Basic amino acid residues in the beta-structure region contribute, but not critically, to presynaptic neurotoxicity of ammodytoxin A

The molecular mechanism of action of presynaptically toxic secreted phospholipases A2 (sPLA2s) isolated from snake venoms is not completely understood. It has been proposed that the positive charge in the beta-structure region is important for their toxic activity. To test this hypothesis, we characterised several mutants of ammodytoxin A (AtxA) possessing substitution of all five basic residues in this region. The mutations had relatively little influence on the catalytic activity of AtxA, either on charge-neutral or anionic phospholipid vesicles. An exception was R72 when replaced by a hydrophobic (higher activity) or an acidic (lower activity) residue. Lethal potencies of the eight single site mutants were up to four times lower than that of the wild-type, whereas the triple mutant (K74S/H76S/R77L) was 13-fold less toxic. The substitutions also lowered the affinity of the toxin, slightly to moderately, for the neuronal receptors R25 and R180. Interaction with calmodulin was only slightly affected by substitutions of K86, more by those of the K74/H76/R77 cluster and most by those of R72 (up to 11-fold lower binding affinity). The results clearly indicate that the basic amino acid residues in the beta-region of AtxA contribute to, but are not necessary for, its neurotoxic effect.     

The effect of seasonality on oxidative metabolism in Nacella (Patinigera) magellanica

We studied the seasonal variation on aerobic metabolism and the response of oxidative stress parameters in the digestive glands of the subpolar limpet Nacella (P.) magellanica. Sampling was carried out from July (winter) 2002 to July 2003 in Beagle Channel, Tierra del Fuego, Argentina. Whole animal respiration rates increased in early spring as the animals spawned and remained elevated throughout summer and fall (winter: 0.09 ± 0.02 μmol O₂ h^− 1 g^− 1; summer: 0.31 ± 0.06 μmol O₂ h^− 1 g^− 1). Oxidative stress was assessed at the hydrophilic level as the ascorbyl radical content / ascorbate content ratio (A / AH⁻). The A / AH⁻ ratio showed minimum values in winter (3.7 ± 0.2 10^− 5 AU) and increased in summer (18 ± 5 10^− 5 AU). A similar pattern was observed for lipid radical content (122 ± 29 pmol mg^− 1 fresh mass [FW] in winter and 314 ± 45 pmol mg^− 1 FW in summer), iron content (0.99 ± 0.07 and 2.7 ± 0.6 nmol mg^− 1 FW in winter and summer, respectively) and catalase activity (2.9 ± 0.2 and 7 ± 1 U mg^− 1 FW in winter and summer, respectively). Since nitrogen derived radicals are thought to be critically involved in oxidative metabolism in cells, nitric oxide content was measured and a significant difference in the content of the Fe–MGD–NO adduct in digestive glands from winter and summer animals was observed. Together, the data indicate that both oxygen and nitrogen radical generation rates in N. (P.) magellanica are strongly dependent on season.     

Molecular characterization of Cryptosporidium isolates from humans and animals in Iran

Isolates of Cryptosporidium spp. from human and animal hosts in Iran were characterized on the basis of both the 18S rRNA gene and the Laxer locus. Three Cryptosporidium species, C. hominis, C. parvum, and C. meleagridis, were recognized, and zoonotically transmitted C. parvum was the predominant species found in humans.     

Trypanosomes and mammalian sperm: one of a kind?

Flagellar-mediated motility is an indispensable function for cell types as evolutionarily distant as mammalian sperm and kinetoplastid parasites, a large group of flagellated protozoa that includes several important human pathogens. Despite the obvious importance of flagellar motility, little is known about the signalling processes that direct the frequency and wave shape of the flagellar beat, or those that provide the motile cell with the necessary environmental cues that enable it to aim its movement. Similarly, the energetics of the flagellar beat and the problem of a sufficient ATP supply along the entire length of the beating flagellum remain to be explored. Recent proteome projects studying the flagella of mammalian sperm and kinetoplastid parasites have provided important information and have indicated a surprising degree of similarities between the flagella of these two cell types.     

