Female striped mice (Rhabdomys pumilio) change their home ranges in response to seasonal variation in food availability

Animals may respond to seasonally changing environments withphysiological and behavioral strategies. Whereas migration isa behavioral strategy used by many taxa, it may not be an optionfor small mammals. However, small mammals can seasonally varythe area of habitat in which they are active. The striped mouseRhabdomys pumilio in the semiarid Succulent Karoo of South Africalives in a seasonal environment, characterized by hot, dry summerswith low food abundance and cold, wet winters, followed by highfood abundance in spring. We radio tracked a total of 28 femalesduring the 2004 dry season, the following breeding season inspring, and the following dry season in 2005 and tested theprediction that females shift their home ranges in relationto food availability. Females shifted their home ranges froman area characterized by evergreen succulent shrubs in the vicinityof a dry riverbed in the dry season to sandy areas that werecharacterized by new plant growth of annuals in spring. Homeranges during the breeding season in spring had a higher percentageof annuals than dry season home ranges measured in spring. Femalehome range size increased during the breeding season. We suggestthat female striped mice shift their home ranges seasonallyto gain access to protein-rich young plant material, which isimportant for breeding.     

The in vivo assessment of mechanical loadings on pectoral pacemaker implants

Reduced sizes of implantable cardiac pacemakers and clinical advances have led to a higher feasibility of using such devices in younger patients including children. Increased structural demands deriving from reduced device size and more active recipients require detailed knowledge of in vivo mechanical conditions to ensure device reliability. Objective of this study was the proof of feasibility of a system for the measurement of in vivo mechanical loadings on pacemaker implants. The system comprised the following: implantable instrumented pacemaker (IPM) with six force sensors, accelerometer and radio-frequency (RF) transceiver; RF data logging system and video capture system. Three Chacma baboons (20.6±1.15 kg) received one pectoral sub-muscular IPM implant. After wound healing, forces were measured during physical activities. Forces during range of motion of the arm were assessed on the anaesthetized animals prior to device explantation. Mass, volume and dimensions of the excised Pectoralis major muscles were determined after device explantation. Remote IPM activation and data acquisition were reliable in the indoor cage environment with transceiver distances of up to 3 m. Sampling rates of up to 1000 Hz proved sufficient to capture dynamic in vivo loadings. Compressive forces on the IPM in conscious animals reached a maximum of 77.2±54.6 N during physical activity and were 22.2±7.3 N at rest, compared with 34.6±15.7 N maximum during range of motion and 13.4±3.3 N at rest in anaesthetized animals. The study demonstrated the feasibility of the developed system for the assessment of in vivo mechanical loading conditions of implantable pacemakers with potential for use for other implantable therapeutic devices.     

The Caenorhabditis elegans P21-activated kinases are differentially required for UNC-6/netrin-mediated commissural motor axon guidance

P21 activated kinases (PAKs) are major downstream effectors of rac-related small GTPases that regulate various cellular processes. We have identified the new PAK gene max-2 in a screen for mutants disrupted in UNC-6/netrin-mediated commissural axon guidance. There are three Caenorhabditis elegans PAKs. We find that each C. elegans PAK represents a distinct group previously identified in other species. Here we examine their roles in the postembryonic migration of the P cell neuroblasts and the axon guidance of the ventral cord commissural motoneurons (VCCMNs). We find that the two PAKs, max-2 and pak-1, are redundantly required for P cell migration and function with UNC-73/Trio and the rac GTPases (CED-10 and MIG-2). During axon guidance of the VCCMNs, PAK-1 also acts with the rac GTPases, CED-10 and MIG-2, and is completely redundant with MAX-2. Interestingly, we find that unlike MAX-2 activity during P cell migration, for motoneuron axon guidance max-2 is also required in parallel to this PAK-1 pathway, independent of rac GTPase signaling. Finally, we provide evidence that MAX-2 functions downstream of the UNC-6/netrin receptor UNC-5 during axon repulsion and is an integral part of its signaling.     

Minimization of aggregation of secreted bivalent anti-human T cell immunotoxin in Pichia pastoris bioreactor culture by optimizing culture conditions for protein secretion

In a bioreactor culture of genetically engineered Pichia pastoris secreting a bivalent immunotoxin, 64% of the secreted immunotoxin was present in aggregate forms and this resulted in a loss of bioactivity. Biochemical analyses of the secreted immunotoxin and an in vitro aggregation study using purified monomeric immunotoxin suggested that aggregation was primarily an extracellular event. By employing limited methanol feeding at 0.75 mlmin(-1) per 10l initial medium, oxygen consumption was reduced, permitting a lowering of the bioreactor agitation speed from 800 to 400 rpm. By increasing the anti-foam reagent to 0.6 mll(-1), the thickness of the air/liquid interfacial foam layer was reduced by 80%. These steps reduced the immunotoxin aggregates from 64% to 5%. Consequently immunotoxin purification yield was increased from 53.0% to 73.8%. Simultaneously this methodology enhanced immunotoxin secretion to 120 mgl(-1) at 163 h of methanol induction in a toxin resistant production strain. We conclude that minimizing shearing force and reducing the air/liquid interfacial foam area are crucial factors in reducing hydrophobic protein aggregation upon secretory expression in yeast bioreactor cultures.     

