Chinchilla "big" and "little" gastrins

Gastrin heptadecapeptides (gastrins I and II which differ in the presence of sulfate on the tyrosine of the latter) have been purified and sequenced from several mammalian species including pig, dog, cat, sheep, cow, human and rat. A 34 amino acid precursor ("big" gastrin), generally accounting for only 5% of total gastrin immunoreactivity, has been purified and sequenced only from the pig, human, dog and goat. Recently we have demonstrated that guinea pig (GP) "little" gastrin is a hexadecapeptide due to a deletion of a glutamic acid in the region 6-9 from its NH2-terminus and that GP "big" gastrin is a 33 amino acid peptide. The chinchilla, like the GP, is a New World hystricomorph. This report describes the extraction and purification of "little" and "big" gastrins from 31 chinchilla antra. Chinchilla "little" gastrin is a hexadecapeptide with a sequence identical to that of the GP and its "big" gastrin is a 33 amino acid peptide with the following sequence: (See text)     

"I" becomes "L": modification of vertical mammaplasty

The problems of the vertical mammaplasty by Lejour (i.e., gathering the skin envelope in one vertical suture, frequent secondary healing problems, and later sagging of the inferior glandular part in the case of large and very large breasts) are well known. A simple modification of the Lejour technique, that is, adding a lateral inframammary scar to shorten the vertical scar length, is presented. The modified L technique was used in 45 patients (90 breasts) between October of 1999 and August of 2001. With an average follow-up of 13 months, the jugular notch-to-nipple distance was 21 cm, the vertical scar length was 8.4 cm, the lateral inframammary scar length was 11 cm, and the average resection weight was 625 g per breast (range, 200 g to 2080 g). Even among patients who had very large glandular bases and resection weights it was possible to achieve a breast base reduction, modeling the glandular corpus to a harmonic, well-projecting, and youthful shape. Slight wound-healing problems with spontaneous cicatrization within 2 weeks occurred in six patients. In two patients who exhibited gigantomastia up to 2080 g per breast, partial mamilla necrosis occurred on one side. Ninety-one percent of the patients reported being "very satisfied" with the outcome, and 9 percent reporting being "satisfied." The authors' modification of the vertical mammaplasty to an L-shaped scar technique enables the surgeon to apply the principles of the Lejour technique for higher resection weights and diminishes wound-healing problems, and it is still a scar-minimizing technique that results in a scar-free cleavage. It is easy to learn and an ideal standard technique for a teaching hospital.     

Nitration in neurodegeneration: deciphering the "Hows" "nYs"

Recent literature has ushered in a new awareness of the diverse post-translational events that can influence protein folding and function. Among these modifications, protein nitration is thought to play a critical role in the onset and progression of several neurodegenerative diseases. While previously considered a late-stage epiphenomenon, nitration of protein tyrosine residues appears to be an early event in the lesions of amyotrophic lateral sclerosis, Parkinson's disease, and Alzheimer's disease. The advent of highly specific biochemical and immunological detection methods reveals that nitration occurs in vivo with biological selectively and site specificity. In fact, nitration of only a single Tyr residue is often sufficient to induce profound changes in the activity of catalytic proteins and the three-dimensional conformation of structural proteins. Presumably, nitration modifies protein function by altering the hydrophobicity, hydrogen bonding, and electrostatic properties within the targeted protein. Most importantly, however, nitrative injury may represent a unifying mechanism that explains how genetic and environmental causes of neurological disease manifest a singular phenotype. In this review and synthesis, we first examine the pathways of protein nitration in biological systems and the factors that influence site-directed nitration. Subsequently, we turn our attention to the structural implications of site-specific nitration and how it affects the function of several neurodegeneration-related proteins. These proteins include Mn superoxide dismutase and neurofilament light subunit in amyotrophic lateral sclerosis, alpha-synuclein and tyrosine hydroxylase in Parkinson's disease, and tau in Alzheimer's disease.     

