Hepatic adenylate cyclase. Development-dependent coupling to the beta-adrenergic receptor in the neonate

Guanine nucleotide-dependent modulation of agonist binding to the beta-receptor reflects coupling of the receptor to the nucleotide regulatory protein. Similarly, guanine nucleotide-dependent stimulation of adenylate cyclase can be used as an index of coupling between the regulatory protein and the catalytic unit of the cyclase. Using both approaches we have studied coupling in the beta-adrenergic receptor-adenylate cyclase system in rabbit liver during neonatal development. With [3H]dihydroalprenolol as ligand, the Bmax was relatively unchanged (200-300 fmol/mg of protein) between birth and end of day 1 and was similar to adult values. Guanyl-5'-yl imidodiphosphate-dependent shift in agonist (l-isoproterenol) competition curves was biphasic, decreasing from 10-fold in membranes isolated from animals at term to about 6-fold in membranes from 6-h-old neonates, and increasing progressively in older animals to a maximal measurable value of 42-fold in the adult. The ability of guanyl-5'-yl imidodiphosphate, GTP, GTP plus isoproterenol, NaF, or forskolin to activate adenylate cyclase was also biphasic and age-dependent. With Mn2+ the measured activity was not at any time greater than the activity at term. Pretreatment of membranes with cholera toxin resulted in differential levels of enhancement of adenylate cyclase activity wherein much lower enhancement was observed in membranes from neonatal animals. With [32P]NAD as substrate, cholera toxin-catalyzed ADP-ribosylation of membranes indicated development-dependent accumulation of Ns peptides. From these results we suggest that there is a decreased efficiency in the coupling of the beta-adrenergic receptor to hepatic adenylate cyclase in early neonatal life. The molecular basis for the biphasic nature of the coupling is presently unclear.     

Tracing paternal ancestry in mice, using the Y-linked, sex-determining locus, Sry

The molecular evolution of mammalian Y-linked DNA sequences is of special interest because of their unique mode of inheritance: most Y- linked sequences are clonally inherited from father to son. Here we investigate the use of Y-linked sequences for phylogenetic inference. We describe a comparative analysis of a 515-bp region from the male sex- determining locus, Sry, in 22 murine rodents (subfamily Murinae, family Muridae), including representatives from nine species of Mus, and from two additional murine genera--Mastomys and Hylomyscus. Percent sequence divergence was < 0.01% for comparisons between populations within a species and was 0.19%-8.16% for comparisons between species. Our phylogenetic analysis of 12 murine taxa resulted in a single most- parsimonius tree that is highly concordant with phylogenies based on mitochondrial DNA and allozymes. A total evidence tree based on the combined data from Sry, mitochondrial DNA, and allozymes supports (1) the monophyly of the subgenus Mus, (2) its division into a Palearctic group (M. musculus, M. domesticus, M. spicilegus, M. Macedonicus, and M. spretus) and an Oriental group (M. cookii++, M. cervicolor, and M. caroli), and (3) sister-group relationships between M. spicilegus and M. macedonicus and between M. cookii and M. cervicolor. We argue that Y- chromosome DNA sequences represent a valuable new source of characters for phylogenetic inference.      

Le ionophore A23187

The acrosomic status of spermatozoa prepared for IVF has been evaluated by means of immunofluorescence test from Fenichel and Hsi using calcium A 23187 ionophore as inductor of acrosome reaction (AR). The spontaneous AR remains slight, even after 6 hour-incubation in Menezo B2 (6,8+2,7%). The response to ionophore, moderate before (11,2+9%), frankly increases after a 6h-capacitation (28,9+8,3%) in a group of 25 IVF couples (tubal indication, normal semen, positive fertilization). Nevertheless, it remains slight or null in 4 cases of unexplained repeated failure of fertilization. The response to ionophore A 23187 allows to explore the kinetics of capacitation of spermatozoa and their ability to perform AR. Its significance in terms of fecondance remains to be precised.     

