After unilateral total knee arthroplasty (TKA), osteoarthritis (OA) in the non-operated often progresses. The altered gait mechanics exhibited by patients after TKA increase the loading on the non-operated knee and predispose it to disease progression. Therefore, our objective was to examine the potentially detrimental changes in frontal plane kinetics and kinematics during walking in patients who underwent unilateral TKA. Thirty one subjects six months after TKA, forty four subjects one year after unilateral TKA and twenty control subjects were recruited. All subjects underwent three dimensional gait analysis. In the TKA groups, the non-operated knee had a higher adduction angle and higher dynamic loading, knee adduction moment and impulse, compared to the operated knee. This increased loading may be an underlying reason for OA progression in the non-operated knee. Measures of loading in the control knee did not differ from that of the non-operated knee in the TKA group, but the TKA group walked with shorter step length. Whilst the non-operated knee loading was not different from controls, there may be greater risk of cumulative loading in the non-operated knee of the TKA group given their shorter step length.
Ultrasound-based real-time molecular imaging in large blood vessels holds promise for early detection and diagnosis of various important and significant diseases, such as stroke, atherosclerosis, and cancer. Central to the success of this imaging technique is the isolation of ligand-receptor bound adherent microbubbles from free microbubbles and tissue structures. In this paper, we present an alternative approach, termed singular spectrum-based targeted molecular (SiSTM) imaging, which separates signal components using singular value spectra content over local regions of complex echo data. Simulations were performed to illustrate the effects of acoustic target motion and harmonic energy on SiSTM imaging-derived measurements of statistical dimensionality. In vitro flow phantom experiments were performed under physiologically realistic conditions (2.7 cm/s flow velocity and 4 mm diameter) with targeted and non-targeted phantom channels. Both simulation and experimental results demonstrated that the relative motion and harmonic characteristics of adherent microbubbles (i.e. low motion and large harmonics) yields echo data with dimensionality that is distinct from free microbubbles (i.e. large motion and large harmonics) and tissue (i.e. low motion and low harmonics). Experimental SiSTM images produced the expected trend of greater adherent microbubble signal in targeted versus non-targeted microbubble experiments (P < 0.05, n = 4). The location of adherent microbubbles was qualitatively confirmed via optical imaging of fluorescent DiI signal along the phantom channel walls after SiSTM imaging. In comparison with two frequency-based real-time molecular imaging strategies, SiSTM imaging provided significantly higher image contrast (P < 0.001, n = 4) and larger area under the receiver operating characteristic curve (P < 0.05, n = 4).
The mechanistic underpinnings of metastatic dormancy and reactivation are poorly understood. A gain-of-function cDNA screen reveals that Coco, a secreted antagonist of TGF-β ligands, induces dormant breast cancer cells to undergo reactivation in the lung. Mechanistic studies indicate that Coco exerts this effect by blocking lung-derived BMP ligands. Whereas Coco enhances the manifestation of traits associated with cancer stem cells, BMP signaling suppresses it. Coco induces a discrete gene expression signature, which is strongly associated with metastatic relapse to the lung but not to the bone or brain in patients. Experiments in mouse models suggest that these latter organs contain niches devoid of bioactive BMP. These findings reveal that metastasis-initiating cells need to overcome organ-specific anti-metastatic signals in order to undergo reactivation.
Within the TGF-β superfamily, there are approximately forty ligands divided into two major branches: the TGF-β/Activin/Nodal ligands and the BMP/GDF ligands. We studied the ligand GDF3 and found that it inhibits signaling by its co-family members, the BMPs; however, GDF3 has been described by others to have Nodal-like activity. Here, we show that GDF3 can activate Nodal signaling, but only at very high doses and only upon mRNA over-expression. In contrast, GDF3 inhibits BMP signaling upon over-expression of GDF3 mRNA, as recombinant protein, and regardless of its dose. We therefore further characterized the mechanism through which GDF3 protein acts as a specific BMP inhibitor and found that the BMP inhibitory activity of GDF3 resides redundantly in the unprocessed, predominant form and in the mature form of the protein. These results confirm and extend the activity that we described for GDF3 and illuminate the experimental basis for the different observations of others. We suggest that GDF3 is either a bi-functional TGF-β ligand, or, more likely, that it is a BMP inhibitor that can artificially activate Nodal signaling under non-physiological conditions.
