1,055 research outputs found
Bioactive Abietane-Type Diterpenoid Glycosides from Leaves of Clerodendrum infortunatum (Lamiaceae)
In this study, two previously undescribed diterpenoids, (5R,10S,16R)-11,16,19-trihydroxy-12-O-β-d-glucopyranosyl-(1→2)-β-d-glucopyranosyl-17(15→16),18(4→3)-diabeo-3,8,11,13-abietatetraene-7-one (1) and (5R,10S,16R)-11,16-dihydroxy-12-O-β-d-glucopyranosyl-(1→2)-β-d-glucopyranosyl-17(15→16),18(4→3)-diabeo-4-carboxy-3,8,11,13-abietatetraene-7-one (2), and one known compound, the C13-nor-isoprenoid glycoside byzantionoside B (3), were isolated from the leaves of Clerodendrum infortunatum L. (Lamiaceae). Structures were established based on spectroscopic and spectrometric data and by comparison with literature data. The three terpenoids, along with five phenylpropanoids: 6'-O-caffeoyl-12-glucopyranosyloxyjasmonic acid (4), jionoside C (5), jionoside D (6), brachynoside (7), and incanoside C (8), previously isolated from the same source, were tested for their in vitro antidiabetic (α-amylase and α-glucosidase), anticancer (Hs578T and MDA-MB-231), and anticholinesterase activities. In an in vitro test against carbohydrate digestion enzymes, compound 6 showed the most potent effect against mammalian α-amylase (IC50 3.4 ± 0.2 μM) compared to the reference standard acarbose (IC50 5.9 ± 0.1 μM). As yeast α-glucosidase inhibitors, compounds 1, 2, 5, and 6 displayed moderate inhibitory activities, ranging from 24.6 to 96.0 μM, compared to acarbose (IC50 665 ± 42 μM). All of the tested compounds demonstrated negligible anticholinesterase effects. In an anticancer test, compounds 3 and 5 exhibited moderate antiproliferative properties with IC50 of 94.7 ± 1.3 and 85.3 ± 2.4 μM, respectively, against Hs578T cell, while the rest of the compounds did not show significant activity (IC50 > 100 μM)
Optimality of mutation and selection in germinal centers
The population dynamics theory of B cells in a typical germinal center could
play an important role in revealing how affinity maturation is achieved.
However, the existing models encountered some conflicts with experiments. To
resolve these conflicts, we present a coarse-grained model to calculate the B
cell population development in affinity maturation, which allows a
comprehensive analysis of its parameter space to look for optimal values of
mutation rate, selection strength, and initial antibody-antigen binding level
that maximize the affinity improvement. With these optimized parameters, the
model is compatible with the experimental observations such as the ~100-fold
affinity improvements, the number of mutations, the hypermutation rate, and the
"all or none" phenomenon. Moreover, we study the reasons behind the optimal
parameters. The optimal mutation rate, in agreement with the hypermutation rate
in vivo, results from a tradeoff between accumulating enough beneficial
mutations and avoiding too many deleterious or lethal mutations. The optimal
selection strength evolves as a balance between the need for affinity
improvement and the requirement to pass the population bottleneck. These
findings point to the conclusion that germinal centers have been optimized by
evolution to generate strong affinity antibodies effectively and rapidly. In
addition, we study the enhancement of affinity improvement due to B cell
migration between germinal centers. These results could enhance our
understandings to the functions of germinal centers.Comment: 5 figures in main text, and 4 figures in Supplementary Informatio
Correcting pervasive errors in RNA crystallography through enumerative structure prediction
Three-dimensional RNA models fitted into crystallographic density maps
exhibit pervasive conformational ambiguities, geometric errors and steric
clashes. To address these problems, we present enumerative real-space
refinement assisted by electron density under Rosetta (ERRASER), coupled to
Python-based hierarchical environment for integrated 'xtallography' (PHENIX)
diffraction-based refinement. On 24 data sets, ERRASER automatically corrects
the majority of MolProbity-assessed errors, improves the average Rfree factor,
resolves functionally important discrepancies in noncanonical structure and
refines low-resolution models to better match higher-resolution models
Ultrasensitive force and displacement detection using trapped ions
The ability to detect extremely small forces is vital for a variety of
disciplines including precision spin-resonance imaging, microscopy, and tests
of fundamental physical phenomena. Current force-detection sensitivity limits
have surpassed 1 (atto ) through coupling of micro or
nanofabricated mechanical resonators to a variety of physical systems including
single-electron transistors, superconducting microwave cavities, and individual
spins. These experiments have allowed for probing studies of a variety of
phenomena, but sensitivity requirements are ever-increasing as new regimes of
physical interactions are considered. Here we show that trapped atomic ions are
exquisitely sensitive force detectors, with a measured sensitivity more than
three orders of magnitude better than existing reports. We demonstrate
detection of forces as small as 174 (yocto ), with a
sensitivity 390 using crystals of Be
ions in a Penning trap. Our technique is based on the excitation of normal
motional modes in an ion trap by externally applied electric fields, detection
via and phase-coherent Doppler velocimetry, which allows for the discrimination
of ion motion with amplitudes on the scale of nanometers. These experimental
results and extracted force-detection sensitivities in the single-ion limit
validate proposals suggesting that trapped atomic ions are capable of detecting
of forces with sensitivity approaching 1 . We anticipate that
this demonstration will be strongly motivational for the development of a new
class of deployable trapped-ion-based sensors, and will permit scientists to
access new regimes in materials science.Comment: Expanded introduction and analysis. Methods section added. Subject to
press embarg
Individual Rights, Economic Transactions, and Recognition: A Legal Approach to Social Economics
Modernity brought the idea of individual property rights as a com- plex phenomenon. However, economics adopted a simplistic view of property as a fundamental institution, understating the complex interaction of different rights and obligations that frame the legal environment of economic processes with an insufficiently elaborated tool. Here, a more elaborate view of legal elements will be propose
