Is it legitimate to characterize muscle strength using a limited number of measures?

The purpose of this systematic review was to examine the legitimacy of using a single measure or a small set of measures of strength to characterize an individual's overall strength. Briefly, the methods involved: (a) a search of electronic databases, article reference lists, and personal files to identify relevant literature; and (b) a summarizing of that literature. As a result of the searches, 25 relevant articles were identified. The articles reported correlation coefficients, Cronbach's alpha, and factor analysis. Together, these statistics suggest a tendency for different strength measures to be related. A close examination of the relationships, however, suggests that caution should be exercised in characterizing overall strength using a single measure such as grip strength. In conclusion, it may be legitimate to use one or several measures obtained from a single limb to characterize the strength of that limb but not the entire body. What this means practically is that the practitioner interested in characterizing strength of a limb can reduce test burden by testing a limited number of muscle actions of that limb.     

Is Atlantic salmon production limited by number of territories?

Thirty Atlantic salmon Salmo salar parr (mean 135 mm total length, L _T) in the River Alta, Norway, were radio‐tagged and tracked during a 11–13 day period. The parr stayed within defined home ranges with a 95% probability of localization within an average area of 1286 m²(241–3484 m²). On average, each parr had overlapping home ranges with 7·7 other parr, and the overlap between pairs of fish covered on average 24% of their home range areas. Mean length of the river stretch used was 90 m (22–383 m). On average, during 38%(16–77%) of the tracking surveys, the fish had moved >10 m since the previous survey. Mean total distance moved during the whole study was 402 m (208–862 m). The Atlantic salmon were most often recorded in riffles, but 27% of the parr alternated between riffles and pools. The extensive movements, flexible habitat utilization and relatively large home ranges, together with the fact that all the parr had home ranges partly overlapping with other radio‐tagged parr, indicate a flexible and variable behaviour and, thereby, a more complex social structure than a rigid defence of a fixed territory. Thus, Atlantic salmon production seems not to be limited by the highest potential number of territories for large parr in a given area.     

May photoinhibition be a consequence, rather than a cause, of limited plant productivity?

Photoinhibition in leaves in response to high and/or excess light, consisting of a decrease in photosynthesis and/or photosynthetic efficiency, is frequently equated to photodamage and often invoked as being responsible for decreased plant growth and productivity. However, a review of the literature reveals that photoinhibited leaves characterized for foliar carbohydrate levels were invariably found to possess high levels of sugars and starch. We propose that photoinhibition should be placed in the context of whole-plant source–sink regulation of photosynthesis. Photoinhibition may represent downregulation of the photosynthetic apparatus in response to excess light when (1) more sugar is produced in leaves than can be utilized by the rest of the plant and/or (2) more light energy is harvested than can be utilized by the chloroplast for the fixation of carbon dioxide into sugars.     

Janus-faced autophagy: a dual role of cellular self-eating in neurodegeneration?

Autophagy is a highly regulated cellular pathway used by eukaryotic cells to consume parts of their constituents during development or starvation. It is associated with extensive rearrangements of intracellular membranes, and involves the cooperation of many gene products in the regulation and execution phase by largely unknown mechanisms. Recent results strongly indicate the role of autophagy in the degradation of damaged macromolecules, in particular misfolded, aberrant proteins, and in organelle turnover; in mutant mice with reduced autophagy, accumulation of abnormal cytosolic proteins as inclusion bodies and massive cell loss occur similarly to human neurodegenerative disorders. Thus, autophagy seems to prevent neurons from undergoing protein aggregation-induced degeneration. In contrast, we have shown that inactivation of genes involved in autophagosome formation suppresses neuronal demise induced by various hyperactivating ion channel mutations or by neurotoxins in the nematode Caenorhabditis elegans. These results raise the possibility that autophagy may also contribute to excitotoxic necrotic-like cell death. This way, autophagic degradation of cytoplasmic materials might have a dual role in the survival of neurons. Depending on the actual cellular milieu and insulting factor, it can act both as a protector and contributor to neuronal damage.     

