2D and 3D crystallization of the wild-type IIC domain of the glucose PTS transporter from Escherichia coli.

The bacterial phosphoenolpyruvate: sugar phosphotransferase system serves the combined uptake and phosphorylation of carbohydrates. This structurally and functionally complex system is composed of several conserved functional units that, through a cascade of phosphorylated intermediates, catalyze the transfer of the phosphate moiety from phosphoenolpyruvate to the substrate, which is bound to the integral membrane domain IIC. The wild-type glucose-specific IIC domain (wt-IIC(glc)) of Escherichia coli was cloned, overexpressed and purified for biochemical and functional characterization. Size-exclusion chromatography and scintillation-proximity binding assays showed that purified wt-IIC(glc) was homogenous and able to bind glucose. Crystallization was pursued following two different approaches: (i) reconstitution of wt-IIC(glc) into a lipid bilayer by detergent removal through dialysis, which yielded tubular 2D crystals, and (ii) vapor-diffusion crystallization of detergent-solubilized wt-IIC(glc), which yielded rhombohedral 3D crystals. Analysis of the 2D crystals by cryo-electron microscopy and the 3D crystals by X-ray diffraction indicated resolutions of better than 6Å and 4Å, respectively. Furthermore, a complete X-ray diffraction data set could be collected and processed to 3.93Å resolution. These 2D and 3D crystals of wt-IIC(glc) lay the foundation for the determination of the first structure of a bacterial glucose-specific IIC domain.

Age-Independent Cartilage Generation for Synovium-Based Autologous Chondrocyte Implantation.

The articular cartilage layer of synovial joints is commonly lesioned by trauma or by a degenerative joint disease. Attempts to repair the damage frequently involve the performance of autologous chondrocyte implantation (ACI). Healthy cartilage must be first removed from the joint, and then, on a separate occasion, following the isolation of the chondrocytes and their expansion in vitro, implanted within the lesion. The disadvantages of this therapeutic approach include the destruction of healthy cartilage-which may predispose the joint to osteoarthritic degeneration-the necessarily restricted availability of healthy tissue, the limited proliferative capacity of the donor cells-which declines with age-and the need for two surgical interventions. We postulated that it should be possible to induce synovial stem cells, which are characterized by high, age-independent, proliferative and chondrogenic differentiation capacities, to lay down cartilage within the outer juxtasynovial space after the transcutaneous implantation of a carrier bearing BMP-2 in a slow-release system. The chondrocytes could be isolated on-site and immediately used for ACI. To test this hypothesis, Chinchilla rabbits were used as an experimental model. A collagenous patch bearing BMP-2 in a slow-delivery vehicle was sutured to the inner face of the synovial membrane. The neoformed tissue was excised 5, 8, 11 and 14 days postimplantation for histological and histomorphometric analyses. Neoformed tissue was observed within the outer juxtasynovial space already on the 5th postimplantation day. It contained connective and adipose tissues, and a central nugget of growing cartilage. Between days 5 and 14, the absolute volume of cartilage increased, attaining a value of 12 mm(3) at the latter juncture. Bone was deposited in measurable quantities from the 11th day onwards, but owing to resorption, the net volume did not exceed 1.5 mm(3) (14th day). The findings confirm our hypothesis. The quantity of neoformed cartilage that is deposited after only 1 week within the outer juxtasynovial space would yield sufficient cells for ACI. Since the BMP-2-bearing patches would be implanted transcutaneously in humans, only one surgical or arthroscopic intervention would be called for. Moreover, most importantly, sufficient numbers of cells could be generated in patients of all ages.

