Plant Conservation in the Caribbean Island Biodiversity Hotspot

While the Caribbean is a recognized “biodiversity hotspot”, plant conservation has not received adequate attention; particularly, given the high levels of endemism in many plant groups. Besides establishing protected areas, there needs to be a sustained effort to study the taxonomy, systematics and ecology of the flora. Recent phylogenetic studies have shown high levels of endemism and conservation studies indicate a large propotion of the flora is threatened with extinction. Eight recommendations are given for plant conservation in the region.     

Expanding the Verrucomicrobial Methanotrophic World: Description of Three Novel Species of Methylacidimicrobium gen. nov.

Methanotrophic Verrucomicrobia have been found in geothermal environments characterized by high temperatures and low pH values. However, it has recently been hypothesized that methanotrophic Verrucomicrobia could be present under a broader range of environmental conditions. Here we describe the isolation and characterization of three new species of mesophilic acidophilic verrucomicrobial methanotrophs from a volcanic soil in Italy. The three new species showed 97% to 98% 16S rRNA gene identity to each other but were related only distantly (89% to 90% on the 16S rRNA level) to the thermophilic genus Methylacidiphilum. We propose the new genus Methylacidimicrobium, including the novel species Methylacidimicrobium fagopyrum, Methylacidimicrobium tartarophylax, and Methylacidimicrobium cyclopophantes. These mesophilic Methylacidimicrobium spp. were more acid tolerant than their thermophilic relatives; the most tolerant species, M. tartarophylax, still grew at pH 0.5. The variation in growth temperature optima (35 to 44°C) and maximum growth rates (µmax; 0.013 to 0.040 h⁻¹) suggested that all species were adapted to a specific niche within the geothermal environment. All three species grew autotrophically using the Calvin cycle. The cells of all species contained glycogen particles and electron-dense particles in their cytoplasm as visualized by electron microscopy. In addition, the cells of one of the species (M. fagopyrum) contained intracytoplasmic membrane stacks. The discovery of these three new species and their growth characteristics expands the known diversity of verrucomicrobial methanotrophs and shows that they are present in many more ecosystems than previously assumed.     

Peptide YY and neuropeptide Y induce villin expression, reduce adhesion, and enhance migration in small intestinal cells through the regulation of CD63, matrix metalloproteinase-3, and Cdc42 activity

Peptide YY (PYY) and neuropeptide Y (NPY) are regulatory peptides synthesized in the intestine and brain, respectively, that modify physiological functions affecting nutrient assimilation and feeding behavior. Because PYY and NPY also alter the expression of intestine-specific differentiation marker proteins and the tetraspanin CD63, which is involved in cell adhesion, we investigated whether intestinal cell differentiation could be linked to mucosal cell adhesion and migration through these peptides. PYY and NPY significantly decreased cell adhesion and increased cell migration in a dose-dependent manner prior to cell confluency in our model system, non-tumorigenic small intestinal hBRIE 380i cells. Both peptides reduced CD63 expression and CD63-dependent cell adhesion. CD63 overexpression increased and antisense CD63 cDNA decreased intestinal cell adhesion. In parallel, both PYY and NPY increased expression of matrix metalloproteinase-3 (MMP-3) to a level sufficient to induce cell migration by activating the Rho GTPase Cdc42. The effects of both peptides on cell migration were blocked in cells constitutively overexpressing dominant-negative Cdc42. PYY and NPY also significantly induced the expression of the differentiation marker villin, which could be eliminated by an MMP inhibitor at a concentration that inhibits cell migration. Increased MMP-3 activity, which enhanced cell migration, also induced villin mRNA levels. Therefore, these data indicate that the alteration of adhesion and migration by PYY and NPY occurs in part by synchronous modulation of three proteins that are involved in extracellular matrix-basolateral membrane interactions, CD63, MMP-3 and Cdc42, and that PYY/NPY regulation of expression of mucosal proteins such as villin is linked to the process of cell migration and adhesion.     

