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Τρίτη 21 Νοεμβρίου 2017
Neostigmine-based reversal of intermediate acting neuromuscular blocking agents to prevent postoperative residual paralysis: A systematic review
BACKGROUND Neostigmine is widely used to antagonise residual paralysis. Over the last decades, the benchmark of acceptable neuromuscular recovery has increased progressively to a train-of-four (TOF) ratio of at least 0.9. Raising this benchmark may impact on the efficacy of neostigmine. OBJECTIVE(S) The systematic review evaluates the efficacy of neostigmine to antagonise neuromuscular block to attain a TOF ratio of at least 0.9. DESIGN We performed a systematic search of the literature from January 1992 to December 2015. DATA SOURCES OR SETTING PubMed, EMBASE and the Cochrane Controlled Clinical Trials database were searched for randomised controlled human studies. Search was performed without language restrictions, using the following free text terms: 'neostigmine', 'sugammadex', 'edrophonium' or 'pyridostigmine' AND 'neuromuscular block', 'reversal' or 'reverse'. ELIGIBILITY CRITERIA Studies were accepted for inclusion if they used quantitative neuromuscular monitoring and neostigmine as the reversal agent. Selected trials were checked by two of the authors for data integrity. Trials relevant for inclusion had to report the number of patients included, the type of anaesthetic maintenance, the type of neuromuscular blocking agent used, the reversal agent and dose used, the depth of neuromuscular block when neostigmine was administered and the reversal time (time from injection of neostigmine until a TOF ratio ≥0.9 was attained). RESULTS 19 trials were eligible for quantitative analysis. In patients with deep residual block [T1 (first twitch height) 25% of baseline), or that a recovery time longer than 15 min be accepted. Correspondence to Thomas Fuchs-Buder, MD, Department of Anaesthesia and Critical Care, University Hospital of Nancy, Rue du Morvan, F-54511 Vandoeuvre-Les-Nancy, France. Cedex E-mail: t.fuchs-buder@chru-nancy.fr © 2017 European Society of Anaesthesiology
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Rapid Gene Family Evolution of a Nematode Sperm Protein Despite Sequence Hyper-conservation
Reproductive proteins are often observed to be the most rapidly evolving elements within eukaryotic genomes. The major sperm protein (MSP) is unique to the phylum Nematoda and is required for proper sperm locomotion and fertilization. Here we annotate the MSP gene family and analyze their molecular evolution in ten representative species across Nematoda. We show that across the phylum, MSPs are hyper-conserved having maintained an amino acid sequence identity of 83.5% to 97.7% for over 500 million years. This extremely slow rate of evolution makes MSPs some of the most highly conserved genes yet identified. At the gene family level, however, we show hyper-variability in both gene copy number and genomic position within species, suggesting rapid, lineage-specific gene family evolution. Additionally, we find evidence that extensive gene conversion contributes to the maintenance of sequence identity within chromosome-level clusters of MSP genes. Thus, while not conforming to the standard expectation for the evolution of reproductive proteins, our analysis of the molecular evolution of the MSP gene family is nonetheless consistent with the widely repeatable observation that reproductive proteins evolve rapidly, in this case in terms of the genomic properties of gene structure, copy number, and genomic organization. This unusual evolutionary pattern is likely generated by strong pleiotropic constraints acting on these genes at the sequence-level balanced against expansion at the level of the whole gene family.
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Caenorhabditis elegans DBL-1/BMP Regulates Lipid Accumulation via Interaction with Insulin Signaling
Metabolic homeostasis is coordinately controlled by diverse inputs. Understanding these regulatory networks is vital to combating metabolic disorders. The nematode Caenorhabditis elegans has emerged as a powerful, genetically tractable model system for the discovery of lipid regulatory mechanisms. Here we introduce DBL-1, the C. elegans homolog of bone morphogenetic protein 2/4 (BMP2/4), as a significant regulator of lipid homeostasis. We used neutral lipid staining and a lipid droplet marker to demonstrate that both increases and decreases in DBL-1/BMP signaling result in reduced lipid stores and lipid droplet count. We find that lipid droplet size, however, correlates positively with the level of DBL 1/BMP signaling. Regulation of lipid accumulation in the intestine occurs through non-cell-autonomous signaling, since expression of SMA-3, a Smad signal transducer, in the epidermis (hypodermis) is sufficient to rescue the loss of lipid accumulation. Finally, genetic evidence indicates that DBL-1/BMP functions upstream of Insulin/IGF-1 Signaling in lipid metabolism. We conclude that BMP signaling regulates lipid metabolism in C. elegans through inter-organ signaling to the Insulin pathway, shedding light on a less well-studied regulatory mechanism for metabolic homeostasis.
