Identification and characterization of the interactive proteins with cytotoxic T-lymphocyte antigen-2α

Cytotoxic T-lymphocyte antigen-2α (CTLA-2α) is a potent inhibitor of cathepsin L-like cysteine proteases. Recombinant CTLA-2α is known to be a potent, competitive inhibitor of cathepsin L-like cysteine proteases. In this study, cathepsin L, cathepsin C, and tubulointerstitial nephritis antigen-related protein 1 (TINAGL1) were identified as novel interactive proteins of CTLA-2α by the yeast two-hybrid screening system. The direct interactions and co-localization of these proteins with CTLA-2α were confirmed using co-immunoprecipitation and immunofluorescence staining, respectively. The disulfide-bonded CTLA-2α/cathepsin L complex was isolated from mouse tissue. CTLA-2α was found to be specific and consistently expressed on the maternal side of the mouse placenta. Double immunofluorescence analysis showed that CTLA-2α was co-localized with cathepsin L, cathepsin C, and TINAGL1 in placenta. A simple cell-based fluorescence assay revealed that CTLA-2α exhibited inhibitory activity toward cathepsin C in live cells, which indicated that CTLA-2α is a novel endogenous inhibitor of cathepsin C.     

Carbohydrate saving or biomass maintenance: which is the main determinant of the plant’s long-term submergence tolerance?

Photosynthesis Research - It is hypothesized that plant submergence tolerance could be assessed from the decline of plant biomass due to submergence, as biomass integrates all eco-physiological...     

Welcome to the Club?: A response to The Cross -Border Connection by Roger Waldinger

Roger Waldinger's provocative book on migrants’ cross-border lives corroborates many insights already established by transnational migration scholarship. He makes a compelling case for the need to understand migration not just as assimilation – neo, segmented, or otherwise – but also as about how people continue to be simultaneously involved in their homelands, the countries where they settle, and other salient places. I am glad that Waldinger has lent his voice to correct the unproductive divide between immigration and emigration scholarship. But the ‘new’ path he charts forward to right what he sees as wrong with current scholarship is, at times, so selectively formulated and argued that it undercuts its effectiveness.     

The mammary gland response to estradiol: monotonic at the cellular level, non-monotonic at the tissue-level of organization?

The role of hormones in mammary gland development has been studied in detail using surgical and genetic models. These studies have indicated roles for estrogen in ductal elongation and terminal end bud formation. However, no comprehensive study has quantified how different doses of estrogen affect morphological parameters of mammary gland development. Additionally, comparisons between the estrogen-responsiveness of the mammary gland and uterus, the model organ for estrogen action are incomplete. In this study, immature mice were ovariectomized and implanted with osmotic pumps releasing one of eight doses of 17β-estradiol for 10 days. As expected from the classical uterotrophic assay, the uterus showed a monotonic dose–response curve for all measured endpoints. In contrast, the mammary gland showed a non-monotonic, inverted-U shaped response to estrogen with regard to morphometric parameters, and a monotonic response with regard to gene expression parameters. These results indicate that estrogen has opposing effects in mammary gland morphogenesis depending on estrogen dose, i.e. low to moderate doses induce terminal end bud formation and ductal elongation while higher doses inhibit these processes. This non-monotonic dose–response in the mammary gland may reflect complex interactions, where estrogen can act on multiple targets either as an agonist or antagonist.     

Coordination, the determinant of velocity specificity?

Almåsbakk, Bjørn, and Jan Hoff. Coordination, thedeterminant of velocity specificity? J. Appl. Physiol.80(5): 2046-2052, 1996.Initial strength gains were examinedin the context of learning a new skill. Forty female volunteers wererandomly assigned to one of four groups: a bench-press training grouputilizing heavy loads in its training, a bench-press training grouputilizing almost no load, an alternative training group using different exercises, or a control group that did not train. Training period was 6 wk, with three training sessions per week. Emphasis was put on keepingthe coordination and muscular adaptation demands in the bench-pressgroups as invariant as possible. Bench-press training with a light orwith a heavy weight was shown to be equally effective in improving themaximal velocity of contraction for a given absolute resistance. Meanvelocity with loads of 0.37, 6.6, 16.6, and 20 kg improved by 21.1, 15.8, 16.9, and 19.5%, respectively. No significant differences in thepercent improvement at the four different loads were apparent,indicating that no significant velocity-specific adaptations werepresent. The bench-press training group, utilizing heavy loads in itstraining, was the only group with improved one repetition maximum.Overall, findings point to the development of coordination as thedetermining factor in early velocity-specific strength gains.

     

Is the response of aphids to alarm pheromone stable?

