Establishment of visceral left-right asymmetry in mammals: The role of ciliary action and leftward fluid flow in the region of Hensen’s node

During individual development of vertebrates, the anteroposterior, dorsoventral, and left-right axes of the body are established. Although the vertebrates are bilaterally symmetric outside, their internal structure is asymmetric. Of special interest is the insight into establishment of visceral left-right asymmetry in mammals, since it has not only basic but also an applied medical significance. As early as 1976, it was hypothesized that the ciliary action could be associated with the establishment of left-right asymmetry in mammals. Currently, the majority of researchers agree that the ciliary action in the region of Hensen’s node and the resulting leftward laminar fluid flow play a key role in the loss of bilateral symmetry and triggering of expression of the genes constituting the Nodal-Ptx2 signaling cascade, specific of the left side of the embryo. The particular mechanism underlying this phenomenon is still insufficiently clear. There are three competing standpoints on how leftward fluid flow induces expression of several genes in the left side of the embryo. The morphogen gradient hypothesis postulates that the leftward flow creates a high concentration of a signaling biomolecule in the left side of Hensen’s node, which, in turn, stimulates triggering of gene expression of the Nodal-Ptx2 cascade. The biomechanical hypothesis (or two-cilia model) states that the immotile cilia located in the periphery of Hensen’s node act as mechanosensors, activate mechanosensory ion channels, and trigger calcium signaling in the left side of the embryo. Finally, the “shuttle-bus model” holds that left-ward fluid flow carries the lipid vesicles, which are crashed when colliding immotile cilia in the periphery of Hensen’s node to release the contained signaling biomolecules. It is also noteworthy that the association between the ciliary action and establishment of asymmetry has been recently discovered in representatives of the lower invertebrates. In this paper, the author considers evolution of concepts on the mechanisms underlying establishment of visceral left-right asymmetry since 1976 until the present and critically reexamines the current concepts in this field of science. According to the author, serious arguments favoring the biomechanical hypothesis for determination of left-right asymmetry in mammals have been obtained.     

The role of interfragmentary strain on the rate of bone healing—A new interpretation and mathematical model

It is postulated that there is a causal relationship between mechanical stimulus and the rate of bone healing post fracture. However, despite numerous experimental studies in the literature, no quantifiable relationship has been proposed. It is hypothesized in the present study that the temporal rate of bone fracture healing, measured in terms of callus stiffening per week, can be described mathematically based on the relative motions between bone fragments at the initial stage of the healing process. To test this, a comparative reanalysis of experimental data found in the literature was conducted. These individual data sets described a relationship between an initial intermittently applied peak interfragmentary strain and the change in interfragmentary motion or the increase in callus stiffness over time. The data were converted into a relative increase in stiffness, which normalised the results and reduced inter-study variability. The rates of healing for the various initial strains were compared, and based on this a mathematical phenomenological model was derived. Error analyses were then performed, which showed a high level of congruence between the in-vivo and simulated rates of healing. The results of the comparative analysis revealed that there is a positive correlation between the rate of callus stiffening and interfragmentary strain. Finally, the proposed model has shown for the first time that a quantifiable cause–and–effect relationship exists between the rate of bone healing and mechanical stimulus.     

Analysis of avian bone response to mechanical loading—Part One: Distribution of bone fluid shear stress induced by bending and axial loading

Mechanical loading-induced signals are hypothesized to be transmitted and integrated by a bone-connected cellular network (CCN) before reaching the bone surfaces where adaptation occurs. Our objective is to establish a computational model to explore how bone cells transmit the signals through intercellular communication. In this first part of the study the bone fluid shear stress acting on every bone cell in a CCN is acquired as the excitation signal for the computational model. Bending and axial loading-induced fluid shear stress is computed in transverse sections of avian long bones for two adaptation experiments (Gross et al. in J Bone Miner Res 12:982-988, 1997 and Judex et al. in J Bone Miner Res 12:1737-1745, 1997). The computed fluid shear stress is found to be correlated with the radial strain gradient but not with bone formation. These results suggest that the radial strain gradient is the driving force for bone fluid flow in the radially distributed lacunar-canalicular system and that bone formation is not linearly related to the loading-induced local stimulus.     

