Antibody responses to galectin-8, TARP and TRAP1 in prostate cancer patients treated with a GM-CSF-secreting cellular immunotherapy

A critical factor in clinical development of cancer immunotherapies is the identification of tumor-associated antigens that may be related to immunotherapy potency. In this study, protein microarrays containing >8,000 human proteins were screened with serum from prostate cancer patients (N = 13) before and after treatment with a granulocyte–macrophage colony-stimulating factor (GM-CSF)-secreting whole cell immunotherapy. Thirty-three proteins were identified that displayed significantly elevated (P ≤ 0.05) signals in post-treatment samples, including three proteins that have previously been associated with prostate carcinogenesis, galectin-8, T-cell alternative reading frame protein (TARP) and TNF-receptor-associated protein 1 (TRAP1). Expanded analysis of antibody induction in metastatic, castration-resistant prostate cancer (mCRPC) patients (N = 92) from two phase 1/2 trials of prostate cancer immunotherapy, G-9803 and G-0010, indicated a significant (P = 0.03) association of TARP antibody induction and median survival time (MST). Antibody induction to TARP was also significantly correlated (P = 0.036) with an increase in prostate-specific antigen doubling time (PSADT) in patients with a biochemical (PSA) recurrence following prostatectomy or radiation therapy (N = 19) from in a previous phase 1/2 trial of prostate cancer immunotherapy, G-9802. RNA and protein encoding TARP and TRAP1 was up-regulated in prostate cancer tissue compared to matched normal controls. These preliminary findings suggest that antibody induction to TARP may represent a possible biomarker for treatment response to GM-CSF secreting cellular immunotherapy in prostate cancer patients and demonstrates the utility of using protein microarrays for the high-throughput screening of patient-derived antibody responses.     

The Empirical Analysis of Cigarette Tax Avoidance and Illicit Trade in Vietnam, 1998-2010

Illicit trade carries the potential to magnify existing tobacco-related health care costs through increased availability of untaxed and inexpensive cigarettes. What is known with respect to the magnitude of illicit trade for Vietnam is produced primarily by the industry, and methodologies are typically opaque. Independent assessment of the illicit cigarette trade in Vietnam is vital to tobacco control policy. This paper measures the magnitude of illicit cigarette trade for Vietnam between 1998 and 2010 using two methods, discrepancies between legitimate domestic cigarette sales and domestic tobacco consumption estimated from surveys, and trade discrepancies as recorded by Vietnam and trade partners. The results indicate that Vietnam likely experienced net smuggling in during the period studied. With the inclusion of adjustments for survey respondent under-reporting, inward illicit trade likely occurred in three of the four years for which surveys were available. Discrepancies in trade records indicate that the value of smuggled cigarettes into Vietnam ranges from $100 million to $300 million between 2000 and 2010 and that these cigarettes primarily originate in Singapore, Hong Kong, Macao, Malaysia, and Australia. Notable differences in trends over time exist between the two methods, but by comparison, the industry estimates consistently place the magnitude of illicit trade at the upper bounds of what this study shows. The unavailability of annual, survey-based estimates of consumption may obscure the true, annual trend over time. Second, as surveys changed over time, estimates relying on them may be inconsistent with one another. Finally, these two methods measure different components of illicit trade, specifically consumption of illicit cigarettes regardless of origin and smuggling of cigarettes into a particular market. However, absent a gold standard, comparisons of different approaches to illicit trade measurement serve efforts to refine and improve measurement approaches and estimates.     

Diet of the Indochinese silvered langur (Trachypithecus germaini) in Kien Luong Karst area,Kien Giang Province

The Indochinese silvered langur (Trachypithecus germaini) is distributed to the west of Mekong River in Cambodia, Lao PDR, Thailand and Vietnam. During a two‐year study, from May 2014 to May 2016, we collected 320.44 hr of behavior, with 17,040 feeding bouts recorded (142 hr) for T. germaini on Chua Hang Karst Mountain, Kien Luong District, Kien Giang Province, Vietnam. Feeding accounted for 45% of the Indochinese silvered langurs’ activity budget. The plant diet of the Indochinese silvered langurs was principally composed of young leaves (58%), followed by mature leaves (9.5%), fruits (22.7%), flowers (4.7%), buds (3.3%), petioles (1.2%), and other (0.5%). A total of 58 plant species were fed on by the silvered langurs, and leaves of eight species (Phyllathus reticulatus, Ficus rumphii, Ficus tinctoria, Ficus microcarpa, Cayratia trifolia, Streblus ilicifolia, Combretum latifolium, and Streblus asper) were fed on throughout the year. P. reticulatus was most frequently eaten (13.9% feeding time, n = 1,733). Food selection differed significantly between months and seasons. The Indochinese silvered langurs ate 27 plant species in the wet season compared with 23 plant species in the dry season. Leaf chemical composition of two food categories, 16 eaten species (with 10 most frequently consumed species and six least consumed species), and four noneaten species, were analyzed. Feeding samples from eaten species in the Indochinese silvered langurs's diet contained lower amounts of condensed tannin, lignin, protein, ash, and lipids, but a higher amount of total sugar compared with samples from noneaten species. Furthermore, the most frequently consumed species contained lower amounts of lignin compared with the less frequently consumed species. Using a generalized linear model with five variables, including neutral detergent fiber (NDF), total sugar, lignin, lipid, and calcium (Ca) indicated that NDF positively correlated and lignin content negatively correlated with feeding records in the diet of these langur.     

