Statistical (n, γ ) cross section model comparison for short-lived nuclei.

Neutron-capture cross sections of neutron-rich nuclei are calculated using a Hauser-Feshbach model when direct experimental cross sections cannot be obtained. A number of codes to perform these calculations exist, and each makes different assumptions about the underlying nuclear physics. We investigated the systematic uncertainty associated with the choice of Hauser-Feshbach code used to calculate the neutron-capture cross section of a short-lived nucleus. The neutron-capture cross section for 73 Zn (n, γ ) 74 Zn was calculated using three Hauser-Feshbach statistical model codes: TALYS, CoH, and EMPIRE. The calculation was first performed without any changes to the default settings in each code. Then an experimentally obtained nuclear level density (NLD) and γ -ray strength function ( γ SF ) were included. Finally, the nuclear structure information was made consistent across the codes. The neutron-capture cross sections obtained from the three codes are in good agreement after including the experimentally obtained NLD and γ SF , accounting for differences in the underlying nuclear reaction models, and enforcing consistent approximations for unknown nuclear data. It is possible to use consistent inputs and nuclear physics to reduce the differences in the calculated neutron-capture cross section from different Hauser-Feshbach codes. However, ensuring the treatment of the input of experimental data and other nuclear physics are similar across multiple codes requires a careful investigation. For this reason, more complete documentation of the inputs and physics chosen is important. Supplementary Information: The online version contains supplementary material available at 10.1140/epja/s10050-023-00920-0.

Navigating at night: fundamental limits on the sensitivity of radical pair magnetoreception under dim light.

Night-migratory songbirds appear to sense the direction of the Earth's magnetic field via radical pair intermediates formed photochemically in cryptochrome flavoproteins contained in photoreceptor cells in their retinas. It is an open question whether this light-dependent mechanism could be sufficiently sensitive given the low-light levels experienced by nocturnal migrants. The scarcity of available photons results in significant uncertainty in the signal generated by the magnetoreceptors distributed around the retina. Here we use results from Information Theory to obtain a lower bound estimate of the precision with which a bird could orient itself using only geomagnetic cues. Our approach bypasses the current lack of knowledge about magnetic signal transduction and processing in vivo by computing the best-case compass precision under conditions where photons are in short supply. We use this method to assess the performance of three plausible cryptochrome-derived flavin-containing radical pairs as potential magnetoreceptors.

Examination of the Staphylococcus aureus nitric oxide reductase (saNOR) reveals its contribution to modulating intracellular NO levels and cellular respiration.

Staphylococcus aureus nitrosative stress resistance is due in part to flavohemoprotein (Hmp). Although hmp is present in all sequenced S. aureus genomes, 37% of analyzed strains also contain nor, encoding a predicted quinol-type nitric oxide (NO) reductase (saNOR). DAF-FM staining of NO-challenged wild-type, nor, hmp and nor hmp mutant biofilms suggested that Hmp may have a greater contribution to intracellular NO detoxification relative to saNOR. However, saNOR still had a significant impact on intracellular NO levels and complemented NO detoxification in a nor hmp mutant. When grown as NO-challenged static (low-oxygen) cultures, hmp and nor hmp mutants both experienced a delay in growth initiation, whereas the nor mutant's ability to initiate growth was comparable with the wild-type strain. However, saNOR contributed to cell respiration in this assay once growth had resumed, as determined by membrane potential and respiratory activity assays. Expression of nor was upregulated during low-oxygen growth and dependent on SrrAB, a two-component system that regulates expression of respiration and nitrosative stress resistance genes. High-level nor promoter activity was also detectable in a cell subpopulation near the biofilm substratum. These results suggest that saNOR contributes to NO-dependent respiration during nitrosative stress, possibly conferring an advantage to nor+ strains in vivo.

A novel canine kidney cell line model for the evaluation of neoplastic development: karyotype evolution associated with spontaneous immortalization and tumorigenicity.

