Traveling waves in cross-diffusion models of population dynamics

"Traveling wave"--type solutions of some models with cross-diffusion were considered. It was shown that "cross-diffusion" terms, as opposed to "diffusion" terms, do not increase the dimensionality of the automodel system. The bifurcation approach was used to study the dependence of the wave solutions on the parameters of the models being considered, and the waves were classified. It was shown that, at the same parameter values, both "fast" and "slow" waves can exist and that these waves are described by different automodel systems.     

关于“弱激光血管内照射疗法”的几个问题

本文从：１．关于“弱激光血管内照射疗法（ＩｎｔｒａｖａｃｕｌａｒＬｏｗ－Ｒｅａｃｔｉｏｎ－ｌｅｖｅｌＬａｓｅｒＩｒｒａｄｉａｔｉｏｎＴｈｅｒａｐｙＩＬＬＬＴ）的中、英文名称问题。２．该疗法引入我国的历史回顾。３．该疗法的临床效果与基础研究。４．该疗法与光量子疗法（ＵＢＩ）的比较。５．该疗法在我国面临的问题及展望等五个方面以较详实的材料对以Ｈｅ—Ｎｅ激光为代表的弱激光血管内照射疗法客观地进行阐述,并以笔者的研究实践及其认识为基础提出看法以期探讨,从而澄清目前国内对该疗法尚存在的某些混乱状况与模糊认识,使其作为弱激光的一种很有前途的临床疗法能走上健康发展的道路。     

Reflections on Ernst Mayr's This is Biology

In this essay I argue that Ernst Mayr's idea that the emergence of evolutionary biology in Western thought was delayed by the pernicious influence of the false ideologies of Platonism, Christianity, and physicalism is ahistorical and anti-evolutionary, that similar ideas, especially his antipathy to physicalism, prejudice his account of the transformation of natural history and medical science into biology, that his organicist resolution of the perennial conflict between mechanism and vitalism is an unstable compound of semi-holism and semi-mechanism, that his conception of biology as the true bridge between the sciences and the humanities, ethics, and social theory is open to question (especially as to the adequacy of the theory of natural selection to account for every aspect of human nature), and that his depiction of science as the sovereign key to understanding everything known to exist or happen in this universe cannot be justified at the bar of reason.     

不同超级杂交稻组合期剑叶14C-同化物的转运及分配与早衰关系的研究

选取具有不同早衰特性的超级杂交稻组合两优培九、Y两优1号和培两优E32为供试材料,借助14C同位素示踪技术对其不同生育期剑叶14C同化物分配及转化进行了研究。结果表明:随着生育期的推进,剑叶(源)同化物向穗中(库)的转运比例逐渐增加,在供试组合中以两优培九分配效率最高,Y两优1号次之,培两优E32最低;剑叶14C-同化物在供试组合中的转运能力也有类似的趋势,在3个超级杂交稻组合中,以两优培九"源、库、流"的协调性最好,Y两优1号次之,培两优E32最差。     

Invasive Non-Typhoidal Salmonella Typhimurium ST313 Are Not Host-Restricted and Have an Invasive Phenotype in Experimentally Infected Chickens

Salmonella enterica serovar Typhimurium Sequence Type (ST) 313 is a major cause of invasive non-Typhoidal salmonellosis in sub-Saharan Africa. No animal reservoir has been identified, and it has been suggested that ST313 is adapted to humans and transmission may occur via person-to-person spread. Here, we show that ST313 cause severe invasive infection in chickens as well as humans. Oral infection of chickens with ST313 isolates {"type":"entrez-nucleotide","attrs":{"text":"D23580","term_id":"427513","term_text":"D23580"}}D23580 and Q456 resulted in rapid infection of spleen and liver with all birds infected at these sites by 3 days post-infection. In contrast, the well-defined ST19 S. Typhimurium isolates F98 and 4/74 were slower to cause invasive disease. Both ST19 and ST313 caused hepatosplenomegaly, and this was most pronounced in the ST313-infected animals. At 3 and 7 days post-infection, colonization of the gastrointestinal tract was lower in birds infected with the ST313 isolates compared with ST19. Histological examination and expression of CXCL chemokines in the ileum showed that both {"type":"entrez-nucleotide","attrs":{"text":"D23580","term_id":"427513","term_text":"D23580"}}D23580 (ST313) and 4/74 (ST19) strains caused increased CXCL expression at 3 days post-infection, and this was significantly higher in the ileum of {"type":"entrez-nucleotide","attrs":{"text":"D23580","term_id":"427513","term_text":"D23580"}}D23580 vs 4/74 infected birds. At 7 days post-infection, reduced chemokine expression occurred in the ileum of the {"type":"entrez-nucleotide","attrs":{"text":"D23580","term_id":"427513","term_text":"D23580"}}D23580 but not 4/74-infected birds. Histological analysis showed that {"type":"entrez-nucleotide","attrs":{"text":"D23580","term_id":"427513","term_text":"D23580"}}D23580 infection resulted in rapid inflammation and pathology including villous flattening and fusion at 3 days post-infection, and subsequent resolution by 7 days. In contrast, 4/74 induced less inflammation and pathology at 3 days post-infection. The data presented demonstrate that ST313 is capable of causing invasive disease in a non-human host. The rapid invasive nature of infection in the chicken, coupled with lower gastrointestinal colonization, supports the hypothesis that ST313 is a distinct pathovariant of S. Typhimurium that has evolved to become a systemic pathogen that can cause disease in several hosts.     