Is productivity of mesic savannas light limited or water limited? Results of a simulation study

A soil–plant–atmosphere model was used to estimate gross primary productivity (GPP) and evapotranspiration (ET) of a tropical savanna in Australia. This paper describes model modifications required to simulate the substantial C4 grass understory together with C3 trees. The model was further improved to include a seasonal distribution of leaf area and foliar nitrogen through 10 canopy layers. Model outputs were compared with a 5‐year eddy covariance dataset. Adding the C4 photosynthesis component improved the model efficiency and root‐mean‐squared error (RMSE) for total ecosystem GPP by better emulating annual peaks and troughs in GPP across wet and dry seasons. The C4 photosynthesis component had minimal impact on modelled values of ET. Outputs of GPP from the modified model agreed well with measured values, explaining between 79% and 90% of the variance and having a low RMSE (0.003–0.281 g C m^?2 day^?1). Approximately, 40% of total annual GPP was contributed by C4 grasses. Total (trees and grasses) wet season GPP was approximately 75–80% of total annual GPP. Light‐use efficiency (LUE) was largest for the wet season and smallest in the dry season and C4 LUE was larger than that of the trees. A sensitivity analysis of GPP revealed that daily GPP was most sensitive to changes in leaf area index (LAI) and foliar nitrogen (N_f) and relatively insensitive to changes in maximum carboxylation rate (V_cmax), maximum electron transport rate (J_max) and minimum leaf water potential (ψ_min). The modified model was also able to represent daily and seasonal patterns in ET, (explaining 68–81% of variance) with a low RMSE (0.038–0.19 mm day^?1). Current values of N_f, LAI and other parameters appear to be colimiting for maximizing GPP. By manipulating LAI and soil moisture content inputs, we show that modelled GPP is limited by light interception rather than water availability at this site.     

The nucleo-junctional interplay of the cellular prion protein: A new partner in cancer-related signaling pathways?

The cellular prion protein PrP^c plays important roles in proliferation, cell death and survival, differentiation and adhesion. The participation of PrP^c in tumor growth and metastasis was pointed out, but the underlying mechanisms were not deciphered completely. In the constantly renewing intestinal epithelium, our group demonstrated a dual localization of PrP^c, which is targeted to cell-cell junctions in interaction with Src kinase and desmosomal proteins in differentiated enterocytes, but is predominantly nuclear in dividing cells. While the role of PrP^c in the dynamics of intercellular junctions was confirmed in other biological systems, we unraveled its function in the nucleus only recently. We identified several nuclear PrP^c partners, which comprise γ-catenin, one of its desmosomal partners, β-catenin and TCF7L2, the main effectors of the canonical Wnt pathway, and YAP, one effector of the Hippo pathway. PrP^c up-regulates the activity of the β-catenin/TCF7L2 complex and its invalidation impairs the proliferation of intestinal progenitors. We discuss how PrP^c could participate to oncogenic processes through its interaction with Wnt and Hippo pathway effectors, which are controlled by cell-cell junctions and Src family kinases and dysregulated during tumorigenesis. This highlights new potential mechanisms that connect PrP^c expression and subcellular redistribution to cancer.     

Heritability of cellular radiosensitivity: a marker of low-penetrance predisposition genes in breast cancer?

