ABSTRACT
The loss of the tail is among the most notable anatomical changes to have occurred along the evolutionary lineage leading to humans and to the 'anthropomorphous apes'1-3, with a proposed role in contributing to human bipedalism4-6. Yet, the genetic mechanism that facilitated tail-loss evolution in hominoids remains unknown. Here we present evidence that an individual insertion of an Alu element in the genome of the hominoid ancestor may have contributed to tail-loss evolution. We demonstrate that this Alu element-inserted into an intron of the TBXT gene7-9-pairs with a neighbouring ancestral Alu element encoded in the reverse genomic orientation and leads to a hominoid-specific alternative splicing event. To study the effect of this splicing event, we generated multiple mouse models that express both full-length and exon-skipped isoforms of Tbxt, mimicking the expression pattern of its hominoid orthologue TBXT. Mice expressing both Tbxt isoforms exhibit a complete absence of the tail or a shortened tail depending on the relative abundance of Tbxt isoforms expressed at the embryonic tail bud. These results support the notion that the exon-skipped transcript is sufficient to induce a tail-loss phenotype. Moreover, mice expressing the exon-skipped Tbxt isoform develop neural tube defects, a condition that affects approximately 1 in 1,000 neonates in humans10. Thus, tail-loss evolution may have been associated with an adaptive cost of the potential for neural tube defects, which continue to affect human health today.
Subject(s)
Alternative Splicing , Evolution, Molecular , Hominidae , T-Box Domain Proteins , Tail , Animals , Humans , Mice , Alternative Splicing/genetics , Alu Elements/genetics , Disease Models, Animal , Genome/genetics , Hominidae/anatomy & histology , Hominidae/genetics , Introns/genetics , Neural Tube Defects/genetics , Neural Tube Defects/metabolism , Phenotype , Protein Isoforms/deficiency , Protein Isoforms/genetics , Protein Isoforms/metabolism , T-Box Domain Proteins/deficiency , T-Box Domain Proteins/genetics , T-Box Domain Proteins/metabolism , Tail/anatomy & histology , Tail/embryology , Exons/geneticsABSTRACT
The signals that regulate peripheral blood vessel formation during development are still under investigation. The hormone leptin promotes blood vessel formation, adipose tissue establishment and expansion, tumor growth, and wound healing, but the underlying mechanisms for these actions are currently unknown. We investigated whether leptin promotes angiogenesis in the developing tail fin using embryonic transgenic xflk-1:GFP Xenopus laevis, which express a green fluorescent protein on vascular endothelial cells to mark blood vessels. We found that leptin protein is expressed in endothelial cells of developing blood vessels and that leptin treatment via injection increased phosphorylated STAT3 signaling, which is indicative of leptin activation of its receptor, in blood vessels of the larval tail fin. Leptin administration via media increased vessel length, branching, and reconnection with the cardinal vein, while decreased leptin signaling via immunoneutralization had an opposing effect on vessel development. We also observed disorganization of major vessels and microvessels of the tail fin and muscle when leptin signaling was decreased. Reduced leptin signaling lowered mRNA expression of cenpk, gpx1, and mmp9, markers for cell proliferation, antioxidation, and extracellular matrix remodeling/cell migration, respectively, in the developing tail, providing insight into three possible mechanisms underlying leptin's promotion of angiogenesis. Together these results illustrate that leptin levels are correlated with embryonic angiogenesis and that leptin coordinates multiple aspects of blood vessel growth and development, showing that leptin is an important morphogen during embryonic development.
Subject(s)
Larva , Leptin , Neovascularization, Physiologic , Signal Transduction , Tail , Xenopus laevis , Animals , Leptin/metabolism , Tail/blood supply , Tail/embryology , Xenopus laevis/embryology , Xenopus laevis/metabolism , Larva/metabolism , Blood Vessels/embryology , Blood Vessels/metabolism , Xenopus Proteins/metabolism , Xenopus Proteins/genetics , Animals, Genetically Modified , STAT3 Transcription Factor/metabolism , Embryo, Nonmammalian/metabolism , Green Fluorescent Proteins/metabolism , Gene Expression Regulation, DevelopmentalABSTRACT
We established a normal embryonic development table for the Anji salamander Hynobius amjiensis, a critically endangered tailed amphibian of the family Hynobiidae with a very limited distribution in East China, following the standards set by the early developmental table of vertebrates. Put together 32 embryonic stages for the Anji salamander was defined. The total embryonic period from oviposition to hatching is approximately 30 days at 9 °C. Stages 1-16 represent early development from cleavage to neurulation. Stages 17-32 represent organogenesis documenting later developmental events such as tail, gill, and limb formation, and hatching (Stage 32). We provided a detailed description of the external morphology and color changes of the head, trunk, limbs, tail, external gills, and balancers at various stages from egg-laying to hatching. We also described several cases of abnormal embryonic development. The establishment of the embryonic development table in H. amjiensis contributes to better understanding of the ontogeny in tailed amphibians, distinguishing closely related species, and identifying abnormal embryonic amphibians.