Putting density dependence in perspective: nest density, nesting phenology, and biome, all matter to survival of simulated mallard Anas platyrhynchos nests

Breeding success in ground-nesting birds is primarily determined by nest survival, which may be density-dependent, but the generality of this pattern remains untested. In a replicated crossover experiment conducted on 30 wetlands, survival of simulated mallard nests was related to "biome" (n=14 mediterranean and 16 boreal wetlands), breeding "phenology" (early vs late nests), and "density" (2 vs 8 nests per 225 m shoreline). Local abundances of "waterfowl", "other waterbirds", and "avian predators" were used as covariates. We used an information-theoretic approach and Program MARK to select among competing models. Nest survival was lower in late nests compared with early ones, and it was lower in the mediterranean than in the boreal study region. High-density treatment nests suffered higher depredation rates than low-density nests during days 1–4 of each experimental period. Nest survival was negatively associated with local abundance of "waterfowl" in the boreal but not in the mediterranean biome. Effect estimates from the highest-ranked model showed that nest "density" (d 1–4) had the strongest impact on model fit; i.e. three times that of "biome" and 1.5 times that of "phenology". The latter's effect, in turn, was twice that of "biome". We argue that our study supports the idea that density-dependent nest predation may be temporally and spatially widespread in waterfowl. We also see an urgent need for research of how waterfowl nesting phenology is matched to that of prey and vegetation.     

The endocrine cells of the rectum of adult ox.

In order to identify the endocrine cell types in various parts of the Ruminant gut, we have applied ultrastructural, both morphological and cytochemical, techniques, in parallel to the histochemical ones, to study the rectal mucosa of the adult Ox. In these studies we show that: "EC" cells, of the intestinal type, contain predominantly pleiomorphic granules, which are very electron dense and heavily reactive to "Masson" and "Grimelius" methods; "L" cells are recognizable by their numerous granules, which are fairly homogeneous in shape and osmiophilia. They do not react with "Masson" and are weak or negative to Grimelius s reaction. These granules occur near to others that are less dense, unreactive to "Masson", and that contain an argyrophilic matrix, with an eccentric electron dense core, which does not react with silver; "F-like" cells contain granules which are variable in shape, size and osmiophilia. They are unreactive to "Masson" and weak or unreactive to Grimelius silver; "H" cells contain few, small and uniformly osmiophilic granules. These are unreactive to "Masson" and uniformly reactive to "Grimelius". Our data suggest that the morphology, frequency and distribution of the cell types we have identified in the mucosa of the bovine rectum correspond with those reported in large intestine and rectum of Monogastrics, as by other authors described.     

Again on language of biology]

Some time ago I proposed in an Editorial in this journal some considerations on the language of biology. I concluded that, to realize an autonomy of such a language (and therefore of biology), we have to develop a valid language for biology. In such a context, it seemed to me that the term "metaphors" referred to the concepts concerning the information carried by genetic code, was a reasonable one. However, Barbieri's article in this issue of Rivista di Biologia / Biology Forum calls for a reply. Of course, we do not know very much in this field, even if we have some evidence that a sequence of bases on a DNA is not determined only by chance. In any case we can exclude that nature in this occasion has "invented" a code. Nature doesn't "invent" anything: it only follows its rules, that we name "laws of nature". Barbieri quotes the Morse code, but forgets to say that such a code is "conventional" in the sense that it is valid only because it is the result of an "agreement" between Morse and the users of that code. There is nothing more unnatural than a "code": with whom nature should actually have to "reach an agreement"? As a matter of fact, we interpret as "information" what happens by law of nature. Also Barbieri's thesis that genes and proteins are molecular artifacts, assembled by external agents, whereas generally molecules are determined by their bonds, i.e. by internal factors, is a disputable one. It is examined how much an external structure plays a role in ordinary chemical reactions. The "information" of physics is not a semantic information. For such information we can refer to history of literature, telegraphic offices, genetics or biochemistry.     