Many inherited cancer-prone conditions show an elevated sensitivity to the induction of chromosome damage in cells exposed to ionizing radiation, indicative of defects in the processing of DNA damage. We earlier found that 40% of patients with breast cancer and 5%-10% of controls showed evidence of enhanced chromosomal radiosensitivity and that this sensitivity was not age related. We suggested that this could be a marker of cancer-predisposing genes of low penetrance. To further test this hypothesis, we have studied the heritability of radiosensitivity in families of patients with breast cancer. Of 37 first-degree relatives of 16 sensitive patients, 23 (62%) were themselves sensitive, compared with 1 (7%) of 15 first-degree relatives of four patients with normal responses. The distribution of radiosensitivities among the family members showed a trimodal distribution, suggesting the presence of a limited number of major genes determining radiosensitivity. Segregation analysis of 95 family members showed clear evidence of heritability of radiosensitivity, with a single major gene accounting for 82% of the variance between family members. The two alleles combine in an additive (codominant) manner, giving complete heterozygote expression. A better fit was obtained to a model that includes a second, rarer gene with a similar, additive effect on radiosensitivity, but the data are clearly consistent with a range of models. Novel genes involved in predisposition to breast cancer can now be sought through linkage studies using this quantitative trait.     

Least-effort pathways?: a GIS analysis of livestock trails in rugged terrain

Livestock trails frequently evolve in pastures when plant growth or establishment cannot keep pace with vegetation disturbance. In some instances, man-made trails are established in rangeland settings to encourage uniform use of forages or facilitate livestock passage through dense vegetation or across rugged terrain. A long-term assumption has been that livestock establish pathways of least resistance between frequented areas of their pastures, but this hypothesis has never been tested. We mapped cattle trails in three 800+ ha pastures with global positioning units. A geographic information system (GIS) helped quantify characteristics of trails and the landscape and was used to plot least-effort pathways between water sources and distant points on selected trails in the pastures. Characteristics of the cattle trails and least-effort pathways were compared to test the hypothesis that cattle develop least-effort routes of travel in rugged terrain. The mean slope of the three pastures was 13.5%, and the average slope of the topography traversed by the cattle trails was 8%. The slope of the trails was reduced to 5.2% by selection of cross-slope routes. When we compared the characteristics of 10 selected cattle trails and least-effort pathways generated by our GIS, the cattle trails were 11% shorter (P=0.046) than the least-effort pathways, and the topography traversed by cattle had a gradient about 1% less than the least-effort pathways (P=0.02). The slope of the selected trails (5.5%) and pathways (5.6%) were similar (P=0.74), however. Analyses of values extracted from cost surfaces indicated that, on the average, 183 units of effort were needed to traverse the trails and 170 units of effort expended to traverse the least-effort pathways (P=0.07). These data support the hypothesis that cattle establish least-effort routes between distant points in rugged terrain and suggest that GIS software may be useful in designing systems of livestock trails in extensive settings.     

Can a hydroxide ligand trigger a change in the coordination number of magnesium ions in biological systems?

Density functional (B3LYP) calculations indicate that a hydroxide ligand is capable of triggering a reduction in the coordination number of Mg(2+) ions from 6 to 5. Since this could be quite relevant in the mode of action of magnesium-containing enzymes (especially hydrolases in which a metal-bound hydroxide species is believed to play a crucial role), we have performed a systematic deprotonation study of biologically relevant magnesium complexes. We explicitly calculated the preferred coordination number of [MgL(1)(x)L(2)(y)L(3)(z)](2)(-)(n) species at the B3LYP/aug-cc-pVTZ level of theory. L(1), L(2), and L(3) represent combinations of water, hydroxide, carboxylate (models Glu and Asp), ammonia ligands (models Lys and His residues), and fluoride ions. As expected, Mg(2+) exclusively prefers an octahedral coordination geometry with H(2)O, HCO(2)(-), or NH(3). Surprisingly, one hydroxide ligand triggers a change to a trigonal bipyramidal geometry. The isoelectronic fluoride ion behaves similarly. When two OH(-) are present, a tetrahedral coordination geometry is preferred. We postulate that a hydroxide (in addition to its role as an active nucleophile) could be employed by magnesium-containing enzymes to trigger a differential coordination behavior.     

How does stochasticity in colonization accelerate the speed of invasion in a cellular automaton model?

