Breaking up the Wall: Metal-Enrichment in Ovipositors,but Not in Mandibles,Co-Varies with Substrate Hardness in Gall-Wasps and Their Associates

The cuticle of certain insect body parts can be hardened by the addition of metals, and because niche separation may require morphological adaptations, inclusion of such metals may be linked to life history traits. Here, we analysed the distribution and enrichment of metals in the mandibles and ovipositors of a large family of gall-inducing wasps (Cynipidae, or Gall-Wasps) (plus one gall-inducing Chalcidoidea), and their associated wasps (gall-parasitoids and gall-inquilines) (Cynipidae, Chalcidoidea and Ichneumonoidea). Both plant types/organs where galls are induced, as well as galls themselves, vary considerably in hardness, thus making this group of wasps an ideal model to test if substrate hardness can predict metal enrichment. Non-galler, parasitic Cynipoidea attacking unconcealed hosts were used as ecological “outgroup”. With varying occurrence and concentration, Zn, Mn and Cu were detected in mandibles and ovipositors of the studied species. Zn tends be exclusively concentrated at the distal parts of the organs, while Mn and Cu showed a linear increase from the proximal to the distal parts of the organs. In general, we found that most of species having metal-enriched ovipositors (independently of metal type and concentration) were gall-invaders. Among gall-inducers, metals in the ovipositors were more likely to be found in species inducing galls in woody plants. Overall, a clear positive effect of substrate hardness on metal concentration was detected for all the three metals. Phylogenetic relationships among species, as suggested by the most recent estimates, seemed to have a weak role in explaining metal variation. On the other hand, no relationships were found between substrate hardness or gall-association type and concentration of metals in mandibles. We suggest that ecological pressures related to oviposition were sufficiently strong to drive changes in ovipositor elemental structure in these gall-associated Hymenoptera.     

Disturbance cue communication is shaped by emitter diet and receiver background risk in Trinidadian guppies

In animal communication systems, individuals that detect a cue (i.e., “receivers”) are often influenced by characteristics of the cue emitter. For instance, in many species, receivers avoid chemical cues that are released by emitters experiencing disturbance. These chemical “disturbance cues” appear to benefit receivers by warning them about nearby danger, such as a predator’s approach. While the active ingredients in disturbance cues have been largely unexplored, by-products of metabolized protein are thought to play a role for some species. If so, the content (quality) and volume (quantity) of the emitter’s diet should affect their disturbance cues, thus altering how receivers perceive the cues and respond. Guppies Poecilia reticulata are a species known to discriminate among disturbance cues from different types of donors, but dietary variation has yet to be explored. In this study, we found evidence that diet quality and quantity can affect disturbance cues released by guppy emitters (i.e., experimental “donors”). Receivers discriminated between donor cue treatments, responding more strongly to cues from donors fed a protein-rich bloodworm diet (Experiment 1), as well as an overall larger diet (Experiment 2). We also found that receivers exposed to higher background risk were more sensitive to disturbance cue variation, with the strongest avoidance responses displayed by high-risk receivers toward disturbance cues from donors fed the high-quality diet. Therefore, diet, and perhaps protein specifically, affects either the concentration or composition of disturbance cues released by guppies. Such variation may be important in information signaling in social species like the guppy.     

Metal Ions May Suppress or Enhance Cellular Differentiation in Candida albicans and Candida tropicalis Biofilms

Candida albicans and Candida tropicalis are polymorphic fungi that develop antimicrobial-resistant biofilm communities that are characterized by multiple cell morphotypes. This study investigated cell type interconversion and drug and metal resistance as well as community organization in biofilms of these microorganisms that were exposed to metal ions. To study this, Candida biofilms were grown either in microtiter plates containing gradient arrays of metal ions or in the Calgary Biofilm Device for high-throughput susceptibility testing. Biofilm formation and antifungal resistance were evaluated by viable cell counts, tetrazolium salt reduction, light microscopy, and confocal laser scanning microscopy in conjunction with three-dimensional visualization. We discovered that subinhibitory concentrations of certain metal ions (CrO₄²⁻, Co²⁺, Cu²⁺, Ag⁺, Zn²⁺, Cd²⁺, Hg²⁺, Pb²⁺, AsO₂⁻, and SeO₃²⁻) caused changes in biofilm structure by blocking or eliciting the transition between yeast and hyphal cell types. Four distinct biofilm community structure types were discerned from these data, which were designated “domed,” “layer cake,” “flat,” and “mycelial.” This study suggests that Candida biofilm populations may respond to metal ions to form cell-cell and solid-surface-attached assemblages with distinct patterns of cellular differentiation.     

