New potent biphalin analogues containing p-fluoro-L-phenylalanine at the 4,4' positions and non-hydrazine linkers

We report the synthesis and the biological evaluation of two new analogues of the potent dimeric opioid peptide biphalin. The performed modification is based on the replacement of two key structural elements of the native biphalin, namely: the hydrazine bridge which joins the two palindromic moieties and the phenylalanine residues at the 4,4′ positions of the backbone. The new analogues 9 and 10 contain 1,2-phenylenediamine and piperazine, respectively, in place of the hydrazidic linker and p-fluoro-l-phenylalanine residues at 4 and 4′ positions. Binding values are: K_\texti^m = 0.51 \textnM K_{\text{i}}^{\mu } = 0.51\,{\text{nM}} and K_\texti^d = 12.8 \textnM K_{\text{i}}^{\delta } = 12.8\,{\text{nM}} for compound 9, K_\texti^m = 0.09 \textnM K_{\text{i}}^{\mu } = 0.09\,{\text{nM}} and K_\texti^d = 0.11 \textnM K_{\text{i}}^{\delta } = 0.11\,{\text{nM}} for analogue 10.     

Effects of environmental oxygen on development and respiration of Australian lungfish (<Emphasis Type="Italic">Neoceratodus forsteri</Emphasis>) embryos

The effects of oxygen partial pressure ( P_\textO2 P_{{{\text{O}}_{2} }} ) on development and respiration were investigated in the eggs of the Australian lungfish, Neoceratodus forsteri. At 20°C, embryonic survival and development was optimal at 15 and 20.9 kPa. Development was slowed at 5 and 10 kPa and embryos did not survive 2 kPa. At lower P_\textO2 P_{{{\text{O}}_{2} }} , the rate of oxygen consumption also decreased. Embryos responded to hypoxia by hatching at an earlier age and stage of development, and hatching wet and dry gut-free masses were reduced. The role of oxygen conductance ( G_\textO2 G_{{{\text{O}}_{2} }} ) in gas exchange was also examined under selected environmental P_\textO2 P_{{{\text{O}}_{2} }} and temperatures. The breakdown of the vitelline membrane changed capsule geometry, allowed water to be absorbed into the perivitelline space and increased capsule G_\textO2 G_{{{\text{O}}_{2} }} . This occurred at embryonic stage 32 under all treatments and was largely independent of both P_\textO2 P_{{{\text{O}}_{2} }} and temperature (15, 20 and 25°C), demonstrating that capsule G_\textO2 G_{{{\text{O}}_{2} }} cannot adaptively respond to altered environmental conditions. The membrane breakdown increased capsule diffusive G_\textO2 G_{{{\text{O}}_{2} }} and stabilised perivitelline P_\textO2 P_{{{\text{O}}_{2} }} , but reduced the convective G_\textO2 G_{{{\text{O}}_{2} }} of the perivitelline fluid, as the large perivitelline volume and inadequate convective current resulted in a P_\textO2 P_{{{\text{O}}_{2} }} gradient within the egg prior to hatch.     

