“Menstrual induction” with sulproston

The PGE₂-analogue Sulproton (16-phenoxy·ω-17,18,19,20-tetranor-PGE₂-mythylsulfonylamide) was administered to 200 medically and gynecologically normal women who were 17±0.4 days beyond their expected menstrual period and who had a positive pregnancy test. The intramuscular impact dose (500 μg repeated after 4 hours) caused an immediate tonic uterine contraction which compromised the estradiol 17β, progesterone and chorionic gonadotropin production within the fetoplacental unit, and thereby allowed the evolution of cyclic uterine activity, cervical dilatation and tissue expulsion.Pregnancy termination was complete in 92% of women, 5.5% required surgical curettage and 2.5% were given a second Sulproston treatment 2–3 weeks after the first to remove retained tissue from the uterus. The medical induction of menstruation was preferred by 83% of the women who had previously experienced surgical termination of pregnancy. Normal menstruation resumed in all women after 36±0.9 days. The majority of 42 women questioned found Sulproston a satisfactory, safe, simple and effective drug regimen for “menstrual induction”.     

“Laughter” and “Smile” in Barbary Macaques (Macaca sylvanus)

In an observational study on semi-free Barbary macaques it was investigated whether the phylogenetic roots of human laughter and smile can be traced back to the genus Macaca. On the basis of morphological similarity a ‘relaxed open-mouth display’ as the phylogenetic precursor of the laughter, and a ‘silent bared-teeth display’ as the possible ancestor of the smile can be distinguished in the repertory of the Barbary macaque. Behavioural sequences from focal animal protocols were analyzed in order to establish message and meaning of both displays. Relaxed open-mouth display is regularly observed in the play interactions of juveniles. It is associated with partner-directed behaviour, it is frequently answered by a relaxed open-mouth display of the receiver, and accompanied by a special vocalization. Although up to 50% of the juvenile's play partners were higher ranking than themselves voluntary participation was the rule. Most characteristically, the behaviour patterns shown by both play partners are highly symmetrical and synchronized. Silent bared-teeth display is typically accompanied by evasive or submissive body movements, and occurs primarily in dyadic interactions, mainly by the lower ranking individual. It is not an unidirectional sign of a linear dominance hierarchy, though. Silent bared-teeth display is a frequent answer to aggressive behaviour shown by the receiver. After its performance, an increase of body contact between sender and receiver was observed. Behavioural sequences of senders and receivers are complementary, but lose their asymmetry after occurrence of the display. It is concluded that these results further support Van Hooff 's (1972) view that human laughter and smile have different phylogenetic roots: while silent bared-teeth display is a signal of submission and appeasement, relaxed open-mouth display is rightly called the ‘play face’, and is an expression of fun.     

Distribution of the Character States “Early Sympetaly” and “Late Sympetaly” Within the “Sympetalae Tetracyclicae” and Presumably Allied Groups*

Within the Asteridae (“Sympetalae Tetracyclicae”) two main developmental patterns can be distinguished as regards the formation of corolla tubes, namely “early” and “late sympetaly”. Since the character “ontogeny of sympetaly”, after intensive studies, proved to be valuable for systematic considerations, we now recognize two blocks of orders within the Asteridae (and related groups): the Asteridae A-block and the Asteridae B-block (Figs. 82 and 83). By and large this bipartition referring mainly to the corolla tube development corresponds well with major lineages indentified by recent molecular data (see, e.g., Chase et al., 1993). Asteridae A-block is characterized predominantely by “late sympetaly” the “early sympetaly” in Rubiales and Oleales can be interpreted as derived within this block or can be linked with that in Asteridae B-block. Asteridae B-block is uniform throughout in its “early sympetaly”. In this block it is a primitive character, as judged from its occasional occurrence in the choripetalous Cornales and Apiales (Apiaceae, Araliaceae, Pittosporaceae), which can be regarded as ancestral for block B.     

Integration of “Innate” and “Learned” Components within the IRME for Mussel Recognition in the European Bitterling Rhodeus amarus (Bloch)

