Energizing the search to target LKB1-mutant tumors.

LKB1 is the third most frequently mutated gene in non-small cell lung cancer and serves as a master regulator of cell metabolism and polarity across a variety of model organisms. Recent studies are beginning to identify therapeutics that exploit defects associated with LKB1 loss. The work presented here by Liu and colleagues shows that deoxythymidylate kinase is a new potential target in LKB1-deficient tumors and highlights the possibility of a new therapeutic option for this subset of patients with cancer.

Acetylated tubulin (AT) as a prognostic marker in squamous cell carcinoma of the head and neck.

Acetylated tubulin (AT) expression has been proposed as a marker for sensitivity to taxane chemotherapy. We wanted to explore AT as a prognostic marker in squamous cell carcinoma of the head and neck (SCCHN). We assessed AT expression in archival tissue from our institutional tissue bank of primary SCCHN specimens.

Fifty years of DNA "breathing": Reflections on old and new approaches.

The coding sequences for genes, and much other regulatory information involved in genome expression, are located 'inside' the DNA duplex. Thus the "macromolecular machines" that read-out this information from the base sequence of the DNA must somehow access the DNA "interior." Double-stranded (ds) DNA is a highly structured and cooperatively stabilized system at physiological temperatures, but is also only marginally stable and undergoes a cooperative "melting phase transition" at temperatures not far above physiological.

Dysregulation of mTOR activity through LKB1 inactivation.

Mammalian target of rapamycin (mTOR) is aberrantly activated in many cancer types, and two rapamycin derivatives are currently approved by the Food and Drug Administration (FDA) of the United States for treating renal cell carcinoma. Mechanistically, mTOR is hyperactivated in human cancers either due to the genetic activation of its upstream activating signaling pathways or the genetic inactivation of its negative regulators. The tumor suppressor liver kinase B1 (LKB1), also known as serine/threonine kinase 11 (STK11), is involved in cell polarity, cell detachment and adhesion, tumor metastasis, and energetic stress response.

Bridging the transition from cancer patient to survivor: pilot study results of the Cancer Survivor Telephone Education and Personal Support (C-STEPS) program.

Objective: To develop a feasibility study of a theory-driven telephone counseling program to enhance psychosocial and physical well-being for cancer survivors after treatment.

Methods: Participants (n=66) were recruited from two Colorado hospitals with self-administered questionnaires at baseline and two weeks post-intervention. The one group, intervention only design included up to six thematic telephone counseling sessions over three months.

LKB1 represses focal adhesion kinase (FAK) signaling via a FAK-LKB1 complex to regulate FAK site maturation and directional persistence.

Liver kinase β1 (LKB1, also known as STK11) is a serine/threonine kinase that has multiple cellular functions including the regulation of cell polarity and motility. Murine proteomic studies show that LKB1 loss causes aberrant adhesion signaling; however, the mechanistic underpinnings of this relationship are unknown. We show that cells stably depleted of LKB1 or its co-activator STRADα have increased phosphorylation of focal adhesion kinase (FAK) at Tyr(397)/Tyr(861) and enhanced adhesion to fibronectin.

Responding to a significant recruitment challenge within three nationwide psychoeducational trials for cancer patients.

Purpose: When faced with a significant recruitment challenge for three nationwide psychoeducational trials targeting prostate and breast cancer patients, the Cancer Information Service Research Consortium initiated outreach efforts to increase accrual. Recruitment is reported by major outreach strategy to inform the use of similar campaigns, either as primary recruitment efforts or to supplement "in-reach" recruitment within oncology settings.

Methods: During a 33-month period, recruitment was tracked from the National Cancer Institute's Cancer Information Service (CIS), the American Cancer Society (ACS), Dr.

A single-molecule view of the assembly pathway, subunit stoichiometry, and unwinding activity of the bacteriophage T4 primosome (helicase-primase) complex.

Single-molecule fluorescence resonance energy transfer (smFRET) methods were used to study the assembly pathway and DNA unwinding activity of the bacteriophage T4 helicase-primase (primosome) complex. The helicase substrates used were surface-immobilized model DNA replication forks "internally" labeled in the duplex region with opposed donor/acceptor (iCy3/iCy5) chromophore pairs in the lagging and leading strands. The time dependence of the smFRET signals was monitored during the unwinding process, and helicase rates and processivities were measured as a function of GTP concentration.