The "Moi-peau"

To construct a coherent identity, humans must distinguish what belongs to the external, perceived world from what belongs to their own inner world and the inner world of other individuals. Based on the theory developed by S. Freud and on work by ethologists, a number of psychoanalysts (J. Bowlby, R.A. Spitz, D.W. Winnicott, etc.) have underlined the importance of early tactile exchanges with the mother if a child is to become an autonomous individual who feels secure within what he or she perceives to be sound and reliable mental and physical boundaries. More recently, other psychoanalysts (E. Bick, W.R. Bion, etc.) have studied the fantasized mental structures that form the limits between an individual's inner mental space and the external world (including other individuals). As part of this theoretical psychoanalytical movement, Didier Anzieu, a French psychoanalyst, started to develop the concept of the "Moi-peau" in 1974. The "Moi-peau" designates a fantasized reality that a child uses during its early development to represent itself as "me", based on its experience of the body surface. The child, enveloped in its mother's care, fantasizes of a skin shared with its mother: on one side the mother (the outer layer of the "Moi-peau"), and on the other side the child (the inner layer of the "Moi-peau"). These two layers must separate gradually if the child is to acquire its own me-skin. D. Anzieu's work allowed dermatologists and other specialists, such as pediatricians, to focus on the quality of early tactile exchanges between a mother and her child, including the child with a chronic skin disorder. It also helped dermatologists to recognize patients with "borderline" states, which are particularly frequent in dermatology (ereutophobia, dysmorphophobia, tattooing, self-mutilation, artefacta dermatitis). These borderline patients are adults who, as a result of their mental conflicts, adopt defense mechanisms derived from both neurotic and psychotic functioning. Their complaints reflect difficulties with the solidity of their mental and physical limits: their real skin is metaphorically linked to the fantasized mental structure that delimits the individual mental space. Among other clinical characteristics, they have a "pathology of action" and frequently attack their own skin, paradoxically, in order to test the solidity and reliability of their own limits. Finally, D. Anzieu's work encouraged dermatologists to use psychotherapeutic approaches in parallel to classical dermatologic approaches, when necessary, and helped them better understand how psychoanalysts work with patients who have not yet acquired their own "Moi-peau". As a result, D. Anzieu was among the first to reconcile dermatologists and psychoanalysts.     

"Ant" and "grasshopper" life-history strategies in Saccharomyces cerevisiae

From the evolutionary and ecological points of view, it is essential to distinguish between the genetic and environmental components of the variability of life-history traits and of their trade-offs. Among the factors affecting this variability, the resource uptake rate deserves particular attention, because it depends on both the environment and the genetic background of the individuals. In order to unravel the bases of the life-history strategies in yeast, we grew a collection of twelve strains of Saccharomyces cerevisiae from different industrial and geographical origins in three culture media differing for their glucose content. Using a population dynamics model to fit the change of population size over time, we estimated the intrinsic growth rate (r), the carrying capacity (K), the mean cell size and the glucose consumption rate per cell. The life-history traits, as well as the glucose consumption rate, displayed large genetic and plastic variability and genetic-by-environment interactions. Within each medium, growth rate and carrying capacity were not correlated, but a marked trade-off between these traits was observed over the media, with high K and low r in the glucose rich medium and low K and high r in the other media. The cell size was tightly negatively correlated to carrying capacity in all conditions. The resource consumption rate appeared to be a clear-cut determinant of both the carrying capacity and the cell size in all media, since it accounted for 37% to 84% of the variation of those traits. In a given medium, the strains that consume glucose at high rate have large cell size and low carrying capacity, while the strains that consume glucose at low rate have small cell size but high carrying capacity. These two contrasted behaviors may be metaphorically defined as "ant" and "grasshopper" strategies of resource utilization. Interestingly, a strain may be "ant" in one medium and "grasshopper" in another. These life-history strategies are discussed with regards to yeast physiology, and in an evolutionary perspective.     

cAMP regulation of "pathogenic" and "saprophytic" fungal spore germination

We report on the elucidation of two separate pathways of spore germination in a plant pathogenic fungus Colletotrichum gloeosporioides f. sp. aeschynomene. Conidia of the fungus can germinate either from one side or from both sides, depending on external conditions. In shake culture that includes an extract made up from fresh peas, the unicellular conidium divides and one of the two cells develops a germ tube. On a solid surface this germ tube differentiates an appressorium. In rich medium without pea extract, germination is highly similar to Aspergillus spore germination: the conidium swells, forms a single germ tube and then divides and forms a second germ tube. Conidia that germinate in a rich medium do not form appressoria even on a solid surface and are non-pathogenic. In rich medium, cAMP stimulates germination in rich liquid cultures and induces appressoria formation on a hard surface. In pea extract cAMP induces swelling and formation of irregular germ tubes and appressoria. Our results suggest that plant surface signals induce pathogenic-specific spore germination in a cAMP-independent manner. cAMP is required for saprophytic germination and for appressorium formation.     

