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Charles Darwin's lifetime illness with its many disabling symptoms may be explained by an inherited pathological mtDNA mutation. Although such a diagnosis explains Darwin's illness and the strange illnesses that afflicted his Wedgwood maternal forebears, it does not explain the illnesses that affected Darwin's children. The sicknesses of the children were very different from those of the father and also different from each other. Although not directly inherited from their father, these illnesses may have been due, at least in part, to inbreeding since they were the inbred progeny from a consanguineous couple (Darwin and his wife were first cousins), a condition known to enhance susceptibility to recessive genetic disorders and infectious diseases. Darwin's inherited illness may be traced back through three, perhaps four maternal generations. Consanguinity was present in the marriage of Darwin's maternal grandparents, but the purported mitochondrial mutation appears to have been present prior to this union. The origin of any mutation appears lost in the mist of unrecorded history. [ABSTRACT FROM AUTHOR] more...

Charles Darwin's long-term illness has been the subject of much speculation. His numerous symptoms have led to conclusions that his illness was essentially psychogenic in nature. These diagnoses have never been fully convincing, however, particularly in regard to the proposed underlying psychological background causes of the illness. Similarly, two proposed somatic causes of illness, Chagas disease and arsenic poisoning, lack credibility and appear inconsistent with the lifetime history of the illness. Other physical explanations are simply too incomplete to explain the range of symptoms. Here, a very different sort of explanation will be offered. We now know that mitochondrial mutations producing impaired mitochondrial function may result in a wide range of differing symptoms, including symptoms thought to be primarily psychological. Examination of Darwin's maternal family history supports the contention that his illness was mitochondrial in nature; his mother and one maternal uncle had strange illnesses and the youngest maternal sibling died of an infirmity with symptoms characteristic of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS syndrome), a condition rooted in mitochondrial dysfunction. Darwin's own symptoms are described here and are in accord with the hypothesis that he had the mtDNA mutation commonly associated with the MELAS syndrome. [ABSTRACT FROM AUTHOR] more...

The article focuses on the history of skin symptoms and complaints by scientist Charles Darwin. It says that Darwin's first skin symptoms were occurred when he was an undergraduate student at the Christ's College in Cambridge, Massachusetts in 1828. It states that Darwin has diagnosed of having a cyclic vomiting syndrome (CVS) with recurrent staphylococcal infection, dental decay, motion sickness, and skin pigmentation. Moreover, an overview of CVS' common related diseases is discussed. more...

The article describes how naturalist Charles Darwin suffered and went through his adult life having cyclical vomiting syndrome. Cyclical vomiting syndrome is related to classic migraine, abdominal migraine and mitochondrial deoxyribonucleic acid (DNA) abnormalities. Its clinical manifestations include abdominal, circulatory and cerebral symptoms. Based on the letters written by Darwin describing his health condition, the author concluded that he has experienced episodes of cyclical vomiting syndrome with comorbidities such as dental decay, atopic dermatitis with staphylococcus infection and esophageal tears. more...

Hematopoiesis requires the spatiotemporal organization of regulatory factors to successfully orchestrate diverse lineage specificity from stem and progenitor cells. Med12 is a regulatory component of the large Mediator complex that enables contact between the general RNA polymerase II transcriptional machinery and enhancer bound regulatory factors. We have identified a new zebrafish med12 allele, syr, with a single missense mutation causing a valine to aspartic acid change at position 1046. Syr shows defects in hematopoiesis, which predominantly affect the myeloid lineage. Syr has identified a hematopoietic cell-specific requirement for Med12, suggesting a new role for this transcriptional regulator. [ABSTRACT FROM AUTHOR] more...

This article explores the treatment of Buruli ulcer (BU), a skin infection caused by Mycobacterium ulcerans. Traditionally, surgery has been the main treatment, but recent studies have shown the effectiveness of oral antibiotics. The article presents four cases where patients were treated with oral antibiotics, either followed by surgery or as the sole treatment. After several weeks of antibiotic therapy, three patients showed no signs of the bacteria. The article provides detailed information about the patients' characteristics, diagnosis, treatment, and histopathology. It suggests that using oral antibiotics before surgery may simplify management and prevent relapse. [Extracted from the article] more...