Subject(s)
Embryo, Nonmammalian , Embryonic Development , Urodela , Animals , Urodela/embryology , Embryonic Development/physiology , Embryo, Nonmammalian/embryology , Female , Organogenesis/physiology , Tail/embryology , ChinaABSTRACT
The striatum can be divided into four anatomically and functionally distinct domains: the dorsolateral, dorsomedial, ventral and the more recently identified caudolateral (tail) striatum. Dopamine transmission in these striatal domains underlies many important behaviours, yet little is known about this phenomenon in the tail striatum. Furthermore, the tail is divided anatomically into four divisions (dorsal, medial, intermediate and lateral) based on the profile of D1 and D2 dopamine receptor-expressing medium spiny neurons, something that is not seen elsewhere in the striatum. Considering this organisation, how dopamine transmission occurs in the tail striatum is of great interest. We recorded evoked dopamine release in the four tail divisions, with comparison to the dorsolateral striatum, using fast-scan cyclic voltammetry in rat brain slices. Contributions of clearance mechanisms were investigated using dopamine transporter knockout (DAT-KO) rats, pharmacological transporter inhibitors and dextran. Evoked dopamine release in all tail divisions was smaller in amplitude than in the dorsolateral striatum and, importantly, regional variation was observed: dorsolateral ≈ lateral > medial > dorsal ≈ intermediate. Release amplitudes in the lateral division were 300% of that in the intermediate division, which also exhibited uniquely slow peak dopamine clearance velocity. Dopamine clearance in the intermediate division was most dependent on DAT, and no alternative dopamine transporters investigated (organic cation transporter-3, norepinephrine transporter and serotonin transporter) contributed significantly to dopamine clearance in any tail division. Our findings confirm that the tail striatum is not only a distinct dopamine domain but also that each tail division has unique dopamine transmission characteristics. This supports that the divisions are not only anatomically but also functionally distinct. How this segregation relates to the overall function of the tail striatum, particularly the processing of multisensory information, is yet to be determined.
Subject(s)
Dopamine , Tail , Rats , Animals , Corpus Striatum , Neostriatum , Dopamine Antagonists/pharmacologyABSTRACT
Benthic annelids belonging to the family Syllidae show a distinctive sexual reproduction mode called "stolonization," in which posterior segments are transformed into a reproductive individual-like unit called a "stolon." Megasyllis nipponica forms a stolon head and a secondary tail in the middle of the trunk before a stolon detaches, while, in the case of posterior amputation, posterior regeneration initiates at the wound after amputation. To understand the difference between posterior regeneration and secondary-tail formation during stolonization, detailed comparisons between the developmental processes of these two tail-formation types were performed in this study. Morphological and inner structural observations (i.e., cell proliferation and muscular/nervous development) showed that some processes of posterior regeneration, such as blastema formation and muscular/nervous regeneration at the amputation site, are missing during secondary-tail formation. In contrast, the secondary tail showed some unique features, such as the formation of ventrolateral half-tail buds that later fused in the middle and muscle/nerve branches formed before the detachment of the stolon. These novel features in the process of stolonization are suggested to be adaptive since the animals need to recover a posterior end quickly to stolonize again.
