Itinerant ferromagnetism in the As 4p conduction band of Ba_{0.6}K_{0.4}Mn_{2}As_{2} identified by X-ray magnetic circular dichroism.

X-ray magnetic circular dichroism (XMCD) measurements on single-crystal and powder samples of Ba_{0.6}K_{0.4}Mn_{2}As_{2} show that the ferromagnetism below T_{C}≈100 K arises in the As 4p conduction band. No XMCD signal is observed at the Mn x-ray absorption edges. Below T_{C}, however, a clear XMCD signal is found at the As K edge which increases with decreasing temperature. The XMCD signal is absent in data taken with the beam directed parallel to the crystallographic c axis indicating that the orbital magnetic moment lies in the basal plane of the tetragonal lattice. These results show that the previously reported itinerant ferromagnetism is associated with the As 4p conduction band and that distinct local-moment antiferromagnetism and itinerant ferromagnetism with perpendicular easy axes coexist in this compound at low temperature.

Infection by the cestode parasite Schistocephalus sp. and effects on diet, body condition and survival of sculpins Cottus aleuticus and Cottus cognatus.

Sampling in Iliamna Lake, Alaska, U.S.A. revealed that a greater proportion of coastrange sculpins Cottus aleuticus were infected by the cestode Schistocephalus solidus than slimy sculpins Cottus cognatus (52 v. 23%), and infected C. aleuticus contained more cestodes than did C. cognatus (2·1 v. 1·3 per fish). Consumption of sockeye salmon Oncorhynchus nerka eggs (the primary diet item) was lower in fishes with cestodes, and a model based on cestode prevalence and age composition estimated higher rates of infection and parasite-associated mortality in C. aleuticus compared with C. cognatus.

Intranasal administration of plasmid DNA nanoparticles yields successful transfection and expression of a reporter protein in rat brain.

Viral vectors are a commonly used method for gene therapy because of their highly efficient transduction of cells. However, many vectors have a small genetic capacity, and their potential for immunogenicity can limit their usefulness. Moreover, for disorders of the central nervous system (CNS), the need for invasive surgical delivery of viruses to the brain also detracts from their clinical applicability. Here, we show that intranasal delivery of unimolecularly compacted DNA nanoparticles (DNA NPs), which consist of single molecules of plasmid DNA encoding enhanced green fluorescent protein (eGFP) compacted with 10 kDa polyethylene glycol (PEG)-substituted lysine 30-mers (CK30PEG10k), successfully transfect cells in the rat brain. Direct eGFP fluorescence microscopy, eGFP-immunohistochemistry (IHC) and eGFP-ELISA all demonstrated eGFP protein expression 2 days after intranasal delivery. eGFP-positive cells were found throughout the rostral-caudal axis of the brain, most often adjacent to capillary endothelial cells. This localization provides evidence for distribution of the nasally administered DNA NPs via perivascular flow. These results are the first report that intranasal delivery of DNA NPs can bypass the blood-brain barrier and transfect and express the encoded protein in the rat brain, affording a non-invasive approach for gene therapy of CNS disorders.

Unusual temperature dependence of band dispersion in Ba(Fe(1-x)Ru(x))2As2 and its consequences for antiferromagnetic ordering.

We have performed detailed studies of the temperature evolution of the electronic structure in Ba(Fe(1-x)Ru(x))(2)As(2) using angle resolved photoemission spectroscopy. Surprisingly, we find that the binding energy of both hole and electron bands changes significantly with temperature in both pure and Ru substituted samples. The hole and electron pockets are well nested at low temperature in unsubstituted (BaFe(2)As(2)) samples, which likely drives the spin density wave and resulting antiferromagnetic order. Upon warming, this nesting is degraded as the hole pocket shrinks and the electron pocket expands. Our results demonstrate that the temperature dependent nesting may play an important role in driving the antiferromagnetic-paramagnetic phase transition.

Stripe antiferromagnetic spin fluctuations in SrCo2As2.