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Rice TSV3 Encoding Obg-Like GTPase Protein Is Essential for Chloroplast Development During the Early Leaf Stage Under Cold Stress
The Spo0B-associated GTP-binding (Obg) proteins are essential for the viability of nearly all bacteria. However, detailed roles of Obg proteins in higher plants have not yet been elucidated. In this study, we identified a novel rice (Oryza sativa L.) thermo-sensitive virescent mutant, tsv3 that displayed albino phenotype at 20°C before the 3-leaf stage while being normal green at 32°C or even at 20°C after the 4-leaf stage. The mutant phenotype was consistent with altered chlorophyll content and chloroplast structure in leaves. Map-based cloning and complementation experiments showed that TSV3 encoded a small GTP-binding protein. Subcellular localization studies revealed that TSV3 was localized to the chloroplasts. Expression of TSV3 was high in leaves and weak or undetectable in other tissues, suggesting a tissue-specific expression of TSV3. In the tsv3 mutant, expression levels of genes associated with the biogenesis of the chloroplast ribosome 50S subunit were severely decreased at the 3-leaf-stage under cold stress (20°C), but could be recovered to normal levels at a higher temperature (32°C). These observations suggest that the rice nuclear-encoded TSV3 plays important roles in chloroplast development at early leaf stage under cold stress.
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Should short-term use of alcohol containing mouthrinse be avoided for fear of worsening xerostomia?
Abstract
Objective
To assess the short-term effect of alcohol-containing mouthrinse versus mouthrinse without alcohol on xerostomia scores reported by xerostomia inventory (XI) scores and short version of the xerostomia inventory (SXI).
Materials and Methods
This study was a two-group parallel arm randomized controlled trial where participants were randomly allocated to twice a day for seven days use of either alcohol-containing or alcohol-free mouthrinse. Allocation was concealed. The participants, the outcome assessors and the statistician were blinded to the allocation status.
Results
163 participants completed the pre-and post-intervention data collection. There were no statistically significant differences between the study groups with respect to demographics or other measured independent variables. After adjusting for age and gender, regression coefficient (95%CI) for XI was 0.02(-1.72 to 2.29) and that for SXI was 0.03(-0.54 to 0.83). Both adjusted and unadjusted models showed no significant differences for change in XI or SXI. The mean difference in scores between the groups for XI was -0.45(-2.45 to 1.55) and for SXI was 0.05(-0.65 to 0.75).
Conclusion
There was no significant difference in the change in xerostomia levels as a result of short-term exposure to alcohol containing mouthrinse, when compared to those exposed to alcohol-free mouthrinse.
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Jaw Closing Movement and Sex Differences in Temporomandibular Joint Energy Densities
Abstract
Energy densities (ED, mJ/mm3) quantify mechanical work imposed on articular cartilages during function. This cross-sectional study examined differences in temporomandibular joint (TMJ) ED during asymmetric versus symmetric jaw closing in healthy females versus males. ED component variables were tested for differences between and within sexes for two types of jaw closing. Seventeen female and 17 male subjects gave informed consent to participate. Diagnostic Criteria for Temporomandibular Disorders and images (magnetic resonance (MR), computed tomography) were used to confirm healthy TMJ status. Numerical modeling predicted TMJ loads (Fnormal) consequent to unilateral canine biting. Dynamic stereometry combined MR imaging and jaw tracking data to measure ED component variables during 10 trials of each type of jaw closing in each subject's TMJs. These data were then used to calculate TMJ ED during jaw closing asymmetrically and symmetrically. Paired and Student's t-tests assessed ED between jaw closing movements and sexes, respectively. Multivariate data analyses assessed ED component variable differences between jaw closing movements and sexes (α=0.05). Contralateral TMJ ED were 3.6-fold and significantly larger (P<0.0001) during asymmetric versus symmetric jaw closing, due to significantly larger (P≤0.001) distances of TMJ stress-field translation in asymmetric versus symmetric movement. During asymmetric jaw closing, contralateral TMJ ED were two-fold and significantly larger (P=0.036) in females versus males, due to 1.5-fold and significantly smaller (P≤0.010) TMJ disc cartilage volumes under stress-fields in females versus males. These results suggest that in healthy individuals asymmetric compared to symmetric jaw closure in females compared to males have higher TMJ mechanical fatigue liabilities.
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Anterior cement augmentation of adjacent levels after vertebral body replacement leads to superior stability of the corpectomy cage under cyclic loading – a biomechanical investigation
In the operative treatment of osteoporotic vertebral body fractures, a dorsal stabilization in combination with a corpectomy of the fractured vertebral body might be necessary with respect to the fracture morphology, whereby the osteoporotic bone quality may possibly increase the risk of implant failure. In order to achieve better stability, it is recommended to use cement-augmented screws for dorsal instrumentation. Beside careful endplate preparation cement augmentation of the adjacent endplates has also been reported to lead to less reduction loss.
