Cortical potentials evoked to response to a signal to make a memory-guided saccade

The difference in parameters of visually guided and memory-guided saccades was shown. Increase in the memory-guided saccade latency as compared to that of the visually guided saccades may indicate the deceleration of saccadic programming on the basis of information extraction from the memory. The comparison of parameters and topography of evoked components N1 and P1 of the evoked potential on the signal to make a memory- or visually guided saccade suggests that the early stage of the saccade programming associated with the space information processing is performed predominantly with top-down attention mechanism before the memory-guided saccade and bottom-up mechanism before the visually guided saccade. The findings show that the increase in the latency of the memory-guided saccades is connected with decision making at the central stage of the saccade programming. We proposed that wave N2, which develops in the middle of the latent period of the memory-guided saccades, is correlated with this process. Topography and spatial dynamics of components N1, P1 and N2 testify that the memory-guided saccade programming is controlled by the frontal mediothalamic system of selective attention and left-hemispheric brain mechanisms of motor attention.     

From a homeostatic to a homeodynamic self

Life as an autonomous homeostatic system is discussed. A mechanism that drives a homeostatic state to an autonomous self-moving state is examined with two computational cell models. The mechanism is met with Ashby's ultrastability, where random parameter searching is activated when a system breaks a viability constraint. Such a random search process is replaced by the membrane shape in the first model and by chaotic population dynamics in the second model. Emergence of sensors, motors and the recursive coupling between them is shown to be a natural outcome of an autonomous homeostatic system.     

Adhesion-mediated mechanosensitivity: a time to experiment, and a time to theorize

Adhesion-mediated signaling provides cells with information about multiple parameters of their microenvironment, including mechanical characteristics. Often, such signaling is based on a unique feature of adhesion structures: their ability to grow and strengthen when force is applied to them, either from within the cell or from the outside. Such adhesion reinforcement is characteristic of integrin-mediated cell-matrix adhesions, but may also operate in other types of adhesion structures. Though the amount of knowledge about adhesion-mediated signaling is growing rapidly, the mechanisms underlying force-dependent regulation of junction assembly are largely unknown. Experiments have been carried out that have started to uncover the major signaling pathways involved in the response of adhesion sites to force. Theoretical models have also been used to address the physical mechanisms underlying adhesion-mediated mechanosensing.     

Effect of a change in step direction from a forward to a lateral target in response to a sensory perturbation

The aim of the current study was to investigate the response of healthy older and young adults to a change in step direction from a forward to a lateral target in response to a sensory perturbation. Nine healthy older (75.1 ± 6.7 years; age range, 65–81 years) and nine young adults (27 ± 3.6 years; age range, 23–31 years) participated in the study. The sensory perturbation was a visual cue presented at random times while subjects stepped over an obstacle from quiet stance. For both young and elderly subjects there was an abrupt change in the slope of both shear ground reaction forces (GRFs) of the stance limb following the perturbation. The slope and peak of the change in GRFs was greater for the young subjects and the onset significantly earlier (205 ms compared to 271 ms). Changes in the GRFs were accompanied by an increase in bilateral gluteus medius and stance limb soleus activity. A late visual cue resulted in a delayed response for elderly subjects. These data show that a stepping response to a sensory perturbation was both delayed and of less magnitude for older adults which has implications for fall risk.     

Vorinostat-induced autophagy switches from a death-promoting to a cytoprotective signal to drive acquired resistance

Histone deacetylase inhibitors (HDACi) have shown promising activity against hematological malignancies in clinical trials and have led to the approval of vorinostat for the treatment of cutaneous T-cell lymphoma. However, de novo or acquired resistance to HDACi therapy is inevitable, and their molecular mechanisms are still unclear. To gain insight into HDACi resistance, we developed vorinostat-resistant clones from the hematological cell lines U937 and SUDHL6. Although cross-resistant to some but not all HDACi, the resistant cell lines exhibit dramatically increased sensitivity toward chloroquine, an inhibitor of autophagy. Consistent with this, resistant cells growing in vorinostat show increased autophagy. Inhibition of autophagy in vorinostat-resistant U937 cells by knockdown of Beclin-1 or Lamp-2 (lysosome-associated membrane protein 2) restores sensitivity to vorinostat. Interestingly, autophagy is also activated in parental U937 cells by de novo treatment with vorinostat. However, in contrast to the resistant cells, inhibition of autophagy decreases sensitivity to vorinostat. These results indicate that autophagy can switch from a proapoptotic signal to a prosurvival function driving acquired resistance. Moreover, inducers of autophagy (such as mammalian target of rapamycin inhibitors) synergize with vorinostat to induce cell death in parental cells, whereas the resistant cells remain insensitive. These data highlight the complexity of the design of combination strategies using modulators of autophagy and HDACi for the treatment of hematological malignancies.     

Methods to test for association between a disease and a multi-allelic marker applied to a candidate region

We report the analysis results of the Genetic Analysis Workshop 14 simulated microsatellite marker dataset, using replicate 50 from the Danacaa population. We applied several methods for association analysis of multi-allelic markers to case-control data to study the association between Kofendrerd Personality Disorder and multi-allelic markers in a candidate region previously identified by the linkage analysis. Evidence for association was found for marker D03S0127 (p < 0.01). The analyses were done without any prior knowledge of the answers.     

