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This article provides general information on women's health, including the leading causes of death, prevention and awareness information, and online resources for consumers seeking answers to personal health questions. The article concludes with an annotated webliography of selected Internet resources that provide information on women's health. [ABSTRACT FROM AUTHOR]

Chronic pain is pain that lasts longer than one month after onset or pain that recurs after onset of injury or illness. Millions of Americans suffer from chronic pain conditions, whether from diseases such as diabetes or HIV infection or as a result of injured nerves, bones, or other tissues. The socioeconomic burden of chronic pain is immense. Estimates of the economic impact alone from health care expenses, lost productivity, and lost wages are $100 billion annually. This article provides a general overview of noncancer causes of chronic pain symptoms, conditions, disease burden, and treatments. Authoritative Web sites for chronic pain information and patient resources are included. [ABSTRACT FROM AUTHOR]

In March and April 2009, a new strain of the virus that causes influenza in swine was identified in Mexico and the United States. This variant, known as influenza A (H1N1), was found to be transmitted from swine to humans and was called 'swine flu' by the general public. Within days, the World Health Organization determined that the outbreak was spreading to many other countries and could become a pandemic. The differences between the response to this threat and those of the pandemics in 1918, 1957, and 1968 are impressive. Governments and organizations are better prepared to meet the challenges presented by the present swine influenza pandemic, putting into place measures developed in response to earlier pandemics. The virus itself causes symptoms similar to those of seasonal influenza, and the treatment is comparable. As of August 2009, a vaccine for H1N1 Influenza is still in development, with government and pharmaceutical manufacturers promising delivery in the fall of 2009. Two of the four antiviral drugs currently in use in the United States for treatment of influenza are effective when used as a prophylactic and can reduce the severity of the flu symptoms if taken within 24 hours after symptoms appear. One of the striking developments of this health crisis has been the use of the Internet and various social media tools to provide information on swine flu. Scientists, government organizations, and public health agencies have all utilized new social media resources to keep professional colleagues, government and other agencies, and the general public informed. Information on the Internet allows consumers and their health providers to be well informed about current progress in preventing the spread of swine flu. [ABSTRACT FROM AUTHOR]

Veterans and their families need reliable health information resources and training to locate health information that is sensitive and pertinent to their needs. Resources are abundant for finding information on general health conditions, mental health resources including those for post-traumatic stress disorder (PTSD), family issues, substance abuse, amputations, support groups, and more. The annotated webliography of selected Web sites provides information on a wide variety of potential topics of interest to veterans and those who assist this population. [ABSTRACT FROM AUTHOR]

Meeting the needs of people with chronic diseases is one of the major challenges facing U.S. health care today. Chronic disease is the leading cause of illness, disability, and death in the United States. It accounts for the majority of health care resources used each year and places substantial burdens on the quality of life of individiuals, families, and communites. Successful chronic disease self-management is a partnership between an informed patient, the patient's family or caregiver, and the health professionals who care for the patient. Information available on the Internet can enable the patient to become an active partner in decision making and care. [ABSTRACT FROM AUTHOR]

Health disparities are inequalities in the quality of health and health care across ethnic, racial, and socioeconomic groups. This article focuses on the health disparities of African Americans and identifies several consumer health Internet resources. [ABSTRACT FROM AUTHOR]

The publication of Oral Health in America: A Report of the Surgeon General was a hallmark for America's oral health. This first-ever report explained why oral health is essential to an American's health and well-being. Oral health's meaning has evolved from a narrow focus on teeth and gums to recognition of the mouth's critical role in health. As a mirror of the body's overall health, oral health can provide insight and clues about other health conditions. This article describes Web sites that provide information about good oral health practices, prevention, treatment options, clinical trials, special populations, and curriculum resources for teachers. [ABSTRACT FROM AUTHOR]

Many parents of children with autism search the Internet to learn more about the condition. Unfortunately, variability in Web site quality, low literacy levels, and language barriers may prevent them from finding reliable information. To assist parents in locating high quality resources, this article provides an annotated list of Web sites on health aspects of autism. Both a health sciences librarian and a parent of a child with autism present their perspectives and discuss the broader is sue about how parents of children with medical conditions use the Internet. [ABSTRACT FROM AUTHOR]