Bioaccumulation of trace metals in shellfish and fish of Bonny River and creeks around Okrika in Rivers State, Nigeria.

Lead, nickel, vanadium and cadmium were determined in fish and shellfish muscles, to assess contamination levels and identify bio-indicators. Vanadium was not detectable. Lead and cadmium were slightly above legal limits used in South East Asia, but lower than those of Australia and New Zealand.

A Combined Activated Sludge Anaerobic Digestion Model (CASADM) to understand the role of anaerobic sludge recycling in wastewater treatment plant performance.

The Combined Activated Sludge-Anaerobic Digestion Model (CASADM) quantifies the effects of recycling anaerobic-digester (AD) sludge on the performance of a hybrid activated sludge (AS)-AD system. The model includes nitrification, denitrification, hydrolysis, fermentation, methanogenesis, and production/utilization of soluble microbial products and extracellular polymeric substances (EPS). A CASADM example shows that, while effluent COD and N are not changed much by hybrid operation, the hybrid system gives increased methane production in the AD and decreased sludge wasting, both caused mainly by a negative actual solids retention time in the hybrid AD.

The Living Well by Faith Health and wellness program for African Americans: an exemplar of community-based participatory research.

Background: Using community-based participatory research (CBPR) as a guiding framework, a faith-based diet, nutrition and physical activity intervention for African Americans was implemented and evaluated as a small-scale randomized trial.

Methods: Five churches were recruited (intervention=3, control=2), resulting in an enrolled sample of 106 adults (intervention=74, control=32). The control group received a minimal intervention consisting of one educational workshop.

Temperature-dependent conformations of a membrane supported zinc porphyrin tweezer by 2D fluorescence spectroscopy.

We studied the equilibrium conformations of a zinc porphyrin tweezer composed of two carboxylphenyl-functionalized zinc tetraphenyl porphyrin subunits connected by a 1,4-butyndiol spacer, which was suspended inside the amphiphilic regions of 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) liposomes. By combining phase-modulation two-dimensional fluorescence spectroscopy (2D FS) with linear absorbance and fluorimetry, we determined that the zinc porphyrin tweezer adopts a mixture of folded and extended conformations in the membrane. By fitting an exciton-coupling model to a series of data sets recorded over a range of temperatures (17-85 °C) and at different laser center wavelengths, we determined that the folded form of the tweezer is stabilized by a favorable change in the entropy of the local membrane environment.

Cancer patient and survivor research from the cancer information service research consortium: a preview of three large randomized trials and initial lessons learned.

The authors describe 3 large randomized trials from the Cancer Information Service Research Consortium. Three web-based multimedia programs are being tested to help newly diagnosed prostate (Project 1) and breast cancer patients (Project 2) make informed treatment decisions and breast cancer patients prepare for life after treatment (Project 3). Project 3 also tests a telephone callback intervention delivered by a cancer information specialist.

Performance of plastic- and sponge-based trickling filters treating effluents from an UASB reactor.

The paper compares the performance of two trickling filters (TFs) filled with plastic- or sponge-based packing media treating the effluent from an upflow anaerobic sludge blanket (UASB) reactor. The UASB reactor was operated with an organic loading rate (OLR) of 1.2 kgCOD m(-3) d(-1), and the OLR applied to the TFs was 0.

Long-term weight gain among Hispanic and non-Hispanic White women with and without breast cancer.

Weight gain following breast cancer diagnosis is common, but limited data exists on whether this gain is in excess of that gained during normal aging. This study investigated weight patterns among women with and without breast cancer to determine the effects of the breast cancer experience on weight change. Using the SHINE 4-Corners Breast Cancer Study, 305 women with breast cancer and 345 women without were followed prospectively.

Analysis of CPD ultraviolet lesion bypass in chicken DT40 cells: polymerase η and PCNA ubiquitylation play identical roles.

Translesion synthesis (TLS) provides a mechanism of copying damaged templates during DNA replication. This potentially mutagenic process may operate either at the replication fork or at post-replicative gaps. We used the example of T-T cyclobutane pyrimidine dimer (CPD) bypass to determine the influence of polymerase recruitment via PCNA ubiquitylation versus the REV1 protein on the efficiency and mutagenic outcome of TLS.

Electronic transition moments of 6-methyl isoxanthopterin--a fluorescent analogue of the nucleic acid base guanine.