Nasolabial symmetry and esthetics in cleft lip and palate: analysis of 3D facial images

OBJECTIVES To determine the relationship between nasolabial symmetry and esthetics in subjects with orofacial clefts. MATERIAL AND METHODS Eighty-four subjects (mean age 10 years, standard deviation 1.5) with various types of nonsyndromic clefts were included: 11 had unilateral cleft lip (UCL); 30 had unilateral cleft lip and alveolus (UCLA); and 43 had unilateral cleft lip, alveolus, and palate (UCLAP). A 3D stereophotogrammetric image of the face was taken for each subject. Symmetry and esthetics were evaluated on cropped 3D facial images. The degree of asymmetry of the nasolabial area was calculated based on all 3D data points using a surface registration algorithm. Esthetic ratings of various elements of nasal morphology were performed by eight lay raters on a 100 mm visual analog scale. Statistical analysis included ANOVA tests and regression models. RESULTS Nasolabial asymmetry increased with growing severity of the cleft (p = 0.029). Overall, nasolabial appearance was affected by nasolabial asymmetry; subjects with more nasolabial asymmetry were judged as having a less esthetically pleasing nasolabial area (p < 0.001). However, the relationship between nasolabial symmetry and esthetics was relatively weak in subjects with UCLAP, in whom only vermilion border esthetics was associated with asymmetry. CONCLUSIONS Nasolabial symmetry assessed with 3D facial imaging can be used as an objective measure of treatment outcome in subjects with less severe cleft deformity. In subjects with more severe cleft types, other factors may play a decisive role. CLINICAL SIGNIFICANCE Assessment of nasolabial symmetry is a useful measure of treatment success in less severe cleft types.

Contact, Mobility and Authenticity: Language Ideologies in Koineisation and Creolisation

Part II - Christoph Neuenschwander: Language ideologies in the legitimisation of Tok Pisin as a lingua franca Pidgins and Creoles all over the world seem to share common aspects in the historical circumstances of their genesis and evolution. They all emerged in the context of colonialism, in which not only colonisers and colonised, but also the various groups of the colonised population spoke different languages. Pidgins and Creoles, quite simply, resulted from the need to communicate.¬¬ Yet, the degree to which they became accepted as a lingua franca or in fact even as a linguistic variety in its own right, strikingly differs from variety to variety. The current research project focuses on two Pacific Creoles: Tok Pisin, spoken on Papua New Guinea, and Hawai'i Creole English (HCE). Whereas Tok Pisin is a highly stabilised and legitimised variety, used as a lingua franca in one of the most linguistically diverse countries on Earth, HCE seems to be regarded as nothing more than broken English by a vast majority of the Hawai'ian population. The aim of this project is to examine the metalinguistic comments about both varieties and to analyse the public discourses, in which the status of Tok Pisin and HCE were and still are negotiated. More precisely, language ideologies shall be identified and compared in the two contexts. Ultimately, this might help us understand the mechanisms that underlie the processes of legitimisation or stigmatisation. As Laura Tresch will run a parallel research project on language ideologies on new dialects (New Zealand English and Estuary English), a comparison between the findings of both projects may produce even more insights into those mechanisms. The next months of the project will be dedicated to investigating the metalinguistic discourse in Papua New Guinea. In order to collect a wide range of manifestations of language ideologies, i.e. instances of (lay and academic) commentary on Tok Pisin, it makes sense to look at a relatively large period of time and to single out events that are likely to have stimulated such manifestations. In the history of Papua New Guinea - and in the history of Tok Pisin, in particular - several important social and political events concerning the use and the status of the language can be detected. One example might be public debates on education policy. The presentation at the CSLS Winter School 2014 will provide a brief introduction to the history of Tok Pisin and raise the methodological question of how to spot potential sites of language-ideological production.

Effects of variation in nest curtain design on pre-laying behaviour of domestic hens