Just a hypothesis: a reply to Hanski

Hanski's critique of the habitat amount hypothesis (Hanski, 2015, Journal of Biogeography, 42 , 989–993) does not actually constitute a test of the hypothesis, but rather a series of arguments for why he suspects that it is not correct. But the habitat amount hypothesis is exactly that – a hypothesis. It will remain ‘just’ a hypothesis until it has been rigorously tested against empirical data. To facilitate such testing, in Fahrig (2013, Journal of Biogeography, 40 , 1649–1663) I presented specific, testable predictions of the hypothesis. Here, I reiterate the main tests needed, in the hope that some readers will be encouraged to carry them out. I appreciate this opportunity to emphasize that the habitat amount hypothesis needs to be tested against empirical data, and I look forward to seeing the results of such tests.     

Group B streptococci adhere to a variant of fibronectin attached to a solid phase

Group B streptococci (GBS) are the leading cause of neonatal pneumonia and meningitis. Adherence of GBS to host tissues may play an important role in the pathogenesis of infection. The host molecules which mediate GBS adherence to host tissues are unknown. Many bacterial pathogens adhere to fibronectin, an important component of the extracellular matrix (ECM). Some pathogens adhere to both immobilized and soluble fibronectin, while others adhere to immobilized fibronectin, but not to soluble fibronectin. Previous data indicated that GBS do not adhere to soluble fibronectin. We studied the ability of GBS to adhere to immobilized fibronectin. Forty-five per cent of the input inoculum of COH1, a virulent GBS isolate, adhered to fibronectin immobilized on polystyrene. COH1 did not adhere to the other ECM proteins tested (laminin, type I collagen, vitronectin, and tenascin). Nine out of nine GBS strains from human sources tested adhered specifically to fibronectin at levels varying from 4–60%. We considered the possibility that GBS were adherent to a contaminant in the fibronectin preparation. Properties of fibronectin, including the presence of an immunologic epitope of fibronectin and binding to collagen, were verified to be properties of the molecule to which GBS adhere. COH1 adhered to fibronectin captured by a monoclonal antibody to fibronectin (FN-15), confirming that the molecule to which GBS adhere bears immunologic determinants of fibronectin. Adherence of COH1 to fibronectin was inhibited by collagen, confirming that the molecule to which GBS adhere binds to collagen. These data strongly suggest that GBS adhere to fibronectin, and not to a contaminant. Protein blot analysis revealed that GBS were adherent to a high-molecular-weight variant of non-reduced fibronectin monomers and dimers. GBS did not adhere to reduced fibronectin monomers. We conclude that GBS adhere to a variant of plasma fibronectin when attached to a solid phase.     

Matching a surface to a given sectional curve

We describe an algorithm to position a rigid surface so as to make its cross-section by a given plane match a given curve in that plane, a problem relevant to model-based medical imaging. After building an atlas of cross-sections of the surface and searching it for a best position to start from, each iteration of the algorithm (1) determines a vector field along the intersection curve that will improve its matching with the target curve, and (2) computes and applies a small displacement of the surface whose effect on the intersection will approximate best the required vector field. Computations use least-square techniques, an exponential formula for Lie groups of transformations, and generic properties of cross-sections. Experiments with an implementation are reported and theoretical tools for justifying and improving the algorithm, some of them based on Catastrophe Theory, are outlined.     

How to choose a mentor

Mentors will play important roles in the careers of most successful scientists. Mentors are trusted advisors that give constructive criticism and provide information in many areas of a scientific life. Mentors will likely change throughout your career as your position changes and thus the areas of advice needed changes. Despite the fact that you gain new mentors, the relationships with the old mentors likely will continue and often grow into strong friendships. The American Physiological Society is a member of MentorNet, which is an award-winning, free, one-on-one electronic mentoring program for graduate students, postdoctoral fellows, and early career scientists who are APS members. Mentees and mentors are matched based on their responses to several questionnaires regarding research interests, mentoring needs, time needed, etc. Once assigned, mentors and mentees are allowed to approve their matches, and once done, contact information is given to each pair. A new mentor can be assigned every eight months. These electronic mentoring relationships are especially helpful if you are not comfortable discussing certain things with your thesis or postdoctoral advisor. APS encourages all members to participate either as a mentee or mentor in this valuable program. To comment on this article, go to http://www.the-aps.org/careers/ careers 1/mentor/mentoring.htm.     

How to build a biofilm: a fungal perspective

Biofilms are differentiated masses of microbes that form on surfaces and are surrounded by an extracellular matrix. Fungal biofilms, especially those of the pathogen Candida albicans, are a cause of infections associated with medical devices. Such infections are particularly serious because biofilm cells are relatively resistant to many common antifungal agents. Several in vitro models have been used to elucidate the developmental stages and processes required for C. albicans biofilm formation, and recent studies have begun to define biofilm genetic control. It is clear that cell-substrate and cell-cell interactions, hyphal differentiation and extracellular matrix production are key steps in biofilm development. Drug resistance is acquired early in biofilm formation, and appears to be governed by different mechanisms in early and late biofilms. Quorum sensing might be an important factor in dispersal of biofilm cells. The past two years have seen the emergence of several genomic strategies to uncover global events in biofilm formation and directed studies to understand more specific events, such as hyphal formation, in the biofilm setting.     

