ABSTRACT
BACKGROUND: More deprived cancer patients are at higher risk of Emergency Presentation (EP) with most studies pointing to lower symptom awareness and increased comorbidities to explain those patterns. With the example of colon cancer, we examine patterns of hospital emergency admissions (HEAs) history in the most and least deprived patients as a potential precursor of EP. METHODS: We analysed the rates of hospital admissions and their admission codes (retrieved from Hospital Episode Statistics) in the two years preceding cancer diagnosis by sex, deprivation and route to diagnosis (EP, non-EP). To select the conditions (grouped admission codes) that best predict emergency admission, we adapted the purposeful variable selection to mixed-effects logistic regression. RESULTS: Colon cancer patients diagnosed through EP had the highest number of HEAs than all the other routes to diagnosis, especially in the last 7 months before diagnosis. Most deprived patients had an overall higher rate and higher probability of HEA but fewer conditions associated with it. CONCLUSIONS: Our findings point to higher use of emergency services for non-specific symptoms and conditions in the most deprived patients, preceding colon cancer diagnosis. Health system barriers may be a shared factor of socio-economic inequalities in EP and HEAs.
Subject(s)
Emergency Service, Hospital , Neoplasms , Socioeconomic Factors , Humans , Male , Female , England/epidemiology , Emergency Service, Hospital/statistics & numerical data , Middle Aged , Aged , Neoplasms/epidemiology , Neoplasms/diagnosis , Adult , Hospitalization/statistics & numerical data , Colonic Neoplasms/epidemiology , Colonic Neoplasms/diagnosis , Healthcare Disparities/statistics & numerical data , Patient Admission/statistics & numerical data , Adolescent , Aged, 80 and over , Young AdultABSTRACT
BACKGROUND: Common bean (Phaseolus vulgaris) is one of the main nutritional resources in the world, and a low environmental impact source of protein. However, the majority of its cultivation areas are affected by drought and this scenario is only expected to worsen with climate change. Stomatal closure is one of the most important plant responses to drought and the MYB60 transcription factor is among the key elements regulating stomatal aperture. If targeting and mutating the MYB60 gene of common bean would be a valuable strategy to establish more drought-tolerant beans was therefore investigated. RESULTS: The MYB60 gene of common bean, with orthology to the Arabidopsis AtMYB60 gene, was found to have conserved regions with MYB60 typical motifs and architecture. Stomata-specific expression of PvMYB60 was further confirmed by q-RT PCR on organs containing stomata, and stomata-enriched leaf fractions. Further, function of PvMYB60 in promoting stomata aperture was confirmed by complementing the defective phenotype of a previously described Arabidopsis myb60-1 mutant. CONCLUSIONS: Our study finally points PvMYB60 as a potential target for obtaining more drought-tolerant common beans in the present context of climate change which would further greatly contribute to food security particularly in drought-prone countries.
Subject(s)
Climate Change , Drought Resistance , Phaseolus , Arabidopsis/genetics , Arabidopsis/physiology , Drought Resistance/genetics , Gene Expression Regulation, Plant/genetics , Phaseolus/genetics , Phaseolus/physiology , Plant Proteins/genetics , Plant Stomata/genetics , Plant Stomata/physiology , Transcription Factors/geneticsABSTRACT
BACKGROUND: The incidence of radial head fractures is increasing, and radial head arthroplasty (RHA) is being more frequently used as treatment for irreparable fractures. Our objective was to compare radiocapitellar pressure between the native joint and 2 radial head prosthesis conditions: (1) a prosthetic head that was aligned to the forearm axis of rotation and (2) the same prosthesis with an axisymmetric nonaligned head. METHODS: Ten cadaveric specimens received a pressfit radial head prosthesis (Align; Skeletal Dynamics) for both prosthetic testing conditions. Anatomic alignment (AL) was defined as the prosthetic head aligned to the forearm axis of rotation. Axisymmetric alignment (AX) was defined as the prosthetic radial head aligned to the axis of the prosthetic stem. Axial load was applied with the elbow in extension and the forearm pronated. Data were collected using a Tekscan 4000 sensor. RESULTS: The mean pressure in the AL and AX groups were significantly higher than the mean pressure in the native joint. Compared with the native joint, the mean pressure was 19% higher in the AL group and 56% higher in the AX group. Peak pressure beyond 5 MPa occurred in 0 specimens in the native joint group, in 1 specimen (10%) in the AL group, and in 5 specimens (50%) in the AX group. DISCUSSION: Our results demonstrated that a pressfit radial head prosthesis aligned with the forearm axis of rotation yields capitellar pressures that were more similar to the native condition than a nonaligned pressfit prosthesis. These findings suggest that anatomic alignment may optimize capitellar wear properties, improving the long-term durability of radial head arthroplasty.