Recruitment of beta-2-glycoprotein 1 to cell surfaces in extrinsic and intrinsic apoptosis

Apoptotic cells and phagocytes have developed a diverse array of distinct ligand-receptor systems that drive the recognition and uptake of dying cells. Phagocytes recognize apoptotic cells either directly, by binding to specific ligands at their cell surface, or indirectly, by binding to bridging proteins that bind these ligands. Previous observations showed that the plasma bridging protein 2GP1, binds PS containing vesicles, and enhances their binding and engulfment by phagocytes in vitro. In this study we show that apoptotic cells injected intravenously and intraperitonealy into syngeneic mice recruited the PS binding protein, 2GP1. Examination of peritoneal exudates and spleen thin sections showed that only the injected apoptotic cells picked up endogenous 2GP1. Recovery of cells from the peritoneum showed that apoptotic cells bearing 2GP1 were clustered around host peritoneal phagocytes. In addition, tissue sections from mice injected with Fas antibody showed colocalization of 2GP1 with TUNEL-positive apoptotic cells. These results provide evidence that endogenous 2GP1 binds apoptotic cells in vivo, suggesting that the protein plays an important physiologic role in the recognition of dying cells.     

The Endoplasmic Reticulum Chaperone BiP/GRP78 Is Important in the Structure and Function of the Human Cytomegalovirus Assembly Compartment

We previously demonstrated that the endoplasmic reticulum (ER) chaperone BiP functions in human cytomegalovirus (HCMV) assembly and egress. Here, we show that BiP localizes in two cytoplasmic structures in infected cells. Antibodies to the extreme C terminus, which includes BiP''s KDEL ER localization sequence, detect BiP in regions of condensed ER near the periphery of the cell. Antibodies to the full length, N terminus, or larger portion of the C terminus detect BiP in the assembly compartment. This inability of C-terminal antibodies to detect BiP in the assembly compartment suggests that BiP''s KDEL sequence is occluded in the assembly compartment. Depletion of BiP causes the condensed ER and assembly compartments to dissociate, indicating that BiP is important for their integrity. BiP and pp28 are in association in the assembly compartment, since antibodies that detect BiP in the assembly compartment coimmunoprecipitate pp28 and vice versa. In addition, BiP and pp28 copurify with other assembly compartment components on sucrose gradients. BiP also coimmunoprecipitates TRS1. Previous data show that cells infected with a TRS1-deficient virus have cytoplasmic and assembly compartment defects like those seen when BiP is depleted. We show that a fraction of TRS1 purifies with the assembly compartment. These findings suggest that BiP and TRS1 share a function in assembly compartment maintenance. In summary, BiP is diverted from the ER to associate with pp28 and TRS1, contributing to the integrity and function of the assembly compartment.Human cytomegalovirus (HCMV), the largest of the human herpesviruses, is capable of encoding over 200 proteins, which are expressed in temporal fashion as immediate-early, early, delayed-early, and late genes. Despite the extensive coding capacity of HCMV, its replication cycle is slow. During this protracted period, the virus must maintain optimal replication conditions in the host cell. However, the increasing strain of the infection induces cellular stress responses with consequences that may be deleterious to the progress of the infection. We and others have previously shown that HCMV has multiple mechanisms to deal with the deleterious aspects of cellular stress responses while maintaining beneficial ones (2, 8-10, 14, 17, 18, 22-24, 26, 27, 50, 51).An example of these mechanisms is the viral control of endoplasmic reticulum (ER) stress and the unfolded protein response (UPR). Due to the number of HCMV proteins that are glycosylated, or receive other ER-dependent posttranslational modifications, the