Polyphosphate in thrombosis, hemostasis, and inflammation

This illustrated review focuses on polyphosphate as a potent modulator of the plasma clotting cascade, with possible roles in hemostasis, thrombosis, and inflammation. Polyphosphates are highly anionic, linear polymers of inorganic phosphates that are widespread throughout biology. Infectious microorganisms accumulate polyphosphates with widely varying polymer lengths (from a few phosphates to over a thousand phosphates long), while activated human platelets secrete polyphosphate with a very narrow size distribution (about 60‐100 phosphates long). Work from our lab and others has shown that long‐chain polyphosphate is a potent trigger of clotting via the contact pathway, while polyphosphate of the size secreted by platelets accelerates factor V activation, blocks the anticoagulant activity of tissue factor pathway inhibitor, promotes factor XI activation by thrombin, and makes fibrin fibrils thicker and more resistant to fibrinolysis. Polyphosphate also modulates inflammation by triggering bradykinin release, inhibiting the complement system, and modulating endothelial function. Polyphosphate and nucleic acids have similar physical properties and both will trigger the contact pathway—although polyphosphate is orders of magnitude more procoagulant than either DNA or RNA. Important caveats in these studies include observations that nucleic acids and polyphosphate may co‐purify, and that these preparations can be contaminated with highly procoagulant microparticles if silica‐based purification methods are employed. Polyphosphate has received attention as a possible therapeutic, with some recent studies exploring the use of polyphosphate in a variety of formulations to control bleeding. Other studies are investigating treatments that block polyphosphate function as novel antithrombotics with the possibility of reduced bleeding side effects.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147856/1/rth212162_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147856/2/rth212162.pd

Observations on Bats from Trinidad, with a Checklist of Species Occurring on the Island

In their comprehensive treatment of the bats of Trinidad, Goodwin and Greenhall (1961) reported 58 species from the island. Subsequent authors (Goodwin and Greenhall, 1962, 1964; Genoways et al., 1973a; LaVal, 1973a, 1973b) have added some species to the list and changed the status of others so that the known chiropteran fauna of Trinidad now comprises 64 species: five emballonurids, one noctilionid, four mormoopids, 36 phyllostomids (see Handley, 1980, for family-group names), one natalid, one furipterid, one thyropterid, seven vespertilionids, and eight molossids. Among the phyllostomids, the subfamilies Phyllostominae (15) and Stenodermatinae (14) are the best represented, whereas only a few species of the other three subfamilies Glossophaginae (four), Carolliinae (one), and Desmodontinae (two)-are present. In this paper, we report additional data on 55 species. These data add to the available information concerning distribution, reproduction, and molt. Where appropriate, we have included taxonomic comments on the status of Trinidadian populations. Material reported here is the result of three collecting trips to Trinidad led by R.J. Baker

Whole body vibration exposure on markers of bone turnover, body composition, and physical functioning in breast cancer patients receiving aromatase inhibitor therapy: A randomized controlled trial

Introduction: Women with breast cancer are often prescribed aromatase inhibitors, which can cause rapid loss of bone mass leading to significant potential for morbidity. Vibration training has been shown to be helpful in reducing bone turnover in postmenopausal women without cancer. Aim: To examine the effect of vibration stimulus on markers of bone turnover in breast cancer patients receiving aromatase inhibitors. Methods: Thirty-one breast cancer survivors undergoing treatment with aromatase inhibitors were randomized to vibration stimulus (n = 14) or usual care control (n = 17). Low-frequency and low-magnitude vibration stimulus (27-32 Hz, 0.3g) was delivered in supervised sessions via standing on a vibration platform for 20 minutes, 3 times per week for 12 weeks. The primary outcome was blood markers of bone resorption (serum N-telopeptide X/creatine) and formation (serum type 1 procollagen N-terminal propeptide; P1NP). Other study outcomes body composition as well as measures of physical functioning. Outcomes were compared between groups using analysis of covariance adjusted for baseline values as well as time on aromatase inhibitors. Outcomes: On average, participants were 61.5 years old and overweight (ie, body mass index = 28.5 kg/m2). Following vibration training, there was no significant difference between groups for bone resorption (adjusted group difference 0.5, P = .929) or formation (adjusted group difference 5.3, P = .286). There were also no changes in any measure of physical functioning body composition. Conclusions: Short-term low-magnitude vibration stimulus does not appear to be useful for reducing markers of bone turnover secondary to aromatase inhibitors in breast cancer patients; nor is it useful in improving physical function or symptoms. However, further investigations with larger samples and higher doses of vibration are warranted. Trial Registration: Australian and New Zealand Clinical Trials Registry (ACTRN12611001094965)