Post-traumatic stress disorder (PTSD) has become a major health issue. Modern society's ills, manifested by war, terrorist attacks, and rising individual exposure to violence, have increased the prevalence of the disorder in the population, as have natural and manmade disasters. While new research and greater media coverage have improved the public's understanding of the condition and have removed much of the stigma attached to PTSD, current and evidence-based resources can ease much of the mental anguish endured by sufferers and their families. This article lists a variety of Web resources to aid individuals in their quest for solid data and support. [ABSTRACT FROM AUTHOR]

Communicable diseases affect everyone-young, old, rich, poor-no matter where they live in the world. This article provides general information on communicable diseases, including the global impact of the six most deadly communicable diseases, factors leading to the emergence and reemergence of these diseases, and prevention tips. The article concludes with an annotated webliography of selected Internet resources that provide information on communicable diseases. [ABSTRACT FROM AUTHOR]

Survivors of traumatic events may experience a large range of emotions after a disaster, including anxiety disorders, posttraumatic stress disorder, depression, and substance abuse. The terms 'post-Katrina stress disorder' and 'post-Katrina stress syndrome' have recently emerged to refer to the grief, shock, mood shifts, confusion, anger, marital discord, guilt, escape fantasies, and substance abuse that have plagued survivors of the 2005 Gulf Coast storms. This review of consumer health Web sites aims to provide a starting point for disaster survivors seeking information on anxiety disorders and mental health services. [ABSTRACT FROM AUTHOR]

The existence of Gulf War Syndrome is a topic of much controversy. Many highly respected scientists initially concluded that no single disease or unique condition affected the veterans of the Gulf War. More recent studies have concluded that there is evidence that some of the conditions suffered by many Gulf War veterans are more common among those who served in the Gulf and are, quite likely, a result of exposure to toxins, whether man-made or naturally occurring, that were present in the area of the Gulf War. This article provides general information on Gulf War Syndrome, controversy surrounding the syndrome, and challenges faced in determining whether the syndrome exists. A bibliography of selected Internet resources provides additional information on the syndrome. [ABSTRACT FROM AUTHOR]

Suicide is a complex, multidimensional event with a host of contributing factors. Suicidal emergencies are among other behavioral and psychiatric emergencies that provide the basis for emergency department visits. Therefore, emergency departments are ideal clinical environments for the assessment of suicidal patients. A case example from an emergency department visit is provided as a basis of discussion as we describe subpopulations at high risk for suicide and review critical assessment parameters for the recognition and treatment of suicidal patients. Finally, factors associated with patient satisfaction and treatment compliance are addressed to promote positive health outcomes among suicidal patients. [ABSTRACT FROM AUTHOR]

Librarians in the federal sector, like librarians in other medical center libraries, increasingly find it necessary to prove their worth to administrators of their facilities in order to keep their libraries open. The Federal Libraries Section of the Medical Library Association developed a survey for use by federal librarians to help them quantify the value of library reference services provided. Using this survey, these librarians gathered statistics to show the library's effect on patient care, education, and administrative questions.

Mef2 is a conserved and significant transcription factor in the control of muscle gene expression. In cell culture Mef2 synergises with MyoD-family members in the activation of gene expression and in the conversion of fibroblasts into myoblasts. Amongst its in vivo roles, Mef2 is required for both Drosophila muscle development and mammalian muscle regeneration. Mef2 has functions in other cell-types too, but this review focuses on skeletal muscle and surveys key findings on Mef2 from its discovery, shortly after that of MyoD, up to the present day. In particular, in vivo functions, underpinning mechanisms and areas of uncertainty are highlighted. We describe how Mef2 sits at a nexus in the gene expression network that controls the muscle differentiation program, and how Mef2 activity must be regulated in time and space to orchestrate specific outputs within the different aspects of muscle development. A theme that emerges is that there is much to be learnt about the different Mef2 proteins (from different paralogous genes, spliced transcripts and species) and how the activity of these proteins is controlled., (Copyright © 2017. Published by Elsevier Ltd.)