GDF3; BMP; TGF-β; Embryo
The United States spends more than any other country on health care. The poor relative performance of the US compared to other high-income countries has attracted attention and raised questions about the performance of the US health system. An important dimension to poor national performance is the large disparities in life expectancy.
We applied a mixed effects Poisson statistical model and Gaussian Process Regression to estimate age-specific mortality rates for US counties from 1985 to 2010. We generated uncertainty distributions for life expectancy at each age using standard simulation methods.
Female life expectancy in the United States increased from 78.0 years in 1985 to 80.9 years in 2010, while male life expectancy increased from 71.0 years in 1985 to 76.3 years in 2010. The gap between female and male life expectancy in the United States was 7.0 years in 1985, narrowing to 4.6 years in 2010. For males at the county level, the highest life expectancy steadily increased from 75.5 in 1985 to 81.7 in 2010, while the lowest life expectancy remained under 65. For females at the county level, the highest life expectancy increased from 81.1 to 85.0, and the lowest life expectancy remained around 73. For male life expectancy at the county level, there have been three phases in the evolution of inequality: a period of rising inequality from 1985 to 1993, a period of stable inequality from 1993 to 2002, and rising inequality from 2002 to 2010. For females, in contrast, inequality has steadily increased during the 25-year period. Compared to only 154 counties where male life expectancy remained stagnant or declined, 1,405 out of 3,143 counties (45%) have seen no significant change or a significant decline in female life expectancy from 1985 to 2010. In all time periods, the lowest county-level life expectancies are seen in the South, the Mississippi basin, West Virginia, Kentucky, and selected counties with large Native American populations.
The reduction in the number of counties where female life expectancy at birth is declining in the most recent period is welcome news. However, the widening disparities between counties and the slow rate of increase compared to other countries should be viewed as a call for action. An increased focus on factors affecting health outcomes, morbidity, and mortality such as socioeconomic factors, difficulty of access to and poor quality of health care, and behavioral, environmental, and metabolic risk factors is urgently required.
Obesity and physical inactivity are associated with several chronic conditions, increased medical care costs, and premature death.
We used the Behavioral Risk Factor Surveillance System (BRFSS), a state-based random-digit telephone survey that covers the majority of United States counties, and the National Health and Nutrition Examination Survey (NHANES), a nationally representative sample of the US civilian noninstitutionalized population. About 3.7 million adults aged 20 years or older participated in the BRFSS from 2000 to 2011, and 30,000 adults aged 20 or older participated in NHANES from 1999 to 2010. We calculated body mass index (BMI) from self-reported weight and height in the BRFSS and adjusted for self-reporting bias using NHANES. We calculated self-reported physical activity—both any physical activity and physical activity meeting recommended levels—from self-reported data in the BRFSS. We used validated small area estimation methods to generate estimates of obesity and physical activity prevalence for each county annually for 2001 to 2011.
Our results showed an increase in the prevalence of sufficient physical activity from 2001 to 2009. Levels were generally higher in men than in women, but increases were greater in women than men. Counties in Kentucky, Florida, Georgia, and California reported the largest gains. This increase in level of activity was matched by an increase in obesity in almost all counties during the same time period. There was a low correlation between level of physical activity and obesity in US counties. From 2001 to 2009, controlling for changes in poverty, unemployment, number of doctors per 100,000 population, percent rural, and baseline levels of obesity, for every 1 percentage point increase in physical activity prevalence, obesity prevalence was 0.11 percentage points lower.
Our study showed that increased physical activity alone has a small impact on obesity prevalence at the county level in the US. Indeed, the rise in physical activity levels will have a positive independent impact on the health of Americans as it will reduce the burden of cardiovascular diseases and diabetes. Other changes such as reduction in caloric intake are likely needed to curb the obesity epidemic and its burden.
