Thrombospondins and Novel TSR-containing Proteins,R-spondins,Regulate Bone Formation and Remodeling

Thrombospondins (TSPs) are a family of five secreted multimeric matricellular proteins that share homology in the type II and III repeats and carboxy-terminal region. Type I repeats, also known as properdin or thrombospondin repeats (TSRs), are found in TSP1/2, but not TSP3-5. A variety of other secreted proteins contain TSRs, including the novel extracellular molecules, R-spondins. TSP family and many TSR-containing proteins, including R-spondins, are highly expressed in skeletal tissues during development and postnatal. TSP2 regulates the osteoblast lineage, influencing bone mass and geometry, as well as response to fracture healing, ovariectomy, and mechanical loading. Compound knockout mice of TSPs have revealed important mechanistic insights. TSP1/2 knockout mice have craniofacial dysmorphism, and TSP1/3/5 compound knockout mice display growth plate abnormalities. R-spondins promote osteoblast differentiation and R-spondin-2 deficiency results in skeletal developmental defects. Overall, TSP and other TSR molecules influence multiple aspects of bone development and remodeling.     

Oscillations of cerebrovascular resistance throughout the menstrual cycle in healthy women.

OBJECTIVES: Increased concentration of endogenous estrogen during a typical menstrual cycle has been shown to correlate with augmentation of blood flow through the internal carotid arteries (ICAs), which may be related to changes in vascular resistance within the brain. In this study we investigated the effects of endogenous estrogen and progesterone on cerebrovascular impedance in young healthy women. METHODS: The blood flow in the ICA and the common (CCA) and external (ECA) carotid arteries was studied with duplex Doppler sonography. The resistance index (RI) was determined and correlated with plasma 17beta-estradiol concentration in 14 young healthy women throughout their menstrual cycle. RESULTS: The concentration of 17beta-estradiol increased in the follicular phase of the cycle and reached a peak on day 14, whereas concentration of progesterone remained low. Along with an increase in estrogen concentration, the ICA RI had decreased from its initial level on average by 9.2% on day 13 and by 6.7% on day 14 (P < 0.05). In contrast, the trend of the ECA RI was to increase during the peak of estrogen concentration. There were no significant changes in the CCA RI or in the systolic blood pressure, heart rate, hematocrit and hemoglobin concentration through the menstrual cycle. CONCLUSIONS: Estrogen-related augmentation of blood flow through the ICA is caused mainly by decreased cerebrovascular impedance, as shown by a decrease in the ICA RI. These changes in RI suggest that estrogen influences cerebral impedance mainly by altering the resistance of cerebral microvasculature.     

Die Bedeutung des Ammoniaks für das Chlorbindungsvermögen des Wassers

Ohne Zusammenfassung     

A novel ferroportin mutation in a Canadian family with autosomal dominant hemochromatosis

We report a new mutation, Asn185Asp, in exon 6 of the ferroportin gene (FPN1) in 15 members of three successive generations of a Canadian family of Scandinavian origin with autosomal dominant hemochromatosis. Hyperferritinemia with low transferrin saturation was noted in younger family members, seven of whom were aged 20 years or less at the time of diagnosis. In those individuals first diagnosed with hemochromatosis in later life, marked hyperferritinemia was accompanied by high transferrin saturation. In contrast to the phenotype of high ferritin with low saturation first reported for ferroportin disease, this family demonstrates a phenotype of iron indices that varies with age.     

Associations of parent and staff factors with parent engagement in after‐school programs

This 2‐study research examined staff and parent predictors of parent engagement in after‐school programs. A parent engagement measure tailored to after‐school programs was developed based on existing theory and literature. Two distinct factors, parent engagement and parent participation, emerged from factor analyses and were subsequently tested. A 2‐level model was run on 4 program/staff and 6 parent predictors using staff and parent data from 26 after‐school program sites (Study 1) and nine sites (Study 2). Program quality, staff educational levels, and length of employment in the after‐school program were significantly associated with parent engagement and parent participation but in opposite directions, with other findings contrary to hypotheses. For parent factors of engagement and participation, there was a significant positive association between parental age and parent engagement, while having more than 2 children in a program was significantly and positively associated with parent participation only. Results and implications are discussed.     