l-Phenylalanyl-l-Glutamate-Stimulated, Chloride-Dependent Glutamate Binding Represents Glutamate Sequestration Mediated by an Exchange System

Stimulation of glutamate binding by the dipeptide L-phenylalanyl-L-glutamate (Phe-Glu) was inhibited by the peptidase inhibitor bestatin, suggesting that the stimulation was caused by glutamate liberated from the dipeptide and not by the dipeptide itself. It further suggests that this form of glutamate binding should be reinterpreted as glutamate sequestration and that stimulation of binding both by dipeptides and after preincubation with high concentrations of glutamate is likely to be due to counterflow accumulation. Several other criteria indicate that most of glutamate binding stimulated by chloride represents glutamate sequestration: Binding is reduced when the osmolarity of the incubation medium is increased, when membranes incubated with [3H]glutamate are lysed before filtration, and when membranes are made permeable by transient exposure to saponin. Moreover, dissociation of bound glutamate after a 100-fold dilution of the incubation medium is accelerated about 50 times by the addition of glutamate to the dilution medium. This result would be anomalous if glutamate were bound to a receptor site; it suggests instead that glutamate is transported in and out of membrane vesicles by a transport system that preferentially mediates exchange between internal and external glutamate. Glutamate binding contains a component of glutamate sequestration even when measured in the absence of chloride. Sequestration is adequately abolished only after treating membranes with detergents; even extensive lysis, sonication, and freezing/thawing may be insufficient.     

Cysteine: Depolarization-Induced Release from Rat Brain In Vitro

Compounds released on depolarization in a Ca2+-dependent manner from rat brain slices were screened to identify candidates for neuroactive substances. Lyophilized superfusates were analyzed by reversed-phase HPLC after derivatization with 9-fluorenyl N-succinimidyl carbonate. One of the compounds that showed an increase of concentration in superfusates in the presence of iodoacetamide was identified as the cysteine (Cys) derivative, S-carboxamidomethylcysteine, by fast atom bombardment mass spectrometry and other methods. This stable Cys derivative originates from endogenous, extracellular Cys. The finding led to a method for quantification of Cys in superfusates by immediate cooling of the superfusates to 0 degrees C and reaction of Cys with N-ethylmaleimide. Depolarization-induced Ca2+-dependent release of Cys was most prominent in the neocortex, followed by the mesodiencephalon, striatum, and cerebellum. This suggests that Cys is released from a neuronal compartment and might be involved in neurotransmission.     

Distinct functional roles of the two intracellular phosphatase like domains of the receptor-linked protein tyrosine phosphatases LCA and LAR.

Protein tyrosine phosphorylation is regulated by both protein tyrosine kinases and protein tyrosine phosphatases (PTPases). Recently, the structures of a family of PTPases have been described. In order to study the structure-function relationships of receptor-linked PTPases, we analyzed the effects of deletion and point mutations within the cytoplasmic region of the receptor-linked PTPases, LCA and LAR. We show that the first of the two domains has enzyme activity by itself, and that one cysteine residue in the first domain of both LCA and LAR is absolutely required for activity. The second PTPase like domains do not have detectable catalytic activity using a variety of substrates, but sequences within the second domains influence substrate specificity. The functional significance of a stretch of 10 highly conserved amino acid residues surrounding the critical cysteine residue located in the first domain of LAR was assessed. At most positions, any substitution severely reduced enzyme activity, while missense mutations at the other positions tested could be tolerated to varying degrees depending on the amino acid substitution. It is suggested that this stretch of amino acids may be part of the catalytic center of PTPases.     

昆虫分子生物学的一些研究进展：生物钟的基因

昆虫分子生物学的一些研究进展：生物钟的基因翟启慧（中国科学院动物研究所北京１０００８０）生物的许多行为和生理现象有周期性波动,称为生物节律或生物钟。长期以来,这是一个十分吸引人却又难以理解的问题。虽然有大量文献描述生物钟的现象,但对其机理却一无所知。...     

Cultivation and carrageenan yield and quality ofKappaphycus alvarezii in the waters of Vietnam

The carrageenan-producing red algaKappaphycus alvarezii (Doty) Doty was brought to Vietnam from Japan in 1993. Branch fragments of this species were cultivated in a pond, lagoon, inlet and offshore in Vietnam for the first time. The best daily growth rate (DGR) of plants grown in the lagoon area attained 9–11 % day^–1 in May to June (cold season). The water temperature and salinity in this area ranged from 27.2–32.4 °C and 31.4–33.7 °C, respectively. DGR of plants grown in the inlet ranged from 7 to 9% day^–1 in June. Grazing by fish has been observed to occur in this area. The DGR of plants grown in the pond ranged from 5–6% in January–July, but decreased to less than 4% day^–1 in August (hot season). K. alvarezii in Vietnam showed a carrageenan yield of 18.8–24.6% and gel strength of 1566–1712 g cm^–2. These values are similar ones obtained fromK. alvarezii cultivated in the Philippines and Indonesia.