Aphid taxa are characterized by a number of biological features, such as their feeding behaviour and host selection, which it is generally accepted are affected by keeping them for several generations under standard conditions in a laboratory. Analyses of three strains of the green pea aphid, Acyrthosiphon pisum (Harris, 1776), reared in culture for long periods, indicate that other characters are also affected. For example, the response of these aphids to alarm pheromone is dramatically reduced. This raises an interesting question regarding the mechanism by which it occurs and has consequences when aphids from laboratory cultures are used for studies in ecology and applied biology and especially the long‐term effectiveness of crop plants genetically engineered to produce EBF as a means of controlling aphids.     

Predicting the potential impact of a cytotoxic T-lymphocyte HIV vaccine: how often should you vaccinate and how strong should the vaccine be?

To stimulate the immune system's natural defenses, a post-infection HIV vaccination program to regularly boost cytotoxic T-lymphocytes has been proposed. We develop a mathematical model to describe such a vaccination program, where the strength of the vaccine and the vaccination intervals are constant. We apply the theory of impulsive differential equations to show that the model has an orbitally asymptotically stable periodic orbit, with the property of asymptotic phase. We show that, on this orbit, the vaccination frequency can be chosen so that the average number of infected CD4(+) T cells can be made arbitrarily low. We illustrate the results with numerical simulations and show that the model is robust with respect to both the parameter choices and the formulation of the model as a system of impulsive differential equations.     

The search for the genetic contribution to autoimmune thyroid disease: the never ending story?

Unlocking the genetic contribution to autoimmune thyroid disease (AITD) will hold one of the keys to understanding disease pathogenesis and developing improved treatments. Significant increases in our understanding of the human genome combined with methodological advances in our ability to search for genetic variation have transformed the way in which we screen the genome for susceptibility loci. From early linkage analysis through to candidate gene studies and most recently genome-wide association screening, each methodology has revealed important insights into not just the heritability of AITD but also the best way of identifying disease causing DNA variants. This review will examine each of the different genome screening techniques, highlighting the successes and failures of each methodology and the lessons learnt which have helped inform the next phase of the disease-gene identification process. We will also look to see where we should be focusing our research efforts in the future.     

The immune response of allophenic mice to the synthetic polymer GLΦ

The immune response of allophenic mice of type C57BL/6(A × SJL) F₁ to GL administered in complete Freund's adjuvant was tested. Control mice of the three strains C57BL/6, A, and SJL are all nonresponders to this antigen. However, the F₁ generations of C57BL/6 × A, C57BL/6 × SJL, and A × SJL were all responders to the antigen, so that the complementarity of at least two genes is confirmed. The allophenic mice showed no further complementation beyond the F₁ generation, a result which may argue against the possibility that more than two genes control the response to GL in these mouse strains. Characterization of the allophenic mice over several months showed that they exhibit chimeric drift, both in their coat color and in peripheral white blood cell population. There is no apparent correlation of coat color to the lymphocyte composition of the mice at any one time. The mice are true chimeras, since killing of the two populations of white blood cells with two different anti-H-2 sera produced a 100 percent killing. The immune response of individual allophenic mice to GL showed a good correlation to the number of A × SJL lympho-cytes in the animal.Abbreviations used in this paper are GL an amino acid polymer of 57 %l-glutamic acid, 38%l-lysine, and 5%l-phenylalanine - GLT¹⁵ an amino acid polymer ofl-glutamic acid,l-lysine, and 15 %l-tyrosine - (T,G)-A-L an amino acid polymer having a polylysine backbone with side chains of polyd-l-alanine, terminating in short sequences of tyrosine and glutamic acid - GAT₁₀ an amino acid polymer of 60%l-glutamic acid, 30%l-alanine, and 10%l-tyrosine - GLA₅ an amino acid polymer of 57%l-glutamic acid, 38%l-lysine, and 5%l-alanine - DNP 2,4 dinitrophenyl - BGG bovine gamma globulin - FCS fetal calf serum - PWBC peripheral white blood cell - SWBC spleen white blood cell - T cell thymus-derived lymphocyte - B cell bone marrow-derived lymphocyte     

Childhood eczema: disease of the advantaged?

OBJECTIVE--To determine whether the increased prevalence of childhood eczema in advantaged socioeconomic groups is due to increased parental reporting. DESIGN--Comparison of parental reports of eczema with visible eczema recorded by medical officers during a detailed physical examination. SETTING--National birth cohort study. SUBJECTS--8279 children from England, Wales, and Scotland born during 3-9 March 1958 and followed up at the ages of 7, 11, and 16. MAIN OUTCOME MEASURES--Prevalence of eczema according to parental report compared with medical officer''s examination at the ages of 7, 11, and 16. RESULTS--Prevalence of both reported and examined eczema increased with rising social class at the ages of 7, 11, and 16 years. The point prevalence of examined eczema at age 7 was 4.8%, 3.6%, 3.6%, 2.4%, 2.2%, and 2.4% in social classes I, II, III non-manual, III manual, IV, and V respectively (chi 2 value for linear trend 12.6, P < 0.001). This trend persisted after adjustment for potential confounders such as region and family size and was not present for examined psoriasis or acne. CONCLUSIONS--Eczema is more prevalent among British schoolchildren in social classes I and II than those in lower classes. Exposures associated with social class are probably at least as important as genetic factors in the expression of childhood eczema.     