Subject(s)
Cadaver , Elbow Joint , Pressure , Radius Fractures , Radius , Humans , Elbow Joint/surgery , Elbow Joint/physiopathology , Radius/surgery , Aged , Radius Fractures/surgery , Arthroplasty, Replacement, Elbow/methods , Male , Female , Elbow Prosthesis , Prosthesis Design , Aged, 80 and over , Middle AgedABSTRACT
BACKGROUND: O'Driscoll popularized the principle of linked column fixation for distal humerus fractures. Despite the linked column concept being widely accepted, there are few reported techniques to accomplish this goal. A novel device was designed based on the principles of linked columns. An interlocking beam is used to connect the medial and lateral plates, creating a unified fixed angle construct. Our primary objective was to report clinical outcomes across multiple institutions for a linking beam used in distal humerus fracture fixation. METHODS: A retrospective series was collected from five institutions for the TiBeam (Skeletal Dynamics, Miami, FL, USA) with a minimum follow-up of six months. Acute and chronic treatment of distal humerus fracture patterns, and all plate configurations were included for analysis. RESULTS: A total of 36 cases were collected at a mean age of 52 years and a mean follow-up of 19.3 months. AO C-type fractures were 56% of the series. The median MEPS was 85 (IQR 76.3 to 90), the median DASH was 21.4 (IQR 15.9 to 30), and the median VASa was 3.5 (IQR 2 to 5). An olecranon osteotomy was used in 86% of cases and an anatomic plate was used for fixation of the osteotomy in 94% of those cases. There were three cases of olecranon plate removal for a rate across the series of 13.7%. DISCUSSION: Our short-term results demonstrate satisfactory clinical outcomes with low rates of revision for distal humerus fracture fixed with a linking beam. Further, the rate of removal for the olecranon osteotomy plate was lower than historical reports for aggregate methods of osteotomy fixation.
ABSTRACT
Transport of K+ to the xylem is a key process in the mineral nutrition of the shoots. Although CIPK-CBL complexes have been widely shown to regulate K+ uptake transport systems, no information is available about the xylem ones. Here, we studied the physiological roles of the voltage-gated K+ channel SlSKOR and its regulation by the SlCIPK23-SlCBL1/9 complexes in tomato plants. We phenotyped gene-edited slskor and slcipk23 tomato knockout mutants and carried out two-electrode voltage-clamp (TEVC) and BiFC assays in Xenopus oocytes as key approaches. SlSKOR was preferentially expressed in the root stele and was important not only for K+ transport to shoots but also, indirectly, for that of Ca2+ , Mg2+ , Na+ , NO3 - , and Cl- . Surprisingly, the SlCIPK23-SlCBL1/9 complexes turned out to be negative regulators of SlSKOR. Inhibition of SlSKOR by SlCIPK23-SlCBL1/9 was observed in Xenopus oocytes and tomato plants. Regulation of SKOR-like channels by CIPK23-CBL1 complexes was also present in Medicago, grapevine, and lettuce but not in Arabidopsis and saltwater cress. Our results provide a molecular framework for coordinating root K+ uptake and its translocation to the shoot by SlCIPK23-SlCBL1/9 in tomato plants. Moreover, they evidenced that CIPK-CBL-target networks have evolved differently in land plants.