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Prognosis of sciatica and back-related leg pain in primary care: the ATLAS cohort.
Evidence is lacking on the prognosis and prognostic factors for back-related leg pain and sciatica in patients seeing their primary care physicians. This could guide timely appropriate treatment and referral decisions.
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Long-term outcomes of transforaminal lumbar interbody fusion in patients with spinal stenosis and degenerative scoliosis
Spinal deformity patients may present with complaints related to either the deformity itself or to the manifestations of the coexisting spinal stenosis. There are reports of successful management of lumbar pathology in the absence of global sagittal or coronal imbalance, with limited decompression and fusion, addressing only the symptomatic segment.
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What does the shape of our back tell us? correlation between sacrum orientation and lumbar lordosis
Sacral slope and lumbar lordosis have been studied extensively in recent years via x-ray examinations and strongly correlate with each other. This raises firstly the question of the reproducibility of this correlation in multiple standing phases and secondly whether this correlation can be achieved using non-radiological measurement tools.
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Pounding tools in HWK EE and EF-HR (Olduvai Gorge, Tanzania): Percussive activities in the Oldowan-Acheulean transition
Source:Journal of Human Evolution
Author(s): Adrián Arroyo, Ignacio de la Torre
In this paper, we present pounded objects from excavations at HWK EE and EF-HR, which are studied from macro and microscopic perspectives. Analysis of HWK EE revealed one of the largest collections of percussive objects from Olduvai Gorge, while excavations at EF-HR have allowed us to recover a much wider collection of percussive tools than previously recorded. Differences are observed between the two localities. At the Acheulean site of EF-HR, percussive tools were predominantly used in the production of flakes and large cutting tools (LCTs). At the Oldowan site of HWK EE, the tool repertoire probably related to a wider range of activities, including bone breaking and bipolar knapping. Comparison of these two assemblages, potentially produced by different hominin species, helps provide a wider picture of pounding activities during the Oldowan-Acheulean transition at Olduvai Gorge.
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The effect of age and body composition on body mass estimation of males using the stature/bi-iliac method
Source:Journal of Human Evolution
Author(s): Juho-Antti Junno, Markku Niskanen, Heli Maijanen, Brigitte Holt, Vladimir Sladek, Sirpa Niinimäki, Margit Berner
The stature/bi-iliac breadth method provides reasonably precise, skeletal frame size (SFS) based body mass (BM) estimations across adults as a whole. In this study, we examine the potential effects of age changes in anthropometric dimensions on the estimation accuracy of SFS-based body mass estimation. We use anthropometric data from the literature and our own skeletal data from two osteological collections to study effects of age on stature, bi-iliac breadth, body mass, and body composition, as they are major components behind body size and body size estimations. We focus on males, as relevant longitudinal data are based on male study samples. As a general rule, lean body mass (LBM) increases through adolescence and early adulthood until people are aged in their 30s or 40s, and starts to decline in the late 40s or early 50s. Fat mass (FM) tends to increase until the mid-50s and declines thereafter, but in more mobile traditional societies it may decline throughout adult life. Because BM is the sum of LBM and FM, it exhibits a curvilinear age-related pattern in all societies. Skeletal frame size is based on stature and bi-iliac breadth, and both of those dimensions are affected by age. Skeletal frame size based body mass estimation tends to increase throughout adult life in both skeletal and anthropometric samples because an age-related increase in bi-iliac breadth more than compensates for an age-related stature decline commencing in the 30s or 40s. Combined with the above-mentioned curvilinear BM change, this results in curvilinear estimation bias. However, for simulations involving low to moderate percent body fat, the stature/bi-iliac method works well in predicting body mass in younger and middle-aged adults. Such conditions are likely to have applied to most human paleontological and archaeological samples.