How does a newly encountered face become familiar? The effect of within-person variability on adults' and children's perception of identity

Adults and children aged 6 years and older easily recognize multiple images of a familiar face, but often perceive two images of an unfamiliar face as belonging to different identities. Here we examined the process by which a newly encountered face becomes familiar, defined as accurate recognition of multiple images that capture natural within-person variability in appearance. In Experiment 1 we examined whether exposure to within-person variability in appearance helps children learn a new face. Children aged 6-13 years watched a 10-min video of a woman reading a story; she was filmed on a single day (low variability) or over three days, across which her appearance and filming conditions (e.g., camera, lighting) varied (high variability). After familiarization, participants sorted a set of images comprising novel images of the target identity intermixed with distractors. Compared to participants who received no familiarization, children showed evidence of learning only in the high-variability condition, in contrast to adults who showed evidence of learning in both the low- and high-variability conditions. Experiment 2 highlighted the efficiency with which adults learn a new face; their accuracy was comparable across training conditions despite variability in duration (1 vs. 10min) and type (video vs. static images) of training. Collectively, our findings show that exposure to variability leads to the formation of a robust representation of facial identity, consistent with perceptual learning in other domains (e.g., language), and that the development of face learning is protracted throughout childhood. We discuss possible underlying mechanisms

Mercury's Magnetopause and Bow Shock from MESSENGER Magnetometer Observations

We have established the average shape and location of Mercury's magnetopause and bow shock from orbital observations by the MESSENGER Magnetometer. We fit empirical models to midpoints of boundary crossings and probability density maps of the magnetopause and bow shock positions. The magnetopause was fit by a surface for which the position R from the planetary dipole varies as [1 + cos(theta)]-alpha, where theta is the angle between R and the dipole-Sun line, the subsolar standoff distance Rss is 1.45 RM (where RM is Mercury's radius), and the flaring parameter alpha = 0.5. The average magnetopause shape and location were determined under a mean solar wind ram pressure PRam of 14.3 nPa. The best fit bow shock shape established under an average Alfvén Mach number (MA) of 6.6 is described by a hyperboloid having Rss = 1.96 RM and an eccentricity of 1.02. These boundaries move as PRam and MA vary, but their shapes remain unchanged. The magnetopause Rss varies from 1.55 to 1.35 RM for PRam in the range of 8.8-21.6 nPa. The bow shock Rss varies from 2.29 to 1.89 RM for MA in the range of 4.12-11.8. The boundaries are well approximated by figures of revolution. Additional quantifiable effects of the interplanetary magnetic field are masked by the large dynamic variability of these boundaries. The magnetotail surface is nearly cylindrical, with a radius of ~2.7 RM at a distance of 3 RM downstream of Mercury. By comparison, Earth's magnetotail flaring continues until a downstream distance of ~10 Rss

Multisensory processing and proprioceptive plasticity during resizing illusions

Bodily resizing illusions typically use visual and/or tactile inputs to produce a vivid experience of one’s body changing size. Naturalistic auditory input (an input that reflects the natural sounds of a stimulus) has been used to increase illusory experience during the rubber hand illusion, whilst non-naturalistic auditory input can influence estimations of finger length. We aimed to use a non-naturalistic auditory input during a hand-based resizing illusion using augmented reality, to assess whether the addition of an auditory input would increase both subjective illusion strength and measures of performance-based tasks. Forty-four participants completed the following three conditions: no finger stretching, finger stretching without tactile feedback and finger stretching with tactile feedback. Half of the participants had an auditory input throughout all the conditions, whilst the other half did not. After each condition, the participants were given one of the following three performance tasks: stimulated (right) hand dot touch task, non-stimulated (left) hand dot touch task, and a ruler judgement task. Dot tasks involved participants reaching for the location of a virtual dot, whereas the ruler task concerned estimates of the participant’s own finger on a ruler whilst the hand was hidden from view. After all trials, the participants completed a questionnaire capturing subjective illusion strength. The addition of auditory input increased subjective illusion strength for manipulations without tactile feedback but not those with tactile feedback. No facilitatory effects of audio were found for any performance task. We conclude that adding auditory input to illusory finger stretching increased subjective illusory experience in the absence of tactile feedback but did not affect performance-based measures

Treatment options for muscle-invasive urothelial cancer for patients who were not eligible for cystectomy or neoadjuvant chemotherapy with methotrexate, vinblastine, doxorubicin, and cisplatin

