Synthesis and characterization of methylated poly(L-histidine) to control the stability of its siRNA polyion complexes for RNAi

Poly(L-histidine) (PLH) with dimethylimidazole groups has been synthesized as a pH-sensitive polypeptide to control the stability of its small interfering RNA (siRNA) polyion complexes for RNA interference (RNAi). The resulting methylated PLH (PLH-Me) was water-soluble despite deprotonation of the imidazole groups at physiological pH, as determined by acid-base titration and solution turbidity measurement. Agarose gel retardation assay proved that the quaternary dimethylimidazole groups worked as cationic groups to retain siRNA. The stability of the PLH-Me/siRNA complexes has depended on the content of hydrophobic groups, that is, τ/π-methylimidazole groups as well as deprotonated imidazole groups. PLH-Me exhibited no significant cytotoxicity despite the existence of cationic dimethylimidazole groups. By use of PLH-Me as a pH-sensitive siRNA carrier, the PLH-Me/siRNA complexes mediated efficient siRNA delivery attributed to the dimethylimidazole groups, and the gene silencing depended on the content balance among dimethyl, τ/π-methyl, and unmodified imidazole groups. These results suggest that PLH-Me controls the stability of siRNA polyion complexes by enhancing noncytotoxic siRNA delivery by optimizing the content balance of dimethyl, τ/π-methyl, and unmodified imidazole groups.     

Intraspecific Variation in the Mating System of Spectral Tarsiers

Historically, a species’ social system was perceived to be a fixed attribute and deviations were usually treated as aberrant or maladaptive. Over the last few decades, socioecologists have started to recognize that variation in social systems is normal and adaptive. Here I explore how ecological variation affects the mating system of a nocturnal primate, the spectral tarsier, Tarsius spectrum. Several studies of the spectral tarsier have illustrated variation in this species’ mating system. Although most groups exhibit a monogamous mating system, a small proportion of the population consistently exhibits a polygynous mating system. I conducted this study at Tangkoko Nature Reserve in Sulawesi, Indonesia during 2007. I found that group size was highly variable, ranging from 2 individuals to as many as 8 individuals per sleeping site. Although most groups (21 of 26) were composed of a single adult male and a single adult female, ca. 19% of the groups contained 2 adult females. Three of the 5 groups with 2 adult females contained 2 young infants. As might be expected, polygynous groups were larger than were monogamous groups. The mean group size of monogamous groups was 2.9, whereas the mean group size of polygynous groups was 6.0. Polygynous groups were also more likely to use Ficus caulocarpa trees than were the monogamous groups. Polygynous groups consistently used more sleeping sites as well as larger diameter sleeping trees, than did monogamous groups. The large-diameter fig trees are ideal homes for the spectral tarsiers in that they offer multiple entrances and exits as well as protection from the elements. Polygynous and monogamous groups exhibited no differences in insect biomass available, home range size, or height of sleeping tree. These results support the hypothesis that ecological variation is an important determinant of mating system within spectral tarsiers.     

Features of the personality component of the psycho-physiological potential of different social and professional groups

This study was conducted to develop the concept of population psychophysiological potential of society by revealing the personality traits most universal for the different social and professional groups. Fourteen groups were interviewed with the Kettle’s 16-factor questionnaire, and the results obtained were summarized. Personality qualities such as activity, aptitude for cooperation, aspiration for advances, audacity, independence, and flexibility were found to be the most important for the population potential of society as a whole. Moreover, different social and professional groups were shown to have typical sets of personality properties that dominated in a given population as the components of rather specific psycho-physiological potentials of the groups.     