Inelastic neutron scattering measurements of paramagnetic SrCo2As2 at T=5 K reveal antiferromagnetic (AFM) spin fluctuations that are peaked at a wave vector of Q(AFM)=(1/2,1/2,1) and possess a large energy scale. These stripe spin fluctuations are similar to those found in AFe2As2 compounds, where spin-density wave AFM is driven by Fermi surface nesting between electron and hole pockets separated by Q(AFM). SrCo2As2 has a more complex Fermi surface and band-structure calculations indicate a potential instability toward either a ferromagnetic or stripe AFM ground state. The results suggest that stripe AFM magnetism is a general feature of both iron and cobalt-based arsenides and the search for spin fluctuation-induced unconventional superconductivity should be expanded to include cobalt-based compounds.

Evolution of magnetic oxygen states in Sr-doped LaCoO3.

Magnetism in La(1-x)Sr(x)CoO(3) as a function of doping is investigated with x-ray absorption spectroscopy and x-ray magnetic circular dicrhoism at the O K edge, and corresponding first principles electronic structure calculations. For small x, the spectra are consistent with the formation of ferromagnetic clusters occurring within a nonmagnetic insulating matrix. Sr-induced, magnetic O-hole states form just above E(F) and grow with increasing Sr doping. Density functional calculations for x=0 yield a nonmagnetic ground state with the observed rhombohedral distortion and indicates that doping introduces holes at the Fermi level in magnetic states with significant O 2p and Co t(2g) character for the undistorted pseudocubic structure. Supercell calculations show stronger magnetism on oxygen atoms having more Sr neighbors.

Ba(1-x)K(x)Mn2As2: an antiferromagnetic local-moment metal.

The compound BaMn2As2 with the tetragonal ThCr2Si2 structure is a local-moment antiferromagnetic insulator with a Néel temperature T(N)=625 K and a large ordered moment µ=3.9µ(B)/Mn. We demonstrate that this compound can be driven metallic by partial substitution of Ba by K while retaining the same crystal and antiferromagnetic structures together with nearly the same high T(N) and large µ. Ba(1-x)K(x)Mn2As2 is thus the first metallic ThCr2Si2-type MAs-based system containing local 3d transition metal M magnetic moments, with consequences for the ongoing debate about the local-moment versus itinerant pictures of the FeAs-based superconductors and parent compounds. The Ba(1-x)K(x)Mn2As2 class of compounds also forms a bridge between the layered iron pnictides and cuprates and may be useful to test theories of high T(c) superconductivity.

Effects of transition metal substitutions on the incommensurability and spin fluctuations in BaFe2As2 by elastic and inelastic neutron scattering.

The spin fluctuation spectra from nonsuperconducting Cu-substituted, and superconducting Co-substituted, BaFe(2)As(2) are compared quantitatively by inelastic neutron scattering measurements and are found to be indistinguishable. Whereas diffraction studies show the appearance of incommensurate spin-density wave order in Co and Ni substituted samples, the magnetic phase diagram for Cu substitution does not display incommensurate order, demonstrating that simple electron counting based on rigid-band concepts is invalid. These results, supported by theoretical calculations, suggest that substitutional impurity effects in the Fe plane play a significant role in controlling magnetism and the appearance of superconductivity, with Cu distinguished by enhanced impurity scattering and split-band behavior.

Incommensurate spin-density wave order in electron-doped BaFe2 As2 superconductors.

Neutron diffraction studies of Ba(Fe(1-x)Co(x))(2)As)(2) reveal that commensurate antiferromagnetic order gives way to incommensurate magnetic order for Co compositions between 0.056 < x < 0.06. The incommensurability has the form of a small transverse splitting (0, ± ε, 0) from the commensurate antiferromagnetic propagation vector Q(AFM) = (1,0,1) (in orthorhombic notation) where ε ≈ 0.02-0.03 and is composition dependent. The results are consistent with the formation of a spin-density wave driven by Fermi surface nesting of electron and hole pockets and confirm the itinerant nature of magnetism in the iron arsenide superconductors.

