What is a 'low dose' of radiation?

Although the expression of radiation-induced biological effects and responses may be at either the cell, organ or organism level, induction of some of these phenomena (e.g. cancer of clastogenic and genetic effects) can have their origin in the interaction of a single charged particle with the target-containing volume (TCV) of the cell, e.g. the cell nucleus. However, the independent variable now used in both organ and cell population studies, the absorbed dose to the organ, provides no information directly on particle-TCV interactions. Even if calculated as a mean to an organized population of cells, the absorbed dose becomes a composite and confounded quantity, (FzN), in which F is the fraction of TCVs 'hit' by a particle during a given exposure, z is the mean value of z1, the energy absorbed in the TCV in a single hit, and N is the mean number of hits per affected TCV. Scientific precepts demand the avoidance of such confounded variables by achieving their isolation. The needed separation can be effected by the use of microdosimetric techniques, which make it possible to hold one component quantity constant while the others are varied. As an example, low-level radiation exposure (LLE) can be used to hold F at a constant value of 0.2 where, on average, there is but one hit per TCV. The probability of a cellular quantal response, as a function of z1 only, can then be determined by use of LLE to radiations covering a wide span of LETs. Conversely, the effect of varying only the fraction of cells hit can be studied by holding z constant. This can be accomplished by working within a narrow band of LET, but only in the LLE range. The effectiveness of preirradiation altering cell sensitivity as a function of the number of hits per TCV can be determined by working within, and somewhat above, the LLE range. In either risk assessment or the application of radiation as a pretreatment, minimal consequences can be assured only if very low-level exposure is employed in order that F will be small, and if the exposure is in a field of radiation of very low LET so that z1 will be as small as possible. That is to say, exposure conditions with low consequences cannot be specified in terms of any single quantity.     

A root is a root is a root? Water uptake rates of Citrus root orders

Knowledge about the physiological function of root orders is scant. In this study, a system to monitor the water flux among root orders was developed using miniaturized chambers. Different root orders of 4‐year‐old Citrus volkameriana trees were analysed with respect to root morphology and water flux. The eight root orders showed a broad overlap in diameter, but differences in tissue densities and specific root area (SRA) were clearly distinguishable. Thirty per cent of the root branch biomass but 50% of the surface area (SA) was possessed by the first root order, while the fifth accounted for 5% of the SA (20% biomass). The root order was identified as a determinant of water flux. First‐order roots showed a significantly higher rate of water uptake than the second and third root orders, whereas the fourth and fifth root orders showed water excess. The water excess suggested the occurrence of hydraulic redistribution (HR) as a result of differences in osmotic potentials. We suggest that plants may utilize hydraulic redistribution to prevent coarse root desiccation and/or to increase nutrient acquisition. Our study showed that the novel ‘miniature depletion chamber’ method enabled direct measurement of water fluxes per root order and can be a major tool for future studies on root order traits.     

Sulfated galactan is a catalyst of antithrombin-mediated inactivation of α-thrombin

Novel compounds presenting anticoagulant activity, such as sulfated polysaccharides, open new perspectives in medicine. Elucidation of the molecular mechanism behind this activity is desirable by itself, as well as because it allows for the design of novel compounds. In the present study, we investigated the action of an algal sulfated galactan, which potentiates α-thrombin inactivation by antithrombin. Our results indicate the following: 1) both the sulfated galactan and heparin potentiate protease inactivation by antithrombin at similar molar concentrations, however they differ markedly in the molecular size required for their activities; 2) this galactan interacts predominantly with exosite II on α-thrombin and, similar to heparin, catalyzes the formation of a covalent complex between antithrombin and the protease; 3) the sulfated galactan has a higher affinity for α-thrombin than for antithrombin. We propose that the preferred pathway of sulfated galactan-induced inactivation of α-thrombin by antithrombin starts with the polysaccharide binding to the protease through a high-affinity interaction. Antithrombin is then added to the complex and the protease is inactivated by covalent interactions. Finally, the antithrombin–α-thrombin covalent complex dissociates from the polysaccharide chain. This mechanism resembles the action of heparin with low affinity for antithrombin, as opposed to heparin with high affinity for serpin.     

What is the significance of a significant TDT?