The influence of females on the initiation of female-to-male sex change in a coral reef fish

In the protogynous coral reef fish Anthias squamipinnis (Peters), all males are sex-reversed females. A sexually mature female can be induced to change sex by removing a male from her social group. The influence of non-sex-changing females on the initiation of sex change was evaluated in 109 social groups in the Gulf of Eilat. When the male and largest female were removed from each of 12 single-male groups, the second-largest female changed sex in 9 groups. This result distinguished between two behavioral hypotheses suggested by previous work and made it tenable that a particular behavioral measure, the profile of behavior-received, that depends on adult females, is critical to the initiation of sex change. This species forms all-female groups as well as bisexual groups. All-female groups can be expected to have some mechanism for the production of a male. The removal of the largest female from each of 8 all-female groups failed to induce sex change in any group. The dominant female in these groups thus does not function in the same way as does the male in bisexual groups, at least in terms of the initiation of sex change. Following the removal of the male from each of 8 bisexual groups containing five or fewer adult females, a female changed sex in only 4 groups. This 50% incidence of sex reversal was lower than the 77–80% incidence in control groups containing more than five adult females. Data suggest that a minimum of four adult females is probably required for the probability of sex change after male removal to equal 75%.     

Interactions between overlapping multimale groups of black and white colobus monkeys (Colobus guereza) in the Kakamega Forest,Kenya

Sixteen out of 18 groups of black and white colobus monkeys, or guerezas (Colobus guereza), observed in the Kakamega Forest, Kenya, included more than one adult male. Each group overlapped in its home range with 4–7 other groups, and no group appeared to have exclusive access to any part of its home range. Groups were engaged in intergroup encounters one-quarter of observation time. Encounters often occurred around preferred feeding sites as different groups were attracted to such sites in their overlapping home ranges. Wins and losses during encounters were not dependent on location and a null model suggested that groups were not increasing their encounter rate to defend boundaries, further demonstrating a lack of territoriality. Although guerezas have repeatedly been described as a territorial species living in one-male groups, nonterritorial multimale groups are common in continuous forests. Territorial one-male groups may be usual in narrow riparian forests where resources are limiting, groups are small, and defendability is high, but such organization cannot be regarded as typical of the species. Habitat affects group size, as well as the potential for territoriality, and group size determines the number of adult males per group; therefore, classifying groups as one-male or multimale appears to be an artificial dichotomy. © 1996 Wiley-Liss, Inc.     

The effects of early and adult social environment on zebrafish (<Emphasis Type="Italic">Danio rerio</Emphasis>) behavior

Because early social experience can have a profound effect on later mate and social choices, the availability of options and decisions made early in development can have major effects on adult behavior. Herein, we use strain differences among zebrafish, Danio rerio, as an experimental tool to test the effects of social experience on behavior. By manipulating the strain composition of groups in which the subject fish are housed at different ages, we tested (1) whether mixing with dissimilar individuals influenced subsequent behavior, (2) whether prolonged mixing during the juvenile stage had a more pronounced effect than a shorter period of mixing during adulthood and (3) whether mixing had a lasting effect after animals were resorted into groups of same strain animals. We found that social experience had a profound impact on social behavior. Both Nadia and TM1 individuals engaged in more frequent biting after having been in mixed strain groups compared to pure strain groups. This was true of groups mixed as juveniles, as well as adults, indicating that this response was not dependent on exposure during a critical developmental period. Also, TM1 fish (but not Nadia) having recently been housed in mixed-strain groups were more willing to leave the immediate vicinity of a shoal than were TM1 fish raised in pure strain groups. This change was more pronounced in groups mixed as juveniles than as adults. In addition, the observed changes persisted after mixed groups were separated into pure strain groups for a month. Other behavioral measures including Activity Level, Predator Response and Stress Recovery were unaffected by previous social experience.     