Evolutionary dynamics of cycle length in pearl millet: the role of farmer��s practices and gene flow

In the Sahel of Africa, farmers often modify their cultivation practices to adapt to environmental changes. How these changes shape the agro-biodiversity is a question of primary interest for the conservation of plant genetic resources. We addressed this question in a case study on pearl millet in south western Niger where farmers used to cultivate landraces with different cycle length in order to cope with rain uncertainty. Early and late landraces were previously grown on distant fields. Nowadays, mostly because of human population pressure and soil impoverishment, it happens that the two types of landraces are grown on adjacent fields, opening the question whether gene flow between them may occur. This question was tackled through a comparative study among contrasting situations pertaining to the spatial distribution of early and late landraces. Observations of flowering periods showed that pollen flow between the two landraces is possible and has a preferential direction from early to late populations.     

Peristaltic flow of Walter’s B fluid in a uniform inclined tube

In this investigation, peristaltic flow of Walter’s B fluid in a uniform inclined tube is discussed. The formulation of the problem is made in a cylindrical coordinate system. The analytical solutions have been calculated by using a regular perturbation method by taking δ as the perturbation parameter. The expressions for pressure rise and friction forces were calculated using numerical integration. The graphical results are presented to discuss the various physical quantities of the Walter’s B fluid parameter α, amplitude ratio φ, angle of inclination β and wave length δ.     

Limited genetic differentiation among breeding,molting, and wintering groups of the threatened Steller’s eider: the role of historic and contemporary factors

Due to declines in the Alaska breeding population, the Steller’s eider (Polysticta stelleri) was listed as threatened in North America in 1997. Periodic non-breeding in Russia and Alaska has hampered field-based assessments of behavioral patterns critical to recovery plans, such as levels of breeding site fidelity and movements among three regional populations: Atlantic-Russia, Pacific-Russia and Alaska. Therefore, we analyzed samples from across the species range with seven nuclear microsatellite DNA loci and cytochrome b mitochondrial (mt)DNA sequence data to infer levels of interchange among sampling areas and patterns of site fidelity. Results demonstrated low levels of population differentiation within Atlantic and Pacific nesting areas, with higher levels observed between these regions, but only for mtDNA. Bayesian analysis of microsatellite data from wintering and molting birds showed no signs of sub-population structure, even though band-recovery data suggests multiple breeding areas are present. We observed higher estimates of F-statistics for female mtDNA data versus male data, suggesting female-biased natal site fidelity. Summary statistics for mtDNA were consistent with models of historic population expansion. Lack of spatial structure in Steller’s eiders may result largely from insufficient time since historic population expansions for behaviors, such as natal site fidelity, to isolate breeding areas genetically. However, other behaviors such as the periodic non-breeding observed in Steller’s eiders may also play a more contemporary role in genetic homogeneity, especially for microsatellite loci.     

Going with the flow: a brief history of the study of the honeybee’s navigational ‘odometer’

Honeybees navigate to a food source using a sky-based compass to determine their travel direction, and an odometer to register how far they have travelled. The past 20 years have seen a renewed interest in understanding the nature of the odometer. Early work, pioneered by von Frisch and colleagues, hypothesized that travel distance is measured in terms of the energy that is consumed during the journey. More recent studies suggest that visual cues play a role as well. Specifically, bees appear to gauge travel distance by sensing the extent to which the image of the environment moves in the eye during the journey from the hive to the food source. Most of the evidence indicates that travel distance is measured during the outbound journey. Accumulation of odometric errors is restricted by resetting the odometer every time a prominent landmark is passed. When making detours around large obstacles, the odometer registers the total distance of the path that is flown to the destination, and not the “bee-line” distance. Finally, recent studies are revealing that bees can perform odometry in three dimensions.     

