Some Aspects of Lipid Metabolism of Chicks Infected with \u3cem\u3eSalomonella pullorum\u3c/em\u3e

The literature concerning the pathology accompanying infectious diseases has concerned, predominantly, gross and microscopic pathology. The biochemical changes in pathologic conditions have had little attention except for the generally accepted clinical procedures. Within the last decade, however, a change in emphasis has begun. A number on investigators have reported studies of enzymatic changes observed in infected animals. Many of these observations, however, have been with unnatural host-parasite systems. The desirability of using a natural host-parasite system is obvious. Among the Enterobacteriaceae there are a limited number of complexes which are suitable for study with experimental animals. One of these is the well documented pullorm disease, a malady which has been accepted as being specific for chicks. The etiologic agent has been known for over half a century, during which the epidemiology and control methods have been worked out in detail. The biochemical pathology has, on the contrary, been studied in detail only in recent years. Reports from this laboratory have described alteration in nitrogen and carbohydrate metabolism. Chromatographic procedures have shown qualitative changes in amino acids occur in the disease. Nitrogen excretion is altered as demonstrated by the high levels of urea in the blood of normally uricotelic animals. The carbohydrate studies have been concerned largely with the components of the Krebs cycle. This has been accomplished by enzyme studies, assay of the concentration of intermediates and by using inhibitors of enzyme activity. Many of these alterations were similar to those encountered in carbon tetrachloride poisoning. One of the most characteristic results of poisoning with carbon tetrachloride is deposition of fat in the liver. Such a change has been observed in histologic preparations of liver from chicks infected with Salmonella pullorum. This and the fact that methionine, an amino acid which exerts a marked lipotropic effect, disappears in the diseased bird led to the study of changes in the lipids which is reported in this thesis. This study has been correlated, in part, with previous studies of amino acid therapy. Certain lipotropic agents have been used similarly in order to compare therapeutic effects and to arrive at a cause for the variations in the fat from the live

Melodies of Many Lands

The melodies of many landsErewhile have charm\u27d my ear,Yet there\u27s butone among them allWhich my heart holds dear:I heard it first from lips I lov\u27d,My tears it then beguil\u27dIt was the song my mother sang,When I was but a child.It was the song my mother sang,When I was but a child. Its words, I well remember now,Were fraught with precepts old;And ev\u27ry line a maxim heldOf far more worth than gold:A lesson \u27twas, tho\u27 simply taught,That cannot pass away.It is my quiding star by night,My comfort in the day.It is my guiding star by night,My comfort in the day. It told me in the hour of need,To seek a solace thereWhere only stricken hearts could find,Meet answer to their prayer.Ah! Much I owe that gentle voice,Whose words my tears beguil\u27d;That song of songs my mother sang,When I was but a child. That song of songs my mother sang,When I was but a child

A Flexible and Qualitatively Stable Model for Cell Cycle Dynamics Including DNA Damage Effects

This paper includes a conceptual framework for cell cycle modeling into which the experimenter can map observed data and evaluate mechanisms of cell cycle control. The basic model exhibits qualitative stability, meaning that regardless of magnitudes of system parameters its instances are guaranteed to be stable in the sense that all feasible trajectories converge to a certain trajectory. Qualitative stability can also be described by the signs of real parts of eigenvalues of the system matrix. On the biological side, the resulting model can be tuned to approximate experimental data pertaining to human fibroblast cell lines treated with ionizing radiation, with or without disabled DNA damage checkpoints. Together these properties validate a fundamental, first order systems view of cell dynamics. Classification Codes: 15A6

Presence of antibiotic resistance genes in the receiving environment of Iqaluit's wastewater treatment plant in water, sediment, and clams sampled from Frobisher Bay, Nunavut : a preliminary study in the Canadian Arctic

