Genetic association of CCR5 promoter single nucleotide polymorphism in seronegative and seropositive rheumatoid arthritis

The aim of this study was to investigate the possible role of the CCR5 59029 A→G promoter point mutation polymorphism in determining the susceptibility to rheumatoid factor-positive and rheumatoid factor-negative rheumatoid arthritis. This polymorphism was assessed in 85 seropositive and 39 seronegative rheumatoid arthritis patients and in 126 healthy individuals of the same geographic and ethnic origin. We found an increase in the genetic frequency of the A allele in the 59029 A→G promoter region of the CCR5 receptor in patients with rheumatoid arthritis compared with healthy controls (p = 0.01; OR = 1.5, 95% CI (1.0-2.2). Likewise, the homozygous state for the A allele was found to be more frequent in rheumatoid arthritis patients, again when compared with healthy controls (p = 0.03; OR = 1.8, 95% CI 1.0-3.0). The increased frequency of the A allele was more evident in the more benign, seronegative rheumatoid arthritis group when compared with controls (p = 0.003; OR 2.4 95% CI 1.3-4.4), and when combining the A homozygous and the AG heterozygous patients compared with healthy subjects. These results suggest that this CCR5 promoter polymorphism seems to play an important role in determining different clinical courses in both forms of rheumatoid arthritis.     

Gender-dependent cellular and biochemical effects of maternal deprivation on the hippocampus of neonatal rats: a possible role for the endocannabinoid system

Adult animals submitted to a single prolonged episode of maternal deprivation (MD) [24 h, postnatal days (PND) 9-10] show behavioral alterations that resemble specific symptoms of schizophrenia. These behavioral impairments may be related to neuronal loss in the hippocampus triggered by elevated glucocorticoids. Furthermore, our previous data suggested functional relationships between MD stress and the endocannabinoid system. In this study, we addressed the effects of MD on hippocampal glial cells and the possible relationship with changes in plasma corticosterone (CORT) levels. In addition, we investigated the putative involvement of the endocannabinoid system by evaluating (a) the effects of MD on hippocampal levels of endocannabinoids (b) The modulation of MD effects by two inhibitors of endocannabinoids inactivation, the fatty acid amide hydrolase inhibitor N-arachidonoyl-serotonin (AA-5-HT), and the endocannabinoid reuptake inhibitor, OMDM-2. Drug treatments were administered once daily from PND 7 to PND 12 at a dose of 5 mg/kg, and the animals were sacrificed at PND 13. MD induced increased CORT levels in both genders. MD males also showed an increased number of astrocytes in CA1 and CA3 areas and a significant increase in hippocampal 2-arachidonoylglycerol. The cannabinoid compounds reversed the endocrine and cellular effects of maternal deprivation. We provide direct evidence for gender-dependent cellular and biochemical effects of MD on developmental hippocampus, including changes in the endocannabinoid system.     

Endosome to Golgi Transport of Ricin Is Independent of Clathrin and of the Rab9- and Rab11-GTPases

The plant toxin ricin is transported to the Golgi and the endoplasmic reticulum before translocation to the cytosol where it inhibits protein synthesis. The toxin can therefore be used to investigate pathways leading to the Golgi apparatus. Except for the Rab9-mediated transport of mannose 6-phosphate receptors from endosomes to the trans-Golgi network (TGN), transport routes between endosomes and the Golgi apparatus are still poorly characterized. To investigate endosome to Golgi transport, we have used here a modified ricin molecule containing a tyrosine sulfation site and quantified incorporation of radioactive sulfate, a TGN modification. A tetracycline-inducible mutant Rab9S21N HeLa cell line was constructed and characterized to study whether Rab9 was involved in transport of ricin to the TGN and, if not, to further investigate the route used by ricin. Induced expression of Rab9S21N inhibited Golgi transport of mannose 6-phosphate receptors but did not affect the sulfation of ricin, suggesting that ricin is transported to the TGN via a Rab9-independent pathway. Moreover, because Rab11 is present in the endosomal recycling compartment and the TGN, studies of transient transfections with mutant Rab11 were performed. The results indicated that routing of ricin from endosomes to the TGN occurs by a Rab11-independent pathway. Finally, because clathrin has been implicated in early endosome to TGN transport, ricin transport was investigated in cells with inducible expression of antisense to clathrin heavy chain. Importantly, endosome to TGN transport (sulfation of endocytosed ricin) was unchanged when clathrin function was abolished. In conclusion, ricin is transported from endosomes to the Golgi apparatus by a Rab9-, Rab11-, and clathrin-independent pathway.     

Hierro intravenoso,recuperación funcional y delirium en pacientes con fractura de cadera. Estudio FEDEREF. Ensayo clínico unicéntrico aleatorizado,controlado con placebo,doble ciego. Número EudraCT: 2014-001923-53

Introduction

There are no previous studies evaluating the effect of intravenous iron therapy on functional and cognitive status of patients with hip fracture (HF).

Investigating the mechanisms underlying phytoprotection by plant growth‐promoting rhizobacteria in Spartina densiflora under metal stress

• Pollution of coasts by toxic metals and metalloids is a worldwide problem for which phytoremediation using halophytes and associated microbiomes is becoming relevant. Metal(loid) excess is a constraint for plant establishment and development, and plant growth promoting rhizobacteria (PGPR) mitigate plant stress under these conditions. However, mechanisms underlying this effect remain elusive. The effect of toxic metal(loid)s on activity and gene expression of ROS‐scavenging enzymes in roots of the halophyte Spartina densiflora grown on real polluted sediments in a greenhouse experiment was investigated.
• Sediments of the metal‐polluted joint estuary of Tinto and Odiel rivers and control, unpollutred samples from the Piedras estuary were collected and submitted to ICP‐OES. Seeds of S. densiflora were collected from the polluted Odiel marshes and grown in polluted and unpolluted sediments. Rhizophere biofilm‐forming bacteria were selected based on metal tolerance and inoculated to S. densiflora and grown for 4 months. Fresh or frozen harvested plants were used for enzyme assays and gene expression studies, respectively.
• Metal excess induced SOD (five‐fold increase), whereas CAT and ascorbate peroxidase displayed minor induction (twofold). A twofold increase of TBARs indicated membrane damage. Our results showed that metal‐resistant PGPR (P. agglomerans RSO6 and RSO7 and B. aryabhattai RSO25) contributed to alleviate metal stress, as deduced from lower levels of all antioxidant enzymes to levels below those of non‐exposed plants. The oxidative stress index (OSI) decreased between 50 and 75% upon inoculation.
• The results also evidenced the important role of PAL, involved in secondary metabolism and/or lignin synthesis, as a pathway for metal stress management in this halophyte upon inoculation with appropriate PGPR, since the different inoculation treatments enhanced PAL expression between 3.75‐ and five‐fold. Our data confirm, at the molecular level, the role of PGPR in alleviating metal stress in S. densiflora and evidence the difficulty of working with halophytes for which little genetic information is available.

     

The eaeA gene is not found in Hafnia alvei from patients with diarrhea in Aragón, Spain

A total of 102 Hafnia alvei clinical strains isolated from different patients with diarrhea has been tested, using polymerase chain reaction and dot-blot hybridization, for the enteropathogenic Escherichia coli attaching and effacing A (eaeA) gene to establish their role as a causative agent of diarrhea in our environment. None of them was positive for the eaeA gene. We cannot consider the eaeA gene as the virulence-associated factor implicated in the H. alvei strains isolated from diarrheal feces in our region.