Effects of Ascorbic Acid Deficiencies on Larvae of \u3ci\u3eLymantria Dispar\u3c/i\u3e (Lepidoptera: Lymantriidae)

We assessed the effects of ascorbic acid and total vitamin deficiencies on growth, food processing efficiencies and survival of larval gypsy moths. Artificial diet lacking ascorbic acid did not alter performance of fourth instars, whereas diet lacking a total vitamin mix margmally reduced growth. All vita- min deficient diets substantially reduced survival of fourth-fifth instars. Mortality occurred primarily during molting periods. providing further evidence of the putative role of ascorbic acid in cuticle formation

Perceived protein needs and measured protein intake in collegiate male athletes: an observational study

<p>Abstract</p> <p>Background</p> <p>Protein needs for athletes are likely higher than those for the general population. However, athletes may perceive their protein needs to be excessively high. The purpose of this research was to compare collegiate athletes' perceived protein needs and measured protein intake to the recommended protein intake (RDI) for healthy adults (i.e. 0.8 g/kg/d) and to the maximum beneficial level for strength-trained athletes (i.e. 2.0 g/kg/day).</p> <p>Methods</p> <p>Perceived protein needs were quantified in 42 strength-trained collegiate male athletes by using a survey that asked the athletes to provide their perception about protein needs in specific quantitative terms (i.e. g/kg/d). Perceived protein needs were also determined by having the athletes select a daylong menu that they perceived to have adequate protein content from a collection of 5 isoenergetic menus, which differed in terms of protein content. Actual protein intake was quantified using 3-day food records and nutrient analysis. Single sample t-tests were used to compare protein intake and perceived protein needs to 0.8 g/kg/day and 2.0 g/kg/day.</p> <p>Results</p> <p>When asked to provide, in quantitative terms, protein needs for athletes, 67% of the athletes indicated "do not know." Of the remaining 33% of athletes, all gave values greater than 2.0 g/kg/d (mean 21.5 ± 11.2 g/kg/d, p = 0.14 vs. 2.0 g/kg/d). Based on the menu selection method for determining perceived protein needs, the athletes indicated that their protein needs were 2.4 ± 0.2 g/kg/d, which was greater than the RDI for protein (p < 0.0001) and tended to be greater than the maximally beneficial protein intake of 2.0 g/kg/d (p = 0.13). Measured protein intake was 2.0 ± 0.1 g/kg/d, which was greater than the RDI (p < 0.0001) but not different from the maximally beneficial protein intake of 2.0 g/kg/d (p = 0.84).</p> <p>Conclusions</p> <p>Male collegiate athletes recognize that their protein needs are higher than that of the general population and consume significantly more protein than recommended in the RDI. However, it also appears that athletes are not aware of objective recommendations for protein intake and may perceive their needs to be excessively high. This study highlights the need for nutrition education in collegiate athletes, in particular nutrition education on macronutrient distribution and protein needs.</p

Characterizing and prognosticating chronic lymphocytic leukemia in the elderly: prospective evaluation on 455 patients treated in the United States.