Elastic behavior of a red blood cell with the membrane’s nonuniform natural state: equilibrium shape,motion transition under shear flow,and elongation during tank-treading motion

Direct numerical simulations of the mechanics of a single red blood cell (RBC) were performed by considering the nonuniform natural state of the elastic membrane. A RBC was modeled as an incompressible viscous fluid encapsulated by an elastic membrane. The in-plane shear and area dilatation deformations of the membrane were modeled by Skalak constitutive equation, while out-of-plane bending deformation was formulated by the spring model. The natural state of the membrane with respect to in-plane shear deformation was modeled as a sphere ( \(\alpha =0\) ), biconcave disk shape ( \(\alpha =1\) ) and their intermediate shapes ( \(0<\alpha <1\) ) with the nonuniformity parameter \(\alpha \) , while the natural state with respect to out-of-plane bending deformation was modeled as a flat plane. According to the numerical simulations, at an experimentally measured in-plane shear modulus of \(2.5\times 10^{-6}\,\hbox {N}/\hbox {m}\) and an out-of-plane bending rigidity of \(2.0\times 10^{-19}\,\hbox {N}\cdot \hbox {m}\) of the cell membrane, the following results were obtained. (i) The RBC shape at equilibrium was biconcave discoid for \(\alpha >0.22\) and cupped otherwise; (ii) the experimentally measured fluid shear stress at the transition between tumbling and tank-treading motions under shear flow was reproduced for \(0.05<\alpha <0.34\) ; (iii) the elongation deformation of the RBC during tank-treading motion from the simulation was consistent with that from in vitro experiments, irrespective of the \(\alpha \) value. Based on our RBC modeling, the three phenomena (i), (ii), and (iii) were mechanically consistent for \(0.22<\alpha <0.34\) . The condition \(0.05<\alpha <0.22\) precludes a biconcave discoid shape at equilibrium (i); however, it gives appropriate fluid shear stress at the motion transition under shear flow (ii), suggesting that a combined effect of \(\alpha \) and the natural state with respect to out-of-plane bending deformation is necessary for understanding details of the RBC mechanics at equilibrium. Our numerical results demonstrate that moderate nonuniformity in a membrane’s natural state with respect to in-plane shear deformation plays a key role in RBC mechanics.     

Neurophysiological aspects of the regulation of the head’s position in the normal state and left- and right-sided forms of spasmodic torticollis

We have studied the spatiotemporal distribution of coherent EEG links in 10 healthy right-handed subjects under the conditions of comfortable wakefulness with a straight position of the head and with the head voluntarily turned to fixed left and right positions. The computations were made separately in each standard range of EEG frequencies (Δ, θ, α, and β). The results were compared with the data obtained during studies of right-handed patients with right-sided (RS, n = 9) and left-sided (LS; n = 8) forms of spasmodic torticollis (ST). It has been shown that, upon a voluntary right turn of the head, the number of strong and moderate coherent EEG links in healthy subjects increases considerably more than upon a left turn. This may be accounted for by the greater functional importance of the control of the right part of the visual space as the area of manipulation of the dominant hand. In patients with RS ST, the number of intra- and interhemispheric strong and moderate coherent EEG links increased in all four frequency ranges, as compared to healthy subjects, upon the right turn of the head. In patients with LS ST, the spatial structure of the bioelectric potential field of the brain is less reorganized upon the voluntary left turn of the head as compared to the level of coherent EEG links in healthy subjects. Presumably, this phenomenon reflects a stronger insufficiency of neurophysiological mechanisms of postural control and compensation for its disturbances in patients with the LS form of ST, which results in a more severe disability as compared to patients with right-sided ST.     

Update on the role of molecular factors and fibroblasts in the pathogenesis of Dupuytren’s disease

The mechanism by which the fibroblast is able to trigger palmar fibromatosis is still not yet fully understood. It would appear certain that the “abnormal” fibroblasts continuously synthesise profibrotic cytokines which are able to determine the activation to myofibroblasts, to stimulate them to the further proliferation and synthesis of other cytokines, to modify the cells’ differentiation and ultrastructural characteristics, as well as the production of matrix and other proteins. Several fibroblast growth factors have been suggested to be responsible of an abnormal cell activation with an aberrantly elevated collagen synthesis and extracellular deposition in Dupuytren’s disease, as TGF-Beta, TNF-Alfa, PDGF, GM-CSF, free radicals, metalloproteinases, sex hormones, gene modified expression, mechanical stimulation. The Authors review the current state of knowledge in the field, by analyzing the role of these cytokines in the palmar fibromatosis.     