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Maturation is prolonged and variable in female chimpanzees
Publication date: January 2018
Source:Journal of Human Evolution, Volume 114
Author(s): Kara K. Walker, Christopher S. Walker, Jane Goodall, Anne E. Pusey
Chimpanzees are important referential models for the study of life history in hominin evolution. Age at sexual maturity and first reproduction are key life history milestones that mark the diversion of energy from growth to reproduction and are essential in comparing life history trajectories between chimpanzees and humans. Yet, accurate information on ages at these milestones in wild chimpanzees is difficult to obtain because most females transfer before breeding. Precise age at first birth is only known from a relatively small number of non-dispersing individuals. Moreover, due to small sample sizes, the degree to which age at maturation milestones varies is unknown. Here we report maturation milestones and explore sources of variance for 36 wild female chimpanzees of known age, including eight dispersing females born in Gombe National Park, Tanzania. Using Kaplan-Meier survival analysis, including censored intervals, we find an average age of 11.5 years (range 8.5–13.9) at sexual maturity and 14.9 years (range 11.1–22.1) at first birth. These values exceed previously published averages for wild chimpanzees by one or more years. Even in this larger sample, age at first birth is likely underestimated due to the disproportionate number of non-dispersing females, which, on average, give birth two years earlier than dispersing females. Model selection using Cox Proportional Hazards models shows that age at sexual maturity is delayed in females orphaned before age eight years and those born to low-ranking mothers. Age at first birth is most delayed in dispersing females and those orphaned before age eight years. These data provide improved estimates of maturation milestones in a population of wild female chimpanzees and indicate the importance of maternal factors in development.
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The biomechanical significance of the frontal sinus in Kabwe 1 (Homo heidelbergensis)
Source:Journal of Human Evolution, Volume 114
Author(s): Ricardo Miguel Godinho, Paul O'Higgins
Paranasal sinuses are highly variable among living and fossil hominins and their function(s) are poorly understood. It has been argued they serve no particular function and are biological 'spandrels' arising as a structural consequence of changes in associated bones and/or soft tissue structures. In contrast, others have suggested that sinuses have one or more functions, in olfaction, respiration, thermoregulation, nitric oxide production, voice resonance, reduction of skull weight, and craniofacial biomechanics. Here we assess the extent to which the very large frontal sinus of Kabwe 1 impacts on the mechanical performance of the craniofacial skeleton during biting. It may be that the browridge is large and the sinus has large trabecular struts traversing it to compensate for the effect of a large sinus on the ability of the face to resist forces arising from biting. Alternatively, the large sinus may have no impact and be sited where strains that arise from biting would be very low. If the former is true, then infilling of the sinus would be expected to increase the ability of the skeleton to resist biting loads, while removing the struts might have the opposite effect. To these ends, finite element models with hollowed and infilled variants of the original sinus were created and loaded to simulate different bites. The deformations arising due to loading were then compared among different models and bites by contrasting the strain vectors arising during identical biting tasks. It was found that the frontal bone experiences very low strains and that infilling or hollowing of the sinus has little effect on strains over the cranial surface, with small effects over the frontal bone. The material used to infill the sinus experienced very low strains. This is consistent with the idea that frontal sinus morphogenesis is influenced by the strain field experienced by this region such that it comes to lie entirely within a region of the cranium that would otherwise experience low strains. This has implications for understanding why sinuses vary among hominin fossils.
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Using the covariation of extant hominoid upper and lower jaws to predict dental arcades of extinct hominins
Source:Journal of Human Evolution, Volume 114
Author(s): Stefanie Stelzer, Philipp Gunz, Simon Neubauer, Fred Spoor
Upper and lower jaws are well represented in the fossil record of mammals and are frequently used to diagnose species. Some hominin species are only known by either their maxillary or mandibular morphology, and in this study, we explore the possibility of predicting their complementary dental arcade shape to aid the recognition of conspecific specimens in the fossil record. To this end, we apply multiple multivariate regression to analyze 3D landmark coordinates collected on associated upper and lower dental arcades of extant Homo, Pan, Gorilla, Pongo, and Hylobates. We first study the extant patterns of variation in dental arcade shape and quantify how accurate predictions of complementary arcades are. Then we explore applications of this extant framework for interpreting the fossil record based on two fossil hominin specimens with associated upper and lower jaws, KNM-WT 15000 (Homo erectus sensu lato) and Sts 52 (Australopithecus africanus), as well as two non-associated specimens of Paranthropus boisei, the maxilla of OH 5 and the Peninj mandible. We find that the shape differences between the predictions and the original fossil specimens are in the range of variation within genera or species and therefore are consistent with their known affinity. Our approach can provide a reference against which intraspecific variation of extinct species can be assessed. We show that our method predicts arcade shapes reliably even if the target shape is not represented in the reference sample. We find that in extant hominoids, the amount of within-taxon variation in dental arcade shape often overlaps with the amount of between-taxon shape variation. This implies that whereas a large difference in dental arcade shape between two individuals typically suggests that they belong to different species or even genera, a small shape difference does not necessarily imply conspecificity.
