“Painting” the target: how local molecular cues define synaptic relationships

A majority of studies on neuronal growth cones focus on the features that particular groups of neurons share. In contrast, questions such as how specific growth cones respond very differently to the same extrinsic cues require cell-specific experimentation. The most succinct cell-specific growth cone responses occur during synaptic targeting. Recent studies have examined one specific growth cone, the Drosophila RP3 motoneuron growth cone, in variously altered microenvironments. In this review, we summarize how such studies are beginning to uncover the repertoire of extrinsic cues that influence the synaptic targeting of a single growth cone. BioEssays 20:941–948, 1998. © 1998 John Wiley & Sons, Inc.     

COMPETITION BETWEEN SEGREGATION DISTORTERS: COEXISTENCE OF “SUPERIOR” AND “INFERIOR” HAPLOTYPES AT THE t COMPLEX

By means of population genetical models, we investigate the competition between sex-specific segregation distorters. Although the models are quite general, they are motivated by a specific example, the t complex of the house mouse. Some variants at this gene complex, the t haplotypes, distort Mendelian segregation in heterozygous males in their favor. The selective advantage at the gamete level is counterbalanced by strong negative fitness effects at the individual level (male sterility or even lethality in both sexes). A plethora of different t haplotypes has been found, both in the field and in the lab. Up to now, however, models have focused on the equilibrium frequency of a single t haplotype. In contrast, we explicitly model the competition between several t haplotypes. A deterministic model for a large, well-mixed population predicts a surprisingly high degree of polymorphism. Haplotypes with seemingly inferior fitness characteristics may easily coexist with “superior” haplotypes. For instance, a lethal haplotype with a low segregation ratio may stably coexist with a sterile haplotype with a high segregation ratio. Stable coexistence is even possible for haplotypes with a segregation disadvantage. A simple stochastic model shows that the same principles apply in the context of a structured metapopulation. Although counterintuitive at first sight, all our results can be explained by the fact that segregation distorters have an inherent advantage when they are rare. We conclude that fitness comparisons are not sufficient to predict the outcome of competition when selective forces are acting at different levels.     

“Hypothetical Mean Organisms” of Mycobacteria

Seven hundred fifty-four strains of mycobacteria were examined using 97 characters, and a “Hypothetical Mean Organism” (HMO) was prepared for each species using numerical classification. The species could be defined as a group of strains showing a mean S-value of 90% or more to a HMO and showing mean S-values of 89% or less to other HMOs. The following species were recognized: (1) M. tuberculosis, combining M. tuberculosis and M. bovis into one species; (2) M. kansasii; (3) M. novum; (4) M. avium, combining M. avium, M. nonchromogenicum, M. gastri, M. intracellulare and M. scrofulaceum into one species; (5) M. marinum; (6) M. thermoresistibile; (7) M. chitae; (8) M. borstelense; (9) M. abscessus; (10) M. fortuitum; (11) M. phlei; (12) M. aurum; (13) M. parafortuitum; (14) M. lacticola; (15) M. smegmatis. Dendrogram of the species showed two main stems, indicating that the genus Mycobacterium be divided into two subgenera, subgenus Mycobacterium (from M. tuberculosis to M. chitae) and subgenus My cornycobacterium (from M. borstelense to M. smegmatis). Some discrepancy was noted between the results of numerical classification using HMOs and that of the “proper” numerical classification, and this discrepancy is discussed.     