Subject(s)
Arabidopsis Proteins , Arabidopsis , Arabidopsis Proteins/metabolism , Potassium Channels/metabolism , Arabidopsis/metabolism , Biological Transport , Potassium/metabolism , Plant Proteins/genetics , Plant Proteins/metabolismABSTRACT
Unobserved individual heterogeneity is a common challenge in population cancer survival studies. This heterogeneity is usually associated with the combination of model misspecification and the failure to record truly relevant variables. We investigate the effects of unobserved individual heterogeneity in the context of excess hazard models, one of the main tools in cancer epidemiology. We propose an individual excess hazard frailty model to account for individual heterogeneity. This represents an extension of frailty modeling to the relative survival framework. In order to facilitate the inference on the parameters of the proposed model, we select frailty distributions which produce closed-form expressions of the marginal hazard and survival functions. The resulting model allows for an intuitive interpretation, in which the frailties induce a selection of the healthier individuals among survivors. We model the excess hazard using a flexible parametric model with a general hazard structure which facilitates the inclusion of time-dependent effects. We illustrate the performance of the proposed methodology through a simulation study. We present a real-data example using data from lung cancer patients diagnosed in England, and discuss the impact of not accounting for unobserved heterogeneity on the estimation of net survival. The methodology is implemented in the R package IFNS.
Subject(s)
Frailty , Lung Neoplasms , Humans , Proportional Hazards Models , Survival Analysis , Models, StatisticalABSTRACT
To reduce the breast cancer burden, the French National Organised Breast Cancer Screening Programme (FNOBCSP) was implemented in 2004. The recommended participation rate has never been achieved and socio-territorial inequities in participation have been reported on several occasions. We investigated the functional forms and consistency of the relationships between neighbourhood deprivation, travel time to the nearest accredited radiology centre and screening uptake. We used two-level hierarchical generalised additive models in 8 types of territories classified by socio-demographic and economic factors. The first level was 368,201 women aged 50-72 invited to the 2013-2014 screening campaign in metropolitan France. They were nested in 41 départements, the level of organisation of the FNOBCSP. The effect of travel time showed two main patterns: it was either linear (with participation decreasing as travel time increased) or participation first increased with increasing travel time to a peak around 5-15 min and decreased afterward. In nearly all types and départements, the probability of participation decreased linearly with increasing deprivation. Territorial inequities in participation were more context-dependent and complex than social inequities. Inequities in participation represent a loss of opportunity for individuals who already have the worst cancer outcomes. Evidence-based public health policies are needed to increase the effectiveness and equity of breast cancer screening.
Subject(s)
Breast Neoplasms , Female , Humans , Breast Neoplasms/diagnosis , Breast Neoplasms/prevention & control , Cross-Sectional Studies , Socioeconomic Factors , Early Detection of Cancer , Mass ScreeningABSTRACT
We study parametric inference on a rich class of hazard regression models in the presence of right-censoring. Previous literature has reported some inferential challenges, such as multimodal or flat likelihood surfaces, in this class of models for some particular data sets. We formalize the study of these inferential problems by linking them to the concepts of near-redundancy and practical nonidentifiability of parameters. We show that the maximum likelihood estimators of the parameters in this class of models are consistent and asymptotically normal. Thus, the inferential problems in this class of models are related to the finite-sample scenario, where it is difficult to distinguish between the fitted model and a nested nonidentifiable (i.e., parameter-redundant) model. We propose a method for detecting near-redundancy, based on distances between probability distributions. We also employ methods used in other areas for detecting practical nonidentifiability and near-redundancy, including the inspection of the profile likelihood function and the Hessian method. For cases where inferential problems are detected, we discuss alternatives such as using model selection tools to identify simpler models that do not exhibit these inferential problems, increasing the sample size, or extending the follow-up time. We illustrate the performance of the proposed methods through a simulation study. Our simulation study reveals a link between the presence of near-redundancy and practical nonidentifiability. Two illustrative applications using real data, with and without inferential problems, are presented.