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Homo naledi pelvic remains from the Dinaledi Chamber, South Africa
Source:Journal of Human Evolution
Author(s): Caroline VanSickle, Zachary Cofran, Daniel García-Martínez, Scott A. Williams, Steven E. Churchill, Lee R. Berger, John Hawks
In the hominin fossil record, pelvic remains are sparse and are difficult to attribute taxonomically when they are not directly associated with craniodental material. Here we describe the pelvic remains from the Dinaledi Chamber in the Rising Star cave system, Cradle of Humankind, South Africa, which has produced hominin fossils of a new species, Homo naledi. Though this species has been attributed to Homo based on cranial and lower limb morphology, the morphology of some of the fragmentary pelvic remains recovered align more closely with specimens attributed to the species Australopithecus afarensis and Australopithecus africanus than they do with those of most (but not all) known species of the genus Homo. As with A. afarensis and A. africanus, H. naledi appears to have had marked lateral iliac flare and either a weakly developed or non-existent acetabulocristal buttress or a distinct, albeit weakly developed, acetabulospinous buttress. At the same time, H. naledi has robust superior pubic and ischiopubic rami and a short ischium with a narrow tuberoacetabular sulcus, similar to those found in modern humans. The fragmentary nature of the Dinaledi pelvic assemblage makes the attribution of sex and developmental age to individual specimens difficult, which in turn diminishes our ability to identify the number of individuals represented in the assemblage. At present, we can only confidently say that the pelvic fossils from Rising Star represent at least four individuals based on the presence of four overlapping right ischial fossils (whereas a minimum of 15 individuals can be identified from the Dinaledi dental assemblage). A primitive, early Australopithecus-like false pelvis combined with a derived Homo-like true pelvis is morphologically consistent with evidence from the lower ribcage and proximal femur of H. naledi. The overall similarity of H. naledi ilia to those of australopiths supports the inference, drawn from the observation of primitive pelvic morphology in the extinct species Homo floresiensis, that there is substantial variation in pelvic form within the genus Homo. In the light of these findings, we urge caution in making taxonomic attributions—even at the genus level—of isolated fossil ossa coxae.
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Assessing the accuracy of body mass estimation equations from pelvic and femoral variables among modern British women of known mass
Source:Journal of Human Evolution
Author(s): Mariel Young, Fjola Johannesdottir, Ken Poole, Colin Shaw, J.T. Stock
Femoral head diameter is commonly used to estimate body mass from the skeleton. The three most frequently employed methods, designed by Ruff, Grine, and McHenry, were developed using different populations to address different research questions. They were not specifically designed for application to female remains, and their accuracy for this purpose has rarely been assessed or compared in living populations. This study analyzes the accuracy of these methods using a sample of modern British women through the use of pelvic CT scans (n = 97) and corresponding information about the individuals' known height and weight. Results showed that all methods provided reasonably accurate body mass estimates (average percent prediction errors under 20%) for the normal weight and overweight subsamples, but were inaccurate for the obese and underweight subsamples (average percent prediction errors over 20%). When women of all body mass categories were combined, the methods provided reasonable estimates (average percent prediction errors between 16 and 18%). The results demonstrate that different methods provide more accurate results within specific body mass index (BMI) ranges. The McHenry Equation provided the most accurate estimation for women of small body size, while the original Ruff Equation is most likely to be accurate if the individual was obese or severely obese. The refined Ruff Equation was the most accurate predictor of body mass on average for the entire sample, indicating that it should be utilized when there is no knowledge of the individual's body size or if the individual is assumed to be of a normal body size. The study also revealed a correlation between pubis length and body mass, and an equation for body mass estimation using pubis length was accurate in a dummy sample, suggesting that pubis length can also be used to acquire reliable body mass estimates. This has implications for how we interpret body mass in fossil hominins and has particular relevance to the interpretation of the long pubic ramus that is characteristic of Neandertals.
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Clinical features of otolith organ-specific vestibular dysfunction
The vestibular end organs consist of three semicircular canals (SCCs) and two otolith organs in each ear. The main symptom caused by dysfunction of the SCCs, which sense rotatory accelerations, is considered to be rotatory vertigo. Acute unilateral peripheral vestibular dysfunction such as vestibular neuritis (VN) causes rotatory vertigo, and the diagnosis of VN requires the objective analysis of canal paresis, which is generally assessed by tests of lateral SCC function, such as caloric testing and/or the horizontal head impulse test (HIT) (Halmagyi et al., 1988; Weber et al., 2009).
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DNA damage response protein TOPBP1 regulates X chromosome silencing in the mammalian germ line [Genetics]
Meiotic synapsis and recombination between homologs permits the formation of cross-overs that are essential for generating chromosomally balanced sperm and eggs. In mammals, surveillance mechanisms eliminate meiotic cells with defective synapsis, thereby minimizing transmission of aneuploidy. One such surveillance mechanism is meiotic silencing, the inactivation of genes located on asynapsed...
