PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-25 (226375)

Clipboard (0)
None

Related Articles

1.  Excessive folate synthesis limits lifespan in the C. elegans: E. coli aging model 
BMC Biology  2012;10:67.
Background
Gut microbes influence animal health and thus, are potential targets for interventions that slow aging. Live E. coli provides the nematode worm Caenorhabditis elegans with vital micronutrients, such as folates that cannot be synthesized by animals. However, the microbe also limits C. elegans lifespan. Understanding these interactions may shed light on how intestinal microbes influence mammalian aging.
Results
Serendipitously, we isolated an E. coli mutant that slows C. elegans aging. We identified the disrupted gene to be aroD, which is required to synthesize aromatic compounds in the microbe. Adding back aromatic compounds to the media revealed that the increased C. elegans lifespan was caused by decreased availability of para-aminobenzoic acid, a precursor to folate. Consistent with this result, inhibition of folate synthesis by sulfamethoxazole, a sulfonamide, led to a dose-dependent increase in C. elegans lifespan. As expected, these treatments caused a decrease in bacterial and worm folate levels, as measured by mass spectrometry of intact folates. The folate cycle is essential for cellular biosynthesis. However, bacterial proliferation and C. elegans growth and reproduction were unaffected under the conditions that increased lifespan.
Conclusions
In this animal:microbe system, folates are in excess of that required for biosynthesis. This study suggests that microbial folate synthesis is a pharmacologically accessible target to slow animal aging without detrimental effects.
doi:10.1186/1741-7007-10-67
PMCID: PMC3583181  PMID: 22849329
aging; microbes; folate; C. elegans; E. coli
2.  The worm in the world and the world in the worm 
BMC Biology  2012;10:57.
Caenorhabditis elegans is a preeminent model organism, but the natural ecology of this nematode has been elusive. A four-year survey of French orchards published in BMC Biology reveals thriving populations of C. elegans (and Caenorhabditis briggsae) in rotting fruit and plant stems. Rather than being simply a 'soil nematode', C. elegans appears to be a 'plant-rot nematode'. These studies signal a growing interest in the integrated genomics and ecology of these tractable animals.
See research article http://www.biomedcentral.com/1741-7007/10/59
doi:10.1186/1741-7007-10-57
PMCID: PMC3382423  PMID: 22731915
3.  Natural genetic variation determines susceptibility to aggregation or toxicity in a C. elegans model for polyglutamine disease 
BMC Biology  2013;11:100.
Background
Monogenic gain-of-function protein aggregation diseases, including Huntington’s disease, exhibit substantial variability in age of onset, penetrance, and clinical symptoms, even between individuals with similar or identical mutations. This difference in phenotypic expression of proteotoxic mutations is proposed to be due, at least in part, to the variability in genetic background. To address this, we examined the role of natural variation in defining the susceptibility of genetically diverse individuals to protein aggregation and toxicity, using the Caenorhabditis elegans polyglutamine model.
Results
Introgression of polyQ40 into three wild genetic backgrounds uncovered wide variation in onset of aggregation and corresponding toxicity, as well as alteration in the cell-specific susceptibility to aggregation. To further dissect these relationships, we established a panel of 21 recombinant inbred lines that showed a broad range of aggregation phenotypes, independent of differences in expression levels. We found that aggregation is a transgressive trait, and does not always correlate with measures of toxicity, such as early onset of muscle dysfunction, egg-laying deficits, or reduced lifespan. Moreover, distinct measures of proteotoxicity were independently modified by the genetic background.
Conclusions
Resistance to protein aggregation and the ability to restrict its associated cellular dysfunction are independently controlled by the natural variation in genetic background, revealing important new considerations in the search for targets for therapeutic intervention in conformational diseases. Thus, our C. elegans model can serve as a powerful tool to dissect the contribution of natural variation to individual susceptibility to proteotoxicity.
Please see related commentary by Kaeberlein, http://www.biomedcentral.com/1741-7007/11/102.
doi:10.1186/1741-7007-11-100
PMCID: PMC3816611  PMID: 24079614
Protein aggregation; Polyglutamine; Conformational disease; Genetic modifier; Natural variation
4.  Deciphering the role of natural variation in age-related protein homeostasis 
BMC Biology  2013;11:102.
Understanding the genetic basis of age-related diseases is a critical step toward developing therapies that promote healthy aging. Numerous genes have been identified that modulate lifespan, but the influence of natural variation in aging has not been well studied. A new report utilizing a transgenic protein aggregation model in Caenorhabditis elegans has provided important tools and insights into the relationship between natural genetic variation, protein aggregation, and age-related pathology.