Ape-like endocast of “ape-man” Taung

I have identified and illustrated a spherical “dimple” or “depression” on the Taung endocast as indicating the most likely position of the medial end of the lunate sulcus but have not drawn an actual lunate sulcus on Taung because one is not visible. In a recent paper, R.L. Holloway (Am. J. Phys. Anthropol. 77:27–33, 1988) drew a lunate sulcus on his copy of the Taung endocast, incorrectly attributed this sulcus to me, and used it to obtain a ratio of 0.254 to describe “Falk's” position of the lunate sulcus. My published ratio of 0.242 for Taung (Falk: Am. J. Phys. Anthropol. 67:313–315, 1985a) was not considered, although the focus of Holloway's paper was my assessment of the position of the lunate sulcus. Holloway also excluded published ratios for a chimpanzee in my collection from his statistical analysis but, even so, my published ratio for Taung is still only 1.5 standard deviations from his chimpanzee mean. If my chimpanzee brain is included in the sample, the ratio for Taung is 1.2 standard deviations from the mean. Furthermore, one of Holloway's own chimpanzees (B60–7) has a ratio of 0.241, just 0.001 below my ratio for Taung. There is no sulcus where Holloway has drawn one on Taung, his “F(LS)” is not mine, his 2 mm error is not mine, and the correct ratio for my measurement of Tuang is the one that I published, not the one that Holloway attributes to me. Assessment of Holloway's chimpanzee data supports my claim that the dimple on the Taung endocast is within the chimpanzee range for the medial end of the lunate sulcus.     

Initiation,calcification, and form of larval “archaeogastropod” shells

The coiled shell of gastropods begins as a cap-shaped lens of organic and calcified material that covers the posterior dorsal side of the larva. During development the cap enlarges to cover the larval visceral mass. Marginal growth then produces the characteristic coiled shell. One model of the initiation of shell coiling in “archaeogastropods” requires that the shell remains flexible and uncalcified until after torsion, and that muscle contraction during torsion deforms the shell. We describe early shell calcification and tested this requirement of the model for the patellogastropod limpets Tectura scutum and Lottia digitalis, the trochids Calliostoma ligatum and Margarites pupillus and the abalone Haliotis kamtschatkana. We determined the stage of initial calcification by staining larvae with the fluorescent calcium marker calcein and observing them with bright field, crossed polarizing filter, and fluorescence microscopy. In T. scutum the earliest observable shell was calcified and calcium was sometimes detected even before the initial shell was visible. Larvae of the other species deposited a noncalcified matrix that was subsequently calcified, and in C. ligatum and M. pupillus this initial calcification was distinctly spotty. Shells of both patellogastropods and the abalone were demonstrably rigid prior to torsion while the shells of the trochids were not. These results suggest that shell coiling in patellogastropods and abalone is not initiated by contraction of the larval retractor muscle during torsion; in trochids this mechanism is possible. However, analysis of camera lucida drawings of pre- and post-torsional shells of T. scutum and C. ligatum did not detect shell shape changes during torsion. J. Morphol. 235:77–89, 1998. © 1998 Wiley-Liss, Inc.     

Chiral Resolution and Absolute Configuration of the Enantiomers of the Psychoactive “Designer Drug” 3,4‐Methylenedioxypyrovalerone

Illicit rac‐MDPV (3,4‐methylenedioxypyrovalerone), manufactured in clandestine labs, has become widely abused for its cocaine‐like stimulant properties. It has recently been found as one of the toxic materials in the so‐called “bath salts,” producing, among other effects, psychosis and tachycardia in humans when introduced by any of the several routes of administration (e.g., intravenous, oral, etc.). The considerable toxicity of this “designer drug” probably resides in one of the enantiomers of the racemate. In order to obtain a sufficient amount of the enantiomers of rac‐MDPV to determine their activity, we improved the known synthesis of rac‐MDPV and found chemical resolving agents, (+)‐ and (–)‐2’‐bromotetranilic acid, that gave the MDPV enantiomers in >96% enantiomeric excess as determined by ¹H nuclear magnetic resonance and chiral high‐performance liquid chromatography. The absolute stereochemistry of these enantiomers was determined by single‐crystal X‐ray diffraction studies. Chirality 27:287‐293, 2015. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.     

“Isogaba Maware”: quality control of genome DNA by checkpoints

Checkpoints maintain the interdependency of cell cycle events by permitting the onset of an event only after the completion of the preceding event. The DNA replication checkpoint induces a cell cycle arrest until the completion of the DNA replication. Similarly, the DNA damage checkpoint arrests cell cycle progression if DNA repair is incomplete. A number of genes that play a role in the two checkpoints have been identified through genetic studies in yeasts, and their homologues have been found in fly, mouse, and human. They form signaling cascades activated by a DNA replication block or DNA damage and subsequently generate the negative constraints on cell cycle regulators. The failure of these signaling cascades results in producing offspring that carry mutations or that lack a portion of the genome. In humans, defects in the checkpoints are often associated with cancer-prone diseases. Focusing mainly on the studies in budding and fission yeasts, we summarize the recent progress. BioEssays 20 :391–399, 1998.© 1998 John Wiley & Sons Inc.     