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Coordinated regulation of heterochromatin inheritance by Dpb3-Dpb4 complex [Genetics]
During DNA replication, chromatin is disrupted ahead of the replication fork, and epigenetic information must be restored behind the fork. How epigenetic marks are inherited through DNA replication remains poorly understood. Histone H3 lysine 9 (H3K9) methylation and histone hypoacetylation are conserved hallmarks of heterochromatin. We previously showed that the...
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Epigenetic switch turns on genetic behavioral variations [Genetics]
What roles do environmental factors, genes, and heredity play in shaping the behaviors of individuals? In his 1963 article entitled "Behavior genetics and individuality understood," the pioneering behavioral geneticist Jerry Hirsch (1) eloquently articulated that "Individual differences are no accident. They are generated by properties of organisms as fundamental to...
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Epigenetic mechanisms modulate differences in Drosophila foraging behavior [Genetics]
Little is known about how genetic variation and epigenetic marks interact to shape differences in behavior. The foraging (for) gene regulates behavioral differences between the rover and sitter Drosophila melanogaster strains, but the molecular mechanisms through which it does so have remained elusive. We show that the epigenetic regulator G9a...
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Ultraaccurate genome sequencing and haplotyping of single human cells [Biophysics and Computational Biology]
Accurate detection of variants and long-range haplotypes in genomes of single human cells remains very challenging. Common approaches require extensive in vitro amplification of genomes of individual cells using DNA polymerases and high-throughput short-read DNA sequencing. These approaches have two notable drawbacks. First, polymerase replication errors could generate tens of...
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Haplotype resolution at the single-cell level [Genetics]
One of the most rapidly advancing areas in genomics in recent years has been the explosion of platforms to assess properties at the single-cell level. The driving force behind these advancements has been a renaissance of sorts in how we think about the architecture and heterogeneity present in a population...
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Key amino acid residues conferring enhanced enzyme activity at cold temperatures in an Antarctic polyextremophilic {beta}-galactosidase [Genetics]
The Antarctic microorganism Halorubrum lacusprofundi harbors a model polyextremophilic β-galactosidase that functions in cold, hypersaline conditions. Six amino acid residues potentially important for cold activity were identified by comparative genomics and substituted with evolutionarily conserved residues (N251D, A263S, I299L, F387L, I476V, and V482L) in closely related homologs from mesophilic haloarchaea....
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Activation of voltage-dependent K+ channels strongly limits hypoxia-induced elevation of [Ca2+]i in rat carotid body glomus cells
Abstract
Large-conductance KCa (BK) and other voltage-dependent K+ channels (Kv) are highly expressed in carotid body (CB) glomus cells, but their role in hypoxia-induced excitation is still not well defined and remains controversial. We addressed this issue by studying the effects of inhibitors of BK (IBTX) and BK/Kv (TEA/4-AP) on [Ca2+]i responses to a wide range of hypoxia at different levels of resting cell Em. IBTX and TEA/4-AP did not affect the basal [Ca2+]i in isolated glomus cells bathed in 5 mm KClo, but elicited transient increases in [Ca2+]i in cells that were moderately depolarized (11–20 mV) by elevation of [KCl]o (12–20 mm). Thus, BK and Kv were mostly closed at rest and activated by depolarization. Four different levels of hypoxia (mild, moderate, severe, and anoxia) were used to produce a wide range of [Ca2+]i elevation (0-700 nm). IBTX did not affect the rise in [Ca2+]i, but TEA/4-AP strongly (∼3-fold) enhanced [Ca2+]i rise by moderate and severe levels of hypoxia. Guangxitoxin, a Kv2 blocker, inhibited the whole-cell current by ∼50%, and enhanced 2-fold the [Ca2+]i rise elicited by moderate and severe levels of hypoxia. Anoxia did not directly affect BK, but activated BK via depolarization. Our findings do not support the view that hypoxia inhibits BK/Kv to initiate or maintain the hypoxic response. Rather, our results show that BK/Kv are activated as glomus cells depolarize in response to hypoxia, which then limits the rise in [Ca2+]i. Inhibition of Kv may provide a mechanism to enhance the chemosensory activity of the CB and ventilation.
