Regulatory mechanism of tyrosine hydroxylase activity

Activity of tyrosine hydroxylase is regulated by feedback inhibition and inactivation by catecholamines, and activation by protein phosphorylation. In this article, reaction mechanisms for the conversion of tyrosine hydroxylase to an inactive/stable form by catecholamines, and activation of tyrosine hydroxylase by phosphorylation at Ser-40 are discussed. Inactivation may be induced by sub-stoichiometric amounts of catecholamines, and activation by phosphorylation of Ser-40 may require phosphorylation of three or all four subunits of a tyrosine hydroxylase molecule. Cooperative phosphorylation at Ser-40 in the subunits is also discussed.     

Lobaplatin-based regimens outperform cisplatin for metastatic breast cancer after anthracyclines and taxanes treatment

The goal of this study was to assess the antitumor efficacy and safety of lobaplatin-based regimens as the second line of treatment in patients with metastatic breast cancer (MBC) resistant to anthracyclines and taxanes, compared with that of cisplatin-based regimens. During August 2012 to April 2015, 87 patients who received lobaplatin-based regimens or cisplatin-based regimens were included. Medical records of the patients noted that lobaplatin (30?mg/m²) or cisplatin (25?mg/m²), combined with another chemotherapeutic agent such as Gemcitabine (1000?mg/m²) or Vinorelbine (25?mg/m²), was intravenously given to the patients on a basis of twenty-one days as one treatment cycle. All the patients were followed until August 2017. The endpoint of this study was progression-free survival (PFS), overall survival (OS), and estimated objective response rate (RR). Safety and drug tolerability data were also obtained. Lobaplatin-based regimens prolonged PFS compared to cisplatin-based regimens (median 13.2 vs 4.7?months, hazard ratio?=?0.37, 95% confidence intervals: 0.21–0.67, P?=?.0007), while OS was not significantly different between the two groups (hazard ratio?=?0.72, 95% confidence intervals: 0.40–1.30, P?=?.2767), as was objective RR (37.8% vs 33.4%, $x^2$ = 0.19, P?=?.6653). Nausea/vomiting and renal injury were more frequent with cisplatin-based regimens. Our results show that lobaplatin-based regimens are superior to cisplatin in terms of efficacy and are better tolerated.     

Attitudes Toward Resolution of Human–Wildlife Conflict Among Forest-Dependent Agriculturalists Near Rajaji National Park,India

Understanding local attitudes towards human–wildlife conflict (HWC) is key to developing successful conflict mitigation strategies. In this paper, in-depth interview and questionnaire data about resolution of HWC in Uttarakhand, India are examined from both qualitative and quantitative approaches (n = 70). Responses are differentiated between and within three subgroups: gender, literacy status, and relative wealth. Overall, the plurality of respondents said that fencing is the best solution, that the Forest Department should take leadership, and that villagers would be willing to participate in a cooperative management institution. However, cooperative action was only actively supported by 27.4% of respondents, suggesting that comanagement of this protected area will require significant capacity building and trust building activities. Intragroup differences show that all three factors are significant, and underscore the importance of addressing gender differences in attitudes about HWC in particular. Women were less likely than men to support compensation, more likely to prefer that the village take leadership, and less willing to participate in a cooperative management institution. The study illustrates the value of mixed-method research, and suggests a number of specific entry points for action.

Dye-induced aggregation of single stranded RNA: a mechanistic approach

The binding of proflavine (D) to single stranded poly(A) (P) was investigated at pH 7.0 and 25 degrees C using T-jump, stopped-flow and spectrophotometric methods. Equilibrium measurements show that an external complex PD(I) and an internal complex PD(II) form upon reaction between P and D and that their concentrations depend on the polymer/dye concentration ratio (C(P)/C(D)). For C(P)/C(D)<2.5, cooperative formation of stacks external to polymer strands prevails (PD(I)). Equilibria and T-jump experiments, performed at I=0.1M and analyzed according to the Schwarz theory for cooperative binding, provide the values of site size (g=1), equilibrium constant for the nucleation step (K( *)=(1.4+/-0.6)x10(3)M(-1)), equilibrium constant for the growth step (K=(1.2+/-0.6)x10(5)M(-1)), cooperativity parameter (q=85) and rate constants for the growth step (k(r)=1.2x10(7)M(-1)s(-1), k(d)=1.1 x 10(2)s(-1)). Stopped-flow experiments, performed at low ionic strength (I=0.01 M), indicate that aggregation of stacked poly(A) strands do occur provided that C(P)/C(D)<2.5.     

