The free energy for hydrolysis of a microtubule-bound nucleotide triphosphate is near zero: all of the free energy for hydrolysis is stored in the microtubule lattice.

The standard free energy for hydrolysis of the GTP analogue guanylyl-(a,b)-methylene-diphosphonate (GMPCPP), which is -5.18 kcal in solution, was found to be -3.79 kcal in tubulin dimers, and only -0.90 kcal in tubulin subunits in microtubules. The near-zero change in standard free energy for GMPCPP hydrolysis in the microtubule indicates that the majority of the free energy potentially available from this reaction is stored in the microtubule lattice; this energy is available to do work, as in chromosome movement. The equilibrium constants described here were obtained from video microscopy measurements of the kinetics of assembly and disassembly of GMPCPP-microtubules and GMPCP-microtubules. It was possible to study GMPCPP-microtubules since GMPCPP is not hydrolyzed during assembly. Microtubules containing GMPCP were obtained by assembly of high concentrations of tubulin-GMPCP subunits, as well as by treating tubulin-GMPCPP-microtubules in sodium (but not potassium) Pipes buffer with glycerol, which reduced the half-time for GMPCPP hydrolysis from > 10 h to approximately 10 min. The rate for tubulin-GMPCPP and tubulin-GMPCP subunit dissociation from microtubule ends were found to be about 0.65 and 128 s-1, respectively. The much faster rate for tubulin-GMPCP subunit dissociation provides direct evidence that microtubule dynamics can be regulated by nucleotide triphosphate hydrolysis

The Nature and Cause of Spectral Variability in LMC X-1

We present the results of a long-term observation campaign of the extragalactic wind-accreting black-hole X-ray binary LMC X-1, using the Proportional Counter Array on the Rossi X-Ray Timing Explorer (RXTE). The observations show that LMC X-1's accretion disk exhibits an anomalous temperature-luminosity relation. We use deep archival RXTE observations to show that large movements across the temperature-luminosity space occupied by the system can take place on time scales as short as half an hour. These changes cannot be adequately explained by perturbations that propagate from the outer disk on a viscous timescale. We propose instead that the apparent disk variations reflect rapid fluctuations within the Compton up-scattering coronal material, which occults the inner parts of the disk. The expected relationship between the observed disk luminosity and apparent disk temperature derived from the variable occultation model is quantitatively shown to be in good agreement with the observations. Two other observations support this picture: an inverse correlation between the flux in the power-law spectral component and the fitted inner disk temperature, and a near-constant total photon flux, suggesting that the inner disk is not ejected when a lower temperature is observed.Comment: 35 pages, 10 figures, to be published in Ap

Estradiol and Bisphenol A Stimulate Androgen Receptor and Estrogen Receptor Gene Expression in Fetal Mouse Prostate Mesenchyme Cells

doi:10.1289/ehp.9804Hormonal alterations during development have lifelong effects on the prostate gland. Endogenous estrogens, including 17β-estradiol (E2), and synthetic estrogenic endocrine disruptors, such as bisphenol A (BPA), have similar effects on prostate development. Increasing exposure to estrogens within the low-dose, physiologic range results in permanent increases in the size and androgen responsiveness of the prostate, whereas exposure within the high-dose, pharmacologic range has the opposite effects

Modeling of oropharyngeal articulatory adaptation to compensate for the acoustic effects of nasalization

Hypernasality is one of the most detrimental speech disturbances that lead to declines of speech intelligibility. Velopharyngeal inadequacy, which is associated with anatomic defects such as cleft palate or neuromuscular disorders that affect velopharygneal function, is the primary cause of hypernasality. A simulation study by Rong and Kuehn [J. Speech Lang. Hear. Res. 55(5), 1438–1448 (2012)] demonstrated that properly adjusted oropharyngeal articulation can reduce nasality for vowels synthesized with an articulatory model [Mermelstein, J. Acoust. Soc. Am. 53(4), 1070–1082 (1973)]. In this study, a speaker-adaptive articulatory model was developed to simulate speaker-customized oropharyngeal articulatory adaptation to compensate for the acoustic effects of nasalization on /a/, /i/, and /u/. The results demonstrated that (1) the oropharyngeal articulatory adaptation effectively counteracted the effects of nasalization on the second lowest formant frequency (F2) and partially compensated for the effects of nasalization on vowel space (e.g., shifting and constriction of vowel space) and (2) the articulatory adaptation strategies generated by the speaker-adaptive model might be more efficacious for counteracting the acoustic effects of nasalization compared to the adaptation strategies generated by the standard articulatory model in Rong and Kuehn. The findings of this study indicated the potential of using oropharyngeal articulatory adaptation as a means to correct maladaptive articulatory behaviors and to reduce nasalit

