Phosphoinositides and phagocytosis

Phosphoinositide 3 kinases (PI3Ks)* are known as regulators of phagocytosis. Recent results demonstrate that class I and III PI3Ks act consecutively in phagosome formation and maturation, and that their respective products, phosphatidylinositol 3,4,5-trisphosphate (PI[3,4,5]P3) and phosphatidylinositol 3-phosphate (PI[3]P), accumulate transiently at different stages. Phagosomes containing Mycobacterium tuberculosis do not acquire the PI(3)P-binding protein EEA1, which is required for phagosome maturation. This suggests a possible mechanism of how this microorganism evades degradation in phagolysosomes

The spectral sensitivity of long period gratings fabricated in elliptical core D-shaped optical fiber

Long period gratings (LPGs) were written into a D-shaped optical fibre, which has an elliptical core with a W-shaped refractive index profile. The LPG's attenuation bands were found to be sensitive to the polarisation of the interrogating light with a spectral separation of about 15nm between the two orthogonal polarisation states. In addition, two spectrally overlapping attenuation bands corresponding to orthogonal polarisation states were observed; modelling successfully reproduced this spectral feature. The spectral sensitivity of both orthogonal states was experimentally measured with respect to temperature, surrounding refractive index, and directional bending. These LPG devices produced blue and red wavelength shifts of the stop-bands due to bending in different directions. The measured spectral sensitivities to curvatures, d?/dR , ranged from -3.56nm m to +6.51nm m. The results obtained with these LPGs suggest that this type of fibre may be useful as a shape/bend sensor. It was also demonstrated that the neighbouring bands could be used to discriminate between temperature and bending and that overlapping orthogonal polarisation attenuation bands can be used to minimise error associated with polarisation

Bending and orientational characteristics of long period gratings written in D-shaped optical fiber

Long period gratings (LPGs) were written into a D-shaped single-mode fiber. These LPGs were subjected to a range of curvatures, and it was found that as curvature increased, there was increasingly strong coupling to certain higher order cladding modes without the usual splitting of the LPGs stopbands. A bend-induced stopband yielded a spectral sensitivity of 12.55 nm · m for curvature and 2.2 × 10-2 nm°C-1 for temperature. It was also found that the wavelength separation between adjacent bend-induced stopbands varied linearly as a function of curvature. Blue and red wavelength shifts of the stopbands were observed as the sensor was rotated around a fixed axis for a given curvature; thus, in principle, this sensor could be used to obtain bending and orientational information. The behavior of the stopbands was successfully modeled using a finite element approach

Stoichiometry and the New Biology: The Future Is Now

There is a call for biological science to move away from the reductionist focus of the past, but there are large-scale integrative efforts already underway; biological stoichiometry provides one such example

Universality of Thermodynamic Constants Governing Biological Growth Rates

Background: Mathematical models exist that quantify the effect of temperature on poikilotherm growth rate. One family of such models assumes a single rate-limiting ‘master reaction ’ using terms describing the temperature-dependent denaturation of the reaction’s enzyme. We consider whether such a model can describe growth in each domain of life. Methodology/Principal Findings: A new model based on this assumption and using a hierarchical Bayesian approach fits simultaneously 95 data sets for temperature-related growth rates of diverse microorganisms from all three domains of life, Bacteria, Archaea and Eukarya. Remarkably, the model produces credible estimates of fundamental thermodynamic parameters describing protein thermal stability predicted over 20 years ago. Conclusions/Significance: The analysis lends support to the concept of universal thermodynamic limits to microbial growth rate dictated by protein thermal stability that in turn govern biological rates. This suggests that the thermal stability of proteins is a unifying property in the evolution and adaptation of life on earth. The fundamental nature of this conclusion has importance for many fields of study including microbiology, protein chemistry, thermal biology, and ecological theory including, for example, the influence of the vast microbial biomass and activity in the biosphere that is poorly described in current climate models

The decoupled nature of basal metabolic rate and body temperature in endotherm evolution

