Genetics web sites

Human Genome Project Information http://www.ornl.gov/TechResources/Human_Genome/home.html

Access Excellence http://www.accessexcellence.org/

Genetics Science Learning Centre at the Eccles Institute of Human Genetics, University of Utah http://gslc.genetics.utah.edu/

Blazing a Genetic Trial http://www.hhmi.org/GeneticTrail/

A Hypermedia Glossary of Genetic Terms prepared and presented by Birgid Schlindwein http://www.weihenstephan.de/~schlind/genglos.html

Virtual Flylab http://vcourseware5.calstatela.edu/VirtualFlyLab/IntroVflyLab.html

Web watch topics coming up…     

A list of personal perspectives with selected quotations,along with lists of tributes,historical notes,Nobel and Kettering awards related to photosynthesis

The history of photosynthesis research can be found in original papers and books. However, a special history is available from the prefatory chapters and the personal perspectives of various researchers who published them in several journals over the last 40 years. We have compiled a list of such perspectives published since 1964. Selection is not easy, especially of authors who were not directly engaged in photosynthesis research; some are included for their special insights related to central issues in the study of photosynthesis. Our journal, Photosynthesis Research, contains other valuable historic data in the occasional tributes, obituaries and historical notes, that have been published. Lists of these items are included. This article ends by listing the Nobel prizes related to photosynthesis and the Kettering Awards for Excellence in Photosynthesis Research. Wherever possible, a web page address is provided. The web page addresses have been taken from the article `Photosynthesis and the Web: 2001' by Larry Orr and Govindjee, available at http://www.life.uiuc.edu/govindjee/photoweb and at http://photoscience.la.asu.edu/photosyn/ photoweb/default.html. ‘When I find a bit of leisure I trifle with my papers. This is one of the lesser frailities. – Horace, Satires I, IV. This revised version was published online in June 2006 with corrections to the Cover Date.     

Association of IL-10 (-819T/C, -592A/C and -1082A/G) and IL-6 -174G/C gene polymorphism and the risk of pneumonia-induced sepsis

Context: Association between inherited variants and the risks of sepsis is controversial.

Objective: To evaluate the risk of pneumonia-induced sepsis by examining its linkage with polymorphisms of IL-6 and IL-10.

Materials and methods: Samples were obtained from 188 pneumonia-induced sepsis patients, 162 pneumonia patients and 200 healthy controls.

Results: Subjects with IL-10 -1082 AA genotypes and IL-6 -174?CC genotype had a higher risk of sepsis and increased mRNA levels.

Conclusion: The variants of IL-10 -1082 A allele and IL-6 -174 C allele contributed to an increased risk of pneumonia-induced sepsis.     

Circulating adiponectin as a biomarker in renal cell carcinoma: a systematic review and meta-analysis

Context: Metabolic imbalance in renal cell carcinoma (RCC) can lead to abnormal adiponectin levels.

Objective: To evaluate circulating adiponectin as a detection or predictive marker for RCC.

Methods: A comprehensive literature search and meta-analysis was performed on studies reporting circulating adiponectin levels and RCC. The meta-analysis was performed using RevMan.

Results: Seven studies compared the circulating adiponection levels between RCC cases and controls. Adiponectin level was significantly lower in RCC cases compared to controls at pre-diagnosis and pre-operative time-points. RCC stage, grade and subtype did not affect adiponectin levels.

Conclusion: Low circulating adiponectin could be a predictive or risk factor for RCC.     

Searching the literature for proteins facilitates the identification of biological processes,if advanced methods of analysis are linked: a case study on microgravity-caused changes in cells

Background: More than one hundred reports were published about the characterization of cells from malignant and healthy tissues, as well as of endothelial cells and stem cells exposed to microgravity conditions.

Methods: We retrieved publications about microgravity related studies on each type of cells, extracted the proteins mentioned therein and analyzed them aiming to identify biological processes affected by microgravity culture conditions.

Results: The analysis revealed 66 different biological processes, 19 of them were always detected when papers about the four types of cells were analyzed.