Novel phenylamino acetamide derivatives as potent and selective kappa opioid receptor agonists

A novel series of phenylamino acetamide derivatives was synthesized. These amides were shown to be potent and selective kappa opioid receptor agonists.     

博尔纳病病毒对BALB/c小鼠感染性检测

目的分析博尔纳病病毒（Borna disease virus,BDV）H1766株对BALB/c小鼠的感染性。方法选择病毒滴度为2.0×107FFU/ml的BDV病毒液分别对新生和成年BALB/c小鼠进行脑内接种,并用相同病毒液对原代培养的新生BALB/c小鼠脑细胞进行接种。经过一定时间的病毒作用后分别提取总RNA,采用巢式RT-PCR方法检测BDV-p40基因,并通过免疫组化方法检测脑内接种脑组织中BDV-P40蛋白。结果脑内接种病毒的小鼠脑组织中可以检测到BDV-p40基因和BDV-P40蛋白,培养的小鼠脑细胞中可以检测到BDV-p40基因。结论BDVH1766株可以感染新生和成年的BALB/c小鼠。     

Structural characterization of proteins using residue environments

A primary challenge for structural genomics is the automated functional characterization of protein structures. We have developed a sequence-independent method called S-BLEST (Structure-Based Local Environment Search Tool) for the annotation of previously uncharacterized protein structures. S-BLEST encodes the local environment of an amino acid as a vector of structural property values. It has been applied to all amino acids in a nonredundant database of protein structures to generate a searchable structural resource. Given a query amino acid from an experimentally determined or modeled structure, S-BLEST quickly identifies similar amino acid environments using a K-nearest neighbor search. In addition, the method gives an estimation of the statistical significance of each result. We validated S-BLEST on X-ray crystal structures from the ASTRAL 40 nonredundant dataset. We then applied it to 86 crystallographically determined proteins in the protein data bank (PDB) with unknown function and with no significant sequence neighbors in the PDB. S-BLEST was able to associate 20 proteins with at least one local structural neighbor and identify the amino acid environments that are most similar between those neighbors.     

An IGF-I promoter polymorphism modifies the relationships between birth weight and risk factors for cardiovascular disease and diabetes at age 36

BACKGROUND: Biochemical testing for pheochromocytoma by measurement of fractionated plasma metanephrines is limited by false positive rates of up to 18% in people without known genetic predisposition to the disease. The plasma normetanephrine fraction is responsible for most false positives and plasma normetanephrine increases with age. The objective of this study was to determine if we could improve the specificity of fractionated plasma measurements, by statistically adjusting for age. METHODS: An age-adjusted metanephrine score was derived using logistic regression from 343 subjects (including 33 people with pheochromocytoma) who underwent fractionated plasma metanephrine measurements as part of investigations for suspected pheochromocytoma at Mayo Clinic Rochester (derivation set). The performance of the age-adjusted score was validated in a dataset of 158 subjects (including patients 23 with pheochromocytoma) that underwent measurements of fractionated plasma metanephrines at Mayo Clinic the following year (validation dataset). None of the participants in the validation dataset had known genetic predisposition to pheochromocytoma. RESULTS: The sensitivity of the age-adjusted metanephrine score was the same as that of traditional interpretation of fractionated plasma metanephrine measurements, yielding a sensitivity of 100% (23/23, 95% confidence interval [CI] 85.7%, 100%). However, the false positive rate with traditional interpretation of fractionated plasma metanephrine measurements was 16.3% (22/135, 95% CI, 11.0%, 23.4%) and that of the age-adjusted score was significantly lower at 3.0% (4/135, 95% CI, 1.2%, 7.4%) (p < 0.001 using McNemar's test). CONCLUSION: An adjustment for age in the interpretation of results of fractionated plasma metanephrines may significantly decrease false positives when using this test to exclude sporadic pheochromocytoma. Such improvements in false positive rate may result in savings of expenditures related to confirmatory imaging.     