We investigate the speed of invasion waves for a single species generated by stochastic short- and/or long-distance colonizations in a time-continuous cellular automaton (CA) model on a two-dimensional homogenous landscape. By simulating the CA models, we demonstrate that stochasticity can dramatically increase the speed of invasion compared to the corresponding deterministic CA model or the corresponding one-dimensional stochastic CA model. To explain this phenomenon, we first develop a mathematical model for the invasion involving only short-distance colonization (i.e., colonization only occurs from the eight adjacent cells), and present several approximation methods for solving the model. Our analyses show that the increased wave speed in the stochastic model is due to irregularity in the shape of the wavefront. Further extension of this model to include long-distance colonization demonstrates that stochasticity influences speeds to even greater extents in this case. Using dimension analysis, we deduced a semi-empirical formula for the speed as a function of three parameters intrinsic to short- and long-distance colonization, which agrees well with simulation results. Based on these results, we discuss how important stochasticity in colonization and spatial dimensionality are in the acceleration of invasion speed.     

Preparation,cellular uptake and angiogenic suppression of shikonin-containing liposomes in?vitro and in?vivo

Shikonin has anticancer activity, but it has not yet been applied into clinical use. In the present study, shikonin was prepared using liposomes. We aimed to examine several aspects of sh-L (shikonin-containing liposomes): preparation, angiogenic suppression and cellular uptake through self-fluorescence. Sh-L were prepared using soybean phospholipid and cholesterol to form the membrane and shikonin was encapsulated into the phospholipid membrane. Three liposomes were prepared with shikonin. They had red fluorescence and were analysed using a flow cytometer. Angiogenic suppression of sh-L was determined using MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide], Transwell tests, chick CAM (chorioallantoic membrane) and Matrigel™ plug assay. MTT assay showed the median IC₅₀ (inhibitory concentrations) as follows: shikonin, sh-L₁ and sh-L₂ were 4.99±0.23, 5.81±0.57 and 7.17±0.69 μM, respectively. The inhibition rates of migration were 53.58±7.05, 46.56±4.36 and 41.19±3.59% for 3.15 μM shikonin, sh-L₁ and sh-L₂, respectively. The results of CAM and Matrigel plug assay demonstrated that shikonin and sh-L can decrease neovascularization. Effect of shikonin was more obvious than sh-L at the same concentration. The results showed that sh-L decreased the toxicity, the rate of inhibition of migration and angiogenic suppression. The cellular uptake of the sh-L could be pictured because of the self-fluorescence. The self-fluorescence will be useful for conducting further research. Sh-L might be an excellent preparation for future clinical application to cancer patients.     

Are aberrant phase transitions a driver of cellular aging?

Why do cells age? Recent advances show that the cytoplasm is organized into many membrane‐less compartments via a process known as phase separation, which ensures spatiotemporal control over diffusion‐limited biochemical reactions. Although phase separation is a powerful mechanism to organize biochemical reactions, it comes with the trade‐off that it is extremely sensitive to changes in physical‐chemical parameters, such as protein concentration, pH, or cellular energy levels. Here, we highlight recent findings showing that age‐related neurodegenerative diseases are linked to aberrant phase transitions in neurons. We discuss how these aberrant phase transitions could be tied to a failure to maintain physiological physical‐chemical conditions. We generalize this idea to suggest that the process of cellular aging involves a progressive loss of the organization of phase‐separated compartments in the cytoplasm.