Conclusion: Since a response to the removal of gravity is common to the different cell types, some of the 19 biological processes could play a role in cellular adaption to microgravity. Applying computer programs, to extract and analyze proteins and genes mentioned in publications becomes essential for scientists interested to get an overview of the rapidly growing fields of gravitational biology and space medicine.     

Notch1 regulates tongue cancer cells proliferation,apoptosis and invasion

Objectives: Notch1 regulates tumor biology in a complex, context-dependent manner. The roles of Notch1 in tongue cancer are still controversial. The aim of this study is to investigate the roles of Notch1 in tongue cancer.

Materials and Methods: The expression of Notch1 was tested between tongue cancer and normal samples by using immunohistochemistry. Tongue cancer cells were transfected with siRNA or plasmid, respectively. Cell proliferation, apoptosis, migration and invasion ability were tested in appropriate ways. The subcutaneous tumor model was established to observe the tumor growth.

Results: Notch1 was upregulated in tongue carcinoma tissues and the expression of Notch1 was related with tumor stage and differentiation. Overexpression of Notch1 could increase tongue cancer cells proliferation, invasion and migration. But inhibited the expression of Notch1 could decrease cells proliferation, invasion and migration and promote cell apoptosis in vitro and in vivo.

Conclusion: Our results prove that the oncogenic role of Notch1 in tongue cancer and provide the direction of targeted therapy of tongue cancer.     

A novel microRNA miR-1165-3p as a potential diagnostic biomarker for allergic asthma

Context: A further examination of a novel miRNA,miR-1165-3p as a biomarker for asthma, which was previously implicated in helper T cells (Th2) in a murine asthma model.

Objective: To determine whether serum miR-1165-3p can serve as a potential diagnostic biomarker for allergic asthma.

Methods: Serum miR-1165-3p was quantified via quantitative real-time PCR (qRT-PCR) in asthmatic and control samples. Serum miR-1165-3p levels were compared between groups and the clinical diagnostic abilities of miR-1165-3p were evaluated. The analyses utilized included a student’s t test, one-way ANOVA, and the generation of receiver operating characteristic (ROC) curves.

Results: Serum miRNA-1165-3p levels were significantly elevated in asthmatics when compared to the healthy controls. Furthermore, the sensitivity and specificity of serum miR-1165-3p were found to be 83% and 68.2%. Additionally, serum miR-1165-3p levels were also found to be significantly elevated in patients with allergic rhinitis (AR) or allergic bronchopulmonary aspergillosis (ABPA).

Conclusions: This study showed that serum miR-1165-3p can potentially be utilized as a noninvasive biomarker that is able to aid in the diagnosis and characterization of allergic asthma.     

Circulating miRs-183-5p, -206-3p and -381-3p may serve as novel biomarkers for 4,4’-methylene diphenyl diisocyanate exposure

Background: Occupational exposure to the most widely used diisocyanate, 4,4’-methylene diphenyl diisocyanate (MDI), is a cause of occupational asthma (OA). Early recognition of MDI exposure and sensitization is essential for the prevention of MDI-OA.

Objective: Identify circulating microRNAs (miRs) as novel biomarkers for early detection of MDI exposure and prevention of MDI-OA.

Materials and methods: Female BALB/c mice were exposed to one of three exposure regimens: dermal exposure to 1% MDI in acetone; nose-only exposure to 4580?±?1497?μg/m³ MDI-aerosol for 60?minutes; or MDI dermal exposure/sensitization followed by MDI-aerosol inhalation challenge. Blood was collected and miRCURY? miRs qPCR Profiling Service was used to profile circulate miRs from dermally exposed mice. Candidate miRs were identified and verified from mice exposed to three MDI-exposure regimens by TaqMan^® miR assays.

Results: Up/down-regulation patterns of circulating mmu-miRs-183-5p, -206-3p and -381-3p were identified and verified. Circulating mmu-miR-183-5p was upregulated whereas mmu-miRs-206-3p and -381-3p were downregulated in mice exposed via all three MDI exposure regimens.

