1,225 research outputs found
Leveraging Multi-Tissue, Single-Cell Atlases as Tools to Elucidate Shared Mechanisms of Immune-Mediated Inflammatory Diseases
\ua9 2024 by the authors. The observation that certain therapeutic strategies for targeting inflammation benefit patients with distinct immune-mediated inflammatory diseases (IMIDs) is exemplified by the success of TNF blockade in conditions including rheumatoid arthritis, ulcerative colitis, and skin psoriasis, albeit only for subsets of individuals with each condition. This suggests intersecting ânodesâ in inflammatory networks at a molecular and cellular level may drive and/or maintain IMIDs, being âsharedâ between traditionally distinct diagnoses without mapping neatly to a single clinical phenotype. In line with this proposition, integrative tumour tissue analyses in oncology have highlighted novel cell states acting across diverse cancers, with important implications for precision medicine. Drawing upon advances in the oncology field, this narrative review will first summarise learnings from the Human Cell Atlas in health as a platform for interrogating IMID tissues. It will then review cross-disease studies to date that inform this endeavour before considering future directions in the field
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Long-term benefit from immune modulation and anti-inflammatory treatment in metastatic mesothelioma.
A 64 year old male heating engineer was investigated for a persistent cough and found to have epithelioid mesothelioma with pleural effusion, lung nodules and increased thoracic lymph nodes. He declined standard of care treatment following his own research and he was enrolled in a named patient programme of IMM-101. He was advised to correct his low vitamin D3 level and to start using anti-inflammatories such as aspirin, bromelain and low dose Naltrexone. At review one year later a CT scan showed no change and he continued on the regimen. Four years after the diagnosis a CT scan showed that there was a modest but definite progression of the left malignant pleural thickening, and a new right-sided effusion, enlargement of several intrathoracic nodes which had been noted on the early scans. The chest wall lump eventually broke down and required local radiotherapy. He then developed abdominal pain and found to have peritoneal disease. Last year he obtained the cannabinoids CBD and THC which slowed down the disease and a CT scan after he had been on this for six months, showed that his disease was fairly stable with marginal progression
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Research data supporting "A fragment profiling approach to inhibitors of the orphan M. tuberculosis P450 CYP144A1"
Fragment-based approaches to targeting CYP144 from Mycobacterium tuberculosi
Using technology to deliver cancer follow-up : a systematic review
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Expanding dispersal studies at hydrothermal vents through species identification of cryptic larval forms
Author Posting. © The Author(s), 2010. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Marine Biology 157 (2010): 1049-1062, doi:10.1007/s00227-009-1386-8.The rapid identification of hydrothermal vent-endemic larvae to the species level is a key
limitation to understanding the dynamic processes that control the abundance and
distribution of fauna in such a patchy and ephemeral environment. Many larval forms
collected near vents, even those in groups such as gastropods that often form a
morphologically distinct larval shell, have not been identified to species. We present a
staged approach that combines morphological and molecular identification to optimize
the capability, efficiency, and economy of identifying vent gastropod larvae from the
northern East Pacific Rise (NEPR). With this approach, 15 new larval forms can be
identified to species. A total of 33 of the 41 gastropod species inhabiting the NEPR, and
26 of the 27 gastropod species known to occur specifically in the 9° 50â N region, can be
identified to species. Morphological identification efforts are improved by new
protoconch descriptions for Gorgoleptis spiralis, Lepetodrilus pustulosus, Nodopelta
subnoda, and Echinopelta fistulosa. Even with these new morphological descriptions, the
majority of lepetodrilids and peltospirids require molecular identification. Restriction
fragment length polymorphism digests are presented as an economical method for
identification of five species of Lepetodrilus and six species of peltospirids. The
remaining unidentifiable specimens can be assigned to species by comparison to an