Physical activity; Obesity; Small area measurement; US counties
Eczema is a prevalent skin disease that is mainly characterized by systemic deviation of immune response and defective epidermal barrier. Th2 cytokines, such as IL-13 and transcription factor STAT6 are key elements in the inflammatory response that characterize allergic disorders, including eczema. Previous genetic association studies showed inconsistent results for the association of single nucleotide polymorphisms (SNPs) with eczema. Our aim was to investigate whether SNPs in IL13 and STAT6 genes, which share a biological pathway, have an interactive effect on eczema risk.
Data from two independent population-based studies were analyzed, namely the Isle of Wight birth cohort study (IOW; n = 1,456) and for the purpose of replication the Swansea PAPA (Poblogaeth Asthma Prifysgol Abertawe; n = 1,445) cross-sectional study. Log-binomial regressions were applied to (i) account for the interaction between IL13 (rs20541) and STAT6 (rs1059513) polymorphisms and (ii) estimate the combined effect, in terms of risk ratios (RRs), of both risk factors on the risk of eczema.
Under a dominant genetic model, the interaction term [IL13 (rs20541) × STAT6 (rs1059513)] was statistically significant in both studies (IOW: adjusted Pinteraction = 0.046; PAPA: Pinteraction = 0.037). The assessment of the combined effect associated with having risk genotypes in both SNPs yielded a 1.52-fold increased risk of eczema in the IOW study (95% confidence interval (CI): 1.05 – 2.20; P = 0.028) and a 2.01-fold higher risk of eczema (95% CI: 1.29 – 3.12; P = 0.002) in the PAPA study population.
Our study adds to the current knowledge of genetic susceptibility by demonstrating for the first time an interactive effect between SNPs in IL13 (rs20541) and STAT6 (rs1059513) on the occurrence of eczema in two independent samples. Findings of this report further support the emerging evidence that points toward the existence of genetic effects that occur via complex networks involving gene-gene interactions (epistasis).
Eczema; Gene-gene Interaction; Epistasis; STAT6; IL13; Genetic Association Study
Muscle impairments associated with knee osteoarthritis (OA) are the primary underlying cause of functional limitations. Understanding the extent of muscle impairments, its relationship with physical function and disease progression, and the evidence behind exercise therapy that targets muscle impairments is crucial.
An electronic search for relevant articles using MEDLINE and CINHAL databases up to September 2011 was performed. In addition to the electronic search, retrieved articles were searched manually for relevant studies.
Quadriceps, hamstrings, and hip muscles are significantly impaired in subjects with knee OA compared with age-matched controls. Muscle strength, especially quadriceps, is a major determinant of both performance-based and self-reported physical function. Whether stronger quadriceps is protective against knee OA onset and progression is not clear. Exercise therapy, including global and targeted resistance training, is effective in reducing pain and improving function in subjects with knee OA.
Subjects with knee OA have significant muscle impairments. These muscle impairments affect physical function and should be targeted in therapy. Further research is needed to explore the relationship between quadriceps strength and knee OA initiation and progression and to determine the optimal exercise prescription that augments outcomes in this patient population.
Osteoarthritis; Impairment; Functional limitation; Knee; Exercise
The most part of our genome encodes for RNA transcripts are never translated into proteins. These include families of RNA molecules with a regulatory function, which can be arbitrarily subdivided in short (less than 200 nucleotides) and long non-coding RNAs (ncRNAs). MicroRNAs, which act post-transcriptionally to repress the function of target mRNAs, belong to the first group. Included in the second group are multi-exonic and polyadenylated long ncRNAs (lncRNAs), localized either in the nucleus, where they can associate with chromatin remodeling complexes to regulate transcription, or in the cytoplasm, acting as post-transcriptional regulators. Pluripotent stem cells, such as embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs), represent useful systems for modeling normal development and human diseases, as well as promising tools for regenerative medicine. To fully explore their potential, however, a deep understanding of the molecular basis of stemness is crucial. In recent years, increasing evidence of the importance of regulation by ncRNAs in pluripotent cells is accumulating. In this review, we will discuss recent findings pointing to multiple roles played by regulatory ncRNAs in ESC and iPSCs, where they act in concert with signaling pathways, transcriptional regulatory circuitries and epigenetic factors to modulate the balance between pluripotency and differentiation.
embryonic stem cells; induced Pluripotent Stem Cells; microRNA; long non-coding RNA; pluripotency; reprogramming
Novel conjugates of gold nanoparticles (13±1nm) functionalized with synthetic microRNAs can enter cells without the aid of cationic co-carriers and mimic the function of endogenous microRNAs. These conjugates can regulate multiple proteins through interactions with 3′ untranslated region of the target mRNA and control cell behavior. The conjugates are a promising new tool for studying miRNA function and new candidates for miRNA replacement therapies.
