20 research outputs found
Verteilung der fünften DNA-Base 5-Methyl-Desoxycytidin im Säugergenom: DNA-Methylierungsmuster endogener retroviraler Sequenzen des Syrischen Hamsters (Mesocricetus auratus) und in den Promotoren menschlicher Erythrozytenmembranskelettproteine (Homo
Acute cervical lymphadenitis and infections of the retropharyngeal and parapharyngeal spaces in children
AI is a viable alternative to high throughput screening: a 318-target study
: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery
CD49d- Treg Cells with High Suppressive Capacity are Remarkably Less Efficient on Activated CD45RA- than on Naive CD45RA+ Teff Cells
Background: Impairment of regulatory T cells (Tregs) in common autoimmune diseases seems likely. However, the extent of Treg deficiency (number, function) or differential susceptibility of T effector cells (Teffs) to suppression is not completely understood. We hypothesize that even in healthy individuals both cell populations are heterogeneous and differ in their suppressive capability and their susceptibility to suppression. Material and Methods: Lymphocytes were enriched by MACS for CD4+CD25+ Tregs or CD4+CD25- Teffs. After multicolour staining (anti-CD25, anti-CD127, anti-CD49d or anti-CD45RA) highly purified Treg and Teff subpopulations were collected by FACS. Functional capacity of Tregs or suppressive susceptibility of Teffs was analyzed in an in vitro assay. Results: When CD4+CD25highCD127-/low CD49d- Tregs were tested on naive CD4+CD127+CD25-CD45RA+ Teffs (93.8 %) suppression was almost complete, while the suppressive capacity of CD4+CD25highCD127-/low CD49d+ Tregs was significantly less (71.8 %). Suppressive activity was low when CD4+CD25highCD127-/low CD49d+ Tregs were analyzed on CD4+CD127+CD25-CD45RA- Teffs (48.7%). Conclusion: Although CD49d+ Tregs are functional, the suppressive capacity is significantly lower compared to CD49d- Tregs. CD45RA+ Teffs can be completely suppressed, while CD45RA- Teffs display relative resistance. Phenotypic and functional heterogeneity of Tregs as well as Teffs has to be considered when analyzing deficiencies in immune regulation
Acute cervical lymphadenitis and infections of the retropharyngeal and parapharyngeal spaces in children
International audienceBackground: Acute cervical adenitis can evolve into suppurative cervical lymphadenitis and may sometimes be associated with infection of the retropharyngeal and parapharyngeal spaces (i.e., retropharyngeal and poststyloid parapharyngeal abscesses). This study aimed to describe the clinical presentation of acute cervical lymphadenitis and infections of the retropharyngeal and parapharyngeal spaces in children and examine the management of these conditions. Methods: This was a retrospective study including children from 3 months to 18 years old who were hospitalized in the Pediatric Department of the Centre-Intercommunal-de-Créteil between January 2003 and May 2010. Selected cases were based on the diagnosis of acute cervical lymphadenitis, suppurative cervical lymphadenitis, or infections of the retropharyngeal or parapharyngeal spaces. Case history, clinical signs, laboratory tests, imaging, treatment and clinical course were collected from patient charts. Results: We included 75 children (54 males [72%]); 62 (83%) were 3 years old (48%) underwent a rapid antigen detection test (RADT) for group A beta-hemolytic Streptococcus pyogenes; results for 10 were positive (48%). Contrast-enhanced CT scan of the neck in children with torticollis (n = 31) demonstrated an abscess in 21 (68%). Fine-needle aspiration was performed in 8 patients (11%) and 8 (11%) required surgical drainage. Bacteriology was positive in 8 patients (11%), with a predominance of Staphylococcus aureus and S. pyogenes. All patients received intravenous antibiotics and the outcome was favorable regardless of surgery. Recurrence was observed in only 1 case among the 34 patients with a follow-up visit after discharge. Conclusion: Our data suggest that presentation with cervical lymphadenitis associated with fever and torticollis requires evaluation by contrast-enhanced CT scan. Furthermore, abscess drainage should be restricted to the most severely affected patients who do not respond to antibiotic therapy
Pushing the limits of de novo genome assembly for complex prokaryotic genomes harboring very long, near identical repeats
Generating a complete, de novo genome assembly for prokaryotes is often considered a solved problem. However, we here show that Pseudomonas koreensis P19E3 harbors multiple, near identical repeat pairs up to 70 kilobase pairs in length, which contained several genes that may confer fitness advantages to the strain. Its complex genome, which also included a variable shufflon region, could not be de novo assembled with long reads produced by Pacific Biosciences' technology, but required very long reads from Oxford Nanopore Technologies. Importantly, a repeat analysis, whose results we release for over 9600 prokaryotes, indicated that very complex bacterial genomes represent a general phenomenon beyond Pseudomonas. Roughly 10% of 9331 complete bacterial and a handful of 293 complete archaeal genomes represented this 'dark matter' for de novo genome assembly of prokaryotes. Several of these 'dark matter' genome assemblies contained repeats far beyond the resolution of the sequencing technology employed and likely contain errors, other genomes were closed employing labor-intense steps like cosmid libraries, primer walking or optical mapping. Using very long sequencing reads in combination with assembly algorithms capable of resolving long, near identical repeats will bring most prokaryotic genomes within reach of fast and complete de novo genome assembly
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CD4 +CD25 +FoxP3 + T lymphocytes fail to suppress myelin basic protein-induced proliferation in patients with multiple sclerosis
Multiple sclerosis (MS) is an autoimmune disorder directed against self antigens of the central nervous system. CD4
+CD25
+FoxP3
+ regulatory T cell (T
reg) mediated suppression is an essential mechanism of self-tolerance. We studied whether changes in the suppressive function of a mixture of CD25
high and CD25
intemediate expressing T
reg cells in myelin basic protein (MBP)-induced proliferation occurred in untreated MS patients. Suppression of MBP-induced proliferation was observed in 13 out of 29 (45%) MS patients; this was significantly (
p
<
0.05) less compared with 17 out of 19 (89%) healthy individuals. Relative T
reg counts was significantly increased in MS patients (mean
±
S.D.; 20
±
8%) compared with healthy individuals (15
±
5%). These findings suggest that impaired T
reg function may be involved in pathogenesis of MS