A unified theory for the energy cost of legged locomotion

Small animals are remarkably efficient climbers but comparatively poor runners, a well-established phenomenon in locomotor energetics that drives size-related differences in locomotor ecology yet remains poorly understood. Here, I derive the energy cost of legged locomotion from two complementary components of muscle metabolism, Activation–Relaxation and Cross-bridge cycling. A mathematical model incorporating these costs explains observed patterns of locomotor cost both within and between species, across a broad range of animals (insects to ungulates), for a wide range of substrate slopes including level running and vertical climbing. This ARC model unifies work- and force-based models for locomotor cost and integrates whole-organism locomotor cost with cellular muscle physiology, creating a predictive framework for investigating evolutionary and ecological pressures shaping limb design and ranging behaviour.     

Proteolytic Remodeling of the Synaptic Cell Adhesion Molecules (CAMs) by Metzincins in Synaptic Plasticity

Cell adhesion molecules participate in the formation, maturation, function and plasticity of synaptic connections. The growing body of evidence indicates that in the regulation of the synaptic plasticity, in which these molecules play pivotal role, also the proteolytic processes are involved. This review focuses on extracellular proteolysis of the cell adhesion molecules by specific subgroup of the matrix metalloproteinases, a disintegrin and metalloproteases and a disintegrin and metalloproteinase with thrombospondin motifs, jointly referred to as metzincins, in driving coordinated synaptic structural and functional modifications underlying synaptic plasticity in the adult brain.     

Cryptic speciation in the field vole: a multilocus approach confirms three highly divergent lineages in Eurasia

Species are generally described from morphological features, but there is growing recognition of sister forms that show substantial genetic differentiation without obvious morphological variation and may therefore be considered ‘cryptic species’. Here, we investigate the field vole (Microtus agrestis), a Eurasian mammal with little apparent morphological differentiation but which, on the basis of previous sex‐linked nuclear and mitochondrial DNA (mtDNA) analyses, is subdivided into a Northern and a Southern lineage, sufficiently divergent that they may represent two cryptic species. These earlier studies also provided limited evidence for two major mtDNA lineages within Iberia. In our present study, we extend these findings through a multilocus approach. We sampled 163 individuals from 46 localities, mainly in Iberia, and sequenced seven loci, maternally, paternally and biparentally inherited. Our results show that the mtDNA lineage identified in Portugal is indeed a distinct third lineage on the basis of other markers as well. In fact, multilocus coalescent‐based methods clearly support three separate evolutionary units that may represent cryptic species: Northern, Southern and Portuguese. Divergence among these units was inferred to have occurred during the last glacial period; the Portuguese lineage split occurred first (estimated at c. 70 000 bp ), and the Northern and Southern lineages separated at around the last glacial maximum (estimated at c. 18 500 bp ). Such recent formation of evolutionary units that might be considered species has repercussions in terms of understanding evolutionary processes and the diversity of small mammals in a European context.     

Cloning of nisin resistance determinant and replication origin on 7.6-kilobase EcoRI fragment of pNP40 from Streptococcus lactis subsp. diacetylactis DRC3

The nisin resistance determinant and an origin of replication on pNP40, a plasmid of about 60 kilobases that is present in Streptococcus lactis subsp. diacetylactis DRC3, was cloned on a 7.6-kilobase EcoRI fragment. When self-ligated, this fragment existed as an independent replicon (pFM011) and contained a 2.6-kilobase EcoRI-XbaI fragment encoding nisin resistance.     

M-MuLV-induced leukemogenesis: Integration and structure of recombinant proviruses in tumors

M-MuLV-specific DNA probes were used to establish the state of integration and amplification of recombinant proviral sequences in Moloney virus-induced tumors of Balb/Mo, Balb/c and 129 mice. The somatically acquired viral sequences contain both authentic M-MuLV genomes and recombinants of M-MuLV with endogenous viral sequences. All reintegrated genomes carry long terminal repeat (LTR) sequences at both termini of their genome. In the preleukemic stage a large population of cells exhibiting a random distribution of reintegrated M-MuLV genomes are seen, but during outgrowth of the tumor, selection of cells occurs leaving one or a few clonal descendants in the outgrown tumor. In this latter stage recombinant genomes can be detected. Although these recombinants constitute a heterogeneous group of proviruses, characteristic molecular markers are conserved among many individual proviral recombinants, lending credence to the notion that a certain recombinant structure is a prerequisite for the onset of neoplasia. The structure of these recombinants shows close structural similarities to the previously described mink cell focus-inducing (MCF)-type viruses.     

Maintenance procedures for the curtailment of genetic instability: Xanthomonas campestris NRRL B-1459.

Characteristics are described of small-colony variants of Xanthomonas campestris NRRL B-1459 which are frequently encountered when routine culture maintenance procedures are employed. In contrast to the parental type, smallcolony variants were shown to be resistant to a number of antibiotics, to acridine orange, and to phage which are virulent for the parent colony type. Sensitivity to ultraviolet radiation was similar in both colony types. A simple method for preservation of viable cells is described. The suitability of the method for providing reproducible inocula free from variant cell types is examined.     

A multisensory integration model of human stance control

A model is presented to study and quantify the contribution of all available sensory information to human standing based on optimal estimation theory. In the model, delayed sensory information is integrated in such a way that a best estimate of body orientation is obtained. The model approach agrees with the present theory of the goal of human balance control. The model is not based on purely inverted pendulum body dynamics, but rather on a three-link segment model of a standing human on a movable support base. In addition, the model is non-linear and explicitly addresses the problem of multisensory integration and neural time delays. A predictive element is included in the controller to compensate for time delays, necessary to maintain erect body orientation. Model results of sensory perturbations on total body sway closely resemble experimental results. Despite internal and external perturbations, the controller is able to stabilise the model of an inherently unstable standing human with neural time delays of 100 ms. It is concluded, that the model is capable of studying and quantifying multisensory integration in human stance control. We aim to apply the model in (1) the design and development of prostheses and orthoses and (2) the diagnosis of neurological balance disorders. Received: 25 August 1997 / Accepted in revised form: 8 December 1998     

Mycobacterium tuberculosis ClpX Interacts with FtsZ and Interferes with FtsZ Assembly

FtsZ assembly at the midcell division site in the form of a Z-ring is crucial for initiation of the cell division process in eubacteria. It is largely unknown how this process is regulated in the human pathogen Mycobacterium tuberculosis. Here we show that the expression of clpX was upregulated upon macrophage infection and exposure to cephalexin antibiotic, the conditions where FtsZ-ring assembly is delayed. Independently, we show using pull-down, solid-phase binding, bacterial two-hybrid and mycobacterial protein fragment complementation assays, that M. tuberculosis FtsZ interacts with ClpX, the substrate recognition domain of the ClpXP protease. Incubation of FtsZ with ClpX increased the critical concentration of GTP-dependent polymerization of FtsZ. Immunoblotting revealed that the intracellular ratio of ClpX to FtsZ in wild type M. tuberculosis is approximately 1∶2. Overproduction of ClpX increased cell length and modulated the localization of FtsZ at midcell sites; however, intracellular FtsZ levels were unaffected. A ClpX-CFP fusion protein localized to the cell poles and midcell sites and colocalized with the FtsZ-YFP protein. ClpX also interacted with FtsZ mutant proteins defective for binding to and hydrolyzing GTP and possibly for interactions with other proteins. Taken together, our results suggest that M. tuberculosis ClpX interacts stoichiometrically with FtsZ protomers, independent of its nucleotide-bound state and negatively regulates FtsZ activities, hence cell division.