Evaluation of four slide test kits for the detection of human chorionic gonadotropin in urine

Three “indirect-type” slide tests utilizing the principle of hemagglutination inhibition and one new “direct-type” slide test employing direct agglutination were evaluated for their sensitivity in detecting human chorionic gonadotropin (HCG) in urine. The results of positive tests in a group of woman in very early pregnancy were correlated with the “days after last menses”. In this series the direct slide test was the most accurate. A control must be used with each direct test to indicate interfering substances and when such are present a different test must be used. All tests were found to be of the relative sensitivity stated by the manufacturer.     

Fibrosing Alveolitis Associated with Renal Tubular Acidosis

The discovery of a case of renal tubular acidosis and fibrosing alveolitis led to the investigation of 19 further patients. Abnormal pulmonary function tests were found in a further four patients with overt renal tubular acidosis and in four out of eight patients with “incomplete” renal tubular acidosis. The response to an ammonium chloride test in seven patients with cryptogenic fibrosing alveolitis was normal. Those patients with a defect of both renal acidification and pulmonary gas transfer had concurrent autoimmune diseases such as Sjögren''s syndrome and primary biliary cirrhosis. It is suggested that the renal and pulmonary abnormalities may be part of a systemic disorder capable of affecting many organs. Moreover, hyperglobulinaemia and autoantibodies in these patients further suggests that immunological mechanisms are concerned in the pathogenesis of these abnormalities.     

Why is Real-World Visual Object Recognition Hard?

Progress in understanding the brain mechanisms underlying vision requires the construction of computational models that not only emulate the brain's anatomy and physiology, but ultimately match its performance on visual tasks. In recent years, “natural” images have become popular in the study of vision and have been used to show apparently impressive progress in building such models. Here, we challenge the use of uncontrolled “natural” images in guiding that progress. In particular, we show that a simple V1-like model—a neuroscientist's “null” model, which should perform poorly at real-world visual object recognition tasks—outperforms state-of-the-art object recognition systems (biologically inspired and otherwise) on a standard, ostensibly natural image recognition test. As a counterpoint, we designed a “simpler” recognition test to better span the real-world variation in object pose, position, and scale, and we show that this test correctly exposes the inadequacy of the V1-like model. Taken together, these results demonstrate that tests based on uncontrolled natural images can be seriously misleading, potentially guiding progress in the wrong direction. Instead, we reexamine what it means for images to be natural and argue for a renewed focus on the core problem of object recognition—real-world image variation.     

Memory for Expectation-Violating Concepts: The Effects of Agents and Cultural Familiarity

Previous research has shown that ideas which violate our expectations, such as schema-inconsistent concepts, enjoy privileged status in terms of memorability. In our study, memory for concepts that violate cultural (cultural schema-level) expectations (e.g., “illiterate teacher”, “wooden bottle”, or “thorny grass”) versus domain-level (ontological) expectations (e.g., “speaking cat”, “jumping maple”, or “melting teacher”) was examined. Concepts that violate cultural expectations, or counter-schematic, were remembered to a greater extent compared with concepts that violate ontological expectations and with intuitive concepts (e.g., “galloping pony”, “drying orchid”, or “convertible car”), in both immediate recall, and delayed recognition tests. Importantly, concepts related to agents showed a memory advantage over concepts not pertaining to agents, but this was true only for expectation-violating concepts. Our results imply that intuitive, everyday concepts are equally attractive and memorable regardless of the presence or absence of agents. However, concepts that violate our expectations (cultural-schema or domain-level) are more memorable when pertaining to agents (humans and animals) than to non-agents (plants or objects/artifacts). We conclude that due to their evolutionary salience, cultural ideas which combine expectancy violations and the involvement of an agent are especially memorable and thus have an enhanced probability of being successfully propagated.     