Discussion and conclusion: Upregulation of circulating miR-183-5p along with downregulation of circulating miRs-206-3p and -381-3p may serve as putative biomarkers of MDI exposure and may be considered as potential candidates for validation in exposed human worker populations.     

Standardization in synthetic biology: an engineering discipline coming of age

Background: Leaping DNA read-and-write technologies, and extensive automation and miniaturization are radically transforming the field of biological experimentation by providing the tools that enable the cost-effective high-throughput required to address the enormous complexity of biological systems. However, standardization of the synthetic biology workflow has not kept abreast with dwindling technical and resource constraints, leading, for example, to the collection of multi-level and multi-omics large data sets that end up disconnected or remain under- or even unexploited.

Purpose: In this contribution, we critically evaluate the various efforts, and the (limited) success thereof, in order to introduce standards for defining, designing, assembling, characterizing, and sharing synthetic biology parts. The causes for this success or the lack thereof, as well as possible solutions to overcome these, are discussed.

Conclusion: Akin to other engineering disciplines, extensive standardization will undoubtedly speed-up and reduce the cost of bioprocess development. In this respect, further implementation of synthetic biology standards will be crucial for the field in order to redeem its promise, i.e. to enable predictable forward engineering.     

Adobe bricks can help identify historic weed flora – a case study from south-western Hungary

Background: The adobe bricks of old buildings can preserve diaspores of cultivated and weed species associated with arable fields. Recovery of these plant remains can provide insight into historical agriculture, and former weed flora.

Aims: This study aims to describe and evaluate the changes in the weed flora in south-western Hungary, based on archaeobotanical findings and contemporary plot surveys.

Methods: Plant remains of 51 adobe bricks dating from 1850 to 1950 were identified in south-western Hungary and compared with the flora of 104 plots from the same region.

Results: A total of 276 species were identified from the adobe bricks, while the present-day plot survey yielded 305 species. A significant difference was found between the historical (60- to 160-year-old) and current species richness of the weed flora. The proportion of rare and threatened species decreased by 38.1%. A total of 142 weed species identified from the adobe bricks have declined, and 40 of them even disappeared in comparison with the contemporary surveys. Today, in Hungary and neighbouring countries, more than 80 of these species are rare or threatened and some of them are extinct or critically endangered.

Conclusions: Our findings show that many weed species that flourished in the early twentieth century have declined. This is most likely due to the intensive management practices of cultivated fields and the spread of invasive neophyte taxa. We showed that analysing the botanical information preserved in adobe bricks is a reliable method that can provide evidence of long-term changes in weed flora.     

Differential expression of circulating vascular cell adhesion molecule-1 in subjects with coronary artery disease and cardiac syndrome X without known diabetes mellitus

Context: Inflammation is one of the mechanisms underlying cardiac syndrome X (CSX).

Objectives: Few studies have compared the expression of inflammatory or adhesion molecules between coronary artery disease (CAD) versus CSX.

Materials and methods: Ninety-two CSX and 145 CAD subjects without known diabetes mellitus underwent coronary angiogram for angina.

Results: Vascular cell adhesion molecule (VCAM)-1 (median, 507 versus 431?ng/ml, p?=?0.001) was significantly higher in the CAD group. In the binary regression, VCAM-1 was a significant differential factor for CAD versus CSX.

Discussion and conclusion: Adhesion molecules might be implicated in the differential expression of macro versus microvascular coronary disease.

Trial registration number: NCT01198730 at https://clinicaltrials.gov     

Effects of floral diversity and pollinator behaviour on the persistence of hybrid zones between plants sharing pollinators

Background: Plant hybrid zones often display a large diversity in floral traits due to segregation and recombination occurring in the second and later hybrid generations. Such diversity can have important effects on pollinator behaviour.

Aims: We hypothesised that the number of floral types and their relative densities may influence pollinator preferences and level of flower constancy.

Methods: To test the influence of floral diversity on the number of visits to inflorescences of the most common type and on the level of flower constancy, we monitored bumblebees’ behaviour in experimental arrays of artificial inflorescences with a common (‘parental’) floral type mixed with either one or three uncommon (‘hybrid’) floral types.