Background: The Veterans Health Administration's Office of Nursing Services launched several initiatives to support evidence-based practice (EBP) initiatives throughout its system. From evaluation of these initiatives and reflection on discussions with nurse leaders and direct care nurses, our thinking about and approach to EBP has evolved from a project-focused to a practice-focused interpretation., Purpose: (a) Offer an expanded view that moves beyond interpreting EBP as process-driven projects to a "way of practicing" where nurses assume ownership for a practice that integrates best available evidence, clinical expertise, and patient preferences, and (b) describe and generate discussion on the educational, cultural, and role modeling implications of this expanded view., Methods: We illustrate EBP integration using a point-of-care interaction scenario., Conclusion: Commitment to EBP is reflected at the point-of-care where each nurse demonstrates the ability to integrate evidence-based interventions, patient preferences, and clinical expertise to arrive at patient-centric health care decisions., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Identifying the steps involved in striatal development is important both for understanding the striatum in health and disease, and for generating protocols to differentiate striatal neurons for regenerative medicine. The most prominent neuronal subtype in the adult striatum is the medium spiny projection neuron (MSN), which constitutes more than 85% of all striatal neurons and classically expresses DARPP-32. Through a microarray study of genes expressed in the whole ganglionic eminence (WGE: the developing striatum) in the mouse, we identified the gene encoding the transcription factor Forkhead box protein P1 (FoxP1) as the most highly up-regulated gene, thus providing unbiased evidence for the association of FoxP1 with MSN development. We also describe the expression of FoxP1 in the human fetal brain over equivalent gestational stages. FoxP1 expression persisted through into adulthood in the mouse brain, where it co-localised with all striatal DARPP-32 positive projection neurons and a small population of DARPP-32 negative cells. There was no co-localisation of FoxP1 with any interneuron markers. FoxP1 was detectable in primary fetal striatal cells following dissection, culture, and transplantation into the adult lesioned striatum, demonstrating its utility as an MSN marker for transplantation studies. Furthermore, DARPP-32 expression was absent from FoxP1 knock-out mouse WGE differentiated in vitro, suggesting that FoxP1 is important for the development of DARPP-32-positive MSNs. In summary, we show that FoxP1 labels MSN precursors prior to the expression of DARPP-32 during normal development, and in addition suggest that FoxP1 labels a sub-population of MSNs that are not co-labelled by DARPP-32. We demonstrate the utility of FoxP1 to label MSNs in vitro and following neural transplantation, and show that FoxP1 is required for DARPP-32 positive MSN differentiation in vitro., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

This article is a retrospective look at the changes in hospital libraries from 1970 to 2014 based on the author's experience and a survey of the literature related to hospital libraries indexed in PubMed from 1970 to the present. New roles for librarians and methods for conveying the value of libraries to administrators are described.

Background: Electronic health records (EHR) have the potential to improve patient care through efficient access to complete patient health information. This potential may not be reached because many of the most important determinants of health outcome are rarely included. Successful health promotion and disease prevention requires patient-reported data reflecting health behaviors and psychosocial issues. Furthermore, there is a need to harmonize this information across different EHR systems., Methods: To fill this gap a three-phased process was used to conceptualize, identify and recommend patient-reported data elements on health behaviors and psychosocial factors for the EHR. Expert panels (n=13) identified candidate measures (phase 1) that were reviewed and rated by a wide range of health professionals (n=93) using the grid-enabled measures wiki social media platform (phase 2). Recommendations were finalized through a town hall meeting with key stakeholders including patients, providers, researchers, policy makers, and representatives from healthcare settings (phase 3)., Results: Nine key elements from three areas emerged as the initial critical patient-reported elements to incorporate systematically into EHR--health behaviors (eg, exercise), psychosocial issues (eg, distress), and patient-centered factors (eg, demographics). Recommendations were also made regarding the frequency of collection ranging from a single assessment (eg, demographic characteristics), to annual assessment (eg, health behaviors), or more frequent (eg, patient goals)., Conclusions: There was strong stakeholder support for this initiative reflecting the perceived value of incorporating patient-reported elements into EHR. The next steps will include testing the feasibility of incorporating these elements into the EHR across diverse primary care settings.

