108 research outputs found
Enteric dysbiosis and fecal calprotectin expression in premature infants.
BackgroundPremature infants often develop enteric dysbiosis with a preponderance of Gammaproteobacteria, which has been related to adverse clinical outcomes. We investigated the relationship between increasing fecal Gammaproteobacteria and mucosal inflammation, measured by fecal calprotectin (FC).MethodsStool samples were collected from very-low-birth weight (VLBW) infants at β€2, 3, and 4 weeks' postnatal age. Fecal microbiome was surveyed using polymerase chain reaction amplification of the V4 region of 16S ribosomal RNA, and FC was measured by enzyme immunoassay.ResultsWe enrolled 45 VLBW infants (gestation 27.9βΒ±β2.2 weeks, birth weight 1126βΒ±β208βg) and obtained stool samples at 9.9βΒ±β3, 20.7βΒ±β4.1, and 29.4βΒ±β4.9 days. FC was positively correlated with the genus Klebsiella (rβ=β0.207, pβ=β0.034) and its dominant amplicon sequence variant (rβ=β0.290, pβ=β0.003), but not with the relative abundance of total Gammaproteobacteria. Klebsiella colonized the gut in two distinct patterns: some infants started with low Klebsiella abundance and gained these bacteria over time, whereas others began with very high Klebsiella abundance.ConclusionIn premature infants, FC correlated with relative abundance of a specific pathobiont, Klebsiella, and not with that of the class Gammaproteobacteria. These findings indicate a need to define dysbiosis at genera or higher levels of resolution
Long gamma-ray bursts and core-collapse supernovae have different environments
When massive stars exhaust their fuel they collapse and often produce the
extraordinarily bright explosions known as core-collapse supernovae. On
occasion, this stellar collapse also powers an even more brilliant relativistic
explosion known as a long-duration gamma-ray burst. One would then expect that
long gamma-ray bursts and core-collapse supernovae should be found in similar
galactic environments. Here we show that this expectation is wrong. We find
that the long gamma-ray bursts are far more concentrated on the very brightest
regions of their host galaxies than are the core-collapse supernovae.
Furthermore, the host galaxies of the long gamma-ray bursts are significantly
fainter and more irregular than the hosts of the core-collapse supernovae.
Together these results suggest that long-duration gamma-ray bursts are
associated with the most massive stars and may be restricted to galaxies of
limited chemical evolution. Our results directly imply that long gamma-ray
bursts are relatively rare in galaxies such as our own Milky Way.Comment: 27 pages, 4 figures, submitted to Nature on 22 August 2005, revised 9
February 2006, online publication 10 May 2006. Supplementary material
referred to in the text can be found at
http://www.stsci.edu/~fruchter/GRB/locations/supplement.pdf . This new
version contains minor changes to match the final published versio
A Glutathione Peroxidase, Intracellular Peptidases and the TOR Complexes Regulate Peptide Transporter PEPT-1 in C. elegans
The intestinal peptide transporter PEPT-1 in Caenorhabditis elegans is a rheogenic H+-dependent carrier responsible for the absorption of di- and tripeptides. Transporter-deficient pept-1(lg601) worms are characterized by impairments in growth, development and reproduction and develop a severe obesity like phenotype. The transport function of PEPT-1 as well as the influx of free fatty acids was shown to be dependent on the membrane potential and on the intracellular pH homeostasis, both of which are regulated by the sodium-proton exchanger NHX-2. Since many membrane proteins commonly function as complexes, there could be proteins that possibly modulate PEPT-1 expression and function. A systematic RNAi screening of 162 genes that are exclusively expressed in the intestine combined with a functional transport assay revealed four genes with homologues existing in mammals as predicted PEPT-1 modulators. While silencing of a glutathione peroxidase surprisingly caused an increase in PEPT-1 transport function, silencing of the ER to Golgi cargo transport protein and of two cytosolic peptidases reduced PEPT-1 transport activity and this even corresponded with lower PEPT-1 protein levels. These modifications of PEPT-1 function by gene silencing of homologous genes were also found to be conserved in the human epithelial cell line Caco-2/TC7 cells. Peptidase inhibition, amino acid supplementation and RNAi silencing of targets of rapamycin (TOR) components in C. elegans supports evidence that intracellular peptide hydrolysis and amino acid concentration are a part of a sensing system that controls PEPT-1 expression and function and that involves the TOR complexes TORC1 and TORC2