Laying hens in loose-housing systems select a nest daily in which to lay their eggs among many identical looking nests, they often prefer corner nests. We investigated whether heterogeneity in nest curtain appearance – via colours and symbols – would influence nest selection and result in an even distribution of eggs among nests. We studied pre-laying behaviour in groups of 30 LSL hens across two consecutive trials with eight groups per trial. Half of the groups had access to six identical rollaway group-nests, while the others had access to six nests of the same type differing in outer appearance. Three colours (red, green, yellow) and three black symbols (cross, circle, rectangle) were used to create three different nest curtain designs per pen. Nest position and the side of entrance to the pens were changed at 28 and 30 weeks of age, respectively, whereby the order of changes was counterbalanced across trials. Nest positions were numbered 1–6, with nest position 1 representing the nest closest to the pen entrance. Eggs were counted per nest daily from week of age 18 to 33. Nest visits were recorded individually with an RFID system for the first 5 h of light throughout weeks 24–33. Hens with access to nests differing in curtain appearance entered fewer nests daily than hens with identical nests throughout the study but both groups entered more nests with increasing age. We found no other evidence that curtain appearance affected nest choice and hens were inconsistent in their daily nest selection. A high proportion of eggs were laid in corner nests especially during the first three weeks of lay. The number of visits per egg depended upon nest position and age: it increased with age and was higher after the nest position change than before in nest position 1, whereas it stayed stable over time in nest position 6. At 24 weeks of age, gregarious nest visits (hens visiting an occupied nest when there was at least one unoccupied nest) and solitary nest visits (hens visiting an unoccupied nest when there was at least one occupied nest) accounted for a similar amount of nest visits, however, after the door switch, gregarious nest visits made up more than half of all nest visits, while the number of solitary nest visits had decreased. The visual cues were too subtle or inadequate for hens to develop individual preferences while nest position, entrance side, age and nest occupancy affected the quantity and type of nest visits.

Primary forest dynamics in lowland dipterocarp forest at Danum Valley, Sabah, Malaysia, and the role of the understorey

Changes in species composition in two 4–ha plots of lowland dipterocarp rainforest at Danum, Sabah, were measured over ten years (1986 to 1996) for trees greater than or equal to 10 cm girth at breast height (gbh). Each included a lower–slope to ridge gradient. The period lay between two drought events of moderate intensity but the forest showed no large lasting responses, suggesting that its species were well adapted to this regime. Mortality and recruitment rates were not unusual in global or regional comparisons. The forest continued to aggrade from its relatively (for Sabah) low basal area in 1986 and, together with the very open upper canopy structure and an abundance of lianas, this suggests a forest in a late stage of recovery from a major disturbance, yet one continually affected by smaller recent setbacks. Mortality and recruitment rates were not related to population size in 1986, but across subplots recruitment was positively correlated with the density and basal area of small trees (10 to <50 cm gbh) forming the dense understorey. Neither rate was related to topography. While species with larger mean gbh had greater relative growth rates (rgr) than smaller ones, subplot mean recruitment rates were correlated with rgr among small trees. Separating understorey species (typically the Euphorbiaceae) from the overstorey (Dipterocarpaceae) showed marked differences in change in mortality with increasing gbh: in the former it increased, in the latter it decreased. Forest processes are centred on this understorey quasi–stratum. The two replicate plots showed a high correspondence in the mortality, recruitment, population changes and growth rates of small trees for the 49 most abundant species in common to both. Overstorey species had higher rgrs than understorey ones, but both showed considerable ranges in mortality and recruitment rates. The supposed trade–off in traits, viz slower rgr, shade tolerance and lower population turnover in the understorey group versus faster potential growth rate, high light responsiveness and high turnover in the overstorey group, was only partly met, as some understorey species were also very dynamic. The forest at Danum, under such a disturbance–recovery regime, can be viewed as having a dynamic equilibrium in functional and structural terms. A second trade–off in shade–tolerance versus drought–tolerance is suggested for among the understorey species. A two–storey (or vertical component) model is proposed where the understorey–overstorey species’ ratio of small stems (currently 2:1) is maintained by a major feedback process. The understorey appears to be an important part of this forest, giving resilience against drought and protecting the overstorey saplings in the long term. This view could be valuable for understanding forest responses to climate change where drought frequency in Borneo is predicted to intensify in the coming decades.