load of proteins in the ER can exceed its capacity, resulting in ER stress and the activation of the UPR (18, 47, 51). However, we and others have shown that HCMV controls and modulates the UPR, maintaining aspects that may benefit the viral infection while inhibiting aspects that would be detrimental (18, 51).The UPR is normally controlled by transmembrane sensors which initiate the complex UPR signaling cascade when activated by ER stress (reviewed in references 20, 35, 38, and 52). The ER molecular chaperone BiP (immunoglobulin heavy chain-binding protein), also called glucose-regulated protein 78 (GRP78), is believed to bind these sensors and keep them inactive during unstressed conditions. However, when unfolded or misfolded proteins accumulate in the ER, BiP leaves these sensors to perform its chaperone function, thus allowing the sensors to activate UPR signaling. We have previously shown that during HCMV infection, BiP is vastly overproduced (8), suggesting that BiP may have other functions in the viral infection. Indeed, it has been shown that BiP binds to the viral proteins US2 and US11; this interaction is necessary for the virus-mediated degradation of major histocompatibility complex class I and II (15, 47). Further, we have shown that depletion of BiP, using either the BiP-specific subtilase cytotoxin SubAB (32) or short hairpin RNAs, caused infectious virion formation in the cytoplasm to cease and nucleocapsids to accumulate just outside the outer nuclear membrane (8). This result suggested that BiP has a significant role in virion formation and cytoplasmic egress.Although the exact mechanism of virion formation in the cytoplasm is not well understood, studies have identified a perinuclear structure, referred to as the cytoplasmic assembly compartment, that is involved in the process. Several viral proteins, for example, tegument proteins (pp28, pp65) (36) and viral glycoproteins (gB, gH, gL, gO, gp65) (36, 46), have been identified as part of this structure. Defining the exact origin of this compartment has been complicated by the observation of specific organellar markers in and around the compartment, while other markers of the same organelles are not detected. For example, immunofluorescence examination suggests that the early endosomal marker early endosome antigen 1 (EEA1) has been observed in the center of the assembly compartment (12, 13); however, Rab4 and Rab5, other early endosomal markers, were not detected (16). Such observations suggest that the virus directs specific viral and cellular proteins to the assembly compartment as needed for assembly compartment function.In the present study, we further examine the role of BiP during an HCMV infection, including its localization and interactions with other proteins. We show here that in infected cells, BiP localizes in two distinct structures, regions of condensed ER near the periphery of the cell and the assembly compartment. The data suggest that BiP diversion from the ER to the assembly compartment is due to occlusion of its ER localization signal. Depletion of BiP causes both condensed ER and assembly compartments to disperse, indicating that BiP is important for their formation or maintenance. BiP and pp28 appear to associate in the assembly compartment, since BiP from the assembly compartment coimmunoprecipitates pp28 and vice versa. In addition, both BiP and pp28 copurify with the assembly compartment on sucrose gradients. BiP also coimmunoprecipitates TRS1. Previous studies (1, 4) have shown that cells infected with HCMV with a mutation in the TRS1 gene show cytoplasmic and assembly compartment defects like those seen when BiP is depleted (reference 8 and the studies presented below). We show that a fraction of TRS1 purifies with the assembly compartment, indicating a shared assembly compartment function with BiP. In summary, our data suggest that BiP is diverted from the ER to associate with pp28 and TRS1, contributing to the integrity and function of the assembly compartment.     