Subject(s)
Regeneration , Tail , Animals , Tail/anatomy & histology , Tail/physiology , Polychaeta/physiology , Polychaeta/anatomy & histology , Polychaeta/growth & development , Reproduction , East Asian PeopleABSTRACT
AbstractPopulation-level variation in rodent tail structures has been variously attributed to facilitating social communication, locomotion, thermoregulation, and predator avoidance. Little is known, however, about the applicability of these ecological and social correlates to explaining the tremendous interspecific diversity of this appendage. To investigate the potential drivers of rodent tail morphology at a macroevolutionary level, we first carefully reviewed the literature and constructed a list of major hypotheses regarding this variation. We then compiled a database of 11 different tail traits related to length, color, texture, and ecological characteristics for 2,101 species of rodents (order Rodentia) and examined their key evolutionary correlates. Using Bayesian phylogenetic mixed models across the entire order and additionally within the five rodent suborders, we found that tail length is correlated with both temperature (Allen's rule) and locomotory mode, that black tips are more common in brightly lit environments, that naked tails are often found in warmer climates, that fluffy-tipped tails are more common in smaller and/or arboreal species, that prehensility is predominant in arboreal species and/or species with longer tails, and that tail autotomy is more common in open environments. Most of our tested predictions, largely drawn from population-level studies, are not recapitulated across the entire order, potentially indicating a role of local ecological context in shaping tail morphology.
Subject(s)
Biological Evolution , Rodentia , Tail , Animals , Tail/anatomy & histology , Rodentia/anatomy & histology , Rodentia/physiology , Phylogeny , Bayes TheoremABSTRACT
PURPOSE: Tail-vein catheterization and subsequent in-magnet infusion is a common route of administration of deuterium (2 H)-labeled substrates in small-animal deuterium (D) MR studies. With mice, because of the tail vein's small diameter, this procedure is challenging. It requires considerable personnel training and practice, is prone to failure, and may preclude serial studies. Motivated by the need for an alternative, the time courses for common small-molecule deuterated substrates and downstream metabolites in brain following subcutaneous infusion were determined in mice and are presented herein. METHODS: Three 2 H-labeled substrates-[6,6-2 H2 ]glucose, [2 H3 ]acetate, and [3,4,4,4-2 H4 ]beta-hydroxybutyrate-and 2 H2 O were administered to mice in-magnet via subcutaneous catheter. Brain time courses of the substrates and downstream metabolites (and semi-heavy water) were determined via single-voxel DMRS. RESULTS: Subcutaneous catheter placement and substrate administration was readily accomplished with limited personnel training. Substrates reached pseudo-steady state in brain within â¼30-40 min of bolus infusion. Time constants characterizing the appearance in brain of deuterated substrates or semi-heavy water following 2 H2 O administration were similar (â¼15 min). CONCLUSION: Administration of deuterated substrates via subcutaneous catheter for in vivo DMRS experiments with mice is robust, requires limited personnel training, and enables substantial dosing. It is suitable for metabolic studies where pseudo-steady state substrate administration/accumulation is sufficient. It is particularly advantageous for serial longitudinal studies over an extended period because it avoids inevitable damage to the tail vein following multiple catheterizations.
Subject(s)
Brain , Tail , Mice , Animals , Deuterium Oxide , Deuterium , Tail/metabolism , Brain/diagnostic imaging , Brain/metabolismABSTRACT
The northern house gecko Hemidactylus flaviviridis exhibits appendage-specific responses to injuries. The autotomized tail regenerates, whereas the severed limb fails to regrow. Many site-specific cellular processes influence tail regeneration. Herein, we analyzed the epithelial-mesenchymal transition contrast in the lizard's amputated appendages (tail and limb). Morphological observations in the healing frame indicated the formation of regeneration blastema in the tail and scar formation in limb. Histology of the tail showed that epithelial cells closer to mesenchyme appeared less columnar and loosely packed, with little intercellular matrix. Whereas in the limb, the columnar epithelial cells remained tightly packed. Collagen deposition was seen in the limb at the intersection of wound epithelium and mesenchyme, favoring scarring by blocking the epithelial-mesenchymal transition. Markers for epithelial-mesenchymal transition were assessed at transcript and protein levels. The regenerating tail showed upregulation of N-cadherin, vimentin, and PCNA, favoring epithelial-mesenchymal transition, cell migration, and proliferation, respectively. In contrast, the scarring limb showed persistently elevated levels of E-cadherin and EpCAM, indicating retention of epithelial characteristics. An attempt was made to screen the resident epithelial stem cell population in both appendages to check their potential role in the epithelial-mesenchymal transition (EMT), hence the differential wound healing. Upregulation in transcript and protein levels of Nanog and Sox2 was observed in the regenerating tail. Fluorescence-activated cell sorting (FACS) provided supporting evidence that the epithelial stem cell population in tail remained significantly higher than in limb. Thus, this study focuses on the mechanistic role of the epithelial-mesenchymal transition in wound healing, highlighting the molecular details of regeneration and scarring events.