Impacts of Technology Adoption: Comparing Returns to the Farming Sector in Maine under Alternative Technology Regimes

This thesis tests if certain technology choices are associated with a reduction in the proportion of farming activities in the agro-food system in Maine. Goodman, Sorj, and Wilkinson define appropriationism as the replacement of farming sector activities by industrial inputs. Based on the concept of appropriationism, industrial fanning systems using large amounts of synthetic inputs contribute less to fanning than more agrarian systems, like organic fanning. Thus, returns to the farming sector should be greater for organic compared with conventional potato fanning in Maine since organic farming uses fewer industrial inputs. Goodman et. al. define substitutionism as the displacement of farming sector commodities and activities by industrial processes in the marketing sector. Based on the concept of substitutionism, returns to the farming sector should be greater for Lay's Classic®™ potato chips made from natural potatoes compared with Baked Lay's®™ potato crisps manufactured from processed dehydrated potatoes. Returns to the farming sector are defined as returns to the farmer or farm family from farming activities, returns to farm labor, and returns to farmers and farm labor producing inputs used on the farm. Results show absolute returns to the farming sector are less for organic compared to conventional tablestock potato farms in Maine. However as a proportion of farm revenues, large organic farms that market at least 25% of their produce to retail stores or directly to consumers do as well as conventional farms. When comparing returns as a proportion of consumer expenditures, these organic farms do better than conventional farms. Returns to the farming sector are less for organic because of yield penalties, cost of marketing services, and diseconomies of size for organic tablestock potato farms. Expanding acreage and reintegrating livestock with cropping systems may increase returns to the fanning sector. Organic farming demonstrates difficulties in providing marketing services at the farm level. Providing marketing services limits the ability to expand production to capture economies of size. Maine organic potato farmers emphasize non-monetary values such as supporting sustainable agriculture, self-sufficiency, the intrinsic value of work, and close community and family connections. Returns to the farming sector as a proportion of consumer expenditures are about three times greater for Lay's Classic®™ potato chips than for Baked Lay's®™ potato crisps, since the value that farmers receive for potatoes used to produce dehydrated potato flakes in one pound of crisps is about half of the value that farmers receive for potatoes used to make one pound of chips. However, this assumes farmers assign a cost to producing low-grade potatoes for dehydration proportionate to their value. Premium potatoes are used to produce potato chips. Low-grade potatoes are used to produce the dehydrated potato flakes used to make potato crisps. Returns to the farming sector are slightly greater for potato crisps if no costs are allocated to producing low-grade potatoes for dehydration. A shift in consumer preferences from potato chips to crisps may result in a geographical shift of potato production from Maine to the Pacific Northwest assuming no food-grade dehydration facilities are built in Maine.

The effectiveness of a promotora-led intervention for Mexican Americans with type 2 diabetes

Purpose. The purpose of this randomized control repeated measures trial was to determine the effectiveness of a self-management intervention led by community lay workers called promotoras on the health outcomes of Mexican Americans with type 2 diabetes living in a major city on the Texas - Mexico border. The specific aims of this study, in relation to the intervention group participants, were to: (1) decrease the glycosylated hemoglobin (A1c) blood levels at the six-month assessment, (2) increase diabetes knowledge at the three and six-month assessments, and (3) strengthen the participants' beliefs in their ability to manage diabetes at the three and six-month assessments.^ Methods. One hundred and fifty Mexican American participants were recruited at a Catholic faith-based clinic and randomized into an intervention group and a usual-care control group. Personal characteristics, acculturation and baseline A1c, diabetes knowledge and diabetes health beliefs were measured. The six-month, two-phase intervention was culturally specific and it was delivered entirely by promotoras. Phase One of the intervention consisted of sixteen hours of participative group education and bi-weekly telephone contact follow-up. Phase Two consisted of bi-weekly follow-up using inspirational faith-based health behavior change postcards. The A1c levels, diabetes knowledge and diabetes health beliefs were measured at baseline, and three and six months post-baseline. The mean changes between the groups were analyzed using analysis of covariance. ^ Results. The 80% female sample, with a mean age of 58 years, demonstrated very low: acculturation, income, education, health insurance coverage, and strong Catholicism. No significant changes were noted at the three-month assessment, but the mean change of the A1c levels (F (1, 148 = 10.28, p < .001) and the diabetes knowledge scores (F (1, 148 = 9.0, p < .002) of the intervention group improved significantly at six months, adjusting for health insurance coverage. The diabetes health belief scores decreased in both groups.^ Conclusions. This study demonstrated that an intervention led by promotoras could result in decreased A1c levels and increased diabetes knowledge in spite of the very low acculturation, educational level and insurance coverage of the intervention group participants. Clinical implications and recommendations for future research are suggested. ^