Stage- and Gender-Specific Proteomic Analysis of Brugia malayi Excretory-Secretory Products
To succeed in infection, parasites must have ways to reach the host, penetrate its tissues and escape its defense systems. As they are not necessarily fatal, most helminth parasites remain viable within their host for many years, exerting a strong influence over the host immune function. Many of these functions are performed by products that are released from the parasite. We exploited the remarkable sensitivity of modern proteomics tools together with the availability of a sequenced genome to identify and compare the proteins released in vitro by adult males, adult females and the microfilariae of the filarial nematode Brugia malayi. This parasite is one of the etiological agents of lymphatic filariasis, a disease that poses continuing and significant threats to human health. The different forms of the parasite inhabit different compartments in the mammalian host. We found that the set of proteins released by each form is unique; they must reflect particular developmental processes and different strategies for evasion of host responses. The identification of these proteins will allow us to illuminate the biology of secretory processes in this organism and to establish a path for developing an understanding of how these parasite proteins function in immune evasion events
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An Ultra Deep Field survey with WFIRST
Studying the formation and evolution of galaxies at the earliest cosmic
times, and their role in reionization, requires the deepest imaging possible.
Ultra-deep surveys like the HUDF and HFF have pushed to mag \mAB30,
revealing galaxies at the faint end of the LF to 911 and
constraining their role in reionization. However, a key limitation of these
fields is their size, only a few arcminutes (less than a Mpc at these
redshifts), too small to probe large-scale environments or clustering
properties of these galaxies, crucial for advancing our understanding of
reionization. Achieving HUDF-quality depth over areas 100 times larger
becomes possible with a mission like the Wide Field Infrared Survey Telescope
(WFIRST), a 2.4-m telescope with similar optical properties to HST, with a
field of view of 1000 arcmin, 100 the area of the
HST/ACS HUDF.
This whitepaper motivates an Ultra-Deep Field survey with WFIRST, covering
100300 the area of the HUDF, or up to 1 deg, to
\mAB30, potentially revealing thousands of galaxies and AGN at the
faint end of the LF, at or beyond \,\,910 in the epoch of
reionization, and tracing their LSS environments, dramatically increasing the
discovery potential at these redshifts.
(Note: This paper is a somewhat expanded version of one that was submitted as
input to the Astro2020 Decadal Survey, with this version including an Appendix
(which exceeded the Astro2020 page limits), describing how the science drivers
for a WFIRST Ultra Deep Field might map into a notional observing program,
including the filters used and exposure times needed to achieve these depths.
The Chemotherapeutic Drug 5-Fluorouracil Promotes PKR-Mediated Apoptosis in a p53- Independent Manner in Colon and Breast Cancer Cells
The chemotherapeutic drug 5-FU is widely used in the treatment of a range of cancers, but resistance to the drug remains a major clinical problem. Since defects in the mediators of apoptosis may account for chemo-resistance, the identification of new targets involved in 5-FU-induced apoptosis is of main clinical interest. We have identified the ds-RNA-dependent protein kinase (PKR) as a key molecular target of 5-FU involved in apoptosis induction in human colon and breast cancer cell lines. PKR distribution and activation, apoptosis induction and cytotoxic effects were analyzed during 5-FU and 5-FU/IFNΞ± treatment in several colon and breast cancer cell lines with different p53 status. PKR protein was activated by 5-FU treatment in a p53-independent manner, inducing phosphorylation of the protein synthesis translation initiation factor eIF-2Ξ± and cell death by apoptosis. Furthermore, PKR interference promoted a decreased response to 5-FU treatment and those cells were not affected by the synergistic antitumor activity of 5-FU/IFNΞ± combination. These results, taken together, provide evidence that PKR is a key molecular target of 5-FU with potential relevance in the clinical use of this drug
Gene Expression in a Drosophila Model of Mitochondrial Disease
Background
A point mutation in the Drosophila gene technical knockout (tko), encoding mitoribosomal protein S12, was previously shown to cause a phenotype of respiratory chain deficiency, developmental delay, and neurological abnormalities similar to those presented in many human mitochondrial disorders, as well as defective courtship behavior.