Oxygen-dependence of metabolic rate in the muscles of craniates

We present evidence that oxygen consumption (V_\textO2 ) (V_{{{\text{O}}_{2} }} ) is oxygen partial pressure (P_\textO2 ) (P_{{{\text{O}}_{2} }} ) dependent in striated muscles and P_\textO2 P_{{{\text{O}}_{2} }} -independent in the vasculature in representatives of three craniate taxa: two teleost fish, a hagfish and a rat. Blood vessel V_\textO2 V_{{{\text{O}}_{2} }} displayed varying degrees of independence in a P_\textO2 P_{{{\text{O}}_{2} }} range of 15–95 mmHg, while V_\textO2 V_{{{\text{O}}_{2} }} by striated muscle tissue slices from all species related linearly to P_\textO2 P_{{{\text{O}}_{2} }} between 0 and 125 mmHg, despite V_\textO2 V_{{{\text{O}}_{2} }} rates varying greatly between species and muscle type. In salmon red muscle, lactate concentrations fell in slices incubated at a P_\textO2 P_{{{\text{O}}_{2} }} of either 30 or 100 mmHg, suggesting aerobic rather than anaerobic metabolism. Consistent with this finding, potential energy, a proxy of ATP turnover, was P_\textO2 P_{{{\text{O}}_{2} }} -dependent. Our data suggest that the reduction in V_\textO2 V_{{{\text{O}}_{2} }} with falling P_\textO2 P_{{{\text{O}}_{2} }} results in a decrease in ATP demand, suggesting that the hypoxic signal is sensed and cellular changes effected. Viability and diffusion limitation of the preparations were investigated using salmon cardiac and skeletal muscles. Following the initial P_\textO2 P_{{{\text{O}}_{2} }} depletion, reoxygenation of the Ringer bathing salmon cardiac muscle resulted in V_\textO2 \texts V_{{{\text{O}}_{2} }} {\text{s}} that was unchanged from the first run. V_\textO2 V_{{{\text{O}}_{2} }} increased in all muscles uncoupled with p-trifluoromethoxylphenyl-hydrazone (FCCP) and 2,4-dinitrophenol (DNP). Mitochondrial succinate dehydrogenase activity, quantified by reduction of 3-(4,5-dimethylthiazol)-2,5-diphenyl-2H-tetrazolium bromide (MTT) to formazan, was constant over the course of the experiment. These three findings indicate that the tissues remained viable over time and ruled out diffusion-limitation as a constraint on V_\textO2 V_{{{\text{O}}_{2} }} .     

Environment and feeding change the ability of heart rate to predict metabolism in resting Steller sea lions (<Emphasis Type="Italic">Eumetopias jubatus</Emphasis>)

The ability to use heart rate (fh) to predict oxygen consumption rates ( [(V)\dot]_\textO2 \dot{V}_{{{\text{O}}_{2} }} ) in Steller sea lions and other pinnipeds has been investigated in fasting animals. However, it is unknown whether established fh: [(V)\dot]_\textO2 \dot{V}_{{{\text{O}}_{2} }} relationships hold under more complex physiological situations, such as when animals are feeding or digesting. We assessed whether fh could accurately predict [(V)\dot]_\textO2 \dot{V}_{{{\text{O}}_{2} }} in trained Steller sea lions while fasting and after being fed. Using linear mixed-effects models, we derived unique equations to describe the fh: [(V)\dot]_\textO2 \dot{V}_{{{\text{O}}_{2} }} relationship for fasted sea lions resting on land and in water. Feeding did not significantly change the fh: [(V)\dot]_\textO2 \dot{V}_{{{\text{O}}_{2} }} relationship on land. However, Steller sea lions in water displayed a different fh: [(V)\dot]_\textO2 \dot{V}_{{{\text{O}}_{2} }} relationship after consuming a 4-kg meal compared with the fasting condition. Incorporating comparable published fh: [(V)\dot]_\textO2 \dot{V}_{{{\text{O}}_{2} }} data from Steller sea lions showed a distinct effect of feeding after a 6-kg meal. Ultimately, our study illustrated that both feeding and physical environment are statistically relevant when deriving [(V)\dot]_\textO2 \dot{V}_{{{\text{O}}_{2} }} from telemetered fh, but that only environment affects the practical ability to predict metabolism from fh. Updating current bioenergetic models with data gathered using these predictive fh: [(V)\dot]_\textO2 \dot{V}_{{{\text{O}}_{2} }} equations will yield more accurate estimates of metabolic rates of free-ranging Steller sea lions under a variety of physiological, behavioral, and environmental states.     