Subject(s)
Epithelial-Mesenchymal Transition , Extremities , Lizards , Regeneration , Tail , Animals , Lizards/metabolism , Epithelial-Mesenchymal Transition/physiology , Extremities/physiology , Regeneration/physiology , Amputation, SurgicalABSTRACT
Wind-hovering birds exhibit remarkable steadiness in flight, achieved through the morphing of their wings and tail. We analysed the kinematics of two nankeen kestrels (Falco cenchroides) engaged in steady wind-hovering flights in a smooth flow wind tunnel. Motion-tracking cameras were used to capture the movements of the birds as they maintained their position. The motion of the birds' head and body, and the morphing motions of their wings and tail were tracked and analysed using correlation methods. The results revealed that wing sweep, representing the flexion/extension movement of the wing, played a significant role in wing motion. Additionally, correlations between different independent degrees of freedom (DoF), including wing and tail coupling, were observed. These kinematic couplings indicate balancing of forces and moments necessary for steady wind hovering. Variation in flight behaviour between the two birds highlighted the redundancy of DoF and the versatility of wing morphing in achieving control. This study provides insights into fixed-wing craft flight control from the avian world and may inspire novel flight control strategies for future fixed-wing aircraft.
Subject(s)
Falconiformes , Flight, Animal , Tail , Wings, Animal , Animals , Flight, Animal/physiology , Wings, Animal/physiology , Wings, Animal/anatomy & histology , Biomechanical Phenomena , Tail/physiology , Tail/anatomy & histology , Falconiformes/physiology , Falconiformes/anatomy & histology , WindABSTRACT
Tail wagging is a conspicuous behaviour in domestic dogs (Canis familiaris). Despite how much meaning humans attribute to this display, its quantitative description and evolutionary history are rarely studied. We summarize what is known about the mechanism, ontogeny, function and evolution of this behaviour. We suggest two hypotheses to explain its increased occurrence and frequency in dogs compared to other canids. During the domestication process, enhanced rhythmic tail wagging behaviour could have (i) arisen as a by-product of selection for other traits, such as docility and tameness, or (ii) been directly selected by humans, due to our proclivity for rhythmic stimuli. We invite testing of these hypotheses through neurobiological and ethological experiments, which will shed light on one of the most readily observed yet understudied animal behaviours. Targeted tail wagging research can be a window into both canine ethology and the evolutionary history of characteristic human traits, such as our ability to perceive and produce rhythmic behaviours.
Subject(s)
Canidae , Tail , Animals , Dogs , Behavior, Animal , Domestication , Social BehaviorABSTRACT
BACKGROUND: The natural abundance of nitrogen (δ15N) and carbon (δ13C) isotopes in animal tissues are used to estimate an animal's efficiency in nitrogen utilization, and their feed conversion efficiency, especially in tropical grazing systems with prolonged protein restriction. It is postulated that selection for improving these two characteristics (δ15N and δ13C) would assist the optimisation of the adaptation in ever-changing environments, particularly in response to climate change. The aim of this study was to determine the heritability of δ15N and δ13C in the tail hair of tropically adapted beef cattle to validate their inclusion in genetic breeding programs. METHODS: In total, 492 steers from two breeds, Brahman (n = 268) and Droughtmaster (n = 224) were used in this study. These steers were managed in two mixed breed contemporary groups across two years (year of weaning): steers weaned in 2019 (n = 250) and 2020 (n = 242). Samples of tail switch hair representing hair segments grown during the dry season were collected and analysed for δ15N and δ13C with isotope-ratio mass spectrometry. Heritability and variance components were estimated in a univariate multibreed (and single breed) animal model in WOMBAT and ASReml using three generations of full pedigree. RESULTS: The estimated heritability of both traits was significantly different from 0, i.e. 0.43 ± 0.14 and 0.41 ± 0.15 for δ15N and δ13C, respectively. These traits had favourable moderate to high genetic and phenotypic correlations (- 0.78 ± 0.16 and - 0.40 ± 0.04, respectively). The study also provides informative single-breed results in spite of the limited sample size, with estimated heritability values of 0.37 ± 0.19 and 0.19 ± 0.17 for δ15N and δ13C in Brahman, and 0.36 ± 0.21 and 0.46 ± 0.22 for δ15N and δ13C in Droughtmaster, respectively. CONCLUSIONS: The findings of this study show, for the first time, that the natural abundances of both nitrogen and carbon isotopes in the tail hair in cattle may be moderately heritable. With further research and validation, tail hair isotopes can become a practical tool for the large-scale selection of more efficient cattle.