Methodology/Principal Findings
Here, we describe a transcriptome-wide analysis of gene expression in tko25t mutant flies that revealed systematic and compensatory changes in the expression of genes connected with metabolism, including up-regulation of lactate dehydrogenase and of many genes involved in the catabolism of fats and proteins, and various anaplerotic pathways. Gut-specific enzymes involved in the primary mobilization of dietary fats and proteins, as well as a number of transport functions, were also strongly up-regulated, consistent with the idea that oxidative phosphorylation OXPHOS dysfunction is perceived physiologically as a starvation for particular biomolecules. In addition, many stress-response genes were induced. Other changes may reflect a signature of developmental delay, notably a down-regulation of genes connected with reproduction, including gametogenesis, as well as courtship behavior in males; logically this represents a programmed response to a mitochondrially generated starvation signal. The underlying signalling pathway, if conserved, could influence many physiological processes in response to nutritional stress, although any such pathway involved remains unidentified.
Conclusions/Significance
These studies indicate that general and organ-specific metabolism is transformed in response to mitochondrial dysfunction, including digestive and absorptive functions, and give important clues as to how novel therapeutic strategies for mitochondrial disorders might be developed.Public Library of Scienc
Markers of gut mucosal inflammation and cow's milk specific immunoglobulins in non-IgE cow's milk allergy
Peer reviewe
Advancing brain barriers RNA sequencing: guidelines from experimental design to publication
Background: RNA sequencing (RNA-Seq) in its varied forms has become an indispensable tool for analyzing differential gene expression and thus characterization of specific tissues. Aiming to understand the brain barriers genetic signature, RNA seq has also been introduced in brain barriers research. This has led to availability of both, bulk and single-cell RNA-Seq datasets over the last few years. If appropriately performed, the RNA-Seq studies provide powerful datasets that allow for significant deepening of knowledge on the molecular mechanisms that establish the brain barriers. However, RNA-Seq studies comprise complex workflows that require to consider many options and variables before, during and after the proper sequencing process.Main body: In the current manuscript, we build on the interdisciplinary experience of the European PhD Training Network BtRAIN (https://www.btrain-2020.eu/) where bioinformaticians and brain barriers researchers collaborated to analyze and establish RNA-Seq datasets on vertebrate brain barriers. The obstacles BtRAIN has identified in this process have been integrated into the present manuscript. It provides guidelines along the entire workflow of brain barriers RNA-Seq studies starting from the overall experimental design to interpretation of results. Focusing on the vertebrate endothelial bloodβbrain barrier (BBB) and epithelial blood-cerebrospinal-fluid barrier (BCSFB) of the choroid plexus, we provide a step-by-step description of the workflow, highlighting the decisions to be made at each step of the workflow and explaining the strengths and weaknesses of individual choices made. Finally, we propose recommendations for accurate data interpretation and on the information to be included into a publication to ensure appropriate accessibility of the data and reproducibility of the observations by the scientific community.Conclusion: Next generation transcriptomic profiling of the brain barriers provides a novel resource for understanding the development, function and pathology of these barrier cells, which is essential for understanding CNS homeostasis and disease. Continuous advancement and sophistication of RNA-Seq will require interdisciplinary approaches between brain barrier researchers and bioinformaticians as successfully performed in BtRAIN. The present guidelines are built on the BtRAIN interdisciplinary experience and aim to facilitate collaboration of brain barriers researchers with bioinformaticians to advance RNA-Seq study design in the brain barriers community
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