BACKGROUND: Median age at diagnosis of patients with chronic lymphocytic leukemia (CLL) is \u3e 70 years. However, the majority of clinical trials do not reflect the demographics of CLL patients treated in the community. We examined treatment patterns, outcomes, and disease-related mortality in patients ≥ 75 years with CLL (E-CLL) in a real-world setting. METHODS: The Connect® CLL registry is a multicenter, prospective observational cohort study, which enrolled 1494 adult patients between 2010-2014, at 199 US sites. Patients with CLL were enrolled within 2 months of initiating first line of therapy (LOT1) or a subsequent LOT (LOT ≥ 2). Kaplan-Meier methods were used to evaluate overall survival. CLL- and infection-related mortality were assessed using cumulative incidence functions (CIF) and cause-specific hazards. Logistic regression was used to develop a classification model. RESULTS: A total of 455 E-CLL patients were enrolled; 259 were enrolled in LOT1 and 196 in LOT ≥ 2. E-CLL patients were more likely to receive rituximab monotherapy (19.3 vs. 8.6%; p \u3c 0.0001) and chemotherapy-alone regimens (p \u3c 0.0001) than younger patients. Overall and complete responses were lower in E-CLL patients than younger patients when given similar regimens. With a median follow-up of 3 years, CLL-related deaths were higher in E-CLL patients than younger patients in LOT1 (12.6 vs. 5.1% p = 0.0005) and LOT ≥ 2 (31.3 vs. 21.5%; p = 0.0277). Infection-related deaths were also higher in E-CLL patients than younger patients in LOT1 (7.4 vs. 2.7%; p = 0.0033) and in LOT ≥ 2 (16.2 vs. 11.2%; p = 0.0786). A prognostic score for E-CLL patients was developed: time from diagnosis to treatment \u3c 3 months, enrollment therapy other than bendamustine/rituximab, and anemia, identified patients at higher risk of inferior survival. Furthermore, higher-risk patients experienced an increased risk of CLL- or infection-related death (30.6 vs 10.3%; p = 0.0006). CONCLUSION: CLL- and infection-related mortality are higher in CLL patients aged ≥ 75 years than younger patients, underscoring the urgent need for alternative treatment strategies for these understudied patients. TRIAL REGISTRATION: The Connect CLL registry was registered at clinicaltrials.gov: NCT01081015 on March 4, 2010

Ablation of an Ovarian Tumor Family Deubiquitinase Exposes the Underlying Regulation Governing the Plasticity of Cell Cycle Progression in \u3cem\u3eToxoplasma gondii\u3c/em\u3e

The Toxoplasma genome encodes the capacity for distinct architectures underlying cell cycle progression in a life cycle stage-dependent manner. Replication in intermediate hosts occurs by endodyogeny, whereas a hybrid of schizogony and endopolygeny occurs in the gut of the definitive feline host. Here, we characterize the consequence of the loss of a cell cycle-regulated ovarian tumor (OTU family) deubiquitinase, OTUD3A of Toxoplasma gondii (TgOTUD3A; TGGT1_258780), in T. gondii tachyzoites. Rather than the mutation being detrimental, mutant parasites exhibited a fitness advantage, outcompeting the wild type. This phenotype was due to roughly one-third of TgOTUD3A-knockout (TgOTUD3A-KO) tachyzoites exhibiting deviations from endodyogeny by employing replication strategies that produced 3, 4, or 5 viable progeny within a gravid mother instead of the usual 2. We established the mechanistic basis underlying these altered replication strategies to be a dysregulation of centrosome duplication, causing a transient loss of stoichiometry between the inner and outer cores that resulted in a failure to terminate S phase at the attainment of 2N ploidy and/or the decoupling of mitosis and cytokinesis. The resulting dysregulation manifested as deviations in the normal transitions from S phase to mitosis (S/M) (endopolygeny-like) or M phase to cytokinesis (M/C) (schizogony-like). Notably, these imbalances are corrected prior to cytokinesis, resulting in the generation of normal progeny. Our findings suggest that decisions regarding the utilization of specific cell cycle architectures are controlled by a ubiquitin-mediated mechanism that is dependent on the absolute threshold levels of an as-yet-unknown target(s). Analysis of the TgOTUD3A-KO mutant provides new insights into mechanisms underlying the plasticity of apicomplexan cell cycle architecture

In Vitro Studies of Cells Grown on the Superconductor PrOxFeAs

The recent discovery of arsenic-based high temperature superconductors has reignited interest in the study of superconductor : biological interfaces. However, the new superconductor materials involve the chemistry of arsenic, their toxicity remain unclear [ Nature, 2008, 452(24):922]. In this study the possible adverse effects of this new family of superconductors on cells have been examined. Cell culture studies in conjunction with microscopy and viability assays were employed to examine the influence of arsenic-based superconductor PrOxFeAs (x=0.75) material in vitro. Imaging data revealed that cells were well adhered and spread on the surface of the superconductor. Furthermore, cytotoxicity studies showed that cells were unaffected during the time-course of the experiments, providing support for the biocompatibility aspects of PrOxFeAs-based superconductor material.Comment: Are the FeAs based superconductors toxic

Real-world clinical experience in the Connect® chronic lymphocytic leukaemia registry: a prospective cohort study of 1494 patients across 199 US centres.

