Table Of Contents Page, PNAS Volume 98, Number 21

The recent discovery of an ancient reservoir of icy bodies at and beyond the orbit of Neptune—the Kuiper belt—has opened a new frontier in astronomy. Measurements of the physical and chemical nature of Kuiper belt objects (KBOs) can constrain our ...

Flavoproteins can function as hydrophobic sites for vitamin B₂ (riboflavin) or, in other structures, with cofactors for catalytic reactions such as glucose oxidation. In this contribution, we report direct observation of charge separation and ...

In this contribution, we report studies of the primary dynamics of the drug–protein complexes of daunomycin with apo riboflavin-binding protein. With femtosecond resolution, we observed the ultrafast charge separation between daunomycin and ...

The binding of tumor necrosis factor alpha (TNF-α) to the type-1 TNF receptor (TNFRc1) plays an important role in inflammation. Despite the clinical success of biologics (antibodies, soluble receptors) for treating TNF-based autoimmune conditions, ...

The foundation of marine coral reef ecosystems is calcium carbonate accumulated primarily by the action of hard corals (Coelenterata: Anthozoa: Scleractinia). Colonial hard coral polyps cover the surface of the reef and deposit calcium carbonate ...

Between A.D. 900 and 1150, more than 200,000 conifer trees were used to build the prehistoric great houses of Chaco Canyon, New Mexico, in what is now a treeless landscape. More than one-fifth of these timbers were spruce (Picea) or fir (Abies) ...

The distribution of aqueous Pb(II) sorbed at the interface between Burkholderia cepacia biofilms and hematite (α-Fe₂O₃) or corundum (α-Al₂O₃) surfaces has been probed by using an application of the long-period x-ray standing wave technique. ...

Copper–oxide-based high-temperature superconductors have complex phase diagrams with multiple ordered phases. It even appears that the highest superconducting transition temperatures for certain cuprates are found in samples that display ...

The nuclear envelope (NE) is one of the least characterized structures of eukaryotic cells. The study of its functional roles is hampered by the small number of proteins known to be specifically located to it. Here, we present a comprehensive ...

The structure of the higher-order chromatin fiber has not been defined in detail. We have used a novel approach based on sucrose gradient centrifugation to compare the conformation of centromeric satellite DNA-containing higher-order chromatin ...

The protein ataxin-3 contains a polyglutamine region; increasing the number of glutamines beyond 55 in this region gives rise to the neurodegenerative disease spinocerebellar ataxia type 3. This disease and other polyglutamine expansion diseases ...

The myeloperoxidase system of neutrophils uses hydrogen peroxide and chloride to generate hypochlorous acid, a potent bactericidal oxidant in vitro. In a mouse model of polymicrobial sepsis, we observed that mice deficient in myeloperoxidase were ...

The high-resolution crystal structure of the N-terminal central region of bovine fibrinogen (a 35-kDa E₅ fragment) reveals a remarkable dimeric design. The two halves of the molecule bond together at the center in an extensive molecular “handshake”...

A crystal structure of the anaerobic Ni-Fe-S carbon monoxide dehydrogenase (CODH) from Rhodospirillum rubrum has been determined to 2.8-Å resolution. The CODH family, for which the R. rubrum enzyme is the prototype, catalyzes the biological ...

A cDNA encoding a protein of 36 kDa, polymerase delta-interacting protein 1 (PDIP1), that interacts with the small subunit (p50) of DNA polymerase δ (pol δ) was identified in a two-hybrid screen of a HepG2 cDNA library by using p50 as bait. The ...

With the identification of eight new polypeptides, we here complete the subunit characterization of the Schizosaccharomyces pombe RNA polymerase II holoenzyme. The complex contains homologs to all 10 essential gene products present in the ...

S1 is the largest ribosomal protein, present in the small subunit of the bacterial ribosome. It has a pivotal role in stabilizing the mRNA on the ribosome. Thus far, S1 has eluded structural determination. We have identified the S1 protein mass in ...

The origin recognition complex (ORC) is the DNA replication initiator protein in eukaryotes. We have reconstituted a functional recombinant Drosophila ORC and compared activities of the wild-type and several mutant ORC variants. Drosophila ORC is ...

