4,823 research outputs found
Accuracy of phylogeny reconstruction methods combining overlapping gene data sets
Background
The availability of many gene alignments with overlapping taxon sets raises the question of which strategy is the best to infer species phylogenies from multiple gene information. Methods and programs abound that use the gene alignment in different ways to reconstruct the species tree. In particular, different methods combine the original data at different points along the way from the underlying sequences to the final tree. Accordingly, they are classified into superalignment, supertree and medium-level approaches. Here, we present a simulation study to compare different methods from each of these three approaches.
Results
We observe that superalignment methods usually outperform the other approaches over a wide range of parameters including sparse data and gene-specific evolutionary parameters. In the presence of high incongruency among gene trees, however, other combination methods show better performance than the superalignment approach. Surprisingly, some supertree and medium-level methods exhibit, on average, worse results than a single gene phylogeny with complete taxon information.
Conclusions
For some methods, using the reconstructed gene tree as an estimation of the species tree is superior to the combination of incomplete information. Superalignment usually performs best since it is less susceptible to stochastic error. Supertree methods can outperform superalignment in the presence of gene-tree conflict
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The Receptor for Advanced Glycation End Products (RAGE) Affects T Cell Differentiation in OVA Induced Asthma
The receptor for glycation end products (RAGE) has been previously implicated in shaping the adaptive immune response. RAGE is expressed in T cells after activation and constitutively in T cells from patients with diabetes. The effects of RAGE on adaptive immune responses are not clear: Previous reports show that RAGE blockade affects Th1 responses. To clarify the role of RAGE in adaptive immune responses and the mechanisms of its effects, we examined whether RAGE plays a role in T cell activation in a Th2 response involving ovalbumin (OVA)-induced asthma in mice. WT and RAGE deficient wild-type and OT-II mice, expressing a T cell receptor specific for OVA, were immunized intranasally with OVA. Lung cellular infiltration and T cell responses were analyzed by immunostaining, FACS, and multiplex bead analyses for cytokines. RAGE deficient mice showed reduced cellular infiltration in the bronchial alveolar lavage fluid and impaired T cell activation in the mediastinal lymph nodes when compared with WT mice. In addition, RAGE deficiency resulted in reduced OT-II T cell infiltration of the lung and impaired IFNγ and IL-5 production when compared with WT mice and reduced infiltration when transferred into WT hosts. When cultured under conditions favoring the differentiation of T cells subsets, RAGE deficient T cells showed reduced production of IFNγ but increased production of IL-17. Our data show a stimulatory role for RAGE in T activation in OVA-induced asthma. This role is largely mediated by the effects of RAGE on T cell proliferation and differentiation. These findings suggest that RAGE may play a regulatory role in T cell responses following immune activation
Botulinum Neurotoxin Detection and Differentiation by Mass Spectrometry
A new rapid, mass spectrometry-based method to detect and differentiate botulinal neurotoxins is described
In vivo evolution of biopsy-proven inflammatory demyelination quantified by R2t* mapping
A 35-year-old man with an enhancing tumefactive brain lesion underwent biopsy, revealing inflammatory demyelination. We used quantitative Gradient-Recalled-Echo (qGRE) MRI to visualize and measure tissue damage in the lesion. Two weeks after biopsy, qGRE showed significant R2t* reduction in the left optic radiation and surrounding tissue, consistent with the histopathological and clinical findings. qGRE was repeated 6 and 14 months later, demonstrating partially recovered optic radiation R2t*, in concert with improvement of the hemianopia to ultimately involve only the lower right visual quadrant. These results support qGRE metrics as in vivo biomarkers for tissue damage and longitudinal monitoring of demyelinating disease
Establishment of a preclinical ovine screening model for the investigation of bone tissue engineering strategies in cancellous and cortical bone defects
Background New tissue engineering strategies for bone regeneration need to be
investigated in a relevant preclinical large animal model before making the
translation into human patients. Therefore, our interdisciplinary group
established a simplified large animal screening model for intramembranous bone
defect regeneration in cancellous and cortical bone. Methods Related to a
well-established model of cancellous drill hole defect regeneration in sheep,
both the proximal and distal epimetaphyseal regions of the femur and the
humerus were used bilaterally for eight drill hole cancellous defects (Ø 6 mm,
15 mm depth). Several improvements of the surgical procedure and equipment for
an easier harvest of samples were invented. For the inclusion of cortical
defect regeneration, a total of eight unicortical diaphyseal drill holes (6 mm
Ø) were placed in the proximal-lateral and distal-medial parts of the
metacarpal (MC) and metatarsal (MT) diaphyseal bone bilaterally. Acting
moments within a normal gait cycle in the musculoskeletal lower limb model
were compared with the results of the biomechanical in vitro torsion test
until failure to ensure a low accidental fracture risk of utilized bones
(ANOVA, p < 0.05). The model was tested in vivo, using thirteen adult, female,
black-face sheep (Ø 66 kg; ± 5 kg; age ≥ 2.5 years). In a two-step surgical
procedure 16 drill holes were performed for the investigation of two different
time points within one animal. Defects were left empty, augmented with
autologous cancellous bone or soft bone graft substitutes. Results The in
vitro tests confirmed this model a high comparability between drilled MC and
MT bones and a high safety margin until fracture. The exclusion of one animal