The molecular mechanisms underlying spontaneous neoplastic transformation in cultured mammalian cells remain poorly understood, confounding recognition of parallels with the biology of naturally occurring cancer. The broad use of tumorigenic canine cell lines as research tools, coupled with the accumulation of cytogenomic data from naturally occurring canine cancers, makes the domestic dog an ideal system in which to investigate these relationships. We developed a canine kidney cell line, CKB1-3T7, which allows prospective examination of the onset of spontaneous immortalization and tumorigenicity. We documented the accumulation of cytogenomic aberrations in CKB1-3T7 over 24 months in continuous culture. The majority of aberrations emerged in parallel with key phenotypic changes in cell morphology, growth kinetics, and tumor incidence and latency. Focal deletion of CDKN2A/B emerged first, preceding the onset and progression of tumorigenic potential, and progressed to a homozygous deletion across the cell population during extended culture. Interestingly, CKB1-3T7 demonstrated a tumorigenic phenotype in vivo prior to exhibiting loss of contact inhibition in vitro. We also performed the first genome-wide characterization of the canine tumorigenic cell line MDCK, which also exhibited CDKN2A/B deletion. MDCK and CKB1-3T7 cells shared several additional aberrations that we have reported previously as being highly recurrent in spontaneous canine cancers, many of which, as with CDKN2A/B deletion, are evolutionarily conserved in their human counterparts. The conservation of these molecular events across multiple species, in vitro and in vivo, despite their contrasting karyotypic architecture, is a powerful indicator of a common mechanism underlying emerging neoplastic activity. Through integrated cytogenomic and phenotypic characterization of serial passages of CKB1-3T7 from initiation to development of a tumorigenic phenotype, we present a robust and readily accessible model (to be made available through the American Type Culture Collection) of spontaneous neoplastic transformation that overcomes many of the limitations of earlier studies.

Altered plasma glutathione levels in bipolar disorder indicates higher oxidative stress; a possible risk factor for illness onset despite normal brain-derived neurotrophic factor (BDNF) levels.

BACKGROUND: Oxidative stress and neurotrophic factors have been implicated in the pathophysiology of bipolar disorder. Our objective was to determine whether plasma glutathione or brain-derived neurotrophic factor (BDNF) levels were abnormal in bipolar disorder and therefore useful as possible biomarkers. METHOD: Blood samples were collected from subsyndromal, medicated bipolar I patients (n = 50), recruited from OXTEXT, University of Oxford, and from 50 matched healthy controls. Total and oxidized glutathione levels were measured using an enzymatic recycling method and used to calculate reduced, percentage oxidized, ratio of reduced:oxidized and redox state. BDNF was measured using an enzyme-linked immunoassay. Self-monitored mood scores for the bipolar group were available (Quick Inventory of Depressive Symptomatology and the Altman Self-Rating Mania Scale) over an 8-week period. RESULTS: Compared with controls, bipolar patients had significantly lower levels of total glutathione and it was more oxidized. BDNF levels were not different. Age of illness onset but not current mood state correlated with total glutathione levels and its oxidation status, so that lower levels of total and reduced glutathione were associated with later onset of disease, not length of illness. CONCLUSIONS: Plasma glutathione levels and redox state detect oxidative stress even in subsyndromal patients with normal BDNF. It may relate to the onset and development of bipolar disorder. Plasma glutathione appears to be a suitable biomarker for detecting underlying oxidative stress and for evaluating the efficacy of antioxidant intervention studies.

Differential NK cell and macrophage killing of hamster cells infected with nononcogenic or oncogenic adenovirus.

Hamster cells infected with highly oncogenic human adenovirus type 12 (Ad12) were resistant to lysis by natural killer cells and macrophages, compared to cells infected with nononcogenic adenovirus type 2 (Ad2). The data suggest that early adenovirus gene expression in hamster cells results in preferential survival of Ad12, compared to Ad2, infected cells in vivo, thus providing an explanation for the differences in the oncogenicities of these two transforming viruses.

A new role for DNA virus early proteins in viral carcinogenesis.

The T antigen proteins encoded by DNA tumor virus early genes are involved in the transformation of normal cells to immortalized neoplastic cells that may or may not be tumorigenic in immunocompetent animals. Studies have been made of the tumorigenicity of DNA virus-transformed cells and the interactions of these cells in vivo and in vitro with immunologically nonspecific host effector cells such as natural killer cells and macrophages. The results imply that the T proteins determine the capacity of transformed cells to induce tumors by governing the level of susceptibility that transformed cells express to destruction by such host cellular defenses.

