PARP14 regulates cyclin D1 expression to promote cell-cycle progression.

Cyclin D1 is an essential regulator of the G1-S cell-cycle transition and is overexpressed in many cancers. Expression of cyclin D1 is under tight cellular regulation that is controlled by many signaling pathways. Here we report that PARP14, a member of the poly(ADP-ribose) polymerase (PARP) family, is a regulator of cyclin D1 expression.

PARI (PARPBP) suppresses replication stress-induced myeloid differentiation in leukemia cells.

Hyperproliferative cancer cells face increased replication stress, which can result in accumulation of DNA damage. As DNA damage can arrest proliferation, and, in the case of myeloid leukemia, induce differentiation of cancer cells, understanding the mechanisms that regulate the replication stress response is paramount. Here, we show that PARI, a replisome protein involved in regulating DNA repair and replication stress, suppresses differentiation of myeloid leukemia cells.

NFκB regulates p21 expression and controls DNA damage-induced leukemic differentiation.

DNA damage exposure is a major modifier of cell fate in both normal and cancer tissues. In response to DNA damage, myeloid leukemia cells activate a poorly understood terminal differentiation process. Here, we show that the NFκB pathway directly activates expression of the proliferation inhibitor p21 in response to DNA damage in myeloid leukemia cells.

Infrared-transparent gold nanoparticles converted by tumors to infrared absorbers cure tumors in mice by photothermal therapy.

Gold nanoparticles (AuNPs) absorb light and can be used to heat and ablate tumors. The "tissue window" at ∼ 800 nm (near infrared, NIR) is optimal for best tissue penetration of light. Previously, large, 50-150 nm, gold nanoshells and nanorods that absorb well in the NIR have been used.

Gold nanoparticle imaging and radiotherapy of brain tumors in mice.

Aim: To test intravenously injected gold nanoparticles for x-ray imaging and radiotherapy enhancement of large, imminently lethal, intracerebral malignant gliomas.

Materials & Methods: Gold nanoparticles approximately 11 nm in size were injected intravenously and brains imaged using microcomputed tomography. A total of 15 h after an intravenous dose of 4 g Au/kg was administered, brains were irradiated with 30 Gy 100 kVp x-rays.

Evaluation of antigen-capture ELISA and immunohistochemical methods for avian surveillance of West Nile virus.

Accurate detection of West Nile virus (WNV) in corvids is essential for monitoring the spread of virus during the mosquito season. Viremia in corvids is very high, with titers approaching 10(8) viral particles/ml. In the presence of such marked viremia, the sensitivity of real-time reverse transcription-polymerase chain reaction (RT-PCR) analysis is unnecessary, and more cost-effective methods should be assessed.

Mortality after epilepsy surgery.

Mortality rates are higher in people with refractory epilepsy than in the general population. We assessed mortality rates in a prospectively followed cohort who had epilepsy surgery, to examine the factors related to mortality and to assess the relationship between seizure control and mortality. Five hundred eighty-three patients were evaluated.

Value of non-invasive testing when there are independent bitemporal seizures in the scalp EEG.

We investigated the value of non-invasive data for predicting the outcome of intracranial EEG and anterior temporal lobectomy (ATL) (follow-up>1 year) in patients who have bitemporal independent seizures in the scalp EEG. No previous report has dealt with this patient group. Independent variables were duration of epilepsy, febrile seizures, interictal and ictal scalp EEG, ictal behavior, MRI, [18F]-fluorodeoxyglucose-PET (PET) and Wada test and dependent variables were surgical outcome (seizure free or not) and localized on intracranial EEG (finding all symptomatic seizures from one temporal lobe).

Lack of association between variations in the brain-derived neurotrophic factor (BDNF) gene and temporal lobe epilepsy.

Recently, an association between the C240T polymorphism in the brain-derived neurotrophic factor (BDNF) gene and partial epilepsy was demonstrated in a Japanese population. In this study we attempted to replicate the initial finding in a patient-control population of European ancestry and in addition tested whether the functional Val66Met polymorphism is associated with temporal lobe epilepsy (TLE). Genotypes of 151 TLE patients and 189 controls did not differ significantly for either of the variations.

Distinguishing regulatory DNA from neutral sites.

We explore several computational approaches to analyzing interspecies genomic sequence alignments, aiming to distinguish regulatory regions from neutrally evolving DNA. Human-mouse genomic alignments were collected for three sets of human regions: (1) experimentally defined gene regulatory regions, (2) well-characterized exons (coding sequences, as a positive control), and (3) interspersed repeats thought to have inserted before the human-mouse split (a good model for neutrally evolving DNA). Models that potentially could distinguish functional noncoding sequences from neutral DNA were evaluated on these three data sets, as well as bulk genome alignments.

Initial sequencing and comparative analysis of the mouse genome.

The sequence of the mouse genome is a key informational tool for understanding the contents of the human genome and a key experimental tool for biomedical research. Here, we report the results of an international collaboration to produce a high-quality draft sequence of the mouse genome. We also present an initial comparative analysis of the mouse and human genomes, describing some of the insights that can be gleaned from the two sequences.

Extravascular collagen in the human epileptic brain: a potential substrate for aberrant cell migration in cases of temporal lobe epilepsy.

Object: Several lines of evidence have demonstrated a number of cellular changes that occur within the hippocampus in patients with temporal lobe epilepsy (TLE). These include aberrant migration of granule cells and sprouting of mossy fibers, processes that have been linked to the hyperexcitability phenomenon observed in cases of TLE. In the present study the authors examined brain tissues obtained in patients undergoing temporal lobectomy surgery and in patients at autopsy (normal human control specimens), and compared the subcellular composition of regions of the hippocampus containing dispersed granule cells.

Extending the beta-Lactamase-Dependent Prodrug Armory: S-Aminosulfeniminocephalosporins as Dual-Release Prodrugs.

Cephalosporins bearing an S-aminosulfenimine (R'(R' ')NSN=) side chain at the 7-position are prototypic examples of a novel class of beta-lactamase-dependent prodrug. Enzyme-catalyzed hydrolysis of the beta-lactam ring in these structures triggers release of both the 3'-acetoxy group and the side chain sulfur-attached S-amino moiety as R'(R' ')NH. This reactivity pattern should allow site-specific corelease of two distinct drug components from a cephalosporin, thereby providing a singular enhancement to the capacity of a cephalosporin as a prodrug nucleus; a key advantage of a dual-release prodrug is the potential to establish synergy between the coreleased structures.