Over-reliance on decontextualized, standardized implementation of efficacy evidence has contributed to slow integration of evidence-based interventions into health policy and practice. This article describes an "evidence integration triangle" (EIT) to guide translation, implementation, prevention efforts, comparative effectiveness research, funding, and policymaking. The EIT emphasizes interactions among three related components needed for effective evidence implementation: (1) practical evidence-based interventions; (2) pragmatic, longitudinal measures of progress; and (3) participatory implementation processes. At the center of the EIT is active engagement of key stakeholders and scientific evidence and attention to the context in which a program is implemented. The EIT model is a straightforward framework to guide practice, research, and policy toward greater effectiveness and is designed to be applicable across multiple levels-from individual-focused and patient-provider interventions, to health systems and policy-level change initiatives., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Muscle is an established paradigm for analysing the cell differentiation programs that underpin the production of specialised tissues during development. These programs are controlled by key transcription factors, and a well-studied regulator of muscle gene expression is the conserved transcription factor Mef2. In vivo, Mef2 is essential for the development of the Drosophila larval musculature: Mef2-null embryos have no differentiated somatic muscle. By contrast, a similar phenotype has not been seen in analyses of the function of Mef2 genes in other examples of myogenesis. These include using conditional mutant mice, using morpholinos in zebrafish and using hypomorphic mutants in Drosophila adult development. However, we show here that Mef2 is absolutely required for a diverse range of Drosophila adult muscle types. These include the dorso-longitudinal muscles (DLMs), the largest flight muscles, which are produced by tissue remodelling. Furthermore, we demonstrate that Mef2 has temporally separable functions in this remodelling and in muscle maintenance. Drosophila adult muscles are multi-fibre and physiologically diverse, in common with vertebrate skeletal muscles, but in contrast to Drosophila larval muscles. These results therefore establish the importance of Mef2 in multiple roles in examples of myogenesis that have parallels in vertebrates and are distinct from that occurring in Drosophila embryogenesis.

Objectives: To describe the formation and work of the Health Maintenance Consortium (HMC), a collaborative of researchers funded by the National Institutes of Health to study long-term behavior change across a variety of diseases and conditions., Methods: The historical development of the program, especially the focus on behavior change maintenance, is briefly described. Previous work on behavior change that paved the way for the HMC is also discussed., Results: Aiming to accelerate the pace of discovery and application, NIH funding to create the HMC has created a strong research base for making progress toward filling key knowledge and intervention gaps in long-term behavior change., Conclusions: Investments in behavior change and maintenance have yielded important information that can be used to guide the development of future programs to improve health.

The transcription factor Mef2 has well established roles in muscle development in Drosophila and in the differentiation of many cell types in mammals, including neurons. Here, we describe a role for Mef2 in the Drosophila pacemaker neurons that regulate circadian behavioral rhythms. We found that Mef2 is normally produced in all adult clock neurons and that Mef2 overexpression in clock neurons leads to long period and complex rhythms of adult locomotor behavior. Knocking down Mef2 expression via RNAi or expressing a repressor form of Mef2 caused flies to lose circadian behavioral rhythms. These behavioral changes are correlated with altered molecular clocks in pacemaker neurons: Mef2 overexpression causes the oscillations in individual pacemaker neurons to become desynchronized, while Mef2 knockdown strongly dampens molecular rhythms. Thus, a normal level of Mef2 activity is required in clock neurons to maintain robust and accurate circadian behavioral rhythms.

During Drosophila metamorphosis some larval tissues escape the general histolysis and are remodelled to form adult tissues. One example is the dorso-longitudinal muscles (DLMs) of the indirect flight musculature. They are formed by an intriguing process in which residual larval oblique muscles (LOMs) split and fuse with imaginal myoblasts associated with the wing disc. These myoblasts arise in the embryo, but remain undifferentiated throughout embryogenesis and larval life, and thus share characteristics with mammalian satellite cells. However, the mechanisms that maintain the Drosophila myoblasts in an undifferentiated state until needed for LOM remodelling are not understood. Here we show that the Him gene is expressed in these myoblasts, but is undetectable in developing DLM fibres. Consistent with this, we found that Him could inhibit DLM development: it inhibited LOM splitting and resulted in fibre degeneration. We then uncovered a balance between mef2, a positive factor required for proper DLM development, and the inhibitory action of Him. Mef2 suppressed the inhibitory effect of Him on DLM development, while Him could suppress the premature myosin expression induced by mef2 in myoblasts. Furthermore, either decreased Him function or increased mef2 function disrupted DLM development. These findings, together with the co-expression of Him and Mef2 in myoblasts, indicate that Him may antagonise mef2 function during normal DLM development and that Him participates in a balance of signals that controls adult myoblast differentiation and remodelling of these muscle fibres. Lastly, we provide evidence for a link between Notch function and Him and mef2 in this balance.

