Protein tyrosine phosphatase–σ regulates hematopoietic stem cell–repopulating capacity

Hematopoietic stem cell (HSC) function is regulated by activation of receptor tyrosine kinases (RTKs). Receptor protein tyrosine phosphatases (PTPs) counterbalance RTK signaling; however, the functions of receptor PTPs in HSCs remain incompletely understood. We found that a receptor PTP, PTPσ, was substantially overexpressed in mouse and human HSCs compared with more mature hematopoietic cells. Competitive transplantation of bone marrow cells from PTPσ-deficient mice revealed that the loss of PTPσ substantially increased long-term HSC-repopulating capacity compared with BM cells from control mice. While HSCs from PTPσ-deficient mice had no apparent alterations in cell-cycle status, apoptosis, or homing capacity, these HSCs exhibited increased levels of activated RAC1, a RhoGTPase that regulates HSC engraftment capacity. shRNA-mediated silencing of PTPσ also increased activated RAC1 levels in wild-type HSCs. Functionally, PTPσ-deficient BM cells displayed increased cobblestone area–forming cell (CAFC) capacity and augmented transendothelial migration capacity, which was abrogated by RAC inhibition. Specific selection of human cord blood CD34⁺CD38^–CD45RA^–lin^– PTPσ^– cells substantially increased the repopulating capacity of human HSCs compared with CD34⁺CD38^–CD45RA^–lin^– cells and CD34⁺CD38^–CD45RA^–lin^–PTPσ⁺ cells. Our results demonstrate that PTPσ regulates HSC functional capacity via RAC1 inhibition and suggest that selecting for PTPσ-negative human HSCs may be an effective strategy for enriching human HSCs for transplantation.     

IMP-51, a Novel IMP-Type Metallo-β-Lactamase with Increased Doripenem- and Meropenem-Hydrolyzing Activities,in a Carbapenem-Resistant Pseudomonas aeruginosa Clinical Isolate

A meropenem-resistant Pseudomonas aeruginosa isolate was obtained from a patient in a medical setting in Hanoi, Vietnam. The isolate was found to have a novel IMP-type metallo-β-lactamase, IMP-51, which differed from IMP-7 by an amino acid substitution (Ser262Gly). Escherichia coli expressing bla_IMP-51 showed greater resistance to cefoxitin, meropenem, and moxalactam than E. coli expressing bla_IMP-7. The amino acid residue at position 262 was located near the active site, proximal to the H263 Zn(II) ligand.     

LOCAL PROGRESSION WITH SPONTANEOUS REGRESSION OF TUBERCULOSIS IN THE BONE MARROW OF RABBITS,CORRELATED WITH A TRANSITORY ANEMIA AND LEUCOPENIA AFTER INTRAVENOUS INOCULATION

In this series of rabbits it was found that the rabbits dying during the 1st month after an injection of I or 2 mg. of bovine tubercle bacilli show the same conditions: extreme tuberculosis of the lungs, acute splenic tumor with tuberculosis, involvement of the lymph glands, an occasional small tubercle in the liver and extensive tuberculosis of the bone marrow. The peripheral blood has shown a sharp fall in the platelet count, an anemia and a fall in the granulocytic strain of white cells, and these changes have been correlated with the condition of the bone marrow. There has also been a rise in monocytes and a fall in lymphocytes, to a reversal of the normal ratio. When the rabbits have survived the first acute phase of the disease longer than 3 to 4 weeks, there have been signs in the peripheral blood of a recovery of the bone marrow; the first indication of this has been an increase in platelets, then a rise in hemoglobin followed in 1 or 2 days by a rise in red cells and later a return of the three strains of granulocytes. The bone marrow has shown a rapid spontaneous disintegration of the epithelioid cells correlated with the appearance of increased evidence of acid-fast debris in clasmatocytes, especially clear in those that lie along the vessels. The animals that have survived into the 3rd month have all shown a hyperplastic phase of the healing marrow, both the red cells and all types of the granulocytes appearing in the peripheral blood in numbers above the normal. The epithelioid cells originally containing many bacilli all disappear from the marrow and the only sign left, possibly suggestive of the tuberculosis, is the acid-fast granules in the clasmatocytes. Finally, the marrow becomes entirely normal, giving the normal number of red cells and granulocytes to the blood. Thus, bone marrow in the rabbit has become involved in every instance with the injection of massive doses of viable bacilli. The findings at autopsy in those animals followed during the early reaction to infection confirm this directly and, since the curves of the cells in the peripheral blood of the more chronic animals were the same during the early stages of the disease as in those that died, the same conclusion seems justified from indirect inference for them. The method of healing has been a rapid disintegration of the epithelioid cells without caseation. The bone marrow heals itself entirely regardless of the progress of the disease elsewhere, so that one sees the remarkable condition of an animal recovering from the anemia and leucopenia while dying of tuberculosis elsewhere. The spleen also shows a tendency toward spontaneous healing. In the animals that have lived beyond 100 days there has been some gradual lessening of the diffuse distribution and extent of pulmonary lesions with the development of cavitation together with a marked involvement of the kidneys and lesions in the eyes.     

Left ventricular strain and left atrial strain are impaired during hemodialysis in children

The International Journal of Cardiovascular Imaging - We aimed to investigate intradialytic changes in ventricular and atrial function using speckle tracking echocardiography (STE) in pediatric...     

Classifying disease outbreak reports using n-grams and semantic features

Introduction

This paper explores the benefits of using n-grams and semantic features for the classification of disease outbreak reports, in the context of the BioCaster disease outbreak report text mining system. A novel feature of this work is the use of a general purpose semantic tagger - the USAS tagger - to generate features.

Background

We outline the application context for this work (the BioCaster epidemiological text mining system), before going on to describe the experimental data used in our classification experiments (the 1000 document BioCaster corpus).

Feature sets

Three broad groups of features are used in this work: Named Entity based features, n-gram features, and features derived from the USAS semantic tagger.

Methodology

Three standard machine learning algorithms - Naïve Bayes, the Support Vector Machine algorithm, and the C4.5 decision tree algorithm - were used for classifying experimental data (that is, the BioCaster corpus). Feature selection was performed using the χ² feature selection algorithm. Standard text classification performance metrics - Accuracy, Precision, Recall, Specificity and F-score - are reported.

Results

A feature representation composed of unigrams, bigrams, trigrams and features derived from a semantic tagger, in conjunction with the Naïve Bayes algorithm and feature selection yielded the highest classification accuracy (and F-score). This result was statistically significant compared to a baseline unigram representation and to previous work on the same task. However, it was feature selection rather than semantic tagging that contributed most to the improved performance.

Conclusion

This study has shown that for the classification of disease outbreak reports, a combination of bag-of-words, n-grams and semantic features, in conjunction with feature selection, increases classification accuracy at a statistically significant level compared to previous work in this domain.