Effects of ambient ozone on respiratory function in healthy adults exercising outdoors

The effect of exposure to ozone (O3) in ambient air on respiratory function was studied in 30 healthy adult nonsmokers engaged in a regular daily program of outdoor exercise in Tuxedo, NY during the summer of 1985. Each subject did the same exercise each day, but exercise intensity and duration varied widely between subjects, with minute ventilation ranging from 20 to 153 L and duration ranging from 15 to 55 min. Spirometry was performed immediately before and after each exercise period. O3 concentrations during exercise ranged from 21 to 124 parts per billion (ppb). All measured functional indexes showed significant (p less than 0.01) O3-associated mean decrements with FVC at -2.1 ml/ppb, FEV1 at -1.4 ml/ppb, PEFR at -9.2 ml/s/ppb, FEF25-75 at -6.0 ml/s/ppb, and FEV1/FVC at -0.038%/ppb. Mean decrements were smaller for 10 subjects with minute ventilations greater than 100 L than for 10 other subjects with minute ventilations between 60 and 100 L or for the 10 subjects with minute ventilations below 60 L. Overall, the functional decrements were similar in magnitude to those we have seen in children engaged in supervised recreational programs in summer camps. For 10 subjects with minute ventilations comparable to those used in controlled 1- and 2-h exposures to O3 in purified air in chambers (50 to 80 L), the effects were about twice as large as those reported for the chamber studies.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of multiple transfer of DNA using mock case scenarios

DNA transfer and its possible role in explaining the presence of a biological sample at a crime scene is becoming more prevalent in criminal investigations and related court proceedings. To assist understanding of DNA transfer and assess the extent to which we can utilise already available information regarding transfer of DNA we compare transfer rates determined from mock multi-step transfer scenarios with transfer rates predicted by the application of currently available transfer rate data. The transfer results obtained from the scenarios tested were, in some instances, different (both lower and higher rates) from those predicted. These discrepancies are most likely the result of the impact of as yet untested variables. These may include the variations in substrate type, transfer area size and environmental factors such as temperature and humidity among others. Whilst detailed re-enactments of proposed transfer scenarios, that take into account the many possibly relevant aspects affecting transfer are desirable, to provide an accurate likelihood estimate, these are not always possible. The application of detailed transfer rate tables that include data on the many factors affecting transfer could provide a useful substitute for evaluating the likelihood of specific transfer events. The value and accuracy derived from applying such tables will improve as more research in this area is conducted and the tables expanded and refined.     

Therapeutic Potentials of Ecto‐Nucleoside Triphosphate Diphosphohydrolase,Ecto‐Nucleotide Pyrophosphatase/Phosphodiesterase,Ecto‐5′‐Nucleotidase,and Alkaline Phosphatase Inhibitors

The modulatory role of extracellular nucleotides and adenosine in relevance to purinergic cell signaling mechanisms has long been known and is an object of much research worldwide. These extracellular nucleotides are released by a variety of cell types either innately or as a response to patho‐physiological stress or injury. A variety of surface‐located ecto‐nucleotidases (of four major types; nucleoside triphosphate diphosphohydrolases or NTPDases, nucleotide pyrophosphatase/phosphodiesterases or NPPs, alkaline phosphatases APs or ALPs, and ecto‐5′‐nucleotidase or e5NT) are responsible for meticulously controlling the availability of these important signaling molecules (at their respective receptors) in extracellular environment and are therefore crucial for maintaining the integrity of normal cell functioning. Overexpression of many of these ubiquitous ecto‐enzymes has been implicated in a variety of disorders including cell adhesion, activation, proliferation, apoptosis, and degenerative neurological and immunological responses. Selective inhibition of these ecto‐enzymes is an area that is currently being explored with great interest and hopes remain high that development of selective ecto‐nucleotidase inhibitors will prove to have many beneficial therapeutic implications. The aim of this review is to emphasize and focus on recent developments made in the field of inhibitors of ecto‐nucleotidases and to highlight their structure activity relationships wherever possible. Most recent and significant advances in field of NTPDase, NPP, AP, and e5NT inhibitors is being discussed in detail in anticipation of providing prolific leads and relevant background for research groups interested in synthesis of selective ecto‐nucleotidase inhibitors.