Cell differentiation is controlled by key transcription factors, and a major question is how they orchestrate cell-type-specific genetic programs. Muscle differentiation is a well studied paradigm in which the conserved Mef2 transcription factor plays a pivotal role. Recent genomic studies have identified a large number of mef2-regulated target genes with distinct temporal expression profiles during Drosophila myogenesis. However, the question remains as to how a single transcription factor can control such diverse patterns of gene expression. In this study we used a strategy combining genomics and developmental genetics to address this issue in vivo during Drosophila muscle development. We found that groups of mef2-regulated genes respond differently to changes in mef2 activity levels: some require higher levels for their expression than others. Furthermore, this differential requirement correlates with when the gene is first expressed during the muscle differentiation program. Genes that require higher levels are activated later. These results implicate mef2 in the temporal regulation of muscle gene expression, and, consistent with this, we show that changes in mef2 activity levels can alter the start of gene expression in a predictable manner. Together these results indicate that Mef2 is not an all-or-none regulator; rather, its action is more subtle, and levels of its activity are important in the differential expression of muscle genes. This suggests a route by which mef2 can orchestrate the muscle differentiation program and contribute to the stringent regulation of gene expression during myogenesis.

Tissue development requires the controlled regulation of cell-differentiation programs. In muscle, the Mef2 transcription factor binds to and activates the expression of many genes and has a major positive role in the orchestration of differentiation. However, little is known about how Mef2 activity is regulated in vivo during development. Here, we characterize a gene, Holes in muscle (Him), which our results indicate is part of this control in Drosophila. Him expression rapidly declines as embryonic muscle differentiates, and consistent with this, Him overexpression inhibits muscle differentiation. This inhibitory effect is suppressed by mef2, implicating Him in the mef2 pathway. We then found that Him downregulates the transcriptional activity of Mef2 in both cell culture and in vivo. Furthermore, Him protein binds Groucho, a conserved, transcriptional corepressor, through a WRPW motif and requires this motif and groucho function to inhibit both muscle differentiation and Mef2 activity during development. Together, our results identify a mechanism that can inhibit muscle differentiation in vivo. We conclude that a balance of positive and negative inputs, including Mef2, Him, and Groucho, controls muscle differentiation during Drosophila development and suggest that one outcome is to hold developing muscle cells in a state with differentiation genes poised to be expressed.

Much remains to be learnt about the in vivo function of specific microRNAs. Recently, the conserved microRNA miR-1 has been found to be essential for Drosophila development. miR-1 mutants die during the rapid larval growth phase with severe muscle defects.

In Tennessee, several medical library outreach projects have involved collaborative work with health-care professionals, public librarians, consumers, faith-based organizations and community service agencies. The authors are medical librarians who worked as consultants, trainers and project directors to promote health literacy using PubMed medline and other health information resources in the several funding projects described here. We explain the programmes briefly, focusing on lessons learned and suggestions for those who follow us.

A key feature of myogenesis is the fusion of myoblasts to form multinucleate myotubes. Recent work in Drosophila has uncovered a collection of genes that operate at different stages of this process. Some interactions between them have been described that begin to define links from outside the cell via the plasma membrane to the cytoskeleton. Future studies will establish the extent to which the molecular mechanisms of myoblast fusion are conserved between Drosophila and other animals, as found in other aspects of myogenesis.

A Drosophila screen aimed at furthering understanding of how tissues develop from the mesoderm has identified a novel signalling molecule that is proposed to signal from somatic muscle progenitors to direct the development of adjacent visceral muscle.

To study the influence of psychosocial resources on psychological recovery after heart transplantation, 28 patients were surveyed during their hospitalization after transplant surgery and 6 months posttransplantation. Scales from the Coping With Serious Illness Battery were used to measure psychosocial resources (social support and personal control) and psychological and functional outcomes. Psychosocial resources assessed during hospitalization were associated with recovery outcomes at 6 months posttransplantation. Personal control was positively correlated with optimism, well-being, and satisfaction with life (r = .41 to .49) and negatively correlated with anger (r = -.57) and depression (r = -.52). Social support network helpfulness and attachment with others were correlated with psychological outcomes (r = .41 to .59) and functional outcome (r = .42 to .47). Efforts directed toward enhancing perceptions of personal control, social support network helpfulness, and attachment may be useful for promoting psychosocial recovery.

