Ovarian cycle of southern brown howler monkey (<Emphasis Type="Italic">Alouatta guariba clamitans</Emphasis>) through fecal progestin measurement

The ovarian cycle in howler monkeys (genus Alouatta) has beean investigated through several biological parameters (ranging between 16.3 and 29.5 days); however, no data exist concerning the ovarian activity of the southern brown howler monkey (Alouatta guariba clamitans). This study aimed to describe the ovarian cycle of A. g. clamitans by profiling fecal progestin concentrations. Over 20 weeks, fecal samples of eight captive adult females of A. g. clamitans were collected. The collections were made at dawn, 5 days a week, and the samples were frozen immediately following collection. Next, they were dried, pulverized and hormonal metabolites were extracted to determine progestin concentrations by enzyme immunoassay. Of the 758 samples tested, the mean concentration of fecal progestins was 2866.40 ± 470.03 ng/g of dry feces, while the mean concentration at baseline was 814.47 ± 164.36 ng/g of dry feces. Among the eight females, one showed no ovarian cyclicity and three presented periods of probable absence of cyclicity and low progestin concentrations. A mean duration of 16 ± 0.52 days was observed for the 35 cycles studied. The interluteal phase lasted 4 ± 0.37 days on average, with a mean concentration of fecal progestins of 467.98 ± 29.12 ng/g of dry feces, while the luteal phase lasted 11 ± 0.50 days, with a mean concentration of 4283.27 ± 193.31 ng/g of dry feces. Besides describing the characteristics of the ovarian cycle, possible causes for the low concentrations of fecal progestins and periods of absence of cyclicity are also discussed.     

Targeting the SASP to combat ageing: Mitochondria as possible intracellular allies?

Anti‐senescence therapies, such as drugs that specifically kill senescent cells, to stave off ageing are currently under investigation. While these interventions show promise, their potential pitfalls are discussed herein. We have shown that the mitochondria are essential for development of senescence and many of the associated phenotypes, including the often detrimental senescence‐associated secretory phenotype (SASP). Here, we disentangle many ways in which the mitochondria may influence senescence and development of the SASP and focus on possible pathways that could be exploited for future generation of anti‐senescence therapies with a clear aim; to specifically eliminate the problematic features of senescent cells, while maintaining their beneficial characteristics.     

A new species of Laranda Walker 1869 (Orthoptera: Grylloidea, Phalangopsidae) from remnant patches of the Brazilian Atlantic Forest

The genus Laranda has six described species and is confined to South and Southeast of Brazil. We describe a new species and discuss the biology and distribution of the genus. The new species can be distinguished from its known congeners by the following characteristics: absence of yellow spots on pronotum and base of posterior tibiae; female copulatory papilla: sclerotization in dorsal view forming opposing acute angles, apical lobes narrow and small; male genitalia: pseudepiphallic median process short and wide; pseudepiphallic paramere with apex incurved and ectophallic fold surpassing apex of the parameres. The genus is distributed within the Atlantic Forest biome; the new species is found on tree trunks, as well as on forest leaf litter.     

Hypoxia induces class III beta-tubulin gene expression by HIF-1alpha binding to its 3' flanking region

Class III beta-tubulin (TUBB3) overexpression represents a major mechanism of drug resistance to microtubule interacting agents such as taxanes and Vinca alkaloids. Here, we tested hypoxia as a possible inducer of TUBB3. The effects of hypoxia on TUBB3 expression were monitored at mRNA and protein level in A2780, in its paclitaxel-resistant counterpart (TC1) and in HeLa cells. Hypoxia was a strong inducer of TUBB3 in A2780, but not in TC1 and HeLa cells. In A2780 HIF-1alpha was knocked down using RNA interference and TUBB3 expression was assessed in normoxia and hypoxia. The silencing abolished the hypoxia-dependent increase of TUBB3, thereby demonstrating that HIF-1alpha mediates TUBB3 induction in hypoxia. To investigate this phenomenon, the 5' flanking region of human TUBB3 was cloned upstream GFP as a reporter. This region contained the promoter gene, but activity of the reporter was unaffected by hypoxia. Thus, we looked at the 3' flanking region and, at +168 nucleotides from the stop codon, an HIF-1alpha binding site was proven to be active in hypoxia, using a construct in which the site was cloned downstream GFP as reporter gene. Deletion of the site in the construct abolished GFP enhancement upon hypoxia. Chromatin immunoprecipitation revealed the engagement by HIF-1alpha of this site in hypoxia. Methylation analysis of this 3' enhancer showed that it was free of methylation in 70% of cells in A2780, while in less than 16% in both TC1 and HeLa cells, thereby suggesting that TUBB3 increase upon hypoxia is abolished through methylation of the 3' enhancer.     