Fluorescent nucleic acid base analogues are important spectroscopic tools for understanding local structure and dynamics of DNA and RNA. We studied the orientations and magnitudes of the electric dipole transition moments (EDTMs) of 6-methyl isoxanthopterin (6-MI), a fluorescent analogue of guanine that has been particularly useful in biological studies. Using a combination of absorption spectroscopy, linear dichroism (LD) and quantum chemical calculations, we identified six electronic transitions that occur within the 25,000-50,000 cm(-1) spectral range.

Integrating image analysis algorithms in a web interface for the quantification of microtubule dynamics.

We present improvements to a web interface and an integrated computational tracking algorithm for quantitative analysis of microtubule dynamics in live-cell microscopy images. Based on a previously implemented system, more new functionalities have been added to the interface. The system also integrates a computational tracking algorithm to aid the analysis.

Fluorescence microscopy is superior to polarized microscopy for detecting amyloid deposits in Congo red-stained trephine bone marrow biopsy specimens.

The classic gold standard for detecting amyloid deposits is Congo red-stained bright field and polarized microscopy (CRPM). A prior study showed that Congo red fluorescence (CRF) microscopy had increased sensitivity compared with traditional CRPM when analyzing fat pad specimens. The purpose of the current study was to determine the sensitivity of CRF for evaluating Congo red-stained bone marrow biopsy specimens, and to compare these results with those of CRPM.

Mailed intervention to promote sun protection of children: a randomized controlled trial.

Background: Sun exposure, especially during childhood, is the most important preventable risk factor for skin cancer, yet few effective interventions to reduce exposure exist.

Purpose: To test the effectiveness of a partially tailored mailed intervention based on the Precaution Adoption Process Model, delivered in the spring over 3 years to parents and children.

Design: RCT, with data collection through telephone interviews of parents and skin exams of children at baseline (Summer 2004) and annually (Summer 2005-2007).

Compressed Sensing for Multidimensional Spectroscopy Experiments.

Compressed sensing is a processing method that significantly reduces the number of measurements needed to accurately resolve signals in many fields of science and engineering. We develop a two-dimensional variant of compressed sensing for multidimensional spectroscopy and apply it to experimental data. For the model system of atomic rubidium vapor, we find that compressed sensing provides an order-of-magnitude (about 10-fold) improvement in spectral resolution along each dimension, as compared to a conventional discrete Fourier transform, using the same data set.

Conformation and electronic population transfer in membrane-supported self-assembled porphyrin dimers by 2D fluorescence spectroscopy.

Two-dimensional fluorescence spectroscopy (2D FS) is applied to determine the conformation and femtosecond electronic population transfer in a dimer of magnesium meso tetraphenylporphyrin. The dimers are prepared by self-assembly of the monomer within the amphiphilic regions of 1,2-distearoyl-sn-glycero-3-phosphocholine liposomes. A theoretical framework to describe 2D FS experiments is presented, and a direct comparison is made between the observables of this measurement and those of 2D electronic spectroscopy (2D ES).

[The 'paper-based' preoperative evaluation: non-optimal health care].

A nationwide preoperative assessment guideline was introduced in the Netherlands in 1997 at the advice of the Health Council of the Netherlands. The preoperative assessment should entail an appropriate interview, a physical examination, additional tests, risk assessment and informing the patient. Dutch and several international guidelines recommend a complete assessment under the responsibility of the anaesthesiologist.

The development and preliminary testing of a multimedia patient-provider survivorship communication module for breast cancer survivors.

Objective: This paper describes the development of a theory-guided and evidence-based multimedia training module to facilitate breast cancer survivors' preparedness for effective communication with their health care providers after active treatment.

Methods: The iterative developmental process used included: (1) theory and evidence-based content development and vetting; (2) user testing; (3) usability testing; and (4) participant module utilization.

Results: Formative evaluation of the training module prototype occurred through user testing (n = 12), resulting in modification of the content and layout.

AMPK regulates mitotic spindle orientation through phosphorylation of myosin regulatory light chain.

The proper orientation of the mitotic spindle is essential for mitosis; however, how these events unfold at the molecular level is not well understood. AMP-activated protein kinase (AMPK) regulates energy homeostasis in eukaryotes, and AMPK-null Drosophila mutants have spindle defects. We show that threonine(172) phosphorylated AMPK localizes to the mitotic spindle poles and increases when cells enter mitosis.