This note summarizes the development of the transmission/disequilibrium test (TDT). The initial purpose of the TDT procedure was to test for linkage between a genetic marker and a disease susceptibility locus when an association had been found between the two. An association between disease and marker had sometimes been taken to imply linkage. An association could, however, be due to population stratification even in the absence of linkage. In contrast, the outcome of the TDT is not affected by such stratification. Furthermore, when linkage is not in doubt, the TDT can, in some cases, also provide a test of association between marker and disease. We discuss these various matters in this paper.     

How is the individuality of a face recognized?

A familiar face is instantly recognized in a crowd. This cannot be achieved through a feature by feature comparison of the observed face with either an average face (norm-based model of face recognition) or with a set of similarly constructed faces stored in memory (exemplar-based model of face recognition). A modified norm-based model is thus proposed. Instead of memorizing an average face, the normal variations for each facial feature are used to construct a multidimensional volume of face-space devoid of unusual features, here defined as features whose metrics lie below the 5th or above the 95th percentiles for that feature. A face consisting of 100 independently variable features will thus have, on average, 10 unusual features. Face identification then becomes exception-reporting. It requires only 10 such rare features to render a given face a one in 10¹³ faces (P=0.05¹⁰=9.8×10⁻¹⁴). In a world containing 6.7×10⁹ people, such a face would be unique. Faces remembered in this way can have their unusual features exaggerated or attenuated without loss of identity. This is the basis of caricatures and anti-caricatures. It also means that individuals belonging to a foreign race, possessing several features with modes beyond the “usual range” of the own-race population, will all look alike. Features that render a face unique in the own-race population are now shared by everyone in the foreign race.Average faces are more beautiful than the faces used in the averaging process. This makes evolutionary sense. Natural selection increases the frequency of fit features at the expense of maladaptive features. “Usual features” are therefore fitter than “unusual features”, and play an important role in mate selection. Such an existing fundamental sexual attribute could easily have been harnessed for the fast and efficient recognition of individuals in the community.     

Dyspepsia: is a trial of therapy appropriate?

Dyspepsia is a common, benign condition that may be distinguished from gastroesophageal reflux, irritable bowel syndrome and pancreatobiliary, coronary or musculoskeletal disease by a careful history and physical examination. However, the presence or absence of a peptic ulcer in dyspepsia can be determined only by an endoscopic examination or a barium-contrast radiograph. Although the American College of Physicians has recommended trying drug therapy for patients with dyspepsia before diagnostic tests are done, new data support early diagnosis. Although therapy is initially cheaper than endoscopic examination, over a year the costs even out because most patients with dyspepsia eventually need an endoscopic examination, and many patients with nonulcer dyspepsia are given medication unnecessarily. Endoscopic examination, if available to general practitioners, is the most cost-effective approach to dyspepsia. An approach that does not include endoscopy lacks the opportunity to offer patients convincing reassurance that their illness is not serious, which is arguably the most important treatment in cases of nonulcer dyspepsia. Studies supporting the use of endoscopic examination predate the treatment of peptic ulcers with antibiotics, which makes an initial endoscopic examination to determine whether the patient has an ulcer even more important.     

How random is the toss of a coin?

Background

The toss of a coin has been a method used to determine random outcomes for centuries. It is still used in some research studies as a method of randomization, although it has largely been discredited as a valid randomization method. We sought to provide evidence that the toss of a coin can be manipulated.

Methods

We performed a prospective experiment involving otolaryngology residents in Vancouver, Canada. The main outcome was the proportion of “heads” coin tosses achieved (out of 300 attempts) by each participant. Each of the participants attempted to flip the coin so as to achieve a heads result.

Results

All participants achieved more heads than tails results, with 7 of the 13 participants having significantly more heads results (p ≤ 0.05). The highest proportion of heads achieved was 0.68 (95% confidence interval 0.62–0.73, p < 0.001).