Evaluation of the relationship between nutrition and functional independence measures among stroke patients undergoing inpatient rehabilitation

Cerebrovascular accidents (CVA) or strokes are now the third leading cause of death in the United States. Many who suffer strokes are admitted to rehabilitation centers in order to receive therapy to help rebuild and recovery function. Nutrition plays a significant role in rehabilitation patient outcomes, and is an essential part of comprehensive care. The purpose of this study is to determine if nutrition and diet consistency are directly and independently associated with changes in the Functional Independence Measure (FIM) scores in stroke patients in an acute rehabilitation unit. This study was a retrospective secondary analysis review of medical chart records, and included a total of 84 patients. Patients were divided into groups based on their admission diet: Regular, Dysphagia Advanced, Dysphagia Mechanically Altered, Dysphagia Pureed, and Nutrition Support. Measurements included admission and discharge Total, Motor, and Cognitive FIM scores; BMI, albumin and prealbumin; age, sex, and race. Patients did show a significant improvement in their FIM scores during their stay, with patients on Regular diets having the highest FIM scores. Patients who were more debilitated and had lower FIM scores were usually in one of the altered texture diet groups, or on nutrition support. Prealbumin and BMI were also the highest in patients who had high FIM scores. Patients who were admitted on an altered diet also tended to advance in their diets, which show improvement in overall function. It is crucial to continue to improve nutrition administration to this population to help prevent morbidity and mortality. Proper nutrition in the acute phase of stroke can lay the essential groundwork for recovery.^

From protein microarray to biology: The discovery of epigenetic regulatory molecules

Chromatin, composed of repeating nucleosome units, is the genetic polymer of life. To aid in DNA compaction and organized storage, the double helix wraps around a core complex of histone proteins to form the nucleosome, and is therefore no longer freely accessible to cellular proteins for the processes of transcription, replication and DNA repair. Over the course of evolution, DNA-based applications have developed routes to access DNA bound up in chromatin, and further, have actually utilized the chromatin structure to create another level of complexity and information storage. The histone molecules that DNA surrounds have free-floating tails that extend out of the nucleosome. These tails are post-translationally modified to create docking sites for the proteins involved in transcription, replication and repair, thus providing one prominent way that specific genomic sequences are accessed and manipulated. Adding another degree of information storage, histone tail-modifications paint the genome in precise manners to influence a state of transcriptional activity or repression, to generate euchromatin, containing gene-dense regions, or heterochromatin, containing repeat sequences and low-density gene regions. The work presented here is the study of histone tail modifications, how they are written and how they are read, divided into two projects. Both begin with protein microarray experiments where we discover the protein domains that can bind modified histone tails, and how multiple tail modifications can influence this binding. Project one then looks deeper into the enzymes that lay down the tail modifications. Specifically, we studied histone-tail arginine methylation by PRMT6. We found that methylation of a specific histone residue by PRMT6, arginine 2 of H3, can antagonize the binding of protein domains to the H3 tail and therefore affect transcription of genes regulated by the H3-tail binding proteins. Project two focuses on a protein we identified to bind modified histone tails, PHF20, and was an endeavor to discover the biological role of this protein. Thus, in total, we are looking at a complete process: (1) histone tail modification by an enzyme (here, PRMT6), (2) how this and other modifications are bound by conserved protein domains, and (3) by using PHF20 as an example, the functional outcome of binding through investigating the biological role of a chromatin reader. ^