Biomarkers and diagnostic guidelines for sporadic Creutzfeldt-Jakob disease
Sporadic Creutzfeldt-Jakob disease is a fatal neurodegenerative disease caused by misfolded prion proteins (PrP^{Sc}). Effective therapeutics are currently not available and accurate diagnosis can be challenging. Clinical diagnostic criteria use a combination of characteristic neuropsychiatric symptoms, CSF proteins 14-3-3, MRI, and EEG. Supportive biomarkers, such as high CSF total tau, could aid the diagnostic process. However, discordant studies have led to controversies about the clinical value of some established surrogate biomarkers. Development and clinical application of disease-specific protein aggregation and amplification assays, such as real-time quaking induced conversion (RT-QuIC), have constituted major breakthroughs for the confident pre-mortem diagnosis of sporadic Creutzfeldt-Jakob disease. Updated criteria for the diagnosis of sporadic Creutzfeldt-Jakob disease, including application of RT-QuIC, should improve early clinical confirmation, surveillance, assessment of PrP^{Sc} seeding activity in different tissues, and trial monitoring. Moreover, emerging blood-based, prognostic, and potentially pre-symptomatic biomarker candidates are under investigation
The Interdisciplinary Curriculum for Oncology Palliative Care Education (iCOPE): Meeting the Challenge of Interprofessional Education
Abstract Background: Interprofessional education is necessary to prepare students of the health professions for successful practice in today's health care environment. Because of its expertise in interdisciplinary practice and team-based care, palliative care should be leading the way in creating educational opportunities for students to learn the skills for team practice and provision of quality patient-centered care. Multiple barriers exist that can discourage those desiring to create and implement truly interdisciplinary curriculum. Design: An interdisciplinary faculty team planned and piloted a mandatory interdisciplinary palliative oncology curriculum and responded to formative feedback. Setting/Subjects: The project took place at a large public metropolitan university. Medical, nursing, and social work students and chaplains completing a clinical pastoral education internship participated in the curriculum. Measurements: Formative feedback was received via the consultation of an interdisciplinary group of palliative education experts, focus groups from students, and student evaluations of each learning modality. Results: Multiple barriers were experienced and successfully addressed by the faculty team. Curricular components were redesigned based on formative feedback. Openness to this feedback coupled with flexibility and compromise enabled the faculty team to create an efficient, sustainable, and feasible interdisciplinary palliative oncology curriculum. Conclusion: Interdisciplinary palliative education can be successful if faculty teams are willing to confront challenges, accept feedback on multiple levels, and compromise while maintaining focus on desired learner outcomes
Neurogenesis Drives Stimulus Decorrelation in a Model of the Olfactory Bulb
The reshaping and decorrelation of similar activity patterns by neuronal
networks can enhance their discriminability, storage, and retrieval. How can
such networks learn to decorrelate new complex patterns, as they arise in the
olfactory system? Using a computational network model for the dominant neural
populations of the olfactory bulb we show that fundamental aspects of the adult
neurogenesis observed in the olfactory bulb -- the persistent addition of new
inhibitory granule cells to the network, their activity-dependent survival, and
the reciprocal character of their synapses with the principal mitral cells --
are sufficient to restructure the network and to alter its encoding of odor
stimuli adaptively so as to reduce the correlations between the bulbar
representations of similar stimuli. The decorrelation is quite robust with
respect to various types of perturbations of the reciprocity. The model
parsimoniously captures the experimentally observed role of neurogenesis in
perceptual learning and the enhanced response of young granule cells to novel
stimuli. Moreover, it makes specific predictions for the type of odor
enrichment that should be effective in enhancing the ability of animals to
discriminate similar odor mixtures
On the avoidability of breast cancer in industrialized societies: older mean age at first birth as an indicator of excess breast cancer risk
Background Breast cancer incidence continuous to increase. We examined at population level the association between the relative excess risk of breast cancer and previous age of mother at first birth. Method Incidence of breast cancer in 34 industrialized countries was obtained from the GLOBOCAN 2002 and SEER databases. Data on age of mother at first birth was collected through national statistics offices. National relative excess risk (RER) was calculated by subtracting the lowest age-specific incidence rate from the rate in each population, and dividing the difference by the latter. Results The national RER in 2002 correlated closely with a higher average age at first birth in 1972, 1982, 1992 and also 2002, Pearson correlation [r] being 0.83, 0.79, 0.72 and 0.61, respectively; P < 0.0001. RER of breast cancer in 2002 for those aged 15–44 years correlated closely with the mean age at first birth in 1982 and 1992 (r: 0.81 and 0.75; P < 0.0001), whereas RER for those aged 45–54 years correlated strongly with age at first birth in 1972 and 1982 (r: 0.81 and 0.76; P < 0.0001), and for those aged 55–64 years with age at first birth in 1972 (r: 0.77; P < 0.0001). Conclusions The rising age at first childbirth of mothers has been followed by marked increases in breast cancer incidence. Later age at first birth seems to characterize secular diffusion of ‘modern’ lifestyles with a potentially large impact on increased breast cancer risk, and hence should be accompanied by greater opportunities for prevention through modifiable risk factors
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