Dental eruption sequence and eruption times in Erythrocebus patas

Erythrocebus patas has a short inter-birth interval, juveniles become independent from their mother early, females are young at first birth, and adult females have a high mortality rate. According to Schultz’s rule, the molars of fast-growing and shorter-lived primate species erupt early relative to the replacement teeth. Based on the life history of E. patas, we hypothesized that the molars would erupt before the replacement teeth and/or that the eruption time of its molars would be early. The purpose of the present study was to determine the dental eruption sequence and eruption times for E. patas and to test our hypothesis. The eruption sequence for the permanent teeth of E. patas is \frac\textM1  \textI1  \textI2  \textM2  \textP3  \textP4  [\textC  \textM3]\textM1  \textI1  \textI2  \textM2  \textP4  [\textP3  \textC]\textM3 \frac{{{\text{M1}}\;{\text{I1}}\;{\text{I2}}\;{\text{M2}}\;{\text{P3}}\;{\text{P4}}\;[{\text{C}}\;{\text{M3}}]}}{{{\text{M1}}\;{\text{I1}}\;{\text{I2}}\;{\text{M2}}\;{\text{P4}}\;[{\text{P3}}\;{\text{C}}]{\text{M3}}}} in males and \frac\textM1  \textI1  \textI2  [\textM2  \textP4  \textP3  \textC]\textM3\textM1  \textI1  \textI2  [\textM2  \textP4  \textP3  \textC]\textM3 \frac{{{\text{M1}}\;{\text{I1}}\;{\text{I2}}\;[{\text{M2}}\;{\text{P4}}\;{\text{P3}}\;{\text{C}}]{\text{M3}}}}{{{\text{M1}}\;{\text{I1}}\;{\text{I2}}\;[{\text{M2}}\;{\text{P4}}\;{\text{P3}}\;{\text{C}}]{\text{M3}}}} in females. Because these sequences constitute the general pattern seen in cercopithecines, Schultz’s rule could not be applied to E. patas. The emergence time of upper and lower first molar (M1) is earlier in E. patas than in macaques, baboons, and mandrills and is similar to that in Chlorocebus aethiops. The emergence time of deciduous upper and lower fourth premolar (dp4) is similar to that in the above-mentioned cercopithecines but is later than that in Ch. aethiops. The emergence times of upper and lower second molar (M2) and upper and lower third molar (M3) in E. patas are earlier than those in the above-mentioned cercopithecines but later than those in Ch. aethiops. However, the intervals of the emergence time between each permanent molar in E. patas are similar to those of the above-mentioned cercopithecines. The early appearance of M2 and M3 in E. patas is related to the short interval of emergence time between dp4 and M1.     

A standard quantitative method to measure acid tolerance of probiotic cells

The aim of this work was to develop a standard quantitative method to measure the acid tolerance of probiotic cells when exposed to a simulated gastric fluid. Three model strains of different cell concentrations were exposed to a standard simulated gastric fluid of fixed volume. The fluid pH ranged from pH 1.5 to 2.5. In general, the death kinetics followed an exponential trend. The overall death constant, k _d, for all strains was found to be in a power relationship with the pH value and the initial cell concentration, and it can be expressed as

Effects of nitrate on intracellular nitrite and growth of Microcystis aeruginosa

Although nitrate is a macronutrient and can serve as good nitrogen source for many species of phytoplankton, high nitrate concentrations do not benefit the growth of phytoplankton. We hypothesise that algae cultured under high nitrate concentrations can accumulate intracellular nitrite, which is produced by nitrate reductase (NR) and can inhibit the growth of algae. To assess the validity of this hypothesis, Microcystis aeruginosa was grown under different nitrate concentrations from 3.57 to 21.43 mM in low CO₂ and high CO₂ conditions for 15 days. We observed that, with increasing nitrate concentrations, the intracellular nitrite concentrations of the alga increased and the growth rates and photosynthesis declined. When grown under high CO₂ conditions, M. aeruginosa showed lower intracellular nitrite concentrations and higher growth rates and \textP_\textm^\textchla {\text{P}}_{\text{m}}^{{\text{chl}}a} , \textR_\textd^\textchla {\text{R}}_{\text{d}}^{{\text{chl}}a} , α^chla than under low CO₂ conditions. These results suggest that the accumulation of intracellular nitrite could be the cause of inhibition of algal growth under high nitrate concentrations.     

