Fermi surface of LaFe2P2-a detailed density functional study.

Angular-dependent de Haas-van Alphen measurements allow the mapping of Fermi surfaces in great detail with high accuracy. Density functional electronic-structure calculations can be carried out with high precision, but depend crucially on the used structural information and the applied calculational approximations. We report in a detailed study the sensitivity of the calculated electronic band structure of the 122 compound LaFe2P2 on (i) the exact P position in the unit cell, parametrized by a so-called z parameter, and on (ii) the treatment of the La 4f  states. Depending on the chosen exchange and correlation-potential approximation, the calculated z parameter varies slightly and corresponding small but distinctive differences in the calculated band structure and Fermi-surface topology appear. Similarly, topology changes appear when the energy of the mostly unoccupied La 4f  states is corrected regarding their experimentally observed position. The calculated results are compared to experimental de Haas-van Alphen data. Our findings show a high sensitivity of the calculated band structure on the pnictide z position and the need for an accurate experimental determination of this parameter at low temperatures, and a particular need for a sophisticated treatment of the La 4f  states. Thus, this is not only crucial for the special case of LaFe2P2 studied here, but of importance for the precise determination of the band structure of related 122 materials and La containing compounds in general.

Demographic and mortality analysis of hospitalized children at a referral hospital in Addis Ababa, Ethiopia.

BACKGROUND: Global childhood mortality rates remain high. Millennium Development Goal 4 focused efforts on reducing rates by two-thirds between 1990 and 2015. In Ethiopia, child mortality rates dropped 71 % from 1990 to 2015, however it is estimated that 184,000 Ethiopian children die each year. There is limited information about pediatric hospital admissions in Ethiopia. Our aims were to examine the temporal relationship of mortality to admission, describe the demographics, and identify cause mortality of children admitted to the Zewditu Memorial Hospital (ZMH). METHODS: A four-year retrospective review of pediatric admissions was conducted at the pediatric emergency room and pediatric hospital ward at ZMH in Addis Ababa, Ethiopia. Admission entries from 2011-2014 of children age 29 days-14 years were reviewed. Age, gender, admission date, disease classification, discharge status and date were obtained. Patient gender was compared using Chi-square analysis. A descriptive analysis was used for age and cause mortality. RESULTS: A total of 6866 patient entries were reviewed. The proportion of admissions younger than age 5 was 0.747 (95 % CI 0.736-0.757). Overall mortality was 0.042 (95 % CI, 0.037-0.047). The proportion of recorded deaths occurring within 2 days of admission was 0.437 (95 % CI 0.380-0.494). The proportion of male admissions was significantly higher than female admissions in all age groups (male 0.575, p < 0.0001, 95 % CI 0.562-0.586). The main causes of mortality were pneumonia (0.253, 95 % CI, 0.203-0.303), severe acute malnutrition (0.222, 95 % CI 0.174-0.27), HIV/AIDS-related complications (0.056, 95 % CI 0.029-0.083), spina bifida (0.049, 95 % CI 0.024-0.074), and hydrocephalus (0.045, 95 % CI 0.021-0.069). CONCLUSIONS: Our study revealed a lower mortality rate than previously reported in Ethiopia. Despite this, 44 % of pediatric hospital mortality occurred early during hospitalization, higher than reported at other Ethiopian hospitals. This adds further evidence that systematic efforts should be dedicated to improve pediatric emergency care. Admissions included 58 % male patients, similar to other reports in Ethiopia implying that this may be a nation-wide phenomenon. The observed disparity may be due to societal factors regarding care-seeking behaviors or male predilection for respiratory illness warranting further investigation. Cause mortality patterns were similar to reports in analogous settings.

ß-Catenin is required for intrinsic but not extrinsic BCR-ABL1 kinase-independent resistance to tyrosine kinase inhibitors in chronic myeloid leukemia.