Gold nanoparticle; siRNA; microRNA; gene regulation; cancer therapy
Proliferation has emerged as a major prognostic factor in luminal breast cancer. The immunohistochemical (IHC) proliferation marker Ki67 has been most extensively investigated but has not gained widespread clinical acceptance.
We have conducted a head-to-head comparison of a panel of proliferation markers, including Ki67. Our aim was to establish the marker of the greatest prognostic utility. Tumour samples from 3093 women with breast cancer were constructed as tissue microarrays. We used IHC to detect expression of mini-chromosome maintenance protein 2, Ki67, aurora kinase A (AURKA), polo-like kinase 1, geminin and phospho-histone H3. We used a Cox proportional-hazards model to investigate the association with 10-year breast cancer-specific survival (BCSS). Missing values were resolved using multiple imputation.
The prognostic significance of proliferation was limited to oestrogen receptor (ER)-positive breast cancer. Aurora kinase A emerged as the marker of the greatest prognostic significance in a multivariate model adjusted for the standard clinical and molecular covariates (hazard ratio 1.3; 95% confidence interval 1.1–1.5; P=0.005), outperforming all other markers including Ki67.
Aurora kinase A outperforms other proliferation markers as an independent predictor of BCSS in ER-positive breast cancer. It has the potential for use in routine clinical practice.
aurora kinase A; Ki67; ER positive; MCM2; prognosis; geminin
Two hundred and three Plasmodium falciparum isolates from Jazan area, southwest Saudi Arabia, were typed for Pfcrt, Pfmdr1, dhps, and dhfr mutations associated with resistance to chloroquine, mefloquine, halofantrine, artemisinin, sulfadoxine-pyrimethamine, and the neutral polymorphic gene Pfg377. A large proportion (33%) of isolates harbored double mutant dhfr genotype (51I,59C,108N). However, only one isolate contained mutation dhps-437G. For Pfcrt, almost all examined isolates (163; 99%) harbored the mutant genotype (72C,73V,74I,75E,76T), whereas only 49 (31%) contained the mutant Pfmdr1 genotype (86Y,184F,1034S,1042N), 109 (66%) harbored the single mutant genotype (86N,184F,1034S,1042N), and no mutations were seen in codons 1034, 1042, and 1246. Nonetheless, three new single-nucleotide polymorphisms were detected at codons 182, 192, and 102. No differences were seen in distribution of drug resistance genes among Saudis and expatriates. There was a limited multiplicity (5%), mean number of clones (1.05), and two dominant multilocus genotypes among infected individuals in Jazan. A pattern consistent with limited cross-mating and recombination among local parasite was apparent.
We report the development of a novel Scanometric MicroRNA (Scano-miR) platform for the detection of relatively low abundance miRNAs with high specificity and reproducibility. The Scano-miR system was able to detect 1 fM concentrations of miRNA in serum with single nucleotide mismatch specificity. Indeed, it provides increased sensitivity for miRNA targets compared to molecular fluorophore-based detection systems, where 88% of the low abundance miRNA targets could not be detected under identical conditions. The application of the Scano-miR platform to high density array formats demonstrates its utility for high throughput and multiplexed miRNA profiling from various biological samples. To assess the accuracy of the Scano-miR system, we analyzed the miRNA profiles of samples from victims of prostate cancer (CaP), the most common noncutaneous malignancy and the second leading cause of cancer death among American men. The platform exhibits 98.8% accuracy when detecting deregulated miRNAs involved in CaP, which demonstrates its potential utility in profiling and identifying clinical and research biomarkers.