The public health applications of law enforcement medical direction: A practical experience with the Dallas Police Department

In 2008, 132 law enforcement officers were killed in the line of duty in The United States. Additionally, some have explored both the public health implications of interactions with law enforcement as well as the potential benefits of the use of law enforcement officers as public health and emergency healthcare providers. By virtue of these novel analyses and techniques, professional medical direction of the emerging specialty of law enforcement medicine is needed. This paper, an analysis of law enforcement medical direction through a look at the Dallas Police Medical Direction Program, seeks to examine origins of law enforcement medicine through a comprehensive literature review, as well as begin to define to core competencies of law enforcement medical direction. ^ The unique intersection of public health, medicine and law enforcement, and the subsequent specialty that is developing to manage this interface, is in its relative infancy. An analysis of this nature is in order to begin to lay down the foundations necessary for future study and improvements in the field. ^

Ethnographic and epidemiologic approaches for the programming of prenatal and birth services in Mesa los Hornos, Mexico

The investigator conducted an action-oriented investigation of pregnancy and birth among the women of Mesa los Hornos, an urban squatter slum in Mexico City. Three aims guided the project: (1) To obtain information for improving prenatal and maternity service utilization; (2) To examine the utility of rapid ethnographic and epidemiologic assessment methodologies; (3) To cultivate community involvement in health development.^ Viewing service utilization as a culturally-bound decision, the study included a qualitative phase to explore women's cognition of pregnancy and birth, their perceived needs during pregnancy, and their criteria of service acceptability. A probability-based community survey delineated parameters of service utilization and pregnancy health events, and probed reasons for decisions to use medical services, lay midwives, or other sources of prenatal and labor and delivery assistance. Qualitative survey of service providers at relevant clinics, hospitals, and practices contributed information on service availability and access, and on coordination among private, social security, and public assistance health service sectors. The ethnographic approach to exploring the rationale for use or non-use of services provided a necessary complement to conventional barrier-based assessment, to inform planning of culturally appropriate interventions.^ Information collection and interpretation was conducted under the aegis of an advisory committee of community residents and service agency representatives; the residents' committee formulated recommendations for action based on findings, and forwarded the mandate to governmental social and urban development offices. Recommendations were designed to inform and develop community participation in health care decision-making.^ Rapid research methods are powerful tools for achieving community-based empowerment toward investigation and resolution of local health problems. But while ethnography works well in synergy with quantitative assessment approaches to strengthen the validity and richness of short-term field work, the author strongly urges caution in application of Rapid Ethnographic Assessments. An ethnographic sensibility is essential to the research enterprise for the development of an active and cooperative community base, the design and use of quantitative instruments, the appropriate use of qualitative techniques, and the interpretation of culturally-oriented information. However, prescribed and standardized Rapid Ethnographic Assessment techniques are counter-productive if used as research short-cuts before locale- and subject-specific cultural understanding is achieved. ^

Confidential inquiry into perinatal mortality in the Lower Rio Grande Valley, 1988

A review of 1985 neonatal death statistics in the Lower Rio Grande Valley of Texas revealed an excessive perinatal death rate among Hispanics compared to Anglos. In order to identify factors contributing to perinatal mortality in the region and to determine if existing perinatal services were adequate, a confidential inquiry into each 1988 perinatal death was performed.^ Medical risk factors in the mothers were infrequent. The most commonly noted pregnancy complication was polyhydramnios. This complication is often associated with anencephalus which was the most frequent birth anomaly detected in the region.^ The study results did not reveal an association between lay midwife deliveries in the region and excessive perinatal mortality nor did perinatal mortality appear to be associated with a lack of neonatal intensive care facilities. Lack of prenatal care was the most commonly encountered preventable factor associated with perinatal death. It was not possible to determine if the level of care for Anglos and Hispanics differed because of the low number of Anglo deaths although the socioeconomic level of deaths in each of the ethnic groups was the same. ^