The origins of endothermy in birds and mammals are important events in vertebrate evolution. Endotherms can maintain their body temperature (Tb) over a wide range of ambient temperatures primarily using the heat that is generated continuously by their high basal metabolic rate (BMR)1. There is also an important positive feedback loop as Tb influences BMR1,2,3. Owing to this interplay between BMRs and Tb, many ecologists and evolutionary physiologists posit that the evolution of BMR and Tb must have been coupled during the radiation of endotherms3,4,5, changing with similar trends6,7,8. However, colder historical environments might have imposed strong selective pressures on BMR to compensate for increased rates of heat loss and to keep Tb constant9,10,11,12. Thus, adaptation to cold ambient temperatures through increases in BMR could have decoupled BMR from Tb and caused different evolutionary routes to the modern diversity in these traits. Here we show that BMR and Tb were decoupled in approximately 90% of mammalian phylogenetic branches and 36% of avian phylogenetic branches. Mammalian BMRs evolved with rapid bursts but without a long-term directional trend, whereas Tb evolved mostly at a constant rate and towards colder bodies from a warmer-bodied common ancestor. Avian BMRs evolved predominantly at a constant rate and without a long-term directional trend, whereas Tb evolved with much greater rate heterogeneity and with adaptive evolution towards colder bodies. Furthermore, rapid shifts that lead to both increases and decreases in BMRs were linked to abrupt changes towards colder ambient temperatures—although only in mammals. Our results suggest that natural selection effectively exploited the diversity in mammalian BMRs under diverse, often-adverse historical thermal environments

How 911 callers and call‐takers impact police encounters with the public: The case of the Henry Louis Gates Jr. arrest

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156456/2/capp12508_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156456/1/capp12508.pd

The Distribution of Phosphatidylinositol 4,5-Bisphosphate in Acinar Cells of Rat Pancreas Revealed with the Freeze-Fracture Replica Labeling Method

Phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] is a phospholipid that has been implicated in multiple cellular activities. The distribution of PI(4,5)P2 has been analyzed extensively using live imaging of the GFP-coupled phospholipase C-δ1 pleckstrin homology domain in cultured cell lines. However, technical difficulties have prevented the study of PI(4,5)P2 in cells of in vivo tissues. We recently developed a method to analyze the nanoscale distribution of PI(4,5)P2 in cultured cells by using the quick-freezing and freeze-fracture replica labeling method. In principle, this method can be applied to any cell because it does not require the expression of artificial probes. In the present study, we modified the method to study cells of in vivo tissues and applied it to pancreatic exocrine acinar cells of the rat. We found that PI(4,5)P2 in the plasma membrane is distributed in an equivalent density in the apical and basolateral domains, but exists in a significantly higher concentration in the gap junction. The intracellular organelles did not show labeling for PI(4,5)P2. The results are novel or different from the reported distribution patterns in cell lines and highlight the importance of studying cells differentiated in vivo

Sizing Up Allometric Scaling Theory

Metabolic rate, heart rate, lifespan, and many other physiological properties vary with body mass in systematic and interrelated ways. Present empirical data suggest that these scaling relationships take the form of power laws with exponents that are simple multiples of one quarter. A compelling explanation of this observation was put forward a decade ago by West, Brown, and Enquist (WBE). Their framework elucidates the link between metabolic rate and body mass by focusing on the dynamics and structure of resource distribution networks—the cardiovascular system in the case of mammals. Within this framework the WBE model is based on eight assumptions from which it derives the well-known observed scaling exponent of 3/4. In this paper we clarify that this result only holds in the limit of infinite network size (body mass) and that the actual exponent predicted by the model depends on the sizes of the organisms being studied. Failure to clarify and to explore the nature of this approximation has led to debates about the WBE model that were at cross purposes. We compute analytical expressions for the finite-size corrections to the 3/4 exponent, resulting in a spectrum of scaling exponents as a function of absolute network size. When accounting for these corrections over a size range spanning the eight orders of magnitude observed in mammals, the WBE model predicts a scaling exponent of 0.81, seemingly at odds with data. We then proceed to study the sensitivity of the scaling exponent with respect to variations in several assumptions that underlie the WBE model, always in the context of finite-size corrections. Here too, the trends we derive from the model seem at odds with trends detectable in empirical data. Our work illustrates the utility of the WBE framework in reasoning about allometric scaling, while at the same time suggesting that the current canonical model may need amendments to bring its predictions fully in line with available datasets