Fauna as passengers and drivers in vegetation restoration: A synthesis of processes and evidence

Efforts to restore terrestrial woody ecosystems to former agricultural land are typically based on plant‐focused actions, often neglecting fauna. However, the processes that maintain or restore the health and integrity of these ecosystems involve many animal–plant interactions. Here, I synthesise information about these relationships and the implications for revegetation practice. Fauna have often been viewed as passengers, responding passively to plant‐focused revegetation. This view involves two surrogacy assumptions: first, that vegetation attributes can indicate habitat sufficiency for fauna; second, that animals will be capable of dispersing to the restored habitat and of establishing populations there. Habitat sufficiency depends on how resources such as food and nest sites can be indicated by vegetation attributes and how they interact with an animal's species‐specific requirements. Dispersal and establishment depend on proximity to source populations in habitat elsewhere, the type of intervening habitat and the intrinsic mobility of different species. Evidence about the effects of age, revegetation type and spatial context in relation to animal communities indicates that it can often be invalid to assume vegetation surrogacy. Fauna can also drive the developmental trajectories of floristic diversity and composition during revegetation, because animal–plant interactions frequently mediate life‐history transitions that determine seedling recruitment. Frugivore‐mediated seed dispersal is the best studied, but animals also directly influence early‐stage tree recruitment, especially through their roles in seed predation, seedling herbivory and indirectly through top‐down cascades that include large carnivores. These processes have been insufficiently recognised or studied, although some recent work highlights their significance. Intervening to alter abundances of functionally important animals could be useful in accelerating the redevelopment of woody vegetation. Further research is needed to clarify animals’ roles as both passengers and drivers during revegetation, especially manipulative experiments and innovative restoration trials, in which animals and plants are considered together from the outset.     

Epigenetic inheritance, genetic assimilation and speciation.

Epigenetic inheritance systems enable the environmentally induced phenotypes to be transmitted between generations. Jablonka and Lamb (1991, 1995) proposed that these systems have a substantial role during speciation. They argued that divergence of isolated populations may be first triggered by the accumulation of (heritable) phenotypic differences that are later followed and strengthened by genetic changes. The plausibility of this idea is examined in this paper. At first, we discuss the "exploratory" behaviour of an epigenetic inheritance system on a one peak adaptive landscape. If a quantitative trait is far from the optimum, then it is advantageous to induce heritable phenotypic variation. Conversely, if the genotypes get closer to the peak, it is more favorable to canalize the phenotypic expression of the character. This process would lead to genetic assimilation. Next we show that the divergence of heritable epigenetic marks acts to reduce or to eliminate the genetic barrier between two adaptive peaks. Therefore, an epigenetic inheritance system can increase the probability of transition from one adaptive state to another. Peak shift might be initiated by (i) slight changes in the inducing environment or by (ii) genetic drift of the genes controlling epigenetic variability. Remarkably, drift-induced transition is facilitated even if phenotypic variation is not heritable. A corollary of our thesis is that evolution can proceed through suboptimal phenotypic states, without passing through a deep adaptive valley of the genotype. We also consider the consequences of this finding on the dynamics and mode of reproductive isolation.     

Epigenetic and genetic analysis of WNT signaling pathway in sporadic colorectal cancer patients from Iran

The WNT signaling is deregulated in most human colorectal cancers (CRC). Promoter methylation has been proposed as an alternative mechanism to inactivate genes in tumors. To gain insight into the methylation silencing of the WNT pathway during colorectal carcinogenesis, we examined the aberrant methylation profile of four genes, APC, Axin1, Axin2, and GSK3β in an unselected series of 112 sporadic colorectal tumors by methylation specific PCR. It has been suggested that the Axin2 C148T SNP is associated with the risk of developing certain types of cancers. To assess the contribution of Axin2 SNP to CRC susceptibility, we examined the Axin2 C148T genotype in CRC patients and 170 healthy controls by PCR-RFLP. The frequency of CRCs with at least one gene methylated was 18.75%. Promoter methylation of Axin2 and APC genes was detected in 7.1 and 11.9% of tumors, respectively. No aberrant methylation was found in Gsk3β and Axin1 gene in these tumor series. The methylation status of APC had no significant association with clinical parameters. But, promoter methylation of Axin2 was sex-related, occurring more frequently in females (P = 0.002). The frequency of Axin2 C148T genotypes were similar in patients and controls. Moreover, we observed no association between the Axin2 SNP and risk of CRC in patients stratified by age, sex, and smoking status. However, the heterozygote CT genotype was associated with a reduced CRC risk in distal patients compared with proximal patients (OR = 0.3; 95% CI 0.1–0.9, P = 0.04). Our findings indicate that Axin1 and GSK3β methylation play a minor role in colorectal carcinogenesis.     

