Functional and evolutionary analysis of DXL1, a non-essential gene encoding a 1-deoxy-D-xylulose 5-phosphate synthase like protein in Arabidopsis thaliana

The synthesis of 1-deoxy-D-xylulose 5-phosphate (DXP), catalyzed by the enzyme DXP synthase (DXS), represents a key regulatory step of the 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway for isoprenoid biosynthesis. In plants DXS is encoded by small multigene families that can be classified into, at least, three specialized subfamilies. Arabidopsis thaliana contains three genes encoding proteins with similarity to DXS, including the well-known DXS1/CLA1 gene, which clusters within subfamily I. The remaining proteins, initially named DXS2 and DXS3, have not yet been characterized. Here we report the expression and functional analysis of A. thaliana DXS2. Unexpectedly, the expression of DXS2 failed to rescue Escherichia coli and A. thaliana mutants defective in DXS activity. Coherently, we found that DXS activity was negligible in vitro, being renamed as DXL1 following recent nomenclature recommendation. DXL1 is targeted to plastids as DXS1, but shows a distinct expression pattern. The phenotypic analysis of a DXL1 defective mutant revealed that the function of the encoded protein is not essential for growth and development. Evolutionary analyses indicated that DXL1 emerged from DXS1 through a recent duplication apparently specific of the Brassicaceae lineage. Divergent selective constraints would have affected a significant fraction of sites after diversification of the paralogues. Furthermore, amino acids subjected to divergent selection and likely critical for functional divergence through the acquisition of a novel, although not yet known, biochemical function, were identified. Our results provide with the first evidences of functional specialization at both the regulatory and biochemical level within the plant DXS family.     

Diagnostic utility of HFE variants in Spanish patients: Association with HLA alleles and role in susceptibility to acute lymphoblastic leukemia

Two single nucleotide polymorphisms (SNPs) in the Human Hemochromatosis (HFE) gene, C282Y and H63D, are the major variants associated to altered iron status and it is well known that these mutations are in linkage disequilibrium with certain Human Leukocyte Antigen (HLA)-A alleles. In addition, the C282Y SNP has been previously suggested to confer susceptibility to acute lymphoblastic leukemia (ALL). We have aimed to assess the diagnosis utility of these polymorphisms in a population of Spanish subjects with suspicion of hereditary iron overload and to evaluate the effect of their associations with HLA-A alleles on the susceptibility to ALL. Both the 63DD [OR = 4.31 (1.7–11.2)] and 282YY (p for trend = 0.02) genotypes were more frequently found among subjects with suspicion of iron overload than among controls. 282YY carriers displayed significantly higher transferrin saturation index (TSI) values (p < 0.001) as well as serum iron (p = 0.01) and ferritin (p = 0.01) levels. In addition, transferrin levels were lower in these subjects (p = 0.01). Likewise, patients who were carriers of the compound heterozygous diplotype (282CY/63HD) showed significantly higher TSI and serum iron and ferritin concentrations. The H63D SNP did not significantly affect the analytical parameters measured. All 282YY carriers and 69.2% of compound heterozygotes showed an altered biochemical index. The frequencies of the HFE SNPs in ALL pediatric patients were lower than those found in controls, whereas the HLA-A*24 allele was significantly overrepresented in the patients group [OR = 3.76 (1.9–7.3)]. No HFE-HLA-A associations were found to modulate the ALL risk. These results suggest that it may be useful to test for both HFE H63D and C282Y polymorphisms in patients with iron overload, as opposed to just genotyping for the C282Y SNP, which is customary in some healthcare centers. These HFE variants and their associations with HLA-A alleles were not observed to be relevant for the susceptibility to ALL in our population.     

The Emerging Role of p38 Mitogen-Activated Protein Kinase in Multiple Sclerosis and Its Models

Multiple sclerosis (MS), the most common disabling neurologic disease of young adults, is considered a classical T cell-mediated disease and is characterized by demyelination, axonal damage, and progressive neurological dysfunction. The currently available disease-modifying therapies are limited in their efficacy, and improved understanding of new pathways contributing to disease pathogenesis could reveal additional novel therapeutic targets. The p38 mitogen-activated protein kinase (MAPK) signaling pathway is known to be triggered by stress stimuli and to contribute to inflammatory responses. Importantly, a number of recent studies have identified this signaling pathway as a central player in MS and its principal animal model, experimental allergic encephalomyelitis. Here, we review the evidence from mouse and human studies supporting the role of p38 MAPK in regulating key immunopathogenic mechanisms underlying autoimmune inflammatory disease of the central nervous system and the potential of targeting this pathway as a disease-modifying therapy in MS.     