Extending the MNREAD sentence corpus: Computer-generated sentences for measuring visual performance in reading.

The MNREAD chart consists of standardized sentences printed at 19 sizes in 0.1 logMAR steps. There are 95 sentences distributed across the five English versions of the chart. However, there is a demand for a much larger number of sentences: for clinical research requiring repeated measures, and for new vision tests that use multiple trials at each print size. This paper describes a new sentence generator that has produced over nine million sentences that fit the MNREAD constraints, and demonstrates that reading performance with these new sentences is comparable to that obtained with the original MNREAD sentences. We measured reading performance with the original MNREAD sentences, two sets of our new sentences, and sentences with shuffled word order. Reading-speed versus print-size curves were obtained for each sentence set from 14 readers with normal vision at two levels of blur (intended to simulate acuity loss in low vision) and with unblurred text. We found no significant differences between the new and original sentences in reading acuity and critical print size across all levels of blur. Maximum reading speed was 7% slower with the new sentences than with the original sentences. Shuffled sentences yielded slower maximum reading speeds and larger reading acuities than the other sentences. Overall, measures of reading performance with the new sentences are similar to those obtained with the original MNREAD sentences. Our sentence generator substantially expands the reading materials for clinical research on reading vision using the MNREAD test, and opens up new possibilities for measuring how text parameters affect reading.

The level of expression of adenovirus type 2 transforming genes governs sensitivity to nonspecific immune cytolysis and other phenotypic properties of adenovirus 2-simian virus 40-transformed cell hybrids.

Syrian hamster embryo cells transformed by adenovirus type 2 (Ad2) or simian virus 40 (SV40) differ markedly in morphology, tumorigenicity, and susceptibility to in vitro lysis by nonspecific cytotoxic cells. Hybrid cells formed by fusing Ad2- and SV40-transformed Syrian hamster embryo cells may express only SV40 T antigens or both SV40 and Ad2 T antigens. Hybrids that express only SV40 T antigens are indistinguishable from the nonhybrid SV40-transformed phenotype, whereas hybrid cells that express T antigens from both viruses closely resemble the nonhybrid parental Ad2-transformed phenotype. Because these hybrid cells have been useful in the study of neoplastic transformation, we determined the amount of viral antigens that they accumulate in an attempt to correlate the level of expression of the transforming viral genes with some of their phenotypic properties. Hybrid cells that expressed proteins from both viruses showed reduced levels of SV40 T antigens compared with those of hybrid cells that did not express Ad2 T antigens. We also found that the production of several cellular proteins that influence cytomorphology was inhibited in hybrid and nonhybrid cells that expressed Ad2 T antigens, and the repression of these cellular proteins correlated with a change in cytomorphology from fibroblastic to spherical. Finally, we showed that the susceptibility of our hybrid cells to in vitro lysis by natural killer cells and activated macrophages, two putative host-effector cells involved in defense against neoplasia, correlated closely with the level of expression of a 58,000-dalton Ad2 protein. The results reported here, together with the results of previous studies, indicate that the oncogenic potential of hybrid cells that express both Ad2 and SV40 antigens is extremely sensitive to Ad2 expression, whereas other phenotypic properties depend on Ad2 expression in a dose-dependent manner.

Association of tumor induction by ultraviolet light-inactivated adenovirus 2-simian virus 40 recombinants with a specific segment of simian virus 40 DNA.

The nondefective (ND) adenovirus 2 (Ad2)-simian virus 40 (SV40) hybrid Ad2+ND4, which contains the segment of the SV40 genome between map positions 0.11 and 0.59, induced tumors in Syrian golden hamsters after inactivation by UV light. Ad2 and the Ad2+ND2 hybrid, which contains the segment of the SV40 genome between map positions 0.11 and 0.43, were not oncogenic after inactivation by UV light. These results showed that the incorporation of a specific segment of SV40 DNA into the Ad2 genome can alter the pathogenesis of the Ad2+ND4 virus by rendering it oncogenic for hamsters.