Dietary Restraint and Control Over “Wanting” Following Consumption of “Forbidden” Food

Eating behavior can be influenced by the rewarding value of food, i.e., “liking” and “wanting.” The objective of this study was to assess in normal‐weight dietary restrained (NR) vs. unrestrained (NU) eaters how rewarding value of food is affected by satiety, and by eating a nonhealthy perceived, dessert‐specific food vs. a healthy perceived, neutral food (chocolate mousse vs. cottage cheese). Subjects (24NR age = 25.0 ± 8.2 years, BMI = 22.3 ± 2.1 kg/m²; 26NU age = 24.8 ± 8.0 years, BMI = 22.1 ± 1.7 kg/m²) came to the university twice, fasted (randomized crossover design). Per test‐session “liking” and “wanting” for 72 items divided in six categories (bread, filling, drinks, dessert, sweets, stationery (placebo)) was measured, before and after consumption of chocolate mousse/cottage cheese, matched for energy content (5.6 kJ/g) and individual daily energy requirements (10%). Chocolate mousse was liked more than cottage cheese (P < 0.05). After consumption of chocolate mousse or cottage cheese, appetite and “liking” vs. placebo were decreased in NR and NU (P < 0.03), whereas “wanting” was only decreased in NR vs. NU (P ≤ 0.01). In NR vs. NU “wanting” was specifically decreased after chocolate mousse vs. cottage cheese; this decrease concerned especially “wanting” for bread and filling (P < 0.05). To conclude, despite similar decreases in appetite and “liking” after a meal in NR and NU, NR decrease “wanting” in contrast to NU. NR decrease “wanting” specifically for a nonhealthy perceived, “delicious,” dessert‐specific food vs. a nutritional identical, yet healthy perceived, slightly less “delicious,” “neutral” food. A healthy perceived food may thus impose greater risk for control of energy intake in NR.     

What are genes “for” or where are traits “from”? What is the question?

For at least a century it has been known that multiple factors play a role in the development of complex traits, and yet the notion that there are genes “for” such traits, which traces back to Mendel, is still widespread. In this paper, we illustrate how the Mendelian model has tacitly encouraged the idea that we can explain complexity by reducing it to enumerable genes. By this approach many genes associated with simple as well as complex traits have been identified. But the genetic architecture of biological traits, or how they are made, remains largely unknown. In essence, this reflects the tension between reductionism as the current “modus operandi” of science, and the emerging knowledge of the nature of complex traits. Recent interest in systems biology as a unifying approach indicates a reawakened acceptance of the complexity of complex traits, though the temptation is to replace “gene for” thinking by comparably reductionistic “network for” concepts. Both approaches implicitly mix concepts of variants and invariants in genetics. Even the basic question is unclear: what does one need to know to “understand” the genetic basis of complex traits? New operational ideas about how to deal with biological complexity are needed.     

Paleodemography: “Not quite dead”

As Kim Hill¹ recently noted in Evolutionary Anthropology, humans are unique among the hominoids with regard to the length of their lives, as well as other elements in the individual life histories. The evolutionary details that modified a basic pongid life history into a hominid one remain obscure, but aspects of recent human demographic history are assailable. Study of the last 10,000 years or so is an important part of ongoing anthropological discourse, for demographic changes may be intimately linked to such major developments as agriculture and urbanization.^2-8 Whether demographic changes are antecedents for or consequences of these major developments is a matter of great contention, but at the least we should attempt to document the nature of human demographic changes in the recent past. Although this documentation can take different forms, the principal sources are archeological information on past settlement patterns and analyses of prehistoric human skeletal material.     