Vascular injury causes neointimal hypertrophy, which is characterized by redox-mediated matrix degradation and smooth muscle cell (SMC) migration and proliferation. We hypothesized that, as compared to the adjacent medial SMCs, neointimal SMCs produce increased superoxide via NADPH oxidase, which induces redox-sensitive intracellular signaling to activate matrix metalloproteinase-9 (MMP-9).
Methods and Results
Two weeks after balloon injury, rat aorta developed a prominent neointima, containing increased expression of NADPH oxidase and reactive oxygen species (ROS) as compared to the medial layer. Next, SMCs were isolated from either the neointima or the media and studied in culture. Neointimal-derived SMCs exhibited increased Nox1 expression and ROS levels as compared to medial SMCs. Neointimal SMCs had higher cell growth rates than medial SMCs. ROS-dependent ERK1/2 phosphorylation was greater in neointimal SMCs. MMP-9 activity, as detected by gel zymography, was greater in neointimal SMCs under resting and stimulated conditions and was prevented by expression of an antisense to Nox1 or treatment with an ERK1/2 inhibitor.
Following vascular injury, the increased expression of Nox1 in SMCs within the neointima initiates redox-dependent phosphorylation of ERK1/2 and subsequent MMP-9 activation.
Restenosis; NADPH oxidases; Oxidative stress; Antioxidants
Hypertension is an important and modifiable risk factor for cardiovascular disease and mortality. Over the last decade, national-levels of controlled hypertension have increased, but little information on hypertension prevalence and trends in hypertension treatment and control exists at the county-level. We estimate trends in prevalence, awareness, treatment, and control of hypertension in US counties using data from the National Health and Nutrition Examination Survey (NHANES) in five two-year waves from 1999–2008 including 26,349 adults aged 30 years and older and from the Behavioral Risk Factor Surveillance System (BRFSS) from 1997–2009 including 1,283,722 adults aged 30 years and older. Hypertension was defined as systolic blood pressure (BP) of at least 140 mm Hg, self-reported use of antihypertensive treatment, or both. Hypertension control was defined as systolic BP less than 140 mm Hg. The median prevalence of total hypertension in 2009 was estimated at 37.6% (range: 26.5 to 54.4%) in men and 40.1% (range: 28.5 to 57.9%) in women. Within-state differences in the county prevalence of uncontrolled hypertension were as high as 7.8 percentage points in 2009. Awareness, treatment, and control was highest in the southeastern US, and increased between 2001 and 2009 on average. The median county-level control in men was 57.7% (range: 43.4 to 65.9%) and in women was 57.1% (range: 43.0 to 65.46%) in 2009, with highest rates in white men and black women. While control of hypertension is on the rise, prevalence of total hypertension continues to increase in the US. Concurrent increases in treatment and control of hypertension are promising, but efforts to decrease the prevalence of hypertension are needed.
The pathophysiology of essential tremor (ET) remains unknown. Standard neuropathological studies have reported no consistent changes but a detailed study found neurodegeneration in all ET cases – 24% demonstrated lower brainstem Lewy body (LB) inclusions and 76% experienced a loss of cerebellar Purkinje cells (PCs) and its sequelae. We review the evidence on neurodegeneration in ET. The prevalence of LB inclusions in ET brains is similar to that in the asymptomatic general population. These incidental LB disease cases have evidence for reduced striatal tyrosine hydroxylase levels, as found in Parkinson’s disease, but there is no evidence for reduced tyrosine hydroxylase levels in ET patients. Reduced mean PC counts in ET cases compared with the controls reported by some studies could not be replicated by others. Most ET cases have the same number of PCs as controls of a comparable age. Neither the lower brainstem LB inclusions nor the cerebellar PC loss represent the neurodegenerative basis of ET. Further studies are needed to determine the pathophysiology of ET.