Orienting reflex: "targeting reaction" and "searchlight of attention"

The concept of orienting reflex based on the principle of vector coding of cognitive and executive processes is proposed. The orienting reflex to non-signal and signal stimuli is a set of orienting reactions: motor, autonomic, neuronal, and subjective emphasizing new and significant stimuli. Two basic mechanisms can be identified within the orienting reflex: a "targeting reaction" and a "searchlight of attention". In the visual system the first one consists in a foveation of a target stimulus. The foveation is performed with participation of premotor neurons excited by saccadic command neurons of the superior colliculi. The "searchlight of attention" is based on the resonance of gamma-oscillations in the reticular thalamus selectively enhancing responses of cortical neurons (involuntary attention). The novelty signal is generated in novelty neurons of the hippocampus, which are selectively tuned to a repeatedly presented standard stimulus. The selective tuning is caused by the depression of plastic synapses representing a "neuronal model" of the standard stimulus. A mismatch of the novel stimulus with the established neuronal model gives rise to a "novelty signal" enhancing the novel input. The novelty signal inhibits current conditioned reflexes (external inhibition) contributing to redirecting the behavior. By triggering the expression of early genes the novelty signal initiates the formation of the long-term memory connected with neoneurogenesis.     

Teaching "Species"

A clear understanding of the term "species" is fundamental to the subject of evolution. However, introductory textbooks often fail to address this topic until one of the later chapters, after having used the term species in all preceding chapters. Furthermore, definitions of terms critical to a clear understanding of this subject are often vague or absent in chapters on species concepts. We feel the popular notion of a "species problem" has been unnecessarily inflated by this less-than-effective educational approach. Clearly addressing this essential subject at the beginning of a course on evolution will prepare students to learn the details and complexities of evolution. Here we provide the background for an alternative approach to this foundational topic, followed by an outlined lesson plan. We emphasize early introduction of this subject in texts and courses using unambiguous terminology and including the historical development of species concepts.     

"Green-like" and "red-like" RubisCO cbbL genes in Rhodobacter azotoformans

We found that Rhodobacter azotoformans IFO 16436T contains two different cbbL genes coding form I ribulose-1,5-bisphosphate carboxylase/oxygenase (RubisCO) large subunits. One gene is located within a "green-like" group of the RubisCO phylogenetic tree, and the other is located within a "red-like" group. This is the first report that one organism contains both green-like and red-like RubisCO genes. Moreover, by PCR using primers which amplify two green-like and red-like cbbL genes alternatively and dot blot hybridization, we demonstrated that Rhodobacter blasticus, Rhodobacter capsulatus, and Rhodobacter veldkampii possess only green-like cbbL genes, and Rhodobacter sphaeroides possesses only a red-like cbbL gene. In the cbbL phylogenic analysis, R. spaeroides and R. azotoformans 1 (red-like) formed a cluster within the red-like group, and R. capsulatus, R. azotoformans 2 (green-like), R. blasticus, and R. veldkampii formed a cluster within the green-like group. This suggests that red-like cbbL genes of Rhodobacter species were derived from one ancestor, and green-like cbbL genes were derived from another ancestor. On the other hand, molecular phylogeny of the bacteria indicates that R. veldkampii, which has only a green-like cbbL gene, is the earliest evolved Rhodobacter species and that R. azotoformans and R. sphaeroides, which have red-like cbbL genes, are the latest evolved. Consequently, the following hypothesis is proposed: the common ancestor of Rhodobacter had a green-like cbbL gene, the common ancestor of R. azotoformans and R. sphaeroides subsequently obtained a red-like cbbL gene by a horizontal gene transfer, and the ancestor of R. sphaeroides later lost the green-like cbbL gene.     