Block in anaphase chromosome separation caused by a telomerase template mutation.

Telomeres are essential for chromosome stability, but their functions at specific cell-cycle stages are unknown. Telomeres are now shown to have a role in chromosome separation during mitosis. In telomeric DNA mutants of Tetrahymena thermophila, created by expression of a telomerase RNA with an altered template sequence, division of the germline nucleus was severely delayed or blocked in anaphase. The mutant chromatids failed to separate completely at the midzone, becoming stretched to up to twice their normal length. These results suggest a physical block in mutant telomere separation.

X-ray magnetic circular dichroism in UGe(2): first-principles calculations.

The electronic structure and x-ray magnetic circular dichroism (XMCD) spectra of UGe(2) at the U N(4,5), N(2,3) and Ge K and L(2,3) edges are investigated theoretically from first principles, using the fully relativistic spin-polarized Dirac linear muffin-tin orbital (LMTO) band structure method. The electronic structure is obtained with the local spin-density approximation (LSDA), as well as the LSDA+U method. The origin of the XMCD spectra in the compound is examined.

Specific interactions of chromatin with the nuclear envelope: positional determination within the nucleus in Drosophila melanogaster.

Specific interactions of chromatin with the nuclear envelope (NE) in early embryos of Drosophila melanogaster have been mapped and analyzed. Using fluorescence in situ hybridization, the three-dimensional positions of 42 DNA probes, primarily to chromosome 2L, have been mapped in nuclei of intact Drosophila embryos, revealing five euchromatic and two heterochromatic regions associated with the NE. These results predict that there are approximately 15 NE contacts per chromosome arm, which delimit large chromatin loops of approximately 1-2 Mb. These NE association sites do not strictly correlate with scaffold-attachment regions, heterochromatin, or binding sites of known chromatin proteins. Pairs of neighboring probes surrounding one NE association site were used to delimit the NE association site more precisely, suggesting that peripheral localization of a large stretch of chromatin is likely to result from NE association at a single discrete site. These NE interactions are not established until after telophase, by which time the nuclear envelope has reassembled around the chromosomes, and they are thus unlikely to be involved in binding of NE vesicles to chromosomes following mitosis. Analysis of positions of these probes also reveals that the interphase nucleus is strongly polarized in a Rabl configuration which, together with specific targeting to the NE or to the nuclear interior, results in each locus occupying a highly determined position within the nucleus.

Calcium chelators induce apoptosis--evidence that raised intracellular ionised calcium is not essential for apoptosis.

A moderate sustained rise in intracellular ionised calcium has been observed to be associated with apoptosis occurring in many experimental systems. The application of extracellular and intracellular chelators of calcium has been reported to produce a decrease in apoptosis, while the addition of calcium ionophores often increases apoptosis. These findings, together with the observation of calcium-induced internucleosomal DNA cleavage in isolated nuclei, have suggested that DNA cleavage (and apoptosis) is a calcium-dependent process. However, a number of studies have shown that apoptosis is not always associated with a rise in the level of intracellular ionised calcium. In the present study, calcium chelators were found to induce apoptosis in cultured cells, concomitant with a decrease in both intracellular ionised calcium and total cell calcium content. Decreased intracellular ionised magnesium was also induced by extracellular chelators. These findings provide further evidence that a raised intracellular ionised calcium is not universally present during the induction of apoptosis. It is proposed that loss of calcium homeostasis, rather than a sustained rise in cytosolic calcium, is a determining factor in cell death by apoptosis.

Apoptosis is the mode of beta-cell death responsible for the development of IDDM in the nonobese diabetic (NOD) mouse.