Physiological characterization of ‘stay green’ wheat cultivars during the grain filling stage under field growing conditions

Rye (Secale cereale L.) chromosome arm 1RS could delay leaf senescence, and change in H₂O₂ content is a useful index for weighing the ability to delay the senescence. Two wheat cultivars, Chuannong12 (CN12) and Chuannong 18 (CN18), harboring the wheat–rye 1BL/1RS translocated chromosome were investigated for H₂O₂ change and physiological index after flowering under field conditions, and MY11, the agronomical parent of both CN12 and CN18, was used as the control. A combined change in the peak value of CdSe/ZnS quantum dot (QD) fluorescence and morphological observation indicated that the H₂O₂ contents in CN12 and CN18 were generally lower than that in MY11. They both had higher values for net photosynthetic rate (P _n), stomatal conductance (G _s), F_\textv /F_\textm^￠ F_{\text{v}} /F_{\text{m}}^{\prime } F_\textv^￠ /F_\textm^￠ F_{\text{v}}^{\prime } /F_{\text{m}}^{\prime } , and photochemical quenching of PSII (qP) than MY11 only in the late measurement stage. Some small differences were also observed, such as CN12 and CN18 wheat cultivars having higher and longer photosynthetic competence than MY11 during the grain filling stage, which perhaps resulted from a mechanism for removing oxidative species, especially H₂O₂.     

Photosynthetic Potential and its Association with Lipid Peroxidation in Response to High Temperature at Different Leaf Ages in Maize

High temperature generally constrains plant growth and photosynthesis in many regions of the world; however, little is known about how photosynthesis responds to high temperature with regard to different leaf ages. The synchronous changes in gas exchange and chlorophyll fluorescence at three leaf age levels (just fully expanded, mature, and older leaves) of maize (Zea mays L.) were determined at three temperatures (30°C as a control and 36 and 42°C as the higher temperatures). High temperature significantly decreased the net CO₂ assimilation rate (A), stomatal conductance (g _s), maximal efficiency of photosystem II (PSII) photochemistry (F _v/F _m), efficiency of excitation energy capture by open PSII reaction centers ( F^￠_\textv /F^￠_\textm F^{\prime}_{\text{v}} /F^{\prime}_{\text{m}} ), photochemical quenching of variable chlorophyll fluorescence (q _P), and the electron transport rate (ETR), whereas minimal fluorescence yield (F ₀) and nonphotochemical quenching of variable chlorophyll fluorescence (q _N) were increased. The youngest fully expanded leaves had higher A, ETR, and q _P compared with older leaves. Higher temperature with old leaves led to significant malondialdehyde (MDA) accumulation, a proxy for lipid peroxidation damage from active oxygen species (AOS). MDA content was significantly negatively correlated with A, F _v/F _m, F^￠_\textv /F^￠_\textm F^{\prime}_{\text{v}} /F^{\prime}_{\text{m}} , and q _P. Thus, the results suggest that photosynthetic potentials, including stomatal regulation and PSII activity, may be restricted at high temperature, together with increasing cell peroxidation, which may be closely associated with leaf age.     

Parameterization of chlorophyll a-specific absorption coefficients and effects of their variations in a highly eutrophic lake: a case study at Lake Kasumigaura, Japan

The chlorophyll a-specific absorption coefficient ( a_\textph^* ( l) a_{\text{ph}}^{*} \left( \lambda \right) ) in a highly eutrophic lake can show characteristics distinct from that in the ocean due to the differences in the structure and composition of phytoplankton. In this study, investigated the variation of a_\textph^* ( l) a_{\text{ph}}^{*} \left( \lambda \right) in Lake Kasumigaura, a highly eutrophic lake in Japan, in association with the package effect and the effect of accessory pigments, and carried out the parameterization of a_\textph^* ( l) a_{\text{ph}}^{*} \left( \lambda \right) . Although a_\textph^* ( l) a_{\text{ph}}^{*} \left( \lambda \right) did not vary spatially, it did show significant temporal variation, with a particularly high value after spring-bloom. This high a_\textph^* ( l) a_{\text{ph}}^{*} \left( \lambda \right) in spring was attributed to a lower package effect and a higher proportion of carotenoid than the other samples. Although the value of a_\textph^* ( l) a_{\text{ph}}^{*} \left( \lambda \right) was correlated with the concentration of chlorophyll-a (Chl-a), the correlation coefficient was lower than those reported in the ocean. Some lake-water samples showed variations of the package effect and the effect of accessory pigments that were independent of the concentration of Chl-a, and these independent variations resulted in the weak correlation between a_\textph^* ( l) a_{\text{ph}}^{*} \left( \lambda \right) and the concentration of Chl-a. Together, these results suggest that the factors controlling a_\textph^* ( l) a_{\text{ph}}^{*} \left( \lambda \right) in highly eutrophic lakes are distinct from that in ocean samples.     