Activation of nuclear ß-catenin and expression of its transcriptional targets promotes chronic myeloid leukemia (CML) progression, tyrosine kinase inhibitor (TKI) resistance, and leukemic stem cell self-renewal. We report that nuclear ß-catenin has a role in leukemia cell-intrinsic but not -extrinsic BCR-ABL1 kinase-independent TKI resistance. Upon imatinib inhibition of BCR-ABL1 kinase activity, ß-catenin expression was maintained in intrinsically resistant cells grown in suspension culture and sensitive cells cultured in direct contact (DC) with bone marrow (BM) stromal cells. Thus, TKI resistance uncouples ß-catenin expression from BCR-ABL1 kinase activity. In ß-catenin reporter assays, intrinsically resistant cells showed increased transcriptional activity versus parental TKI-sensitive controls, and this was associated with restored expression of ß-catenin target genes. In contrast, DC with BM stromal cells promoted TKI resistance, but had little effects on Lef/Tcf reporter activity and no consistent effects on cytoplasmic ß-catenin levels, arguing against a role for ß-catenin in extrinsic TKI resistance. N-cadherin or H-cadherin blocking antibodies abrogated DC-based resistance despite increasing Lef/Tcf reporter activity, suggesting that factors other than ß-catenin contribute to extrinsic, BM-derived TKI resistance. Our data indicate that, while nuclear ß-catenin enhances survival of intrinsically TKI-resistant CML progenitors, it is not required for extrinsic resistance mediated by the BM microenvironment.

Nucleoskeleton and nucleo-cytoplasmic transport in oocytes and early development of Xenopus laevis.

We use amphibian oocytes and eggs as favorite biological systems to study various cell biological phenomena. We have analyzed the role of the zinc finger protein TFIIIA and ribosomal protein L5 in nucleo-cytoplasmic transfer of 5S ribosomal RNA and report on the structural requirements of the 5S RNA for the interaction with TFIIIA. Furthermore, we have used the oocyte/egg system to analyze the kinetics of the posttranslational isoprenylation of oocyte nuclear lamin B3 and its fate during egg maturation. We demonstrate, that isoprenylation of newly synthesized lamins takes place in the oocyte cytoplasm before uptake into the nucleus and show, that the isoprene modifications alone are not sufficient to maintain stable association of lamins with nuclear envelope derived membranes in eggs. Finally, initial results of the identification of cis-acting sequence elements, involved in translational repression of lamin mRNAs in oocytes, are reported.

Analysis of nuclear lamin isoprenylation in Xenopus oocytes: isoprenylation of lamin B3 precedes its uptake into the nucleus.

Protein prenylation is a posttranslational modification involving the covalent attachment of a prenyl lipid to a cysteine at or near the COOH terminus of a protein. It is required for membrane localization and efficient function of a number of cytoplasmic as well as nuclear proteins including the proto-oncogenic and activated forms of Ras. Farnesylation in conjunction with a nuclear localization signal has been shown to be necessary to target newly synthesized nuclear lamins to the inner nuclear envelope membrane. It is, however, not clear where in the cell isoprenylation of nuclear lamins takes place. In this study we describe in vivo and in vitro experiments on the isoprenylation of the Xenopus oocyte nuclear lamin B3. We show by kinetic analysis that newly synthesized lamins are isoprenylated in the cytosol of oocytes before uptake into the nucleus. From our data it can be concluded that isoprenylation of lamins in the nucleus, as it is observed under certain conditions of isoprene starvation, represents a default pathway rather than the physiological situation. We further analyzed the capacity of isolated nuclei to carry out isoprenylation of B3. Our results are in line with a dual localization of a protein farnesyltransferase in the cytosol and nuclei of amphibian oocytes. Implications for the possible functions of a nuclear protein farnesyltransferase as well as possible mechanisms of the selective inhibition of farnesylation of cytoplasmic proteins by peptidomimetics are discussed.

Application of actigraphy in the clinical setting: use in children with attention-deficit hyperactivity disorder.

Clinicians rely primarily on subjective behavioral questionnaires in assessing attention-deficit hyperactivity disorder (ADHD). The new mini-motion logger actigraph, which is a wrist-worn minicomputer, can add an objective element to this assessment and is especially useful in children due to its small size. We applied this technology as an outcome measure in evaluating drug therapy in two children with ADHD who were receiving methylphenidate and pemoline, respectively. We also assessed preliminary findings from an additional 13 children.

The role of CaaX-dependent modifications in membrane association of Xenopus nuclear lamin B3 during meiosis and the fate of B3 in transfected mitotic cells.

Recent evidence shows that the COOH-terminal CaaX motif of lamins is necessary to target newly synthesized proteins to the nuclear envelope membranes. Isoprenylation at the CaaX-cysteine has been taken to explain the different fates of A- and B-type lamins during cell division. A-type lamins, which loose their isoprenylation shortly after incorporation into the lamina structure, become freely soluble upon mitotic nuclear envelope breakdown. Somatic B-type lamins, in contrast, are permanently isoprenylated and, although depolymerized during mitosis, remain associated with remnants of nuclear envelope membranes. However, Xenopus lamin B3, the major B-type lamin of amphibian oocytes and eggs, becomes soluble after nuclear envelope breakdown in meiotic metaphase. Here we show that Xenopus lamin B3 is permanently isoprenylated and carboxyl methylated in oocytes (interphase) and eggs (meiotic metaphase). When transfected into mouse L cells Xenopus lamin B3 is integrated into the host lamina and responds to cell cycle signals in a normal fashion. Notably, the ectopically expressed Xenopus lamin does not form heterooligomers with the endogenous lamins as revealed by a coprecipitation experiment with mitotic lamins. In contrast to the situation in amphibian eggs, a significant portion of lamin B3 remains associated with membranes during mitosis. We conclude from these data that the CaaX motif-mediated modifications, although necessary, are not sufficient for a stable association of lamins with membranes and that additional factors are involved in lamin-membrane binding.