     

BAR domain proteins—a linkage between cellular membranes,signaling pathways,and the actin cytoskeleton

Actin filament assembly typically occurs in association with cellular membranes. A large number of proteins sit at the interface between actin networks and membranes, playing diverse roles such as initiation of actin polymerization, modulation of membrane curvature, and signaling. Bin/Amphiphysin/Rvs (BAR) domain proteins have been implicated in all of these functions. The BAR domain family of proteins comprises a diverse group of multi-functional effectors, characterized by their modular architecture. In addition to the membrane-curvature sensing/inducing BAR domain module, which also mediates antiparallel dimerization, most contain auxiliary domains implicated in protein-protein and/or protein-membrane interactions, including SH3, PX, PH, RhoGEF, and RhoGAP domains. The shape of the BAR domain itself varies, resulting in three major subfamilies: the classical crescent-shaped BAR, the more extended and less curved F-BAR, and the inverse curvature I-BAR subfamilies. Most members of this family have been implicated in cellular functions that require dynamic remodeling of the actin cytoskeleton, such as endocytosis, organelle trafficking, cell motility, and T-tubule biogenesis in muscle cells. Here, we review the structure and function of mammalian BAR domain proteins and the many ways in which they are interconnected with the actin cytoskeleton.     

Functional alterations in endothelial NO, PGI₂ and EDHF pathways in aorta in ApoE/LDLR⁻/⁻ mice

Adequate endothelial production of nitric oxide (NO), endothelium-derived hyperpolarizing factor (EDHF), and prostacyclin (PGI?) is critical to the maintenance of vascular homeostasis. However, it is not clear whether alterations in each of these vasodilatory pathways contribute to the impaired endothelial function in murine atherosclerosis. In the present study, we analyze the alterations in NO-, EDHF- and PGI?-dependent endothelial function in the thoracic aorta in relation to the development of atherosclerotic plaques in apoE/LDLR?/? mice. We found that in the aorta of 2-month-old apoE/LDLR?/? mice there was no lipid deposition, subendothelial macrophage accumulation; and matrix metalloproteinase (MMP) activity was low, consistent with the absence of atherosclerotic plaques. Interestingly, at this stage the endothelium was already activated and hypertrophic as evidenced by electron microscopy, while acetylcholine-induced NO-dependent relaxation in the thoracic aorta was impaired, with concomitant upregulation of cyclooxygenase-2 (COX-2)/PGI? and EDHF (epoxyeicosatrienoic acids, EETs) pathways. In the aorta of 3-6-month-old apoE/LDLR?/? mice, lipid deposition, macrophage accumulation and MMP activity in the intima were gradually increased, while impairment of NO-dependent function and compensatory upregulation of COX-2/PGI? and EDHF pathways were more accentuated. These results suggest that impairment of NO-dependent relaxation precedes the development of atherosclerosis in the aorta and early upregulation of COX-2/PGI? and EDHF pathways may compensate for the loss of the biological activity of NO.     

Unfolding retinal dystrophies: a role for molecular chaperones?

Inherited retinal dystrophy is a major cause of blindness worldwide. Recent molecular studies have suggested that protein folding and molecular chaperones might play a major role in the pathogenesis of these degenerations. Incorrect protein folding could be a common consequence of causative mutations in retinal degeneration disease genes, particularly mutations in the visual pigment rhodopsin. Furthermore, several retinal degeneration disease genes have recently been identified as putative facilitators of correct protein folding, molecular chaperones, on the basis of sequence homology. We also consider whether manipulation of chaperone levels or chaperone function might offer potential novel therapies for retinal degeneration.     

Is there a fixed number of niches for endoparasites of fish?

Kennedy and Guégan, based on Cornell and Lawton (J Anim Ecol 1992;61:1–12), found a curvilinear relationship (the fundamental form of the relationship for parasite communities) between infracommunity and component community richness, and interpreted this as meaning that only processes acting within the infracommunities can explain the limitation in the number of parasite species in a given host. The research described here shows that an asymptotic relationship is the consequence of the differential likelihoods of parasite species to appear in an infracommunity as determined by transmission rates and intrinsic lifespans. Processes operating at the infracommunity level are not necessary to explain the curvilinear relationship. Even communities much richer than those found in European freshwater fishes cannot be assumed to be saturated in the sense that further species cannot be added over evolutionary time.