The clinical course of chronic lymphocytic leukaemia (CLL) is heterogeneous, and treatment options vary considerably. The Connect® CLL registry is a multicentre, prospective observational cohort study that provides a real-world perspective on the management of, and outcomes for, patients with CLL. Between 2010 and 2014, 1494 patients with CLL and that initiated therapy, were enrolled from 199 centres throughout the USA (179 community-, 17 academic-, and 3 government-based centres). Patients were grouped by line of therapy at enrolment (LOT). We describe the clinical and demographic characteristics of, and practice patterns for, patients with CLL enrolled in this treatment registry, providing patient-level observational data that represent real-world experiences in the USA. Fluorescence in&nbsp;situ hybridization (FISH) analyses were performed on 49·3% of patients at enrolment. The most common genetic abnormalities detected by FISH were del(13q) and trisomy 12 (45·7% and 20·8%, respectively). Differences in disease characteristics and comorbidities were observed between patients enrolled in LOT1 and combined LOT2/≥3 cohorts. Important trends observed include the infrequent use of genetic prognostic testing, and differences in patient characteristics for patients receiving chemoimmunotherapy combinations. These data represent experiences of patients with CLL in the USA, which may inform treatment decisions in everyday practice

Natural history of murine gamma-herpesvirus infection

Murine gamma-herpesvirus 68 (MHV-68) is a natural pathogen of small rodents and insectivores (mice, voles and shrews). The primary infection is characterized by virus replication in lung epithelial cells and the establishment of a latent infection in B lymphocytes. The virus is also observed to persist in lung epithelial cells, dendritic cells and macrophages. Splenomegaly is observed two weeks after infection, in which there is a CD4+ T-cell-mediated expansion of B and T cells in the spleen. At three weeks post-infection an infectious mononucleosis-like syndrome is observed involving a major expansion of Vbeta4+CD8+ T cells. Later in the course of persistent infection, ca. 10% of mice develop lymphoproliferative disease characterized as lymphomas of B-cell origin. The genome from MHV-68 strain g2.4 has been sequenced and contains ca. 73 genes, the majority of which are collinear and homologous to other gamma-herpesviruses. The genome includes cellular homologues for a complement-regulatory protein, Bcl-2, cyclin D and interleukin-8 receptor and a set of novel genes M1 to M4. The function of these genes in the context of latent infections, evasion of immune responses and virus-mediated pathologies is discussed. Both innate and adaptive immune responses play an active role in limiting virus infection. The absence of type I interferon (IFN) results in a lethal MHV-68 infection, emphasizing the central role of these cytokines at the initial stages of infection. In contrast, type II IFN is not essential for the recovery from infection in the lung, but a failure of type II IFN receptor signalling results in the atrophy of lymphoid tissue associated with virus persistence. Splenic atrophy appears to be the result of immunopathology, since in the absence of CD8+ T cells no pathology occurs. CD8+ T cells play a major role in recovery from the primary infection, and also in regulating latently infected cells expressing the M2 gene product. CD4+ T cells have a key role in surveillance against virus recurrences in the lung, in part mediated through 'help' in the genesis of neutralizing antibodies. In the absence of CD4+ T cells, virus-specific CD8+ T cells are able to control the primary infection in the respiratory tract, yet surprisingly the memory CD8+ T cells generated are unable to inhibit virus recurrences in the lung. This could be explained in part by the observations that this virus can downregulate major histocompatibility complex class I expression and also restrict inflammatory cell responses by producing a chemokine-binding protein (M3 gene product). MHV-68 provides an excellent model to explore methods for controlling gamma-herpesvirus infection through vaccination and chemotherapy. Vaccination with gp150 (a homologue of gp350 of Epstein-Barr virus) results in a reduction in splenomegaly and virus latency but does not block replication in the lung, nor the establishment of a latent infection. Even when lung virus infection is greatly reduced following the action of CD8+ T cells, induced via a prime-boost vaccination strategy, a latent infection is established. Potent antiviral compounds such as the nucleoside analogue 2'deoxy-5-ethyl-beta-4'-thiouridine, which disrupts virus replication in vivo, cannot inhibit the establishment of a latent infection. Clearly, devising strategies to interrupt the establishment of latent virus infections may well prove impossible with existing methods