Modelling the effects of loss of soil biodiversity on ecosystem function

There are concerns about whether accelerating worldwide loss of biodiversity will adversely affect ecosystem functioning and services such as forage production. Theoretically, the loss of some species or functional groups might be compensated for by changes in abundance of other species or functional groups such that ecosystem processes are unaffected. A simulation model was constructed for carbon and nitrogen transfers among plants and functional groups of microbes and soil fauna. The model was based on extensive information from shortgrass prairie, and employed stabilizing features such as prey refuges and predator switching in the trophic equations. Model parameters were derived either from the literature or were estimated to achieve a good fit between model predictions and data. The model correctly represented (i) the major effects of elevated atmospheric CO₂ and plant species on root and shoot biomass, residue pools, microbial biomass and soil inorganic nitrogen, and (ii) the effects on plant growth of manipulating the composition of the microbial and faunal community. The model was evaluated by comparing predictions to data not used in model development. The 15 functional groups of microbes and soil fauna were deleted one at a time and the model was run to steady state. Only six of the 15 deletions led to as much as a 15% change in abundance of a remaining group, and only two deletions (bacteria and saprophytic fungi) led to extinctions of other groups. Functional groups with greater effect on abundance of other groups were those with greater biomass or greater number of consumers, regardless of trophic position. Of the six deletions affecting the abundance of other groups, only three (bacteria, saprophytic fungi, and root‐feeding nematodes) caused as much as 10% changes in indices of ecosystem function (nitrogen mineralization and primary production). While the soil fauna as a whole were important for maintenance of plant production, no single faunal group had a significant effect. These results suggest that ecosystems could sustain the loss of some functional groups with little decline in ecosystem services, because of compensatory changes in the abundance of surviving groups. However, this prediction probably depends on the nature of stabilizing mechanisms in the system, and these mechanisms are not fully understood.     

Design of aminated poly(1-vinylimidazole) for a new pH-sensitive polycation to enhance cell-specific gene delivery

Poly(1-vinylimidazole) (PVIm) with aminoethyl groups has been synthesized as a new pH-sensitive polycation to enhance cell-specific gene delivery. The resulting aminated PVIm (PVIm-NH2) was water-soluble despite deprotonation of the imidazole groups at physiological pH, as determined by acid-base titration and solution turbidity measurement. Hemolysis assay showed that PVIm-NH2 enhanced membrane disruptive ability at endosomal pH, owing to the protonation of the imidazole groups with a pKa value around 6.0. Agarose gel retardation assay proved that the introduced aminoethyl groups worked as anchor groups to retain DNA. Furthermore, the ternary complex of DNA, PVIm-NH2, and a poly(L-lysine) conjugated with lactose molecules, PLL-Lac, at pH 7.4 dissociated the PLL-Lac polycation by protonation of the imidazole groups of PVIm-NH2 at pH 6.0. The resulting PVIm-NH2/DNA binary complexes easily released DNA, as compared with the PLL-Lac/PVIm-NH2/DNA ternary complex, which was examined by competitive exchange with dextran sulfate. By using PVIm-NH2 as a pH-sensitive DNA carrier, as well as PLL-Lac as a cell-targeting DNA carrier, the resulting ternary complex specifically mediated the gene expression, which depended on the protonation of the imidazole groups, on human hepatoma HepG2 cells with asialoglycoprotein receptors. These results suggest that the cell-specific gene delivery mediated by PLL-Lac was enhanced by PVIm-NH2 as a new pH-sensitive polycation.     

Exploring the effect of oxygen-containing functional groups on the water-holding capacity of lignite

Graphene oxide with different degrees of oxidation was prepared and selected as a model compound of lignite to study quantitatively, using both experiment and theoretical calculation methods, the effect on water-holding capacity of oxygen-containing functional groups. The experimental results showed that graphite can be oxidized, and forms epoxy groups most easily, followed by hydroxyl and carboxyl groups. The prepared graphene oxide forms a membrane-state as a single layer structure, with an irregular surface. The water-holding capacity of lignite increased with the content of oxygen-containing functional groups. The influence on the configuration of water molecule clusters and binding energy of water molecules of different oxygen-containing functional groups was calculated by density functional theory. The calculation results indicated that the configuration of water molecule clusters was totally changed by oxygen-containing functional groups. The order of binding energy produced by oxygen-containing functional groups and water molecules was as follows: carboxyl > edge phenol hydroxyl >epoxy group. Finally, it can be concluded that the potential to form more hydrogen bonds is the key factor influencing the interaction energy between model compounds and water molecules.     

