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Like many epithelial tumors, head and neck squamous cell carcinoma (HNSCC) contains a heterogeneous population of cancer cells. We developed an immunodeficient mouse model to test the tumorigenic potential of different populations of cancer cells derived from primary, unmanipulated human HNSCC samples. We show that a minority population of CD44⁺ cancer cells, which typically comprise <10% of the cells in a HNSCC tumor, but not the CD44⁻ cancer cells, gave rise to new tumors in vivo. Immunohistochemistry revealed that the CD44⁺ cancer cells have a primitive cellular morphology and costain with the basal cell marker Cytokeratin 5/14, whereas the CD44⁻ cancer cells resemble differentiated squamous epithelium and express the differentiation marker Involucrin. The tumors that arose from purified CD44⁺ cells reproduced the original tumor heterogeneity and could be serially passaged, thus demonstrating the two defining properties of stem cells: ability to self-renew and to differentiate. Furthermore, the tumorigenic CD44⁺ cells differentially express the BMI1 gene, at both the RNA and protein levels. By immunohistochemical analysis, the CD44⁺ cells in the tumor express high levels of nuclear BMI1, and are arrayed in characteristic tumor microdomains. BMI1 has been demonstrated to play a role in self-renewal in other stem cell types and to be involved in tumorigenesis. Taken together, these data demonstrate that cells within the CD44⁺ population of human HNSCC possess the unique properties of cancer stem cells in functional assays for cancer stem cell self-renewal and differentiation and form unique histological microdomains that may aid in cancer diagnosis.

Fire influences the distribution of fauna in terrestrial biomes throughout the world. Use of fire to achieve a mosaic of vegetation in different stages of succession after burning (i.e., patch-mosaic burning) is a dominant conservation practice in many regions. Despite this, knowledge of how the spatial attributes of vegetation mosaics created by fire affect fauna is extremely scarce, and it is unclear what kind of mosaic land managers should aim to achieve. We selected 28 landscapes (each 12.6 km 2 ) that varied in the spatial extent and diversity of vegetation succession after fire in a 104,000 km 2 area in the semiarid region of southeastern Australia. We surveyed for reptiles at 280 sites nested within the 28 landscapes. The landscape-level occurrence of 9 of the 22 species modeled was associated with the spatial extent of vegetation age classes created by fire. Biogeographic context and the extent of a vegetation type influenced 7 and 4 species, respectively. No species were associated with the diversity of vegetation ages within a landscape. Negative relations between reptile occurrence and both extent of recently burned vegetation (≤10 years postfire, n = 6) and long unburned vegetation (>35 years postfire, n = 4) suggested that a coarse-grained mosaic of areas (e.g. >1000 ha) of midsuccessional vegetation (11-35 years postfire) may support the fire-sensitive reptile species we modeled. This age class coincides with a peak in spinifex cover, a keystone structure for reptiles in semiarid and arid Australia. Maintaining over the long term a coarse-grained mosaic of large areas of midsuccessional vegetation in mallee ecosystems will need to be balanced against the short-term negative effects of large fires on many reptile species and a documented preference by species from other taxonomic groups, particularly birds, for older vegetation. El fuego influye en la distribución de la fauna en biomas terrestres en todo el mundo. El uso de fuego para obtener un mosaico de vegetación en diferentes etapas sucesionales después de la quema (i.e., quema de mosaico de parches) es una práctica de conservación dominante en muchas regiones. No obstante lo anterior, el conocimiento de la forma en que los mosaicos de vegetación creados por fuego afectan a la fauna es muy escaso, y no es claro el tipo de mosaico que deben tener en cuenta los manejadores de tierras. Seleccionamos 28 paisajes (12.6 km 2 cada uno) que variaron en extensión y diversidad de sucesión vegetal después de fuego en una región semiárida de 104,000 km 2 en el sureste de Australia. Muestreamos reptiles en 280 sitios ubicados en los 28 paisajes. La ocurrencia a nivel paisaje de 9 de las 22 especies modeladas se asoció con la extensión espacial de las clases de edad de la vegetación creadas por el fuego. El contexto biogeográfico y la extensión del tipo de vegetación influyeron en 7 y 4 especies, respectivamente. Ninguna especie se asoció con la diversidad de edades de la vegetación en el paisaje. Las relaciones negativas entre la ocurrencia de reptiles y la extensión de vegetación quemada recientemente (≤10 años postfuego, n = 6) y de vegetación no quemada por largo tiempo (<35 años postfuego, n = 4) sugieren que un mosaico de grano grueso de áreas (e.g., >1,000 ha) con vegetación en etapa sucesional media (11-35 años postfuego) puede soportar a las especies de reptiles sensibles al fuego que modelamos. Esta clase de edad coincide con un pico en la cobertura de spinifex, una estructura clave para reptiles en ambientes semiáridos y áridos de Australia. El mantenimiento a largo plazo del mosaico de grano grueso de áreas con vegetación en etapa sucesional media en ecosistemas de mallee tendrá que balancearse con los efectos negativos a corto plazo de incendios extensivos sobre muchas especies de reptiles y la preferencia documentada de otros grupos taxonómicos, particularmente aves, por vegetación más madura.