Antibiotic resistance (AR) is a growing health concern worldwide, and the Arctic represents an understudied region in terms of AR. This study aimed to quantify AR genes from effluent released from a wastewater treatment plant (WWTP) in Iqaluit, Nunavut, Canada, thus creating a baseline reference for future evaluations. Water, sediment, and truncate softshell clam (Mya truncata) tissue samples were compared from the wastewater, the receiving environment of Frobisher Bay, and nearby undisturbed freshwaters. The pharmaceuticals and personal care products (PPCPs) atenolol, carbamazepine, metoprolol, naproxen, sulfapyridine, and trimethoprim were found in the wastewater, but the PPCPs were undetectable in the receiving environment. However, the relative abundances of ARGs were significantly higher in wastewater than in the receiving environment or reference sites. Abundances did not significantly differ in Frobisher Bay compared to undisturbed reference sites. ARGs in clams near the WWTP had similar relative abundances as those from pristine areas. The lack of ARG detection is likely due to Frobisher Bay tides flushing inputs to levels below detection. These data suggest that the WWTP infrastructure does not influence the receiving environment based on the measured parameters; more importantly, further research must elucidate the impact and fate of AR and PPCPs in Arctic communities

Mutational analysis of disease relapse in patients allografted for acute myeloid leukemia

Disease relapse is the major cause of treatment failure after allogeneic stem cell transplantation (allo-SCT) in acute myeloid leukemia (AML). To identify AML-associated genes prognostic of AML relapse post–allo-SCT, we resequenced 35 genes in 113 adults at diagnosis, 49 of whom relapsed. Two hundred sixty-two mutations were detected in 102/113 (90%) patients. An increased risk of relapse was observed in patients with mutations in WT1 (P = .018), DNMT3A (P = .045), FLT3 ITD (P = .071), and TP53 (P = .06), whereas mutations in IDH1 were associated with a reduced risk of disease relapse (P = .018). In 29 patients, we additionally compared mutational profiles in bone marrow at diagnosis and relapse to study changes in clonal structure at relapse. In 13/29 patients, mutational profiles altered at relapse. In 9 patients, mutations present at relapse were not detected at diagnosis. In 15 patients, additional available pre–allo-SCT samples demonstrated that mutations identified posttransplant but not at diagnosis were detectable immediately prior to transplant in 2 of 15 patients. Taken together, these observations, if confirmed in larger studies, have the potential to inform the design of novel strategies to reduce posttransplant relapse highlighting the potential importance of post–allo-SCT interventions with a broad antitumor specificity in contrast to targeted therapies based on mutational profile at diagnosis

Custom fitted compression garments enhance recovery from muscle damage in rugby players

PURPOSE: To evaluate the effects of custom fitted compression garments (CG) on recovery from muscle damage in rugby players. METHODS: Forty-five players were tested for lower body strength, power, and indices of muscle-damage before completing a damaging protocol (20 x 20 m sprints with 5 m deceleration, 100 drop-jumps). Players were randomly assigned to wear either custom fitted (CF, n = 13), or standard sized CG (SSG, n = 16), or to received sham ultrasound therapy (CON, n = 16) immediately post-exercise. Players were re-tested immediately, then after 24 h and 48 h. RESULTS: Strength recovery was significantly different between groups (F = 2.7, p = 0.02), with only CF recovering to baseline values by 48 h (p = 0.973). Time x condition effects were also apparent for creatine kinase activity (χ = 30.4, p < 0.001) and mid-thigh girth (F = 3.7, p = 0.005), with faster recovery apparent in CF compared to both CON and SSG (p < 0.05). CONCLUSIONS: Custom fitted CG improved strength recovery and indices of muscle damage in rugby players, compared to controls and standard sized garments. PRACTICAL APPLICATIONS: Athletes and coaches would be advised to use appropriately fitted CG to enhance strength recovery following damaging exercise

HAWAII ALGAL BIOFUEL

This report investigates the feasibility and affordability of producing algae-derived biofuel in Hawaii for military aviation. The authors evaluated methods for cultivation of algae, investigated the processes necessary to locally refine bio-oil into bio-kerosene, researched the environmental impacts of cultivation and refinement facilities in Hawaii, and studied the resultant cost per gallon of bio-kerosene production. Based on the current state of technology and the proposed system of systems architecture, this report estimates that bio-kerosene can be produced for $8.00 - 22.87/gal, indicating that although this system is technically feasible, it is unlikely to be affordable at current fuel prices without ongoing subsidy or further technical innovation.http://archive.org/details/hawaiialgalbiofu109453289

Striatopallidal dysfunction underlies repetitive behavior in Shank3-deficient model of autism