Subject(s)
Proportional Hazards Models , Likelihood Functions , Computer SimulationABSTRACT
Introduction: Menopause is a vital stage in which the risk of the appearance of metabolic syndrome and cardiovascular diseases is increased. Cardiovascular risk in menopausal women must be monitored because it is one of the most common causes of mortality in these women. Smoking is an important risk factor for the development of many diseases, including cardiovascular diseases, so promoting smoking cessation in these women is important for the maintenance of cardiovascular health. Material and methods: Current smoking cessation programs mainly include nicotine and varenicline as therapeutic agents, due to their history of success, safety, and efficacy in aiding in cessation, but they do not include "new" agents such as cytisine as coadjuvant in the elimination of the habit of smoking. Results: Cytisine is a therapeutic agent traditionally used in Eastern Europe, which has demonstrated efficacy and safety in smoking cessation, also showing other new pharmacological actions. It has been widely used since World War II as a nicotine substitute. Conclusions: These pharmacological actions, together with their efficacy in smoking cessation, should be explored to evaluate the convenience of the use of cytisine in premenopausal and postmenopausal women, so that cytisine can be identified as a useful therapeutic tool in smoking cessation programs and in particular in menopausal women.
ABSTRACT
In cancer epidemiology using population-based data, regression models for the excess mortality hazard is a useful method to estimate cancer survival and to describe the association between prognosis factors and excess mortality. This method requires expected mortality rates from general population life tables: each cancer patient is assigned an expected (background) mortality rate obtained from the life tables, typically at least according to their age and sex, from the population they belong to. However, those life tables may be insufficiently stratified, as some characteristics such as deprivation, ethnicity, and comorbidities, are not available in the life tables for a number of countries. This may affect the background mortality rate allocated to each patient, and it has been shown that not including relevant information for assigning an expected mortality rate to each patient induces a bias in the estimation of the regression parameters of the excess hazard model. We propose two parametric corrections in excess hazard regression models, including a single-parameter or a random effect (frailty), to account for possible mismatches in the life table and thus misspecification of the background mortality rate. In an extensive simulation study, the good statistical performance of the proposed approach is demonstrated, and we illustrate their use on real population-based data of lung cancer patients. We present conditions and limitations of these methods and provide some recommendations for their use in practice.
Subject(s)
Computer Simulation , Life Tables , Proportional Hazards Models , Bias , Female , Humans , Lung Neoplasms/epidemiology , MaleABSTRACT
The high-affinity K+ transporter HAK5 from Arabidopsis (Arabidopsis thaliana) is essential for K+ acquisition and plant growth at low micromolar K+ concentrations. Despite its functional relevance in plant nutrition, information about functional domains of HAK5 is scarce. Its activity is enhanced by phosphorylation via the AtCIPK23/AtCBL1-9 complex. Based on the recently published three-dimensionalstructure of the bacterial ortholog KimA from Bacillus subtilis, we have modeled AtHAK5 and, by a mutational approach, identified residues G67, Y70, G71, D72, D201, and E312 as essential for transporter function. According to the structural model, residues D72, D201, and E312 may bind K+, whereas residues G67, Y70, and G71 may shape the selective filter for K+, which resembles that of K+shaker-like channels. In addition, we show that phosphorylation of residue S35 by AtCIPK23 is required for reaching maximal transport activity. Serial deletions of the AtHAK5 C-terminus disclosed the presence of an autoinhibitory domain located between residues 571 and 633 together with an AtCIPK23-dependent activation domain downstream of position 633. Presumably, autoinhibition of AtHAK5 is counteracted by phosphorylation of S35 by AtCIPK23. Our results provide a molecular model for K+ transport and describe CIPK-CBL-mediated regulation of plant HAK transporters.
Subject(s)
Arabidopsis Proteins/metabolism , Arabidopsis/genetics , Arabidopsis/metabolism , Biological Transport/genetics , Biological Transport/physiology , Cation Transport Proteins/metabolism , Potassium-Hydrogen Antiporters/genetics , Potassium-Hydrogen Antiporters/metabolism , Cation Transport Proteins/genetics , Gene Expression Regulation, Plant , Genes, Plant , Genetic Variation , MutationABSTRACT
Cancer survival represents one of the main indicators of interest in cancer epidemiology. However, the survival of cancer patients can be affected by several factors, such as comorbidities, that may interact with the cancer biology. Moreover, it is interesting to understand how different cancer sites and tumour stages are affected by different comorbidities. Identifying the comorbidities that affect cancer survival is thus of interest as it can be used to identify factors driving the survival of cancer patients. This information can also be used to identify vulnerable groups of patients with comorbidities that may lead to worst prognosis of cancer. We address these questions and propose a principled selection and evaluation of the effect of comorbidities on the overall survival of cancer patients. In the first step, we apply a Bayesian variable selection method that can be used to identify the comorbidities that predict overall survival. In the second step, we build a general Bayesian survival model that accounts for time-varying effects. In the third step, we derive several posterior predictive measures to quantify the effect of individual comorbidities on the population overall survival. We present applications to data on lung and colorectal cancers from two Spanish population-based cancer registries. The proposed methodology is implemented with a combination of the R-packages mombf and rstan. We provide the code for reproducibility at https://github.com/migariane/BayesVarImpComorbiCancer .
