Discovering adaptation-capable biological network structures using control-theoretic approaches

Constructing biological networks capable of performing specific biological functionalities has been of sustained interest in synthetic biology. Adaptation is one such ubiquitous functional property, which enables every living organism to sense a change in its surroundings and return to its operating condition prior to the disturbance. In this paper, we present a generic systems theory-driven method for designing adaptive protein networks. First, we translate the necessary qualitative conditions for adaptation to mathematical constraints using the language of systems theory, which we then map back as ‘design requirements’ for the underlying networks. We go on to prove that a protein network with different input–output nodes (proteins) needs to be at least of third-order in order to provide adaptation. Next, we show that the necessary design principles obtained for a three-node network in adaptation consist of negative feedback or a feed-forward realization. We argue that presence of a particular class of negative feedback or feed-forward realization is necessary for a network of any size to provide adaptation. Further, we claim that the necessary structural conditions derived in this work are the strictest among the ones hitherto existed in the literature. Finally, we prove that the capability of producing adaptation is retained for the admissible motifs even when the output node is connected with a downstream system in a feedback fashion. This result explains how complex biological networks achieve robustness while keeping the core motifs unchanged in the context of a particular functionality. We corroborate our theoretical results with detailed and thorough numerical simulations. Overall, our results present a generic, systematic and robust framework for designing various kinds of biological networks.     

Proinflammatory cytokines secreted by monocytes of filarial patients.

The levels of interleukin 1, granulocyte macrophage colony stimulating factor (GM-CSF) and tumour necrosis factor (TNF)-alpha secreted by the monocytes of filarial patients, such as asymptomatic microfilaremics (MF), chronic pathology (CP), and normal individuals, residing in a Wuchereria bancrofti endemic area (EN) in response to whole Brugia malayi antigen (BmA) and Setaria digitata (Sd-cuticular) and a recombinant filarial antigen (pRJ51) were studied. Stimulation of peripheral blood adherent cells with whole parasite antigen showed marked increase in IL-1 levels in MF as compared to CP or EN. The recombinant antigen stimulation, however, resulted in similar levels of IL-1 in MF and CP. In contrast, stimulation of peripheral blood adherent cells with whole parasite antigen produced high levels of GM-CSF and TNF-alpha in CP as opposed to MF or EN. Recombinant antigen stimulation, however, produced high levels of GM-CSF in EN as compared to MF or CP, while no significant change in the release of TNF-alpha was observed in these patients. These results suggest that monocytes from filarial patients exhibit functional activity similar to that observed by the monocytes of endemic normals (control group).     

Arthropod prey of shelterbelt-associated birds: linking faecal samples with biological control of agricultural pests

Abstract  The value of insectivorous birds as agents for biological control of arthropod pests has been little studied, especially in Australia. This paper reports on the extent to which arthropods from various pest and non-pest taxa feature in the diets of birds captured in farm shelterbelts in central western New South Wales. The parameters examined were the types of arthropod fragments in bird faeces and percentage volume and frequency of occurrence of each component. The faecal data were compared with samples of the arthropod fauna trapped in shelterbelts during the period the birds were captured. In 26 of 29 faecal samples, arthropod fragments were the predominant components, the most common being from Coleoptera, Hymenoptera (especially Formicidae), Orthoptera and Araneae. The recognisable pest taxa in faecal samples were Scarabaeidae and wingless grasshopper Phaulacridium vittatum (Sjöstedt) (Orthoptera: Acrididae). The results indicate that the native bird species common in farm shelterbelts preyed on a range of arthropod taxa including several that are pests of crops and pastures. Accordingly, conservation of birds in farmlands could contribute to suppression of arthropod pests.     