The purpose of this study was to evaluate the psychosocial impact of heart transplantation on spouses and compare the adjustment of spouses and their partners. Data were collected from 51 couples prior to transplant and 12 months posttransplant. The Psychosocial Adjustment to Illness Scale (PAIS) was used to measure adjustment in seven domains. Prior to the transplant, spouses experienced profound psychosocial distress related to their partner's illness. From pretransplant to posttransplant, PAIS total score decreased (lower scores indicate better adjustment) for spouses (M = 42, SD = 16, vs. M = 26, SD = 13). Spouses showed improvement in all domains. Posttransplant, patients' and spouses' PAIS total scores (overall adjustment) were not significantly different. Spouses reported more psychological distress than patients; patients reported more problems than spouses in vocational and domestic function. Study findings highlight the importance of sensitivity in the clinical setting to the distinct psychosocial needs of spouses.

The fusion of myoblasts to make multinucleate muscle fibres is central to muscle development. Recent work on Drosophila has identified two members of the immunoglobulin superfamily that have key roles in controlling the specificity of myoblast fusion.

Aggregation and fusion of myoblasts to form myotubes is essential for myogenesis in many organisms. In Drosophila the formation of syncytial myotubes is seeded by founder myoblasts. Founders fuse with clusters of fusion-competent myoblasts. Here we identify the gene dumbfounded (duf) and show that it is required for myoblast aggregation and fusion. duf encodes a member of the immunoglobulin superfamily of proteins that is an attractant for fusion-competent myoblasts. It is expressed by founder cells and serves to attract clusters of myoblasts from which myotubes form by fusion.

It is unknown how the general patterning mechanisms that subdivide the mesoderm initiate different pathways of cell differentiation. One route to understanding these events is to isolate and analyse genes specifically expressed early in this differentiation process. I have therefore undertaken a novel molecular screen in Drosophila in a systematic search for such genes. The approach utilised subtractive hybridisation coupled to directional cDNA library construction. Libraries were made from as little as 20 microg total RNA isolated from hand-picked embryos of defined stage of development and genotype. In a one-step procedure, the subtraction was 6.5- to 7.25-h wild-type embryos minus 6.5- to 7.25-h twist (twi) zygotic mutant embryos. A two-step procedure in which maternally expressed sequences were subtracted from each of these cDNA libraries, before subtracting twi from wild-type, increased the subtraction efficiency. It resulted in a cDNA population enriched more than 100-fold for mesodermal cDNAs. This was screened by determination of the embryonic expression pattern of each clone in a high throughput procedure and then DNA sequencing. The method, which is comprehensive and does not discriminate against rarer cDNAs, is generally applicable and calculations show that it would work for just 10 embryos. Analysis of one clone, Dmeso18E, that encodes a putative nuclear protein and fulfils the screen's aims is described. It is novel and its expression is mesoderm-specific, twi-dependent, and early during somatic, visceral, and heart muscle differentiation. Two pivotal regulators of mesoderm development and gene expression are Dmef2 and tinman (tin). Analysis of Dmeso18E expression revealed new aspects to their roles: there are effects of Dmef2 on developing muscle much earlier than hitherto believed, and there is tin-independent gene expression in, and invagination of, prospective midgut visceral muscle cells. Dmeso18E expression is regulated by Dmef2, although some expression is Dmef2-independent. The tin-independent and Dmef2-independent expression of Dmeso18E indicates that it either occupies a link between twi and genes like tin and Dmef2 or it lies in a parallel pathway of gene activation., (Copyright 2000 Academic Press.)

mef2 genes encode alternatively spliced transcription factor isoforms that function in muscle differentiation in both Drosophila and vertebrates. Drosophila mef2 (Dmef2) has been shown to be required for the differentiation of a variety of distinct muscle types. However, many possible aspects of its function in muscle remain unexplored. There has also been no analysis in vivo of the activity of different MEF2 isoforms in any species. Our investigation centred on the role of different levels of DMEF2 in the Drosophila embryo in regulating diverse events of muscle differentiation and on the functional significance of Dmef2 alternative splicing. We used the GAL4/UAS system to both misexpress and overexpress individual DMEF2 isoforms and to rescue the different aspects of the Dmef2 mutant phenotype. Ectopic ectodermal expression of DMEF2 activated muscle gene expression and inhibited epidermal differentiation. Overexpression of DMEF2 in the mesoderm disrupted differentiation of the somatic and visceral muscle and the heart. The use of different DMEF2 levels in the rescue experiments revealed an activity range compatible with differentiation of the different muscle types: the consequence of too little or too much DMEF2 activity was disrupted differentiation. These rescue experiments also revealed that distinct DMEF2 thresholds are required for different properties within a cell and also for different cells within a muscle type and for different muscle types. Finally, each isoform functioned equivalently in these experiments, including in the stringent test of rescue of the Dmef2 mutant phenotype., (Copyright 1999 Academic Press.)