Opossum (Didelphis virginiana) "little" and "big" gastrins

1. "Little" gastrins from most mammalian species are 17 amino acid peptides and the precursor "big" gastrins are 34 amino acid peptides. 2. "Little" gastrins of the New World hystricomorphs, guinea-pig and chinchilla, are 16 amino acid peptides due to deletion of a glutamic acid in the region 6-9 from their NH2-terminus and the corresponding "big" gastrins are 33 amino acid peptides. 3. Antral gastrins from the opossum, a New World marsupial, have a glutamic acid deletion in the same region as the hystricomorph gastrins. 4. Opossum "big" gastrin is a 33 amino acid peptide with the following sequence: less than ELGPQDLPYLTADLSKKQGPWLEEEEAYGWMDF#.     

"Craziness" and "visions": experiences after a stroke.

For a stroke victim there may be at least three types of strange occurrences: incorrect saying, seeing, and thinking. To the patient only the third seems to be "crazy". After a stroke (left hemisphere), which mainly produced serious aphasia, I (the patient) felt crazy two or three times when someone said something I expected him to say. On the other hand, my initial aphasic "gibberish speech" and an occasional false vision did not seem crazy. In my case the vision is always a car or a child, seen on my extreme right, where I am otherwise blind from the stroke. I am always driving when it happens; in recent years this phenomenon occurs when I am tired or tense, or the light is poor. These rapid visions do not seem insane but merely physical problems in my eyes, much like ordinary people''s dreams.     

Physical separation of "suppressor" from "helper" thymocytes.

Thymocytes from 1-month-old NZB/W mice were separated at unit gravity and then studied for helper or suppressor effects in a GVH assay. Thymocytes with a settling rate of 4 to 6 mm/hr suppressed but did not help. In contrast, help but no suppression characterized thymocytes settling at 6 to 10 mm/hr. Thus helper and suppressor thymocytes in this GVH assay were physically separated.     

Coding "what" and "when" in the Archer fish retina

Traditionally, the information content of the neural response is quantified using statistics of the responses relative to stimulus onset time with the assumption that the brain uses onset time to infer stimulus identity. However, stimulus onset time must also be estimated by the brain, making the utility of such an approach questionable. How can stimulus onset be estimated from the neural responses with sufficient accuracy to ensure reliable stimulus identification? We address this question using the framework of colour coding by the archer fish retinal ganglion cell. We found that stimulus identity, “what”, can be estimated from the responses of best single cells with an accuracy comparable to that of the animal''s psychophysical estimation. However, to extract this information, an accurate estimation of stimulus onset is essential. We show that stimulus onset time, “when”, can be estimated using a linear-nonlinear readout mechanism that requires the response of a population of 100 cells. Thus, stimulus onset time can be estimated using a relatively simple readout. However, large nerve cell populations are required to achieve sufficient accuracy.

Authors Summary

In our interaction with the environment we are flooded with a stream of numerous objects and events. Our brain needs to understand the nature of these complex and rich stimuli in order to react. Research has shown ways in which a ‘what’ stimulus was presented can be encoded by the neural responses. However, to understand ‘what was the nature of the stimulus’ the brain needs to know ‘when’ the stimulus was presented. Here, we investigated how the onset of visual stimulus can be signalled by the retina to higher brain regions. We used archer fish as a framework to test the notion that the answer to the question of ‘when’ something has been presented lies within the larger cell population, whereas the answer to the question of ‘what’ has been presented may be found at the single-neuron level. The utility of the archer fish as model animal stems from its remarkable ability to shoot down insects settling on the foliage above the water level, and its ability to distinguish between artificial targets. Thus, the archer fish can provide the fish equivalent of a monkey or a human that can report psychophysical decisions.     

Binding of lectins to "young" and "old" human erythrocytes

"Old" human erythrocytes showed a 21.2% decrease in cell surface area and a 2% decrease in the number of WGA receptor sites, but a 27% increase in the distribution density of the WGA (lectin) receptor site, when compared with "young" human erythrocytes. For a list of lectin abbreviations, see Materials and methods). Both "young" and "old" erythrocytes exhibited very weak binding activity for 125I-labeled PNA, but there was no difference in binding activity for PNA between "young" erythrocytes and "old" ones. Compared with "young" erythrocytes, decreases in the number and distribution density of receptor sites for five lectins including LPA, Con A, RCA-II, SBA and BPA on the cell surface were observed in aged erythrocytes. "Old" erythrocytes also showed a decrease in the number of PHA-E receptor sites, while the distribution density of the same receptor site remained unchanged. In view of these and other observations, it is thought that human erythrocyte aging is accompanied by elimination of some glycoconjugates which have affinity for six lectins, LPA, Con A, RCA-II, PHA-E, SBA and BPA, whereas no WGA receptor-containing glycoconjugates are released from erythrocyte membranes. Elimination of the glycoconjugates results in shrinkage of erythrocytes to reduce their cell surface areas.     

