Gli as a Novel Therapeutic Target in Malignant Pleural Mesothelioma

Malignant pleural mesothelioma (MPM) is a highly aggressive tumor with poor prognosis. Current treatment is rarely curative, thus novel meaningful therapies are urgently needed. Inhibition of Hedgehog (Hh) signaling at the cell membrane level in several cancers has shown anti-cancer activity in recent clinical studies. Evidence of Hh-independent Gli activation suggests Gli as a more potent therapeutic target. The current study is aimed to evaluate the potential of Gli as a therapeutic target to treat MPM. The expression profiles of Gli factors and other Hh signaling components were characterized in 46 MPM patient tissue samples by RT-PCR and immunohistochemistry. Cultured cell lines were employed to investigate the requirement of Gli activation in tumor cell growth by inhibiting Gli through siRNA or a novel small molecule Gli inhibitor (Gli-I). A xenograft model was used to evaluate Gli-I in vivo. In addition, a side by side comparison between Gli and Smoothened (Smo) inhibition was conducted in vitro using siRNA and small molecule inhibitors. Our study reported aberrant Gli1 and Gli2 activation in a large majority of tissues. Inhibition of Gli by siRNAs or Gli-I suppressed cell growth dramatically both in vitro and in vivo. Inhibition of Gli exhibited better cytotoxicity than that of Smo by siRNA and small molecule inhibitors vismodegib and cyclopamine. Combination of Gli-I and pemetrexed, as well as Gli-I and vismodegib demonstrated synergistic effects in suppression of MPM proliferation in vitro. In summary, Gli activation plays a critical role in MPM. Inhibition of Gli function holds strong potential to become a novel, clinically effective approach to treat MPM.     

Dysfunction and Post-Traumatic Stress Disorder in Fracture Victims 50 Months after the Sichuan Earthquake

Background

This study aimed to evaluate the effectiveness of a rehabilitation intervention on physical dysfunction (PDF) and post-traumatic stress disorder (PTSD) in fracture victims 50 months after the Sichuan earthquake of 2008 and to identify risk factors for PTSD.

Methods

This is a retrospective cohort study. Four hundred and fifty-nine earthquake-related fracture victims from Mianzhu city, Sichuan Province who did not qualify for disability pension participated. Two hundred and forty-five subjects received regular rehabilitation and 214 did not. Muscle strength, joint range of motion (ROM),sensory function, and sit-to-stand balance capacity were evaluated to assess PDF. The PTSD Checklist-Civilian Version (PCL-C) was administered to screen for PTSD. An ordinary least square regression was used to predict PTSD, and a logistic regression was used to predict PDF. In addition a Least Angle Regression (LARS) was carried out for PTSD to study the effects of rehabilitation and PDF at the same time.

Results

Unadjusted and adjusted group differences in physical dysfunction (p<0.01) and PTSD prevalence (p<0.05) were significant in favor of the rehabilitation group. In addition, being female, average or above family income, having witnessed death and fearfulness were found risk factors for PTSD symptoms 50 months after the earthquake. Both PDF and rehabilitation were selected predictors by LARS demonstrating opposite effects.

Conclusion

PDF and PTSD were significantly reduced by the rehabilitation intervention. Future medical intervention strategies should consider rehabilitation in order to assist survivors in dealing with both physical and psychological effects of natural disaster.     

Ecological analyses to inform management targets for the culling of crown-of-thorns starfish to prevent coral decline

The crown-of-thorns starfish (COTS), Acanthaster cf. solaris, is one of the main contributors to declines in coral cover on the Great Barrier Reef (GBR) and remains one of the major acute disturbances on coral reefs throughout much of the Indo-Pacific. Extensive control programs on the GBR involve manual culling of COTS in the field, and research is needed to inform these management efforts. Data from the Great Barrier Reef Marine Park Authority’s (GBRMPA) COTS control program provide near-real-time CPUE (Catch-Per-Unit-Effort, COTS culled per minute) data ideal for operational decision-making but these must be converted to density estimates before they can be related to ecological status of reefs or incorporated into ecological models. We developed conversions between common COTS field survey methods (i.e. manta tow, SCUBA transect searches) and COTS control program CPUE data using estimates of sightability and detectability. We used a population model and COTS size-structure data from COTS control program culling efforts to estimate that, on average, only 19% of 1-yr-old COTS (1–15 cm) are available to be culled. Finally, we developed a CPUE-COTS density relationship to estimate the threshold levels of COTS that prevent net growth of hard corals. Culling programs should therefore aim to achieve CPUEs below these ecological thresholds in order to effectively promote coral growth and recovery. These ecologically sustainable thresholds of COTS density varied depending on hard coral cover. For example, for 35% fast-growing coral cover, COTS culling needs to continue until CPUE decreases to below 0.05 COTS/min (1 COTS per 20 min) in order to prevent coral decline, whereas if coral cover is higher (80%), then a higher target threshold CPUE of ca. 0.08 COTS/min (ca. 3 COTS per 40 min) may be ecologically sustainable. These estimates underpin the current pest management rules being implemented by the GBRMPA in its COTS control program.

     

Improvement in cyst recovery and molecular detection of Giardia duodenalis from stool samples

Molecular Biology Reports - Molecular detection of Giardia duodenalis by polymerase chain reaction (PCR) is difficult in faecal samples due to inhibitors that contaminate DNA preparations, or due...     

