PU.1 is regulated by NF-kappaB through a novel binding site in a 17 kb upstream enhancer element

The majority of patients with acute myeloid leukemia (AML) still die of their disease, and novel therapeutic concepts are needed. Timely expression of the hematopoietic master regulator PU.1 is crucial for normal development of myeloid and lymphoid cells. Targeted disruption of an upstream regulatory element (URE) located several kb upstream in the PU.1 promoter decreases PU.1 expression thereby inducing AML in mice. In addition, suppression of PU.1 has been observed in specific subtypes of human AML. Here, we identified nuclear factor-kappaB (NF-kappaB) to activate PU.1 expression through a novel site within the URE. We found sequence variations of this particular NF-kappaB site in 4 of 120 AML patients. These variant NF-kappaB sequences failed to mediate activation of PU.1. Moreover, the synergistic activation of PU.1 together with CEBPB through these variant sequences was also lost. Finally, AML patients with such variant sequences had suppressed PU.1 mRNA expression. This study suggests that changes of a single base pair in a distal element critically affect the regulation of the tumor suppressor gene PU.1 thereby contributing to the development of AML.

Regulation of sodium/glucose cotransporter expression in LLC-PK$\sb1$ cells

Expression of the Na$\sp+$/glucose cotransporter (SGLT1), a differentiated function of the pig kidney epithelial cell line LLC-PK$\sb1$ derived from proximal tubule, was further investigated. The differentiation inducer hexamethylene bisacetamide (HMBA) and IBMX, an inhibitor of cAMP phosphodiesterase, each stimulated a significant increase in Na$\sp+$/glucose cotransport activity, levels of the 75 kD cotransporter subunit and steady-state levels of the SGLT1 message. The action of HMBA is associated with involvement of polyamines and protein kinase C, and is synergistic with cAMP. We provide evidence that cAMP-elevating agents increase Na$\sp+$/glucose cotransporter expression, at least in part, via a post-transcriptional mechanism. Two molecular species of SGLT1 mRNA (3.9 kb and 2.2 kb) are transcribed from the same gene in LLC-PK$\sb1$ cells and differ only in the length of the 3$\sp\prime$ untranslated region (3$\sp\prime$ UTR). cAMP elevation differentially stabilized the 3.9 kb SGLT1 transcript from degradation but not the 22 kb species. UV-cross-linking and label transfer experiments indicated that cyclic AMP elevation was associated with formation of a 48 kD protein complex with a specific domain within the 3$\sp\prime$ UTR of SGLT1 mRNA. The binding was competitively inhibited by poly (U) and other U-rich RNA species such as c-fos ARE, and modulated by a protein kinase A-mediated phosphorylation/dephosphorylation mechanism. The binding site was mapped to a 120-nucleotide 3$\sp\prime$ UTR sequence which contains a uridine-rich region (URE). Our study provides the first demonstration that renal SGLT1 is post-transcriptionally regulated by a phosphorylation/dephosphorylation mechanism, and provides a deeper insight into gene regulation of this physiologically important cotransporter. ^

Community College Student Participation in Undergraduate Research: An Explanatory Case Study for Faculty and Research Mentors

This study adapted the current model of science undergraduate research experiences (URE's) and applied this novel modification to include community college students. Numerous researchers have examined the efficacy of URE's in improving undergraduate retention and graduation rates, as well as matriculation rates for graduate programs. However, none have detailed the experience for community college students, and few have employed qualitative methodologies to gather relevant descriptive data from URE participants. This study included perspectives elicited from both non-traditional student participants and the established laboratory community. The purpose of this study was to determine the effectiveness of the traditional model for a non-traditional student population. The research effort described here utilized a qualitative design and an explanatory case study methodology. Six non-traditional students from the Maine Community College System participated in this study. Student participants were placed in six academic research laboratories located throughout the state. Student participants were interviewed three times during their ten-week internship and asked to record their personal reflections in electronic format. Participants from the established research community were also interviewed. These included both faculty mentors and other student laboratory personnel. Ongoing comparative analysis of the textual data revealed that laboratory organizational structure and social climate significantly influence acculturation outcomes for non-traditional URE participants. Student participants experienced a range of acculturation outcomes from full integration to marginalization. URE acculturation outcomes influenced development of non-traditional students? professional and academic self-concepts. Positive changes in students? self-concepts resulted in greater commitment to individual professional goals and academic aspirations. The findings from this study suggest that traditional science URE models can be successfully adapted to meet the unique needs of a non-traditional student population – community college students. These interpretations may encourage post-secondary educators, administrators, and policy makers to consider expanded access and support for non-traditional students seeking science URE opportunities.