See research article: http://www.biomedcentral.com/1741-7007/11/100
doi:10.1186/1741-7007-11-102
PMCID: PMC3849513  PMID: 24228595
5.  Prospects for automated diagnosis of verbal autopsies 
BMC Medicine  2014;12:18.
Verbal autopsy is a method for assessing probable causes of death from lay reporting of signs, symptoms and circumstances by family members or caregivers of a deceased person. Several methods of automated diagnoses of causes of death from standardized verbal autopsy questionnaires have been developed recently (Inter-VA, Tariff, Random Forest and King-Lu). Their performances have been assessed in a series of papers in BMC Medicine. Overall, and despite high specificity, the current strategies of automated computer diagnoses lead to relatively low sensitivity and positive predictive values, even for causes which are expected to be easily assessed by interview. Some methods have even abnormally low sensitivity for selected diseases of public health importance and could probably be improved. Ways to improve the current strategies are proposed: more detailed questionnaires; using more information on disease duration; stratifying for large groups of causes of death by age, sex and main category; using clusters of signs and symptoms rather than quantitative scores or ranking; separating indeterminate causes; imputing unknown cause with appropriate methods.
Please see related articles: http://www.biomedcentral.com/1741-7015/12/5; http://www.biomedcentral.com/1741-7015/12/19; http://www.biomedcentral.com/1741-7015/12/20; http://www.biomedcentral.com/1741-7015/12/21; http://www.biomedcentral.com/1741-7015/12/22; http://www.biomedcentral.com/1741-7015/12/23.
doi:10.1186/1741-7015-12-18
PMCID: PMC3912493  PMID: 24495788
Cause of death; Verbal autopsy; Automated diagnosis; Health information system; Evaluation of health programs; Public health
6.  Regulation of metabolism in Caenorhabditis elegans longevity 
Journal of Biology  2010;9(1):7.
The nematode Caenorhabditis elegans is a favorite model for the study of aging. A wealth of genetic and genomic studies show that metabolic regulation is a hallmark of life-span modulation. A recent study in BMC Biology identifying metabolic signatures for longevity suggests that amino-acid pools may be important in longevity.
See research article http://www.biomedcentral.com/1741-7007/8/14.
doi:10.1186/jbiol215
PMCID: PMC2871526  PMID: 20156326
7.  Metformin Retards Aging in C. elegans by Altering Microbial Folate and Methionine Metabolism 
Cell  2013;153(1):228-239.
Summary
The biguanide drug metformin is widely prescribed to treat type 2 diabetes and metabolic syndrome, but its mode of action remains uncertain. Metformin also increases lifespan in Caenorhabditis elegans cocultured with Escherichia coli. This bacterium exerts complex nutritional and pathogenic effects on its nematode predator/host that impact health and aging. We report that metformin increases lifespan by altering microbial folate and methionine metabolism. Alterations in metformin-induced longevity by mutation of worm methionine synthase (metr-1) and S-adenosylmethionine synthase (sams-1) imply metformin-induced methionine restriction in the host, consistent with action of this drug as a dietary restriction mimetic. Metformin increases or decreases worm lifespan, depending on E. coli strain metformin sensitivity and glucose concentration. In mammals, the intestinal microbiome influences host metabolism, including development of metabolic disease. Thus, metformin-induced alteration of microbial metabolism could contribute to therapeutic efficacy—and also to its side effects, which include folate deficiency and gastrointestinal upset.
PaperClip
Graphical Abstract
Highlights
► The antidiabetic drug metformin disrupts bacterial folate and methionine cycles ► This effect in C. elegans microbiota increases lifespan via methionine restriction ► Metformin increases lifespan only if microbiota are present and is otherwise toxic ► Microbiota may mediate metformin effects on mammalian health and aging
Metformin, widely prescribed to treat diabetes, induces longevity in worms by altering host-microbiota interactions. By disrupting microbial folate and methionine cycles, metformin induces methionine restriction in the worm, which increases lifespan.
doi:10.1016/j.cell.2013.02.035
PMCID: PMC3898468  PMID: 23540700
8.  Regeneration review reprise 
Journal of Biology  2010;9(2):15.
There have been notable advances in the scientific understanding of regeneration within the past year alone, including two recently published in BMC Biology. Increasingly, progress in the regeneration field is being inspired by comparisons with stem cell biology and enabled by newly developed techniques that allow simultaneous examination of thousands of genes and proteins.
