Bystander suppression of collagen-induced arthritis in mice fed ovalbumin

We wanted to assess whether B-cell and/or T-cell responses to collagen and thereby the course of collagen-induced arthritis could be suppressed by regulatory mechanisms associated with oral tolerance to an unrelated protein. DBA/1 mice were fed ovalbumin (OVA)-containing pellets ad libitum for 1 week and subsequently coimmunized twice, with a mixture of bovine collagen type II (BCII) and OVA in Freund's complete adjuvant. Mice fed OVA before coimmunization with BCII and OVA had significantly lower arthritic scores than mice immunized with BCII only. Their body weight increased during the study period and their anti-BCII antibody activity was significantly IgG_2a lower. The frequency of spleen cells producing IgG anti-BCII antibody was also reduced. Coimmunization per se slightly ameliorated the development of arthritis, resulting in an early, transient reduction. It resulted in significantly higher IgG₁ anti-BCII antibody activity and increased splenocyte secretion of IFN-γ and IL-10 in response to BCII. Our findings demonstrate that OVA-specific regulatory events induced by feeding OVA, i.e. bystander suppression, reduced the severity of arthritis in animals immunized with BCII and OVA. Anti-BCII specific antibody responses and cytokine secretion by types 1 and 2 T helper cells were also decreased.     

B30.2-like domain proteins: update and new insights into a rapidly expanding family of proteins

The B30.2 domain is a conserved region of around 170 amino acids associated with several different protein domains, including the immunoglobulin folds of butyrophilin and the RING finger domain of ret finger protein. We recently reported several novel members of this family as well as previously undescribed protein families possessing the B30.2 domain. Many proteins have subsequently been found to possess this domain, including pyrin/marenostrin and the midline 1 (MID1) protein. Mutations in the B30.2 domain of pyrin/marenostrin are implicated in familial Mediterranean fever, and partial loss of the B30.2 domain of MID1 is responsible for Opitz G/BBB syndrome, characterized by developmental midline defects. In this study, we scrutinized the available sequence data bases for the identification of novel B30.2 domain proteins using highly sensitive database-searching tools. In addition, we discuss the chromosomal localization of genes in the B30.2 family, since the encoded proteins are likely to be involved in other forms of periodic fever, autoimmune, and genetic diseases.      

Neonatal hyperleptinaemia programmes anxiety-like and novelty seeking behaviours but not memory/learning in adult rats

Leptin treatment during lactation programmes for leptin resistance at adulthood, evidenced by hyperleptinaemia, hyperphagia and overweight. Since leptin is known to affect stress response, emotional behaviour and memory/learning performance, the objective of the present study was to evaluate whether neonatal hyperleptinaemia programmes anxiety-like and novelty-seeking behaviours as well as memory/learning in adult male rats. During the first 10 days of lactation (from PN1 to PN10), pups were s.c. injected once per day with either 50 μL of saline (SAL) or murine leptin (LEP — 8 μg/100 g of body mass, saline diluted). Serum leptin was assessed at PN10 and at PN150. Two separate experiments were carried out: 1) experiment one: at PN137, 29 SAL and 30 LEP rats were tested in the elevated plus-maze (EPM) and, at PN142, their behaviour was assessed in the hole board (HB) arena; 2) experiment two: at PN140, a different group of rats consisting of 53 SAL and 56 LEP animals were tested in the radial arm water maze (RAWM). Serum leptin concentration was higher in the LEP group at PN10 and at PN150. LEP animals spent significantly less time in the open arms of the EPM. Furthermore, the number of nose-pokes in the HB arena was higher in LEP rats. There were no differences between groups regarding latency to find the hidden platform in the RAWM. Our results suggests that a central mechanism of leptin resistance at adulthood, caused by neonatal hyperleptinaemia, is associated with an increased level of anxiety and also that it intensifies novelty seeking-behaviour.     

Mechanism of Formation of Novel Covalent Drug·DNA Interstrand Cross-Links and Monoadducts by Enediyne Antitumor Antibiotics

The potent enediyne antitumor antibiotic C1027 has been previously reported to induce novel DNA interstrand cross-links and drug monoadducts under anaerobic conditions [Xu et al. (1997) J. Am. Chem. Soc. 119, 1133-1134]. In the present study, we explored the mechanism of formation of these anaerobic DNA lesions. We found that, similar to the aerobic reaction, the diradical species of the activated drug initiates anaerobic DNA damage by abstracting hydrogen atoms from the C4', C1', and C5' positions of the A1, A2, and A3 nucleotides, respectively, in the most preferred 5'GTTA1T/5'ATA2A3C binding sequence. It is proposed that the newly generated deoxyribosyl radicals, which cannot undergo oxidation, likely add back onto the nearby unsaturated ring system of the postactivated enediyne core, inducing the formation of interstrand cross-links, connecting either A1 to A2 or A1 to A3, or drug monoadducts mainly on A2 or A3. Comparative studies with other enediynes, such as neocarzinostatin and calicheamicin gamma1I under similar reaction conditions indicate that the anaerobic reaction process is a kinetically competitive one, depending on the proximity of the drug unsaturated ring system or dioxygen to the sugar radicals and their quenching by other hydrogen sources such as solvent or thiols. It was found that C1027 mainly generates interstrand cross-links, whereas most of the anaerobic lesions produced by neocarzinostatin are drug monoadducts. Calicheamicin gamma1I was found to be less efficient in producing both lesions. The anaerobic DNA lesions induced by enediyne antitumor antibiotics may have important implications for their potent cytotoxicity in the central regions of large tumors, where relative anaerobic conditions prevail.     