Sulfisoxazole, an endothelin receptor antagonist, protects retinal neurones from insults of ischemia/reperfusion or lipopolysaccharide

Endothelins exert pathological effects in the eye and much interest centres on their role in causing retinal neuronal death in ischemic diseases like glaucoma. In the present study the influence of the non-selective endothelin antagonist, sulfisoxazole on raised intraocular pressure-induced ischemia to the rat retina was investigated. Moreover, in vitro studies on primary rat retinal cultures were undertaken to see whether sulfisoxazole is able to blunt the toxic effect of lipopolysaccharide (LPS) to retinal neurones.

In order to determine whether sulfisoxazole provides protection to the retina the a- and b-wave amplitudes of the electroretinogram (ERG), the localisation of retinal choline acetyltransferase (ChAT), nitric oxide synthase (nNOS) and Thy-1 and the retinal mRNA levels of Thy-1 and FGF-2 were deduced in retinas subjected to ischemia in the absence or presence of sulfisoxazole. The results showed that the ischemia-induced changes to the a- and b-wave amplitudes of the ERG and changes associated with the localisation of ChAT, nNOS and Thy-1 to be significantly blunted by sulfisoxazole. However, while the ischemia-induced changes to Thy-1 and FGF-2 mRNAs were reduced by sulfisoxazole, the reduction was non-significant.

The in vitro studies provided support for the protective effect of sulfisoxazole. Here, it was clearly shown that sulfisoxazole attenuated the elevation of nitric oxide (deduced by measuring nitrite) and the reduction in numbers of GABA-containing neurones caused by LPS.

The present study provides evidence for the first time that endothelin antagonist can protect the retina from ischemic-like insults as occurs in glaucoma.     

Avoiding Spurious Submovement Decompositions II: A Scattershot Algorithm

Evidence for the existence of discrete submovements underlying continuous human movement has motivated many attempts to “extract” them. Although they produce visually convincing results, all of the methodologies that have been employed are prone to produce spurious decompositions. In previous work, a branch-and-bound algorithm for submovement extraction, capable of global nonlinear minimization, and hence, capable of avoiding spurious decompositions, was presented [Rohrer and Hogan (Biol Cybern 39:190–199, 2003)]. Here, we present a scattershot-type global nonlinear minimization algorithm that requires approximately four orders of magnitude less time to compute. A sensitivity analysis reveals that the scattershot algorithm can reliably detect changes in submovement parameters over time, e.g., over the course of neuromotor recovery.     

Interactions Between Pattern Formation and Domain Growth

In this paper we develop a theoretical framework for investigating pattern formation in biological systems for which the tissue on which the spatial pattern resides is growing at a rate which is itself regulated by the diffusible chemicals that establish the spatial pattern. We present numerical simulations for two cases of interest, namely exponential domain growth and chemically controlled growth. Our analysis reveals that for domains undergoing rapid exponential growth dilution effects associated with domain growth influence both the spatial patterns that emerge and the concentration of chemicals present in the domain. In the latter case, there is complex interplay between the effects of the chemicals on the domain size and the influence of the domain size on the formation of patterns. The nature of these interactions is revealed by a weakly nonlinear analysis of the full system. This yields a pair of nonlinear equations for the amplitude of the spatial pattern and the domain size. The domain is found to grow (or shrink) at a rate that depends quadratically on the pattern amplitude, the particular functional forms used to model the local tissue growth rate and the kinetics of the two diffusible species dictating the resulting behaviour.     

Analysis of major intracellular proteins of Aspergillus fumigatus by MALDI mass spectrometry: identification and characterisation of an elongation factor 1B protein with glutathione transferase activity

Aspergillus fumigatus is a recognised human pathogen, especially in immunocompromised individuals. The availability of the annotated A. fumigatus genome sequence will significantly accelerate our understanding of this organism. However, limited information is available with respect to the A. fumigatus proteome. Here, both a direct proteomic approach (2D-PAGE and MALDI-MS) and a sub-proteomic strategy involving initial glutathione affinity chromatography have been deployed to identify 54 proteins from A. fumigatus primarily involved in energy metabolism and protein biosynthesis. Furthermore, two novel eukaryotic elongation factor proteins (eEF1Bgamma), termed ElfA and B have been identified and phylogenetically confirmed to belong to the eEF1Bgamma class of GST-like proteins. One of these proteins (ElfA) has been purified to homogeneity, identified as a monomeric enzyme (molecular mass=20 kDa; pI=5.9 and 6.5), and found to exhibit glutathione transferase activity specific activities (mean+/-standard deviation, n=3) of 3.13+/-0.27 and 3.43+/-1.0 micromol/min/mg, using CDNB and ethacrynic acid, respectively. Overall, these data highlight the importance of new approaches to dissect the proteome of, and elucidate novel functions within, A. fumigatus.