The article presents several case studies related to the treatment of buruli ulcer (BU) using oral antibiotics prior to a surgical excision. It says that all the patients were diagnosed with Mycobacterium ulcerans using the positive polymerase chain reaction (PCR) and the patients received rifampicin combined with moxifloxacin and clarithromycin. It states that BU is a destructive soft tissue infection which can be treted by surgical excision, in combination with oral antibiotics. more...

Presents a case study of a free rectus flap repair of a cutaneous mycobacterium ulcerans ulcer with joint involvement. Determination of bacterial presence in a seven year-old girl through polymerase chain-reaction; Histology of the area affected by the bacterial infection; Initial debridement of a free rectus abdominis muscle flap. more...

This article discusses a case of spontaneous clearance of Mycobacterium ulcerans, the bacteria that causes Buruli ulcer. The patient, a 72-year-old man from Australia, had a slowly progressive lesion on his ankle. The diagnosis of Buruli ulcer was made through testing and confirmed by PCR and culture. The patient underwent excision of the lesion without antibiotics, and subsequent tests showed no presence of the bacteria. This case highlights the potential for spontaneous resolution of Buruli ulcer and the importance of understanding the immune response to develop effective treatments and vaccines. [Extracted from the article] more...

The article presents the case of 72-year-old man who presented with a slowly progressive painless papule with a punctate centre on his left ankle. From a dry swab specimen sample from the patient's ankle, he was diagnosed with buruli ulcer (BU) caused by Mycobacterium ulcerans, which was confirmed by polymerase chain reaction (PCR). The article discusses the BU's potential for progressive tissue destruction and the clinical appearance and laboratory characteristics. more...

Background: Buruli ulcer (BU), caused by Mycobacterium ulcerans (M. ulcerans), is a necrotizing skin disease found in more than 30 countries worldwide. BU incidence is highest in West Africa; however, cases have substantially increased in coastal regions of southern Australia over the past 30 years. Although the mode of transmission remains uncertain, the spatial pattern of BU emergence in recent years seems to suggest that there is an environmental niche for M. ulcerans and BU prevalence. Methodology/Principal Findings: Network analysis was applied to BU cases in Victoria, Australia, from 1981-2008. Results revealed a non-random spatio-temporal pattern at the regional scale as well as a stable and efficient BU disease network, indicating that deterministic factors influence the occurrence of this disease. Monthly BU incidence reported by locality was analyzed with landscape and climate data using a multilevel Poisson regression approach. The results suggest the highest BU risk areas occur at low elevations with forested land cover, similar to previous studies of BU risk in West Africa. Additionally, climate conditions as far as 1.5 years in advance appear to impact disease incidence. Warmer and wetter conditions 18-19 months prior to case emergence, followed by a dry period approximately 5 months prior to case emergence seem to favor the occurrence of BU. Conclusions/Significance: The BU network structure in Victoria, Australia, suggests external environmental factors favor M. ulcerans transmission and, therefore, BU incidence. A unique combination of environmental conditions, including land cover type, temperature and a wet-dry sequence, may produce habitat characteristics that support M. ulcerans transmission and BU prevalence. These findings imply that future BU research efforts on transmission mechanisms should focus on potential vectors/reservoirs found in those environmental niches. Further, this study is the first to quantitatively estimate environmental lag times associated with BU outbreaks, providing insights for future transmission investigations. [ABSTRACT FROM AUTHOR] more...

Part II. Reports on the status of global infectious diseases. Tropical infectious diseases pathology in Malaysia; Tropical pathogens in Far North Queensland and Torres Strait; Clinicopathologic classification of mycobacterium ulcerans disease; Histopathology of Buruli ulcer. more...

