A simple strategy for detecting moving objects during locomotion revealed by animal-robot interactions

An important role of visual systems is to detect nearby predators, prey, and potential mates, which may be distinguished in part by their motion. When an animal is at rest, an object moving in any direction may easily be detected by motion-sensitive visual circuits. During locomotion, however, this strategy is compromised because the observer must detect a moving object within the pattern of optic flow created by its own motion through the stationary background. However, objects that move creating back-to-front (regressive) motion may be unambiguously distinguished from stationary objects because forward locomotion creates only front-to-back (progressive) optic flow. Thus, moving animals should exhibit an enhanced sensitivity to regressively moving objects. We explicitly tested this hypothesis by constructing a simple fly-sized robot that was programmed to interact with a real fly. Our measurements indicate that whereas walking female flies freeze in response to a regressively moving object, they ignore a progressively moving one. Regressive motion salience also explains observations of behaviors exhibited by pairs of walking flies. Because the assumptions underlying the regressive motion salience hypothesis are general, we suspect that the behavior we have observed in Drosophila may be widespread among eyed, motile organisms.     

Antitumor Effects of Combining Docetaxel (Taxotere) with the Antivascular Action of Ultrasound Stimulated Microbubbles

Ultrasound stimulated microbubbles (USMB) are being investigated for their potential to promote the uptake of anticancer agents into tumor tissue by exploiting their ability to enhance microvascular permeability. At sufficiently high ultrasound transmit amplitudes it has also recently been shown that USMB treatments can, on their own, induce vascular damage, shutdown blood flow, and inhibit tumor growth. The objective of this study is to examine the antitumor effects of ‘antivascular’ USMB treatments in conjunction with chemotherapy, which differs from previous work which has sought to enhance drug uptake with USMBs by increasing vascular permeability. Conceptually this is a strategy similar to combining vascular disrupting agents with a chemotherapy, and we have selected the taxane docetaxel (Taxotere) for evaluating this approach as it has previously been shown to have potent antitumor effects when combined with small molecule vascular disrupting agents. Experiments were conducted on PC3 tumors implanted in athymic mice. USMB treatments were performed at a frequency of 1 MHz employing sequences of 50 ms bursts (0.00024 duty cycle) at 1.65 MPa. USMB treatments were administered on a weekly basis for 4 weeks with docetaxel (DTX) being given intravenously at a dose level of 5 mg/kg. The USMB treatments, either alone or in combination with DTX, induced an acute reduction in tumor perfusion which was accompanied at the 24 hour point by significantly enhanced necrosis and apoptosis. Longitudinal experiments showed a modest prolongation in survival but no significant growth inhibition occurred in DTX–only and USMB-only treatment groups relative to control tumors. The combined USMB-DTX treatment group produced tumor shrinkage in weeks 4–6, and significant growth inhibition and survival prolongation relative to the control (p<0.001), USMB-only (p<0.01) and DTX-only treatment groups (p<0.01). These results suggest the potential of enhancing the antitumor activity of docetaxel by combining it with antivascular USMB effects.     

Comparison of collagen and glycosaminoglycan synthesis in attaching control and diabetic human skin fibroblasts

Summary Cultured fibroblasts derived from normal subjects and juvenile diabetics attach in the absence of serum to plastic culture dishes and secrete macromolecules, including collagenous components, hyaluronic acid, and proteoglycans into the medium and onto the plastic surface where they form a microexudate carpet. Most diabetic fibroblasts examined did not spread as well as normal cells during a 4-hr interval after the initial attachment. There were no significant differences between normal and diabetic cells with respect to proline and lysine incorporation and lysine hydroxylation. The percentage glycosylation of hydroxylysine was marginally higher in the media proteins of diabetic cells, but glycosylation in both normal and diabetic cells was elevated over that typically observed in human skin collagen. Collagenous components were estimated to constitute approximately 15–20% of the microexudate carpet fraction in both normal and diabetic cell strains. Diabetic fibroblasts exhibited a marginally lower ratio of heparan sulfate to chondroitin sulfate in the cell surface to matrix microexudate carpet fraction (trypsinate) than did normal fibroblasts. The hyaluronate and chondroitin sulfate contents of this fraction of diabetic cells were not significantly different from those of normal cells. This work was supported by Grants AM 11821 and AM 19606 from the National Institutes of Health, United States Public Health Service, by a grant from the American Diabetes Association (Leon W. Cunningham, Principal Investigator) and by the Vanderbilt Diabetes Endocrinology Center grant, AM 17026. R. E. Branson was the recipient of a research fellowship of the Juvenile Diabetes Foundation and of a National Institutes of Health Postdoctoral Fellowship AM 05636.     

Pathologic diagnosis of breast cancer patients: evolution of the traditional clinical-pathologic paradigm toward “precision” cancer therapy

We present an updated account of breast cancer treatment and of progress toward “precision” cancer therapy; we focus on new developments in diagnostic molecular pathology and breast cancer that have emerged during the past 2 years. Increasing awareness of new prognostic and predictive methodologies, and introduction of next generation sequencing has increased understanding of both tumor biology and clinical behavior, which offers the possibility of more appropriate therapeutic choices. It remains unclear which of these testing methodologies provides the most informative and cost-effective actionable results for predictive and prognostic pathology. It is likely, however, that an integrated “step-wise” approach that uses the traditional clinical-pathologic paradigms coordinated with molecular characterization of breast tumor tissue, will offer the most comprehensive and cost-effective options for individualized, “precision” therapy for patients with breast cancer.     