When to refer an infertile mare to a theriogenologist

Most equine infertility cases can be solved with a methodical, thorough physical and reproductive examination and appropriate diagnostic laboratory aids. Repeated examinations may be needed in some cases to identify subtle anatomical abnormalities or irregularities between hormonal and physiological relationships of the reproductive tract. For pregnancy to occur, hormonal signaling must be exquisitely synchronized with physical changes of the reproductive tract and deposition of fertile semen in the uterus. Asynchrony of these events, infection, inflammation, previous trauma to the reproductive tract or "stress" can interfere with conception or maintenance of pregnancy. Infertile mares are presented for three common problems: (1) accumulation of intra-uterine fluid during or immediately after estrus; (2) long standing infection and/or chronic inflammation; or (3) irregular or no estrous cycles. By defining the problem, diagnostics can be chosen to determine the cause. Treatment protocols should be designed around the diagnosis and antibiotics, ecbolics or steroids should not be used indiscriminately. In all cases of mare infertility, semen quality needs to be determined to be satisfactory as a subfertile stallion bred to a subfertile mare greatly decreases the likelihood of pregnancy.     

Easy Rider: Monkeys Learn to Drive a Wheelchair to Navigate through a Complex Maze

The neurological bases of spatial navigation are mainly investigated in rodents and seldom in primates. The few studies led on spatial navigation in both human and non-human primates are performed in virtual, not in real environments. This is mostly because of methodological difficulties inherent in conducting research on freely-moving monkeys in real world environments. There is some incertitude, however, regarding the extrapolation of rodent spatial navigation strategies to primates. Here we present an entirely new platform for investigating real spatial navigation in rhesus monkeys. We showed that monkeys can learn a pathway by using different strategies. In these experiments three monkeys learned to drive the wheelchair and to follow a specified route through a real maze. After learning the route, probe tests revealed that animals successively use three distinct navigation strategies based on i) the place of the reward, ii) the direction taken to obtain reward or iii) a cue indicating reward location. The strategy used depended of the options proposed and the duration of learning. This study reveals that monkeys, like rodents and humans, switch between different spatial navigation strategies with extended practice, implying well-conserved brain learning systems across different species. This new task with freely driving monkeys provides a good support for the electrophysiological and pharmacological investigation of spatial navigation in the real world by making possible electrophysiological and pharmacological investigations.     

Response to a Respiratory Survey

Respondents to a respiratory survey of Berlin, New Hampshire, residents in 1961 have been studied to assess the relationship between co-operation and respiratory disease prevalence. Two hundred and forty-three unco-operative subjects, interviewed at home, had significantly more morning phlegm and a lower vital capacity than carefully matched subjects who attended the central clinic. Fifty-one volunteers had the same prevalence of respiratory disease symptoms and physiological abnormalities as carefully matched subjects drawn from a probability sample of the city.It is concluded that respiratory disease prevalence will be underestimated if calculated from studies of co-operative subjects who attend a clinic. Case-finding by respiratory disease screening clinics will also miss many persons who suffer from chronic bronchitis.     

Import of a mutant mitochondrial precursor fails to respond to stimulation by a cytosolic factor

Import of the precursor to ornithine carbamyltransferase is stimulated by a partially-purified, NEM-sensitive soluble factor from rabbit reticulocyte lysate. A mutant in which the carboxy-terminal 73 amino acids were deleted, had a sharply reduced response to this factor. The NEM-sensitive, import-stimulating factor interacts with the surface of mitochondria in the absence of precursor protein. Thus reticulocyte lysate contains an NEM-sensitive, import stimulating factor which interacts both with the surface of mitochondria and whose activity appears to be dependent upon the structure of the mature portion of the precursor.     

From a phylogenetic tree to a reticulated network.

In many phylogenetic problems, assuming that species have evolved from a common ancestor by a simple branching process is unrealistic. Reticulate phylogenetic models, however, have been largely neglected because the concept of reticulate evolution have not been supported by using appropriate analytical tools and software. The reticulate model can adequately describe such complicated mechanisms as hybridization between species or lateral gene transfer in bacteria. In this paper, we describe a new algorithm for inferring reticulate phylogenies from evolutionary distances among species. The algorithm is capable of detecting contradictory signals encompassed in a phylogenetic tree and identifying possible reticulate events that may have occurred during evolution. The algorithm produces a reticulate phylogeny by gradually improving upon the initial solution provided by a phylogenetic tree model. The new algorithm is compared to the popular SplitsGraph method in a reanalysis of the evolution of photosynthetic organisms. A computer program to construct and visualize reticulate phylogenies, called T-Rex (Tree and Reticulogram Reconstruction), is available to researchers at the following URL: www.fas.umontreal.ca/biol/casgrain/en/labo/t-rex.