The cattle tick Rhipicephalus microplus is an ectoparasite with high economic importance to bovine culture, mainly in tropical and subtropical regions. The resistance of the tick from the commercial acaricides has hindered its control, thus motivating the search for new strategies. The purpose of this study was to perform a critical review about the main molecular targets of R. microplus that are useful for the discovery of new acaricides. Bibliographic search was conducted in the databases PubMed, ScienceDirect and CAB Direct, using the following descriptors: ‘Rhipicephalus microplus’, ‘Boophilus microplus’, ‘molecular targets’ and ‘action’, published between 2010 and 2021. Out of the 212 publications identified, 17 articles were selected for study inclusion. This review described 14 molecular targets and among these 4 are targets from commercial acaricides. Most of them are enzymes to catalyse important reactions to tick survival, related to energetic metabolism, mechanisms of biotransformation and neurotransmission. The data will be helpful in the development of new more effective and selective acaricides.

Clinically important differences exist between antipsychotic agents and formulations in terms of safety and tolerability. Features of the biochemical interaction between the antipsychotic and the D2-receptor may underlie these differences. This article reviews current information on the relationship between antipsychotic receptor occupancy and clinical response. A literature search was performed using the keywords ‘antipsychotic or neuroleptic’, ‘receptor’ and ‘occupancy’ and ‘dopamine’ and ‘D2’ supplemented by the authors’ knowledge of the literature. Imaging and clinical data have generally supported the hypotheses that optimal D2-receptor occupancy in the striatum lies in a ‘therapeutic window’ between ∼65 and ∼80%, however, pharmacokinetic and pharmacodynamic properties of a drug should also be taken into account to fully evaluate its therapeutic effects. Additional research, perhaps in preclinical models, is needed to establish D2-receptor occupancy in various regions of the brain and the optimal duration of D2-receptor blockade in order to maximise efficacy and tolerability profiles of atypical antipsychotics and thereby improve treatment outcomes for patients with schizophrenia.

Reverse-transcription polymerase chain reaction (RT-PCR) investigation of the expression of the components supposedly taking part in serotonin regulation of the early development of Paracentrotus lividus has shown the presence of transcripts of five receptors, one of which has conservative amino acid residues characteristic of monoaminergic receptors. At the early stages of embryogenesis the expressions of serotonin transporter (SERT) and noradrenaline transporter (NET) were also recognized. The activities of the enzymes of serotonin synthesis and serotonin transporter were shown using immunohistochemistry and incubation with para-chlorophenylalanine (PСРА) and 5-hydroxytryptophan (HTP). Pharmacological experiments have shown a preferential cytostatic activity of ligands characterized as mammalian 5-hydroxytryptamine (5-HT)1-antagonists. On the basis of the sum of the data from molecular biology and embryo physiological experiments, it is suggested that metabotropic serotonin receptors and membrane transporters take part in the regulatory processes of early sea urchin embryogenesis.

An eletrical potential recorded from the cornea, the a-wave of the ERG, is evaluated as a measure of human photoreceptor activity by comparing its behavior to a model derived from in vitro recordings from rod photoreceptors. The leading edge of the ERG exhibits both the linear and nonlinear behavior perdicted by this model. The capability for recording the electrical activity of humans photoreceptors in in vivo opens new avenues for assessing normal and abnormal receptor activity in humans. Furthermore, the quantitative model of the receptor response can be used to isolate the inner retinal contribution, Granit's PII, to the gross ERG. Based on this analysis, the practice of using the trough-to-peak amplitude of the b-wave as a proxy for the amplitude of the inner nuclear layer activity is evaluated.

The leading edge of the a–wave of the electroretinogram (ERG) was evaluated as a measure of human cone photoreceptor activity. The amplitude of the cone a–wave elicited by flashes of different energy was compared to the predictions of a class of models from in vitro studies of cone photoreceptors. These models successfully describe the leading edge of the a–wave. Thus, the human cone a–wave can be used to test hypotheses about normal and abnormal cone receptors. The ability of the human cone to adjust its sensitivity in the presence of steady adapting lights was assessed by recording cone a–waves to flashes on adapting fields up to 3.9 log td in intensity and by comparing these responses to quantitative models of adaptation. The first 10 ms of the cone's response is little affected by field intensities up to 2.9 log td. The 3.9 log td field reduced the response to weak flashes by about a factor of 2.5 (0.4 log unit). This relatively small reduction in sensitivity can be attributed to a combination of response compression, pigment bleaching, and an adaptation mechanism that changes the gain without changing the time course. We conclude that either the human cones show relatively little adaptation or that they have an adaptation mechanism that involves a time-course change. That is, as we are limited with the a–wave to the first 10 ms or so of the cone's response, we cannot rule out a gain mechanism linked to a time-course change.

Recent studies have shown that several receptor populations in cat visual cortex undergo alterations in their laminar distributions during postnatal development (Shaw et al., 1984a, b; 1986b). These redistributions occur during the first few months of postnatal life, coincident with the physiologically defined critical period for cortical plasticity. In the present communication, we demonstrate that receptor redistributions can be prevented from occurring, or progressing once started, by surgically isolating the visual cortex at appropriate postnatal ages. These data suggest that the maturation of the chemical circuitry of the visual cortex is dependent on factors of extrinsic origin.