The introduction of a new influenza strain into human circulation leads to rapid global spread. This review summarizes innate and adaptive immunity to influenza viruses, with an emphasis on T-cell responses that provide cross-protection between distinct subtypes and strains. We discuss antigenic variation within T-cell immunogenic peptides and our understanding of pre-existing immunity towards the pandemic A(H1N1) 2009 strain.
influenza virus; adaptive immunity; innate immunity; H1N1 2009; antigenic variation
The date palm Phoenix dactylifera has played an important role in the day-to-day life of the people for the last 7000 years. Today worldwide production, utilization and industrialization of dates are continuously increasing since date fruits have earned great importance in human nutrition owing to their rich content of essential nutrients. Tons of date palm fruit wastes are discarded daily by the date processing industries leading to environmental problems. Wastes such as date pits represent an average of 10% of the date fruits. Thus, there is an urgent need to find suitable applications for this waste. In spite of several studies on date palm cultivation, their utilization and scope for utilizing date fruit in therapeutic applications, very few reviews are available and they are limited to the chemistry and pharmacology of the date fruits and phytochemical composition, nutritional significance and potential health benefits of date fruit consumption. In this context, in the present review the prospects of valorization of these date fruit processing by-products and wastes’ employing fermentation and enzyme processing technologies towards total utilization of this valuable commodity for the production of biofuels, biopolymers, biosurfactants, organic acids, antibiotics, industrial enzymes and other possible industrial chemicals are discussed.
Date palm; Phoenix dactylifera; Fruit by-products; Wastes; Valorization; Bioprocessing
Two fluorescent heteroditopic ligands (2a and 2b) for zinc ion were synthesized and studied. The efficiencies of two photophysical processes, intramolecular charge transfer (ICT) and photoinduced electron transfer (PET), determine the magnitudes of emission bathochromic shift and enhancement, respectively, when a heteroditopic ligand forms mono- or dizinc complexes. The electron-rich 2b is characterized by a high degree of ICT in the excited state with little propensity for PET, which is manifested in a large bathochromic shift of emission upon Zn2+ coordination without enhancement in fluorescence quantum yield. The electron-poor 2a displays the opposite photophysical consequence where Zn2+ binding results in greatly enhanced emission without significant spectral shift. The electronic structural effects on the relative efficiencies of ICT and PET in 2a and 2b as well as the impact of Zn2+-coordination are probed using experimental and computational approaches. This study reveals that the delicate balance between various photophysical pathways (e.g. ICT and PET) engineered in a heteroditopic ligand is sensitively dependent on the electronic structure of the ligand, i.e. whether the fluorophore is electron-rich or poor, whether it possesses a donor–acceptor type of structure, and where the metal binding occurs.
The target of rapamycin (TOR) is a critical intracellular regulator of the immune system. Recent studies have suggested that immunosuppression by TOR inhibition may be mediated by modulating differentiation of both effector and regulatory CD4 T cell subsets. However, it was paradoxically shown that inhibiting TOR signaling has immunostimulatory effects on the generation of long-lived memory CD8 T cells. Beneficial effects of TOR inhibition have also been observed with dendritic cells and hematopoietic stem cells. This immune modulation may contribute to lifespan extension seen in mice with mTOR inhibition. Here, we review recent findings on TOR modulation of innate and adaptive immune responses, and discuss potential applications of regulating TOR to provide longer and healthier immunity.
The family Microthyriaceae sensu
Lumbsch and Huhndorf 2010 is a poorly known but interesting family comprising 50 genera consisting of foliar epiphytes or saprobes on dead leaves and stems. We re-visited the family based on examinations of generic types where possible. Members are distributed in Aulographaceae, Asterinaceae, Microthyriaceae, Micropeltidaceae and Palmulariaceae and notes are provided on each of these families. Nine genera are transferred from Microthyriaceae to Asterinaceae, and two to Aulographaceae based on the splitting or dissolving nature of the thyriothecia to release ascospores. New sequence data for a number of species and genera are provided. Microthyriaceous members growing on other fungi and lichens differ from Microthyriaceae sensu stricto and the family Trichothyriaceae is reinstated to accommodate these taxa. Other genera of Microthyriaceae belong in Rhytismataceae, Stictidaceae, Venturiales incertae cedis, Dothideomyetes genera incertae cedis, Hypocreales incertae cedis and Ascomycota genera incertae cedis. The family Microthyriaceae is reduced to seven genera characterised by superficial, flattened thyriothecia, with the cells of the upper wall radiating in parallel arrangement from the distinct central ostiolar opening, while the lower peridium is generally poorly developed. Sequence data is provided for five species with thyriothecia and Paramicrothyrium and Neomicrothyrium are described as new genera and Micropeltis zingiberacicola is introduced as a new species. Our phylogenetic analysis underscores the high genetic diversity for thyriotheciate species and there is no clear clade that can be well defined as Microthyriales. Nuclear ribosomal data support multiple polyphyletic lineages within Microthyriaceae and Micropeltidaceae. Some unexpected DNA based phylogenetic relationships such as those between Muyocopron and Saccardoella will require corroboration with more complete taxon sampling as well as additional non ribosomal markers. There are few differences between Aulographaceae, Asterinaceae and Palmulariaceae and these families may need synonymising.