A new specimen of the azhdarchoid pterosaur Tapejara wellnhoferi

A new specimen of the Early Cretaceous azhdarchoid Tapejara wellnhoferi is described from the Romualdo Member of the Santana Formation, NE Brazil, providing the first detailed account of the postcranial skeleton. Although limited in its preservation, the osteology is typical of other azhdarchoid pterosaurs from these deposits and represents a juvenile animal with a relatively small wing span of < 1.5 m. The ratios of the pedal elements are identical to those noted for larger, indeterminate azhdarchoids of the Nova Olinda Member of the Crato Formation, where the unguals of the pes are greatly enlarged relative to those of the ornithocheiroids that co-inhabited the Santana lagoon. The ratios of these elements suggest that, as part of a larger suite of characters, these animals were likely better adapted for life on the ground than their ornithocheiroid relatives.     

An unusual edentulous pterosaur from the Early Cretaceous Romualdo Formation of Brazil

Numerous taxa make up the Early Cretaceous fauna of Brazil, including Ornithocheiroidea, Tapejaridae, Thalassodromidae, Chaoyangopteridae and a purported member of Azhdarchidae. Dsungaripteridae has only been tentatively assumed to be present in the form of ‘Santanadactylus’ spixi. New study of NMSG SAO 251093 (a specimen referred to Thalassodromeus sethi) suggests it is a previously unknown species of dsungaripterid, Banguela oberlii, tax. nov., differing from Thalassodromeus and other pterosaurs from the Early Cretaceous of Brazil by a unique combination of characters, including an upturned jaw tip, a short dorsal mandibular symphyseal shelf (dmss), and an autapomorphic thin crest placed halfway along the fused mandibular symphysis without a keel along the ventral margin of the jaw. B. oberlii, tax. nov., is referred to Dsungaripteridae based on a dmss no longer than the ventral shelf, U-shaped caudal margin of the ventral shelf and lateral margins of the mandibular symphysis concave in dorsal view. B. oberlii, tax. nov., is the youngest known dsungaripterid, and expands known morphological diversity in the clade as well as the Early Cretaceous pterosaur fauna of South America.     

Global biostratigraphic comparison and correlation of an early Cisuralian palynoflora from Bolivia

This paper presents new data about Early Permian (Cisuralian) strata, palynostratigraphy and absolute dating from the Copacabana Formation in central Bolivia. Recent stratigraphic and palynologic data from marine and transitional rocks at Apillapampa refine the age of Cisuralian palynomorphs in South America. Twelve samples interbedded with five volcanic ashes (processed and productive) yielded 94 palynomorph species arranged in two informal palynoassemblages: the lower assemblage Vittatina costabilis corresponds to one sample near the base of the Copacabana Formation and the upper Lueckisporites virkkiae assemblage occurs in overlying marine and coal-bearing transitional intervals. Ages were also independently refined by a modern review of conodonts, fusulinids, along with those U–Pb radiometric ages (Isotope Dilution Thermal Ionization Mass Spectrometry [ID-TIMS] of zircon-bearing interbedded tuffs). These data suggest that the lower marine member of the Copacabana Formation at this location is Asselian and Sakmarian. Lueckisporites virkkiae is a key species of palynomorph utilised in South American and global Permian biostratigraphic reconstructions. Hence, a thorough global comparison of these palynofloras and correlations is addressed in this contribution, considering first appearances of mainly cosmopolitan diagnostic taxa. Correlations are established with many similar Permian palynofloras, some also constrained with radiometric data, in South America (Brazil, Uruguay and Argentina) and elsewhere.     

Packing Features of the all-AT Oligonucleotide d(AAATTT)

Abstract

We describe the packing features of the oligonucleotide duplex d(AAATTT)₂, as determined by X-ray diffraction. There is little information on sequences that only contain A and T bases. The present structure confirms that these sequences tend to pack as a helical arrangement of stacked oligonucleotides in a B conformation with Watson-Crick hydrogen bonding. Our results demonstrate that the virtual TA base step between stacked duplexes has a negative twist that improves base stacking. This observation is consistent with the low stability of TA base steps in B-form DNA.     