Adsorption and structure of benzene confined in disordered porous carbons: effect of pore heterogeneity and surface chemistry

Molecular simulations are used to study the adsorption of benzene at 300?K in atomistic models of disordered nanoporous carbons. These models, named as CS400, CS1000 and CS1000a, differ in density and chemical compositions, and reproduce the morphological and topological features present in real nanoporous carbons. We found that the adsorption phenomena depend upon the local structure of nanoporous carbons. To understand the effect of surface chemistry on adsorption and structure of confined benzene, functional groups (–COOH and –C=O) were added to these models. The presence of functional groups led to the onset of adsorption process at a low pressure. The carboxyl groups (–COOH) have a greater impact on adsorption as compared to carbonyl (–C=O) groups. The CS1000a models have wide micropores and thus it exhibits a jump in adsorption isotherm. The jump shifts towards lower pressure on the addition of functional groups, with –COOH groups showing a larger shift. The presence of functional groups also increases the isosteric heat of adsorption, with –COOH groups showing higher values. The coulombic contribution to total fluid–wall interaction energy is higher for –COOH functional groups and decreases on increasing pressure. Benzene confined in CS1000a models exhibit a liquid-like structure.     

The chirality of ground DNA knots and links.

The chirality of ground DNA knots and links is described and characterized in terms of color symmetry groups (CSG), i.e. color symmetry groups I and II, which correspond to topochirality (topological chirality) and topoachirality (topological achirality) which bear an uncanny resemblance to point groups I (proper) and point groups II (improper) used for testing geochirality (geometrical chirality) and geoachirality (geometrical achirality), respectively. By regarding these two crossing modes in mirror images as white and black vertices, DNA knots and links with minimal crossings can be mapped to vertex-bicolored graphs under a working hypothesis that DNA knots and links exist in ground states with minimal energy m0. The color symmetry group of a vertex-bicolored graph G is defined as the set of all permutations and permutation asymmetrizations of the vertices of G that preserve its topology (connectivity), where asymmetrization, denoted as (a), is the operation of changing vertices' colors, and a permutation followed by an (a) is a permutation asymmetrization. The color symmetry groups I contains only permutations, whereas color symmetry groups II comprise permutation asymmetrizations as well as permutations. Four DNA knots and links in nature are analyzed and tabulated consisely. In addition, the well-known figure-of-eight knot and Borromean rings are discussed in much the same way.     

Histochemical blockade of the antigen-antibody reaction using immunoperoxidase demonstration of lysozyme in paneth cells and lamina propria mononucleocytes of human small intestine as a model system

Nitrosation and acetylation, two histochemical blocking procedures for amino groups, were used to establish the extent to which these groups intervene in the antigen-antibody reaction in immunohistochemistry. We used the peroxidase-antiperoxidase method (PAP) to demonstrate lysozyme in Paneth cells and in lamina propria mononucleocytes of human small intestine as a model system. We studied the relationship of these groups to fixation, concentration of the primary antiserum, and length of blockade, as well as the possibility of reversing blockade as proof of specificity. Our findings support the contention that amino groups are also an important factor in antigen-antibody binding, even in fixed tissue. Fixatives influence the binding process in many ways, with acetylation producing a more successful result than nitrosation in tissue fixed in Bouin without acetic acid, whereas the reverse is true in formaldehyde-fixed tissue.     