Representation of moving stimuli by somatosensory neurons.

The findings obtained in neurophysiological and psychophysical investigations using tactile stimuli that move at constant velocity across the skin are reviewed. For certain neurons in the postcentral gyrus of the cerebral cortex (S-I) of macaque monkeys, direction of stimulus motion is a "trigger feature" i.e., moving tactile stimuli evoke vigorous discharge activity in these neurons only if the stimuli are moved in a particular direction across the receptive field. This directional selectivity is maximal when stimulus velocity is between 5 and 50 cm/sec, and falls off rapidly at lower or higher velocities. The capacity for human subjects to correctly identify the direction of stimulus motion on the skin exhibits a similar dependence on stimulus velocity. The similar effects of velocity on neural and psychophysical measures of directional sensitivity support the idea that direction of stimulus motion on the skin can only be recognized if the moving stimulus optimally activates the group of S-I neurons for which that directions of simulus motion is the trigger feature.     

Behavioural and chemical mechanisms behind a Mediterranean ant–ant association

1. Interspecific competition among ants is common, and so is competitive exclusion among dominant ant species. In contrast, specific associations between non‐parasitic ant species are rare, especially in the temperate zones. As an exception, the subordinate ant Camponotus lateralis frequently co‐occurs with the dominant Crematogaster scutellaris but rarely with other dominant ants. 2. This association is one of various associations between Camponotus and Crematogaster species across the world. However, the mechanisms behind these co‐occurences are largely unknown. 3. In the present study, we therefore investigated the association of Ca. lateralis and Cr. scutellaris. We studied the spatial association of the nests, interspecific aggression, both species' cuticular hydrocarbon profiles, and their propensity to follow the other species' pheromone trails. 4. Crematogaster scutellaris usually attacked and displaced the generally submissive Ca. lateralis, but was significantly less aggressive at jointly used trails. Camponotus nests were always in close proximity to Crematogaster nests. 5. The cuticular hydrocarbons of both species consisted of alkanes with chain lengths between C21 and C35. The two species had 25 hydrocarbons in common, including mono‐, di‐, and tetramethyl alkanes. Despite this qualitative similarity, however, the quantitative hydrocarbon composition differed between the two species. 6. Camponotus lateralis followed artificial trails containing trail pheromones of Cr. scutellaris, but the latter did not follow Ca. lateralis trail pheromones. Interspecific trail‐following by Camponotus, but not vice versa, has been observed in another Camponotus–Crematogaster association and may be a more general mechanism that facilitates associations between the two ant genera.     

Stability of rapidly adapting afferent entrainment vs responsivity

Spike discharge activity was recorded from low-threshold, rapidly adapting, skin mechanoreceptive afferents (RA afferents) dissected from the median (forelimb) or tibial (hindlimb) nerves in anesthetized monkeys and cats. The spike activity was evoked by delivery of controlled sinusoidal vertical skin displacement ("flutter") stimuli to the receptive field (RF). The stimuli (15-30 Hz; 30-400 microm peak-to-peak amplitude; duration 0.8-15 s) were superimposed on a static skin indentation (0.5-1.0 mm) which was either maintained continuously throughout the run or applied trial-by-trial. The neural activity and the analog signal of the position of the stimulator probe were digitized at 10 kHz resolution and stored for off-line analysis. The main goal was to determine whether changes in the RA afferent response to skin flutter stimulation may be responsible for the enhanced capacity to discriminate stimulus frequency that accompanies a relatively brief (approximately 1 min) pre-exposure to such stimulation in humans. To this end, the spike train data were evaluated using methods that enabled independent measurement of entrainment and responsivity. Responsivity (response intensity) was measured as the average number of spikes/stimulus cycle, while entrainment (the degree to which evoked spike train activity is phase-locked to the stimulus) was quantitatively assessed using statistical techniques developed for the analysis of "circular" (directional) data, supplemented by methods based on the calculation of power spectra from point process data. The methods are demonstrated to enable quantification of RA afferent entrainment over a range of stimulus durations and amplitudes substantially greater than reported in previous studies. While RA afferent responsivity was found to decline to a minor extent (10-20%) both across and within stimulus trials, entrainment remained consistently high and stable, and exhibited no temporal trends or dependence on any other measured factor. The average phase angle of the entrained RA afferent response also remained stable both within and across trials, showing only a tendency to increase slightly during the initial 100-500 ms after stimulus onset. The results imply that the improved capacity to discriminate stimulus frequency that develops in response to an exposure to cutaneous flutter stimulation is not attributable to a change in RA afferent entrainment per se.     