Kinetics of styrene biodegradation by <Emphasis Type="Italic">Pseudomonas</Emphasis> sp. E-93486

The research into kinetics of styrene biodegradation by bacterial strain Pseudomonas sp. E-93486 coming from VTT Culture Collection (Finland) was presented in this work. Microbial growth tests in the presence of styrene as the sole carbon and energy source were performed both in batch and continuous cultures. Batch experiments were conducted for initial concentration of styrene in the liquid phase changed in the range of 5–90 g m⁻³. The Haldane model was found to be the best to fit the kinetic data, and the estimated constants of the equation were: μ _m = 0.1188 h⁻¹, K _S = 5.984 mg l⁻¹, and K _i = 156.6 mg l⁻¹. The yield coefficient mean value Y_\textxs^\textapp Y_{\text{xs}}^{\text{app}} for the batch culture was 0.72 g_{dry cells weight} (g_substrate)⁻¹. The experiments conducted in a chemostat at various dilution rates (D = 0.035–0.1 h⁻¹) made it possible to determine the value of the coefficient for maintenance metabolism m _d = 0.0165 h⁻¹ and the maximum yield coefficient value Y_\textxs^\textM = 0.913 Y_{\text{xs}}^{\text{M}} = 0.913 . Chemostat experiments confirmed the high value of yield coefficient Y_\textxs^\textapp Y_{\text{xs}}^{\text{app}} observed in the batch culture. The conducted experiments showed high activity of the examined strain in the styrene biodegradation process and a relatively low sensitivity to inhibition of its growth at higher concentrations of styrene in the solution. Such exceptional features of Pseudomonas sp. E-93486 make this bacterial strain the perfect candidate for technical applications.     

Influence of {\text{NH - }}{{\text{S}}^\gamma } bonding interactions on the structure and dynamics of metallothioneins

Mammalian metallothioneins ( \textM₇^\textIIMTs {\text{M}}_7^{\text{IIMTs}} ) show a clustered arrangement of the metal ions and a nonregular protein structure. The solution structures of Cd₃-thiolate cluster containing β-domain of mouse β-MT-1 and rat β-MT-2 show high structural similarities, but widely differing structure dynamics. Molecular dynamics simulations revealed a substantially increased number of \textNH - \textS^g {\text{NH - }}{{\text{S}}^\gamma } hydrogen bonds in β-MT-2, features likely responsible for the increased stability of the Cd₃-thiolate cluster and the enfolding protein domain. Alterations in the \textNH - \textS^g {\text{NH - }}{{\text{S}}^\gamma } hydrogen-bonding network may provide a rationale for the differences in dynamic properties encountered in the β-domains of MT-1, -2, and -3 isoforms, believed to be essential for their different biological function.     

Changes in partial pressures of respiratory gases during submerged voluntary breath hold across odontocetes: is body mass important?

Odontocetes have an exceptional range in body mass spanning 10³ kg across species. Because, size influences oxygen utilization and carbon dioxide production rates in mammals, this lineage likely displays an extraordinary variation in oxygen store management compared to other marine mammal groups. To examine this, we measured changes in the partial pressures of respiratory gases ( P_\textO2 P_{{{\text{O}}_{2} }} , P_\textCO2 P_{{{\text{CO}}_{2} }} ), pH, and lactate in the blood during voluntary, quiescent, submerged breath holds in Pacific white-sided dolphins (Lagenorhynchus obliquidens), bottlenose dolphins (Tursiops truncatus), and a killer whale (Orcinus orca) representing a mass range of 96–3,850 kg. These measurements provided an empirical determination of the effect of body size on the variability in blood biochemistry during breath hold and experimentally determined aerobic dive limits (ADL) within one taxonomic group (odontocetes). For the species in this study, maximum voluntary breath-hold duration was positively correlated with body mass, ranging from 3.5 min in white-sided dolphins to 13.3 min for the killer whale. Variation in breath-hold duration was associated with differences in the rate of change for P_\textO2 P_{{{\text{O}}_{2} }} throughout breath hold; P_\textO2 P_{{{\text{O}}_{2} }} decreased twice as fast for the two smaller species (−0.6 mmHg O₂ min⁻¹) compared to the largest species (−0.3 mmHg O₂ min⁻¹). In contrast, the rate of increase in P_\textCO2 P_{{{\text{CO}}_{2} }} during breath hold was similar across species. These results demonstrate that large body size in odontocetes facilitates increased aerobic breath-hold capacity as mediated by decreased mass-specific metabolic rates (rates of change in P_\textO2 P_{{{\text{O}}_{2} }} served as a proxy for oxygen utilization). Indeed the experimentally determined 5 min ADL for bottlenose dolphins was surpassed by the 13.3 min maximum breath hold of the killer whale, which did not end in a rise in lactate. Rather, breath hold ended voluntarily as respiratory gases and pH fell within a narrow range for both large and small species, likely providing cues for ventilation.     

