The bone and the kidney

Renal tubular diseases may present with osteopenia, osteoporosis or osteomalacia, as a result of significant derangements in body electrolytes. In case of insufficient synthesis of calcitriol, as in renal failure, the more complex picture of renal osteodystrophy may develop. Hypothetically, also disturbed renal production of BMP-7 and Klotho could cause bone disease. However, the acknowledgment that osteocytes are capable of producing FGF23, a phosphaturic hormone at the same time modulating renal synthesis of calcitriol, indicates that it is also bone that can influence renal function. Importantly, a feed-back mechanism exists between FGF23 and calcitriol synthesis, while Klotho, produced by the kidney, determines activity and selectivity of FGF23. Identification of human diseases linked to disturbed production of FGF23 and Klotho underlines the importance of this new bone-kidney axis. Kidney and bone communicate reciprocally to regulate the sophisticated machinery responsible for divalent ions homeostasis and for osseous or extraosseous mineralisation processes.     

Maximum Likelihood Estimation of Exponential Polynomial Rate for Poisson Data

The heterogeneous Poisson process with discretized exponential quadratic rate function is considered. Maximum likelihood estimates of the parameters of the rate function are derived for the case when the data consists of numbers of occurrences in consecutive equal time periods. A likelihood ratio test of the null hypothesis of exponential quadratic rate is presented. Its power against exponential linear rate functions is estimated using Monte Carlo simulation. The maximum likelihood method is compared with a log-linear least squares techniques. An application of the technique to the analysis of mortality rates due to congenital malformations is presented.     

Rapid reprogramming of haemoglobin structure‐function exposes multiple dual‐antimicrobial potencies

The intrinsic cytotoxicity of cell‐free haemoglobin (Hb) has hampered the development of reliable Hb‐based blood substitutes for over seven decades. Notably, recent evidence shows that the Hb deploys this cytotoxic attack against invading microbes, albeit, through an unknown mechanism. Here, we unraveled a rapid molecular reprogramming of the Hb structure‐function triggered by virulent haemolytic pathogens that feed on the haem‐iron. On direct contact with the microbe, the Hb unveils its latent antimicrobial potency, where multiple antimicrobial fragments are released, each harbouring coordinated ‘dual‐action centres’: microbe binding and pseudoperoxidase (POX) cycle activity. The activated Hb fragments anchor onto the microbe while the juxtaposed POX instantly unleashes a localized oxidative shock, killing the pathogen‐in‐proximity. This concurrent action conceivably restricts the diffusion of free radicals. Furthermore, the host astutely protects itself from self‐cytotoxicity by simultaneously releasing endogenous antioxidants. We found that this decryption mechanism of antimicrobial potency is conserved in the ancient invertebrate respiratory protein, indicating its fundamental significance. Our definition of dual‐antimicrobial centres in the Hb provides vital clues for designing a safer Hb‐based oxygen carrier blood substitute.     

On the Green’s function for a one-dimensional random walk

The Green’s function of a random walk on a lattice is defined as the inverse of the operatorK-z1, whereK is the matrix of transition rates and z is an arbitrary complex parameter. The Green’s function for a symmetrical random walk in one dimension is here explicitly given in closed form for reflecting, periodic, and absorbing boundaries, and also for an infinite lattice.     

Does boron play only a structural role in the growing tissues of higher plants?

In species in which boron (B) mobility is limited, B deficiency only occurs in growing plant organs. As a consequence of the highly localized patterns of plant growth and the general immobility of B it has been extremely difficult to determine the primary function of B in plants. In species in which B is phloem mobile, the removal of B from the growth medium results in the depletion of B present in mature leaves. Thus, it is possible to develop mature leaves with increasingly severe levels of B depletion, thereby overcoming the complications of experiments based on growing tissues. Utilizing this approach we demonstrate here that B depletion of mature plum (Prunus salicina) leaves did not result in any discernible change in leaf appearance, membrane integrity or photosynthetic capacity even though B concentrations were reduced to 6-8 µg/g dwt, which is less than 30% of the reported tissue B requirement. Boron depletion, however, results in a severe disruption of plant growth and metabolism in young growing tissues. This experimental evidence and theoretical considerations suggest that the primary and possibly sole function of B, is as a structural component of growing tissues.     

Differentiation of subspecies and sexes of Beringian Dunlins using morphometric measures

Five subspecies of Dunlins (Calidris alpina) that breed in Beringia are potentially sympatric during the non‐breeding season. Studying their ecology during this period requires techniques to distinguish individuals by subspecies. Our objectives were to determine (1) if five morphometric measures (body mass, culmen, head, tarsus, and wing chord) differed between sexes and among subspecies (C. a. actites, arcticola, kistchinski, pacifica, and sakhalina), and (2) if these differences were sufficient to allow for correct classification of individuals using equations derived from discriminant function analyses. We conducted analyses using morphometric data from 10 Dunlin populations breeding in northern Russia and Alaska, USA. Univariate tests revealed significant differences between sexes in most morphometric traits of all subspecies, and discriminant function equations predicted the sex of individuals with an accuracy of 83–100% for each subspecies. We provide equations to determine sex and subspecies of individuals in mixed subspecies groups, including the (1) Western Alaska group of arcticola and pacifica (known to stage together in western Alaska) and (2) East Asia group of arcticola, actites, kistchinski, and sakhalina (known to winter together in East Asia). Equations that predict the sex of individuals in mixed groups had classification accuracies between 75% and 87%, yielding reliable classification equations. We also provide equations that predict the subspecies of individuals with an accuracy of 22–96% for different mixed subspecies groups. When the sex of individuals can be predetermined, the accuracy of these equations is increased substantially. Investigators are cautioned to consider limitations due to age and feather wear when using these equations during the non‐breeding season. These equations will allow determination of sexual and subspecies segregation in non‐breeding areas, allowing implementation of taxonomic‐specific conservation actions.     

Functional assignment to JEV proteins using SVM

Identification of different protein functions facilitates a mechanistic understanding of Japanese encephalitis virus (JEV) infection and opens novel means for drug development. Support vector machines (SVM), useful for predicting the functional class of distantly related proteins, is employed to ascribe a possible functional class to Japanese encephalitis virus protein. Our study from SVMProt and available JE virus sequences suggests that structural and nonstructural proteins of JEV genome possibly belong to diverse protein functions, are expected to occur in the life cycle of JE virus. Protein functions common to both structural and non-structural proteins are iron-binding, metal-binding, lipid-binding, copper-binding, transmembrane, outer membrane, channels/Pores - Pore-forming toxins (proteins and peptides) group of proteins. Non-structural proteins perform functions like actin binding, zinc-binding, calcium-binding, hydrolases, Carbon-Oxygen Lyases, P-type ATPase, proteins belonging to major facilitator family (MFS), secreting main terminal branch (MTB) family, phosphotransfer-driven group translocators and ATP-binding cassette (ABC) family group of proteins. Whereas structural proteins besides belonging to same structural group of proteins (capsid, structural, envelope), they also perform functions like nuclear receptor, antibiotic resistance, RNA-binding, DNA-binding, magnesium-binding, isomerase (intra-molecular), oxidoreductase and participate in type II (general) secretory pathway (IISP).     

An Efficient Timer and Sizer of Biomacromolecular Motions

1. Download : Download high-res image (92KB)
2. Download : Download full-size image