Effects of high-frequency skin stimulation on SI cortex: mechanisms and functional implications

Optical intrinsic signal (OIS) imaging methods were used to record the responses of contralateral SI cortex to 25 Hz ("flutter") and also to 200 Hz ("vibration") stimulation of the skin. Anesthetized cats and squirrel monkeys were subjects. Separate series of experiments were carried out to evaluate the contralateral SI response to continuous, multisecond 25 Hz vs. 200 Hz stimulation (a) at multiple skin sites arranged along the proximal-distal axis of the fore- or hindlimb (Series I); (b) in the presence and absence of a ring placed in firm contact with the skin surrounding the stimulus site (Series II); (c) before and after topical application of local anesthetic to the stimulus site (Series III); and, finally, (c) to continuous 25 Hz or 200 Hz stimulation applied independently, and also concomitantly ("complex waveform stimulation") to the same skin site (Series IV). The principal findings are: (a) the relationship between the SI optical responses to 25 Hz vs. 200 Hz stimulation of a skin site varies systematically with position of the stimulus site on the limb-at a distal site both 25 Hz and 200 Hz stimulation evoke a well-maintained increase in absorbance, and as the stimulus site is shifted proximally on the limb the response to 200 Hz, but not the response to 25 Hz stimulation, converts to a frank decrease in absorbance; (b) placement of a ring about a skin site at which in the absence of a ring 200 Hz stimulation evoked a decrease in SI absorbance converts the response to 200 Hz to one consistent with increased SI RA neuronal activation (i.e., with the ring in place 200 Hz stimulation evokes a change in SI absorbance approximating the response to 25 Hz stimulation); (c) topical local anesthetic preferentially and reversibly decreases the magnitude of the absorbance increase associated with 25 Hz flutter stimulation; and (d) complex waveform stimulation consistently is associated with a smaller increase in absorbance than obtained with same-site 25 Hz stimulation. Collectively, the findings are consistent with the idea that the Pacinian (PC) afferent activity which unavoidably accompanies cutaneous flutter stimulation triggers CNS mechanisms that "funnel" (sharpen) the spatially distributed contralateral SI response to the flutter stimulus. Viewed in this context, the fact that a flutter stimulus unavoidably co-activates RA and PC afferents appears functionally beneficial because the CNS mechanisms activated by PC afferent drive modify the SI response to skin flutter in a manner predicted to enable more accurate perceptual localization than would be possible if the flutter stimulus only activated RA afferents.     

Intra‐floral resource partitioning between endemic and invasive flower visitors: consequences for pollinator effectiveness