The NOD/Lt mouse, a widely used model of human autoimmune IDDM, was used to establish the mode of beta-cell death responsible for the development of IDDM. Apoptotic cells were present within the islets of Langerhans in hematoxylin and eosin-stained sections of pancreases harvested from 3- to 18-week-old female NOD/Lt mice (a range of 11-50 apoptotic cells per 100 islets). Immunohistochemical localization of insulin to the dying cells confirmed the beta-cell origin of the apoptosis. Although some islets from age-matched control female NOD/scid mice contained apoptotic cells, virtually all of these cells were insulin negative as determined by immunohistochemistry. The small number of apoptotic insulin-positive cells identified in islets from NOD/scid mice (a range of 0-1 apoptotic cells per 100 islets) was not statistically significant, compared with the numbers recorded in NOD/Lt mice. All dying cells showed the morphological changes characteristic of cell death by apoptosis and stained positively with the TUNEL method for end-labeling DNA strand breaks. The maximum mean amount of beta-cell apoptosis occurring in NOD/Lt mice was at week 15 (50 apoptotic cells per 100 islets), which coincided with the earliest onset of diabetes as determined by blood glucose, urine glucose, and pancreatic immunoreactive insulin measurements. While there was no peak incidence of beta-cell apoptosis throughout the time period studied (weeks 3-18), the incidence of apoptosis decreased at week 18, by which time 50% of the animals had overt diabetes. The low levels of beta-cell apoptosis observed is indicative of a gradual deletion of the beta-cell population throughout the extensive preclinical period seen in this model and would be sufficient to account for the beta-cell loss resulting in IDDM. Apoptosis of beta-cells preceded the appearance of T-cells (CD3-positive by immunohistochemistry) in islets. Lymphocytic infiltration of islets (insulitis) was not detected until week 6. The results show that beta-cell apoptosis is responsible for the development of IDDM in the NOD/Lt mouse and that its onset precedes lymphocytic infiltration of the islets.

Isolation of antimicrobial peptides from avian heterophils.

Five bactericidal peptides (chicken heterophil peptides CHP1 and CHP2; turkey heterophil peptides THP1, THP2, and THP3) were purified from avian heterophil granules. All peptides were cationic and rich in cysteine, arginine, and lysine. The complete amino acid sequence, consisting of 39 amino acids, was determined for CHP1. This peptide had a molecular weight of 4481 as determined by mass spectrometry. Partial NH2-terminal amino acid sequences were obtained for the remaining peptides. Both chicken peptides and THP1 shared sequence homology at 22 residues and a cysteine motif which was similar to that of bovine beta-defensins. THP2 and THP3 were homologous to each other but were not homologous to the other three and had a unique cysteine motif. Peptides CHP1, CHP2, and THP1 killed Staphylococcus aureus and Escherichia coli in vitro, whereas THP2 and THP3 killed only S. aureus in vitro.

Decoherence by a chaotic many-spin bath.

We numerically investigate decoherence of a two-spin system (central system) by a bath of many spins 1/2. By carefully adjusting parameters, the dynamical regime of the bath has been varied from quantum chaos to regular, while all other dynamical characteristics have been kept practically intact. We explicitly demonstrate that for a many-body quantum bath, the onset of quantum chaos leads to significantly faster and stronger decoherence compared to an equivalent non-chaotic bath. Moreover, the non-diagonal elements of the system's density matrix, the linear entropy, and the fidelity of the central system decay differently for chaotic and non-chaotic baths. Therefore, knowledge of the basic parameters of the bath (strength of the system-bath interaction, and the bath's spectral density of states) is not always sufficient, and much finer details of the bath's dynamics can strongly affect the decoherence process.

Neuronal ceroid-lipofuscinosis in a Holstein steer.

A young, partially blind Holstein steer was affected by mild cerebral atrophy. Formalin-fixed cerebral gray matter was diffusely yellow brown. Microscopically, there were eosinophilic, autofluorescent granules primarily in the cytoplasm of cerebral neurons. There was also extensive retinal atrophy with complete loss of the rod and cone layers. Ultrastructural examination of affected cerebral neurons revealed a mixture of granular osmiophilic and lamellar patterns in the cytoplasmic storage bodies. This suggests the existence of neuronal ceroid-lipofuscinosis in the Holstein breed.