Subject(s)
Colorectal Neoplasms , Lung , Bayes Theorem , Colorectal Neoplasms/epidemiology , Humans , Reproducibility of Results , Spain/epidemiologyABSTRACT
In this paper, we aim to open up new perspectives in the field of autonomous aerial surveillance and target tracking systems, by exploring an alternative that, surprisingly, and to the best of the authors' knowledge, has not been addressed in that context by the research community thus far. It can be summarized by the following two questions. Under the scope of such applications, what are the implications and possibilities offered by mounting several steerable cameras onboard of each aerial agent? Second, how can optimization algorithms benefit from this new framework, in their attempt to provide more efficient and cost-effective solutions on these areas? The paper presents the idea as an additional degree of freedom to be exploited, which can enable more efficient alternatives in the deployment of such applications. As an initial approach, the problem of the optimal positioning with respect to a set of targets of one single agent, equipped with several onboard tracking cameras with different or variable focal lengths, is addressed. As a consequence of this allowed heterogeneity in focal lengths, the notion of distance needs to be adapted into a notion of optical range, as the agent can trade longer Euclidean distances for correspondingly longer focal lengths. Moreover, the proposed optimization indices try to balance, in an optimal way, the verticality of the viewpoints along with the optical range to the targets. Under these premises, several positioning strategies are proposed and comparatively evaluated.
Subject(s)
Sports , Unmanned Aerial Devices , AlgorithmsABSTRACT
Regulation of root transport systems is essential under fluctuating nutrient supply. In the case of potassium (K+ ), HAK/KUP/KT K+ transporters and voltage-gated K+ channels ensure root K+ uptake in a wide range of K+ concentrations. In Arabidopsis, the CIPK23/CBL1-9 complex regulates both transporter- and channel-mediated root K+ uptake. However, research about K+ homeostasis in crops is in demand due to species-specific mechanisms. In the present manuscript, we studied the contribution of the voltage-gated K+ channel LKT1 and the protein kinase SlCIPK23 to K+ uptake in tomato plants by analysing gene-edited knockout tomato mutant lines, together with two-electrode voltage-clamp experiments in Xenopus oocytes and protein-protein interaction analyses. It is shown that LKT1 is a crucial player in tomato K+ nutrition by contributing approximately 50% to root K+ uptake under K+ -sufficient conditions. Moreover, SlCIPK23 was responsible for approximately 100% of LKT1 and approximately 40% of the SlHAK5 K+ transporter activity in planta. Mg+2 and Na+ compensated for K+ deficit in tomato roots to a large extent, and the accumulation of Na+ was strongly dependent on SlCIPK23 function. The role of CIPK23 in Na+ accumulation in tomato roots was not conserved in Arabidopsis, which expands the current set of CIPK23-like protein functions in plants.
Subject(s)
Plant Proteins/genetics , Potassium/metabolism , Protein Serine-Threonine Kinases/genetics , Sodium/metabolism , Solanum lycopersicum/genetics , Solanum lycopersicum/metabolism , Plant Proteins/metabolism , Protein Serine-Threonine Kinases/metabolismABSTRACT
We introduce a numerically tractable formulation of Bayesian joint models for longitudinal and survival data. The longitudinal process is modeled using generalized linear mixed models, while the survival process is modeled using a parametric general hazard structure. The two processes are linked by sharing fixed and random effects, separating the effects that play a role at the time scale from those that affect the hazard scale. This strategy allows for the inclusion of nonlinear and time-dependent effects while avoiding the need for numerical integration, which facilitates the implementation of the proposed joint model. We explore the use of flexible parametric distributions for modeling the baseline hazard function which can capture the basic shapes of interest in practice. We discuss prior elicitation based on the interpretation of the parameters. We present an extensive simulation study, where we analyze the inferential properties of the proposed models, and illustrate the trade-off between flexibility, sample size, and censoring. We also apply our proposal to two real data applications in order to demonstrate the adaptability of our formulation both in univariate time-to-event data and in a competing risks framework. The methodology is implemented in rstan.