The postsynaptic scaffolding protein SH3 and multiple ankyrin repeat domains 3 (SHANK3) is critical for the development and function of glutamatergic synapses. Disruption of the SHANK3-encoding gene has been strongly implicated as a monogenic cause of autism, and Shank3 mutant mice show repetitive grooming and social interaction deficits. Although basal ganglia dysfunction has been proposed to underlie repetitive behaviors, few studies have provided direct evidence to support this notion and the exact cellular mechanisms remain largely unknown. Here, we utilized the Shank3B mutant mouse model of autism to investigate how Shank3 mutation may differentially affect striatonigral (direct pathway) and striatopallidal (indirect pathway) medium spiny neurons (MSNs) and its relevance to repetitive grooming behavior in Shank3B mutant mice. We found that Shank3 deletion preferentially affects synapses onto striatopallidal MSNs. Striatopallidal MSNs showed profound defects, including alterations in synaptic transmission, synaptic plasticity, and spine density. Importantly, the repetitive grooming behavior was rescued by selectively enhancing the striatopallidal MSN activity via a Gq-coupled human M3 muscarinic receptor (hM3Dq), a type of designer receptors exclusively activated by designer drugs (DREADD). Our findings directly demonstrate the existence of distinct changes between 2 striatal pathways in a mouse model of autism and indicate that the indirect striatal pathway disruption might play a causative role in repetitive behavior of Shank3B mutant mice.National Institute of Mental Health (U.S.) (Grant 5R01MH097104

Combined HIV-1 Envelope Systemic and Mucosal Immunization of Lactating Rhesus Monkeys Induces a Robust Immunoglobulin A Isotype B Cell Response in Breast Milk

ABSTRACT Maternal vaccination to induce anti-HIV immune factors in breast milk is a potential intervention to prevent postnatal HIV-1 mother-to-child transmission (MTCT). We previously demonstrated that immunization of lactating rhesus monkeys with a modified vaccinia Ankara (MVA) prime/intramuscular (i.m.) protein boost regimen induced functional IgG responses in milk, while MVA prime/intranasal (i.n.) boost induced robust milk Env-specific IgA responses. Yet, recent studies have suggested that prevention of postnatal MTCT may require both Env-specific IgA and functional IgG responses in milk. Thus, to investigate whether both responses could be elicited by a combined systemic/mucosal immunization strategy, animals previously immunized with the MVA prime/i.n. boost regimen received an i.n./i.m. combined C.1086 gp120 boost. Remarkably, high-magnitude Env-specific IgA responses were observed in milk, surpassing those in plasma. Furthermore, 29% of vaccine-elicited Env-specific B cells isolated from breast milk were IgA isotype, in stark contrast to the overwhelming predominance of IgG isotype Env-specific B cells in breast milk of chronically HIV-infected women. A clonal relationship was identified between Env-specific blood and breast milk B cells, suggesting trafficking of that cell population between the two compartments. Furthermore, IgA and IgG monoclonal antibodies isolated from Env-specific breast milk B cells demonstrated diverse Env epitope specificities and multiple effector functions, including tier 1 neutralization, antibody-dependent cellular cytotoxicity (ADCC), infected cell binding, and inhibition of viral attachment to epithelial cells. Thus, maternal i.n./i.m. combined immunization is a novel strategy to enhance protective Env-specific IgA in milk, which is subsequently transferred to the infant via breastfeeding. IMPORTANCE Efforts to increase the availability of antiretroviral therapy to pregnant and breastfeeding women in resource-limited areas have proven remarkably successful at reducing HIV vertical transmission rates. However, more than 200,000 children are infected annually due to failures in therapy implementation, monitoring, and adherence, nearly half by postnatal HIV exposure via maternal breast milk. Intriguingly, in the absence of antiretroviral therapy, only 10% of breastfed infants born to HIV-infected mothers acquire the virus, suggesting the existence of naturally protective immune factors in milk. Enhancement of these protective immune factors through maternal vaccination will be a critical strategy to reduce the global pediatric AIDS epidemic. We have previously demonstrated that a high magnitude of HIV Env-specific IgA in milk correlates with reduced risk of infant HIV acquisition. In this study, we describe a novel HIV vaccine regimen that induces potent IgA responses in milk and therefore could potentially protect against breast milk HIV MTCT