B Cell Receptor-induced Phosphorylation of Pyk2 and Focal Adhesion Kinase Involves Integrins and the Rap GTPases and Is Required for B Cell Spreading

Signaling by the B cell receptor (BCR) promotes integrin-mediated adhesion and cytoskeletal reorganization. This results in B cell spreading, which enhances the ability of B cells to bind antigens and become activated. Proline-rich tyrosine kinase (Pyk2) and focal adhesion kinase (FAK) are related cytoplasmic tyrosine kinases that regulate cell adhesion, cell morphology, and cell migration. In this report we show that BCR signaling and integrin signaling collaborate to induce the phosphorylation of Pyk2 and FAK on key tyrosine residues, a modification that increases the kinase activity of Pyk2 and FAK. Activation of the Rap GTPases is critical for BCR-induced integrin activation as well as for BCR- and integrin-induced reorganization of the actin cytoskeleton. We now show that Rap activation is essential for BCR-induced phosphorylation of Pyk2 and for integrin-induced phosphorylation of Pyk2 and FAK. Moreover Rap-dependent phosphorylation of Pyk2 and FAK required an intact actin cytoskeleton as well as actin dynamics, suggesting that Rap regulates Pyk2 and FAK via its effects on the actin cytoskeleton. Importantly B cell spreading induced by BCR/integrin co-stimulation or by integrin engagement was inhibited by short hairpin RNA-mediated knockdown of either Pyk2 or FAK expression and by treatment with PF-431396, a chemical inhibitor that blocks the kinase activities of both Pyk2 and FAK. Thus Pyk2 and FAK are downstream targets of the Rap GTPases that play a key role in regulating B cell morphology.Antibodies (Abs)² made by B lymphocytes play a critical role in host defense against infection. Antigen-induced signaling by the B cell receptor (BCR) initiates an activation program that leads to B cell proliferation and subsequent differentiation into Ab-producing cells. BCR clustering by antigens or by anti-immunoglobulin (anti-Ig) Abs used as surrogate antigens initiates multiple signaling pathways that control gene expression, cell survival, and proliferation pathways (1–3).BCR signaling also promotes integrin activation (4, 5), localized actin polymerization, reorganization of the actin cytoskeleton, and changes in B cell morphology (6, 7), all of which may facilitate B cell activation. Integrin activation and cell spreading is critical for the activation of B cells by membrane-bound antigens. Macrophages, dendritic cells, and follicular dendritic cells can present arrays of captured antigens to B cells (8, 9), and this may be one of the main ways in which B cells encounter antigens (10). BCR-induced integrin activation prolongs the interaction between the B cell and the antigen-presenting cell and also allows the B cell to spread on the surface of the antigen-presenting cell such that more BCRs can encounter and bind membrane-bound antigens (11). Subsequent contraction of the B cell membrane allows the B cells to gather the BCR-bound antigen into an immune synapse in which clustered antigen-engaged BCRs are surrounded by a ring of ligand-bound integrins. Formation of this immune synapse reduces the amount of antigen that is required for B cell activation (12, 13).Recent work has shown that B cells in lymphoid organs may contact soluble antigens by extending membrane processes into a highly organized network of lymph-filled conduits (14). These conduits are created by fibroblastic reticular cells that partially ensheathe collagen fibrils. In addition to being rich in collagen, fibronectin, and other extracellular matrix (ECM) components, the fibroblastic reticular cells that form these conduits express high levels of intercellular adhesion molecule-1, the ligand for the α_Lβ₂ integrin (lymphocyte function-associated antigen-1 (LFA-1)) on B cells (10). Thus B cells interacting with these conduits are likely to be in contact with integrin ligands, and integrin-dependent spreading may enhance the ability of B cells to extend membrane processes into the fibroblastic reticular cell conduit.In addition to promoting cell spreading, integrins can act as co-stimulatory receptors that enhance signaling by many receptors including the T cell receptor and the BCR (15–17). Thus signaling proteins that regulate B cell spreading and that are also targets of BCR/integrin co-stimulation may play a key role in the activation of B cells by membrane-bound antigens as well as soluble antigens that are delivered to lymphoid organs by fibroblastic reticular cell conduits.Proline-rich tyrosine kinase (Pyk2) and focal adhesion kinase (FAK) are related non-receptor protein-tyrosine kinases that integrate signals from multiple receptors and play an important role in regulating cell adhesion, cell morphology, and cell migration in many cell types (18–20). Integrins, receptor tyrosine kinases, antigen receptors, and G protein-coupled chemokine receptors all stimulate tyrosine phosphorylation of Pyk2 and FAK, a modification that increases the enzymatic activity of these kinases and allows them to bind SH2 domain-containing signaling proteins (21). FAK, which is expressed in almost all tissues (21), is a focal adhesion component that mediates integrin-dependent cell migration (22), cell spreading, and cell adhesion (18) in adherent cells as well as co-clustering of LFA-1 with the T cell receptor in lymphocytes (23). Pyk2 is expressed mainly in hematopoietic cells, osteoclasts, and the central nervous system (24) and is critical for chemokine-induced migration of B cells, macrophages, and natural killer cells (20, 25, 26) as well as the spreading of osteoclasts on vitronectin (27). FAK and Pyk2 are thought to mediate overlapping but distinct functions because Pyk2 expression only partially reverses the cell adhesion and migration defects in FAK-deficient fibroblasts (28).In B cells, clustering of the BCR, β₁ integrins, or β₇ integrins induces tyrosine phosphorylation of both Pyk2 and FAK (29–33). FAK is involved in the chemokine-induced adhesion of B cell progenitors (34), and Pyk2 is required for chemokine-induced migration of mature B cells (25). However, the role of these kinases in BCR- and integrin-induced B cell spreading has not been investigated, and the signaling pathways that link the BCR and integrins to tyrosine phosphorylation of Pyk2 and FAK have not been elucidated.We have shown previously that the ability of the BCR to induce integrin activation, B cell spreading, and immune synapse formation requires activation of the Rap GTPases (6, 17). In addition to binding effector proteins such as RapL and Rap1-interacting adaptor molecule (RIAM) that promote integrin activation (35–37), the active GTP-bound forms of Rap1 and Rap2 bind multiple proteins that control actin dynamics and cell morphology (38). Moreover we showed that BCR/integrin-induced phosphorylation of Pyk2 in B cells is dependent on Rap activation (17). However, this previous study did not address how Rap-GTP links the BCR and integrins to Pyk2 phosphorylation, whether Rap activation is important for FAK phosphorylation in B cells, or whether B cell spreading is regulated by Pyk2 or FAK. We now show that Pyk2 and FAK are differentially expressed and localized in B cells, that Pyk2 and FAK are important for B cell spreading, and that integrin engagement enhances BCR-induced phosphorylation of Pyk2 and FAK, a process that depends on both Rap activation and actin dynamics.     

Is there anything "autonomous" in the nervous system?