The stress responsive and morphologically regulated <Emphasis Type="Italic">hsp90</Emphasis> gene from <Emphasis Type="Italic">Paracoccidioides brasiliensis</Emphasis> is essential to cell viability

Background  

Paracoccidioides brasiliensis is a dimorphic fungus that causes the most prevalent systemic mycosis in Latin America. The response to heat shock is involved in pathogenesis, as this pathogen switches from mycelium to yeast forms in a temperature dependent fashion that is essential to establish infection. HSP90 is a molecular chaperone that helps in the folding and stabilization of selected polypeptides. HSP90 family members have been shown to present important roles in fungi, especially in the pathogenic species, as an immunodominant antigen and also as a potential antifungal therapeutic target.     

Kinetic characterization of yeast pyruvate carboxylase isozyme pyc1

Yeast (Saccharomyces cerevisiae) is unusual in being the only organism thus far identified as having two genes for pyruvate carboxylase. The expression of the two isozymes Pyc1 and Pyc2 appears to be differentially regulated, and since both are expressed cytoplasmically, this suggests that they have different properties. To the present, little has been done to characterize these isozymes, and almost all of the published kinetic information on yeast pyruvate carboxylase comes from measurements of enzyme prepared from bakers' yeast which is likely to be a mixture of both isozymes. Here we have measured basic kinetic parameters for Pyc1 and found that the K(a) of this isozyme for acetyl CoA is in the order of 8-10-fold higher than previously recorded, suggesting that Pyc1 and Pyc2 may be differentially regulated by this effector. Pyc1 is highly dependent on the presence of acetyl CoA for activity and in this respect is similar to chicken liver pyruvate carboxylase. However, unlike the chicken liver enzyme, the quaternary structure of the enzyme is quite stable in the absence of acetyl CoA, and the major locus of action of this effector appears to lie outside of the stimulation of the biotin carboxylation reaction.     

Serological, virological and histopathological study of an outbreak of sleeping disease in farmed rainbow trout Oncorhynchus mykiss

A prospective longitudinal survey for sleeping disease (SD) was carried out over a 20 wk period on a caged freshwater population of farmed rainbow trout Oncorhynchus mkyiss. Pancreas, heart and red and white skeletal muscle were examined histologically and the presence and severity of lesions recorded. Sera were tested for viraemia with Salmonid Alphavirus (SAV) and for virus neutralizing (VN) antibodies. Viraemia was detected for 4 wk, beginning at Week 6 and with a peak prevalence of 57.9% at Week 7. Clinical signs and mortalities appeared at Week 8. Total mortality in the study cage from Week 6 onward was 6.3 %, but other cages at the site had mortality levels of up to 47.2%. VN antibodies were first detected at Week 9, with seroprevalence increasing to 80% by the end of the study (Week 20). Geometric mean antibody titres peaked at 1/89.4 at Week 17. Histological lesions were first detected at Week 7 (pancreas only), before increasing in prevalence and severity to peak at Weeks 9 and 10. The majority of lesions were resolved by Week 15.     

HIV Testing among Outpatients with Medicaid and Commercial Insurance

Objective

To assess HIV testing and factors associated with receipt of testing among persons with Medicaid and commercial insurance during 2012.

Methods

Outpatient and laboratory claims were analyzed from two databases: all Medicaid claims from six states and all claims from Medicaid health plans from four other states and a large national convenience sample of patients with commercial insurance in the United States. We excluded those aged <13 years and >64 years, enrolled <9 of the 12 months, pregnant females, and previously diagnosed with HIV. We identified patients with new HIV diagnoses that followed (did not precede) the HIV test, using HIV ICD-9 codes. HIV testing percentages were assessed by patient demographics and other tests or diagnoses that occurred during the same visit.

Results

During 2012, 89,242 of 2,069,536 patients (4.3%) with Medicaid had at least one HIV test, and 850 (1.0%) of those tested received a new HIV diagnosis. Among 27,206,804 patients with commercial insurance, 757,646 (2.8%) had at least one HIV test, and 5,884 (0.8%) of those tested received a new HIV diagnosis. During visits that included an HIV test, 80.2% of Medicaid and 83.0% of commercial insurance claims also included a test or diagnosis for a sexually transmitted infection (STI), and/or Hepatitis B or C virus at the same visit.

Conclusions

HIV testing primarily took place concurrently with screening or diagnoses for STIs or Hepatitis B or C. We found little evidence to suggest routine screening for HIV infection was widespread.     

Monitoring HIV Testing in the United States: Consequences of Methodology Changes to National Surveys

Objective

In 2011, the National Health Interview Survey (NHIS), an in-person household interview, revised the human immunodeficiency virus (HIV) section of the survey and the Behavioral Risk Factor Surveillance System (BRFSS), a telephone-based survey, added cellphone numbers to its sampling frame. We sought to determine how these changes might affect assessment of HIV testing trends.

Methods

We used linear regression with pairwise contrasts with 2003-2013 data from NHIS and BRFSS to compare percentages of persons aged 18-64 years who reported HIV testing in landline versus cellphone-only households before and after 2011, when NHIS revised its in-person questionnaire and BRFSS added cellphone numbers to its telephone-based sample.

Results

In NHIS, the percentage of persons in cellphone-only households increased 13-fold from 2003 to 2013. The percentage ever tested for HIV was 6%–10% higher among persons in cellphone-only than landline households. The percentage ever tested for HIV increased significantly from 40.2% in 2003 to 45.0% in 2010, but was significantly lower in 2011 (40.6%) and 2012 (39.7%). In BRFSS, the percentage ever tested decreased significantly from 45.9% in 2003 to 40.2% in 2010, but increased to 42.9% in 2011 and 43.5% in 2013.

Conclusions

HIV testing estimates were lower after NHIS questionnaire changes but higher after BRFSS methodology changes. Data before and after 2011 are not comparable, complicating assessment of trends.