Subject(s)
Nitrogen , Tail , Cattle/genetics , Animals , Carbon Isotopes , Tail/chemistry , Phenotype , HairABSTRACT
BACKGROUND: Previous research showed that deviations in longitudinal data are heritable and can be used as a proxy for pigs' general resilience. However, only a few studies investigated the relationship between these resilience traits and other traits related to resilience and welfare. Therefore, this study investigated the relationship between resilience traits derived from deviations in longitudinal data and traits related to animal resilience, health and welfare, such as tail and ear biting wounds, lameness and mortality. RESULTS: In our experiment, 1919 finishing pigs with known pedigree (133 Piétrain sires and 266 crossbred dams) were weighed every 2 weeks and scored for physical abnormalities, such as lameness and ear and tail biting wounds (17,066 records). Resilience was assessed via deviations in body weight, deviations in weighing order and deviations in observed activity during weighing. The association between these resilience traits and physical abnormality traits was investigated and genetic parameters were estimated. Deviations in body weight had moderate heritability estimates (h2 = 25.2 to 36.3%), whereas deviations in weighing order (h2 = 4.2%) and deviations in activity during weighing (h2 = 12.0%) had low heritability estimates. Moreover, deviations in body weight were positively associated and genetically correlated with tail biting wounds (rg = 0.22 to 0.30), lameness (rg = 0.15 to 0.31) and mortality (rg = 0.19 to 0.33). These results indicate that events of tail biting, lameness and mortality are associated with deviations in pigs' body weight evolution. This relationship was not found for deviations in weighing order and activity during weighing. Furthermore, individual body weight deviations were positively correlated with uniformity at the pen level, providing evidence that breeding for these resilience traits might increase both pigs' resilience and within-family uniformity. CONCLUSIONS: In summary, our findings show that breeding for resilience traits based on deviations in longitudinal weight data can decrease pigs' tail biting wounds, lameness and mortality while improving uniformity at the pen level. These findings are valuable for pig breeders, as they offer evidence that these resilience traits are an indication of animals' general health, welfare and resilience. Moreover, these results will stimulate the quantification of resilience via longitudinal body weights in other species.
Subject(s)
Bites and Stings , Lameness, Animal , Tail , Animals , Swine , Tail/injuries , Bites and Stings/psychology , Female , Male , Body Weight , Breeding/methods , Quantitative Trait, Heritable , Phenotype , Swine Diseases/geneticsABSTRACT
The genetic foundation of chicken body plumage color has been extensively studied. However, little attention has been paid to the inheritance patterns and molecular mechanisms underlying the formation of distal feather colors (tail and wingtip). Differences in these colors are common; for example, the Chinese Huiyang Beard chicken has black tail feathers, but yellow body plumage. Here, the hybrid offspring of Huiyang Beard and White Leghorn chickens were used to study the inheritance patterns of tail-feather color. The expression levels of pigment genes in differently colored feather follicles were analyzed using quantitative real-time PCR. The results showed that genetic regulation of tail-feather color was independent of body-plumage color. The Dominant White locus inhibited eumelanin synthesis in tail feathers without affecting the formation of yellow body plumage, whereas the Silver locus had the opposite effect. The expression of agouti signaling protein (ASIP) gene class 1 transcripts was significantly lower in black tail-feather follicles than in yellow body follicles, whereas tyrosinase-related protein 1 (TYRP1) gene expression was significantly higher in black tail feathers. These differentially expressed genes were confirmed to exert an effect on eumelanin and pheomelanin formation in feathers, thus influencing the regulation of chicken tail-feather color. In conclusion, this study lays the foundation for further research on the genetic mechanisms of regional differences in feather color, contributing to a better understanding of plumage pigmentation in chickens.
