Sexually dimorphic response of the mouse submandibular gland to fasting

Summary The submandibular gland of male mice contained 18% more DNA, 34% more RNA and 63% more protein than that of female mice. After a 48-h fasting, the percent loss of gland weight, protein, RNA and DNA was greater in the female than in the male.This study was supported by the U.S. Public Health Service Research Grant CA 17038. The authors are indebted to Mr I. Borcsanyi for his technical assistance.     

Computer optimization of a minimal biped model discovers walking and running

Although people's legs are capable of a broad range of muscle-use and gait patterns, they generally prefer just two. They walk, swinging their body over a relatively straight leg with each step, or run, bouncing up off a bent leg between aerial phases. Walking feels easiest when going slowly, and running feels easiest when going faster. More unusual gaits seem more tiring. Perhaps this is because walking and running use the least energy. Addressing this classic conjecture with experiments requires comparing walking and running with many other strange and unpractised gaits. As an alternative, a basic understanding of gait choice might be obtained by calculating energy cost by using mechanics-based models. Here we use a minimal model that can describe walking and running as well as an infinite variety of other gaits. We use computer optimization to find which gaits are indeed energetically optimal for this model. At low speeds the optimization discovers the classic inverted-pendulum walk, at high speeds it discovers a bouncing run, even without springs, and at intermediate speeds it finds a new pendular-running gait that includes walking and running as extreme cases.     

A novel oxidative cyclization of 4-arylthiosemicarbazides and related compounds

Résumé Il est démontré que les 4-arylthiosemicarbazides sont oxydés par le brome dissous en chloroforme aux 2-hydrazinobenzothiazoles avec de modestes rendements. Une telle réaction sur les thiosémicarbazones correspondants donne les 1-arylidénè 2-(2-benzothiazolyle)hydrazines avec de très bons rendements. Ceux-ci purent, par la suite, être oxydés par le chlorure de fer⁺³ en solution éthanolique aux 3-aryl-s-triazolo (3,4-b)benzothiazoles. La présence de quelques substituants dans les restes 4-aryl et/ou 1-arylidène dans la moitié thiosemicarbazone favoriserait la cyclisation aux 3:4-diaryl-5-mercapto-1:2:4-triazoles.     

Modelling disease outbreaks in realistic urban social networks

Most mathematical models for the spread of disease use differential equations based on uniform mixing assumptions or ad hoc models for the contact process. Here we explore the use of dynamic bipartite graphs to model the physical contact patterns that result from movements of individuals between specific locations. The graphs are generated by large-scale individual-based urban traffic simulations built on actual census, land-use and population-mobility data. We find that the contact network among people is a strongly connected small-world-like graph with a well-defined scale for the degree distribution. However, the locations graph is scale-free, which allows highly efficient outbreak detection by placing sensors in the hubs of the locations network. Within this large-scale simulation framework, we then analyse the relative merits of several proposed mitigation strategies for smallpox spread. Our results suggest that outbreaks can be contained by a strategy of targeted vaccination combined with early detection without resorting to mass vaccination of a population.     

Olfaction: scent-triggered navigation in honeybees

The honeybee, Apis mellifera, navigates rapidly and accurately to food sources that are often kilometres away. They achieve this by learning visual cues, such as the location and colour of nectar-bearing flowers, and chemical cues, such as the scent and the taste of the nectar. Here we train bees to visit differently scented sugar feeders placed at specific outdoor locations and find that they can be induced to visit the same locations simply by having the corresponding scent blown into the hive, even when the destinations no longer have the food or carry the scent. A familiar nectar scent can trigger specific memories of a route and therefore expedite navigation to the food source.     

Real-time prediction of hand trajectory by ensembles of cortical neurons in primates

Signals derived from the rat motor cortex can be used for controlling one-dimensional movements of a robot arm. It remains unknown, however, whether real-time processing of cortical signals can be employed to reproduce, in a robotic device, the kind of complex arm movements used by primates to reach objects in space. Here we recorded the simultaneous activity of large populations of neurons, distributed in the premotor, primary motor and posterior parietal cortical areas, as non-human primates performed two distinct motor tasks. Accurate real-time predictions of one- and three-dimensional arm movement trajectories were obtained by applying both linear and nonlinear algorithms to cortical neuronal ensemble activity recorded from each animal. In addition, cortically derived signals were successfully used for real-time control of robotic devices, both locally and through the Internet. These results suggest that long-term control of complex prosthetic robot arm movements can be achieved by simple real-time transformations of neuronal population signals derived from multiple cortical areas in primates.     

The phylogenetic history of immunodeficiency viruses

Knowledge of the phylogenetic history of the human immunodeficiency viruses (HIV-1 and HIV-2) is important for our understanding of the epidemiology of AIDS, the disease caused by these viruses. Reconstruction of the evolutionary tree is hampered, however, by two problems. One is the high variation in nucleotide sequence between the known HIV isolates which can create formidable difficulties in identifying homologous genomic sites that may be used in a molecular phylogenetic reconstruction. Another impediment has been the lack of unequivocal time calibration points: there is only a sparse 'fossil record' for HIV and limited historical epidemiological data. We have largely overcome these difficulties by: (1) a thorough optimal-sequence alignment analysis; (2) the inclusion of sequences of an early (1976) HIV-1 isolate, a recent (1986) HIV-2 isolate and two simian immunodeficiency viruses (SIV) along with five other HIV-1 isolates; and (3) the reconstruction of a minimum-length evolutionary tree based on the envelope-gene variable positions. We conclude that HIV-1 may have evolved from its common ancestor with HIV-2 as recently as 40 years ago.     

Role of corin in trophoblast invasion and uterine spiral artery remodelling in pregnancy

In pregnancy, trophoblast invasion and uterine spiral artery remodelling are important for lowering maternal vascular resistance and increasing uteroplacental blood flow. Impaired spiral artery remodelling has been implicated in pre-eclampsia, a major complication of pregnancy, for a long time but the underlying mechanisms remain unclear. Corin (also known as atrial natriuretic peptide-converting enzyme) is a cardiac protease that activates atrial natriuretic peptide (ANP), a cardiac hormone that is important in regulating blood pressure. Unexpectedly, corin expression was detected in the pregnant uterus. Here we identify a new function of corin and ANP in promoting trophoblast invasion and spiral artery remodelling. We show that pregnant corin- or ANP-deficient mice developed high blood pressure and proteinuria, characteristics of pre-eclampsia. In these mice, trophoblast invasion and uterine spiral artery remodelling were markedly impaired. Consistent with this, the ANP potently stimulated human trophoblasts in invading Matrigels. In patients with pre-eclampsia, uterine Corin messenger RNA and protein levels were significantly lower than that in normal pregnancies. Moreover, we have identified Corin gene mutations in pre-eclamptic patients, which decreased corin activity in processing pro-ANP. These results indicate that corin and ANP are essential for physiological changes at the maternal-fetal interface, suggesting that defects in corin and ANP function may contribute to pre-eclampsia.