Effect of hematocrit on wall shear rate in oscillatory flow: do the elastic properties of blood play a role?

Porcine blood was used to examine the relationship between hematocrit levels and wall shear rate patterns in straight and curved artery models under fixed oscillatory flow conditions characteristic of larger arteries. It is demonstrated that porcine blood models both the viscous and elastic components of the 2 Hz complex viscosity of human blood quite accurately over a broad range of shear rates (1-1000 s-1) and hematocrits (20%-80%). For a fixed oscillatory flow waveform (Poiseuille peak shear rate = 168 s-1; mean shear rate 84 s-1), increases in hematocrit produced a decrease in the peak wall shear rate in both the straight and curved artery models and a corresponding decrease in wall shear rate reversal on the inside wall of the curved artery model. The same trends were also observed for oscillatory flows of aqueous glycerin solutions of increasing viscosity in the range of viscosity of the blood samples tested. Aqueous glycerin solutions produced wall shear rate waveforms of the same magnitude and shape as the porcine blood. This indicates that variations in the shear rate, and therefore the shear stress, were caused primarily by changes in the viscous and not the elastic properties of blood. The results suggest that simple Newtonian fluids may be sufficient for in vitro determination of the first order effects to be expected of human blood flow in large vessels having complex geometries and shear rates in or above the range of the present study.     

Visualization of Reinke’s crystals in normal and cryptorchid testis

Within the human testis, Reinke’s crystals are found in Leydig cells but their nature and function are poorly understood. The aim of our study was to investigate the properties of Reinke’s crystals in man with the normal morphology of the testis (control group) and infertile patients diagnosed with cryptorchidism. 20 biopsies from infertile patients and six biopsies from men with regular spermatogenesis (20–30 years.) were used. Sections of the testis tissue were stained with haematoxylin and eosin and a modified Masson’s method. Specimens were observed by bright field, confocal and transmission electron microscopy (TEM). The number of Reinke’s crystals in investigated groups was determined applying stereological methods. In both groups, Reinke’s crystals were noted within the cytoplasm and nuclei of Leydig cells. Some “free” crystals were found within the interstitial space, outside Leydig cells. Confocal microscopy proved to be very useful in the assessment of the shape and 3D reconstruction of the crystal. TEM analysis confirmed a hexagonal form of the crystal, while crystallographic data on sections of 70–300 nm thickness provided a better insight into the organization of the crystal lattice. Stereological analysis revealed a significant increase in the number of crystals in cryptorchid testes when compared with controls. Increased number of crystals in cryptorchid specimens leads to the assumption that the prolonged exposure to higher (abdominal) temperature might stimulate enzymes involved in the synthesis of the proteins of the crystal. However, the exact molecular nature of the crystal lattice remains in both normal and cryptorchid testis obscure.     

Infant monkeys’ concept of animacy: the role of eyes and fluffiness

Both human and nonhuman primates have been suggested to possess some essential knowledge about animate entities, but it remains unclear whether the concept of animacy is shared across species, which properties are used as an "animacy marker," and whether such ability is present at birth. We investigated infant Japanese monkeys' looking responses towards novel objects varying in both physical appearance and self-propelled motion, with the aim of depicting the role of eyes and fluffiness in the early recognition of animacy. Presented with an inanimate natural stone, three-month-old monkeys showed longer looking times at the stone's self-propelled motion than at its baseline still posture. This effect became significantly smaller when artificial fur was attached to the stone, while adding artificial eyes did not elicit a departing pattern in their looking behavior. In contrast, one-month-old monkeys showed no systematic differences in their looking behavior. This suggests that the concept of animacy in terms of self-propelledness may develop between one and three?months of age, with sensitivity to texture emerging by three?months. Development of biological knowledge is discussed in relation to social knowledge from both ontogenetic and phylogenetic perspectives.