A descriptive study of syphilis infection in Houston, Texas, 1999--2008

The rate of syphilis nationally has been on the rise since 2001. Syphilis, if left untreated can facilitate the transmission of HIV infection. An epidemiologic study describing the trends of syphilis is important to the public health community to lay the foundation for the development and implementation of programs to prevent and eliminate syphilis in the United States. ^ The objective of this study was to describe the trends of syphilis among the population in Houston/Harris County, Texas. ^ We reviewed surveillance data that included 11,605 unique cases from the Houston Department of Human and Health Service from 1999 through 2008. The rates were calculated per 100,000 population. ^ We show the prevalence of syphilis at testing (excluding congenital) increased 40% in Houston/Harris County, Texas from 2001 through 2008, and the ratio of syphilis comparing men to women was 2:1. The 18–29 years age group had the highest percentage of cases of syphilis among all age groups in Houston/Harris County. Primary and Secondary (P&S) syphilis, the most infectious stage, had an 85% increase in rate among males from 1999 through 2008. ^ Between 1999 and 2000, 71% of cases were identified through public facilities compared to private facilities. However, after 2001 rates shifted over more to the private facilities. By 2008, private facilities identified 54.7% of cases, compared to 45.3% identified through public facilities. This may be due to an increase among individuals who have a higher socio-economic status with access to health care insurance. ^ In conclusion, syphilis rates from 1999 through 2008 increased among all race ethnicities, age groups, and genders in Houston/Harris County. Blacks still are disproportionally affected by syphilis infections, and for the first time, White males displayed a significant increase in cases among males. It is vital to Houston public health professionals to have improved surveillance techniques to track syphilis trends and engage high risk groups to better understand their risks in hope of treating and preventing syphilis.^

MicroRNA Regulation of Prostate Cancer Stem/Progenitor Cells and Prostate Cancer Development

Most human tumors contain a population of cells with stem cell properties, called cancer stem cells (CSCs), which are believed to be responsible for tumor establishment, metastasis, and resistance to clinical therapy. It’s crucial to understand the regulatory mechanisms unique to CSCs, so that we may design CSC-specific therapeutics. Recent discoveries of microRNA (miRNA) have provided a new avenue in understanding the regulatory mechanisms of cancer. However, how miRNAs may regulate CSCs is still poorly understood. Here, we present miRNA expression profiling in six populations of prostate cancer (PCa) stem/progenitor cells that possess distinct tumorigenic properties. Six miRNAs were identified to be commonly and differentially expressed, namely, four miRNAs (miR-34a, let-7b, miR-106a and miR-141) were under-expressed, and two miRNAs (miR-301 and miR-452) were over-expressed in the tumorigenic subsets compared to the corresponding marker-negative subpopulations. Among them, the expression patterns of miR-34, let-7b, miR-141 and miR-301 were further confirmed in the CD44+ human primary prostate cancer (HPCa) samples. We then showed that miR-34a functioned as a critical negative regulator in prostate CSCs and PCa development and metastasis. Over-expression of miR-34a in either bulk or CD44+ PCa cells significantly suppressed clonal expansion, tumor development and metastasis. Systemic delivery of miR-34a in tumor-bearing mice demonstrated a potent therapeutic effect again tumor progression and metastasis, leading to extended animal survival. Of great interest, we identified CD44 itself as a direct and relevant downstream target of miR-34a in mediating its tumor-inhibitory effects. Like miR-34a, let-7 manifests similar tumor suppressive effects in PCa cells. In addition, we observed differential mechanisms between let-7 and miR-34a on cell cycle, with miR-34a mainly inducing G1 cell-cycle arrest followed by cell senescence and let-7 inducing G2/M arrest. MiR-301, on the other hand, exerted a cell type dependent effect in regulating prostate CSC properties and PCa development. In summary, our work reveals that the prostate CSC populations display unique miRNA expression signatures and different miRNAs distinctively and coordinately regulate various aspects of CSC properties. Altogether, our results lay a scientific foundation for developing miRNA-based anti-cancer therapy.