Various strategies for obtaining artificial hemoproteins: From “hemoabzymes” to “hemozymes”

The design of artificial hemoproteins that could lead to new biocatalysts for selective oxidation reactions of organic compounds presents a huge interest especially in pharmacology, both for a better understanding of the metabolic profile of drugs and for the synthesis of enantiomerically pure molecules that could be involved in the design of drugs.The present results show that the so-called “host-guest strategy” that involves the non-covalent incorporation of anionic water-soluble iron-porphyrins into xylanase A from Streptomyces lividans, a low cost protein, leads to such an artificial hemoprotein that is able to perform the stereoselective oxidation of sulfides.     

An evolutionary interpretation of the “motivation to oviposit”

The ovipositional behavior of parasitoids and other insects is often described by phrases such as “motivation to oviposit” or “ovipositional drive”. This paper shows how an evolutionary (i.e. functional) interpretation can be given to such phrases. A detailed model for the parasitisation of Sycamore aphids by M. pseudoplatani is developed, using experiments by Collins and Dixon (1986). Two models are developed: i) one in which egg complement is the only state variable and ii) one in which egg complement and information concerning host densities are state variables. Comparisons of the behaviour of simulated parasitoids, using the decisions associated with the models, and the experiments suggest that both egg complement and information are important for the parasitoid's decision making. Accepting previously parasitized hosts may be optimal, and not simply an error in parasitoid perception. A number of other detailed predictions are made, such as the relative fitness of first and second eggs in superparasitized hosts and the nature of the memory of the parasitoid.     

Chromosomal localization of the mouse titin gene and its relationto “muscular dystrophy with myositis” and nebulin genes on chromosome 2

In the mouse, the genes for the structural components of the myofibril titin and nebulin, Ttn and Neb, map to proximal Chr 2, as does the gene for a muscle disease, “muscular dystrophy with myositis,” mdm. To facilitate the evaluation of Ttn and Neb as possible candidates for mdm, we have determined their relative map positions, using a Mus spretus/Mus musculus interspecific backcross. The gene order (distances in cM) cen-Vim-16.9 ± 4.7-Neb-7.6 ± 3.0-Ttn, Acra-18.0 ± 4.9-Pax-6-17.7 ± 4.9-ahas been determined. Considering the standard deviations, Neb, Ttn, and Acra could colocalize with mdm. Using Ttn and Neb probes, DNAs from mdm/mdm and mdm/+ mice were tested for restriction fragment variants in comparison to the M. musculus wildtype. No variants have been found with 11 restriction nucleases. Our data corroborate a conserved synteny comprising genes NEB, TTN, CHRNA1 on human Chr 2q.     

“Patient-Like” nude mouse metastatic model of advanced human pleural cancer

Pleural Cancer in humans is a frequently occuring tumor, Recently, clinical ltrials have suggested that chemotherapy and immunotherapy administered intrapleually may elicit responses in early-stage diseases. However, atradiological and pleural endoscopic evaluation, most of the patients are found to have a visceral pleural involvement that is generally refractory to therapy and leads to a poor prognosis. The goal of this study was to construct a nude mouse model of human parietal- and visceral-pleural cancer that could reflect the clinical picture for this disease. The model could then be useful for drug discovery for pleural cancer. A well-differentiated human lung adenocarcinoma was used as intact tissue for implantation. Ten mice underwent parietal-pleural implantation and ten mice visceral-pleural implantation via a novel thoracotomy procedure we have developed. Symptoms of tumor growth were determined from weight loss, repiratory distress, or debilitation. Actual tumor growth and spread were measured at autopsy. The mouse survival curves of each group were estimated by the Kaplan-Meier Method and the difference of the median survial timje was assessed by the Log-rank test. The slopes of mean-mouse weight curves were compared using a standard two-sample t-test. 100% take rate was achieved in constructing the pleural cancer models. Tumor growth was initially assessed by symptomatology and survival: the median survival time was, repectively, 27.9 days 31 days for visceral-pleural and parietal-pleural implanted groups (P<0.05). The comparison between the slopes of the mean weight curves of corresponding groups demonstrated that visceral-pleural implanted animals lost significantly more weight than the parietal-pleural implanted animals (P <.001). Both in the visceral- and pariental-pleural implanted groups, post-mortem analysis revealed that tumor grew in all mic demonstrating local and regional spread mimicking clinical features. However, mediastinal lymph node metastases were observed only in mice with visceral pleural implantation. Patient-like models of human parietal-pleural and visceral-pleural cancer were constructed in nude mice using histologically ilntact human specimens. Tumor symptoms, growth, and spread as well as survival indicated that the parietal-pleural and visceral-pleural models represent, respectively, early-and advanced-stage disease. The “Patient-like” nude mouse models of pleural cancer now allow a rational basis for futher studies of pleural cancer biology, pathophysiology, and therapeutics.     

