (from 26.59±0.70 to 26.02±0.62 s, p<0.01) and had a likely beneficial impact on the percentage decrement score of the RSA test (from 4.07±1.28 to 3.55±1.01%) but induced a very likely impairment in RSA_t (from 83.81±2.37 to 84.65±2.27 s). The distance covered in the Yo-Yo Intermittent Recovery test level 2 was 10.1% (p<0.001) and 3.8% (p<0.05) higher after SEP and SEM training, respectively, with possibly greater improvements following SEP compared to SEM. No differences were observed in the 20- and 40-m sprint performances. In conclusion, these two training strategies target different determinants of soccer-related physical performance. SEP improved repeated sprint and high-intensity intermittent exercise performance, whereas SEM increased muscles’ ability to maximize fatigue tolerance and maintain speed development during both repeated all-out and continuous short-duration maximal exercises. These results provide new insight into the precise nature of a stimulus necessary to improve specific types of athletic performance in trained young soccer players.     

Association of Hematological Variables with Team-Sport Specific Fitness Performance

Purpose

We investigated association of hematological variables with specific fitness performance in elite team-sport players.

Methods

Hemoglobin mass (Hb_mass) was measured in 25 elite field hockey players using the optimized (2 min) CO-rebreathing method. Hemoglobin concentration ([Hb]), hematocrit and mean corpuscular hemoglobin concentration (MCHC) were analyzed in venous blood. Fitness performance evaluation included a repeated-sprint ability (RSA) test (8 x 20 m sprints, 20 s of rest) and the Yo-Yo intermittent recovery level 2 (YYIR2).

Results

Hb_mass was largely correlated (r = 0.62, P<0.01) with YYIR2 total distance covered (YYIR2_TD) but not with any RSA-derived parameters (r ranging from -0.06 to -0.32; all P>0.05). [Hb] and MCHC displayed moderate correlations with both YYIR2_TD (r = 0.44 and 0.41; both P<0.01) and RSA sprint decrement score (r = -0.41 and -0.44; both P<0.05). YYIR2_TD correlated with RSA best and total sprint times (r = -0.46, P<0.05 and -0.60, P<0.01; respectively), but not with RSA sprint decrement score (r = -0.19, P>0.05).

Conclusion

Hb_mass is positively correlated with specific aerobic fitness, but not with RSA, in elite team-sport players. Additionally, the negative relationships between YYIR2 and RSA tests performance imply that different hematological mechanisms may be at play. Overall, these results indicate that these two fitness tests should not be used interchangeably as they reflect different hematological mechanisms.     

Clinical Profiles and Factors Associated with Death in Adults with Dengue Admitted to Intensive Care Units,Minas Gerais,Brazil

The purpose of our study was to describe the clinical profile of dengue-infected patients admitted to Brazilian intensive care units (ICU) and evaluate factors associated with death. A longitudinal, multicenter case series study was conducted with laboratory-confirmed dengue patients admitted to nine Brazilian ICUs situated in Minas Gerais state, southeastern Brazil from January 1, 2008, to December 31, 2013. Demographic, clinical and laboratory data; disease severity scores; and mortality were evaluated. A total of 97 patients were studied. The in-ICU and in-hospital mortality rates were 18.6% and 19.6%, respectively. Patients classified as having severe dengue according to current World Health Organization classifications showed an increased risk of death in a univariate analysis. Nonsurvivors were older, exhibited lower serum albumin concentrations and higher total leukocyte counts and serum creatinine levels. Other risk factors (vomiting, lethargy/restlessness, dyspnea/respiratory distress) were also associated with death in a univariate analysis. Multivariate analysis indicated that in-hospital mortality was significantly associated with Acute Physiology and Chronic Health Evaluation II and the Sequential Organ Failure Assessment score. The ICU and in-hospital mortality observed in this study were higher than values reported in similar studies. An increased frequency of ICU admission due to severe organ dysfunction, higher severity indices and scarcity of ICU beds may partially explain the higher mortality.