Block of the Kir2.1 Channel Pore by Alkylamine Analogues of Endogenous Polyamines

Inward rectification induced by mono- and diaminoalkane application to inside-out membrane patches was studied in Kir2.1 (IRK1) channels expressed in Xenopus oocytes. Both monoamines and diamines block Kir2.1 channels, with potency increasing as the alkyl chain length increases (from 2 to 12 methylene groups), indicating a strong hydrophobic interaction with the blocking site. For diamines, but not monoamines, increasing the alkyl chain also increases the steepness of the voltage dependence, at any concentration, from a limiting minimal value of ∼1.5 (n = 2 methylene groups) to ∼4 (n = 10 methylene groups). These observations lead us to hypothesize that monoamines and diamines block inward rectifier K⁺ channels by entering deeply into a long, narrow pore, displacing K⁺ ions to the outside of the membrane, with this displacement of K⁺ ions contributing to “extra” charge movement. All monoamines are proposed to lie with the “head” amine at a fixed position in the pore, determined by electrostatic interaction, so that zδ is independent of monoamine alkyl chain length. The head amine of diamines is proposed to lie progressively further into the pore as alkyl chain length increases, thus displacing more K⁺ ions to the outside, resulting in charge movement (zδ) increasing with the increase in alkyl chain length.     

Blood Pressure: A Consideration of Terminology

Concepts of hypertension have changed and changes in terminology to reflect this state of affairs are suggested. Statistically, the best mortality experience is associated with blood pressure commonly regarded as subnormal, and increments of blood pressure above this level are associated with progressive increases in mortality. The terms “normal”, “benign” and “essential” in relation to blood pressure should be abandoned. “Optimal”, “acceptable” and “hypertensive” ranges of blood pressure are suggested. Hypertension is regarded as a symptom of disease, rather than as a disease in itself, and “hypertension”, when used as a diagnostic label, should be qualified always by the primary disease, if known, or by the modifying phrase, “of unknown cause”, if not known.     

Double-barreled and Concentric Microelectrodes for Measurement of Extracellular Ion Signals in Brain Tissue

Electrical activity in the brain is accompanied by significant ion fluxes across membranes, resulting in complex changes in the extracellular concentration of all major ions. As these ion shifts bear significant functional consequences, their quantitative determination is often required to understand the function and dysfunction of neural networks under physiological and pathophysiological conditions. In the present study, we demonstrate the fabrication and calibration of double-barreled ion-selective microelectrodes, which have proven to be excellent tools for such measurements in brain tissue. Moreover, so-called “concentric” ion-selective microelectrodes are also described, which, based on their different design, offer a far better temporal resolution of fast ion changes. We then show how these electrodes can be employed in acute brain slice preparations of the mouse hippocampus. Using double-barreled, potassium-selective microelectrodes, changes in the extracellular potassium concentration ([K⁺]_o) in response to exogenous application of glutamate receptor agonists or during epileptiform activity are demonstrated. Furthermore, we illustrate the response characteristics of sodium-sensitive, double-barreled and concentric electrodes and compare their detection of changes in the extracellular sodium concentration ([Na⁺]_o) evoked by bath or pressure application of drugs. These measurements show that while response amplitudes are similar, the concentric sodium microelectrodes display a superior signal-to-noise ratio and response time as compared to the double-barreled design. Generally, the demonstrated procedures will be easily transferable to measurement of other ions species, including pH or calcium, and will also be applicable to other preparations.     

Higher Landing Accuracy in Expert Pilots is Associated with Lower Activity in the Caudate Nucleus

The most common lethal accidents in General Aviation are caused by improperly executed landing approaches in which a pilot descends below the minimum safe altitude without proper visual references. To understand how expertise might reduce such erroneous decision-making, we examined relevant neural processes in pilots performing a simulated landing approach inside a functional MRI scanner. Pilots (aged 20–66) were asked to “fly” a series of simulated “cockpit view” instrument landing scenarios in an MRI scanner. The scenarios were either high risk (heavy fog–legally unsafe to land) or low risk (medium fog–legally safe to land). Pilots with one of two levels of expertise participated: Moderate Expertise (Instrument Flight Rules pilots, n = 8) or High Expertise (Certified Instrument Flight Instructors or Air-Transport Pilots, n = 12). High Expertise pilots were more accurate than Moderate Expertise pilots in making a “land” versus “do not land” decision (CFII: d′ = 3.62±2.52; IFR: d′ = 0.98±1.04; p<.01). Brain activity in bilateral caudate nucleus was examined for main effects of expertise during a “land” versus “do not land” decision with the no-decision control condition modeled as baseline. In making landing decisions, High Expertise pilots showed lower activation in the bilateral caudate nucleus (0.97±0.80) compared to Moderate Expertise pilots (1.91±1.16) (p<.05). These findings provide evidence for increased “neural efficiency” in High Expertise pilots relative to Moderate Expertise pilots. During an instrument approach the pilot is engaged in detailed examination of flight instruments while monitoring certain visual references for making landing decisions. The caudate nucleus regulates saccade eye control of gaze, the brain area where the “expertise” effect was observed. These data provide evidence that performing “real world” aviation tasks in an fMRI provide objective data regarding the relative expertise of pilots and brain regions involved in it.     