The Role of Cadmium as a Causative Agent of Recurrent Abortion in Egyptian Women

Environmental pollution is one of the ever surging problems receiving careful attention in Egypt, as well as in the world. It has been evidenced that environmental pollutants play an important role in the manifestations of severe reproductive-associated disorders. Among them, an environmental pollutant, Cd, has contributed to several deleterious effects. Maternal exposure to Cd is associated with low birthweight and an increase in spontaneous abortion. Spontaneous abortion is highly frustrating for both patients and physicians. The data from the present study reveal that there was a significant increase in blood level of Cd in the aborter groups as compared to the control group of healthy women. Also there was a significant decrease in serum ferritin, which correlated positively with abortion. Also, plasma levels of malondialdehyde were significantly elevated in aborter groups. There was also a highly significant increase in plasma 8-hydroxyl-2-deoxyguanosine in the aborter groups as compared to the control group, accompanied by a significant decrease in plasma carnosine in aborter groups as compared with the control group. In the same manner there was a reduction in the progesterone hormone in aborter groups. Our results suggest that exposure to Cd is associated with an increased risk of recurrent spontaneous abortion in Egyptian women.     

Regulatory mechanisms of cellular respiration; the role of soluble sulfhydryl groups as shown by the effect of sulfhydryl reagents on the respiration of sea urchin sperm

Oxidizing agents of sulfhydryl groups such as iodosobenzoate, alkylating agents such as iodoacetamide, and mercaptide-forming agents such as cadmium chloride, mercuric chloride, p-chloromercuribenzoate, sodium arsenite, and p-carboxyphenylarsine oxide, added in small concentrations to a suspension of sea urchin sperm produced an increase in respiration. When the concentration was increased there was an inhibition. These effects are explained by postulating the presence in the cells of two kinds of sulfhydryl groups: soluble sulfhydryl groups, which regulate cellular respiration, and fixed sulfhydryl groups, present in the protein moiety of enzymes. Small concentrations of sulfhydryl reagents combine only with the first, thus producing an increase in respiration; when the concentration is increased, the fixed sulfhydryl groups are also attacked and inhibition of respiration is the consequence. Other inhibitors of cell respiration, such as cyanide and urethanes, which do not combine with -SH groups, did not stimulate respiration in small concentration.     

A Statistical Approach to the Definition of Bacterial Species

A statistical method is proposed for recognition of a bacterial species or for differentiation of two groups of bacterial strains. Comparison between two groups is done by the “t”-test. When the mean S-values (similarity value) of two groups are A and B, and the mean S-value for all possible combinations between strains of both groups is S, a condition necessary for defining the two groups as different species is to demonstrate the existence of equations A > S and B > S. Unless this condition is fulfilled, the two groups should be considered unseparable. The condition necessary for recognition of two groups as one species is to demonstrate the existence of equations A:= S and B = S. A few examples of the test were shown using the mycobacteria, and it was suggested that this statistical method is useful in the recognition of a species.     

Mating system of an exceptional primate, the olive colobus (Procolobus verus)

In the olive colobus (Procolobus verus), many groups have multiple males and the males have large testes. This indicates that even though this species lives in small groups, single males do not monopolize the groups. We investigated the strategies employed by males to secure their mating success, and sought to determine whether the lack of male monopolization was a result of female mating strategies, as indicated by the exaggerated sexual swellings of the females. Four study groups were monitored for demographic changes, and group composition was determined in six additional groups in Taï National Park, Ivory Coast, between 1994 and 1999. Social behavior was recorded by scan and focal sampling in the study groups. The almost permanent association of olive colobus with Diana monkeys (Cercopithecus diana) in effect provided males a resource at which they could expect females to visit and sometimes even permanently join them, as well as protection from predators. As alternative strategies for obtaining females, one male took over the group of another male and one male immigrated into a bisexual group. Within bi‐male groups, dominant males mated most frequently and males defended their groups during intergroup interactions. Lone females that visited groups or solitary males had a swelling more often than expected, and generally mated with the males they visited. Females had long receptive periods, several consecutive receptive cycles, and some overlap in receptive periods within groups. Females mated with extragroup males, and during infertile periods. We concluded that the males used the Diana monkeys for safety reasons and to obtain mating partners, and that female reproductive biology and behavior prevented the monopolization of groups of females by single males. Our data were inconclusive as regards the benefits to females of avoiding monopolization by males. Am. J. Primatol. 62:261–273, 2004. © 2004 Wiley‐Liss, Inc.     