Mechanistic aspects of biosynthesis of silver nanoparticles by several <Emphasis Type="Italic">Fusarium oxysporum</Emphasis> strains

Extracellular production of metal nanoparticles by several strains of the fungus Fusarium oxysporum was carried out. It was found that aqueous silver ions when exposed to several Fusarium oxysporum strains are reduced in solution, thereby leading to the formation of silver hydrosol. The silver nanoparticles were in the range of 20–50 nm in dimensions. The reduction of the metal ions occurs by a nitrate-dependent reductase and a shuttle quinone extracellular process. The potentialities of this nanotechnological design based in fugal biosynthesis of nanoparticles for several technical applications are important, including their high potential as antibacterial material.     

Leptin-programmed rats respond to cold exposure changing hypothalamic leptin receptor and thyroid function differently from cold-exposed controls

We showed that neonatal leptin treatment programmes for hyperleptinemia and central leptin resistance both at 30days-old and adulthood, while programmes for lower serum T3 at 30days-old, but higher thyroid hormones (TH) at adulthood. As in these animals, acute cold at 30days-old normalized leptinemia and restored the expression of hypothalamic leptin receptor (OBR), here we evaluate the effect of cold exposure on the thyroid function and OBR in adult rats programmed by neonatal hyperleptinemia. Pups were divided into 2 groups: Lep-injected with leptin (8μg/100g/BW, sc) for the first 10days of lactation, and C-injected with saline. At 150days, both groups were subdivided into: LepC and CC, which were exposed to 8°C for 12h. Serum leptin, TH, TSH, liver type I and brown adipose tissue (BAT) type II deiodinases (D1 and D2) activities, liver mitochondrial alpha-glycerol-3-phosphate dehydrogenase (mGPD) activity and adrenal catecholamine content were measured. Hypothalamic and thyroid OBR protein contents were evaluated. Differences were significant when p<0.05. Lep group had hyperleptinemia (+19%), higher T4 (+20%) and T3 (+30%) with lower TSH (-55%), higher liver D1 (1.4 fold-increase), lower BAT D2 (-44%) and liver mGPD activities (-55%), higher adrenal catecholamines (+44%), lower hypothalamic OBR (-51%) and normal thyroid OBR. Cold exposure normalized leptinemia, D1, mGPD, catecholamine and hypothalamic OBR. However, cold exposure further increased TH and decreased D2. Thus, cold exposure normalizes most of the changes programmed by neonatal hyperleptinemia, at the expense of worsening the hyperthyroidism and BAT thermogenesis.     

Poor physical fitness is independently associated with mild cognitive impairment in elderly Koreans

The purpose of this study was to investigate the association between physical fitness and mild cognitive impairment (MCI) in elderly Koreans. This was a cross-sectional study that involved 134 men and 299 women aged 65 to 88 years. Six senior fitness tests were used as independent variables: 30 s chair stand for lower body strength, arm curl for upper body strength, chair-sit-and-reach for lower body flexibility, back scratch for upper body flexibility, 8-ft up-and-go for agility/dynamic balance, and 2-min walk for aerobic endurance. Global cognitive function was assessed using the Korean version of the Mini-Mental State Examination (MMSE). Potential covariates such as age, education levels, blood lipids, and insulin resistance (IR) markers were also assessed. Compared to individuals without MMSE-based MCI, individuals with MMSE-based MCI had poor physical fitness based on the senior fitness test (SFT). There were significant positive trends observed for education level (p=0.001) and MMSE score (p<0.001) across incremental levels of physical fitness in this study population. Individuals with moderate (OR=0.341, p=0.006) and high (OR=0.271, p=0.007) physical fitness based on a composite score of the SFT measures were less likely to have MMSE-based MCI than individuals with low physical fitness (referent, OR=1). The strength of the association between moderate (OR=0.377, p=0.038) or high (OR=0.282, p=0.050) physical fitness and MMSE-based MCI was somewhat attenuated but remained statistically significant even after adjustment for the measured compounding factors. We found that poor physical fitness was independently associated with MMSE-based MCI in elderly Koreans.     

Cell signaling as a cognitive process

Cellular identity as defined through morphology and function emerges from intracellular signaling networks that communicate between cells. Based on recursive interactions within and among these intracellular networks, dynamical solutions in terms of biochemical behavior are generated that can differ from those in isolated cells. In this way, cellular heterogeneity in tissues can be established, implying that cell identity is not intrinsically predetermined by the genetic code but is rather dynamically maintained in a cognitive manner. We address how to experimentally measure the flow of information in intracellular biochemical networks and demonstrate that even simple causality motifs can give rise to rich, context‐dependent dynamic behavior. The concept how intercellular communication can result in novel dynamical solutions is applied to provide a contextual perspective on cell differentiation and tumorigenesis.