The role of dorsal root ganglia activation and brain-derived neurotrophic factor in multiple sclerosis

Multiple sclerosis (MS) is characterized by focal destruction of the white matter of the brain and spinal cord. The exact mechanisms underlying the pathophysiology of the disease are unknown. Many studies have shown that MS is predominantly an autoimmune disease with an inflammatory phase followed by a demyelinating phase. Recent studies alongside current treatment strategies, including glatiramer acetate, have revealed a potential role for brain-derived neurotrophic factor (BDNF) in MS. However, the exact role of BDNF is not fully understood. We used the experimental autoimmune encephalomyelitis (EAE) model of MS in adolescent female Lewis rats to identify the role of BDNF in disease progression. Dorsal root ganglia (DRG) and spinal cords were harvested for protein and gene expression analysis every 3 days post-disease induction (pdi) up to 15 days. We show significant increases in BDNF protein and gene expression in the DRG of EAE animals at 12 dpi, which correlates with peak neurological disability. BDNF protein expression in the spinal cord was significantly increased at 12 dpi, and maintained at 15 dpi. However, there was no significant change in mRNA levels. We show evidence for the anterograde transport of BDNF protein from the DRG to the dorsal horn of the spinal cord via the dorsal roots. Increased levels of BDNF within the DRG and spinal cord in EAE may facilitate myelin repair and neuroprotection in the CNS. The anterograde transport of DRG-derived BDNF to the spinal cord may have potential implications in facilitating central myelin repair and neuroprotection.     

High prevalence of malaria in Zambezia, Mozambique: the protective effect of IRS versus increased risks due to pig-keeping and house construction

Background

African countries are scaling up malaria interventions, especially insecticide treated nets (ITN) and indoor residual spraying (IRS), for which ambitious coverage targets have been set. In spite of these efforts infection prevalence remains high in many parts of the continent. This study investigated risk factors for malaria infection in children using three malaria indicator surveys from Zambezia province, Mozambique. The impact of IRS and ITNs, the effects of keeping farm animals and of the construction material of roofs of houses and other potential risk factors associated with malaria infection in children were assessed.

Methods

Cross-sectional community-based surveys were conducted in October of 2006, 2007 and 2008. A total of 8338 children (ages 1–15 years) from 2748 households were included in the study. All children were screened for malaria by rapid diagnostic tests. Caregiver interviews were used to assess household demographic and wealth characteristics and ITN and IRS coverage. Associations between malaria infection, vector control interventions and potential risk factors were assessed.

Results

Overall, the prevalence of malaria infection was 47.8% (95%CI: 38.7%–57.1%) in children 1–15 years of age, less than a quarter of children (23.1%, 95%CI: 19.1%–27.6%) were sleeping under ITN and almost two thirds were living in IRS treated houses (coverage 65.4%, 95%CI: 51.5%–77.0%). Protective factors that were independently associated with malaria infection were: sleeping in an IRS house without sleeping under ITN (Odds Ratio (OR)  = 0.6; 95%CI: 0.4–0.9); additional protection due to sleeping under ITN in an IRS treated house (OR = 0.5; 95%CI: 0.3–0.7) versus sleeping in an unsprayed house without a ITN; and parental education (primary/secondary: OR = 0.6; 95%CI: 0.5–0.7) versus parents with no education. Increased risk of infection was associated with: current fever (OR = 1.2; 95%CI: 1.0–1.5) versus no fever; pig keeping (OR = 3.2; 95%CI: 2.1–4.9) versus not keeping pigs; living in houses with a grass roof (OR = 1.7; 95%CI: 1.3–2.4) versus other roofing materials and bigger household size (8–15 people: OR = 1.6; 95%CI: 1.3–2.1) versus small households (1–4 persons).

Conclusion

Malaria infection among children under 15 years of age in Zambezia remained high but conventional malaria vector control methods, in particular IRS, provided effective means of protection. Household ownership of farm animals, particularly pigs, and living in houses with a grass roof were independently associated with increased risk of infection, even after allowing for household wealth. To reduce the burden of malaria, national control programs need to ensure high coverage of effective IRS and promote the use of ITNs, particularly in households with elevated risks of infection, such as those keeping farm animals, and those with grass roofs.