Dispersal and dormancy strategies among insect species competing for a pulsed resource

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Social Tolerance in Wild Female Crested Macaques (Macaca nigra) in Tangkoko‐Batuangus Nature Reserve,Sulawesi, Indonesia

In primates, females typically drive the evolution of the social system and present a wide diversity of social structures. To understand this diversity, it is necessary to document the consistency and/or flexibility of female social structures across and within species, contexts, and environments. Macaques (Macaca sp.) are an ideal taxon for such comparative study, showing both consistency and variation in their social relations. Their social styles, constituting robust sets of social traits, can be classified in four grades, from despotic to tolerant. However, tolerant species are still understudied, especially in the wild. To foster our understanding of tolerant societies and to assess the validity of the concept of social style, we studied female crested macaques, Macaca nigra, under entirely natural conditions. We assessed their degree of social tolerance by analyzing the frequency, intensity, and distribution of agonistic and affiliative behaviors, their dominance gradient, their bared‐teeth display, and their level of conciliatory tendency. We also analyzed previously undocumented behavioral patterns in grade 4 macaques: reaction upon approach and distribution of affiliative behavior across partners. We compared the observed patterns to data from other populations of grade 4 macaques and from species of other grades. Overall, female crested macaques expressed a tolerant social style, with low intensity, frequently bidirectional, and reconciled conflicts. Dominance asymmetry was moderate, associated with an affiliative bared‐teeth display. Females greatly tolerated one another in close proximity. The observed patterns matched the profile of other tolerant macaques and were outside the range of patterns of more despotic species. This study is the first comprehensive analysis of females’ social behavior in a tolerant macaque species under natural conditions and as such, contributes to a better understanding of macaque societies. It also highlights the relevance of the social style concept in the assessment of the degree of tolerance/despotism in social systems. Am. J. Primatol. 75:361‐375, 2013. © 2013 Wiley Periodicals, Inc.     

Effects of different thermal treatments during embryonic development on the artificial incubation efficiency of crayfish (Austropotamobius pallipes Lereboullet) eggs. Control of the embryogenetic duration and implications for commercial production

Summary

The development and improvement of artificial incubation techniques for freshwater crayfish eggs and their incorporation into the working schedule of breeding centres is of great interest for commercial production. Factors such as the water circulation system, flow rate, thermal treatment, etc., could strongly influence the success of the process. The present study attempts to test the possible influence of one of these variables, the thermal regime, on both the duration of embryonic development and the efficiency rates obtained in the artificial incubation of white-clawed crayfish (Austropotamobius pallipes) eggs. Four different thermal treatments were tested (three of them included a period at low temperature: 4°-5°C). Survival rates to juvenile stage 2 were similar in the four cases, ranging between 66.7 and 72.7%. We conclude that water cooling (an expensive management procedure) is not necessary in astacid breeding centres provided that egg development takes place at moderately low temperatures (8°-10°C) with a subsequent increase of up to 15°C from the eyed stage. However, the inclusion of periods at low temperature (4°-5°C) allows the staggered production of juvenile batches throughout a 3-week period without adverse effects on efficiency rates. This could be useful to breeding centres in meeting seasonal market requirements. In our study, egg and juvenile losses (mortality rate: 15–20%) were concentrated during the last phases of embryogenesis, particularly from the eyed stage to juvenile stage 2, during which they amounted to more than 90% of the overall mortality which took place during the artificial incubation process.     

Ultrastructural study of metamorphosis in the freshwater bryozoan Plumatella fungosa (Bryozoa,Phylactolaemata)

Summary

At metamorphosis the attachment of the Plumatella larva to the substrate is effected by secretions from glandular cells in the apical plate, the leading pole during swimming. The larval mantle folds back and slides down towards the substrate. By ciliary activity an adhesive secretion is spread over the metamorphosing larva and the attachment area. Two polypides appear through the larval terminal opening. The mantle fold, together with gland cells, nerve cells, sensory cells, and muscle cells from the larva form a nutritive cell mass. Reduction of this nutritive cell mass is accomplished by autolysis and phagocytosis. An invaginated area of the nutritive cell mass is provided with a dense layer of microvilli, which seem to have an absorbtive function. The nutritive cell mass consisting of transitory larval tissues provides a significant source of nutrient for the developing polypide buds.     

Wolbachia endosymbiont in a species of the Anastrepha fraterculus complex (Diptera: Tephritidae)

Summary

In Anastrepha sp.2 aff. fraterculus, the egg-cell harbours a large population of endosymbionts. The bacteria were identified as belonging to genus Wolbachia by PCR assay using primers of the ftsZ gene followed by sequencing of the amplified band. Newly deposited eggs stained in toto by Hoechst show that the bacteria are unevenly dispersed throughout the egg-cell, with a higher accumulation at the posterior pole, and that the degree of infestation varies from egg to egg. Analysis by transmission electron microscopy shows that bacteria are present in the female germ line of embryonic and larval stages, as well as in the different cell types of the ovaries at the adult stage. Mature ova within the follicles harbour a large population of the symbionts. The results indicate the existence of a transovarian transmission of the endosymbionts in this fly.     

Evaluation of the larvicide effect of an aqueous extract of Persea americana (Miller, 1768), Lauraceae,on Anopheles gambine (Giles, 1902), Diptera Culicidae

Summary

In-laboratory evaluation of the larvicide effect of an aqueous extract of Persea americana (Miller 1768) on the various larval stages of Anopheles gambiae (Giles 1902) has shown that larvae at all stages are sensitive to this extract. Inversely proportional to the larval stage, their sensitivity proved to depend on the level of concentration: the higher the latter, the higher the former. Indeed, after a 24-h exposure, concentrations of 510 μg/ml resulted in the death of 100% of larvae at stages 1 and 2, whereas for the same time of exposure there was need to resort to concentrations of 850 μg/ml to kill them at stages 3 and 4. The aqueous extract of Persea americana has therefore a poisonous effect on larvae of Anopheles gambiae. This extract has direct lethal effects and acts as an inhibitor of larval development at sublethal concentration levels.