To assess the impact of Bordetella pertussis infections in South Australia during an epidemic and determine vulnerable populations, data from notification reports for pertussis cases occurring between July 2008 and December 2009 were reviewed to determine the distribution of disease according to specific risk factors and examine associations with hospitalizations. Although the majority (66%) of the 6230 notifications for pertussis occurred in adults aged >24 years, the highest notification and hospitalization rate occurred in infants aged <1 year. For these infants, factors associated with hospitalization included being aged <2 months [relative risk (RR) 2·3, 95% confidence interval (CI) 1·60–3·32], Indigenous ethnicity (RR 1·7, 95% CI 1·03–2·83) and receiving fewer than two doses of pertussis vaccine (RR 4·1, 95% CI 1·37–12·11). A combination of strategies aimed at improving direct protection for newborns, vaccination for the elderly, and reducing transmission from close contacts of infants are required for prevention of severe pertussis disease.

Solid tumors arise in organs that contain stem cell populations. The tumors in these tissues consist of heterogeneous populations of cancer cells that differ markedly in their ability to proliferate and form new tumors. In both breast cancers and central nervous system tumors, cancer cells differ in their ability to form tumors. While the majority of the cancer cells have a limited ability to divide, a population of cancer stem cells that has the exclusive ability to extensively proliferate and form new tumors can be identified based on marker expression. Growing evidence suggests that pathways that regulate the self-renewal of normal stem cells are deregulated in cancer stem cells resulting in the continuous expansion of self-renewing cancer cells and tumor formation. This suggests that agents that target the defective self-renewal pathways in cancer cells might lead to improved outcomes in the treatment of these diseases.

1. There is considerable debate about whether tropical forests can be managed for timber production and to conserve biodiversity. Few 'sustainable forestry' systems have been evaluated adequately in this respect. Microchiropteran bats may be model taxa for this purpose. They are an important component of mammalian diversity, play key roles in forest dynamics and are indicators of disturbance in neotropical forests. 2. We investigated the effect of Trinidad's periodic block system (PBS) on bat species diversity and community organization. PBS is a polycyclic system of selective logging with a 30-year harvesting rotation. We captured bats in primary forest and PBS-managed forest logged 33, 31, 21, 20 and 10 years previously. 3. Selective logging did not affect species diversity but did affect community structure. Frugivorous bats were significantly more abundant in logged forest whereas gleaning animalivores were more abundant in primary forest, suggesting that frugivores benefited and gleaning animalivores were adversely affected by logging. 4. The bat community showed evidence of recovery. The number of years since forest disturbance was positively correlated with the abundance and number of species of gleaning animalivores and negatively correlated with the proportional abundance of the most common species. Gleaning animalivores increased in abundance with forest regeneration, whereas the community became less dominated by a single generalist frugivore. 5. Synthesis and applications. PBS selective logging appears to be compatible with the conservation of bat diversity. This provides evidence that neotropical forests can be managed for timber production in an ecologically sustainable way and that significant biodiversity conservation efforts can occur outside national parks and nature reserves in areas set aside for sustainable development. PBS could serve as a basic blueprint for sustainable forestry in the Guianan Shield where there are forests similar in species composition to those of Trinidad. Key attributes that could be adopted by many tropical countries to manage their forests in an ecologically sustainable way are a low intensity harvest, a long rotation and multiple controls on harvesting.

Naked mole-rat colonies exhibit a high reproductive skew, breeding being typically restricted to one female (the 'queen') and one to three males. Other colony members are reproductively suppressed, although this suppression can be reversed following the removal or death of the queen. We examined dominance and queen succession within captive colonies to investigate the relationship between urinary testosterone and cortisol, dominance rank and reproductive status; and to determine if behavioural and/or physiological parameters can be used as predictors of queen succession. Social structure was characterized by a linear dominance hierarchy before and after queen removal. Prior to queen removal, dominance rank was negatively correlated with body weight and urinary testosterone and cortisol titres in males and females.Queen removal results in social instability and aggression between high ranking individuals. Dominance rank appears to be a good predictor of reproductive status:queens are the highest ranking colony females and are succeeded by the next highest ranking females. The intense dominance-related aggression that accompanies reproductive succession in naked mole-rats provides empirical support for optimal skew theory.