Asterinaceae; Aulographaceae; Dothideales; Leaf fungi; Micropeltidaceae; Molecular phylogeny; Trichothyriaceae
In this paper we revisit the Capnodiaceae with notes on selected genera. Type specimens of the ascomycetous genera Aithaloderma, Anopeltis, Callebaea, Capnodaria, Echinothecium, Phragmocapnias and Scorias were re–examined, described and illustrated. Leptoxyphium is anamorphic Capnodiaceae and Polychaeton is a legitimate and earlier name for Capnodium, but in order to maintain nomenclatural stability we propose that the teleomorphic name should be conisdered for the approved lists of names currently in preparation for fungi. Notes are provided on the ascomycetous genus Scoriadopsis. However, we were unable to locate the type of this genus during the time frame of this study. The ascomycetous genera Aithaloderma, Ceramoclasteropsis, Hyaloscolecostroma and Trichomerium are excluded from Capnodiaceae on the basis of having ascostromata and trans-septate hyaline ascospores and should be accommodated in Chaetothyriaceae. Callebaea is excluded as the ascomata are thyriothecia and the genus is placed in Micropeltidaceae. Echinothecium is excluded as synonym of Sphaerellothecium and is transferred to Mycosphaerellaceae. The type specimen of Capnophaeum is lost and this should be considered as a doubtful genus. The coelomycetous Microxiphium is polyphyletic, while the status of Fumiglobus, Polychaetella and Tripospermum is unclear. Fourteen new collections of sooty moulds made in Thailand were isolated and sequenced. The nuclear large and small rDNA was partially sequenced and compared in a phylogeny used to build a more complete understanding of the relationships of genera in Capnodiaceae. Four new species are described and illustrated, while Phragmocapnias and Scorias are epitypified with fresh collections.
Chaetothyriaceae; Micropeltidaceae; Molecular phylogeny; Sooty moulds
We sequenced and compared the genomes of the Dothideomycete fungal plant pathogens Cladosporium fulvum (Cfu) (syn. Passalora fulva) and Dothistroma septosporum (Dse) that are closely related phylogenetically, but have different lifestyles and hosts. Although both fungi grow extracellularly in close contact with host mesophyll cells, Cfu is a biotroph infecting tomato, while Dse is a hemibiotroph infecting pine. The genomes of these fungi have a similar set of genes (70% of gene content in both genomes are homologs), but differ significantly in size (Cfu >61.1-Mb; Dse 31.2-Mb), which is mainly due to the difference in repeat content (47.2% in Cfu versus 3.2% in Dse). Recent adaptation to different lifestyles and hosts is suggested by diverged sets of genes. Cfu contains an α-tomatinase gene that we predict might be required for detoxification of tomatine, while this gene is absent in Dse. Many genes encoding secreted proteins are unique to each species and the repeat-rich areas in Cfu are enriched for these species-specific genes. In contrast, conserved genes suggest common host ancestry. Homologs of Cfu effector genes, including Ecp2 and Avr4, are present in Dse and induce a Cf-Ecp2- and Cf-4-mediated hypersensitive response, respectively. Strikingly, genes involved in production of the toxin dothistromin, a likely virulence factor for Dse, are conserved in Cfu, but their expression differs markedly with essentially no expression by Cfu in planta. Likewise, Cfu has a carbohydrate-degrading enzyme catalog that is more similar to that of necrotrophs or hemibiotrophs and a larger pectinolytic gene arsenal than Dse, but many of these genes are not expressed in planta or are pseudogenized. Overall, comparison of their genomes suggests that these closely related plant pathogens had a common ancestral host but since adapted to different hosts and lifestyles by a combination of differentiated gene content, pseudogenization, and gene regulation.