from the in vivo study, due to a spiral fracture of the left MC bone led to a
tolerable failure rate of 8 %. Conclusions As a screening tool, promising
biomaterials can be tested in this cancellous and cortical bone defect model
prior to the application in a more complex treatment site
Fatigue in Multiple Sclerosis Is Associated With Childhood Adversities
Fatigue is a common and disabling symptom in patients with Multiple Sclerosis (PwMS). Its pathogenesis, however, is still not fully understood. Potential psychological roots, in particular, have received little attention to date. The present study examined the association of childhood adversities, specific trait characteristics, and MS disease characteristics with fatigue symptoms utilizing path analysis. Five hundred and seventy-one PwMS participated in an online survey. Standardized psychometric tools were applied. The Childhood Trauma Questionnaire (CTQ) served to assess childhood adversities. Trait variables were alexithymia (Toronto Alexithymia Scale; TAS-26) and early maladaptive schemas (Young Schema Questionnaire; YSQ). Current pathology comprised depression (Beck's Depression Inventory FastScreen; BDI-FS) and anxiety symptoms (State-Trait Anxiety Inventory; STAI-state), as well as physical disability (Patient determined Disease Steps; PDDS). The Fatigue Scale for Motor and Cognitive Functions (FSMC) was the primary outcome variable measuring fatigue. PwMS displayed high levels of fatigue and depression (mean FSMC score: 72; mean BDI-II score: 18). The final path model revealed that CTQ emotional neglect and emotional abuse remained as the only significant childhood adversity variables associated with fatigue. There were differential associations for the trait variables and current pathology: TAS-26, the YSQ domain impaired autonomy and performance, as well as all current pathology measures had direct effects on fatigue symptoms, accounting for 28.2% of the FSMC variance. Bayesian estimation also revealed indirect effects from the two CTQ subscales on FSMC. The final model fitted the data well, also after a cross-validation check and after replacing the FSMC with the Chalder Fatigue Questionnaire (CFQ). This study suggests an association psychological factors on fatigue in Multiple Sclerosis. Childhood adversities, as well as specific trait characteristics, seem to be associated with current pathology and fatigue symptoms. The article discusses potential implications and limitations
Evaluating brain damage in multiple sclerosis with simultaneous multi-angular-relaxometry of tissue
OBJECTIVE: Multiple sclerosis (MS) is a common demyelinating central nervous system disease. MRI methods that can quantify myelin loss are needed for trials of putative remyelinating agents. Quantitative magnetization transfer MRI introduced the macromolecule proton fraction (MPF), which correlates with myelin concentration. We developed an alternative approach, Simultaneous-Multi-Angular-Relaxometry-of-Tissue (SMART) MRI, to generate MPF. Our objective was to test SMART-derived MPF metric as a potential imaging biomarker of demyelination.
METHODS: Twenty healthy control (HC), 11 relapsing-remitting MS (RRMS), 22 progressive MS (PMS), and one subject with a biopsied tumefactive demyelinating lesion were scanned at 3T using SMART MRI. SMART-derived MPF metric was determined in normal-appearing cortical gray matter (NAGM), normal-appearing subcortical white matter (NAWM), and demyelinating lesions. MPF metric was evaluated for correlations with physical and cognitive test scores. Comparisons were made between HC and MS and between MS subtypes. Furthermore, correlations were determined between MPF and neuropathology in the biopsied person.
RESULTS: SMART-derived MPF in NAGM and NAWM were lower in MS than HC (p \u3c 0.001). MPF in NAGM, NAWM and lesions differentiated RRMS from PMS (p \u3c 0.01, p \u3c 0.001, p \u3c 0.001, respectively), whereas lesion volumes did not. MPF in NAGM, NAWM and lesions correlated with the Expanded Disability Status Scale (p \u3c 0.01, p \u3c 0.001, p \u3c 0.001, respectively) and nine-hole peg test (p \u3c 0.001, p \u3c 0.001, p \u3c 0.01, respectively). MPF was lower in the histopathologically confirmed inflammatory demyelinating lesion than the contralateral NAWM and increased in the biopsied lesion over time, mirroring improved clinical performance.
INTERPRETATION: SMART-derived MPF metric holds potential as a quantitative imaging biomarker of demyelination and remyelination
Complementary Patents and Market Structure
Many high technology goods are based on standards that require several essential patents owned by different IP holders. This gives rise to a complements and a double mark-up problem. We compare the welfare effects of two different business strategies dealing with these problems. Vertical integration of an IP holder and a downstream producer solves the double mark-up problem between these firms. Nevertheless, it may raise royalty rates and reduce output as compared to non-integration. Horizontal integration of IP holders solves the complements problem but not the double mark-up problem. Vertical integration discourages entry and reduces innovation incentives, while horizontal integration always benefits from entry and innovatio
Dual Magnetic Separator for TRIP
The TRIP facility, under construction at KVI, requires the production
and separation of short-lived and rare isotopes. Direct reactions,
fragmentation and fusion-evaporation reactions in normal and inverse kinematics
are foreseen to produce nuclides of interest with a variety of heavy-ion beams
from the superconducting cyclotron AGOR. For this purpose, we have designed,
constructed and commissioned a versatile magnetic separator that allows
efficient injection into an ion catcher, i.e., gas-filled stopper/cooler or
thermal ionizer, from which a low energy radioactive beam will be extracted.
The separator performance was tested with the production and clean separation
of Na ions, where a beam purity of 99.5% could be achieved. For
fusion-evaporation products, some of the features of its operation as a
gas-filled recoil separator were tested.Comment: accepted by Nucl.Instr. Meth., final versio
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