Sleep disturbances and epileptiform activity in a subpopulation of children with attention deficit hyperactivity disorder (ADHD): a literature review generating an hypothesis with implications for drug therapy.

The use of electroencephalography and sleep studies in attention deficit hyperactivity disorder (ADHD), and the associated behavioral disorders is reviewed. Based on the available literature, we propose a hypothesis indicating four subtypes of ADHD. The usefulness of EEGs and sleep laboratory indices in detecting a subgroup of patients with submaximal responses to methylphenidate is also discussed.

tyk2, prototype of a novel class of non-receptor tyrosine kinase genes.

We previously identified a novel protein tyrosine kinase gene, tyk2, by screening a human lymphoid cDNA library with a tyrosine kinase domain specific c-fms restriction fragment under low stringency hybridization conditions. We have now isolated and sequenced a full length tyk2 cDNA clone; demonstrated that this gene is widely expressed in hematopoietic and non-hematopoietic cell lines; and mapped it to chromosome 19p13.2. The cDNA clone is 4176 nucleotides long and codes for a putative protein with a molecular weight of 134 kilodaltons. Hydrophobicity analysis of our sequence does not identify a transmembrane domain, which is found in all members of the receptor class of protein tyrosine kinases; nor can we detect an SH2 domain, found in all previously identified non-receptor protein kinases. We therefore propose that tyk2 is the prototype of a new class of non-receptor protein tyrosine kinases.

Type A behavior, self-involvement, and coronary atherosclerosis.

Prior to coronary angiography, 150 men were assessed for Type A behavior using the structured interview and two questionnaire measures. The results show no relationship between Type A behavior and extent of coronary artery disease (CAD). A second finding is that the number of self-references (I, me, my) derived from speech in the structured interview correlated positively with the number of previous myocardial infarctions and the extent of CAD; self-references correlated negatively with time on the treadmill and catheterization ejection fraction. Multiple regression analyses show self-references to remain a significant correlate of extent of disease when controlled for age, blood pressure, cholesterol, and Type A behavior.

[Antigenicity and resorptive behavior of the usual gelatin preparations and of dry fibrin foam]. / Uber Antigenität und Resorptionsverhalten gebräuchlicher Gelatinepräparate und von Trockenfibrinschaum.

Immunofluorescence studies of Gelastypt, Gelfoam, and Fibrospum showed species-specific, protein-dependent antigen characteristics. Additional experimental studies using guinea pigs revealed that, after subcutaneous implantation, these materials do not lose their antigen characteristics during the resorptive process. Remnants of subcutaneously implanted material could be demonstrated intracellularly (macrophages) in the spleens of the experimental animals four weeks later.

Functional independence of donor and recipient cardiac tissues of single and double heart transplant patients revealed by chronobiology.

3 total (single) and 1 double-heart-transplant patients were studied for temporal changes in the electrical events of cardiac function. Results of statistical analyses document the existence of circadian rhythms in the donor and recipient P--P or R--R intervals. However, for 1 total-heart-transplant patient studied at intervals during the year following implant and the double-heart-transplant patient 5 mth after surgery, the period (tau) of the rhythm in the P--P or R--R interval of the recipient tissue deviated greatly from that of 24.0 h. For the total-heart-transplant patient studied 1 mth prior to death, the tau was 32.3 h; for the double-heart-transplant patient, the tau was 29.0 h. In both patients, the donor heart tissue continued to exhibit a 24-h rhythm. These findings imply that changes in tau for the rhythm in P--P or R--R interval may reflect aspects of disrupted physiologic, feedback, regulatory mechanisms or perhaps graft rejection. Although additional study is required, the possibility that alteration in tau is associated with rejection is intriguing since if documented, then the noninvasive monitoring of ECG and subsequent analysis of data for significant deviations of tau from 24.0 h will be useful as an additional tool for monitoring host tolerance for the heart implant.