Effects of antibody on viral kinetics in simian/human immunodeficiency virus infection: implications for vaccination

Passive antibody treatment of macaques prior to simian/human immunodeficiency virus infection produces "sterilizing immunity" in some animals and long-term reductions in viral loads in others. Analysis of viral kinetics suggests that antibody mediates sterilizing immunity by its effects on the initial viral inoculum. By contrast, reduction in peak viral load later in infection prevents CD4 depletion and contributes to long-term viral control.     

Efectos del Modelo de Atención Centrado en la Persona en la calidad de vida de personas con deterioro cognitivo de centros gerontológicos

Introduction

The Model of Person Centered Care has attracted increasing interest for use in gerontology centers. Therefore, the contributions about its impact are scarce in our context. The objective of this paper is to establish the impact that the interventions associated with the Model of Person Centered Care in the «Etxean Ondo» Project have on the quality of life of residents with cognitive impairment.

Material and methods

One hundred and ninetten residents with cognitive impairment were selected: 59 in the control group and 60 in the experimental group. Subjects in each group were sorted by cognitive impairment: mild or severe. Changes were implemented in the physical and organizational environments for the promotion of autonomy and wellbeing. Quality of life was assessed before and 6 months after intervention using the Fumat Scales (mild cognitive impairment) and Qualid (severe cognitive impairment). The t-Student test was used for comparison of means.

Results

In intergroup comparisons, significant differences in the Fumat Scale for the control group with mild cognitive impairment were initially identified. These differences were not recorded in the post assessment. The experimental group with severe cognitive impairment was significantly improved in the Qualid Scale post assessment. In intragroup comparisons, significant improvements were evident in the quality of life of experimental subjects, both with severe cognitive impairment (Qualid) and mild (Fumat).

Conclusions

The findings support the effectiveness of the interventions and identify methodological and conceptual issues that have been considered to analyze the Model of Person Centered Care efects.     

Proposed standard nomenclature for the alpha- and beta-globin gene families

The globin family of genes and proteins has been a recurrent object of study for many decades. This interest has generated a vast amount of knowledge. However it has also created an inconsistent and confusing nomenclature, due to the lack of a systematic approach to naming genes and failure to reflect the phylogenetic relationships among genes of the gene family. To alleviate the problems with the existing system, here we propose a standardized nomenclature for the alpha and beta globin family of genes, based on a phylogenetic analysis of vertebrate alpha and beta globins, and following the Guidelines for Human Gene Nomenclature.     

HIV persistence: Chemokines and their signalling pathways

Latently infected resting CD4+ T cells are the major barrier to curing HIV. We have recently demonstrated that chemokines, which bind to the chemokine receptors CCR7, CXCR3 and CCR6, facilitate efficient HIV nuclear localisation and integration in resting CD4+ T cells, leading to latency. As latently infected cells are enriched in lymphoid tissues, where chemokines are highly concentrated, this may provide a mechanism for the generation of latently infected cells in vivo. Here we review the role of chemokines in HIV persistence; the main signalling pathways that are involved; and how these pathways may be exploited to develop novel strategies to reduce or eliminate latently infected cells.     

The effects of inbreeding, genetic dissimilarity and phenotype on male reproductive success in a dioecious plant

Pollen fate can strongly affect the genetic structure of populations with restricted gene flow and significant inbreeding risk. We established an experimental population of inbred and outbred Silene latifolia plants to evaluate the effects of (i) inbreeding depression, (ii) phenotypic variation and (iii) relatedness between mates on male fitness under natural pollination. Paternity analysis revealed that outbred males sired significantly more offspring than inbred males. Independently of the effects of inbreeding, male fitness depended on several male traits, including a sexually dimorphic (flower number) and a gametophytic trait (in vitro pollen germination rate). In addition, full-sib matings were less frequent than randomly expected. Thus, inbreeding, phenotype and genetic dissimilarity simultaneously affect male fitness in this animal-pollinated plant. While inbreeding depression might threaten population persistence, the deficiency of effective matings between sibs and the higher fitness of outbred males will reduce its occurrence and counter genetic erosion.