Counter-gradient variation in gene expression between fish populations facilitates colonization of low-dissolved oxygen environments.

The role of phenotypic plasticity during colonization remains unclear due to the shifting importance of plasticity across timescales. In the early stages of colonization, plasticity can facilitate persistence in a novel environment; but over evolutionary time, processes such as genetic assimilation may reduce variation in plastic traits such that species with a longer evolutionary history in an environment can show lower levels of plasticity than recent invaders. Therefore, comparing species in the early stages of colonization to long-established species provides a powerful approach for uncovering the role of phenotypic plasticity during different stages of colonization. We compared gene expression between low-dissolved oxygen (DO) and high-DO populations of two cyprinid fish: Enteromius apleurogramma, a species that has undergone a recent range expansion, and E. neumayeri, a long-established native species in the same region. We sampled tissue either immediately after capture from the field or after a 2-week acclimation under high-DO conditions, allowing us to test for both evolved and plastic differences in low-DO vs high-DO populations of each species. We found that most genes showing candidate-evolved differences in gene expression did not overlap with those showing plastic differences in gene expression. However, in the genes that did overlap, there was counter-gradient variation such that plastic and evolved gene expression responses were in opposite directions in both species. Additionally, E. apleurogramma had higher levels of plasticity and evolved divergence in gene expression between field populations. We suggest that the higher level of plasticity and counter-gradient variation may have allowed rapid genetic adaptation in E. apleurogramma and facilitated colonization. This study shows how counter-gradient variation may impact the colonization of divergent oxygen environments.

Bioinspired Synthesis of a Sedaxane Metabolite Using Catalytic Vanadyl Acetylacetonate and Molecular Oxygen.

A bioinspired synthesis of the sedaxane metabolite 2 from intermediate 3 using catalytic VO(acac)2 and O2 is described. Intermediate 3 was synthesized starting from 2-bromostyrene in four steps. The inner cyclopropyl ring of 3 was assembled with trans geometry using a highly diastereoselective Nishiyama cyclopropanation, and the outer hydroxycyclopropyl ring was installed using the Kulinkovich cyclopropanation. Additionally, conversion of 3 into 2 was demonstrated in in vitro microbial culture experiments consisting of bacteria and fungi.

A paradigm shift for evaluating pharmacotherapy for Alzheimer's disease: the 10-patient screening protocol.

OBJECTIVE: Discuss etiology of Alzheimer's disease (AD) and offer a paradigm shift-a change in basic assumptions-from present standards in clinical trials. DATA SOURCE: PubMed search for studies into AD pathophysiology and assessment of disease progression. Searched terms: amyloid precursor protein/amyloid beta pathology, senile plaques, mitochondrial dysfunction, reactive oxygen species , advanced glycation end products, neuro-inflammation, dysfunctional microglia/astrocytes, proinflammatory cytokines, ApoE4 allele, Tau phosphorylation, Chlamydia pneumoniae, Dementia Severity Rating Scale, Clinical Dementia Rating Scale, Relative's Assessment of Global Symptomatology-Elderly, and Alzheimer's Disease Assessment Scale-cognitive. STUDY SELECTION: All prospective, randomized, placebo- or cohort-controlled, peer-reviewed English language publications from 1980 to 2012. Studies in animals, AD patients, and AD brain specimens. DATA EXTRACTION: Objectives, methods, statistical design, and results reviewed to assess soundness of trials and validity of results. Trials with flawed methods or uninterpretable results excluded. DATA SYNTHESIS: Primary pathophysiology comprises: amyloid precursor protein/amyloid beta pathology with deposition of senile plaques; mitochondrial dysfunction with insufficient ATP synthesis and release of reactive oxygen species; oxidative stress; and neuro-inflammation from dysfunction of microglia and astrocytes. Other factors include abnormal ApoE4 allele protein and aberrant Tau phosphorylation. Role of Chlamydia pneumoniae is unproven. Dementia Severity Rating Scale (DSRS) is optimal assessment tool for assessing AD progression. CONCLUSION: AD's complex pathophysiology may require polypharmacy to mitigate symptoms and progression. DSRS-driven, 10-patient pilot studies offer practical, valid, and reliable screening for potentially effective pharmacotherapy in AD. The simplicity of this paradigm shift should expedite research and may promote earlier discovery of effective pharmacotherapy for AD.

Effects of insularity on genetic diversity within and among natural populations.

We conducted a quantitative literature review of genetic diversity (GD) within and among populations in relation to categorical population size and isolation (together referred to as "insularity"). Using populations from within the same studies, we were able to control for between-study variation in methodology, as well as demographic and life histories of focal species. Contrary to typical expectations, insularity had relatively minor effects on GD within and among populations, which points to the more important role of other factors in shaping evolutionary processes. Such effects of insularity were sometimes seen-particularly in study systems where GD was already high overall. That is, insularity influenced GD in a study system when GD was high even in non-insular populations of the same study system-suggesting an important role for the "scope" of influences on GD. These conclusions were more robust for within population GD versus among population GD, although several biases might underlie this difference. Overall, our findings indicate that population-level genetic assumptions need to be tested rather than assumed in nature, particularly for topics underlying current conservation management practices.

1-Methyl-4H-3,1-benzoxazine-2,4(1H)dione.

In its crystal structure, the title compound, C(9)H(7)NO(3), forms π-stacked dimers, with a centroid-centroid distance of 3.475 (5) Šbetween the benzenoid and the 2,4 dicarbonyl oxazine rings. These dimers then form staircase-like linear chains through further π-stacking between the benzenoid rings [centroid-centroid distance of 3.761 (2) Å]. The methyl-H atoms are disordered due to rotation about the C-N bond and were modeled with equal occupancy.

Development of Small Molecular Proteasome Inhibitors Using a Caenorhabditis elegans Screen.

We have developed a screening protocol to identify compounds with characteristics of small molecule proteasome inhibitors using the real-time analysis of the Caenorhabditis elegans germ line. This screen is able to identify compounds that induce germ line phenotypes characteristic of a reduction in proteasome function such as changes in polarity, aberrant nuclear morphology, and stimulation of apoptosis. This basic protocol is amenable to a high throughput (96-well) format and has been used successfully to identify multiple compounds for further analysis based on structural elements from the naturally occurring compounds lactacystin and the ß-lactone homologs omuralide and salinosporamide A. The further development of this assay system should allow for the generation of novel small molecule proteasome inhibitors in a genetically tractable whole animal amenable to biochemical analysis.