Spectrum of tumorigenic phenotypes among adenovirus 2-, adenovirus 12-, and simian virus 40-transformed Syrian hamster cells defined by host cellular immune-tumor cell interactions.

The tumor-inducing capacities of adenovirus type 2-, adenovirus type 12-, and SV40-transformed LSH hamster embryo cell define a spectrum of four distinct tumorigenic phenotypes: type I, nononcogenic for newborn hamsters but oncogenic for nude mice; type II, oncogenic for newborn hamsters but nononcogenic in syngeneic adults; type III, oncogenic for both newborns and syngeneic adults; and type IV, almost equally oncogenic for syngeneic and allogeneic adult hamsters. Modulation of the cellular immune response of the recipient hamster by immunosuppression or by alloimmunization alters tumor susceptibility, suggesting that dynamic transformed cell-host cellular immune interactions determine the tumorigenic phenotype of a transformed cell line. There is no correlation between the immunogenicities of the transformed cell lines tested and their tumor-inducing capacities. However, a strong correlation exists between the ability of transformed hamster embryo cells expressing phenotype IV to produce tumors in allogeneic CB hamsters and their resistance to cytolysis in vitro by activated macrophages. These data suggest that, in addition to transformation, DNA viruses may convey specific tumorigenic phenotypes to the cells that they infect by inducing cellular traits that determine the inherent susceptibility or resistance of a cell to host cell-mediated immune destruction.

Age-related and thymus-dependent rejection of adenovirus 2-transformed cell tumors in the Syrian hamster.

Adenovirus type 2-transformed hamster cell-induced newborn tumor lines were usually rejected when transplanted s.c. into 21-day-old syngeneic, weanling hamsters. The tumor-inducing capacity of two of these lines (Ad2HTL3 and Ad2HTL6) was tested in intact and neonatally thymectomized hosts. After s.c. injection of suspensions prepared from these lines, none of the weaning hamsters developed tumors while 100% of the newborns and 35.2% of neonatally thymectomized, weanling hamsters developed progressively enlarging neoplasms. The susceptibility of neonatally thymectomized hamsters to tumor challenge was directly related to the degree of immunosuppression observed following thymectomy as indicated by the amplitude of the in vitro response of blood leukocytes to concanavalin A. Pretreatment of thymectomized weanlings with syngeneic adult lymphoid cells (i.p.) resulted in a significant reduction in tumor susceptibility (p = 0.03). These findings suggest that acquisition of resistance to adenovirus type 2-transformed cells during the first 21 days of life may be a thymus-dependent cellular immune process.

Rejection of adenovirus 2-transformed cell tumors and immune responsiveness in Syrian hamsters.

Transplantation of adenovirus type 2-transformed cell-induced newborn tumor lines to different aged hamsters revealed that the cell-mediated host defenses responsible for tumor graft rejection matured early in the second week of life. When light microscopic examinations were performed during the course of tumor development, the primary histopathological difference between progressing tumors removed from newborn or thymectomized weanling hamsters and regressing lesions from normal weanlings was the lack of an early, mononuclear cell infiltrate in neoplasms from newborn and thymectomized hosts. These results suggest that the maturation of cellular immunity determines resistance to tumor transplantation in this system. This conclusion was supported by the in vitro detection of concanavalin A-responsive lymphocytes in spleens from tumor-resistant suckling but not tumor-susceptible neonatal hamsters. Although the incomplete seeding of thymus-dependent lymphocytes to the peripheral lymphoid tissues of newborn hamsters may partially explain the deficient concanavalin A responses of neonatal spleen cells, there appears to be an additional requirement for a radioresistant, adherent accessory cell population. These findings suggest that the development of a cell-mediated immune response is necessary for the rejection of adenovirus type 2-transformed cells and transformed cell-induced tumors and that this response requires the interaction of T-cells and accessory cell populations.

Suppression of the simian virus 40 tumorigenic phenotype in hybrid cells formed from simian virus 40- and adenovirus 2-transformed hamster embryo cells.