UDP-xylose is a sugar donor required for the synthesis of diverse and important glycan structures in animals, plants, fungi, and bacteria. Xylose-containing glycans are particularly abundant in plants and in the polysaccharide capsule that is the ...

The phospholipase D (PLD) superfamily is a diverse group of proteins that includes enzymes involved in phospholipid metabolism, a bacterial toxin, poxvirus envelope proteins, and bacterial nucleases. Based on sequence comparisons, we show here ...

A generic statistical mechanical model is presented for the self-assembly of chiral rod-like units, such as β-sheet-forming peptides, into helical tapes, which with increasing concentration associate into twisted ribbons (double tapes), fibrils (...

Flavoproteins can function as hydrophobic sites for vitamin B₂ (riboflavin) or, in other structures, with cofactors for catalytic reactions such as glucose oxidation. In this contribution, we report direct observation of charge separation and ...

In this contribution, we report studies of the primary dynamics of the drug–protein complexes of daunomycin with apo riboflavin-binding protein. With femtosecond resolution, we observed the ultrafast charge separation between daunomycin and ...

Designed peptides that fold autonomously to specific conformations in aqueous solution are useful for elucidating protein secondary structural preferences. For example, autonomously folding model systems have been essential for establishing the ...

Uridine-rich small nuclear ribonucleoproteins (U snRNPs) are components of the splicing machinery that removes introns from precursor mRNA. Like other splicing factors, U snRNPs are diffusely distributed throughout the nucleus and, in addition, ...

Peroxisomes are single membrane-bound organelles present in virtually all eukaryotes. These organelles participate in several important metabolic processes, and defects in peroxisome function and biogenesis are a significant contributor to human ...

Recent studies suggested that simian virus 40 (SV40) may cause malignant mesothelioma, although the pathogenic mechanism is unclear. We found that in SV40-positive malignant mesothelioma cells, the hepatocyte growth factor (HGF) receptor (Met) was ...

Molecular chaperones are involved in the protection of cells against protein damage through their ability to hold, disaggregate, and refold damaged proteins or their ability to facilitate degradation of damaged proteins. Little is known about how ...

Chromatid catenation is actively monitored in human cells, with progression from G₂ to mitosis being inhibited when chromatids are insufficiently decatenated. Mitotic delay was quantified in normal and checkpoint-deficient human cells during ...

It has been recently reported that insulin recruits a novel signaling machinery to lipid rafts required for insulin-stimulated GLUT4 translocation [Baumann, A., Ribon, V., Kanzaki, M., Thurmond, D. C., Mora, S., Shigematsu, S., Bickel, P. E., ...

Inflammation in asthma, sepsis, transplant rejection, and many neurodegenerative diseases associates an up-regulation of NO synthesis with increased protein nitration at tyrosine. Nitration can cause protein dysfunction and is implicated in ...

Skeletal muscle fibers are defined by patterned covariation of key traits that determine contractile and metabolic characteristics. Although the functional properties of most skeletal muscles result from their proportional content of a few ...

Although kin selection is central to the modern study of social evolution, recent studies of social species have revealed that no simple relationship exists between levels of kinship and sociality. The soldier-producing aphids are unique among ...

Mammalian cells can respond to damage or stress by entering a state of arrested growth and altered function termed cellular senescence. Several lines of evidence suggest that the senescence response suppresses tumorigenesis. Cellular senescence is ...

The breast and ovarian susceptibility protein 1 (BRCA1) heterodimerizes with its structural relative, the BRCA1-associated RING domain protein (BARD1), which may have tumor suppressing function in its own right. Both proteins have evolved from a ...

Recent genetic studies have suggested that many genes contribute to differences between closely related species that prevent gene exchange, particularly hybrid male sterility and female species preferences. We have examined the genetic basis of ...

Sex is thought to facilitate accumulation of initially rare beneficial mutations by allowing simultaneous allele replacements at many loci. However, this advantage of sex depends on a restrictive assumption that the fitness of a genotype is ...