Subject(s)
Models, Statistical , Bayes Theorem , Computer Simulation , Humans , Linear Models , Longitudinal StudiesABSTRACT
Digital technologies are transforming the automotive industry and disrupting traditional business models. New business opportunities related to Industry 4.0 are emerging, so companies must adapt to the new environment. The study presents an application of fuzzy-set qualitative comparative analysis (fsQCA) to analyze the future impact of digital transformation on business performance models and the different actors' satisfaction. A wide range of aspects and actors derived from the digital transformation process in the automotive industry are considered. The study covers connected and autonomous driving, mobility as a service, digital information sources in car purchasing, big data, etc. The disruptive effect of the gradual introduction of electric vehicles into the market is also considered, which is boosted by environmental policies on climate change and directives for the potential use of renewable energy sources to power electric vehicles. On the other hand, the study analyses the impacts of digital transformation on the automotive industry from the point of view of different actors, ranging from automobile manufacturers, service providers, public transportation providers, and consumers to governments. The methodology has been successfully applied to a complex case study-based empirical analysis. It presents a novel application of fsQCA to digital transformation in the automotive industry in Spain. The conclusions show that it is necessary to invest in adequate measures for adaptation to digital transformation, and manufacturers will end up having greater profits, productivity, and competitiveness. From the point of view of consumers, there will be access to more and better services and greater satisfaction with the required services.
ABSTRACT
Salinization of agricultural lands is a major threat to agriculture. Many different factors affect and determine plant salt tolerance. Nonetheless, there is a consensus on the relevance of maintaining an optimal cytosolic potassium : sodium ion (K+ : Na+ ) ratio for salinity tolerance in plants. This ratio depends on the operation of plasma membrane and tonoplast transporters. In the present review we focus on some aspects related to the energetic cost of maintaining that K+ : Na+ ratio. One of the factors that affect the cost of the first step of K+ acquisition - root K+ uptake through High Affinity K+ transporter and Arabidopsis K+ transport system 1 transport systems - is the value of the plasma membrane potential of root cells, a parameter that may differ amongst plant species. In addition to its role in nutrition, cytosolic K+ also is important for signalling, and K+ efflux through gated outward-rectifying K+ and nonselective cation channels can be regarded as a switch to redirect energy towards defence reactions. In maintaining cytosolic K+ , the great buffer capacity of the vacuole should be considered. The possible role of high-affinity K+ transporters (HKT)2s in mediating K+ uptake under saline conditions and the importance of cycling of K+ throughout the plant also are discussed.
Subject(s)
Energy Metabolism , Homeostasis , Intracellular Space/metabolism , Plants/metabolism , Potassium/metabolism , SalinityABSTRACT
Root K+ acquisition is a key process for plant growth and development, extensively studied in the model plant Arabidopsis thaliana. Because important differences may exist among species, translational research supported by specific studies is needed in crops such as tomato. Here we present a reverse genetics study to demonstrate the role of the SlHAK5 K+ transporter in tomato K+ nutrition, Cs+ accumulation and its fertility. slhak5 KO lines, generated by CRISPR-Cas edition, were characterized in growth experiments, Rb+ and Cs+ uptake tests and root cells K+ -induced plasma membrane depolarizations. Pollen viability and its K+ accumulation capacity were estimated by using the K+ -sensitive dye Ion Potassium Green 4. SlHAK5 is the major system for high-affinity root K+ uptake required for plant growth at low K+ , even in the presence of salinity. It also constitutes a pathway for Cs+ entry in tomato plants with a strong impact on fruit Cs+ accumulation. SlHAK5 also contributes to pollen K+ uptake and viability and its absence produces almost seedless fruits. Knowledge gained into SlHAK5 can serve as a model for other crops with fleshy fruits and it can help to generate tools to develop low Cs+ or seedless fruits crops.