Social suppression of female reproductive maturation and infanticidal behavior in cooperatively breeding Mongolian gerbils

In several cooperatively breeding species, reproductively suppressed, nonbreeding females are attracted to infants and routinely provide alloparental care, while breeding females may attack or kill other females' infants. The mechanisms underlying the transition from alloparental to infanticidal behavior are unknown. In this study, we tested the hypothesis that this transition is associated with cessation of reproductive suppression and onset of ovarian activity in the Mongolian gerbil (Meriones unguiculatus), a cooperatively breeding rodent. Young female gerbils were housed with their natal family (FH), with a female pairmate (PH) or singly (SH). When females were either 11-13 or 16-18 weeks of age, we characterized their behavioral responses to an unfamiliar pup, reproductive development, and plasma progesterone, cortisol, and prolactin concentrations. In both age groups, FH females were significantly less likely to attack pups than PH or SH females and in fact never did so. FH females also had smaller ovaries and uteri, less developed scent glands, and lower progesterone levels, and were more likely to be anovulatory than PH or SH females, especially in the 11- to 13-week-old age group. Prolactin concentrations did not differ with reproductive status but were significantly higher in females that did not attack pups than in those that did. We found no other significant associations, however, between reproductive or endocrine measures and behavioral responses to pups. These results suggest that cohabitation with the natal family inhibits both infanticidal behavior and reproductive maturation in young female gerbils but that these two effects may not be causally related.     

Diet of two sympatric Pheidole spp. ants in the central Monte desert: implications for seed–granivore interactions

Ants of the genus Pheidole are important seed consumers in several desert ecosystems. In South American deserts, although several Pheidole spp. have been characterized as seed harvesters, studies on their diet and ecological role are still missing. Pheidole spininodis (Mayr) and Pheidole bergi (Mayr) are capable of removing seeds in the central Monte desert. The aim of this study was to quantify and compare the diet of these species and to interpret the results in the context of seed–granivore interactions. Diet was estimated during mid-summer by collecting items brought back to the nest by foragers in ten colonies per species. While P. spininodis was mainly granivorous, P. bergi was mainly insectivorous. However, they both collected ~40% of other types of items. Among seeds, the diet of P. spininodis included mostly grass seeds, whereas the diet of P. bergi was mainly made up of shrub and tree seeds, usually retrieved cooperatively. This behavior allowed P. bergi to carry larger seeds, resulting in diet partitioning in terms of seed size. However, diet of P. spininodis is very similar to that of three sympatric Pogonomyrmex species. Thus, specialized harvester ants remove large quantities of grass seeds in the central Monte desert during the summer, potentially affecting their abundance in the soil seed bank. P. bergi directs its feeding pressure to shrub and tree seeds, and although seeds constitute ~10% of its diet, its high colony density and high activity levels, added to the lower proportion of large seeds in the soil seed bank, indicate that their importance as seed consumers cannot be ruled out.     

The B-matrix harbors significant and sex-specific constraints on the evolution of multicharacter sexual dimorphism

The extent to which sexual dimorphism can evolve within a population depends on an interaction between sexually divergent selection and constraints imposed by a genetic architecture that is shared between males and females. The degree of constraint within a population is normally inferred from the intersexual genetic correlation, r(mf) . However, such bivariate correlations ignore the potential constraining effect of genetic covariances between other sexually coexpressed traits. Using the fruit fly Drosophila serrata, a species that exhibits mutual mate preference for blends of homologous contact pheromones, we tested the impact of between-sex between-trait genetic covariances using an extended version of the genetic variance-covariance matrix, G, that includes Lande's (1980) between-sex covariance matrix, B. We find that including B greatly reduces the degree to which male and female traits are predicted to diverge in the face of divergent phenotypic selection. However, the degree to which B alters the response to selection differs between the sexes. The overall rate of male trait evolution is predicted to decline, but its direction remains relatively unchanged, whereas the opposite is found for females. We emphasize the importance of considering the B-matrix in microevolutionary studies of constraint on the evolution of sexual dimorphism.     