Recent studies have substantially advanced our understanding of the transcriptional program regulating development of the different muscle types in Drosophila. For body wall muscle, a pathway can now be drawn that links the transcription factor Dorsal, inherited from the egg, with the differentiated-muscle protein tropomyosin.

Experiments manipulating the level of the basic helix-loop-helix transcription factor Twist in the Drosophila embryo have revealed a novel role for this protein in a 'myogenic switch' during early development.

Analysis of flies with mutations in the gene encoding the D-mef2 transcription factor identifies it as a controller of differentiation in multiple muscle cell types; it is the first such gene to be described.

We describe a group of Drosophila cDNAs that encode MADs box proteins and which are members of the MEF2 (myocyte enhancer-binding factor 2) family of transcription factors. Drosophila has a single MEF2 gene, DMEF2, that is alternatively spliced to produce different transcripts and which is expressed in the mesodermal primordium before gastrulation. The mechanisms responsible for the subsequent subdivision of the mesoderm are unknown. However, DMEF2 may play a role in this important event because our experiments show that it is a downstream target for twist and that its early expression pattern modulates as the mesoderm is organising into cell groupings with distinct fates. DMEF2 is also expressed in both the segregating primordia and the differentiated cells of the somatic, visceral and heart musculature. It is the only known gene expressed in these three main types of muscle throughout differentiation.

Two alternatively spliced products of the human E2A gene, E12 and E47, encode helix-loop-helix DNA-binding proteins. Here we describe the isolation of two Xenopus cDNAs; one, XE12, is structurally similar to human E12 and the other contains a sequence similar to E47. Transcripts of both cDNAs are present at all the stages of Xenopus development tested and in all regions of the embryo. The DNA binding properties of in vitro translated XE12 are indistinguishable from those of human E12. We have shown previously that an embryonic muscle DNA-binding activity, EMF1, that binds to a promoter sequence required for the expression of the cardiac actin gene, contains the Xenopus myogenic factor XMyoD. Here we show that it also contains protein that interacts with an anti-E12 antiserum, suggesting that XE12 and XMyoD proteins, or very similar ones, are present in EMF1. We have addressed the functional role of XE12 in muscle gene transcription in Xenopus embryos by injecting in vitro synthesized RNA into the two cell embryo. Overexpression of XE12 and XMyoD augments by greater than 10-fold the ectopic activation of the endogenous cardiac actin gene that can be produced by XMyoD alone. Our DNA binding results strongly suggest that this effect is mediated through a direct interaction of the XE12-XMyoD complex with specific sites in the cardiac actin promoter. We suggest that XE12 is functionally important in muscle gene activation in embryonic development.

We identify the "M region" of the muscle-specific Xenopus cardiac actin gene promoter from -282 to -348 as necessary for the embryonic expression of a cardiac actin-beta-globin reporter gene injected into fertilized eggs. Four DNA-binding activities in embryo extracts, embryonic M-region factors 1-4 (EMF1-4), are described that interact specifically with this region. One of these, EMF1, is detected in extracts from microdissected somites, which differentiate into muscle, but not in extracts from the adjacent neurectoderm, which differentiates into a variety of other cell types. Moreover, EMF1 is detected in embryo animal caps induced to form mesoderm, which includes muscle, and in which the cardiac actin gene is activated, but not in uninduced animal caps. EMF1 is also first detectable when cardiac actin transcripts begin to accumulate; therefore, both its temporal and spatial distributions during Xenopus development are consistent with a role in activating cardiac actin expression. Two lines of evidence suggest that EMF1 contains the myogenic factor Xenopus MyoD (XMyoD): (1) XMyoD synthesized in vitro can bind specifically to the same site as EMF1; and (2) antibodies raised against XMyoD bind to EMF1. DNA-binding studies indicate that EMF1 may be a complex between XMyoD and proteins found in muscle and other tissues. Our results suggest that the myogenic factor XMyoD, as a component of somite EMF1, regulates the activation of the cardiac actin gene in developing embryonic muscle by binding directly to a necessary region of the promoter.