Hamster cells transformed by adenovirus 2 (Ad2) or simian virus 40 (SV40) have different tumorigenic phenotypes. In the present study, somatic cell hybrids formed from Ad2- and SV40-transformed hamster cells were used to determine whether possible interactions between the integrated viral genomes would influence the tumorigenic phenotype of hybrid transformed cells. These somatic cell hybrids were of two types, one expressing both Ad2 and SV40 T-antigens and the other expressing only SV40 T-antigens. Tumor induction by hybrid cells that expressed both Ad2 and SV40 T-antigens was reduced in adult syngeneic hamsters and abrogated in adult allogeneic hamsters. These results indicate that the tumorigenic phenotype of transformed somatic cell hybrids that contain both the Ad2 and SV40 genome is governed by the genetic expression of Ad2. This expression may alter the ability of SV40-transformed hamster cells to resist the immunologically nonspecific defenses of the host.

Characterization of hamster tumors induced by simian virus 40 small t deletion mutants as true histiocytic lymphomas.

Random bred Syrian hamsters given s.c. injections of SV40 small t deletion mutants dl883, dl884, and dl890 rapidly develop reticulum cell sarcomas in the abdominal cavity in addition to slowly developing s.c. fibrosarcomas at the site of virus inoculation. Injection of wild type SV40 s.c. induces only fibrosarcomas at the site of inoculation. In an attempt to understand why mutations in the SV40 small t gene should lead to this difference in tumor-inducing capacity in hamsters, we studied cells from 12 abdominal reticulum cell sarcomas which were induced by the s.c. injection of SV40 mutants. Morphological and functional analyses indicate that these tumor cells are derived from MAC-2+ macrophages. They are highly granulated, vacuolated, and multinucleated, and they generally adhere to glass and plastic. In addition, they (a) phagocytose latex beads; (b) express high levels of class II major histocompatibility complex antigens; (c) contain beta-glucuronidase, acid phosphatase, and fluoride-inhibited nonspecific esterase; (d) contain lysozyme and fibronectin; and (e) express cell surface MAC-2 antigens. Thus, the small t deletions in the SV40 genome appear to permit the virus to transform cells that are distant from the site of virus inoculation; at this distant site, the cells transformed are of a specific lineage, MAC-2+ peritoneal macrophages. This specific tropism may reflect a unique characteristic of MAC-2+ cells or their precursors that renders these cells susceptible to SV40 mutants which are otherwise restricted in the range of cells that they can transform.

Biochemical properties of media conditioned by simian virus 40-induced hamster tumor cells: correlation with distinct cell phenotypes but not with oncogenicity.

Hamster cells, transformed in vitro by SV40, have been reported to secrete an unidentified factor(s) that inhibits thymidine uptake (TU) by various normal cell types, including activated lymphocytes. It has been postulated that this apparent antiproliferative effect may play an in vivo role in the high tumorigenic capacity of SV40-transformed hamster cells. In keeping with this hypothesis, Adenovirus type 2-transformed hamster cells, which are only weakly tumorigenic, do not inhibit TU by indicator cells in vitro. To study the biological relevance of this phenomenon, we assayed 11 cell lines derived from different fibrosarcomas, induced in Syrian hamsters by SV40, for their ability to inhibit TU by normal rabbit kidney indicator cells. In contrast to cells transformed in vitro by SV40, media conditioned by 6 of 11 tumor-derived cell lines did not inhibit TU. Our results do not support the hypothesis that an antiproliferative factor secreted by SV40-transformed cells promotes the tumor-inducing capacity of these cells. Furthermore, inhibition of TU does not appear to be due to the production of a specific antimitotic peptide, but rather to other biochemical properties of the media conditioned by transformed cells. Finally, these biochemical properties do appear to correlate with specific morphological and growth characteristics of the tumor cells, but probably as an effect and not a cause.

Collapse of Water-Stress Emboli in the Tracheids of Thuja occidentalis L.