The European bitterling (Rhodeus amarus Bloch) practises a rather unusual method of spawning by using the favorable conditions in the gills of a living freshwater mussel (genera Unio and Anodonta) for the embryonic development of its fry. The capacity of mussel recognition was studied in inexperienced individuals with the aid of simultaneous preference tests in which pairs of dummies with increasing similarity to mussels were presented to the animals. The frequency of mussel-referred motor patterns, which were supposed to be species-specific (Wiepkema 1961), supplied the evaluation criterion. The results revealed a hierarchy of effectiveness within the class of relevant stimuli and showed certain effects of additivity typical of an Innate Releasing Mechanism or IRM. By far the most effective stimulus consisted in the specific smell of the mussel which is composed of at least three constituents (protein, hyaluronic acid, ammonium). The water flow itself, produced by the mussel in order to maintain nutritive and respiratory functions, was effective depending on its velocity (3 < v < 12 cm/s), its orientation (suction produced no effect), its direction (vertical > horizontal) and the shape of its field (oval). Within the visual modality only two simple perceptory patterns could be detected (dark spot on a clearer surface, straight horizontal edge), but the visual shape of the mussel as a whole was ignored by inexperienced individuals. Nevertheless the bitterlings are able to learn the shape when exposed to a living mussel and, in addition, it was even possible to condition the animals to an artificial object (inverted pot of clay) by using the mussel-smell flow as a reinforcing stimulus. The final discussion deals with the question of whether it is possible to interpret these “innate” respectively “learned” components of the IRME as sensory counterparts of behavioral structures which simply serve different functions by referring to correspondingly different sectors of the environment. In such a case the epistemological dichotomy regularly associated with the notions of “innate” (= “pre-given phylogenetical knowledge”) and “learned” (= “cognitive increase during ontogeny”) would suffer incisive questioning.     

A critique of the “ultra‐high risk” and “transition” paradigm

The transdiagnostic expression of psychotic experiences in common mental disorder (anxiety/depression/substance use disorder) is associated with a poorer prognosis, and a small minority of people may indeed develop a clinical picture that meets criteria for schizophrenia. However, it appears neither useful nor valid to observe early states of multidimensional psychopathology in young people through the “schizo”‐prism, and apply misleadingly simple, unnecessary and inefficient binary concepts of “risk” and “transition”. A review of the “ultra‐high risk” (UHR) or “clinical high risk” (CHR) literature indicates that UHR/CHR samples are highly heterogeneous and represent individuals diagnosed with common mental disorder (anxiety/depression/substance use disorder) and a degree of psychotic experiences. Epidemiological research has shown that psychotic experiences are a (possibly non‐causal) marker of the severity of multidimensional psychopathology, driving poor outcome, yet notions of “risk” and “transition” in UHR/CHR research are restrictively defined on the basis of positive psychotic phenomena alone, ignoring how baseline differences in multidimensional psychopathology may differentially impact course and outcome. The concepts of “risk” and “transition” in UHR/CHR research are measured on the same dimensional scale, yet are used to produce artificial diagnostic shifts. In fact, “transition” in UHR/CHR research occurs mainly as a function of variable sample enrichment strategies rather than the UHR/CHR “criteria” themselves. Furthermore, transition rates in UHR/CHR research are inflated as they do not exclude false positives associated with the natural fluctuation of dimensional expression of psychosis. Biological associations with “transition” thus likely represent false positive findings, as was the initial claim of strong effects of omega‐3 polyunsatured fatty acids in UHR samples. A large body of UHR/CHR intervention research has focused on the questionable outcome of “transition”, which shows lack of correlation with functional outcome. It may be more productive to consider the full range of person‐specific psychopathology in all young individuals who seek help for mental health problems, instead of “policing” youngsters for the transdiagnostic dimension of psychosis. Instead of the relatively inefficient medical high‐risk approach, a public health perspective, focusing on improved access to a low‐stigma, high‐hope, small scale and youth‐specific environment with acceptable language and interventions may represent a more useful and efficient strategy.     

“Stone-grooming” in Macaca fuscata

During study of mother-infant interactions of Macaca fuscata, a low-ranking female was observed to use a stone to groom her infant. At times a twig or piece of chow was used in the same fashion. The grooming involved a circular movement of the object around the infant's eye. The use of the stone appears to fit recent definitions of tool-use. Suggestions are offered regarding the functions of this occasional behavior; however, because of the rarity of its occurrence no conclusion is offered.     

Evolution of Protein Targeting into “Complex” Plastids: The “Secretory Transport Hypothesis”

Abstract: In algae different types of plastids are known, which vary in pigment content and ultrastructure, providing an opportunity to study their evolutionary origin. One interesting feature is the number of envelope membranes surrounding the plastids. Red algae, green algae and glaucophytes have plastids with two membranes. They are thought to originate from a primary endocytobiosis event, a process in which a prokaryotic cyanobacterium was engulfed by a eukaryotic host cell and transformed into a plastid. Several other algal groups, like euglenophytes and heterokont algae (diatoms, brown algae, etc.), have plastids with three or four surrounding membranes, respectively, probably reflecting the evolution of these organisms by so‐called secondary endocytobiosis, which is the uptake of a eukaryotic alga by a eukaryotic host cell. A prerequisite for the successful establishment of primary or secondary endocytobiosis must be the development of suitable protein targeting machineries to allow the transport of nucleus‐encoded plastid proteins across the various plastid envelope membranes. Here, we discuss the possible evolution of such protein transport systems. We propose that the secretory system of the respective host cell might have been the essential tool to establish protein transport into primary as well as into secondary plastids.     