Dynamic Models of Language Evolution: The Linguistic Perspective

Language is probably the key defining characteristic of humanity, an immensely powerful tool which provides its users with an infinitely expressive means of representing their complex thoughts and reflections, and of successfully communicating them to others. It is the foundation on which human societies have been built and the means through which humanity’s unparalleled intellectual and technological achievements have been realized. Although we have a natural intuitive understanding of what a language is, the specification of a particular language is nevertheless remarkably difficult, if not impossible, to pin down precisely. All languages contain many separate yet integral systems which work interdependently to allow the expression of our thoughts and the interpretation of others’ expressions: each has, for instance, a set of basic meaningless sounds (e.g. [e], [l], [s]) which can be combined to make different meaningful words and parts of words (e.g. else, less, sell, -less ); these meaningful units can be combined to make complex words (e.g. spinelessness, selling ), and the words themselves can then be combined in very many complex ways into phrases, clauses and an infinite number of meaningful sentences; finally each of these sentences can be interpreted in dramatically different ways, depending on the contexts in which it is uttered and on who is doing the interpretation. Languages can be analysed at any of these different levels, which make up many of the sub-fields of linguistics, and the primary job of linguistic theorists is to try to explain the rules which best explain these complex combinations

Endocrine disruptors and obesity

The purpose of this review is to summarise current evidence that some environmental chemicals may be able to interfere in endocrine regulation of energy metabolism and adipose tissue structure. Recent findings demonstrate that such endocrine disrupting chemicals, termed “obesogens”, can promote adipogenesis and cause weight gain. This includes compounds to which the human population is exposed in daily life through their use in pesticides/herbicides, industrial and household products, plastics, detergents, flame retardants and ingredients in personal care products. Animal models and epidemiological studies have shown that an especially sensitive time for exposure is in utero or the neonatal period. In summarising the actions of obesogens, it is noteworthy that as their structures are mainly lipophilic, their ability to increase fat deposition has the added consequence of increasing the capacity for their own retention. This has the potential for a vicious spiral not only of increasing obesity but also increasing retention of other lipophilic pollutant chemicals with an even broader range of adverse actions. This might offer an explanation as to why obesity is an underlying risk factor for so many diseases including cancer

Gestational Exposure to Low Dose Bisphenol A Alters Social Behavior in Juvenile Mice

Bisphenol A (BPA) is a man-made compound used to make polycarbonate plastics and epoxy resins; public health concerns have been fueled by findings that BPA exposure can reduce sex differences in brain and some behaviors. We asked if a low BPA dose, within the range measured in humans, ingested during pregnancy, would affect social behaviors in prepubertal mice. We noted sex differences in social interactions whereby females spent more time sitting side-by-side, while males engaged in more exploring and sitting alone. In addition BPA increased display of nose-to-nose contacts, play solicitations and approaches in both sexes. Interactions between sex and diet were found for self grooming, social interactions while sitting side-by-side and following the other mouse. In all these cases interactions were produced by differences between control and BPA females. We examined brains from embryos during late gestation to determine if gene expression differences might be correlated with some of the sexually dimorphic or BPA affected behaviors we observed. Because BPA treatments ended at birth we took the brains during embryogenesis to increase the probability of discovering BPA mediated effects. We also selected this embryonic age (E18.5) because it coincides with the onset of sexual differentiation of the brain. Interestingly, mRNA for the glutamate transporter, Slc1a1, was enhanced by exposure to BPA in female brains. Also we noted that BPA changed the expression of two of the three DNA methyltransferase genes, Dnmt1 and Dnmt3a. We propose that BPA affects DNA methylation of Sc1a1 during neural development. Sex differences in juvenile social interactions are affected by BPA and in particular this compound modifies behavior in females

A Microsatellite Guided Insight into the Genetic Status of Adi, an Isolated Hunting-Gathering Tribe of Northeast India

Tibeto-Burman populations of India provide an insight into the peopling of India and aid in understanding their genetic relationship with populations of East, South and Southeast Asia. The study investigates the genetic status of one such Tibeto-Burman group, Adi of Arunachal Pradesh based on 15 autosomal microsatellite markers. Further the study examines, based on 9 common microsatellite loci, the genetic relationship of Adi with 16 other Tibeto-Burman speakers of India and 28 neighboring populations of East and Southeast Asia. Overall, the results support the recent formation of the Adi sub-tribes from a putative ancestral group and reveal that geographic contiguity is a major influencing factor of the genetic affinity among the Tibeto-Burman populations of India

Dating the Origin of Language Using Phonemic Diversity

Language is a key adaptation of our species, yet we do not know when it evolved. Here, we use data on language phonemic diversity to estimate a minimum date for the origin of language. We take advantage of the fact that phonemic diversity evolves slowly and use it as a clock to calculate how long the oldest African languages would have to have been around in order to accumulate the number of phonemes they possess today. We use a natural experiment, the colonization of Southeast Asia and Andaman Islands, to estimate the rate at which phonemic diversity increases through time. Using this rate, we estimate that present-day languages date back to the Middle Stone Age in Africa. Our analysis is consistent with the archaeological evidence suggesting that complex human behavior evolved during the Middle Stone Age in Africa, and does not support the view that language is a recent adaptation that has sparked the dispersal of humans out of Africa. While some of our assumptions require testing and our results rely at present on a single case-study, our analysis constitutes the first estimate of when language evolved that is directly based on linguistic data