Number conservation is related to children's prefrontal inhibitory control: an fMRI study of a piagetian task

Although young children can accurately determine that two rows contain the same number of coins when they are placed in a one-to-one correspondence, children younger than 7 years of age erroneously think that the longer row contains more coins when the coins in one of the rows are spread apart. To demonstrate that prefrontal inhibitory control is necessary to succeed at this task (Piaget's conservation-of-number task), we studied the relationship between the percentage of BOLD signal changes in the brain areas activated in this developmental task and behavioral performance on a Stroop task and a Backward Digit Span task. The level of activation in the right insula/inferior frontal gyrus was selectively related to inhibitory control efficiency (i.e., the Stroop task), whereas the activation in the left intraparietal sulcus (IPS) was selectively related to the ability to manipulate numerical information in working memory (i.e., the Backward Digit Span task). Taken together, the results indicate that to acquire number conservation, children's brains must not only activate the reversibility of cognitive operations (supported by the IPS) but also inhibit a misleading length-equal-number strategy (supported by the right insula/inferior frontal gyrus).     

Substitution of pseudokinase domain residue Val-617 by large non-polar amino acids causes activation of JAK2

Explaining the uniqueness of the acquired somatic JAK2 V617F mutation, which is present in more than 95% of polycythemia vera patients, has been a challenge. The V617F mutation in the pseudokinase domain of JAK2 renders the unmutated kinase domain constitutively active. We have performed random mutagenesis at position 617 of JAK2 and tested each of the 20 possible amino acids for ability to induce constitutive signaling in Ba/F3 cells expressing the erythropoietin receptor. Four JAK2 mutants, V617W, V617M, V617I, and V617L, were able to induce cytokine independence and constitutive downstream signaling. Only V617W induced a level of constitutive activation comparable with V617F. Also, only V617W stabilized tyrosine-phosphorylated suppressor of cytokine signaling 3 (SOCS3), a mechanism by which JAK2 V617F overcomes inhibition by SOCS3. The V617W mutant induced a myeloproliferative disease in mice, mainly characterized by erythrocytosis and megakaryocytic proliferation. Although JAK2 V617W would predictably be pathogenic in humans, the substitution of the Val codon, GTC, by TTG, the codon for Trp, would require three base pair changes, and thus it is unlikely to occur. We discuss how the predicted conformations of the activated JAK2 mutants can lead to better screening assays for novel small molecule inhibitors.     

Comparative use patterns of plant resources in rural areas of South Africa and Zimbabwe

Documentation of use patterns of plants across national boundaries is of relevance in understanding the importance of plant resources to livelihood strategies of different ethnic groups. Plant resources have gained prominence as a natural asset through which families derive food, firewood, income, medicines and timber, enabling particularly poor communities to achieve self-sufficiency. The objective of this study was to investigate the trends in plant usage in South Africa and Zimbabwe. An ethnobotanical investigation was conducted between January 2012 and January 2013 in the Limpopo Province, South Africa and the Midlands Province, Zimbabwe. The study used questionnaire surveys and interviews with a total of 143 participants to explore plant use patterns in South Africa and Zimbabwe. A total of 98 plant species were identified, with Zimbabwe contributing 70 species and 47 species from South Africa. The uses were classified into 15 categories, major use categories were firewood, food plants, medicine and timber. Food plant was a major plant use category in Zimbabwe, contributing 55.1%, followed by medicinal plants (36.8%), firewood (35.7%) and timber (31.6%). In contrast, firewood was the major plant use category in South Africa, contributing 18.4%, followed by food plants (17.3%), medicinal (14.3%) and timber (1.0%). Comparison of the two countries demonstrated remarkable differences in plant use patterns. The results showed that rural households in Zimbabwe were more reliant on plant resources than their counterparts in South Africa. Such a trend could be attributed to a close relationship between the local people, and their natural and agricultural environment leading to a rich knowledge base on plants, plant use and related practices. This comparative analysis strengthens the firm belief that utilization of plant resources represents an important shared heritage, preserved over the centuries, which must be exploited in order to provide further new and useful body of ethnobotanical knowledge.     

Reduced proportions of natural killer T cells are present in the relatives of lupus patients and are associated with autoimmunity

Introduction

Systemic lupus erythematosus is a genetically complex disease. Currently, the precise allelic polymorphisms associated with this condition remain largely unidentified. In part this reflects the fact that multiple genes, each having a relatively minor effect, act in concert to produce disease. Given this complexity, analysis of subclinical phenotypes may aid in the identification of susceptibility alleles. Here, we used flow cytometry to investigate whether some of the immune abnormalities that are seen in the peripheral blood lymphocyte population of lupus patients are seen in their first-degree relatives.

Methods

Peripheral blood mononuclear cells were isolated from the subjects, stained with fluorochrome-conjugated monoclonal antibodies to identify various cellular subsets, and analyzed by flow cytometry.

Results

We found reduced proportions of natural killer (NK)T cells among 367 first-degree relatives of lupus patients as compared with 102 control individuals. There were also slightly increased proportions of memory B and T cells, suggesting increased chronic low-grade activation of the immune system in first-degree relatives. However, only the deficiency of NKT cells was associated with a positive anti-nuclear antibody test and clinical autoimmune disease in family members. There was a significant association between mean parental, sibling, and proband values for the proportion of NKT cells, suggesting that this is a heritable trait.

Conclusions

The findings suggest that analysis of cellular phenotypes may enhance the ability to detect subclinical lupus and that genetically determined altered immunoregulation by NKT cells predisposes first-degree relatives of lupus patients to the development of autoimmunity.     

A European focus on proteomics

A report on the First International Symposium of the Austrian Proteomics Platform, Seefeld, Austria, 26-29 January 2004.     

Superbugs in the coming new decade; multidrug resistance and prospects for treatment of Staphylococcus aureus, Enterococcus spp. and Pseudomonas aeruginosa in 2010

New resistance problems have emerged recently among hospital and community-acquired pathogens such as in Staphylococcus aureus, Enterococcus faecium and Pseudomonas aeruginosa. Hospital-acquired and now community-acquired methicillin-resistant S. aureus are emerging worldwide whereas vancomycin-resistant S. aureus remain extremely rare. Hospital-acquired outbreaks of vancomycin-resistant enterococci and multidrug resistant Pseudomonas aeruginosa infections are increasingly reported worldwide. Whereas novel molecules are being developed for treating Gram-positive infections, difficult to non possible-to-treat pandrug-resistant P. aeruginosa infections may become a therapeutic challenge soon.