Interpretation

Certain people are able to successfully manipulate the toss of a coin. This throws into doubt the validity of using a coin toss to determine a chance result.The toss or flip of a coin to randomly assign a decision traditionally involves throwing a coin into the air and seeing which side lands facing up. This method may be used to resolve a dispute, see who goes first in a game or determine which type of treatment a patient receives in a clinical trial. There are only 2 possible outcomes, “heads” or “tails,” although, in theory, landing on an edge is possible. (Research suggests that when the coin is allowed to fall onto a hard surface, the chance of this happening is in the order of 1 in 6000 tosses.¹)When a coin is flipped into the air, it is supposedly made to rotate about an axis parallel to its flat surfaces. The coin is initially placed on a bent forefinger, and the thumb is released from under the coin surface, where it has been held under tension. The thumbnail strikes the part of the coin unsupported by the index finger, sending it rotating upward. All this is done with an upward movement of the hand and forearm. The coin may be allowed to fall to the floor or other surface or it may be caught by the “tosser” and sometimes turned onto the back of the opposite hand and then revealed. The catching method should not matter, provided it is consistent for each toss. The opponent often calls the toss when the coin is airborne, although in the case of randomization for clinical trials, this is unnecessary because one is simply looking for an outcome.Open in a separate windowThe appeal of the coin toss that it is a simple, seemingly unbiased, method of deciding between 2 options. Although the outcome of a coin toss should be at even odds, the outcome may well not be. Historically, the toss of a coin before a duel reputedly decided which person had his back to the sun — an obvious advantage when taking aim! In medical trials, a simple statistical manipulation can have a dramatic effect on the treatment a patient receives. Our hypothesis is that with minimal training, the outcome of the toss can be weighted heavily to the call of the tosser, thus abolishing the 50:50 chance result that is expected and allowing for manipulation of an apparently random event.     

Oxidation of proteins: is it a programmed process?

Proteins represent extremely susceptible targets for oxidants. Oxidative modifications of proteins may bring about violation of their structure and functionality. It implies that the structures of proteins are not infallible in terms of their antioxidant defence. The protection mechanisms in preventing oxidative damages for proteins within cells are mainly related to a large variety of antioxidant enzymatic systems. In contrast, plasma proteins are scarcely protected by these systems, so the mechanism that provides their functioning in the conditions of generating reactive oxygen species (ROS) seems to be much more complicated. Oxidation of many proteins was long considered as a random process. However, the highly site-specific oxidation processes was convincingly demonstrated for some proteins, indicating that protein structure could be adapted to oxidation. According to our hypothesis, some of the structural elements present in proteins are capable of scavenging ROS to protect other protein structures against ROS toxicity. Various antioxidant elements (distinct subdomains, domains, regions, and polypeptide chains) may act as ROS interceptors, thus mitigating the ROS action on functionally crucial amino acid residues of proteins. In the review, the oxidative modifications of certain plasma proteins, such as α₂-macroglobulin, serum human albumin, fibrinogen, and fibrin-stabilising factor, which differ drastically in their spatial structures and functions, are analysed. The arguments that demonstrate the possibility of existing hypothetical antioxidant structures are presented. For the first time, the emphasis is being placed on the programmed mechanism of protein oxidation.     

What is the risk of a deadly adenovirus pandemic?

Many of us had refresher courses in virology, immunology, and epidemiology in 2020, and we were reminded of the fact that Homo sapiens, the wiliest predator on the planet, has been hunting everything that moves for millennia. These repeated interspecies contacts inherently lead to recurrent zoonosis (nonhuman to human) and anthroponosis (human to nonhuman). Given the accelerating changes in our ecosystems since the neolithic revolution, it was not surprising to see a virus that spreads via aerosolization and liquid droplets cause a pandemic in a few months. The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic begs the question—which viruses could cause a global threat? In this Opinion, the characteristics that make adenoviruses a risk, which include efficient intra- and interspecies transmission, thermostable particles, persistent/latent infections in diverse hosts, and the ability to readily recombine and escape herd immunity, are discussed.     

Synaptic vesicles: is kissing a matter of competence?

The "kiss-and-run" model of exocytosis and endocytosis predicts that synaptic vesicles can undergo fast and efficient recycling, after fusion with the plasmalemma, without intermixing of membranes. Evidence is mounting from several new experimental approaches that kiss-and-run occurs at synapses. Distinct vesicle pools, which initially were identified in morphological terms, are now being characterized in biochemical and functional terms. In addition, at least two functional recycling pathways, operating on different time scales (from milliseconds to tens of seconds), have been shown to coexist in the same synaptic system, and the two pathways appear to be differentially regulated. Taken together, these data suggest that kiss-and-run operates in parallel with the classical, coated-vesicle recycling. Here, we review recent evidence for kiss-and-run recycling and discuss whether it is a distinct process, dependent on the molecular organization of the fusing vesicle. We propose that vesicles undergo a process of "competence maturation". According to this view, the specific molecular make-up of the vesicles, their location and their interactions with nerve terminal proteins might determine not only the differential availability of the vesicles for fusion and neurotransmitter release but also the recycling path that they will follow.     