1. Sympatric flower visitor species often partition nectar and pollen and thus affect each other's foraging pattern. Consequently, their pollination service may also be influenced by the presence of other flower visiting species. Ants are solely interested in nectar and frequent flower visitors of some plant species but usually provide no pollination service. Obligate flower visitors such as bees depend on both nectar and pollen and are often more effective pollinators. 2. In Hawaii, we studied the complex interactions between flowers of the endemic tree Metrosideros polymorpha (Myrtaceae) and both, endemic and introduced flower‐visiting insects. The former main‐pollinators of M. polymorpha were birds, which, however, became rare. We evaluated the pollinator effectiveness of endemic and invasive bees and whether it is affected by the type of resource collected and the presence of ants on flowers. 3. Ants were dominant nectar‐consumers that mostly depleted the nectar of visited inflorescences. Accordingly, the visitation frequency, duration, and consequently the pollinator effectiveness of nectar‐foraging honeybees (Apis mellifera) strongly decreased on ant‐visited flowers, whereas pollen‐collecting bees remained largely unaffected by ants. Overall, endemic bees (Hylaeus spp.) were ineffective pollinators. 4. The average net effect of ants on pollination of M. polymorpha was neutral, corresponding to a similar fruit set of ant‐visited and ant‐free inflorescences. 5. Our results suggest that invasive social hymenopterans that often have negative impacts on the Hawaiian flora and fauna may occasionally provide neutral (ants) or even beneficial net effects (honeybees), especially in the absence of native birds.     

Trophic ecology of parabiotic ants: Do the partners have similar food niches?

Organisms associated with another species may experience both costs and benefits from their partner. One of these costs is competition, which is the more likely if the two species are ecologically similar. Parabioses are associations between two ant species that share a nest and often attend the same food sources. Albeit parabioses are probably mutualistic, parabiotic partners may compete for food. We therefore investigated feeding niches and dietary overlap of two parabiotically associated ants in Borneo using cafeteria experiments and stable isotope analyses. The two species strongly differed in their food choices. While Crematogaster modiglianii mostly foraged at carbohydrate‐rich baits, Camponotus rufifemur preferred urea‐rich sources. Both species also consumed animal protein. The ¹⁵N concentration in Ca. rufifemur workers was consistently lower than in Cr. modiglianii. Camponotus rufifemur but not Cr. modiglianii possesses microbial endosymbionts, which can metabolize urea and synthesize essential amino acids. Its lower ¹⁵N signature may result from a relatively higher intake of plant‐based or otherwise ¹⁵N‐depleted nitrogen. Isotopic signatures of the two partners in the same parabiosis showed strongly parallel variation across nests. As we did not find evidence for spatial autocorrelation, this correlation suggests an overlap of food sources between the two ant species. Based on model simulations, we estimated a diet overlap of 22–66% for nitrogen sources and 45–74% for carbon sources. The overlap may arise from either joint exploitation of the same food sources or trophallactic exchange of food. This suggests an intense trophic interaction and potential for competition between the parabiotic partners.     

Inter-proteomic posttranslational modifications of the SARS-CoV-2 and the host proteins ‒ A new frontier

Posttranslational modification of proteins, which include both the enzymatic alterations of protein side chains and main-chain peptide bond connectivity, is a fundamental regulatory process that is crucial for almost every aspects of cell biology, including the virus-host cell interaction and the SARS-CoV-2 infection. The posttranslational modification of proteins has primarily been studied in cells and tissues in an intra-proteomic context (where both substrates and enzymes are part of the same species). However, the inter-proteomic posttranslational modifications of most of the SARS-CoV-2 proteins by the host enzymes and vice versa are largely unexplored in virus pathogenesis and in the host immune response. It is now known that the structural spike (S) protein of the SARS-CoV-2 undergoes proteolytic priming by the host serine proteases for entry into the host cells, and N- and O-glycosylation by the host cell enzymes during virion packaging, which enable the virus to spread. New evidence suggests that both SARS-CoV-2 and the host proteins undergo inter-proteomic posttranslational modifications, which play roles in virus pathogenesis and infection-induced immune response by hijacking the host cell signaling. The purpose of this minireview is to bring attention of the scientific community to recent cutting-edge discoveries in this understudied area. It is likely that a better insight into the molecular mechanisms involved may open new research directions, and thereby contribute to novel therapeutic modality development against the SARS-CoV-2. Here we briefly discuss the rationale and touch upon some unanswered questions in this context, especially those that require attention from the scientific community.