Articles selected by Faculty of 1000: plant comparative mitochondrial genomics; open source proteomics database; identifying disease-associated enzymes; predicting microRNA targets; genome annotation using polymorphisms

Background

Phylogenetic analysis of human complete mitochondrial DNA sequences has largely contributed to resolving phylogenies and antiquity of different lineages belonging to the majorhaplogroups L, N and M (East-Asian lineages). In the absence of whole mtDNA sequence information of M lineages reported in India that exhibits highest diversity within the sub-continent, the present study was undertaken to provide a detailed analysis of this haplogroup to precisely characterize the lineages and unravel their intricate phylogeny.

Results

The phylogenetic tree constructed from sequencing information of twenty four whole mtDNA genome revealed novel substitutions in the previously defined M2a and M6 lineages. The most striking feature of this phylogenetic tree is the formulation of a new lineage M30, distinguished by the presence of 12007 transition, and comprises of the recently defined M18 and a potential new sub-lineage possessing substitution at 16223 and 16300. M30 further branches into M30a sub-lineage, defined by 15431 and 195A substitution. The age of M30 lineage was estimated at 33,042 YBP, indicating a more recent expansion time than M2 (49,686 YBP). Contradictory to earlier reports, the M5 lineage does not always include a 12477 substitution, and is more appropriately defined by a transversion at 10986A. The phylogenetic tree also identifies a potential new lineage M* with HVSI sequence 16223,16325. No new substitutions were found in M25 and the M3 mt DNA genome could only be tentatively rooted by 16126 mutation. M4 and M*(16251, 16267) lineages could not be resolved distinctly.

Conclusions

This study describes seven new basal mutations and fourteen lineages that substantially contribute to the present understanding of superhaplogroup M. The phylogenetic tree supported by median-joining network helps in distinctly identifying the genetic relation between different M lineages that could not be achieved solely by control region sequence information. Although high control region diversity has been reported in the different M lineages distributed in India, complete sequencing of M* and defined lineages suggests that these mt DNA genomes emerged from a limited number of branches arising from the M trunk.     

Flies,fish and food

Dried fish are an important part of the traditional diet in many developing countries. But, during sun drying, the fish can become infested by maggots, leading to comprehensive destruction of the crop. Understanding the life cycles and seasonal abundance of the flies and their larvae is an essential step in the development of sustainable management programmes to reduce losses.     

“They See Us As Machines:” The Experience of Recent Immigrant Women in the Low Wage Informal Labor Sector

This study explores the organization of work and occupational health risk as elicited from recently immigrated women (n = 8) who have been in the US for less than three years and employed in informal work sectors such as cleaning and factory work in the greater Boston area in Massachusetts. Additional interviews (n = 8) with Community Key Informants with knowledge of this sector and representatives of temporary employment agencies in the area provides further context to the interviews conducted with recent immigrant women. These results were also compared with our immigrant occupational health survey, a large project that spawned this study. Responses from the study participants suggest health outcomes consistent with being a day-laborer scholarship, new immigrant women are especially at higher risk within these low wage informal work sectors. A difference in health experiences based on ethnicity and occupation was also observed. Low skilled temporary jobs are fashioned around meeting the job performance expectations of the employer; the worker’s needs are hardly addressed, resulting in low work standards, little worker protection and poor health outcomes. The rising prevalence of non-standard employment or informal labor sector requires that policies or labor market legislation be revised to meet the needs presented by these marginalized workers.     

Prevalence of Undiagnosed Depression among Persons with Hypertension and Associated Risk Factors: A Cross-Sectional Study in Urban Nepal

BackgroundDespite an increasing number of studies exploring prevalence of depression among hypertensive patients in high income countries, limited data is available from low and middle income countries, particularly Nepal. Our aim was to investigate the prevalence of undiagnosed (sub clinical) depression and associated risk factors among hypertensive patients attending a tertiary health care clinic in Nepal.MethodsThe study was based on a cross-sectional study design, with 321 hypertensive patients attending the Out-Patient Department of a central hospital in Nepal. Blood measure was recorded via a mercury column sphygmomanometer. Depression levels were assessed using the Beck Depression Inventory-Ia (BDI) scale. Demographics and risk factors were assessed.ResultThe proportion of participants with undiagnosed depression was 15%. Multivariable analyses demonstrated an increase in BDI scores with increased aging. Approximately a 1 point increase in the BDI score was observed for each additional decade of aging in hypertensive patients. Additional factors associated with increased risk of depression included being female (4.28 point BDI score increase), smoking (5.61 point BDI score increase), being hypertensive with no hypertensive medication (4.46 point BDI score increase) and being illiterate (4.46 point BDI score increase).ConclusionsAmong persons with hypertension in outpatient settings in Nepal, demographic (age, sex, education), behavioural (smoking,) and adherence factors (anti-hypertensive medication) were associated with undiagnosed depression. Screening programs in Nepal may assist early intervention in hypertensive patients with sub clinical depression.     