αB-crystallin polydispersity is a consequence of unbiased quaternary dynamics

The inherent heterogeneity of many protein assemblies complicates characterization of their structure and dynamics, as most biophysical techniques require homogeneous preparations of isolated components. For this reason, quantitative studies of the molecular chaperone αB-crystallin, which populates a range of interconverting oligomeric states, have been difficult, and the physicochemical basis for its polydispersity has remained unknown. Here, we perform mass spectrometry experiments to study αB-crystallin and extract detailed information as to its oligomeric distribution and exchange of subunits under a range of conditions. This allows a determination of the thermodynamic and kinetic parameters that govern the polydisperse ensemble and enables the construction of a simple energy profile for oligomerization. We find that the quaternary structure and dynamics of the protein can be explained using a simple model with just two oligomer-independent interactions (i.e., interactions that are energetically identical in all oligomers from 10mers to 40mers) between constituent monomers. As such, the distribution of oligomers is governed purely by the dynamics of individual monomers. This provides a new means for understanding the polydispersity of αB-crystallin and a framework for interrogating other heterogeneous protein assemblies.     

What is a category? The case of rough-and-tumble play

The intent of this paper is to outline a process by which we redefined an ambiguous behavioral category, rough-and-tumble play (R&T), using ethological and ethnographic methods (i.e., factor analyses, motivational/functional analyses, and interviews). Results suggest that sociometrically rejected and popular elementary school children have different concepts of R&T. For the former group, R&T and aggression seem to be interrelated and serve similar functions, while for the latter group R&T is a playful, social affiliative category. Interview results suggest that a cognitive processing difference between the groups may be at the root of this difference.     

Pr is a member of a restricted class of σ70-dependent promoters that lack a recognizable ?10 element

The Pr promoter is the first verified member of a class of bacterial σ⁷⁰-promoters that only possess a single match to consensus within its −10 element. In its native context, the activity of this promoter determines the ability of Pseudomonas putida CF600 to degrade phenolic compounds, which provides proof-of-principle for the significance of such promoters. Lack of identity within the −10 element leads to non-detection of Pr-like promoters by current search engines, because of their bias for detection of the −10 motif. Here, we report a mutagenesis analysis of Pr that reveals strict sequence requirements for its activity that includes an essential −15 element and preservation of non-consensus bases within its −35 and −10 elements. We found that highly similar promoters control plasmid- and chromosomally- encoded phenol degradative systems in various Pseudomonads. However, using a purpose-designed promoter-search algorithm and activity analysis of potential candidate promoters, no bona fide Pr-like promoter could be found in the entire genome of P. putida KT2440. Hence, Pr-like σ⁷⁰-promoters, which have the potential to be a widely distributed class of previously unrecognized promoters, are in fact highly restricted and remain in a class of their own.     

Pentosome — a new connective tissue component —is a subunit of amyloid P

Summary A new minute connective tissue structure, referred to as pentosome, has been investigated by electron microscopy and its nature has been examined by immunoperoxidase tests. Pentosomes are 3.5-nm wide, particulate structures that have been observed in the posterior chamber of the eye, the connective tissue spaces of the mouse foot-pad and the matrix of the mouse EHS tumor. They are usually found in the vicinity of microfibrils whether they are free or associated with elastic fibers. They tend to be organized into groups forming a three-dimensional semi-crystalline lattice at 10-nm intervals, but are connected by fine filaments. At high magnification, pentosomes appear as hollow structures composed of two parallel pentagons, which respectively measure 2.7 and 3.5 nm, and are held together by a cross-bar. A series of immunoperoxidase tests has only shown antigenicity against a serum protein, the amyloid P component. However, pentosomes are only about one-third the size of the 8.5-nm wide, disk-like segments of the amyloid P molecule. Since they could be subunits of these molecules, such subunits were prepared and compared with pentosomes; they appeared to be identical. It is concluded that the pentosomes found in connective tissue are AP subunits.