Genes and structural patterns in ciliates: Vance tartar and the “cellular architects”

The one form of cytoplasmic inheritance that has not been assimilated into the Central Dogma is the inheritance of surface structural patterns, a phenomenon most clearly expressed in cilates. Vance Tartar, although he worked with a genetically undomesticated organism (Stentor coeruleus), provided early evidence for the crucial role of clonally propagated features of the cell cortex. He showed that the capacity for development of cortical organelle systems is associated with a particular relational feature, the “locus of stripe contrast” (LSC), and that clonally inherited cortical variants (homopolar doublets) could be created at will by microsurgical operations that duplicated the LSC. Tartar also hoped to demonstrate the existence of what David Nanney called “cellular architects” by provoking stentors to carry out entirely novel types of morphogenetic performances. He eventually acknowledged failure, although the bizarre juxtapositions by which he attempted to elicit such novel performances did bring about specific and illuminating defects in cortical development. Subsequent analyses of similar defects in other ciliates revealed not the unitary “pattern factor” postulated by Tartar, but rather a hierarchy of distinct patterning mechanisms. Nonetheless, by pursuing an embryological approach toward morphogenesis in a highly regulative ciliate, Tartar uncovered relational aspects of pattern-determination; this, in my view, delineates the major problem that we must solve to gain understanding of intracellular patterning. © 1992 Wiley-Liss, Inc.     

“Candidatus Phytoplasma asteris” and “Candidatus Phytoplasma mali” strains infecting sweet and sour cherry in the Czech Republic

A survey for phytoplasma diseases was conducted in a sweet and sour cherry germplasm collection and in cherry orchards within the Czech Republic during 2014–2015. Phytoplasmas were detected in 21 symptomatic trees. Multiple infections of cherry trees by diverse phytoplasmas of 16SrI and 16SrX groups and 16SrI‐A, 16SrI‐B, 16SrI‐L, 16SrX‐A subgroups were detected by restriction fragment length polymorphism (RFLP). Nevertheless, phylogenetic analysis placed subgroups 16SrI‐B and 16SrI‐L inseparable together onto one branch of phylogenetic tree. This is the first report of subgroups 16SrI‐A and 16SrI‐L in Prunus spp., and subgroup 16SrX‐A in sour cherry trees. Additionally, novel RFLP profiles for 16SrI‐A and 16SrI‐B‐related phytoplasmas were found in cherry samples. Phytoplasmas with these novel profiles belong, however, to their respective 16SrI‐A or 16SrI‐B phylogenetic clades.     

Speciation and the “shifting balance” in a continuous population

Shifts between adaptive peaks, caused by sampling drift, are involved in both speciation and adaptation via Wright's “shifting balance.” We use techniques from statistical mechanics to calculate the rate of such transitions for a population in a single panmictic deme and for a population which is continuously distributed over one- and two-dimensional regions. This calculation applies in the limit where transitions are rare. Our results indicate that stochastic divergence is feasible despite free gene flow, provided that neighbourhood size is low enough. In two dimensions, the rate of transition depends primarily on neighbourhood size N and only weakly on selection pressure (≈s^k exp(− cN)), where k is a number determined by the local population structure, in contrast with the exponential dependence on selection pressure in one dimension (≈exp(− cN √s)) or in a single deme (≈exp(− cNs)). Our calculations agree with simulations of a single deme and a one-dimensional population.     

“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.     

“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.