See research articles http://www.biomedcentral.com/1741-7007/7/83 and http://www.biomedcentral.com/1741-7007/8/5.
doi:10.1186/jbiol224
PMCID: PMC2871519  PMID: 20236485
9.  Isomin: a novel cytoplasmic intermediate filament protein from an arthropod species 
BMC Biology  2011;9:17.
Background
The expression of intermediate filaments (IFs) is a hallmark feature of metazoan cells. IFs play a central role in cell organization and function, acting mainly as structural stress-absorbing elements. There is growing evidence to suggest that these cytoskeletal elements are also involved in the integration of signalling networks. According to their fundamental functions, IFs show a widespread phylogenetic expression, from simple diblastic animals up to mammals, and their constituent proteins share the same molecular organization in all species so far analysed. Arthropods represent a major exception in this scenario. Only lamins, the nuclear IF proteins, have so far been identified in the model organisms analysed; on this basis, it has been considered that arthropods do not express cytoplasmic IFs.
Results
Here, we report the first evidence for the expression of a cytoplasmic IF protein in an arthropod - the basal hexapod Isotomurus maculatus. This new protein, we named it isomin, is a component of the intestinal terminal web and shares with IFs typical biochemical properties, molecular features and reassembly capability. Sequence analysis indicates that isomin is mostly related to the Intermediate Filament protein C (IFC) subfamily of Caenorhabditis elegans IF proteins, which are molecular constituents of the nematode intestinal terminal web. This finding is coherent with, and provides further support to, the most recent phylogenetic views of arthropod ancestry. Interestingly, the coil 1a domain of isomin appears to have been influenced by a substantial molecular drift and only the aminoterminal part of this domain, containing the so-called helix initiation motif, has been conserved.
Conclusions
Our results set a new basis for the analysis of IF protein evolution during arthropod phylogeny. In the light of this new information, the statement that the arthropod phylum lacks cytoplasmic IFs is no longer tenable.
See commentary article: http://www.biomedcentral.com/1741-7007-9-16.
doi:10.1186/1741-7007-9-17
PMCID: PMC3065449  PMID: 21356109
10.  Travelling within the fetal gut: simple rules for an arduous journey 
BMC Biology  2014;12:50.
The complex physiology of the gastrointestinal tract is regulated by intricate neural networks embedded within the gut wall. How neural crest cells colonize the intestine to form the enteric nervous system is of great interest to developmental biologists, but also highly relevant for understanding gastrointestinal disorders. A recent paper in BMC Biology addresses this issue with live imaging of gut explants from mouse embryos.
See research article: http://www.biomedcentral.com/1741-7007/12/23.
doi:10.1186/s12915-014-0050-z
PMCID: PMC4096386  PMID: 25184534
11.  Genome of a songbird unveiled 
Journal of Biology  2010;9(3):19.
An international collaborative effort has recently uncovered the genome of the zebra finch, a songbird model that has provided unique insights into an array of biological phenomena.
See research articles http://www.biomedcentral.com/1471-2164/9/131, http://www.biomedcentral.com/1471-2164/11/220/, http://www.biomedcentral.com/1471-2202/11/46/ and http://www.biomedcentral.com/1741-7007/8/28/
doi:10.1186/jbiol222
PMCID: PMC2871510  PMID: 20359317
12.  Time is of the essence for ParaHox homeobox gene clustering 
BMC Biology  2013;11:72.
ParaHox genes, and their evolutionary sisters the Hox genes, are integral to patterning the anterior-posterior axis of most animals. Like the Hox genes, ParaHox genes can be clustered and exhibit the phenomenon of colinearity - gene order within the cluster matching gene activation. Two new instances of ParaHox clustering provide the first examples of intact clusters outside chordates, with gene expression lending weight to the argument that temporal colinearity is the key to understanding clustering.
See research articles: http://www.biomedcentral.com/1741-7007/11/68 and http://www.biomedcentral.com/1471-2148/13/129
doi:10.1186/1741-7007-11-72
PMCID: PMC3694477  PMID: 23803337
13.  The water flea Daphnia - a 'new' model system for ecology and evolution? 
Journal of Biology  2010;9(2):21.
Daphnia pulex is the first crustacean to have its genome sequenced. Availability of the genome sequence will have implications for research in aquatic ecology and evolution in particular, as addressed by a series of papers published recently in BMC Evolutionary Biology and BMC Genomics.