Some personal and historical notes on the utility of “deep-etch” electron microscopy for making cell structure/function correlations

This brief essay talks up the advantages of metal replicas for electron microscopy and explains why they are still the best way to image frozen cells in the electron microscope. Then it explains our approach to freezing, namely the Van Harreveld trick of “slamming” living cells onto a supercold block of metal sprayed with liquid helium at −269ºC, and further talks up this slamming over the alternative of high-pressure freezing, which is much trickier but enjoys greater favor at the moment. This leads me to bemoan the fact that there are not more young investigators today who want to get their hands on electron microscopes and use our approach to get the most “true to life” views of cells out of them with a minimum of hassle. Finally, it ends with a few perspectives on my own career and concludes that, personally, I''m permanently stuck with the view of the “founding fathers” that cell ultrastructure will ultimately display and explain all of cell function, or as Palade said in his Nobel lecture,electron micrographs are “irresistible and half transparent … their meaning buried under only a few years of work,” and “reasonable working hypotheses are already suggested by the ultrastructural organization itself.”     

The Snakelike Chain Character of Unstructured RNA

In the absence of base-pairing and tertiary structure, ribonucleic acid (RNA) assumes a random-walk conformation, modulated by the electrostatic self-repulsion of the charged, flexible backbone. This behavior is often modeled as a Kratky-Porod “wormlike chain” (WLC) with a Barrat-Joanny scale-dependent persistence length. In this study we report measurements of the end-to-end extension of poly(U) RNA under 0.1 to 10 pN applied force and observe two distinct elastic-response regimes: a low-force, power-law regime characteristic of a chain of swollen blobs on long length scales and a high-force, salt-valence-dependent regime consistent with ion-stabilized crumpling on short length scales. This short-scale structure is additionally supported by force- and salt-dependent quantification of the RNA ion atmosphere composition, which shows that ions are liberated under stretching; the number of ions liberated increases with increasing bulk salt concentration. Both this result and the observation of two elastic-response regimes directly contradict the WLC model, which predicts a single elastic regime across all forces and, when accounting for scale-dependent persistence length, the opposite trend in ion release with salt concentration. We conclude that RNA is better described as a “snakelike chain,” characterized by smooth bending on long length scales and ion-stabilized crumpling on short length scales. In monovalent salt, these two regimes are separated by a characteristic length that scales with the Debye screening length, highlighting the determining importance of electrostatics in RNA conformation.     

A model of naturalistic decision making in preference tests

Decisions as to whether to continue with an ongoing activity or to switch to an alternative are a constant in an animal’s natural world, and in particular underlie foraging behavior and performance in food preference tests. Stimuli experienced by the animal both impact the choice and are themselves impacted by the choice, in a dynamic back and forth. Here, we present model neural circuits, based on spiking neurons, in which the choice to switch away from ongoing behavior instantiates this back and forth, arising as a state transition in neural activity. We analyze two classes of circuit, which differ in whether state transitions result from a loss of hedonic input from the stimulus (an “entice to stay” model) or from aversive stimulus-input (a “repel to leave” model). In both classes of model, we find that the mean time spent sampling a stimulus decreases with increasing value of the alternative stimulus, a fact that we linked to the inclusion of depressing synapses in our model. The competitive interaction is much greater in “entice to stay” model networks, which has qualitative features of the marginal value theorem, and thereby provides a framework for optimal foraging behavior. We offer suggestions as to how our models could be discriminatively tested through the analysis of electrophysiological and behavioral data.     

European population substructure: clustering of northern and southern populations

Using a genome-wide single nucleotide polymorphism (SNP) panel, we observed population structure in a diverse group of Europeans and European Americans. Under a variety of conditions and tests, there is a consistent and reproducible distinction between “northern” and “southern” European population groups: most individual participants with southern European ancestry (Italian, Spanish, Portuguese, and Greek) have >85% membership in the “southern” population; and most northern, western, eastern, and central Europeans have >90% in the “northern” population group. Ashkenazi Jewish as well as Sephardic Jewish origin also showed >85% membership in the “southern” population, consistent with a later Mediterranean origin of these ethnic groups. Based on this work, we have developed a core set of informative SNP markers that can control for this partition in European population structure in a variety of clinical and genetic studies.     