Taking the "I" out of IRB--and putting "community" in

If one looks back on the history of American research ethics, a bold pattern emerges. Since World War II, about every twenty years or so a breach of the social contract between investigators and human research subjects galvanizes public and professional interest in the ethical foundations and oversight mechanisms governing research with humans.     

The use of multifolded pericranial flaps as "plugs" and "pads"

Pericranial flaps are thin and, hence, their volumes are small. Therefore, their use for soft-tissue augmentation has not been popular. In this article, the author introduces a new concept: the use of a multifolded pericranial flap as a "plug" or a "pad" for localized contour defects. Eight patients were included in the study. In all cases, an anteriorly based pericranial flap was used, and the flap was folded on itself several times to increase its bulk. The results were satisfactory in all patients. The literature on the topic is reviewed, and the blood supply of pericranial flaps is discussed.     

Revisiting "scale-free" networks

Recent observations of power-law distributions in the connectivity of complex networks came as a big surprise to researchers steeped in the tradition of random networks. Even more surprising was the discovery that power-law distributions also characterize many biological and social networks. Many attributed a deep significance to this fact, inferring a "universal architecture" of complex systems. Closer examination, however, challenges the assumptions that (1) such distributions are special and (2) they signify a common architecture, independent of the system's specifics. The real surprise, if any, is that power-law distributions are easy to generate, and by a variety of mechanisms. The architecture that results is not universal, but particular; it is determined by the actual constraints on the system in question.     

Short electric-field pulses convert DNA from "condensed" to "free" conformation

Electric-field pulses of e.g. 20 kV/cm and 100 μs induce a strong decrease in the scattered light intensity of DNA condensed by spermine. Analysis of this effect demonstrates that the decrease of the scattered light intensity results from decondensation of DNA. The decondensation reaction requires an electric-field strength exceeding a threshold value. Complete decondensation can be achieved at field strength that are only slightly higher than the threshold value. The decondensation process is strongly accelerated at high electric-field strengths. At 30 kV/cm, the decondensation time constant is ～8 μs, corresponding to an acceleation factor of 10⁵ relative to the field-free decondensation reaction. The dependence of the time constants on the electric-field strength suggests that the field-induced decondensation is due to a dissociation field effect. The condensation process observed after electric-field pulses at low concentrations of DNA and spermine shows a characteristic induction period, which strongly depends on the spermine concentration. This induction period reflects the time required for the binding of spermine to DNA, until the degree of binding is sufficiently high for the condensation reaction. The fast dissociation of condensed DNA by electric-field pulses together with a relatively long lifetime of the free DNA results in a reaction cycle resembling a hysteresis loop.     

THE POWER OF THE " A" -" NOT A" METHOD

The " A" - " Not A" method is a rating method with two categories. It is often treated as a discrimination method. Unlike forced choice procedures, the Thurstonian model for this method involves a choice criterion. In statistical tests, it is treated as a comparison of two proportions. In this paper, the power for hypothesis tests involving the monadic and replicated monadic " A" - " Not A" method is discussed. The power functions and the sample sizes needed for 80% power are given based on Thurstone's δ. Designs with equal and unequal allocations for A and A (Not A) samples are considered. The power of the method is also compared with that of four forced choice methods under the assumption that the perceptual variance is identical among methods. The comparison shows that, in general, the power for the five methods ranks from high to low: the 3-AFC, 2-AFC, " A" - " Not A", triangular and duo-trio. The comparison also shows that, based on the same number of panelists and/or the same sample size for the A and A⁻ samples for the methods, if the panelists are not too discrepant and the choice criterion in the " A" - " Not A" method is not too strict or too lax, the power of the " A" - " Not A" method is very close to that of the 2-AFC method.