The terms "autonomous" or "vegetative" are currently used to identify one part of the nervous system composed of sympathetic, parasympathetic, and gastrointestinal divisions. However, the concepts that are under the literal meaning of these words can lead to misconceptions about the actual nervous organization. Some clear-cut examples indicate that no element shows "autonomy" in an integrated body. Nor are they solely "passive" or generated "without mental elaboration." In addition, to be "not consciously controlled" is not a unique attribute of these components. Another term that could be proposed is "homeostatic nervous system" for providing conditions to the execution of behaviors and maintenance of the internal milieu within normal ranges. But, not all homeostatic conditions are under the direct influence of these groups of neurons, and some situations clearly impose different ranges for some variables that are adaptative (or hazardous) in the tentative of successfully coping with challenging situations. Finally, the name "nervous system for visceral control" emerges as another possibility. Unfortunately, it is not only "viscera" that represent end targets for this specific innervation. Therefore, it is commented that no quite adequate term for the sympathetic, parasympathetic, and gastrointestinal divisions has already been coined. The basic condition for a new term is that it should clearly imply the whole integrated and collaborative functions that the components have in an indivisible organism, including the neuroendocrine, immunological, and respiratory systems. Until that, we can call these parts simply by their own names and avoid terms that are more "convenient" than appropriate.     

Raising consciousness in ecosystem health

New knowledge and theory developed by physicists in the first half of the 20th century radically changed our concepts of the nature of reality and the place of the human species in it. This information has not yet penetrated the other natural sciences nor day-to-day life. This paper argues that it is essential that we leave behind the World as Machine world view, or paradigm, which has led us to global crisis. Instead we must more rapidly incorporate the information from the 20th century new physics, and shift the dominant social paradigm to a Systems view of the world, in our efforts towards defining and implementing ecosystem health and the closely-related sustainable development. Some of the key implications of new physics to ecosystem health are that the biosphere and the surrounding universe is an indivisible whole; that the human species, especially our consciousness, is integral to the biosphere; that nothing is static; and that dynamism and function are primary, whereas structure is secondary. It is suggested that the understanding of the connectedness of humans to the rest of the biosphere will alter the behaviour of the human species towards more ecologically sustainable actions.     

Dynamics of the interaction of polyreactive immunoglobulins with immobilized antigens]

The kinetic of polyreactive immunoglobulins (PRIG) and immobilized antigen interaction was examined at different temperatures. It was shown that this process can be described by the so-called "competitive" model, and the relatively simple method for the rate constant determination for this process was developed. According to the "competitive" model PRIG molecule could be either in "active" or in "inactive" state and dynamic equilibrium exist between "active" and "inactive" molecules which strongly depend on incubation temperature. Only "active" PRIG can interact with antigens, and this is the reason of strong temperature dependence of PRIG-antigen interaction. The data also show that the mechanism of PRIG-antigen interaction differ from that of antibody-antigen interaction.     

The Units of Selection Revisited: The Modules of Selection

Richard Lewontin's (1970) early work on the units of selection initiated the conceptual and theoretical investigations that have led to the hierarchical perspective on selection that has reached near consensus status today. This paper explores other aspects of his work, work on what he termed continuity and quasi-independence, that connect to contemporary explorations of modularity in development and evolution. I characterize such modules and argue that they are the true units of selection in that they are what evolution by natural selection individuates, selects among, and transforms.     