AMP-activated protein kinase plays a role in initiating metabolic rate suppression in goldfish hepatocytes

In the present study, we test the hypothesis that AMP-activated protein kinase (AMPK) initiates metabolic rate suppression in isolated goldfish hepatocytes. To accomplish this, we attempted to pharmacologically activate AMPK in goldfish hepatocytes with 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) and the thienopyridone, A769662, to examine the effects of AMPK activation on eukaryotic elongation factor-2 (eEF2), protein synthesis, and cellular oxygen consumption rate ( [(M)\dot]_{\textO 2} \dot{M}_{{{\text{O}}_{ 2} }} ). Goldfish hepatocytes treated with 1 mM AICAR under normoxic conditions (>200 μM O₂) showed a modest but significant 1.1-fold increase in AMPK phosphorylation, a 7.5-fold increase in AMPK activity, a 1.4-fold increase in eEF2 phosphorylation, and a 24% decrease in [(M)\dot]_{\textO 2} \dot{M}_{{{\text{O}}_{ 2} }} . At physiologically relevant [O₂] (<40 μM O₂), the addition of 1 mM AICAR resulted in only a 13% decrease in cellular [(M)\dot]_{\textO 2} \dot{M}_{{{\text{O}}_{ 2} }} with no change in sensitivity to [O₂] as assessed by estimates of cellular P₅₀ and P₉₀ values. The addition of compound C, a general protein kinase inhibitor, after AICAR incubation did not reverse the effects of AICAR on [(M)\dot]_{\textO 2} \dot{M}_{{{\text{O}}_{ 2} }} in normoxia. Treatment of hepatocytes with ≤200 μM A769662 did not affect AMPK activity, AMPK phosphorylation, eEF2 phosphorylation, or cellular [(M)\dot]_{\textO 2} \dot{M}_{{{\text{O}}_{ 2} }} . These data suggest that A769662 is not an activator of AMPK in goldfish hepatocytes. Although our study provides support for the hypothesis that AMPK plays a role in initiating metabolic rate suppression in goldfish hepatocytes, this support must be viewed cautiously because of the known off-target effects of the pharmacological agents used.     

HNCA-TOCSY-CANH experiments with alternate <Superscript>13</Superscript>C-<Superscript>12</Superscript>C labeling: a set of 3D experiment with unique supra-sequential information for mainchain resonance assignment