Spin-dependent twist-4 matrix elements from the instanton vacuum: Flavor-singlet and nonsinglet

We estimate the twist-4 spin-1 nucleon matrix element f_2 in an instanton-based description of the QCD vacuum. In addition to the flavor-nonsinglet we compute also the flavor-singlet matrix element, which appears in next-to-leading order of the (1/N_c)-expansion. The corresponding twist-3 spin-2 matrix elements d_2 are suppressed in the packing fraction of the instanton medium, (\bar \rho)/(\bar R) << 1. We use our results to estimate the leading (1/Q^2) power corrections to the first moment of the proton and neutron spin structure functions G_1, as well as the intrinsic charm contribution to the nucleon spin.Comment: 17 pages, 4 eps figures include

DNA cleavage and antitumour activity of platinum(II) and copper(II) compounds derived from 4-methyl-2-N-(2-pyridylmethyl)aminophenol: spectroscopic, electrochemical and biological investigation

The reaction of the redox-active ligand, Hpyramol (4-methyl-2-N-(2-pyridylmethyl)aminophenol) with K2PtCl4 yields monofunctional square-planar [Pt(pyrimol)Cl], PtL-Cl, which was structurally characterised by single-crystal X-ray diffraction and NMR spectroscopy. This compound unexpectedly cleaves supercoiled double-stranded DNA stoichiometrically and oxidatively, in a non-specific manner without any external reductant added, under physiological conditions. Spectro-electrochemical investigations of PtL-Cl were carried out in comparison with the analogue CuL-Cl as a reference compound. The results support a phenolate oxidation, generating a phenoxyl radical responsible for the ligand-based DNA cleavage property of the title compounds. Time-dependent in vitro cytotoxicity assays were performed with both PtL-Cl and CuL-Cl in various cancer cell lines. The compound CuL-Cl overcomes cisplatin-resistance in ovarian carcinoma and mouse leukaemia cell lines, with additional activity in some other cells. The platinum analogue, PtL-Cl also inhibits cell-proliferation selectively. Additionally, cellular-uptake studies performed for both compounds in ovarian carcinoma cell lines showed that significant amounts of Pt and Cu were accumulated in the A2780 and A2780R cancer cells. The conformational and structural changes induced by PtL-Cl and CuL-Cl on calf thymus DNA and phi X174 supercoiled phage DNA at ambient conditions were followed by electrophoretic mobility assay and circular dichroism spectroscopy. The compounds induce extensive DNA degradation and unwinding, along with formation of a monoadduct at the DNA minor groove. Thus, hybrid effects of metal-centre variation, multiple DNA-binding modes and ligand-based redox activity towards cancer cell-growth inhibition have been demonstrated. Finally, reactions of PtL-Cl with DNA model bases (9-Ethylguanine and 5'-GMP) followed by NMR and MS showed slow binding at Guanine-N7 and for the double stranded self complimentary oligonucleotide d(GTCGAC)(2) in the minor groove