Epigenetic and genetic factors affect transgene methylation imprinting

In some lines of transgenic mice, the methylation of MspI sites within or adjacent to the transgene locus is affected by the sex of the parent from which the transgene is inherited. These differences are consistent with a role for DNA methylation in genome imprinting. In a previous report, we noted that in one such line, all offspring of females exhibited hypermethylation of the transgene while only some offspring of males carried a hypomethylated transgene. In this report, we provide evidence that this phenomenon is controlled by at least two factors, one of which acts in cis and is dependent on the transgene locus, and one of which acts in trans and is supplied by the maternal genome. We also provide evidence that there are genetic differences between inbred mouse strains in the trans-acting factor.     

An integrated approach to uncover drivers of cancer

Systematic characterization of cancer genomes has revealed a staggering number of diverse aberrations that differ among individuals, such that the functional importance and physiological impact of most tumor genetic alterations remain poorly defined. We developed a computational framework that integrates chromosomal copy number and gene expression data for detecting aberrations that promote cancer progression. We demonstrate the utility of this framework using a melanoma data set. Our analysis correctly identified known drivers of melanoma and predicted multiple tumor dependencies. Two dependencies, TBC1D16 and RAB27A, confirmed empirically, suggest that abnormal regulation of protein trafficking contributes to proliferation in melanoma. Together, these results demonstrate the ability of integrative Bayesian approaches to identify candidate drivers with biological, and possibly therapeutic, importance in cancer.     

Epigenetic gene regulation in stem cells and correlation to cancer

Through the classic study of genetics, much has been learned about the regulation and progression of human disease. Specifically, cancer has been defined as a disease driven by genetic alterations, including mutations in tumor-suppressor genes and oncogenes, as well as chromosomal abnormalities. However, the study of normal human development has identified that in addition to classical genetics, regulation of gene expression is also modified by ‘epigenetic’ alterations including chromatin remodeling and histone variants, DNA methylation, the regulation of polycomb group proteins, and the epigenetic function of non-coding RNA. These changes are modifications inherited during both meiosis and mitosis, yet they do not result in alterations of the actual DNA sequence. A number of biological questions are directly influenced by epigenetics, such as how does a cell know when to divide, differentiate or remain quiescent, and more importantly, what happens when these pathways become altered? Do these alterations lead to the development and/or progression of cancer? This review will focus on summarizing the limited current literature involving epigenetic alterations in the context of human cancer stems cells (CSCs). The extent to which epigenetic changes define cell fate, identity, and phenotype are still under intense investigation, and many questions remain largely unanswered. Before discussing epigenetic gene silencing in CSCs, the different classifications of stem cells and their properties will be introduced. This will be followed by an introduction to the different epigenetic mechanisms. Finally, there will be a discussion of the current knowledge of epigenetic modifications in stem cells, specifically what is known from rodent systems and established cancer cell lines, and how they are leading us to understand human stem cells.     

Epigenetic processes and cancer risk assessment

The U.S. Environmental Protection Agency's Guidelines for Carcinogen Risk Assessment encourages the use of mechanistic data in the assessment of human cancer risk at low (environmental) exposure levels. The key events that define a particular mode of action for tumor formation have been concentrated to date more on mutational responses that are broadly the result of induced DNA damage and enhanced cell proliferation. While it is clear that these processes are important in terms of tumor induction, other modes that fall under the umbrella of epigenetic responses are increasingly being considered to play an important role in susceptibility to tumor induction by environmental chemicals and as significant modifiers of tumor responses. Alterations in gene expression, DNA repair, cell cycle control, genome stability and genome reprogramming could be the result of modification of DNA methylation and chromatin remodeling patterns as a consequence of exposure to environmental chemicals. These concepts are described and discussed.     

On the road: Croatian truck drivers, commercial sex and HIV/AIDS

The primary aims of this study were to examine Croatian truck drivers' sexual contact with sex workers, estimate the frequency of condom use, and assess knowledge of HIV/AIDS within this population. The research was conducted from June 14 to September 16, 2005 at customs offices and accompanying parking lots in four Croatian cities. The sample consists of 69 truck drivers. Information about sexual behavior and condom use were gathered by using a semi-structured interview. Knowledge of HIV/AIDS, measured with a self-administered questionnaire, was found to be low. Six respondents (8.7%) had correctly answered all 13 questions. By contrast, 73% of drivers considered themselves well informed about HIV/AIDS, indicating that most drivers overestimate their knowledge. The majority of respondents (n=62) assumed that most of their colleagues engage in sexual contact with sex workers while on the road, although only one third of respondents reported that they personally have paid for sex. All of the respondents who reported engaging in sexual contact with sex workers stated that they always use condoms. Fear of being infected with a sexually transmitted infection was reported as the main reason for condom use.     