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Identification of microRNAs involved in drought stress responses in early-maturing cotton by high-throughput sequencing
Abstract
Drought stress is one of the most important abiotic stresses. Cotton is classified as drought tolerant crop but the regulatory mechanism is unknown. MicroRNAs (miRNAs) have been implicated important roles in stress responses in many plants. However, the study of miRNAs in cotton responsive to drought stress is limited, especially in early-maturing cotton. In this study, we performed deep sequencing of small RNAs to identify known and novel miRNAs involved in the regulation of drought stress and understand the expression profile of miRNAs in early-maturing cotton. Three cotton small RNA libraries: non-stressed Shizao1 (early-maturing cotton variety) library (NSS), drought-stressed Shizao1 library (DSS) and non-stressed Jimian958 (medium-maturing cotton variety) library (NSJ) were constructed for deep sequencing. As a result, we identified a total of 64 known and 67 novel miRNAs in the 3 libraries and 88 of them were dramatically differentially expressed (greater than twofold) during drought stress. In addition, we found the expression of 41 miRNAs increased or reduced more than twofold in early-maturing cotton variety compared with that in medium-maturing cotton variety. Our results significantly increased the number of miRNAs in cotton and revealed for the first time the expression profile of miRNAs for early-maturing cotton.
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In vivo evidence on the functional variation within fatty acid synthase gene associated with lipid metabolism in bovine longissimus dorsi muscle tissue
Abstract
In Korean cattle, intramuscular fat (IMF), or marbling, of the longissimus dorsi muscle (LM) cross section is one of the most important indicators of beef quality and are influenced by environmental and genetic factors. This study was to evaluate the effect of SNPs on the beef quality in Korean cattle for functional studies, such as site-directed mutagenesis based on bovine adipocytes. The fatty acid synthase (FASN) gene plays an important role in lipogenesis. FASN is an essential metabolic and multifunctional enzyme in fatty acid synthesis. Several studies have reported that SNPs g.841G, g.16024A, g.16039T, and g.17924G have a significant impact on marbling scores in Korean cattle and Japanese Black cattle population. These SNPs are located in transcription factor binding sites, the beta-ketoacyl reductase, and thioesterase domains. Our results revealed that the g.17924 A>G SNP is located in the thioesterase domain of the FASN protein, and changes from polar, neutral, and hydrophilic to nonpolar, aliphatic, and hydrophobic, respectively. In in vivo LM tissue of Korean cattle, the g.17924A>G SNP has an effect on increasing fat deposition. Therefore, g.17924A>G SNP could be a causal mutation for increasing fat deposition in Korean cattle LM tissue.
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Characterization of the dynamic change of microRNA expression in mice hypothalamus during the time of female puberty
Abstract
Puberty onset is a milestone in sexual development. A tumor suppress gene (TSG) network had been reported to be involved in the regulation of female puberty onset. The observations in rodents and primates showed a potential link between microRNAs and puberty onset. To figure out what miRNAs play roles in this important biological process, profilings of microRNAs in the hypothalamus of female mice from three different pubertal stages, juvenile [postnatal day (P10)], early pubertal (P25) and pubertal (P30) were performed on the Affymetrix GeneChip miRNA 3.0 Arrays, the cerebral cortex (CTX) was used as a control tissue. 20 miRNAs were shown to be differentially expressed in hypothalamus (fold change > 1.5, P < 0.05), but not in CTX during the transition from juvenile to pubertal. Four of them were validated by real-time quantitative RT-PCR (qRT-PCR) method. 1018 genes were predicted as the targets of these miRNAs. Further bioinformatics analysis suggested that these target genes were involved in many important signaling pathways, especially in the cancer related pathways. We also found that about 90% of these target genes were expressed in the hypothalamus, as well as in the immortalized GnRH-producing GT1-7 cells, which provided additional evidence that these miRNAs could be female puberty onset related. Here we present a novel comprehensive data set of miRNA gene expression during the puberty onset; and it provides an important recourse for the future functional characterization of individual miRNAs and their targets in mouse hypothalamus and in GT1-7 cells.
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Acute intermittent hypoxia with concurrent hypercapnia evokes P2X and TRPV1 receptor dependent sensory long-term facilitation in naïve carotid bodies
Abstract
Apneas constitute an acute existential threat to neonates and adults. In large part, this threat is detected by the carotid bodies, the primary peripheral chemoreceptors, and combatted by arousal and acute cardiorespiratory responses, including increased sympathetic output. Similar responses occur with repeated apneas but they continue beyond the last apnea and can persist for hours (i.e. ventilatory and sympathetic LTF). These long-term effects may be adaptive during acute episodic apnea, but may prolong hypertension causing chronic cardiovascular impairment. We report a novel mechanism of acute carotid body (CB) plasticity (sensory LTF) induced by repeated apnea-like stimuli i.e. acute intermittent hypoxia with concurrent hypercapnia (AIH-Hc). This plasticity did not require chronic intermittent hypoxia (CIH) preconditioning, was dependent on P2X receptors and PKC, and involved heat-sensitive TRPV1 receptors. ROS (O2·−) were involved in initiating plasticity only; no evidence was found for H2O2 involvement. Angiotensin II and 5HT receptor antagonists, losartan and ketanserin, severely reduced CB responses to individual hypoxic-hypercapnic challenges and prevented induction of sLTF but, if applied after AIH-Hc, failed to reduce plasticity-associated activity. Conversely, TRPV1 receptor antagonism had no effect on responses to individual hypoxic-hypercapnic challenges but reduced plasticity-associated activity by ∼50%. Further, TRPV1 receptor antagonism in vivo reduced sympathetic LTF caused by AIH-Hc, but only if the CBs were functional. These data demonstrate a new mechanism of CB plasticity and suggest P2X-TRPV1 dependent sensory LTF as a novel target for pharmacological intervention in some forms of neurogenic hypertension associated with recurrent apneas.