The concept of ant slavery rests on the untested assumption that slave-making ants impose fitness costs on colonies of the species they raid. We tested that assumption by comparing the summertime seasonal productivity of Leptothorax spp. colonies ...

RNA viruses exist as quasispecies, heterogeneous and dynamic mixtures of mutants having one or more consensus sequences. An adequate description of the genomic structure of such viral populations must include the consensus sequence(s) plus a ...

Open reading frame expressed sequences tags (ORESTES) differ from conventional ESTs by providing sequence data from the central protein coding portion of transcripts. We generated a total of 696,745 ORESTES sequences from 24 human tissues and used ...

Vertebrate cells have evolved two major pathways for repairing DNA double-strand breaks (DSBs), homologous recombination (HR) and nonhomologous DNA end-joining (NHEJ). To investigate the role of DNA ligase IV (Lig4) in DSB repair, we knocked out ...

We have analyzed the pattern of core histone acetylation across 250 kb of the telomeric region of the short arm of human chromosome 16. This gene-dense region, which includes the α-globin genes and their regulatory elements embedded within widely ...

Murine erythroleukemia (MEL) cells are a model system to study reorganization of the eukaryotic nucleus during terminal differentiation. Upon chemical induction, MEL cells undergo erythroid differentiation, leading to activation of globin gene ...

The abnormal oocyte (abo) gene of Drosophila melanogaster is a peculiar maternal effect gene whose mutations cause a maternal-effect lethality that can be rescued by specific regions of heterochromatin during early embryogenesis. Here we show that ...

RNA editing changes the read-out of genetic information, increasing the number of different protein products that can be made from a single gene. One form involves the deamination of adenosine to form inosine, which is subsequently translated as ...

CD26 is a T cell activation antigen that contains dipeptidyl peptidase IV activity and is known to bind adenosine deaminase. The mechanism by which CD26 costimulation potentiates T cell receptor-mediated T cell activation, leading to subsequent ...

HIV-1-infected cells can avoid cytotoxic T lymphocyte killing by Nef-mediated down-regulation of surface MHC I. Here, we show that HIV-1 Nef inhibits MHC II restricted peptide presentation to specific T cells and thus may affect the induction of ...

We recently reported that the nonclassical HLA class I molecule HLA-G was expressed in the endomyocardial biopsies and sera of 16% of heart transplant patients studied. The aim of the present report is to identify cells that may be responsible for ...

Toll-like receptor 4 (TLR4), the principal signaling receptor for lipopolysaccharide (LPS) in mammals, requires the binding of MD-2 to its extracellular domain for maximal responsiveness. MD-2 contains a leader sequence but lacks a transmembrane ...

Tumor necrosis factor-α (TNF-α) is well recognized for its role in mediating innate immune responses. However, the mechanisms of TNF-α that influence the adaptive immune response to virus infections are not well understood. In this study, we have ...

The invariant chain (Ii) binds to newly synthesized MHC class II molecules with the CLIP region of Ii occupying the peptide-binding groove. Here we demonstrate that recombinant Ii proteins with the CLIP region replaced by antigenic self-epitopes ...

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by cyst formation in the kidney, liver, and pancreas and is associated often with cardiovascular abnormalities such as hypertension, mitral valve prolapse, and intracranial ...

The efficacy and safety of an immunoconjugate (icon) molecule, composed of a mutated mouse factor VII (mfVII) targeting domain and the Fc effector domain of an IgG1 Ig (mfVII/Fc icon), was tested with a severe combined immunodeficient (SCID) mouse ...

Presenilin proteins play critical roles in the proteolytic processing of both Notch and amyloid precursor protein (APP). Presenilin itself undergoes endoproteolytic processing to generate an N-terminal and C-terminal fragment. As demonstrated ...

Suppressor of cytokine signaling 3 (SOCS-3) is a negative feedback regulator of IFN-γ signaling, shown up-regulated in mouse bone marrow cells by the proinflammatory cytokines interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and IFN-γ. IL-...

The mechanisms through which luteinizing hormone (LH)-releasing hormone (LHRH) antagonists suppress pituitary gonadotroph functions and LHRH-receptor (LHRH-R) expression are incompletely understood. Consequently, we investigated the direct effect ...