Interannual variation in effective number of breeders and estimation of effective population size in long‐lived iteroparous lake sturgeon (Acipenser fulvescens)

Quantifying interannual variation in effective adult breeding number (N_b) and relationships between N_b, effective population size (N_e), adult census size (N) and population demographic characteristics are important to predict genetic changes in populations of conservation concern. Such relationships are rarely available for long‐lived iteroparous species like lake sturgeon (Acipenser fulvescens). We estimated annual N_b and generational N_e using genotypes from 12 microsatellite loci for lake sturgeon adults (n = 796) captured during ten spawning seasons and offspring (n = 3925) collected during larval dispersal in a closed population over 8 years. Inbreeding and variance N_b estimated using mean and variance in individual reproductive success derived from genetically identified parentage and using linkage disequilibrium (LD) were similar within and among years (interannual range of N_b across estimators: 41–205). Variance in reproductive success and unequal sex ratios reduced N_b relative to N on average 36.8% and 16.3%, respectively. Interannual variation in N_b/N ratios (0.27–0.86) resulted from stable N and low standardized variance in reproductive success due to high proportions of adults breeding and the species' polygamous mating system, despite a 40‐fold difference in annual larval production across years (437–16 417). Results indicated environmental conditions and features of the species' reproductive ecology interact to affect demographic parameters and N_b/N. Estimates of N_e based on three single‐sample estimators, including LD, approximate Bayesian computation and sibship assignment, were similar to annual estimates of N_b. Findings have important implications concerning applications of genetic monitoring in conservation planning for lake sturgeon and other species with similar life histories and mating systems.     

Enhancing Safety,Security, and Environmental Protection of the Straits of Malacca and Singapore: The Cooperative Mechanism

In November 2004, the International Maritime Organization, as part of its Protection of Vital Shipping Lanes Initiative, decided to convene a high-level conference to address the security of ships plying the Straits of Malacca and Singapore in collaboration with the three littoral states of Indonesia, Malaysia, and Singapore. Three meetings were held over the period 2005 to 2007. The outcome was the creation of a framework for cooperation between the users of the straits and the littoral states known as the Cooperative Mechanism, a historic breakthrough as Article 43 of the Law of the Sea Convention was implemented for the first time. This article outlines the decisions made at the three meetings, analyzes the responses of the various stakeholders during the meetings, explains the reasons for the success of the Cooperative Mechanism, and concludes by proposing ways in which the momentum of cooperation between the users and the littoral states could be sustained.     

The causes of physiological suppression among female meerkats: a role for subordinate restraint due to the threat of infanticide?

In many animal societies, subordinates exhibit down-regulated reproductive endocrine axes relative to those of dominants, but whether this 'physiological suppression' arises from active interference by dominants or subordinate self-restraint is a matter of debate. Here we investigate the roles that these processes play in precipitating physiological suppression among subordinate female meerkats, Suricata suricatta. We show that, while subordinate females are known to suffer stress-related physiological suppression during periodic temporary evictions by the dominant female, their low estrogen levels while within their groups cannot be readily attributed to chronic stress, as their fecal glucocorticoid metabolite levels during this time are comparable to those of dominants. The low estrogen levels of subordinate females also cannot be explained simply by self-restraint due to factors that could reduce their payoff from maintaining their fertility regardless of the presence of the dominant female (young age, a lack of unrelated mates, poor body condition and limited breeding experience), as substantial rank-related differences in fecal total-estrogen metabolite levels remain when such factors are controlled. We suggest that this residual difference in estrogen levels may reflect a degree of subordinate restraint due in part to the dominant female's ability to kill their young. Accordingly, subordinate female estrogen levels vary in association with temporal variation in the likelihood of infanticide by the dominant. Attempts to identify the causes of physiological suppression should be cautious if rejecting any role for dominant interference in favor of subordinate restraint, as the dominant's capacity to interfere may often be the reason why subordinates exercise restraint.