We report the kinetics of embolus formation and collapse in the tracheids of Thuja occidentalis L. stem segments. Radial wood sections were trimmed to 4 mm long paralleling the tracheids by 1 mm wide and 0.1 mm thick. They were observed under a dissecting microscope at 128x while sections were dehydrated and rehydrated. During dehydration, cavitations resulted in the formation of emboli in tracheids, but we concluded that the cavitated tracheids did not immediately fill with air at atmospheric pressure. This conclusion was based on the time required for the emboli to collapse after the rewetting of the dehydrated segment. By hypothesis, the time for the emboli to collapse should be proportional to the amount of air in the emboli. The time for all the emboli to collapse was a linear function of the dehydration time for times up to 15 min. For dehydrations greater than 80 min, the time for collapse after rewetting was constant, and we concluded that the tracheids have saturated with air by 80 min of dehydration. The kinetics of embolus formation is discussed in terms of the air-seeding hypothesis for cavitation, and collapse is discussed in terms of the physics of gas dissolution and diffusion. Embolus formation and dissolution in intact herbaceous and woody plants should follow the same physical laws.

Effect of age on serum immunoreactive parathyroid hormone and its biological effects.

Immunoreactive parathyroid hormone (iPTH) levels, nephrogenous cAMP (ncAMP), and tubular maximum phosphate reabsorption (TmP) were measured in 10 young and 12 healthy volunteers. The fasting urinary calcium to creatinine ratio (Ca:Cr) was also quantitated as an index of bone resorption. Aging was attended by increased iPTH levels (6.9 +/- 0.8 vs. 3.4 +/- 0.4 mu leq/ml; P less than 0.01) as well as increased ncAMP levels (2.48 +/- 0.28 vs. 1.12 +/- 0.21 nmol/100 ml glomerular filtrate; P less than 0.005) and decreased TmP (2.9 +/- 0.2 vs. 4.1 +/- 0.2 mg/100 ml glomerular filtrate; P less than 0.005), indicating that the increased iPTH levels reflected the biological effects of the hormone. A significant positive correlation of iPTH and ncAMP and a significant negative correlation of iPTH and TmP were observed. The Ca:Cr was increased in the older volunteers (0.10 +/- 0.02 vs. 0.05 +/- 0.01; P less than 0.05). The elderly subjects had significantly decreased daily calcium ingestion, serum phosphate and albumin, and creatinine clearance. Our findings suggest that the increased biological effects of PTH in the elderly subjects may contribute to the increases in Ca:Cr and bone loss that occur with age.

Free amino acid levels in the blood of patients undergoing parenteral alimentation.

Free amino acid levels were determined in the blood of patients undergoing parenteral alimentation. During amino acid infusions, alanine, valine, glycine, isoleucine, leucine, proline, threonine, serine, methionine, phenylalanine, and lysine levels increased. Bivariate regression analysis was then done to determine the average rise in each amino acid when 1 mmole/hr of that amino acid was infused and when 1 mmole/hr of glucose was infused. This analysis was done on both arterial plasma and arterial wh-le blood increments. The average rise in the amino acid level with 1 mmole of infusion per hour varied from 32 to 133 mumole/liter. Only alanine levels were positively correlated with glucose infusion, while the branched chain levels were all negatively correlated. In no instance could a significant positive arteriovenous difference across the forearm be correlated with the infusion of an amino acid, despite amino acid levels as much as five times normal. Methionine, proline, valine, threonine, and lysine showed the greatest rise in blood concentration per millimole of amino acid infused per hour suggesting that their degradation or use in protein synthesis was limited. While the blood concentration rise in glycine was only about half as much per millimole per hour infused as was found in the previously mentioned group of amino acids, high rates of infusion of this amino acid resulted in large increments inglycine levels. It may be desirable to reduce the amounts of these amino acids in parenteral amino acid formulations.

Cardiovascular response to rapid phenytoin infusion during seizures in paralyzed rats.

The maximum rate at which phenytoin may be safely administered without inducing hypotension has been evaluated in nonconvulsing animals and man; no comparable information during convulsions of either animals or man is available. Comparison of blood pressure and ECG responses to rapid phenytoin infusion in nonconvulsing rats and in rats during bicuculline-induced status epilepticus suggests that the hypertensive response of convulsions may protect against phenytoin-induced hypotension, thus indicating that more rapid administration of phenytoin during convulsions might be possible with careful monitoring.