Disentangling the paradox of insect phenology: are temporal trends reflecting the response to warming?

The strength and direction of phenological responses to changes in climate have been shown to vary significantly both among species and among populations of a species, with the overall patterns not fully resolved. Here, we studied the temporal and spatial variability associated with the response of several insect species to recent global warming. We use hierarchical models within a model comparison framework to analyze phenological data gathered over 40 years by the Japan Meteorological Agency on the emergence dates of 14 insect species at sites across Japan. Contrary to what has been predicted with global warming, temporal trends of annual emergence showed a later emergence day for some species and sites over time, even though temperatures are warming. However, when emergence data were analyzed as a function of temperature and precipitation, the overall response pointed out an earlier emergence day with warmer conditions. The apparent contradiction between the response to temperature and trends over time indicates that other factors, such as declining populations, may be affecting the date phenological events are being recorded. Overall, the responses by insects were weaker than those found for plants in previous work over the same time period in these ecosystems, suggesting the potential for ecological mismatches with deleterious effects for both suites of species. And although temperature may be the major driver of species phenology, we should be cautious when analyzing phenological datasets as many other factors may also be contributing to the variability in phenology.     

The evolutionary basis of leaf senescence: method to the madness?

Recent studies on the differential expression of genes associated with leaf senescence support the long-standing interpretation of plant senescence as an organized, genetically controlled process. Sequence identities of genes that are differentially expressed in senescing leaves indicate roles in the salvage of nutrients. By considering this salvage function as the selected trait and the degeneration and death of the tissue a pleiotropic consequence of nutrient redistribution, the process of leaf senescence can be reconciled with evolutionary theories on the origins of senescence in animals.     

Does the response of the intestinal epithelium to keratinocyte growth factor vary according to the method of administration?

BACKGROUND: Keratinocyte growth factor (KGF) is a potent mitogen and may be of value for the treatment of conditions such as short bowel syndrome and chemotherapy-induced mucositis. However the most efficacious route and method of administration is unclear. METHODS: Rats maintained by total parenteral nutrition (TPN) were given KGF (1 mg/kg/rat/day, i.v.) infused continuously or as a once-daily injection. The same dose was also given s.c. to chow-fed rats. Changes in gut growth were assessed by measurement of wet weight, proliferation (vincristine induced metaphase arrest) and crypt branching index. Changes in gut hormone profile were also determined to examine if any trophic effects were mediated via this mechanism. RESULTS: KGF caused a 70-100% increase in wet weight of the stomach, small and large intestine of TPN-fed rats (P < 0.01) with no significant differences seen between the two methods of administration. The increase in metaphase counts was greatest in the stomach (about seven-fold P < 0.01), but was less pronounced in the distal small intestine and colon (about 50% increase). The trophic effect of KGF was much less prominent in orally-fed rats. Crypt branching index was significantly reduced by KGF in the proximal small intestine of TPN, but not orally-fed rats. Plasma gastrin, PYY, total glucagon, enteroglucagon and GLP-1 all increased by two-three-fold (all P < 0.01) in response to KGF whereas insulin levels fell by about 25% in the TPN group. CONCLUSIONS: The mitogenic action of KGF occurred predominantly in the stomach and proximal small intestine. Its efficacy was less pronounced in orally-fed animals, suggesting KGF may be of greatest benefit in conditions associated with lowered intestinal proliferation. Clinical trials of KGF can probably use single daily i.v. injections without reduction in efficacy.     

Is the cellular response to cigarette smoke predictive of the phenotypic variation of COPD?

The adverse health consequences of cigarette smoking are not limited to the lung but also include effects on multiple other organ systems that are exposed directly or indirectly to the hazardous gaseous and soluble compounds generated by burning tobacco. Cigarette smoking (CS) is a risk factor for many major diseases including chronic obstructive pulmonary disease (COPD), atherosclerosis, cerebral and coronary vascular diseases, hypertension, and many types of cancer. Within the diagnosis category of COPD, it is widely recognized that there is substantial phenotypic heterogeneity with respect to both pulmonary and extrapulmonary manifestations. To understand the variability in responses to CS, it becomes essential to decipher the involved mechanisms at a cellular and molecular level that contribute to cigarette-related pathology. In this issue of the Journal, there are three papers (1, 4, 6) that provide insight regarding the molecular pathogenesis of CS-related COPD that could be related to phenotypic variation, by examining three classes of cell types of lung: endothelial cells, epithelial cells, and immune effector cells.