See research articles http://www.biomedcentral.com/1471-2148/9/78, http://www.biomedcentral.com/1471-2164/10/527, http://www.biomedcentral.com/1471-2148/9/79, http://www.biomedcentral.com/1471-2164/10/175, http://www.biomedcentral.com/1471-2164/10/172, http://www.biomedcentral.com/1471-2164/10/169, http://www.biomedcentral.com/1471-2164/10/170 and http://www.biomedcentral.com/1471-2148/9/243.
doi:10.1186/jbiol212
PMCID: PMC2871515  PMID: 20478012
14.  Regulation of lipid droplet turnover by ubiquitin ligases 
BMC Biology  2010;8:94.
Mutation of the protein spartin is a cause of one form of spastic paraplegia. Spartin interacts with ubiquitin ligases of the Nedd4 family, and a recent report in BMC Biology now shows that it acts as an adaptor to recruit and activate the ubiquitin ligase AIP4 onto lipid droplets, leading to the ubiquitination and degradation of droplet-associated proteins. A deficiency of spartin apparently causes lipid droplets to accumulate.
See research article: http://www.biomedcentral.com/1741-7007/8/72/
doi:10.1186/1741-7007-8-94
PMCID: PMC2906420  PMID: 20646264
15.  Bed bug deterrence 
BMC Biology  2010;8:117.
A recent study in BMC Biology has determined that the immature stage of the bed bug (the nymph) signals its reproductive status to adult males using pheromones and thus avoids the trauma associated with copulation in this species. The success of this nymphal strategy of deterrence is instructive. Against the background of increasing problems with bed bugs, this research raises the question whether pheromones might be used to control them.
See research article http://www.biomedcentral.com/1741-7007/8/121
doi:10.1186/1741-7007-8-117
PMCID: PMC2936290  PMID: 20828375
16.  Selecting the right medical student 
BMC Medicine  2013;11:245.
Medical student selection is an important but difficult task. Three recent papers by McManus et al. in BMC Medicine have re-examined the role of tests of attainment of learning (A’ levels, GCSEs, SQA) and of aptitude (AH5, UKCAT), but on a much larger scale than previously attempted. They conclude that A’ levels are still the best predictor of future success at medical school and beyond. However, A’ levels account for only 65% of the variance in performance that is found. Therefore, more work is needed to establish relevant assessment of the other 35%.
Please see related research articles http://www.biomedcentral.com/1741-7015/11/242, http://www.biomedcentral.com/1741-7015/11/243 and http://www.biomedcentral.com/1741-7015/11/244.
doi:10.1186/1741-7015-11-245
PMCID: PMC3827327  PMID: 24229397
Medical School Admission; Predictors of performance; Aptitude testing
17.  Response to Klütsch and Crapon de Caprona 
BMC Biology  2010;8:120.
This article is a response to Klütsch and Crapon de Caprona
See correspondence article http://www.biomedcentral.com/1741-7007/8/119 and our original research article http://www.biomedcentral.com/1741-7007/8/16.
doi:10.1186/1741-7007-8-120
PMCID: PMC2944130  PMID: 20825654
18.  Answer to Wang and Luo, "Polyploidization increases meiotic recombination frequency in Arabidopsis: a close look at statistical modelling and data analysis" 
BMC Biology  2012;10:31.
This article is a response to Wang and Luo.
See correspondence article http://www.biomedcentral.com/1741-7007/10/30/ [WEBCITE] and the original research article http://www.biomedcentral.com/1741-7007/9/24 [WEBCITE].
doi:10.1186/1741-7007-10-31
PMCID: PMC3353204  PMID: 22513141
19.  Response to Wang and Luo 
BMC Biology  2012;10:32.
This article is a response to Wang and Luo.
See correspondence article http://www.biomedcentral.com/1741-7007/10/30 and the original research article http://www.biomedcentral.com/1741-7007/9/24.
doi:10.1186/1741-7007-10-32
PMCID: PMC3379956  PMID: 22513177
20.  No severe and global X chromosome inactivation in meiotic male germline of Drosophila 
BMC Biology  2012;10:50.
This article is a response to Vibranovski et al.