A review of family-based tests for linkage disequilibrium between a quantitative trait and a genetic marker

Quantitative trait transmission/disequilibrium tests (quantitative TDTs) are commonly used in family-based genetic association studies of quantitative traits. Despite the availability of various quantitative TDTs, some users are not aware of the properties of these tests and the relationships between them. This review aims at outlining the broad features of the various quantitative TDT procedures carried out in the frequently used QTDT and FBAT packages. Specifically, we discuss the “Rabinowitz” and the “Monks-Kaplan” procedures, as well as the various “Abecasis” and “Allison” regression-based procedures. We focus on the models assumed in these tests and the relationships between them. Moreover, we discuss what hypotheses are tested by the various quantitative TDTs, what testing procedures are best suited to various forms of data, and whether the regression-based tests overcome population stratification problems. Finally, we comment on power considerations in the choice of the test to be used. We hope this brief review will shed light on the similarities and differences of the various quantitative TDTs.     

Observations on Immunochemical Assays of Human Chorionic Gonadotropin

Commercial immunochemical tests, “UCG” and “Prepuerin”, detected standardized human chorionic gonadotropin (HCG) in concentrations comparable to the rat ovarian hyperemia test. These in vitro systems also cross-reacted with pituitary luteinizing hormone (LH) but not with follicle-stimulating hormone (FSH) of animal origin. The latex agglutination slide tests required a higher concentration of HCG for a positive test than did the bioassay. In cases of abnormal pregnancies the immunochemical assays remained positive longer than the bioassay, which is apparently due to their detection of biologically inactive HCG. Several non-pregnant patients with ovarian cysts and cystic teratomas excreted in their urine some substances which reacted with the UCG test. After surgical removal of the tumour these substances disappeared from the urine.     

Network modeling of dynamic brain interactions predicts emergence of neural information that supports human cognitive behavior

How cognitive task behavior is generated by brain network interactions is a central question in neuroscience. Answering this question calls for the development of novel analysis tools that can firstly capture neural signatures of task information with high spatial and temporal precision (the “where and when”) and then allow for empirical testing of alternative network models of brain function that link information to behavior (the “how”). We outline a novel network modeling approach suited to this purpose that is applied to noninvasive functional neuroimaging data in humans. We first dynamically decoded the spatiotemporal signatures of task information in the human brain by combining MRI-individualized source electroencephalography (EEG) with multivariate pattern analysis (MVPA). A newly developed network modeling approach—dynamic activity flow modeling—then simulated the flow of task-evoked activity over more causally interpretable (relative to standard functional connectivity [FC] approaches) resting-state functional connections (dynamic, lagged, direct, and directional). We demonstrate the utility of this modeling approach by applying it to elucidate network processes underlying sensory–motor information flow in the brain, revealing accurate predictions of empirical response information dynamics underlying behavior. Extending the model toward simulating network lesions suggested a role for the cognitive control networks (CCNs) as primary drivers of response information flow, transitioning from early dorsal attention network-dominated sensory-to-response transformation to later collaborative CCN engagement during response selection. These results demonstrate the utility of the dynamic activity flow modeling approach in identifying the generative network processes underlying neurocognitive phenomena.

How is cognitive task behavior generated by brain network interactions? This study describes a novel network modeling approach and applies it to source electroencephalography data. The model accurately predicts future information dynamics underlying behavior and (via simulated lesioning) suggests a role for cognitive control networks as key drivers of response information flow.     

A method for the epidemiologic study of early diabetes

A diabetic survey was conducted among 4048 subjects well enough to report for work, using a questionnaire covering past, present, family and obstetric history, and a capillary blood glucose determination at least 1½ hours after eating. A “positive screen” was obtained in 267 individuals, in 67 on the basis of elevated blood glucose value alone, in 179 on the basis of questionnaire responses alone, and in 21 by both criteria. Glucose tolerance tests were performed on 130 subjects (49% of eligible individuals) and yielded diabetic curves in 18, 6 and 33% respectively for the three categories of positive screening tests.It is suggested that the magnitude of the group with positive history only is such that future natural history studies must take this subsample into consideration.