In the starfish, spermatozoa undergo the acrosome reaction upon encountering the jelly coat of eggs. A highly sulphated glycoprotein in the jelly coat is called acrosome-reaction-inducing substance (ARIS) because it is the key signal molecule to trigger the acrosome reaction. The activity of ARIS is mainly attributed to its sulphate and saccharide residues. The extremely large molecular size and speciesspecific action of ARIS suggest the presence of a specific ARIS receptor on the sperm surface, but no experimental evidence for the receptor has been presented. We therefore measured specific binding of ARIS and its pronase digest (P-ARIS), which retains the full activity of ARIS, to homologous spermatozoa by using fluorescien-isothiocyanate-labelled ARIS and125 I-labelled P-ARIS, respectively. The spermatozoa had the ability to bind ARIS, as well as P-ARIS, specifically. The binding was species-specific, and mostly localised to the head region of spermatozoa. Scatchard plot analysis indicated the presence of one class of ARIS receptor on the surface of acrosome-intact speramatozoa. Furthermore, the specific binding of P-ARIS to the anterior region of sperm heads was microscopically confirmed by using P-ARIS conjugated to polystyrene latex beads with intense fluorescence. It is concluded that starfish spermatozoa have a specific receptor for ARIS on the surface of the anterior region of heads.

Hay diferencias clínicamente importantes en la seguridad y tolerabilidad de los antipsicóticos dependiendo de los distintos tipos y de sus formulaciones. Las características de la interacción bioquímica entre el antipsicótico y el receptor D2 pueden ser la base de estas diferencias. Este artículo revisa la información actual sobre la relación entre la ocupación del antipsicótico por el receptor y la respuesta clínica. Se hizo una búsqueda en la literatura introduciendo las palabras clave “antipsicótico o neuroléptico”, “receptor”, “ocupación”, “dopamina” y “D2” y se complementó con búsquedas manuales en la literatura. Los datos de las pruebas de neuroimagen y clínicas, generalmente, confirmaron que la ocupación óptima de los receptores D2 del núcleo estriado se sitúa en “una ventana térapeutica” entre ∼ 65% y ∼ 80%; sin embargo, las propiedades farmacocinéticas y farmacodinámicas del fármaco también deberían tenerse en cuenta para evaluar totalmente sus efectos terapéuticos. Deberían realizarse nuevas investigaciones, quizá, en modelos preclínicos, para deetrminar la ocupación de los receptores D2 en varias regiones cerebrales y la duración óptima del bloqueo de los receptores D2 para maximizar los perfiles de eficacia y tolerabilidad de los antipsicóticos atípicos y mejorar los resultados del tratamiento de los pacientes con esquizofrenia.

Escherichia coli is one of the most important causes of postweaning diarrhea in pigs. This diarrhea is responsible for economic losses due to mortality, morbidity, decreased growth rate, and cost of medication. The E. coli causing postweaning diarrhea mostly carry the F4 (K88) or the F18 adhesin. Recently, an increase in incidence of outbreaks of severe E. coli-associated diarrhea has been observed worldwide. The factors contributing to the increased number of outbreaks of this more severe form of E. coli-associated diarrhea are not yet fully understood. These could include the emergence of more virulent E. coli clones, such as the O149:LT:STa:STb:EAST1:F4ac, or recent changes in the management of pigs. Development of multiple bacterial resistance to a wide range of commonly used antibiotics and a recent increase in the prevalence and severity of the postweaning syndromes will necessitate the use of alternative measures for their control. New vaccination strategies include the oral immunization of piglets with live avirulent E. coli strains carrying the fimbrial adhesins or oral administration of purified F4 (K88) fimbriae. Other approaches to control this disease include supplementation of the feed with egg yolk antibodies from chickens immunized with F4 or F18 adhesins, breeding of F18- and F4-resistant animals, supplementation with zinc and/or spray-dried plasma, dietary acidification, phage therapy, or the use of probiotics. To date, not a single strategy has proved to be totally effective and it is probable that the most successful approach on a particular farm will involve a combination of diet modification and other preventive measures.

Aims: To identify subgroups of patients with squamous cell carcinoma (SCC) of the larynx, characterized by the specific deregulation mechanism of the epidermal growth factor receptor (EGFR) gene, and to evaluate EGFR protein expression levels and correlate these with biological and clinicopathological parameters.

Materials and methods: Using tissue microarray technology, 50 formalin-fixed, paraffin-embedded primary laryngeal SCCs were cored and re-embedded into one block. Immunohistochemistry and chromogenic in situ hybridization were performed.

Results: Epidermal growth factor receptor protein over-expression was observed in 27/50 (54 per cent) cases and was statistically associated with tumour grade (p=0.028). Epidermal growth factor receptor gene alterations were identified in 5/50 (10 per cent) cases, which demonstrated amplification (n=4) and deletion (n=1). Chromosome 7 instability was detected in 8/50 (16 per cent) cases.