The AKV Murine Leukemia Virus Is Restricted and Hypermutated by Mouse APOBEC3

APOBEC3 proteins are potent restriction factors against retroviral infection in primates. This restriction is accompanied by hypermutations in the retroviral genome that are attributable to the cytidine deaminase activity of the APOBEC3 proteins. Studies of nucleotide sequence diversity among endogenous gammaretroviruses suggest that the evolution of endogenous retroelements could have been shaped by the mutagenic cytidine deaminase activity of APOBEC3. In mice, however, APOBEC3 appears to restrict exogenous murine retroviruses in the absence of detectable levels of deamination. AKV is an endogenous retrovirus that is involved in causing a high incidence of thymic lymphoma in AKR mice. A comparative analysis of several mouse strains revealed a relatively low level of APOBEC3 expression in AKR mice. Here we show that endogenous mouse APOBEC3 restricts AKV infection and that this restriction likely reflects polymorphisms affecting APOBEC3 abundance rather than differences in the APOBEC3 isoforms expressed. We also observe that restriction of AKV by APOBEC3 is accompanied by G→A hypermutations in the viral genome. Our findings demonstrate that APOBEC3 acts as a restriction factor in rodents affecting the strain tropism of AKV, and they provide good support for the proposal that APOBEC3-mediated hypermutation contributed to the evolution of endogenous rodent retroviral genomes.Viruses that are restrained to infect only a specific animal species, subspecies, or strain have acquired particular features that enable them to circumvent the immune defenses of that particular host. Conversely, the natural hosts for these pathogens are alive today because they have evolved strategies to restrain the infectivities of their own pathogens. A virus with a broad host tropism will typically have evolved under selective pressure from several host factors that it will have encountered and successfully evaded. Ecotropic murine retroviruses generally have a restricted host range, due not only to the limited availability of their cellular receptor, mCAT-1 (58), but also to the various intrinsic restriction factors present in a specific host (7). Fv1 and Fv4 are the expression products of defective endogenous retroviruses that are present as germ line integrations and can interfere with and even block the infectivities of ecotropic retroviruses (6, 25).Mouse APOBEC3 is another type of host-encoded intrinsic restriction factor that can display deoxycytidine deaminase activity on single-stranded DNA (16, 54). APOBEC3 proteins have a potent inhibitory effect on retroelements ranging from primate lentiviruses to murine retrotransposons (reviewed in reference 17). In humans and primates there are seven APOBEC3 genes, most of which have been proposed to act as restriction elements for viruses and retroelements. The most extensively characterized of the primate APOBEC3 proteins are APOBEC3F and APOBEC3G, which constitute powerful restriction factors for human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) (reviewed in reference 17). The evidence that these lentiviruses are targets for APOBEC3 action does not come just from in vitro experiments: tissue samples from HIV type 1 (HIV-1)-infected humans contain retroviral sequences exhibiting a pattern of G→A hypermutation that is characteristic of APOBEC3F/G-dependent deoxycytidine deamination (4, 12, 26, 56, 57).In contrast to primates, mice have only a single APOBEC3 gene. This murine APOBEC3 has been shown to be able to inhibit retrotransposition of mouse MusD and intracisternal A particle elements in cotransfection assays (22, 23). However, the lack of any obvious signs of disease, developmental defect, or infertility in APOBEC3-deficient mice indicates that APOBEC3 may not play an essential role in suppressing the transposition of endogenous retroelements in laboratory mice (38, 40). With regard to exogenous retroviruses, mouse APOBEC3 has been shown to hinder the in vivo infectivity of the betaretrovirus mouse mammary tumor virus (MMTV) as well as that of the gammaretrovirus Friend murine leukemia virus (MLV) (40, 55); its activity against Moloney MLV (MoMLV), another gammaretrovirus, is apparently considerably weaker—likely reflecting the fact that MoMLV may have found ways to avoid APOBEC3-mediated restriction (14, 34, 46, 61). In none of these cases, however, does it appear that mouse APOBEC3 hypermutates the retroviral replication intermediates, suggesting that deamination is not central to its mechanism of restricting these retroviruses. Notwithstanding this failure to observe hypermutation of mouse retroviruses by mouse APOBEC3, recent studies of nucleotide sequence diversity among endogenous gammaretroviruses have suggested that the evolution of endogenous retroelements has been shaped by the mutagenic cytidine deaminase activity of APOBEC3 (28, 42). Thus, the picture which emerges is that APOBEC3 acts as one of several restriction factors of mouse retroelements, with some viruses having found ways to avoid APOBEC3-mediated restriction.Different mouse strains exhibit different patterns of APOBEC3 expression (41, 47, 55). Thus, two major mouse APOBEC3 alleles have been identified: one encodes a protein whose sequence is similar to that of the allele expressed in C57BL/6 mice, and the other resembles that of BALB/c mice (47, 55). Two major splicing isoforms of APOBEC3, which either do or do not include exon 5, have also been detected: the relative abundance of these two isoforms differs between strains (36, 41, 47, 55). The restriction of Friend MLV and that of MMTV both appear to be dependent on the identity of the mouse strain, and it has been proposed that this reflects the polymorphism in the sequence and splicing isoforms of APOBEC3 (41, 47, 55).In the course of our work on mouse APOBEC3, we discovered that APOBEC3 was expressed only at a low level in AKR mice. The AKR mouse strain harbors several germ line insertions of an endogenous ecotropic MLV designated AKV, which belongs to the gammaretrovirus family (5, 15, 27, 44, 45). A complex set of recombination events between AKV and nonecotropic endogenous retroviruses results in the production of leukemogenic mink cell focus-inducing viruses that are responsible for inducing a lethal form of thymic lymphoma of T-cell origin in these mice (19, 53). We were interested in determining whether the susceptibility of AKR mice to AKV infection could in part be explained by a failure of the APOBEC3 allele expressed in AKR mice to restrict this virus.Here we show that endogenous murine APOBEC3 in C57BL/6 mice not only acts to restrict AKV infection but also hypermutates AKV replication intermediates, likely providing a powerful block to natural transmission of the virus between mouse strains. We find that the different isoforms of APOBEC3 (whether or not they include exon 5) are effective in AKV restriction and that the differential resistance of lymphocytes from different mouse strains/mutants to AKV infection correlates with the abundance of endogenous APOBEC3 mRNA. Our results indicate that APOBEC3 confers effective protection against germ line integration of retroviral pathogens in rodents, and they provide tangible support to the proposal that DNA editing by APOBEC3 may have participated in the evolution of endogenous retroviral genomes.     