Subject(s)
Chickens , Tail , Animals , Chickens/genetics , Agouti Signaling Protein/genetics , Feathers/physiology , Gene Expression , Pigmentation/geneticsABSTRACT
Lobsters and crayfish in Australasia can develop a condition known as Tail Fan Necrosis (TFN syndrome). Many attempts have been made to find a primary pathogen or link the syndrome to commercial activities, but a solution remains elusive. TFN syndrome is a 'wicked problem', a problem difficult or impossible to solve because of incomplete and contradictory information forming a matrix of potential outcomes with no simple solution. Reviewing the literature shows TFN syndrome is sometimes reported to develop in association with sterile blisters on the telson and uropods which may rupture permitting invasion by environmental fungal and/or bacterial flora. Whether blisters form prior to, or because of, infection is unknown. TFN syndrome sometimes develops in captivity, sometimes requires a previous insult to the telson and uropods, and prevalence is patchy in the wild. The literature shows the cause of blisters associated with TFN syndrome remains an enigma, for which we suggest several possible initiating factors. We strongly urge that researchers not 'jump to conclusions' as to the aetiology of TFN syndrome. It cannot be explained without carefully exploring alternative aetiologies whilst being cognisant of the age-old lesson that 'correlation does not equal causation'.
Subject(s)
Decapoda , Fish Diseases , Animals , Tail , Blister/veterinary , Necrosis/microbiologyABSTRACT
BACKGROUND: The thyroid gland is an important endocrine gland in animals that secretes thyroid hormones and acts on various organs throughout the body. lncRNAs are long non-coding RNAs that play an important role in animal reproduction; however, there is a lack of understanding of their expression patterns and potential roles in the thyroid gland of the Small Tail Han (STH) sheep. In this study, we used RNA-Seq technology to examine the transcriptome expression pattern of the thyroid from the luteal phase (LP) and follicular phase (FP) of FecB BB (MM) STH sheep. RESULTS: We identified a total of 122 and 1287 differential expression lncRNAs (DELs) and differential expression mRNAs (DEGs), respectively, which were significantly differentially expressed. These DELs target genes and DEGs can be enriched in several signalling pathways related to the animal reproduction process. CONCLUSIONS: The expression profiles of DELs and DEGs in thyroid glands provide a more comprehensive resource for elucidating the reproductive regulatory mechanisms of STH sheep.
Subject(s)
RNA, Long Noncoding , Thyroid Gland , Female , Sheep/genetics , Animals , RNA, Long Noncoding/genetics , RNA, Messenger/genetics , Tail , Gene Expression Profiling/veterinary , GenotypeABSTRACT
Intramuscular fat (IMF) is vital for meat tenderness and juiciness. This study aims to explore the IMF deposition mechanism and the related molecular markers in sheep. Two populations, Small-tail Han Sheep (STH) and STH × Suffolk (SFK) F1 (SFK × STH), were used as the research object. Histological staining techniques compared the differences in the longissimus dorsi muscle among populations. A combination of transcriptome sequencing and biological information analysis screened and identified IMF-related target genes. Further, sequencing technology was employed to detect SNP loci of target genes to evaluate their potential as genetic markers. Histological staining revealed that the muscle fiber gap in the SFK × STH F1 was larger and the IMF content was higher. Transcriptome analysis revealed that PIK3R1 and PPARA were candidate genes. Histological experiments revealed that the expressions of PIK3R1 mRNA and PPARA mRNA were lower in SFK × STH F1 compared with the STH. Meanwhile, PIK3R1 and PPARA proteins were located in intramuscular adipocytes and co-located with the lipid metabolism marker molecule (FASN). SNP locus analysis revealed a mutation site in exon 7 of the PIK3R1 gene, which served as a potential genetic marker for IMF deposition. This study's findings will provide a new direction for meat quality breeding in sheep.