Colonies of Damaraland mole-rats Cryptomys damarensis exhibit a high reproductive skew. Typically one female breeds and the others are anovulatory. Two models, the dominant control model (DCM) and the self-restraint model (SRM), have been proposed to account for this reproductive suppression. The DCM proposes that suppression is under the control of the dominant breeder and is imposed by mechanisms such as aggression, pheromones and interference with copulation, whereas the SRM does not involve aggression directed towards non-breeders and may function in order to minimize inbreeding.We investigated potential proximate mechanisms involved in the suppression of females in a series of experiments. Socially induced stress through aggression did not appear to be responsible for anovulation. Nor did breeders actively interfere with subordinate copulation. Females were physiologically suppressed when housed in intact colonies. However, as predicted by the DCM, they did not become reproductively active when removed from the presence of breeders. We found no evidence that pheromonal cues block ovulation. We suggest that the SRM is the basic model found in the Damaraland mole-rat and that self-restraint functions in order to minimize inbreeding by restricting reproduction until an unrelated male is present. This would explain the rapid onset of reproductive activation in females when paired with an unrelated male, as demonstrated in this study.

Naked mole-rat colonies are societies with a high reproductive skew, breeding being restricted to one dominant female (the 'queen') and 1 to 3 males. Other colony members of both sexes are reproductively suppressed. Experimental removal of breeding males allowed us to investigate the relationship between urinary testosterone and cortisol, dominance rank, and male reproductive status. Dominance rank was strongly correlated with body weight, age, and urinary testosterone titres in males. No relationship between urinary cortisol levels and male reproductive status or dominance was found. Breeding males were among the highest-ranking, heaviest and oldest males in their respective colonies, and were succeeded by other high-ranking, large, old colony males. In contrast to females, no evidence of competition over breeding status was observed among males. Male-male agonism was low both before and after removal of breeders and mate guarding was not observed. The lower reproductive skew for males compared with female skew or queen control over male reproduction may explain why males compete less strongly than females over breeding status after removal of same-sexed breeders.

A central issue in stem cell biology is to understand the mechanisms that regulate the self-renewal of haematopoietic stem cells (HSCs), which are required for haematopoiesis to persist for the lifetime of the animal. We found that adult and fetal mouse and adult human HSCs express the proto-oncogene Bmi-1. The number of HSCs in the fetal liver of Bmi-1-/- mice was normal. In postnatal Bmi-1-/- mice, the number of HSCs was markedly reduced. Transplanted fetal liver and bone marrow cells obtained from Bmi-1-/- mice were able to contribute only transiently to haematopoiesis. There was no detectable self-renewal of adult HSCs, indicating a cell autonomous defect in Bmi-1-/- mice. A gene expression analysis revealed that the expression of stem cell associated genes, cell survival genes, transcription factors, and genes modulating proliferation including p16Ink4a and p19Arf was altered in bone marrow cells of the Bmi-1-/- mice. Expression of p16Ink4a and p19Arf in normal HSCs resulted in proliferative arrest and p53-dependent cell death, respectively. Our results indicate that Bmi-1 is essential for the generation of self-renewing adult HSCs.

Naked mole-rats are fossorial, eusocial rodents that naturally exhibit high levels of inbreeding. Persistent inbreeding in animals often results in a substantial decline in fitness and, thus, dispersal and avoidance of kin as mates are two common inbreeding avoidance mechanisms. In the naked mole-rat evidence for the former has recently been found. Here we address the latter mechanism by investigating kin recognition and female mate choice using a series of choice tests in which the odour, social and mate preferences of females were determined. Discrimination by females appears to be dependent on their reproductive status. Reproductively active females prefer to associate with unfamiliar males, whereas reproductively inactive females do not discriminate. Females do not discriminate between kin and non-kin suggesting that the criterion for recognition is familiarity, not detection of genetic similarity per se. In the wild, naked mole-rats occupy discrete burrow systems and dispersal and mixing with non-kin is thought to be comparatively rare. Thus, recognition by familiarity may function as a highly efficient kin recognition mechanism in the naked mole-rat. A preference by reproductively active females for unfamiliar males is interpreted as inbreeding avoidance. These findings suggest that, despite an evolutionary history of close inbreeding, naked mole-rats may not be exempt from the effects of inbreeding depression and will attempt to outbreed should the opportunity arise.