Subject(s)
Cesium/metabolism , Plant Proteins/physiology , Plant Roots/metabolism , Potassium Channels/physiology , Potassium/metabolism , Solanum lycopersicum/metabolism , CRISPR-Associated Protein 9 , CRISPR-Cas Systems , Flowers/metabolism , Fruit/growth & development , Gene Editing , Solanum lycopersicum/physiology , Plant Proteins/metabolism , Plants, Genetically Modified , Pollen Tube/growth & development , Potassium Channels/metabolism , Reproduction , Seeds/growth & developmentABSTRACT
The high-affinity K+ transporter HAK5 is the major contributor to root K+ uptake from dilute solutions in K+-starved Arabidopsis plants. Its functionality is tightly regulated and its activity is enhanced under K+ starvation by the transcriptional induction of the AtHAK5 gene, and by the activation of the transporter via the AtCBL1-AtCIPK23 complex. In the present study, the 26 members of the Arabidopsis CIPK protein kinase family were screened in yeast for their capacity to activate HAK5-mediated K+ uptake. Among them, AtCIPK1 was the most efficient activator of AtHAK5. In addition, AtCIPK9, previously reported to participate in K+ homeostasis, also activated the transporter. In roots, the genes encoding AtCIPK1 and AtCIPK9 were induced by K+ deprivation and atcipk1 and atcipk9 Arabidopsis KO mutants showed a reduced AtHAK5-mediated Rb+ uptake. Activation of AtHAK5 by AtCIPK1 did not occur under hyperosmotic stress conditions, where AtCIPK1 function has been shown to be required to maintain plant growth. Taken together, our data contribute to the identification of the complex regulatory networks that control the high-affinity K+ transporter AtHAK5 and root K+ uptake.
Subject(s)
Arabidopsis Proteins , Arabidopsis , Symporters , Arabidopsis/genetics , Arabidopsis/metabolism , Arabidopsis Proteins/genetics , Arabidopsis Proteins/metabolism , Gene Expression Regulation, Plant , Plant Roots/metabolism , Potassium/metabolism , Potassium Channels/metabolism , Potassium-Hydrogen Antiporters/genetics , Potassium-Hydrogen Antiporters/metabolism , Protein Kinases , Protein Serine-Threonine Kinases/genetics , Symporters/genetics , Symporters/metabolismABSTRACT
HYPOTHESIS: The proximal radius is asymmetrical, is mostly articular, and rotates through a large arc of motion. Because of these anatomic factors, there is limited space for hardware. This is magnified in the setting of complex fractures. The portion of the radial head where a radial head plate can be placed without compromising forearm motion has been termed the "safe zone." We hypothesized that the bicipital tuberosity could be used as a reproducible intraoperative fluoroscopic landmark to confirm radial head plate position in the safe zone. METHODS: Seventeen cadaveric radii were evaluated. First, the anatomic safe zone was identified using the method previously described by Caputo et al. A proximal radial plate was then placed in the center of this safe zone. The relationship of the plate to the tuberosity was evaluated, and the angle from the point of the greatest tuberosity profile to the center of the safe zone was measured. RESULTS: The maximum profile of the bicipital tuberosity is 166° ± 10° from the center of the safe zone as described by Caputo et al. By use of radiographic imaging, a radial head plate placed directly opposite the bicipital tuberosity will be within the safe zone. This position can be ascertained fluoroscopically with an anteroposterior view of the proximal forearm, in which the surgeon rotates the forearm into full supination. The plate should be placed opposite the bicipital tuberosity as seen on the greatest profile at maximum supination. With this method, the plate will be consistently placed within the safe zone. CONCLUSION: The bicipital tuberosity can be used as a consistent radiographic anatomic landmark to ensure proximal radial plate placement within the safe zone. If the proximal radial head plate is placed 166° ± 10° opposite the bicipital tuberosity, a landmark easily identified on intraoperative imaging, the implant will be in the safe zone and will not impinge on the ulna in rotation.