RESPONSES OF INDICATOR AND PATHOGENIC BACTERIA TO THE PRESENCE OF CARBARYL IN WATER

Biodegradability is a desirable, if not a necessary characteristic of pesticides. Carbaryl, as Sevin, is one of the more widely used insecticides for the control of agricultural pests and has been reported to be readily degraded by microorganisms. Because of its broad application, the concentration of Sevin in surface waters has been reported to reach nearly four parts per million (PPM) in surface waters, where it has been reported to affect the growth and metabolic rates of aquatic bacterial populations. Following these reports, it is of public health importance to determine the effects of this insecticide on the growth and metabolic rates of bacteria used to indicate water pollution, and on pathogenic organisms which are found in polluted water.^ This study was conducted to determine the effect of carbaryl on the growth and metabolic rates of indicator and pathogenic organisms. Escherichia coli and Streptococcus faecalis were used as indicators, while Staphylococcus aureus and Salmonella typhimurium were the pathogens studied. Pure and mixed cultures of these organisms were exposed to two concentrations of carbaryl (Sevin).^ The study demonstrated that the fecal pollution indicator organisms, E. coli and S. faecalis respond differently to the presence of small concentrations of carbaryl in water as do the two pathogens tested, (S. typhimurium and S. aureus). The growth of all test organisms as measured by spread plate counts, was reduced by the presence of either one mg/l or five mg/l carbaryl within a period of eight days. Survival of the organisms in the presence of five mg/l carbaryl varied dependent upon whether the organism was in pure or mixed culture. In the presence of five mg/l carbaryl, both pure and mixed culture of E. coli showed longer survival. S. faecalis survived for more than eight days in pure culture, neither S. typhimurium nor S. aureus survived for eight days in pure culture.^ The metabolic rate of S. faecalis and S. aureus was reduced by both five mg/l and one mg/l Sevin concentrations, contrary to E. coli and S. typhimurium which had reduced metabolic rate with the introduction of five mg/l Sevin but showed an increase in the metabolic rate with one mg/l Sevin. There was no difference between the test and control when mixed populations were exposed to five mg/l Sevin and the metabolic rate tested. A mixture of E. coli and S. typhimurium populations showed a respiration increase over the control when exposed to one mg/l Sevin concentration. If similar effects occur in polluted surface waters, misleading results from bacteriological water quality testing may occur. ^

Ser, hacer y decir

El artículo cuestiona la interacción y la comunicación en tanto fenómenos intencionales desde una perspectiva ontológica. Recorre críticamente el esencialismo que supone la teoría de la sustancia y las tesis básicas de las vertientes analíticas antimetafísicas, con el fin de descubrir la relación entre la palabra en cuanto signo y la palabra entendida como donación. Así, acentúa el carácter constituible de la persona y la función plenificadora de la coexistencia en su concreción pragmático-lingüística.

Propuesta de modalidad de trabajo práctico de laboratorio para el nivel universitario básico

Se presenta el proceso de diseño e implementación de dos trabajos prácticos de laboratorio. Ambos trabajos responden a un formato elaborado como una propuesta superadora a partir de la constatación de que los estudiantes suelen llevarlos a cabo mecánicamente, sin tener en claro el objetivo de la tarea. Las prácticas se inician con una pregunta que los estudiantes pueden responder, no necesariamente con certeza pero sí al menos concebir diferentes respuestas. Los estudiantes deben proponer los pasos a seguir para responder. De la evaluación de las implementaciones se desprende que los estudiantes se comprometieron con la tarea, haciendo suyo el objetivo del laboratorio. Finalmente se discuten las implicaciones de los resultados obtenidos. Este trabajo se enmarca en un proyecto de investigación con una metodología cualitativa y exploratoria.

Propuesta de modalidad de trabajo práctico de laboratorio para el nivel universitario básico

Se presenta el proceso de diseño e implementación de dos trabajos prácticos de laboratorio. Ambos trabajos responden a un formato elaborado como una propuesta superadora a partir de la constatación de que los estudiantes suelen llevarlos a cabo mecánicamente, sin tener en claro el objetivo de la tarea. Las prácticas se inician con una pregunta que los estudiantes pueden responder, no necesariamente con certeza pero sí al menos concebir diferentes respuestas. Los estudiantes deben proponer los pasos a seguir para responder. De la evaluación de las implementaciones se desprende que los estudiantes se comprometieron con la tarea, haciendo suyo el objetivo del laboratorio. Finalmente se discuten las implicaciones de los resultados obtenidos. Este trabajo se enmarca en un proyecto de investigación con una metodología cualitativa y exploratoria.