Described here is a set of three-dimensional (3D) NMR experiments that rely on CACA-TOCSY magnetization transfer via the weak ³ \textJ_{\textCa\textCa} ^{ 3} {\text{J}}_{{{\text{C}}\alpha {\text{C}}\alpha }} coupling. These pulse sequences, which resemble recently described ¹³C detected CACA-TOCSY (Takeuchi et al. 2010) experiments, are recorded in ¹H₂O, and use ¹H excitation and detection. These experiments require alternate ¹³C-¹²C labeling together with perdeuteration, which allows utilizing the small ³ \textJ_{\textCa\textCa} ^{ 3} {\text{J}}_{{{\text{C}}\alpha {\text{C}}\alpha }} scalar coupling that is otherwise masked by the stronger ¹J_CC couplings in uniformly ¹³C labeled samples. These new experiments provide a unique assignment ladder-mark that yields bidirectional supra-sequential information and can readily straddle proline residues. Unlike the conventional HNCA experiment, which contains only sequential information to the ^{1 3} \textC^a ^{ 1 3} {\text{C}}^{\alpha } of the preceding residue, the 3D hnCA-TOCSY-caNH experiment can yield sequential correlations to alpha carbons in positions i−1, i + 1 and i−2. Furthermore, the 3D hNca-TOCSY-caNH and Hnca-TOCSY-caNH experiments, which share the same magnetization pathway but use a different chemical shift encoding, directly couple the ¹⁵N-¹H spin pair of residue i to adjacent amide protons and nitrogens at positions i−2, i−1, i + 1 and i + 2, respectively. These new experimental features make protein backbone assignments more robust by reducing the degeneracy problem associated with the conventional 3D NMR experiments.     

3D-QSAR studies of triazolopyrimidine derivatives of <Emphasis Type="Italic">Plasmodium falciparum</Emphasis> dihydroorotate dehydrogenase inhibitors using a combination of molecular dynamics,docking, and genetic algorithm-based methods

A series of 35 triazolopyrimidine analogues reported as Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) inhibitors were optimized using quantum mechanics methods, and their binding conformations were studied by docking and 3D quantitative structure–activity relationship studies. Genetic algorithm-based criteria was adopted for selection of training and test sets while maintaining structural diversity of training and test sets, which is also very crucial for model development and validation. Both the comparative molecular field analyses ( q_\textLOO² = 0.841 q_{\text{LOO}}^2 = 0.{841} , r_\textncv² = 0.99 r_{\text{ncv}}^2 = 0.{99} ) and comparative molecular similarity indices analyses ( q_\textLOO² = 0.757 q_{\text{LOO}}^2 = 0.{757} , r_\textncv² = 0.943 r_{\text{ncv}}^2 = 0.{943} ) show excellent correlation and high predictive power. Furthermore, molecular dynamics simulations were performed to explore the binding mode of the two of the most active compounds of the series, 10 and 14. Harmonization in the two simulation results validate the analysis and therefore applicability of docking parameters based on crystallographic conformation of compound 14 bound to receptor molecule. This work provides useful information about the inhibition mechanism of this class of molecules and will assist in the design of more potent inhibitors of PfDHODH.     

Genetic parameters and predicted selection responses for timber production traits in a Castanea sativa progeny trial: developing a breeding program

Total height, diameter, index volume, stem straightness, apical dominance, and survival were assessed at 8 years from seed in an open-pollinated progeny test of 36 families of European chestnut (Castanea sativa Miller) established at two sites in the Atlantic area of Galicia, Spain. Iterative spatial analysis was applied to eliminate the effect of the spatial dependence in the original data and to estimate accurately genetic parameters for evaluating the potential for selection of the measured trees. Spatial analysis was very beneficial for growth traits and survival, but less so if at all for form traits. Estimated individual heritabilities ranged from moderate to high for growth traits ([^(h)]_i² = 0.29 - 0.42 \widehat{h}_i^2 = 0.29 - 0.42 ) and stem straightness ([^(h)]_i² = 0.24 - 0.42 \widehat{h}_i^2 = 0.{24} - 0.{42} ). High coefficients of additive genetic variance were obtained for volume ( [^(\textC)]\textV_\textA = 36.5 - 41.5% \widehat{\text{C}}{{\text{V}}_{\text{A}}} = {36}.{5} - {41}.{5}\% ) and straightness ( [^(\textC)]\textV_\textA = 44.26 - 53.84% \widehat{\text{C}}{{\text{V}}_{\text{A}}} = {44}.{26} - {53}.{84}\% ). Phenotypic and estimated genetic correlations between growth traits were very high, and correlations between sites indicated that there was no important family × site interaction. No adverse correlations between traits were evident. The results indicate the ample potential for selection in the current progeny trial, where responses to within-family and combined selection for growth traits may be high. Accordingly, three selection scenarios were addressed with the aim to initiate the selection of individuals for implementing the Forest Breeding Plan of Galicia for European chestnut.