Conservation biogeography in North-east India: hierarchical analysis of cross-taxon distributional congruence

Distributional similarity (congruence) between phylogenetically independent taxonomic groups has important biogeographical as well as conservation implications. When multiple groups show congruence, one or two of them can be used as surrogates of diversity in others; thus, simplifying some of the challenges of area prioritization for conservation action. Here we test for congruence in complementarity between amphibians, reptiles and birds across seven tropical rainforest sites in the Eastern Himalaya and Indo-Burma global biodiversity hotspots. The results show that while frogs and lizards are strongly congruent with each other, birds as a whole do not show congruence with either of them. However, certain bird subgroups delineated on the basis of broad ecological niche and life history attributes are significantly congruent with both frogs and lizards. Multiple Mantel regression between environmental variable and species distribution dissimilarity matrices indicate that along with differential response to between-site ecological differences, inherent life-history characteristics shared by certain groups contributes to observed patterns of congruence. Our analyses indicate that examining biologically distinct subsets of larger groups can improve the resolution of congruence analyses. This approach can refine area-prioritization initiatives by revealing fine-scale discordances between otherwise concordant groups, and vice versa. Given that monetary resources do not always allow inclusion of multiple groups in biodiversity inventorying efforts, performing such analyses also makes economic sense because it can provide better resolution even with single-group data. In the context of conservation in North-east India, the results highlight the biogeographical complexity of the region, and also point at future priorities for biodiversity inventorying and conservation prioritization, both in terms of areas as well as taxonomic groups.     

Plant Community Structure in Tropical Rain Forest Fragments of the Western Ghats,India1

Changes in tree, liana, and understory plant diversity and community composition in five tropical rain forest fragments varying in area (18–2600 ha) and disturbance levels were studied on the Valparai plateau, Western Ghats. Systematic sampling using small quadrats (totaling 4 ha for trees and lianas, 0.16 ha for understory plants) enumerated 312 species in 103 families: 1968 trees (144 species), 2250 lianas (60 species), and 6123 understory plants (108 species). Tree species density, stem density, and basal area were higher in the three larger (> 100 ha) rain forest fragments but were negatively correlated with disturbance scores rather than area per se. Liana species density, stem density, and basal area were higher in moderately disturbed and lower in heavily disturbed fragments than in the three larger fragments. Understory species density was highest in the highly disturbed 18‐ha fragment, due to weedy invasive species occurring with rain forest plants. Nonmetric multidimensional scaling and Mantel tests revealed significant and similar patterns of floristic variation suggesting similar effects of disturbance on community compositional change for the three life‐forms. The five fragments encompassed substantial plant diversity in the regional landscape, harbored at least 70 endemic species (3.21% of the endemic flora of the Western Ghats–Sri Lanka biodiversity hotspot), and supported many endemic and threatened animals. The study indicates the significant conservation value of rain forest fragments in the Western Ghats, signals the need to protect them from further disturbances, and provides useful benchmarks for restoration and monitoring efforts.     

Cytological analysis of constitutive heterochromatin in two species of birds

Two species of birds, the myna (Acridotheres tristis L.) and the jungle babbler (Turdoides malcolmi Sykes), have been studied cytologically. Their modal diploid numbers are 78±2 and 68±2 respectively. In T. malcolmi the heterochromatin is located on the centromeres of all the macros and most of the microchromosomes, heterochromatin comprises predominantly GC-sequences and at least one pair of microchromosomes is responsible for nucleolus organization. The occasional occurrence of silver deposition on more than one pair of microchromosomes suggests the possibility that more than one pair of micros may be associated with the synthesis of rRNA. The heterochromatin in A. tristis is AT-rich and restricted to the macro-chromosomes, though most of the micros are also C-band positive; no particular chromosome stains with silver nitrate, though when interphase cells are stained with acridine orange the nucleolus is surrounded by brightly fluorescing chromatin. Apparently unlike other species, the microchromosomes in the myna do not harbour NORs.     

Gluconeogenesis from glycine and serine in fasted normal and diabetic rats.

1. Non-anaesthetized normal and diabetic rats were fasted for 1 day, and [U-14C]glycine, or [U-14C]serine, or [U-14C]- plus [3-3H]-glucose was injected intra-arterially. The rates of synthesis de novo/irreversible disposal for glycine, serine and glucose, as well as the contribution of carbon atoms by the amino acids to plasma glucose, were calculated from the integrals of the specific-radioactivity-versus-time curves in plasma. 2. The concentrations of both glycine and serine in blood plasma were lower in diabetic than in fasted normal animals. 3. The rates of synthesis de novo/irreversible disposal of both amino acids tended to be lower in diabetic animals, but the decrease was statistically significant only for serine (14.3 compared with 10.5 mumol/min per kg). 4. Of the carbon atoms of plasma glucose, 2.9% arose from glycine in both fasted normal and diabetic rats, whereas 4.46% of glucose carbon originated from serine in fasted normal and 6.77% in diabetic rats. 5. As judged by their specific radioactivities, plasma serine and glycine exchange carbon atoms rapidly and extensively. 6. It was concluded that the turnover of glycine remains essentially unchanged, whereas that of serine is decreased in diabetic as compared with fasted normal rats. The plasma concentration of both amino acids was lower in diabetic rats. Both glycine and serine are glucogenic. In diabetic rats the contribution of carbon atoms from glycine to glucose increases in direct proportion to the increased glucose turnover, whereas the contribution by serine becomes also proportionally higher.     