Propuesta de modalidad de trabajo práctico de laboratorio para el nivel universitario básico

Se presenta el proceso de diseño e implementación de dos trabajos prácticos de laboratorio. Ambos trabajos responden a un formato elaborado como una propuesta superadora a partir de la constatación de que los estudiantes suelen llevarlos a cabo mecánicamente, sin tener en claro el objetivo de la tarea. Las prácticas se inician con una pregunta que los estudiantes pueden responder, no necesariamente con certeza pero sí al menos concebir diferentes respuestas. Los estudiantes deben proponer los pasos a seguir para responder. De la evaluación de las implementaciones se desprende que los estudiantes se comprometieron con la tarea, haciendo suyo el objetivo del laboratorio. Finalmente se discuten las implicaciones de los resultados obtenidos. Este trabajo se enmarca en un proyecto de investigación con una metodología cualitativa y exploratoria.

A general implementation framework for tabled CLP

This paper describes a framework to combine tabling evalua- tion and constraint logic programming (TCLP). While this combination has been studied previously from a theoretical point of view and some implementations exist, they either suffer from a lack of efficiency, flex- ibility, or generality, or have inherent limitations with respect to the programs they can execute to completion (either with success or fail- ure). Our framework addresses these issues directly, including the ability to check for answer / call entailment, which allows it to terminate in more cases than other approaches. The proposed framework is experimentally compared with existing solutions in order to provide evidence of the mentioned advantages.

Inactivation of the survival motor neuron gene, a candidate gene for human spinal muscular atrophy, leads to massive cell death in early mouse embryos

Proximal spinal muscular atrophy is an autosomal recessive human disease of spinal motor neurons leading to muscular weakness with onset predominantly in infancy and childhood. With an estimated heterozygote frequency of 1/40 it is the most common monogenic disorder lethal to infants; milder forms represent the second most common pediatric neuromuscular disorder. Two candidate genes—survival motor neuron (SMN) and neuronal apoptosis inhibitory protein have been identified on chromosome 5q13 by positional cloning. However, the functional impact of these genes and the mechanism leading to a degeneration of motor neurons remain to be defined. To analyze the role of the SMN gene product in vivo we generated SMN-deficient mice. In contrast to the human genome, which contains two copies, the mouse genome contains only one SMN gene. Mice with homozygous SMN disruption display massive cell death during early embryonic development, indicating that the SMN gene product is necessary for cellular survival and function.

TnrA, a transcription factor required for global nitrogen regulation in Bacillus subtilis.

Expression of the Bacillus subtilis nrgAB operon is derepressed during nitrogen-limited growth. We have identified a gene, tnrA, that is required for the activation of nrgAB expression under these growth conditions. Analysis of the DNA sequence of the tnrA gene revealed that it encodes a protein with sequence similarity to GlnR, the repressor of the B. subtilis glutamine synthetase operon. The tnrA mutant has a pleiotropic phenotype. Compared with wild-type cells, the tnrA mutant is impaired in its ability to utilize allantoin, gamma-aminobutyrate, isoleucine, nitrate, urea, and valine as nitrogen sources. During nitrogen-limited growth, transcription of the nrgAB, nasB, gabP, and ure genes is significantly reduced in the tnrA mutant compared with the levels seen in wild-type cells. In contrast, the level of glnRA expression is 4-fold higher in the, tnrA mutant than in wild-type cells during nitrogen restriction. The phenotype of the tnrA mutant indicates that a global nitrogen regulatory system is present in B. subtilis and that this system is distinct from the Ntr regulatory system found in enteric bacteria.

[Latin exercise], undated

Small piece of paper containing a handwritten Latin text beginning, "Ego, en omni erga ure affectione..." The verso has the note: "Pro Don. Pup."

Elements of the art of dyeing and bleaching /

Spine title: Dyeing & bleaching.

The origin of tyranny,

Arguments in favor of the view that the earliest tyrannies were founded on wealth.

Encyklopädisches Handbuch der technischen Chemie /

Added t.p.: Muspratts' Theoretische, praktische und analytische Chemie in Anwendung auf Künste und Gewerbe.