Conclusions: Epidermal growth factor receptor over-expression is a frequent event in SCCs, but it does not predict a specific molecular mechanism of gene deregulation for targeted therapeutic strategies via monoclonal antibodies.

Although the effects of trematode infection on snail host physiology or host responses on parasite development have been well described in the literature, very little is known regarding the underlying mechanisms and specific molecules responsible for mediating those effects. It is presumed that many host–parasite interactions are communicated through receptor-mediated events, in particular those involving haemocytic immune responses to invading parasites, larval motility and migration through host tissues, and larval acquisition of host molecules either as nutrients or critical developmental factors. The intent of this chapter is to review current knowledge of molecules (both receptors and their ligands or counter-receptors) involved in molecular communication at the interface between larval trematodes, especially the mother or primary sporocyst stage, and host cells/tissues in intimate proximity to developing larvae. Information to date suggests that the molecular exchange at this interface is a highly complex and dynamic process, and appears to be regulated in specific cases. Topics discussed will focus on snail cell receptor interactions with the sporocyst tegument and its secretions, host cell–cell and cell–substrate adhesion receptors and their related signal transduction pathways, and sporocyst tegumental surface receptors and ligands involved in the binding of soluble host molecules.

In the retina of the African clawed frog (Xenopus laevis), melatonin is synthesized by the photoreceptors at night, and binds to receptors that likely mediate paracrine responses. Melatonin appears to alter the sensitivity of the retinal cells to light, and may play a key role in regulating important circadian events that occur in the eye. A polyclonal antibody was raised against a 13 amino acid peptide corresponding to a region of the third cytoplasmic loop of the Xenopus laevis Mel1c melatonin receptor. Western blot analysis revealed a major immunoreactive band of approximately 60 kD in neural retina and retinal pigment epithelium (RPE) membranes. Immunocytochemical labeling of sections of Xenopus eyes demonstrated intense melatonin receptor-like immunoreactivity in the inner plexiform layer (IPL). Immunolabeling with antibodies to glutamate decarboxylase (GAD) or tyrosine hydroxylase (TOH) appeared to co-localize with the melatonin receptor immunoreactivity in different sublaminas of the IPL. This suggests that both GABAergic and dopaminergic amacrine cells express melatonin receptor protein. There were also some melatonin receptor immunoreactive varicose fibers in the IPL that did not co-localize with either TOH or GAD, and may represent efferent fibers, since they could be followed into the optic nerve. Melatonin receptor immunoreactivity was also present on cell soma in the ganglion cell layer. Furthermore, a moderate level of melatonin receptor immunoreactivity was observed in the RPE and rod and cone photoreceptor cells. The presence of melatonin receptor immunoreactivity in these cells supports previous observations of melatonin receptor RNA expression in multiple cell types in the Xenopus retina. Expression of melatonin receptor protein in the photoreceptors suggests that melatonin may have a direct action on these cells.

The binding capacity of the L-leucine receptor from Escherichia coli was measured with L-phenylalanine and 4-fluoro-L-phenylalanine as substrates by fluorescence. The apparent dissociation constants (KD) for L-leucine, L-phenylalanine, and 4-fluoro-L-phenylalanine are 0.40, 0.18, and 0.26 respectively. 19F NMR data show protein-induced shifts for the 4-fluoro-L-phenylalanine peak and 3-fluoro-L-phenylalanine when receptor is present. Evidence points to the binding of only the L-isomers of these fluorine analogs.

The aim of the present study was to investigate whether growth hormone (GH) has any effect on the development of cultured rat pre-antral follicles. Pre-antral follicles with a diameter between 120 μm and 160 μm were mechanically isolated from 10-day-old rat ovaries and cultured in groups for 6 days in serum-free medium without GH or with GH supplemented at concentrations of 1, 10 and 100 ng/ml, respectively. DNA content of the follicles before and after culture was measured to determine whether possible growth is due to proliferation of follicular cells. To investigate the quality of follicles cultured under different conditions, the ultrastructure of the cultured follicles was studied with transmission electron microscopy. Furthermore, reverse transcriptase polymerase chain reaction (RT-PCR) was used to assess the expression of growth hormone receptor (GHR) in pre-antral follicles. GH, regardless of the concentration, stimulated the growth of pre-antral follicles. However, follicles cultured in medium supplemented with high-dose GH (100 ng/ml) showed a significantly lower survival rate compared with the other groups. Follicles cultured in GH-containing medium showed a better ultrastructure in comparison with those cultured in medium without GH. Remarkably, scattered cortical granules were observed in oocytes of follicles cultured in the presence of GH. With RT-PCR, the presence of the mRNA of GHR was demonstrated in pre-antral follicles. It can be concluded that GH promotes rat pre-antral follicle development in vitro and better supports the morphology of cultured pre-antral follicles. The gene expression of GHR suggests that the action of GH could be mediated by its receptors present in pre-antral follicles.