NEUROTOXICITY OF A NON-METABOLIZABLE AMINO ACID, 1-AMINOCYCLOPENTANE-1-CARBOXYLIC ACID: ANTAGONISM BY AMINO ACIDS IN CULTURES OF CEREBELLUM

Abstract— The non-metabolizable amino acid 1-aminocyclopentane-1-carboxylic acid (ACPC) induced degeneration of myelinated axons but spared nerve cell bodies in well myelinated organotypic cultures of cerebellum. The ACPC concentrations used were comparable to those which induce axonal degeneration in vivo. Developing unmyelinated cultures were more sensitive to ACPC than mature cultures and newly myelinating axons appeared to be particularly affected. Supplementing the medium with amino acids, but not with vitamins, prevented toxicity at the lower concentrations of ACPC and afforded considerable protection against the highest concentrations. The protective effect of amino acids could not be accounted for by inhibition of intracellular ACPC transport. These results are considered in terms of other evidence indicating defective protein metabolism in ACPC-treated mice.     

Hemoglobin synthesis studies of a family with α-thalassemia trait and sickle cell trait

The ratio of total globin alpha to beta chain synthesis was determined in reticulocytes isolated from the blood of the members of a black family, some of whom had sickle cell trait with low blood HbS concentrations (25-30%). The results support the hypothesis that sickle cell trait individuals with low HbS concentrations also carry a gene for alpha-thalassemia.     

Deterioration of High-Moisture Corn

Two small, leaky silos were filled with normal high-moisture corn (HMC), and two with HMC severely infested by Helminthosporium maydis. Counts of mesophilic bacteria, lactobacilli, coliforms, yeasts, and molds were made on corn samples as received and periodically thereafter during 220 days of storage. Temperature and gas levels also were monitored. Sequential changes in the populations of lactobacilli, yeasts, and molds were determined during spoilage of HMC. These population changes were compared on the basis of the variables encountered in the present study as well as with the results of previous studies conducted on normal HMC stored under adequate conditions. Heavy infestation by H. maydis had no appreciable effect on HMC preservation.     

Antigenic similarities to HCG subunits among chorionic gonadotropins of nonhuman primates.

Comparison of antigenic similarity between human chorionic gonadotropin (HCG) subunits and the chorionic gonadotropins of six species of nonhuman primates indicates marked similarity of antigenic determinants between both subunits of HCG and the chorionic gonadotropins of chimpanzees, gorillas, and orangutans. Antisera to HCG subunits (alpha or beta) did not cross-react with the chorionic gonadotropins of baboons, macaques, or marmosets. Because of the relative availability of chimpanzees for laboratory studies, we suggest that chimpanzees may be the optimal nonhuman primate model for determining the advisability of vaccinations in man using conjugates of HCG fragments to achieve fertility control or for suppression of HCG-producing neoplasms.     

Drugs derived from phage display: From candidate identification to clinical practice

Phage display, one of today’s fundamental drug discovery technologies, allows identification of a broad range of biological drugs, including peptides, antibodies and other proteins, with the ability to tailor critical characteristics such as potency, specificity and cross-species binding. Further, unlike in vivo technologies, generating phage display-derived antibodies is not restricted by immunological tolerance. Although more than 20 phage display-derived antibody and peptides are currently in late-stage clinical trials or approved, there is little literature addressing the specific challenges and successes in the clinical development of phage-derived drugs. This review uses case studies, from candidate identification through clinical development, to illustrate the utility of phage display as a drug discovery tool, and offers a perspective for future developments of phage display technology.     