Characterization of global molecular shape transitions between “open” and “closed” protein conformations

Induced-fit configurational transitions in proteins can take many forms. In cases, we find small “closures” of a loop onto the substrate. In other cases, the structural changes triggered by a ligand involve large rearrangements that affect entire domains. The nature of these transitions is normally assessed by a visual analysis or in terms of simple local geometrical parameters, such as interresidue distances, backbone dihedral angles, and relative displacements between domains. This approach is limited and rather undiscriminating. In this work, we apply recently introduced ideas from macromolecular shape analysis to characterize the global shape changes accompanying “open closed” transitions in proteins. Here, we monitor two distinct properties simultaneously: molecular size and self-entanglements. The method is applied to some proteins exhibiting pairs of structurally different conformations (adenylate kinase, hexokinase, citrate synthase, alcohol dehydrogenase, triosephosphate isomerase, thioredoxin, and aspartate amino-transferase). The conformational change associated with these proteins is classified according to an order parameter that considers various molecular shape features. The results allow one to recognize, in a nonvisual fashion, the likely occurrence of local or global structural rearrangements. In addition, the technique provides an insight into folding features that may remain invariant during the configurational transitions. © 1996 John Wiley & Sons, Inc.     

Transfemoral catheterization of the cavernous sinus outflow with comparison of “central” and “peripheral” gonadotropin patterns in bonnet monkeys

Concentrations of follicle stimulating hormone (FSH) and luteinizing hormone (LH) in central (C) samples obtained by transfemorally catheterizing the inferior petrosal sinus of female bonnet monkeys were compared with those in peripheral (P) samples obtained simultaneously from the saphenous veins of two intact and two oophorectomized bonnet monkeys, before, during, and after luteinizing hormone releasing hormone (LHRH) stimulation. Significant differences between central and peripheral gonadotropin concentrations were detected intermittently in the resting state, and tended to be magnified by LHRH administration. In one animal in which LHRH was fortuitously administered during the course of a spontaneous LH surge, a C/P ratio for LH of 12.71, the maximum observed, was obtained. Spectral analysis exhibited periodicity for LH and, to a lesser extent, for FSH in the oophorectomized, but not in the intact, animals.     

“Impoverished” and “enriched” living conditions influence the proliferation and survival of neurons in crayfish brain

New neurons are added to two bilateral clusters of neurons in crayfish brain throughout their lives. These interneurons are associated with the olfactory and accessory lobes, areas of the brain that receive primary olfactory information and higher order inputs from the visual and tactile receptor systems. The rate of cell proliferation in these four clusters, revealed by BrdU labeling, is sensitive to the living conditions of the animals: individuals isolated in small spaces (impoverished condition) exhibit a lower rate of cell proliferation in comparison to their siblings living together in larger areas (enriched condition), although both groups were fed to satiation. Reduction in the rate of proliferation can be measured 1 to 2 weeks after the animals are subjected to the impoverished condition. Counts of the labeled neurons that survive after 4 weeks of subjection to the two conditions show that fewer new neurons survive in the brains of animals that have lived for 2 weeks in the impoverished condition in comparison to their siblings living in the enriched conditions. Factors such as surface area, depth of water, and social interaction can all play a role in determining both the rate of new neuron production and the incorporation of the new neurons into the brain of freshwater crayfish. The results indicate a high degree of neuronal plasticity in the crayfish brain that is highly sensitive to the conditions under which the animals are kept. © 2000 John Wiley & Sons, Inc. J Neurobiol 45: 215–226, 2000     

Application of the “-Omic-” technologies in phytomedicine

The proof of efficacy of phytopreparations and the determination of their mode of action are permanent challenges for an evidence-based phytotherapy. The technology platform of genomics, proteomics and metabolomics ("-omic-" technologies) are high-throughput technologies. They increase substantially the number of proteins/genes that can be detected simultaneously and have the potential to relate complex mixtures to complex effects in the form of gene/protein expression profiles. Provided that phytopreparation-specific signatures in the form of gene/protein expression profiles can be developed, these technologies will be useful for the chemical and pharmacological standardization and the proof of the toxicological potential of a plant extract. Over a long-term perspective they may economize the proof of efficacy, the determination of the mode of action of phytomedicines and allow to investigate herbal extracts without prominent active principle(s). The application of this genomics revealed already that gene expression profiles induced by single drugs and the ones induced by the combination of the same drugs can be entirely different. These results make the information of the mode of action of isolated "active principles/lead substances" of phytopreparations questionable. The application of the "-omic-" technologies may lead to a change of paradigms towards the application of complex mixtures in medicine and open the new field of phytogenomics, -proteomics and -metabolomics.