Results: We found that pollinators preferentially visited the most common flower colour and showed slightly greater constancy when the number of uncommon floral types was increased.

Conclusions: We conclude that diversity in flower colour could promote moderate pollinator constancy in some types of hybrid zones. Segregation of floral phenotypes due to hybridisation may result in small levels of pollinator-mediated assortative mating and contribute, to a small extent, and most probably in combination with other factors, to the persistence of some hybrid zones.     

A systems biology-led insight into the role of the proteome in neurodegenerative diseases

Introduction: Multifactorial disorders are the result of nonlinear interactions of several factors; therefore, a reductionist approach does not appear to be appropriate. Proteomics is a global approach that can be efficiently used to investigate pathogenetic mechanisms of neurodegenerative diseases.

Areas covered: Here, we report a general introduction about the systems biology approach and mechanistic insights recently obtained by over-representation analysis of proteomics data of cellular and animal models of Alzheimer’s disease, Parkinson’s disease and other neurodegenerative disorders, as well as of affected human tissues.

Expert commentary: As an inductive method, proteomics is based on unbiased observations that further require validation of generated hypotheses. Pathway databases and over-representation analysis tools allow researchers to assign an expectation value to pathogenetic mechanisms linked to neurodegenerative diseases. The systems biology approach based on omics data may be the key to unravel the complex mechanisms underlying neurodegeneration.     

A new nitrobenzoxadiazole-based GSTP1-1 inhibitor with a previously unheard of mechanism of action and high stability

Context: The nitrobezoxadiazole derivative NBDHEX is a potent inhibitor of glutathione transferase P1-1 (GSTP1-1) endowed with outstanding anticancer activity in different tumor models.

Objective: To characterize by in vitro biochemical and in silico studies the NBDHEX analogues named MC2752 and MC2753.

Materials and methods: Synthesis of MC2752 and MC2753, biochemical assays and in silico docking and normal-mode analyses.

Results: The presence of a hydrophobic moiety in the side chain of MC2753 confers unique features to this molecule. Unlike its parent drug NBDHEX, MC2753 does not require GSH to trigger the dissociation of the complex between GSTP1-1 and TRAF2, and displays high stability towards the nucleophilic attack of the tripeptide under physiological conditions.

Discussion and conclusion: MC2753 may represent a lead compound for the development of novel GSTP1-1 inhibitors not affected in their anticancer action by fluctuations of cellular GSH levels, and characterized by an increased half-life in vivo.     

Associations of rs1883832 and rs4810485 polymorphisms of CD40 gene with myocardial infarction in the Tunisian population

Context: Cluster of differentiation 40 (CD40), and its ligand CD40L, are major co-stimulatory molecules whose interactions are important in both cellular and humoral immunity, and has been suggested to play a role in the pathogenesis of acute coronary syndrome.

Objective: The aim of this study was to examine the association of CD40 polymorphisms (-1?C>T (rs1883832) and 945G>T (rs4810485)) and myocardial infarction (MI), and to test the association of CD40 gene haplotypes with MI in Tunisians.

Materials and methods: Three hundred and fifty MI patients and 301 apparently healthy controls were included in the study. The polymorphisms of CD40 were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).

Results: There were significant differences in the genotype and allele frequencies of CD40 gene -1?C>T (rs1883832) polymorphism between cases and controls. Stratifying according to gender, the association between the TT genotype and MI was statistically significant in males, only. Haplotype analysis revealed that the C-T and T-G haplotypes were associated with an increased risk of MI (p?=?0.012 and p?<?0.001, respectively).

Conclusions: Our work showed a significant association between the -1?C>T (rs1883832) polymorphism of the CD40 gene and MI in the Tunisians.     

Epidermal growth factor,growth differentiation factor-15, and survivin as novel biocompatibility markers in children on chronic dialysis

Context: Chronic dialysis results in aggravation of apoptosis and cell damage, triggered by bioincompatibility of dialysis membranes and peritoneal fluids.

Objective: The aim of study was to assess the usefulness of epidermal growth factor (EGF), growth differentiation factor (GDF)-15, and survivin as novel markers of biocompatibility in dialyzed children.