Permeance of Cs+ and Rb+ through the inwardly rectifying K+ channel in guinea pig ventricular myocytes

Summary Inward currents carried by external Cs, Rb, NH₄ and K through theI _K1 channel were studied using a whole-cell voltage clamp technique. Cs, NH₄, and Rb currents could be recorded negative to –40 mV following depolarizing prepulses (0 mV and 200–1000 msec in duration). The current activation displayed an instantaneous component followed by a monoexponential increase () to a peak amplitude. Subsequent inactivation was fit by a single exponential, _i. With hyperpolarization, and _i decreasede-fold per 36 and 25 mV, respectively. In Ca-free external solutions (pipette [Mg]0.3mm), inactivation was absent, consistent with the hypothesis that inactivation represents time- and voltage-dependent block of Cs, NH₄, and Rb currents by external Ca. The inactivation and degree of steady-state block was greatest when Cs was the charge carrier, followed by NH₄, and then Rb. K currents, however, did not inactivate in the presence of Ca. Na and Li did not carry any significant current within the resolution of our recordings. Comparison ofpeak inward current ratios (I _x/I_K) as an index of permeability revealed a higher permeance of Cs (0.15), NH₄ (0.30), and Rb (0.51) relative to K (1.0) than that obtained by comparing thesteady-state current ratios (CsNH₄RbK0.010.060.211.0). At any given potential, was smaller the more permeant the cation. In the absence of depolarizing prepulses, the amplitude of was reduced. Divalent-free solutions did not significantly affect activatio in the presence of 0.3mm pipette [Mg]. When pipette [Mg] was buffered to 50 m, however, removal of external Ca and Mg lead to a four- to fivefold increase in Cs currents and loss of both time-dependent activation and inactivation (reversible upon repletion of external Ca).These results suggest that (i) permeability ratios forI _K1 should account for differences in the degree to which monovalent currents are blocked by extracellular Ca and (ii) extracellular or intracellular divalent cations contribute to the slow phase of activation which may represent either (a) the actual rate of Mg or Ca extrusion from the channel into the cell, a process which may be enhanced by repulsive interaction with the incoming permeant monovalent cation or (b) an intrinsic gating process that is strongly modulated by the permeant monovalent ion and divalent cations.     

Purification of mitochondria and mitochondrial nucleic acids from embryogenic suspension cultures of a gymnosperm,Larix x leptoeuropaea

After a number of attempts to isolate mitochondria from different conifer tissues, embryogenic suspension cultures of hybrid larch (Larix x leptoeuropaea) were developed which enabled the purification of mitochondria using slight modifications to standard techniques. The mitochondrial purity was verified by analysis of the mitochondrial RNA, DNA and proteins. The larch mitochondrial genome size is surprisingly large (> 1000 kbp) and the polypeptide pattern differs greatly from those of wheat or potato mitochondria, suggesting that valuable evolutionary insights will be gained from comparisons between gymnosperm and angiosperm mitochondria. The ease with which embryogenic conifer suspensions can be initiated and used for mitochondrial purification implies that they will be the material of choice for future studies of this type.Abbreviations PCR polymerase chain reaction - mtDNA mitochondrial DNA - 2,4-D 2,4-dichlorophenoxyacetic acid - BA N⁶-benzyladenine - Tris tris(hydroxymethyl)aminomethane - EDTA ethylenediaminetetraacetic acid - BSA bovine serum albumin - EGTA ethylene glycol-bis(ß-aminoethyl ether) N,N,N,N-tetraacetic acid - SDS sodium dodecyl sulphate - DEPC diethyl pyrocarbonate - PAGE polyacrylamide gel electrophoresis - IEF iso-electric focusing