See correspondence article http://www.biomedcentral.com/1741-7007/10/49 and the original research article http://www.biomedcentral.com/1741-7007/9/29
We have previously reported a high propensity of testis-expressed X-linked genes to activation in meiotic cells, a similarity in global gene expression between the X chromosome and autosomes in meiotic germline, and under-representation of various types of tissue-specific genes on the X chromosome. Based on our findings and a critical review of the current literature, we believe that there is no global and severe silencing of the X chromosome in the meiotic male germline of Drosophila. The term 'meiotic sex chromosome inactivation' (MSCI) therefore seems misleading when used to describe the minor underexpression of the X chromosome in the testis of Drosophila, because this term erroneously implies a profound and widespread silencing of the X-linked genes, by analogy to the well-studied MSCI system in mammals, and therefore distracts from identification and analysis of the real mechanisms that orchestrate gene expression and evolution in this species.
doi:10.1186/1741-7007-10-50
PMCID: PMC3391177
21.  Tracking down the sources of experimental contamination in microbiome studies 
Genome Biology  2014;15(12):564.
A recent report warns that DNA extraction kits and other laboratory reagents are considerable sources of contamination in microbiome experiments. The issue of contamination is particularly problematic for samples of low biomass.
See related research, http://www.biomedcentral.com/1741-7007/12/87
doi:10.1186/s13059-014-0564-2
PMCID: PMC4311479  PMID: 25608874
22.  Increased uracil misincorporation in lymphocytes from folate-deficient rats 
British Journal of Cancer  2000;83(11):1532-1537.
The development of certain human cancers has been linked with inadequate intake of folates. The effects of folate deficiency in vivo on DNA stability (strand breakage, misincorporated uracil and oxidative base damage) in lymphocytes isolated from rats fed a diet deficient in folic acid was determined. Because the metabolic pathways of folate and other methyl donors are closely coupled, the effects of methionine and choline deficiency alone or in combination with folate deficiency were determined. Feeding male Hooded Lister rats a folate-free diet for 10 weeks created a moderate folate deficiency (25–50% (approx.) decrease in plasma, red blood cell and hepatic folate concentrations (P < 0.05) and a 20% rise in plasma homocysteine (P < 0.05)). Lymphocyte DNA strand breakage was increased successively in all groups after 4 weeks and 8 weeks on the diet (50–100% (approx.) after 8 weeks). Only low folate specifically and progressively induced uracil misincorporation throughout the study (100% (approx.) after 8 weeks). Neither folate deficiency nor choline/methionine deficiency altered oxidative DNA base damage. In summary, moderate folate deficiency in vivo is associated with a decrease in DNA stability, measured as increased DNA strand breakage and misincorporated uracil. © 2000 Cancer Research Campaign http://www.bjcancer.com
doi:10.1054/bjoc.2000.1481
PMCID: PMC2363426  PMID: 11076664
folic acid deficiency; methyl-donor deficiency; rat lymphocytes; misincorporated uracil; oxidized DNA bases
23.  Systems-biology dissection of eukaryotic cell growth 
BMC Biology  2010;8:62.
A recent article in BMC Biology illustrates the use of a systems-biology approach to integrate data across the transcriptome, proteome and metabolome of budding yeast in order to dissect the relationship between nutrient conditions and cell growth.
See research article http://jbiol.com/content/6/2/4 and http://www.biomedcentral.com/1741-7007/8/68
doi:10.1186/1741-7007-8-62
PMCID: PMC2875221  PMID: 20529234
24.  Proteasome inhibition, the pursuit of new cancer therapeutics, and the adaptor molecule p130Cas 
BMC Biology  2011;9:72.
Current interest in proteasome inhibitors for cancer therapy has stimulated considerable research efforts to identify the molecular pathway to their cytotoxicity with a view to identifying the mechanisms of sensitivity and resistance as well as informing the development of new drugs. Zhao and Vuori describe this month in BMC Biology experiments indicating a novel role of the adaptor protein p130Cas in sensitivity to apoptosis induced not only by proteasome inhibitors but also by the unrelated drug doxorubicin.
See research article: http:// http://www.biomedcentral.com/1741-7007/9/73
doi:10.1186/1741-7007-9-72
PMCID: PMC3203852  PMID: 22034840
25.  Smart biomaterials - regulating cell behavior through signaling molecules 
BMC Biology  2010;8:59.
Important advances in the field of tissue engineering are arising from increased interest in novel biomaterial designs with bioactive components that directly influence cell behavior. Following the recent work of Mitchell and co-workers published in BMC Biology, we review how spatial and temporal control of signaling molecules in a matrix material regulates cellular responses for tissue-specific applications.
See research article http://www.biomedcentral.com/1741-7007/8/57
doi:10.1186/1741-7007-8-59
PMCID: PMC2873335  PMID: 20529238

Results 1-25 (226375)