Materials and methods: Parameters were assessed by ELISA in 19 patients on hemodialysis and 22 children on peritoneal dialysis.

Results: Serum concentrations of analyzed parameters in children on chronic dialysis differed significantly from controls and depended strongly on the dialysis technique.

Conclusions: EGF, GDF-15, and survivin may serve as new biocompatibility markers in children on chronic dialysis.     

Circulating microRNAs in human obesity: a systematic review

Context: Differential expression profiles of microRNAs have been reported in human obesity suggesting a miRNAs role in the development of obesity and associated disorders.

Objective: To review circulating microRNAs (c-miRNAs) dysregulated in human obesity and to predict their possible target genes.

Methods: We performed a systematic review on PubMed database (PROSPERO, CRD42017077742) for original works on c-miRNAs and human obesity and recorded c-miRNAs with differential expression profiles. Potential target genes and metabolic pathways for dysregulated miRNAs with at least two independent reports were searched using bioinformatic tools.

Results: Twenty-two c-miRNAs are overexpressed, nine underexpressed and two c-miRNAs dysregulated in both directions in people with obesity compared to lean controls. Bioinformatic analyses suggest these c-miRNAs target on genes associated with fatty acid metabolism and PI3k/Akt pathway.

Conclusion: Literature records 33 c-miRNAs confirmedly dysregulated in human obesity. Their predicted target genes are involved in pathways that could explain the development of obesity and its comorbidities. Further research will clarify the role of these miRNAs on metabolic diseases and their usefulness for the prognosis, prevention and treatment of obesity.     

Breeding biology of Western Bonelli’s Warblers Phylloscopus bonelli in the Mediterranean region

Capsule: The Western Bonelli’s Warbler Phylloscopus bonelli has a nest success of only 25% in the core of its range in western Europe.

Aims: To investigate the breeding biology of Western Bonelli’s Warbler P. bonelli, focusing on possible altitude effects and potential reproductive problems.

Methods: Three Western Bonelli’s Warbler populations were monitored during the 2012 and 2013 breeding seasons in the massif range of Sierra Nevada, Spain. We determined all the breeding parameters and calculated daily survival and success rates for each reproductive period.

Results: The three studied populations did not differ in any breeding parameters. Altitude showed a positive relationship with clutch size and duration of incubation period, but a negative relationship with nestling tarsus growth and body mass gain. Daily survival rates during incubation and nestling periods were similar to those of common warblers, but the species presented a low breeding success of 25%.

Conclusion: The absence of differences among the three populations suggests that the information provided here could be representative of its distribution in the woodlands of Sierra Nevada. The novel and detailed information reported is crucial not only for expanding our understanding of this species but also to draw attention to the potential risks that it might face in the near future, considering the reduction that this species has suffered in Sierra Nevada during recent decades.     

Biosystematic studies on the mountain plant Gentiana lutea L. reveal variability in reproductive traits among subspecies

Background: Taxonomic analysis provides a basic understanding for taxon identification and contributes to preliminary information for several branches of applied biology, while studies on reproductive strategies and plant fitness are essential to interpret population status and dynamics.

Aims: We tested the reliability of diagnostic characters for identification and to characterise sexual resource allocation, the breeding system and seed predation among subspecies of Gentiana lutea.

Methods: We analysed morphological characters in 70 herbarium specimens. In five natural populations we counted pollen and ovule numbers, assessed reproductive output after pollination treatments and evaluated pre-dispersal predation.

Results: Taxonomic traits previously indicated as diagnostic were not sufficient to discriminate among subspecies. The pollen number and pollen:ovule (P:O) ratio varied strongly among subspecies; self-pollinated flowers produced a significantly lower number of seeds than open-pollinated flowers. Retention of empty fruits and high levels of pre-dispersal seed predation were observed in every case.

Conclusions: The variation of P:O ratios among subspecies suggests different efficiency in pollen transfer. The species is self-compatible, nevertheless all subspecies require pollen vectors to enhance cross pollination and viable seed production. Fruit retention may have evolved as a strategy to reduce predation, ensuring higher plant fitness.