Evaluation of APOE polymorphisms and the risk for age-related macular degeneration in a Southeastern Brazilian population

This study aimed to evaluate the role of APOE polymorphisms (rs429358 and rs7412) in the risk of age-related macular degeneration in a sample of the Southeastern Brazilian population. Seven hundred and five unrelated individuals were analyzed, 334 with age-related macular degeneration (case group), and 371 without the disease (control group). In the case group, patients were further stratified according to disease phenotypes, divided into dry and wet age-related macular degeneration, and non-advanced and advanced age-related macular degeneration. APOE polymorphisms (rs429358 and rs7412) were evaluated through polymerase chain reaction and direct sequencing. In the comparison of cases vs. controls, none of the associations reached statistical significance, considering the Bonferroni-adjusted P-value, although there was a suggestive protection for the E3/E4 genotype (OR = 0.626; P-value = 0.037) and E4 carriers (OR = 0.6515; P-value = 0.047). Statistically significant protection for both the E3/E4 genotype and E4 carriers was observed in the comparisons: advanced age-related macular degeneration vs. controls (OR = 0.3665, P-value = 0.491 × 10⁻³ and OR = 0.4031, P-value = 0.814 × 10⁻³, respectively), advanced age-related macular degeneration vs. non-advanced age-related macular degeneration (OR = 0.2529, P-value = 0.659 × 10⁻⁴ and OR = 0.2692, P-value = 0.631 × 10⁻⁴, respectively). In the comparison of wet age-related macular degeneration vs. control, protection was statistically significant only for E3/E4 (OR = 0.4052, P-value = 0.001). None of the comparisons demonstrated any significant association for E2 genotypes or E2 carriers in age-related macular degeneration risk in this study. Findings suggest a protective role of the E4 haplotype in the APOE gene in the risk for advanced and wet forms of age-related macular degeneration, in a sample of the Brazilian population. To our knowledge, this is the first Brazilian study to show the association between APOE polymorphisms and age-related macular degeneration.     

Combining genome-wide association mapping and transcriptional networks to identify novel genes controlling glucosinolates in Arabidopsis thaliana

Background

Genome-wide association (GWA) is gaining popularity as a means to study the architecture of complex quantitative traits, partially due to the improvement of high-throughput low-cost genotyping and phenotyping technologies. Glucosinolate (GSL) secondary metabolites within Arabidopsis spp. can serve as a model system to understand the genomic architecture of adaptive quantitative traits. GSL are key anti-herbivory defenses that impart adaptive advantages within field trials. While little is known about how variation in the external or internal environment of an organism may influence the efficiency of GWA, GSL variation is known to be highly dependent upon the external stresses and developmental processes of the plant lending it to be an excellent model for studying conditional GWA.

Methodology/Principal Findings

To understand how development and environment can influence GWA, we conducted a study using 96 Arabidopsis thaliana accessions, >40 GSL phenotypes across three conditions (one developmental comparison and one environmental comparison) and ∼230,000 SNPs. Developmental stage had dramatic effects on the outcome of GWA, with each stage identifying different loci associated with GSL traits. Further, while the molecular bases of numerous quantitative trait loci (QTL) controlling GSL traits have been identified, there is currently no estimate of how many additional genes may control natural variation in these traits. We developed a novel co-expression network approach to prioritize the thousands of GWA candidates and successfully validated a large number of these genes as influencing GSL accumulation within A. thaliana using single gene isogenic lines.

Conclusions/Significance

Together, these results suggest that complex traits imparting environmentally contingent adaptive advantages are likely influenced by up to thousands of loci that are sensitive to fluctuations in the environment or developmental state of the organism. Additionally, while GWA is highly conditional upon genetics, the use of additional genomic information can rapidly identify causal loci en masse.     

The commercial red seaweed <Emphasis Type="Italic">Kappaphycus alvarezii</Emphasis>—an overview on farming and environment

Commercial cultivation of the red alga Kappaphycus alvarezii (Doty) Doty has been satisfying the demand of the carrageenan industry for more than 40 years. For the past four decades, this species has been globally introduced to many maritime countries for experimental and commercial cultivation as a sustainable alternate livelihood for coastal villagers. Accompanying the introduction is an increasing concern over the species effects on the biodiversity of endemic ecosystems. The introductions of non-endemic cultivars have resulted in the adaptation of quarantine procedures to minimize bioinvasions of additional invasive species. The present review focuses on Kappaphycus farming techniques through the application of biotechnological tools, ecological interactions with endemic ecosystems, future K. alvarezii farming potentials in Asia, Africa, and the Pacific, and the challenges for prospective farmers, i.e., low raw material market value, diseases, grazing, etc. The introduction of Kappaphycus cultivation to tropical countries will continue due to the high production values realized, coastal villages searching for alternative livelihoods, and the increased global industrial demand for carrageenan.     

Novel pyrrolo[2,1-f][1,2,4]triazin-4-amines: Dual inhibitors of EGFR and HER2 protein tyrosine kinases

A novel series of 5-((4-aminopiperidin-1-yl)methyl)-pyrrolo[2,1-f][1,2,4]triazin-4-amines with small aniline substituents at the C4 position were optimized for dual EGFR and HER2 protein tyrosine kinase inhibition. Compound 8l exhibited promising oral efficacy in both EGFR and HER2-driven human tumor xenograft models.