Subject(s)
Gene Expression Profiling , Tail , Sheep/genetics , Animals , Tail/metabolism , Meat , Genetic Markers , RNA, Messenger/geneticsABSTRACT
It has been reported that, in the spontaneously hypertensive rat (SHR) model of hypertension, different components of the G-protein/adenylate cyclase (AC)/Calcium-activated potassium channel of high conductance (BK) channel signaling pathway are altered differently. In the upstream part of the pathway (G-protein/AC), a comparatively low efficacy has been established, whereas downstream BK currents seem to be increased. Thus, the overall performance of this signaling pathway in SHR is elusive. For a better understanding, we focused on one aspect, the direct targeting of the BK channel by the G-protein/AC pathway and tested the hypothesis that the comparatively low AC pathway efficacy in SHR results in a reduced agonist-induced stimulation of BK currents. This hypothesis was investigated using freshly isolated smooth muscle cells from WKY and SHR rat tail artery and the patch-clamp technique. It was observed that: (1) single BK channels have similar current-voltage relationships, voltage-dependence and calcium sensitivity; (2) BK currents in cells with a strong buffering of the BK channel activator calcium have similar current-voltage relationships; (3) the iloprost-induced concentration-dependent increase of the BK current is larger in WKY compared to SHR; (4) the effects of activators of the PKA pathway, the catalytic subunit of PKA and the potent and selective cAMP-analogue Sp-5,6-DCl-cBIMPS on BK currents are similar. Thus, our data suggest that the lower iloprost-induced stimulation of the BK current in freshly isolated rat tail artery smooth muscle cells from SHR compared with WKY is due to the lower efficacy of upstream elements of the G-Protein/AC/BK channel pathway.
Subject(s)
Calcium , Hypertension , Iloprost , Large-Conductance Calcium-Activated Potassium Channels , Muscle, Smooth, Vascular , Rats, Inbred SHR , Rats, Inbred WKY , Vasodilator Agents , Animals , Large-Conductance Calcium-Activated Potassium Channels/metabolism , Muscle, Smooth, Vascular/drug effects , Muscle, Smooth, Vascular/metabolism , Muscle, Smooth, Vascular/cytology , Rats , Calcium/metabolism , Iloprost/pharmacology , Hypertension/metabolism , Hypertension/drug therapy , Vasodilator Agents/pharmacology , Myocytes, Smooth Muscle/metabolism , Myocytes, Smooth Muscle/drug effects , Male , Arteries/drug effects , Arteries/metabolism , Tail/blood supply , Signal Transduction/drug effectsABSTRACT
AIMS: To undertake a survey of the prevalence of tail deviations, trauma and shortening on a representative selection of New Zealand dairy farms, and to assess whether sampling based on milking order could be used instead of random sampling across the herd to estimate prevalence. METHODS: This was a cross-sectional observational study, with 200 randomly selected farms enrolled across nine regions of New Zealand via selected veterinary practices (one/region). Veterinary clinics enrolled 20-25 farms each depending on region, with 1-2 trained technicians scoring per region. All cows (n = 92,348) present at a milking or pregnancy testing event were tail scored using a modified version of the New Zealand Veterinary Association Industry Scoring System. Palpated lesions were recorded as deviated (i.e. non-linear deformity), shortened (tail shorter than normal) or traumatic (all other lesions). The location of lesions was defined by dividing the tail into three equal zones: upper, middle and lower. A cow could have more than one lesion type and location, and/or multiple lesions of the same type, but for the prevalence calculation, only the presence or absence of a particular lesion was assessed. Prevalence of tail damage calculated using whole herd scoring was compared to random sampling across the herd and sampling from the front and back of the milking order. Bootstrap sampling with replacement was used to generate the sampling distributions across seven sample sizes ranging from 40-435 cows. RESULTS: When scoring all cows, the median prevalence for deviation was 9.5 (min 0.9, max 40.3)%; trauma 0.9 (min 0, max 10.7)%, and shortening was 4.5 (min 1.3, max 10.8)%. Deviation and trauma prevalence varied between regions; the median prevalence of deviations ranged from 6% in the West Coast to 13% in Waikato, and the median prevalence of all tail damage from 7% in the West Coast to 29% in Southland. Sampling based on milking order was less precise than random sampling across the herd. With the latter and using 157 cows, 95% of prevalence estimates were within 5% of the whole herd estimate, but sampling based on milking order needed > 300 cows to achieve the same precision. CONCLUSIONS AND CLINICAL RELEVANCE: The proportion of cows identified as having damaged tails was consistent with recent reports from New Zealand and Ireland, but at 11.5%, the proportion of cows with trauma or deviation is below acceptable standards. An industry-wide programme is needed to reduce the proportion of affected cows.