Neonatal hyperleptinaemia programmes anxiety-like and novelty seeking behaviours but not memory/learning in adult rats

Leptin treatment during lactation programmes for leptin resistance at adulthood, evidenced by hyperleptinaemia, hyperphagia and overweight. Since leptin is known to affect stress response, emotional behaviour and memory/learning performance, the objective of the present study was to evaluate whether neonatal hyperleptinaemia programmes anxiety-like and novelty-seeking behaviours as well as memory/learning in adult male rats. During the first 10 days of lactation (from PN1 to PN10), pups were s.c. injected once per day with either 50 μL of saline (SAL) or murine leptin (LEP — 8 μg/100 g of body mass, saline diluted). Serum leptin was assessed at PN10 and at PN150. Two separate experiments were carried out: 1) experiment one: at PN137, 29 SAL and 30 LEP rats were tested in the elevated plus-maze (EPM) and, at PN142, their behaviour was assessed in the hole board (HB) arena; 2) experiment two: at PN140, a different group of rats consisting of 53 SAL and 56 LEP animals were tested in the radial arm water maze (RAWM). Serum leptin concentration was higher in the LEP group at PN10 and at PN150. LEP animals spent significantly less time in the open arms of the EPM. Furthermore, the number of nose-pokes in the HB arena was higher in LEP rats. There were no differences between groups regarding latency to find the hidden platform in the RAWM. Our results suggests that a central mechanism of leptin resistance at adulthood, caused by neonatal hyperleptinaemia, is associated with an increased level of anxiety and also that it intensifies novelty seeking-behaviour.     

Multisensory integration in the superior colliculus: a neural network model

Neurons in the superior colliculus (SC) are known to integrate stimuli of different modalities (e.g., visual and auditory) following specific properties. In this work, we present a mathematical model of the integrative response of SC neurons, in order to suggest a possible physiological mechanism underlying multisensory integration in SC. The model includes three distinct neural areas: two unimodal areas (auditory and visual) are devoted to a topological representation of external stimuli, and communicate via synaptic connections with a third downstream area (in the SC) responsible for multisensory integration. The present simulations show that the model, with a single set of parameters, can mimic various responses to different combinations of external stimuli including the inverse effectiveness, both in terms of multisensory enhancement and contrast, the existence of within- and cross-modality suppression between spatially disparate stimuli, a reduction of network settling time in response to cross-modal stimuli compared with individual stimuli. The model suggests that non-linearities in neural responses and synaptic (excitatory and inhibitory) connections can explain several aspects of multisensory integration.     

Novel C-seco-taxoids possessing high potency against paclitaxel-resistant cancer cell lines overexpressing class III β-tubulin

Novel C-seco-taxoids were synthesized from 10-deacetylbaccatin III and their potencies evaluated against drug-sensitive and drug-resistant cancer cell lines. The drug-resistant cell lines include ovarian cancer cell lines resistant to cisplatin, topotecan, adriamycin and paclitaxel overexpressing class III β-tubulin, A2780TC1 and A2780TC3. The last two cell lines were selected through chronic exposure of A2780wt to paclitaxel and Pgp blocker cyclosporine. All novel C-seco-taxoids exhibited remarkable potency against A2780TC1 and A2780TC3 cell lines, and no cross resistance to cisplatin- and topotecan-resistant cell lines, A2780CIS and A2780TOP. Four of those C-seco-taxoids exhibit much higher activities than IDN5390 against paclitaxel-resistant cell lines, A2780ADR, A2780TC1 and A2780TC3. SB-CST-10202 possesses the best all-round high potencies across different drug-resistant cell lines. Molecular modeling studies, including molecular dynamics simulations, on the drug-protein complexes of class I and III β-tubulins were performed to identify possible cause of the remarkable potency of these C-seco-taxoids against paclitaxel-resistant cell lines overexpressing class III β-tubulin.     

Group size and composition of black-and-gold howler monkeys (<Emphasis Type="Italic">Alouatta caraya</Emphasis>) on the Upper Paraná River,Southern Brazil

In social mammals, group size, sex and age-class composition are important parameters that are required to understand population dynamics and determine conservation strategies. These parameters are known only poorly for the black-and-gold howler monkey (Alouatta caraya). Here, we studied groups of A. caraya on islands and adjacent banks of the Upper Paraná River of southern Brazil, to examine variability in group size and composition. This location is important for this species because of the high density of howlers. Group size was large, varying from 6 to 18 individuals (average = 11.5, standard deviation = 3.3, n = 13). Groups were multi-male, and adult females outnumbered adult males. On average, groups had the following ratios: 1 adult male: 0.5 subadult male: 1.9 adult females: 0.9 juveniles: 0.5 infants. The ratio of 0.2 infant: 1 adult female is less than that in other species, but typical of other studies of the black-and-gold howlers. Here, we discuss environmental and social pressures that may impose structure on large groups of howlers in terms of strategies for living in high densities. We also compare these data with those of the area of sympatry shared between A. caraya and A. clamitans, and suggest that competition may occur between the two species and that reduced fitness may be a consequence of mixed groups. Contribution number 1,746 of the Departamento de Zoologia of Universidade Federal do Paraná (UFPR).