"占群"还是"挑战"?不同时间限制条件下麋鹿个体的交配计策

在麋鹿的发情交配季节 ,雄性麋鹿可区分为 3种类型 :“群主”、“挑战者”和“单身汉”。“群主”是一头圈占并控制雌鹿活动的优势雄性。“挑战者”不占有雌性繁殖群 ,但在发情场附近地点展示炫耀。当雌性繁殖群的雌鹿外出采食靠近“挑战者”的展示炫耀地点时 ,“挑战者”会积极地寻求机会与之交配。“单身汉”在繁殖季节不表现发情行为。他们像非繁殖季节一样采食 ,采食后蹲在水塘中休息。我们对何种因素决定麋鹿个体的发情交配计策感兴趣。 1996至 1998年夏天 ,我们在北京麋鹿苑观察麋鹿发情交配行为以分析导致这些行为差异的原因。结果发现 ,“群主”、“挑战者”和“单身汉”用于维持生命的时间预算与用于发情的时间预算成反比 ,并且 ,“群主”、“挑战者”和“单身汉”用于维持生命的时间预算与用于发情的时间预算差异显著。“群主”的绝大部分时间用于发情占群 ,而用于采食、饮水的时间很少 ,所以 ,“群主”在发情期间基本上处于禁食状态 ,靠消耗体内脂肪维持生命。“单身汉”则相反 ,绝大部分时间用于采食、休息和反刍 ,基本上没有发情行为。“挑战者”在发情行为与维持生命行为之间的时间则居于“群主”与“单身汉”之间。交配次数是偏态分布的 ,与雄性发情时间呈正比。“群主”的交配概率最高     

Origin of the novel chemoreceptor Aesthetasc "Y" in Ostracoda: morphogenetical thresholds and evolutionary innovation

SUMMARY The morphology and developmental processes of the two types of ostracod chemoreceptors, the Aesthetasc "Y" and the "Grouped setae," were compared. Cypridoidea and Pontocypridoidea, belonging to Cypridocopina, have a large baseball bat-like seta as an autapomorphic character on the second antenna, whereas most ostracod taxa with plesiomorphic characters bear "Grouped setae" consisting of multiple setae on the second antenna. Their budding positions, morphology, and ontogenetic changes were compared, and our deduction is that the Aesthetasc "Y" originated from "Grouped setae-like" organ in the Paleozoic. The morphogenetic processes in the molting period of these chemoreceptors were compared at the cellular level. The observations suggest that the "Grouped setae" are formed by hypodermal cells and share sheath cells corresponding to those of the Aesthetasc "Y" as a common constraint in the molting process of setae. We conclude that modification of the morphogenetic processes in the molting period of the "Grouped setae" gave rise to the Aesthetasc "Y" as a novel organ in the evolutionary pathway of the Ostracoda.     

Response to Striefel and Glaros

In this response to the comments of Drs. Striefel and Glaros, we take issue with Dr. Striefel's assertion that the Declaration of Helsinki should not be regarded as a core ethical document, and demonstrate that his claim that the Declaration has no significance in or recognition by agencies of the United States Federal Government is in error. A reading of FDA and DHHS documents shows that the Declaration is not, as Dr. Striefel suggested, only an aspirational document, but also is clearly regarded as mandatory. Dr. Glaros' observations regarding the slippery concept of efficacy is very much on point, and we certainly agree with his call for more data. It is the means by which that can be accomplished that is problematic. We have suggested that the logic of placebo controls developed to render drug efficacy studies more rigorous and scientifically grounded does not translate well to many psychological and behavioral studies of efficacy. It is important for our discipline to rethink the standards by which new behavioral and psychological (including psychophysiological) interventions can be demonstrated to be efficacious. One possible approach that avoids ethical pitfalls and design impossibilities is the active control, which requires good demonstration of assay sensitivity. We hope that this discussion may stimulate further discussion about other approaches that do not depend upon the flawed placebo orthodoxy.     

The ovalbumin split gene: molecular cloning of Eco RI fragments "c" and "d".

The Eco RI fragments "c" and "d" of the ovalbumin gene (1, 2) have been isolated by molecular cloning. Restriction enzyme mapping and electron microscopy have confirmed that the two fragments contain the same ovalbumin mRNA coding sequences. These sequences are split into two regions which have been mapped in fragments "c" and "d". There is no evidence that the ovalbumin mRNA sequences contained in these fragments could be further interrupted. Our results confirm that the presence of Eco RI fragment "d" in some chickens is due to the existence of an allelic variant of the ovalbumin gene which contains an additional Eco RI site within the region corresponding to Eco RI fragment "c". This additional Eco RI site appears to be the main difference between the two alleles. Finally, our results provide a direct demonstration that most of the ovalbumin mRNA sequences are encoded for by Eco RI fragments "a", "b" and "c".