Synthesis and evaluation of non-basic inhibitors of urokinase-type plasminogen activator (uPA)

Recent drug discovery programs targeting urokinase plasminogen activator (uPA) have resulted in nonpeptidic inhibitors consisting of amidine or guanidine functional groups attached to aromatic or heteroaromatic scaffolds. There is a general problem of poor oral bioavailability of these charged inhibitors. In this paper, we report the synthesis and evaluation of a series of naphthamide and naphthalene sulfonamides as uPA inhibitors containing non-basic groups as substitute for amidine or guanidine groups.     

The problem of species revisited

Hypothetical-deductive analysis is an alternative to both induction and deduction, the difference between which is considered less important. The hypothetical-deductive approach requires a scientist to abandon the synthetic theory of evolution in favor of the epigenetic theory. This latter treats species as a discrete level of biodiversity and, particularly, the one where sympatric biparental groups show reproductive independence. In the case of uniparental (asexual and parthenogenetic groups), as well as in bisexual allopatric groups, the species level of divergence is identifiable by analogy to sympatric biparental relatives. The biological and evolutionary species concepts are disproved: the former contradicts observation, and the latter is non-operational.     

Variation of group composition and spatial structure with group size in a sex-changing fish

Current knowledge of stable social groups of different size and structure suffers from a paucity of data on processes of group formation and development. If, for stable groups of one species, fission, growth, or other features of development reflect a uniform process operating on all groups, one might expect any group at one point in time to represent a single stage in the developmental process. Thus, unless group development is synchronous, a population should contain groups at all stages. A simple way to provide information about group development is to describe a large number of groups in a uniform habitat and to arrange the data along a variable axis, such as group size, that is thought to vary directly with development. A study was conducted on the tropical marine fish Anthias squamipinnis. Groups ranged in size from 1 to 370 fish. Small groups were spatially unitary. Intermediate-sized groups were divided into two spatially separate subgroups, i.e. were bipartite. Large groups were divided into three subgroups, i.e. were tripartite. Subgroups within each group were classified by relative size as small, medium, or large. Unitary groups were statistically similar to the larger subgroups in bi- and tripartite groups, but differed from smaller subgroups in sex ratio, juvenile membership, and relation to the substrate. While subdivision of groups could, in theory, be explained by proximity among randomly dispersed aggregations or by discontinuity of underlying substrate or available food, existing evidence does not favour these hypotheses. Group subdivision is probably the consequence of successive fissions of a previously unitary group.     

Chemical modification of the surfaces of bacterial cell walls.

The surfaces of the isolated cell walls of four bacterial species were studied by microelectrophoresis following chemical treatments intended to remove specific charged groups. Acid-base titrations of the walls were used to assess specificity and extent of the modifications. Carboxyl groups were specifically and completely modified by activation with a water-soluble carbodiimide and subsequent reaction with a nucleophile, such as glycinamide, to give an uncharged pH-stable product. Aqueous media and mild reaction conditions make the method suitable for modifying carboxyl groups on cell surfaces too labile to withstand the harsh conditions required for conventional esterification reactions. Use of the carbodiimide-mediated reaction for discharging carboxyl groups, along with fluorodinitrobenzene for discharging amino groups and extraction procedures for removing constituents carrying phosphoester groups (teichoic acids), made it possible to obtain information about the spatial arrangement of charged groups on the wall surfaces. Removal of the exterior negative charge dominating wall surfaces allowed underlying amino groups to become electrokinetically effective and, in the case of E. coli, also revealed a lipophilic region with an affinity for a cationic surfactant.