Buruli ulcer (BU) occurs in >30 countries. The causative organism, Mycobacterium ulcerans, is acquired from the environment, but the exact mode of transmission is unknown. We investigated an outbreak of BU in a small coastal town in southeastern Australia and screened by PCR mosquitoes caught there. All cases of BU were confirmed by culture or PCR. Mosquitoes were trapped in multiple locations during a 26-month period. BU developed in 48 residents of Point Lonsdale/Queenscliff and 31 visitors from January 2001 through April 2007. We tested 11,504 mosquitoes trapped at Point Lonsdale (predominantly Aedes camptorhynchus). Forty-eight pools (5 species) were positive for insertion sequence IS2404 (maximum likelihood estimate 4.3/1,000), and we confirmed the presence of M. ulcerans in a subset of pools by detection of 3 additional PCR targets. [ABSTRACT FROM AUTHOR] more...

Summary: In the zebrafish embryo, primitive hematopoiesis initiates in two spatially distinct regions. Rostrally, the cells of the anterior lateral plate mesoderm (ALPM) give rise exclusively to cells of the myeloid lineage in a pu.1-dependent manner . Caudally, in the posterior lateral plate mesoderm (PLPM), the expression of gata1 defines a precursor pool that gives rise predominantly to the embryonic erythrocytes . The transcription factor scl acts upstream of both gata1 and pu.1 in these precursor pools, activating a series of conserved transcription factors that cell-autonomously specify either myeloid or erythroid fates . However, the mechanisms underlying the spatial separation of the hematopoietic precursor pools and the induction of differential gene expression within these pools are not well understood. We show here that the Bmp receptor lost-a-fin/alk8 is required for rostral pu.1 expression and myelopoiesis, identifying an early genetic event that distinguishes between the induction of anterior and posterior hematopoiesis. Introducing a constitutively active version of the Alk8 receptor led to increased pu.1 expression, but the role of alk8 was independent of the scl-dependent cell-fate pathway. Furthermore, the role of Alk8 in myelopoiesis was genetically separable from its earlier role in dorsal-ventral embryonic patterning. [Copyright &y& Elsevier] more...

Mycobacterium ulcerans produces an extracellular cutaneous infection (Buruli ulcer) characterized by immunosuppression. This is in stark contrast to all other pathogenic Mycobacteria species that cause intracellular, granulomatous infections. The unique mycobacterial pathology of M. ulcerans infection is attributed to a plasmid-encoded immunomodulatory macrolide toxin, mycolactone. In this article we explore the role of mycolactone in the virulence of M. ulcerans using mycolactone and genetically defined mycolactone negative mutants. In a guinea pig infection model wild-type (WT) M. ulcerans produces an extracellular infection whereas mycolactone negative mutants produce an intracellular inflammatory infection similar to that of Mycobacterium marinum. Although mycolactone negative mutants are avirulent, they persist for at least 6 weeks. Chemical complementation of M. ulcerans mutants with mycolactone restores WT M. ulcerans pathology. Mycolactone negative mutants are capable of growth within macrophages in vitro whereas macrophages are killed by WT M. ulcerans. The ability of mycolactone to caused delayed cell death via apoptosis has been reported. However, mycolactone also causes cell death via necrosis. In vitro mycolactone has antiphagocytic properties. Neither WT M. ulcerans nor mycolactone negative strains are strong neutrophil attractants. These results suggest that mycolactone is largely responsible for the unique pathology produced by M. ulcerans. [ABSTRACT FROM AUTHOR] more...

Focuses on Buruli Ulcer or Mycobacterium ulcerans infection. History and epidemiology; Causative organism and pathology; Clinical features.

Discusses an experiment in which mycolactone was isolated as a polyketide toxin derived from Mycobacterium ulcerans, the causative agen of Buruli ulcer, a human skin disease. Possible representation by the toxin of a family of virulance factors associated with pathology in mycobacterial diseases such as leprosy and tuberculosis; Suggestions of the presence of histopathological changes distant from the site of infection. more...

Presents a letter to the editor about hormone related proteins.