Description of Bacillus toyonensis sp. nov., a novel species of the Bacillus cereus group,and pairwise genome comparisons of the species of the group by means of ANI calculations

Strain BCT-7112^T was isolated in 1966 in Japan from a survey designed to obtain naturally occurring microorganisms as pure cultures in the laboratory for use as probiotics in animal nutrition. This strain, which was primarily identified as Bacillus cereus var toyoi, has been in use for more than 30 years as the active ingredient of the preparation TOYOCERIN^®, an additive for use in animal nutrition (e.g. swine, poultry, cattle, rabbits and aquaculture). Despite the fact that the strain was initially classified as B. cereus, it showed significant genomic differences from the type strains of the B. cereus group that were large enough (ANI values below 92%) to allow it to be considered as a different species within the group. The polyphasic taxonomic study presented here provides sufficient discriminative parameters to classify BCT-7112^T as a new species for which the name Bacillus toyonensis sp. nov. is proposed, with BCT-7112^T (=CECT 876^T; =NCIMB 14858^T) being designated as the type strain. In addition, a pairwise comparison between the available genomes of the whole B. cereus group by means of average nucleotide identity (ANI) calculations indicated that besides the eight classified species (including B. toyonensis), additional genomospecies could be detected, and most of them also had ANI values below 94%. ANI values were on the borderline of a species definition only in the cases of representatives of B. cereus versus B. thuringiensis, and B. mycoides and B. weihenstephanensis.     

Depression in Medical School: The Influence of Morningness‐Eveningness

Medical students are at higher risk for depression, affecting not only their lives but also patient care. This article studied a population of medical students engaged in lecture‐based learning regarding the presence of depressive symptoms and its relation to morningness‐eveningness. Depressive symptoms were assessed by the Beck Depressive Inventory scale (BDI>10), and diurnal preference was assessed by the Horne & Östberg Morningness/Eveningness Questionnaire (MEQ). Family history of depression and involvement in regular physical activity were also investigated. A total of 161 students, 77 (47.8%) males, aged 19 to 30 yrs (22.1±2.1) living in a city close to the equator were evaluated. Fifty‐three individuals (32.9%) had depressive symptoms. Depressive individuals showed a trend to be female (p=0.07). Also, female gender showed a non‐significant shift toward morningness. Fifty‐eight (36.0%) subjects participated in regular physical activity. In 57 cases (35.4%), there was a history of depression in the family. Fifteen individuals (9.3%) were definitely evening type, 42 (26.1%) were moderately evening type, 44 (27.3%) were indifferent, 42 (26.1%) were moderately morning type, and 18 (11.2%) were definitely morning type. Family history of depression (OR=0.29, 95% CI=1.37–6.12) and sedentary life (OR=0.28, 95% CI=0.12–0.65) were associated with depressive symptoms. Eveningness was associated with depressive symptoms (OR=0.66, 95% CI=0.50–0.88), and this association remained significant after adjusting for the presence of familial depression and physical activity (OR=0.71, 95% CI=0.52–0.95). In conclusion, depressive symptoms are independently associated with “eveningness” in medical students. These results should be confirmed by future studies involving a larger number of subjects.     

Regularity of Daily Activities in Stroke

Various studies have been performed using the Social Rhythm Metric (SRM), though none has been developed with stroke patients. Stroke is a pathology that provokes a strong physical and social impact caused by an abnormality in cerebral circulation. Consequently, we performed two studies to validate the SRM and translate it into Portuguese, and to evaluate the regularity of the daily activities of stroke patients. Both healthy individuals and patients with unilateral cerebral lesions were evaluated. Subjects were of both sexes and between 45 and 65 yrs of age. Participants underwent clinical evaluation and recorded the time of 17 daily activities on the SRM for two weeks. Data were analyzed by the Pearson correlation and Fisher tests. After conceptual translation into Portuguese, corrections were made to arrive at the final version. Normative SRM scores varied from 3.2 to 7.0, suggesting that the activities presented in SRM adequately represented the daily routines of the patients. A correlation was found in SRM between the weeks (r=0.84; p=0.0001), indicating instrument reliability. The mean (±SD) score of the stoke patients was 4.8 (±1.0), and the correlation between the SRM and level of neurological damage showed that patients with lower SRM values were more physically compromised (r=?0.29; p=0.04), suggesting that SRM may be a clinical predictor. Activities related to eating and the sleep‐wake cycle were rated by most patients. In all, 71% of the patients did not work, while 84% of healthy individuals did (p=0.001). Only 64% of patients left home compared to 90% of the healthy subjects (p=0.001), and 59% of patients recorded the activity of going home compared to 82% of healthy individuals (p=0.001). According to the results, there is evidence of the validity and reliability of the SRM, enabling it to be reliably used in chronobiological studies of stroke patients. Given that a less regular lifestyle may be associated with neurological compromise and a decrease in social activities, we suggest new studies with the repeated application of this instrument over the clinical evolution of the disease to better define improvement or worsening of the patient's condition in terms of their social and health aspects.