Our objective was to determine whether overexpression and underexpression of human heme oxygenase (HHO)-1 could be controlled on a long-term basis by introduction of the HO-1 gene in sense (S) and antisense (AS) orientation with an appropriate ...

The distribution of aqueous Pb(II) sorbed at the interface between Burkholderia cepacia biofilms and hematite (α-Fe₂O₃) or corundum (α-Al₂O₃) surfaces has been probed by using an application of the long-period x-ray standing wave technique. ...

We recently proposed a dynamic copy-choice model for retroviral recombination in which a steady state between the rates of polymerization and RNA degradation determines the frequency of reverse transcriptase (RT) template switching. The relative ...

Streptomyces avermitilis is a soil bacterium that carries out not only a complex morphological differentiation but also the production of secondary metabolites, one of which, avermectin, is commercially important in human and veterinary medicine. ...

Most facultative intracellular bacteria replicate in specialized phagosomes after being taken up by mammalian cells. Relatively few intracellular bacteria escape the phagosomal compartment with the help of cytolytic (pore-forming) proteins and ...

Excessive activation of poly(ADP-ribose) polymerase 1 (PARP1) leads to NAD⁺ depletion and cell death during ischemia and other conditions that generate extensive DNA damage. When activated by DNA strand breaks, PARP1 uses NAD⁺ as substrate to form ...

Soluble N-ethylmaleimide-sensitive fusion attachment protein receptor (SNARE)-mediated fusion of synaptic vesicles with the presynaptic-plasma membrane is essential for communication between neurons. Disassembly of the SNARE complex requires the ...

Visual stimuli that are frequently seen together become associated in long-term memory, such that the sight of one stimulus readily brings to mind the thought or image of the other. It has been hypothesized that acquisition of such long-term ...

Alzheimer's disease and Parkinson's disease are associated with the cerebral accumulation of β-amyloid and α-synuclein, respectively. Some patients have clinical and pathological features of both diseases, raising the possibility of overlapping ...

Evidence that protein synthesis inhibitors induce amnesia in a variety of species and learning paradigms indicates that the consolidation of newly acquired information into stable memories requires the synthesis of new proteins. Because extinction ...

We report experiments combining assessment of spatial tactile discrimination behavior and measurements of somatosensory-evoked potentials in human subjects before and after short-term plastic changes to demonstrate a causal link between the degree ...

Neural receptive fields are plastic: with experience, neurons in many brain regions change their spiking responses to relevant stimuli. Analysis of receptive field plasticity from experimental measurements is crucial for understanding how neural ...

Interpretations of steroid hormone actions as slow, nuclear, transcriptional events have frequently been seen as competing against inferences of rapid membrane actions. We have discovered conditions where membrane-limited effects potentiate later ...

KCNQ2 and KCNQ3 are two homologous K⁺ channel subunits that can combine to form heterotetrameric channels with properties of neuronal M channels. Loss-of-function mutations in either subunit can lead to benign familial neonatal convulsions (BFNC), ...

Estrogens are powerful modulators of neuronal physiology and in humans may affect a broad range of functions, including reproductive, emotional, and cognitive behaviors. We studied the contribution of estrogen receptors (ERs) in modulation of ...

Stress-induced mitogen-activated protein kinase (MAP) p38 is activated in various forms of heart failure, yet its effects on the intact heart remain to be established. Targeted activation of p38 MAP kinase in ventricular myocytes was achieved in ...

Light controls the translation of several mRNAs in fully developed chloroplasts via at least two regulatory pathways. In the first, the light signal is transduced as a thiol-mediated signal that modulates translation in parallel to light ...

We recently isolated the AtBI-1 (Arabidopsis Bax Inhibitor-1) gene, the expression of which suppressed Bax-induced cell death in yeast. To determine whether the same is true in the plant system, transgenic Arabidopsis plants overexpressing Bax ...

The extent to which sound identification and sound localization depend on specialized auditory pathways was examined by using functional magnetic resonance imaging and event-related brain potentials. Participants performed an S1–S2 match-to-sample ...