BACKGROUND. Many patients with invasive urothelial cell cancer are poor candidates for cisplatin-based chemotherapy, and many are high risk for cystectomy. Southwest Oncology Group Trial 8733 was designed to address treatment for such patients. METHODS. Eligible patients had primary or recurrent muscle-invasive disease with transitional cell or squamous cell histology, a performance status from 0 to 2, no extrapelvic disease, a life expectancy >3 months, and adequate hematologic function. The treating clinician assigned patients to operable or inoperable groups. All patients received 2 cycles of 5-fluorouracil (5-FU) at a dose of 1000mg/m 2 per day × 4 starting concurrently with radiation at a dose of 200 centigrays per day × 10 each cycle. After 2 cycles, operable patients with positive biopsies underwent cystectomy, and patients with negative biopsies received a third cycle of chemoradiotherapy. Patients in the inoperable group received 3 cycles without interim biopsy. RESULTS. Eighteen of 24 eligible patients in the operable group were evaluable for response. Five patients had a complete response (CR), 9 patients had stable disease, 1 patient had progressive disease, and 3 patients were not assessable. The median progression-free survival was 10 months (95% confidence interval [95% CI], 4–14 months), and the median overall survival was 18 months (95% CI, 7–28 months). In the inoperable group, 35 of 37 eligible patients were evaluable for response with 17 CRs (49%; 95% CI, 31%–66%). The median progression-free survival was 13 months (95% CI, 10–17 months), and the median overall survival was 20 months (95% CI, 11–53 months). There were no episodes of grade 4 toxicity. CONCLUSIONS. In the current study, the combination of 5-FU and radiation was found to be tolerated well by patients with numerous comorbidities who could not tolerate cisplatin-based therapy or cystectomy. Cancer 2008. © 2008 American Cancer Society.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/58591/1/23420_ftp.pd

The role of North Brazil Current transport in the paleoclimate of the Brazilian Nordeste margin and paleoceanography of the western tropical Atlantic during the late Quaternary

Author Posting. © The Author(s), 2014. This is the author's version of the work. It is posted here by permission of Elsevier for personal use, not for redistribution. The definitive version was published in Palaeogeography, Palaeoclimatology, Palaeoecology 415 (2014): 3-13, doi:10.1016/j.palaeo.2014.05.030.Reconstructions of surface paleoceanographic conditions of the western equatorial Atlantic and past climates of the adjacent Northeast Brazilian (the "Nordeste") continental margin were undertaken by analyzing sediments from a piston core and associated gravity and box cores recovered from 3107 meter water depth at 0° 20’ N on the equatorial Brazilian continental slope. The record is dated by radiocarbon analysis and oxygen isotopic stratigraphy of planktonic foraminifers and spans from near- modern to approximately 110 Ka. High-resolution XRF analysis provides insight into the paleoclimate history of the Nordeste during the last glacial interval. Several large-amplitude and abrupt peaks are observed in the time series of Ti/Ca and are usually accompanied by peaks of Fe/K. Together these record periods of increased precipitation and intense weathering on the adjacent continent and increased terrestrial sediment discharge from Nordeste rivers into the Atlantic. Within the limits of dating accuracy, most Ti/Ca peaks correlate with Heinrich events in the North Atlantic. This record thus corroborates, and extends back in time, the previous record of Arz et al (1998) determined on sediment cores from farther southeast along the Nordeste margin. Stable oxygen isotopic analysis and Mg/Ca paleothermometry on the near- surface-dwelling planktonic foraminiferal species Globierinoides ruber find that mean sea-surface temperature (SST) during glacial time (20 to 55 Ka, n = 97) was 23.89 ± 0.79 °C and the mean SST during the late Holocene (0 to 5 Ka, n = 14) was 26.89 ± 0.33 °C. SSTs were 0.5 to 2 °C higher and inferred sea-surface salinities were lower during most of the periods of elevated Ti/Ca, thus, as observed in previous studies, the western equatorial Atlantic was warm (at least locally) and the adjacent southern tropical continent was wet at the same time that the high-latitude North Atlantic was cold. Using the SYNTRACE-CCSM3 fully coupled climate model with transient forcing for the period 22 Ka to present, we find that decreased transport of the North Brazil Current co-occurs with reduced Atlantic meridional overturning circulation, and colder-than-normal SSTs in the North Atlantic region. These simulated conditions are invariably associated with significantly increased precipitation in the Nordeste region.Funding for the cruise and post-cruise science was provided to PAB by NSF-OCE-0823650