Proteomic Insights into Endometrial Receptivity and Embryo‐Endometrial Epithelium Interaction for Implantation Reveal Critical Determinants of Fertility

In vitro fertilization has overcome infertility issues for many couples. However, achieving implantation of a viable embryo into the maternal endometrium remains a limiting step in optimizing pregnancy success. The molecular mechanisms which characterize the transient state of endometrial receptivity, critical in enabling embryo‐endometrial interactions, and proteins which underpin adhesion at the implantation interface, are limited in humans despite these temporally regulated processes fundamental to life. Hence, failure of implantation remains the “final frontier” in infertility. A human coculture model is utilized utilizing spheroids of a trophectoderm (trophoblast stem) cell line, derived from pre‐implantation human embryos, and primary human endometrial epithelial cells, to functionally identify “fertile” versus “infertile” endometrial epithelium based on adhesion between these cell types. Quantitative proteomics identified proteins associated with human endometrial epithelial receptivity (“epithelial receptome”) and trophectoderm adhesion (“adhesome”). As validation, key “epithelial receptome” proteins (MAGT‐1/CDA/LGMN/KYNU/PC4) localized to the epithelium of receptive phase (mid‐secretory) endometrium obtained from fertile, normally cycling women but is largely absent from non‐receptive (proliferative) phase tissues. Factors involved in embryo‐epithelium interaction in successive temporal stages of endometrial receptivity and implantation are demonstrated and potential targets for improving fertility are provided, enhancing potential to become pregnant either naturally or in a clinical setting.     

Effect of deltamethrin-incorporated nets on mobility and survivorship of Halyomorpha halys (Hemiptera: Pentatomidae) adults and nymphs in the laboratory

The brown marmorated stink bug, Halyomorpha halys Stål (Hemiptera: Pentatomidae), is an invasive pest that attacks specialty and row crops in North America and Europe. There has been a concerted effort to reduce frequent broad-spectrum insecticide applications made on vulnerable crops. One tool that has emerged recently is the use of long-lasting insecticide-treated nets (LLINs) as a killing agent. Here, we conducted bioassays to evaluate the effect of direct contact on deltamethrin-impregnated LLINs on the behaviour and survivorship of H. halys nymphs and adults in the laboratory. Following exposure at three different durations (1.25, 4.25 or 7.25 min), vertical and horizontal mobility of adults and nymphs and the flight capacity of adults were recorded and compared with individuals that were not exposed (control). Exposure to LLINs reduced the horizontal distance and velocity and increased the angular velocity of adults only but reduced vertical mobility of adults and nymphs. Adult flights were not significantly affected by LLIN exposure. Mortality of adults and nymphs at 7-day post-exposure ranged from 73% to 77% regardless of exposure time. We discuss our findings within the context of the potential for and limitations of deploying LLINs in vulnerable crops to manage H. halys populations.     

Metapopulation dynamics and foraging plasticity in a highly vagile seabird,the southern rockhopper penguin

Population connectivity is driven by individual dispersal potential and modulated by natal philopatry. In seabirds, high vagility facilitates dispersal yet philopatry is also common, with foraging area overlap often correlated with population connectivity. We assess the interplay between these processes by studying past and current connectivity and foraging niche overlap among southern rockhopper penguin colonies of the coast of southern South America using genomic and stable isotope analyses. We found two distinct genetic clusters and detected low admixture between northern and southern colonies. Stable isotope analysis indicated niche variability between colonies, with Malvinas/Falklands colonies encompassing the species entire isotopic foraging niche, while the remaining colonies had smaller, nonoverlapping niches. A recently founded colony in continental Patagonia differed in isotopic niche width and position with Malvinas/Falklands colonies, its genetically identified founder population, suggesting the exploitation of novel foraging areas and/or prey items. Additionally, dispersing individuals found dead across the Patagonian shore in an unusual mortality event were also assigned to the northern cluster, suggesting northern individuals reach southern localities, but do not breed in these colonies. Facilitated by variability in foraging strategies, and especially during unfavorable conditions, the number of dispersing individuals may increase and enhance the probability of founding new colonies. Metapopulation demographic dynamics in seabirds should account for interannual variability in dispersal behavior and pay special attention to extreme climatic events, classically related to negative effects on population trends.