expanded database of 18S ribosomal DNA. The broad utility of the staged approach was
exemplified by the revelation of species-level variation in daily planktonic samples and
the identification and characterization of egg capsules belonging to a conid gastropod
Gymnobela sp. A. The improved molecular and morphological capabilities nearly double
the number of species amenable to field studies of dispersal and population connectivity.Funding was provided by as Woods Hole Oceanographic Institution Deep Ocean
Exploration Institute grant to L.M and S. Beaulieu, National Science Foundation grants
OCE-0424953, OCE-9712233, and OCE-9619605 to L.M, OCE-0327261 to T.S., and
OCE-0002458 to K. Von Damm, and a National Defense Science and Engineering
Graduate fellowship to D.A
Searching for Exoplanets Using a Microresonator Astrocomb
Detection of weak radial velocity shifts of host stars induced by orbiting
planets is an important technique for discovering and characterizing planets
beyond our solar system. Optical frequency combs enable calibration of stellar
radial velocity shifts at levels required for detection of Earth analogs. A new
chip-based device, the Kerr soliton microcomb, has properties ideal for
ubiquitous application outside the lab and even in future space-borne
instruments. Moreover, microcomb spectra are ideally suited for astronomical
spectrograph calibration and eliminate filtering steps required by conventional
mode-locked-laser frequency combs. Here, for the calibration of astronomical
spectrographs, we demonstrate an atomic/molecular line-referenced,
near-infrared soliton microcomb. Efforts to search for the known exoplanet HD
187123b were conducted at the Keck-II telescope as a first in-the-field
demonstration of microcombs
Recurrence of complement factor H-related protein 5 nephropathy in a renal transplant.
Complement factor H-related protein 5 (CFHR5) nephropathy is a familial renal disease endemic in Cyprus. It is characterized by persistent microscopic hematuria, synpharyngitic macroscopic hematuria and progressive renal impairment. Isolated glomerular accumulation of complement component 3 (C3) is typical with variable degrees of glomerular inflammation. Affected individuals have a heterozygous internal duplication in the CFHR5 gene, although the mechanism through which this mutation results in renal disease is not understood. Notably, the risk of progressive renal failure in this condition is higher in males than females. We report the first documented case of recurrence of CFHR5 nephropathy in a renal transplant in a 53-year-old Cypriot male. Strikingly, histological changes of CFHR5 nephropathy were evident in the donor kidney 46 days post-transplantation. This unique case demonstrates that renal-derived CFHR5 protein cannot prevent the development of CFHR5 nephropathy
Protracted timescales of lower crustal growth at the fast-spreading East Pacific Rise
Author Posting. © The Author(s), 2011. This is the author's version of the work. It is posted here by permission of Nature Publishing Group for personal use, not for redistribution. The definitive version was published in Nature Geoscience 5 (2012): 275-278, doi:10.1038/ngeo1378.Formation of the oceanic crust at mid-ocean ridges is a fundamental component of
plate tectonics. A majority of the crust at many ridges is composed of plutonic rocks
that form by crystallization of mantle-derived magmas within the crust. Recent
application of U/Pb dating to samples from in-situ oceanic crust has begun to
provide exciting new insight into the timing, duration and distribution of
magmatism during formation of the plutonic crust1-4. Previous studies have focused
on samples from slow-spreading ridges, however, the time scales and processes of
crustal growth are expected to vary with plate spreading rate. Here we present the
first high-precision dates from plutonic crust formed at the fast-spreading East
Pacific Rise (EPR). Individual zircon minerals yielded dates from 1.420â1.271
million years ago, with uncertainties of ± 0.006â0.081 million years. Within
individual samples, zircons record a range of dates of up to ~0.124 million years,
consistent with protracted crystallization or assimilation of older zircons from
adjacent rocks. The variability in dates is comparable to data from the Vema
lithospheric section on the Mid-Atlantic Ridge (MAR)3, suggesting that time scales
of magmatic processes in the lower crust may be similar at slow- and fast-spreading
ridges.This research was partially funded by NSF grant OCE-0727914 (SAB), a Cardiff
University International Collaboration Award (CJL) and NERC grant NE/C509023/1
(CJM).2012-07-2
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