Variation among pathologists in the histologic grading of canine cutaneous mast cell tumors with uniform use of a single grading reference.

Ten veterinary pathologists independently assigned histologic grades to the same 60 canine cutaneous mast cell tumors using the Patnaik classifications. The degree of agreement in grading among the pathologists was compared with the degree of agreement among the same pathologists in a previous study, in which each pathologist used the reference for grading that he/she uses routinely. Mean agreement improved significantly from 50.3% to 62.1% with uniform use of the Patnaik classifications (P = 0.00001), suggesting that there is value in uniform application of a single grading scheme for canine cutaneous mast cell tumors. Agreement among pathologists was still not 100%, suggesting that a more objective grading scheme should be developed and that other histologic indicators of prognosis should be investigated.

Prevention of disseminated Mycobacterium avium complex infection with reduced dose clarithromycin in patients with advanced HIV disease.

OBJECTIVE: To evaluate the ability of once daily reduced dose clarithromycin to prevent disseminated Mycobacterium avium complex (dMAC) infection in patients with advanced HIV disease. DESIGN: Non-randomized, retrospective study. SETTING: Outpatient clinic of an urban university-affiliated municipal hospital. PATIENTS: A group of 192 HIV-infected patients with a CD4 count < 100 x 10(6) cells/l who were followed for at least 90 days during a 6-year period (1991-1996) before the use of protease inhibitors. INTERVENTIONS: Clarithromycin 500 mg orally once daily (n = 84), rifabutin 300 mg orally once daily (n = 47) or no prophylaxis (n = 61). MAIN OUTCOME MEASURES: Positive blood culture for M. avium complex (MAC), time to development of dMAC, and time to death. RESULTS: When compared with no prophylaxis or rifabutin, the incidence of dMAC and time to development of dMAC were improved among those patients receiving clarithromycin (P < 0.001). Prolonged survival was associated with both clarithromycin and rifabutin use when compared with no prophylaxis (P < 0.002). In patients who failed prophylaxis, resistance to clarithromycin and rifabutin was observed. CONCLUSIONS: In the era prior to protease inhibitor use, once daily clarithromycin at a dose of 500 mg was associated with a reduction in the incidence of dMAC, appeared to be superior to rifabutin, and was associated with prolonged survival in patients with advanced HIV disease.

Spermatogonial apoptosis has three morphologically recognizable phases and shows no circadian rhythm during normal spermatogenesis in the rat.

In this study we examined the possibility that regular or circadian fluctuations occur in the frequency of spontaneous spermatogonial apoptosis. Apoptosis of A2, A3 and A4 type spermatogonia occurring spontaneously in the normal rat testis was studied by light and electron microscopy. Normal and apoptotic A3 spermatogonia were quantified in 36 animals killed at two-hourly intervals over a 24 h period. Three sequential phases of spermatogonial apoptosis were defined and quantified separately: (i) an early phase in which cells showed margination of nuclear chromatin, (ii) an intermediate phase in which phagocytosed apoptotic bodies were partly degraded and (iii) a late phase in which only debris of degraded apoptotic bodies was evident. Groups of spermatogonia linked by intercellular bridges underwent apoptosis synchronously. Normal and apoptotic A3 spermatogonia occurred at a mean frequency of 33.4 and 9.6 per 10 seminiferous tubule profiles respectively; there was a large variation in these frequencies between animals, but no peaks or circadian periodicity were detected. Progressive degradation of apoptotic bodies was evident, the average ratios of intermediate and late bodies to early bodies being 1.5 and 3.5, respectively. Absence of a circadian rhythm in these data does not exclude the possibility that initiation of apoptosis in susceptible spermatogonial clones is synchronous, and that affected clones undergo lag periods of differing duration before expressing morphological apoptosis.