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Kairomones from an estuarine fish increase visual sensitivity in brine shrimp ( Artemia franciscana) from Great Salt Lake, Utah, USA
Abstract
Chemical cues from fish, or kairomones, often impact the behavior of zooplankton. These behavioral changes are thought to improve predator avoidance. For example, marine and estuarine crustacean zooplankton become more sensitive to light after kairomone exposure, which likely deepens their vertical distribution into darker waters during the day and thereby reduces their visibility to fish predators. Here, we show that kairomones from an estuarine fish induce similar behavioral responses in adult brine shrimp (Artemia franciscana) from an endorheic, hypersaline lake, Great Salt Lake, Utah, USA. Given downwelling light stimuli, kairomone-exposed A. franciscana induce a descent response upon dimmer light flashes than they do in the absence of kairomones. Using extracellular electroretinogram (ERG) recordings, we also find that kairomones induce physiological changes in the retina that may lead to increased visual sensitivity, suggesting that kairomone-induced changes to photobehavior are mediated at the photoreceptor level. However, kairomones did not induce structural changes within the eye. Although A. franciscana inhabit endorheic environments that are too saline for most fish, kairomones from an estuarine fish amplify photobehavior in these branchiopod crustaceans. The mechanism for this behavioral change has both similarities to and differences from that described in marine malacostracan crustaceans.
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The ubiquity of pleiotropy in human disease
Abstract
Pleiotropy has long been thought to be a common phenomenon in the human genome; however, until recently appropriate data was unavailable to test this hypothesis. Prior studies focused on assessing the prevalence of pleiotropy in only small subsets of phenotypes (≤ 53 phenotypes), without a truly comprehensive assessment of pleiotropy in the human genome. In this study, we determined the prevalence of pleiotropy, using the entire GWAS catalog (1094 disease phenotypes, 14,459 genes), as well as investigate the relationship between the degree of pleiotropy and the average effect size for each associating gene. The number of associating phenotypes per gene ranged from 1 to 53, with 44% of genes reported in the GWAS catalog associating with more than one phenotype. The proportion of genes shown to be pleiotropic has continued to increase as more studies are added to the catalog. We also found the degree of pleiotropy scales positively with a gene's average effect size (r = 0.04, p value = 0.0003) and negatively with the variance of effect sizes in genes with a given number of associating phenotypes (r = − 0.590, p value = 0.0019). Based on this and prior work, it is becoming evident that pleiotropy is a common, if not ubiquitous, phenomenon. These results have implications in understanding disease etiologies, potentially common biology underlying even disparate diseases, and in elucidating the genotype–phenotype map.
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GABA concentration in sensorimotor cortex following high-intensity exercise and relationship to lactate levels
Abstract
High-intensity exercise increases the concentration of circulating lactate. Cortical uptake of blood borne lactate increases during and following exercise, however the potential relationship with changes in the concentration of neurometabolites remains unclear. While changes in neurometabolite concentration have previously been demonstrated in primary visual cortex following exercise, it remains unknown whether these changes extend to regions such as sensorimotor cortex (SM) or executive regions such as dorsolateral prefrontal cortex (DLPFC). Here we explored the acute aftereffects of high-intensity interval training (HIIT) on the concentration of gamma-amino butyric acid (GABA), a combined glutamate-glutamine-glutathione spectral peak (Glx), and their balance in SM and DLPFC, as well as the relationship to blood lactate levels. Following HIIT, there was a robust increase in GABA concentration in sensorimotor cortex, evident across the majority of participants. This change was not observed in DLPFC. Furthermore, the increase in sensorimotor cortex GABA was positively correlated with an increase in blood lactate. There were no changes in Glx concentration in either region. The observed increase in sensorimotor cortex GABA concentration implies functional relevance while the correlation with lactate levels may relate to the metabolic fate of exercise-derived lactate that crosses the blood-brain barrier.
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