We compared the genomes of two closely related pathogens with very different lifestyles and hosts: C. fulvum (Cfu), a biotroph of tomato, and D. septosporum (Dse), a hemibiotroph of pine. Some differences in gene content were identified that can be directly related to their different hosts, such as the presence of a gene involved in degradation of a tomato saponin only in Cfu. However, in general the two species share a surprisingly large proportion of genes. Dse has functional homologs of Cfu effector genes, while Cfu has genes for biosynthesis of dothistromin, a toxin probably associated with virulence in Dse. Cfu also has an unexpectedly large content of genes for biosynthesis of other secondary metabolites and degradation of plant cell walls compared to Dse, contrasting with its host preference and lifestyle. However, many of these genes were not expressed in planta or were pseudogenized. These results suggest that evolving species may retain genetic signatures of the host and lifestyle preferences of their ancestor and that evolution of new genes, gene regulation, and pseudogenization are important factors in adaptation.
Background. Adult intussusception is a rare entity representing less than 1% of all intestinal obstructions. Diagnosis of the condition is difficult requiring a high index of suspicion and the utilization of imaging studies, especially CT scans. Diagnostic laparoscopy and/or exploratory laparotomy can be used as a diagnostic and therapeutic intervention. In over 90% of cases, an underlying lead point is identified. In the patient described here, it was a gastrointestinal stromal tumor (GIST), a relatively rare mesenchymal tumor comprising only 0.2–1.0% of the gastrointestinal tract neoplasms and believed to originate from neoplastic transformation of the interstitial cells of Cajal. GISTs may occur anywhere along the gastrointestinal tract, but most commonly arise in the stomach and small intestine. Literature review revealed only few cases reporting GISTs as a leading point of adult's intussusception. Case Presentation. In this report, we are presenting a rare case of jejunojejunal intussusception in a 78-year-old female patient with a GIST located in the terminal jejunum being the leading point, demonstrating the importance of imaging studies, especially CT scan, laparoscopy, and exploratory laparotomy as diagnostic and therapeutic interventions.
The Venturiaceae was traditionally assigned to Pleosporales although its diagnostic characters readily distinguish it from other pleosporalean families. These include a parasitic or saprobic lifestyle, occurring on leaves or stems of dicotyledons; small to medium-sized ascomata, often with setae; deliquescing pseudoparaphyses; 8-spored, broadly cylindrical to obclavate asci; 1-septate, yellowish, greenish or pale brown to brown ascospores; and hyphomycetous anamorphs. Phylogenetically, core genera of Venturiaceae form a monophyletic clade within Dothideomycetes, and represent a separate sister lineage from current orders, thus a new order—Venturiales is introduced. A new family, Sympoventuriaceae, is introduced to accommodate taxa of a well-supported subclade within Venturiales, which contains Sympoventuria, Veronaeopsis simplex and Fusicladium-like species. Based on morphology and DNA sequence analysis, eight genera are included in Venturiaceae, viz. Acantharia, Apiosporina (including Dibotryon), Caproventuria, Coleroa, Pseudoparodiella, Metacoleroa, Tyrannosorus and Venturia. Molecular phylogenetic information is lacking for seven genera previously included in Venturiales, namely Arkoola, Atopospora, Botryostroma, Lasiobotrys, Trichodothella, Trichodothis and Rhizogenee and these are discussed, but their inclusion in Venturiaceae is doubtful. Crotone, Gibbera, Lineostroma, Phaeocryptopus, Phragmogibbera, Platychora, Polyrhizon, Rosenscheldiella, Uleodothis and Xenomeris are excluded from Venturiales, and their ordinal placement needs further investigation. Zeuctomorpha is treated as a synonym of Acantharia.
Fusicladium; Generic type; Sympoventuriaceae; Taxonomy; Venturiaceae