Early onset gastric cancer: on the road to unraveling gastric carcinogenesis

Gastric cancer is thought to result from a combination of environmental factors and the accumulation of specific genetic alterations due to increasing genetic instability, and consequently affects mainly older patients. Less than 10% of patients present with the disease before 45 years of age (early onset gastric carcinoma) and these patients are believed to develop gastric carcinomas with a molecular genetic profile differing from that of sporadic carcinomas occurring at a later age. In young patients, the role of genetics is presumably greater than in older patients, with less of an impact from environmental carcinogens. As a result, hereditary gastric cancers and early onset gastric cancers can provide vital information about molecular genetic pathways in sporadic cancers and may aid in the unraveling of gastric carcinogenesis. This review focuses on the molecular genetics of gastric cancer and also focuses on early onset gastric cancers as well as familial gastric cancers such as hereditary diffuse gastric cancer. An overview of the various pathways of importance in gastric cancer, as discovered through in-vitro, primary cancer and mouse model studies, is presented and the clinical importance of CDH1 mutations is discussed.     

Epi-drugs to fight cancer: from chemistry to cancer treatment, the road ahead

In addition to genetic events, a variety of epigenetic events have been widely reported to contribute to the onset of many diseases including cancer. DNA methylation and histone modifications (such as acetylation, methylation, sumoylation, and phosphorylation) involving chromatin remodelling are among the most studied epigenetic mechanisms for regulation of gene expression leading, when altered, to some diseases. Epigenetic therapy tries to reverse the aberrations followed to the disruption of the balance of the epigenetic signalling ways through the use of both natural compounds and synthetic molecules, active on specific epi-targets. Such epi-drugs are, for example, inhibitors of DNA methyltransferases, histone deacetylases, histone acetyltransferases, histone methyltransferases, and histone demethylases. In this review we will focus on the chemical aspects of such molecules, joined to their effective (or potential) application in cancer therapy.     

Epigenetic control, development and natural genetic variation in plants

Plant life strategies differ radically from those of most animals. Plants are not motile, and can only face stress by developing appropriate physiological responses. In addition, many developmental decisions take place during post-embryonic life in plants, whereas vertebrate and invertebrate development is nearly complete by the time of birth. For instance, while the germ line is typically set aside early during embryogenesis in animals, plants produce gametes from stem cell populations that were previously used for the vegetative growth of shoots. Nevertheless, plants and animals have similar nuclear organization, chromatin constitution and gene content, which raises the question as to whether or not fundamental differences in the use of genetic information underlie their distinct life strategies. More specifically, we would like to know if chromatin and the epigenetically defined, heritable cell fates that it can confer play comparable roles in plants and animals. Here we review our current knowledge on chromatin-mediated epigenetic processes in plants. Based on available evidence, we argue that epigenetic regulation of gene expression plays a relatively minor role in plants compared to mammals. Conversely, plants appear to be more prone than other multicellular organisms to the induction of chromatin-based, epigenetically modified gene activity states that can be transmitted over many generations. These so-called "epimutations" may therefore represent a significant proportion of the natural genetic variation seen in plants. In humans, epimutations are frequently observed in cancers, and given their metastable nature, they could also play an important role in familial disorders that do not demonstrate clear Mendelian inheritance.     

Epigenetic deregulation of the COX pathway in cancer

Inflammation is a major cause of cancer and may condition its progression. The deregulation of the cyclooxygenase (COX) pathway is implicated in several pathophysiological processes, including inflammation and cancer. Although, its targeting with nonsteroidal antiinflammatory drugs (NSAIDs) and COX-2 selective inhibitors has been investigated for years with promising results at both preventive and therapeutic levels, undesirable side effects and the limited understanding of the regulation and functionalities of the COX pathway compromise a more extensive application of these drugs. Epigenetics is bringing additional levels of complexity to the understanding of basic biological and pathological processes. The deregulation of signaling and biosynthetic pathways by epigenetic mechanisms may account for new molecular targets in cancer therapeutics. Genes of the COX pathway are seldom mutated in neoplastic cells, but a large proportion of them show aberrant expression in different types of cancer. A growing body of evidence indicates that epigenetic alterations play a critical role in the deregulation of the genes of the COX pathway. This review summarizes the current knowledge on the contribution of epigenetic processes to the deregulation of the COX pathway in cancer, getting insights into how these alterations may be relevant for the clinical management of patients.     

Prostate cancer vaccines: the long road to clinical application

Cancer vaccines as a modality of immune-based cancer treatment offer the promise of a non-toxic and efficacious therapeutic alternative for patients. Emerging data suggest that response to vaccination largely depends on the magnitude of the type I immune response generated, epitope spreading and immunogenic modulation of the tumor. Moreover, accumulating evidence suggests that cancer vaccines will likely induce better results in patients with low tumor burden and less aggressive disease. To induce long-lasting clinical responses, vaccines will need to be combined with immunoregulatory agents to overcome tumor-related immune suppression. Immunotherapy, as a treatment modality for prostate cancer, has received significant attention in the past few years. The most intriguing characteristics that make prostate cancer a preferred target for immune-based treatments are (1) its relative indolence which allows sufficient time for the immune system to develop meaningful antitumor responses; (2) prostate tumor-associated antigens are mainly tissue-lineage antigens, and thus, antitumor responses will preferentially target prostate cancer cells. But, also in the event of eradication of normal prostate epithelium as a result of immune attack, this will have no clinical consequences because the prostate gland is not a vital organ; (3) the use of prostate-specific antigen for early detection of recurrent disease allows for the initiation of vaccine immunotherapy while tumor burden is still minimal. Finally, for improving clinical outcome further to increasing vaccine potency, it is imperative to recognize prognostic and predictive biomarkers of clinical benefit that may guide to select the therapeutic strategies for patients most likely to gain benefit.     

Acquired and genetic susceptibility to cervical cancer

Infection with high-risk human papilloma virus (HPV) is a necessary risk factor for the development of cervical cancer (CC). However, there are many factors that contribute to the development of CC. We have been investigating the role of polymorphisms in chemical metabolizing genes and life-style factors in the development of CC between two countries with significantly different prevalence of CC. Our data confirm that infection with high-risk HPV is the most significant risk factor for CC in both Venezuela and US. In Venezuela, having multiple sex partners and early sexual activities are significant risk factors (OR=4.7, 95% CI=1.7-13.1; OR=6.7, 95% CI=2.3-20.1, respectively). On the other hand, cigarette smoking is the significant risk factor for women in the US (OR=6.4, 95% CI=1.8-23.2). Genotype analyses were conducted using specimens from the US population only. The GSTM1 null genotype was associated with a significant 3.4 fold increase in risk (95% CI=1.0-11.8) compared with those who were GSTM1 positive, after adjustment for smoking and HPV infection. Polymorphosis in CYP2E1 and mEH are associated with a non-significant increase in risk. Our study indicates that different acquired and genetic susceptibility factors can make significant contributions to the development of environmental disease such as cervical cancer.     

Epigenetic regulation of glycosylation and the impact on chemo-resistance in breast and ovarian cancer

Glycosylation is one of the most fundamental posttranslational modifications in cellular biology and has been shown to be epigenetically regulated. Understanding this process is important as epigenetic therapies such as those using DNA methyltransferase inhibitors are undergoing clinical trials for the treatment of ovarian and breast cancer. Previous work has demonstrated that altered glycosylation patterns are associated with aggressive disease in women presenting with breast and ovarian cancer. Moreover, the tumor microenvironment of hypoxia results in globally altered DNA methylation and is associated with aggressive cancer phenotypes and chemo-resistance, a feature integral to many cancers. There is sparse knowledge on the impact of these therapies on glycosylation. Moreover, little is known about the efficacy of DNA methyltransferase inhibitors in hypoxic tumors. In this review, we interrogate the impact that hypoxia and epigenetic regulation has on cancer cell glycosylation in relation to resultant tumor cell aggressiveness and chemo-resistance.     

Natural and anthropogenic drivers of genetic structure and low genetic variation in the endangered freshwater cod, Maccullochella mariensis

Population genetic theory has identified several threats to small populations that have the potential to endanger species in the short and long term. Understanding these threats is particularly pertinent when management actions, such as stocking, have the potential to exacerbate them. In this study we explore existing genetic variation in the threatened Mary River Cod, Maccullochella mariensis, which has had a long stocking history in its endemic populations (Mary River and Tinana–Coondoo Creek) and has been translocated into other catchments in Southeast Queensland (SEQ). Using Bayesian clustering analysis, two genetically distinct sub-populations were detected (Mary and SEQ vs. Tinana–Coondoo), despite decades of stocking from one population (Tinana–Coondoo) into the other (Mary). Overall, genetic diversity (1–9 alleles per locus) and N _e (18–56) were low, but bigger in the Mary, relative to Tinana–Coondoo. Interestingly, evidence for historical unidirectional gene flow from Tinana–Coondoo into the Mary was detected, which was not as strongly reflected using contemporary estimators, suggesting stocking has not dramatically altered the existing genetic structure for this species. These results provide an opportunity for managers to strategically design stocking protocols and to improve the condition of this species in the wild.     

A suite of new Dre recombinase drivers markedly expands the ability to perform intersectional genetic targeting

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RNA on the road to myelin

In oligodendrocytes some mRNAs are transported from the perikaryon to the distal processes and localized in the myelin compartment where they are translated. This review describes the cis-acting signals and trans-acting factors that mediate intracellular trafficking of myelin basic protein (MBP) RNA, the prototype for such mRNAs in myelinating glia.