Contributions To Physiology Research Articles

Adult bone marrow progenitors become decidual cells and contribute to embryo implantation and pregnancy.

Decidua is a transient uterine tissue shared by mammals with hemochorial placenta and is essential for pregnancy. The decidua is infiltrated by many immune cells promoting pregnancy. Adult bone marrow (BM)-derived cells (BMDCs) differentiate into rare populations of nonhematopoietic endometrial cells in the uterus. However, whether adult BMDCs become nonhematopoietic decidual cells and contribute functionally to pregnancy is unknown. Here, we show that pregnancy mobilizes mesenchymal stem cells (MSCs) to the circulation and that pregnancy induces considerable adult BMDCs recruitment to decidua, where some differentiate into nonhematopoietic prolactin-expressing decidual cells. To explore the functional importance of nonhematopoietic BMDCs to pregnancy, we used Homeobox a11 (Hoxa11)-deficient mice, having endometrial stromal-specific defects precluding decidualization and successful pregnancy. Hoxa11 expression in BM is restricted to nonhematopoietic cells. BM transplant (BMT) from wild-type (WT) to Hoxa11−/− mice results in stromal expansion, gland formation, and marked decidualization otherwise absent in Hoxa11−/− mice. Moreover, in Hoxa11+/− mice, which have increased pregnancy losses, BMT from WT donors leads to normalized uterine expression of numerous decidualization-related genes and rescue of pregnancy loss. Collectively, these findings reveal that adult BMDCs have a previously unrecognized nonhematopoietic physiologic contribution to decidual stroma, thereby playing important roles in decidualization and pregnancy.

TMEM16B Calcium-Activated Chloride Channels Regulate Action Potential Firing in Lateral Septum and Aggression in Male Mice.

The lateral septum (LS) plays an important role in regulating aggression. It is well recognized that LS lesions lead to a dramatic increase in aggressive behaviors. A better understanding of LS neurophysiology and its functional output is therefore important to assess LS involvement in regulating aggression. The LS is a heterogeneous structure that maintains inputs and outputs with multiple brain regions, and is also divided into subregions that innervate one another. Thus, it is challenging to identify the exact cell type and projections for characterization. In this study, we determined the expression pattern of the calcium-activated chloride channel, TMEM16B, in the LS of both male and female mice. We then investigated the physiological contribution of the calcium-activated chloride channel to LS neuronal signaling. By performing whole-cell patch-clamp recording, we showed that TMEM16B alters neurotransmitter release at the hippocampal-LS synapse, and regulates spike frequency and spike frequency adaptation in subpopulations of LS neurons. We further demonstrated that loss of TMEM16B function promotes lengthened displays of aggressive behaviors by male mice during the resident intruder paradigm. In conclusion, our findings suggest that TMEM16B function contributes to neuronal excitability in subpopulations of LS neurons and the regulation of aggression in male mice.SIGNIFICANCE STATEMENT Aggression is a behavior that arose evolutionarily from the necessity to compete for limited resources and survival. One particular brain region involved in aggression is the lateral septum (LS). In this study, we characterized the expression of the TMEM16B calcium-activated chloride channel in the LS and showed that TMEM16B regulates the action potential firing frequency of LS neurons. We discovered that loss of TMEM16B function lengthens the displays of aggressive behaviors in male mice. These findings suggest that TMEM16B plays an important role in regulating LS neuronal excitability and behaviors associated with LS function, thereby contributing to our understanding of how the LS may regulate aggression.

The Emerging Field of Human Endogenous Retroviruses: Understanding Their Physiological Role and Contribution to Diseases

The Emerging Field of Human Endogenous Retroviruses: Understanding Their Physiological Role and Contribution to Diseases

Neuro-genetic plasticity of Caenorhabditis elegans behavioral thermal tolerance

BackgroundAnimal responses to thermal stimuli involve intricate contributions of genetics, neurobiology and physiology, with temperature variation providing a pervasive environmental factor for natural selection. Thermal behavior thus exemplifies a dynamic trait that requires non-trivial phenotypic summaries to appropriately capture the trait in response to a changing environment. To characterize the deterministic and plastic components of thermal responses, we developed a novel micro-droplet assay of nematode behavior that permits information-dense summaries of dynamic behavioral phenotypes as reaction norms in response to increasing temperature (thermal tolerance curves, TTC).ResultsWe found that C. elegans TTCs shift predictably with rearing conditions and developmental stage, with significant differences between distinct wildtype genetic backgrounds. Moreover, after screening TTCs for 58 C. elegans genetic mutant strains, we determined that genes affecting thermosensation, including cmk-1 and tax-4, potentially play important roles in the behavioral control of locomotion at high temperature, implicating neural decision-making in TTC shape rather than just generalized physiological limits. However, expression of the transient receptor potential ion channel TRPA-1 in the nervous system is not sufficient to rescue rearing-dependent plasticity in TTCs conferred by normal expression of this gene, indicating instead a role for intestinal signaling involving TRPA-1 in the adaptive plasticity of thermal performance.ConclusionsThese results implicate nervous system and non-nervous system contributions to behavior, in addition to basic cellular physiology, as key mediators of evolutionary responses to selection from temperature variation in nature.

039 Characterization of Female Periurethral Tissue: Potential Impact of Mid-urethral Sling Surgeries on Female Sexual Function

The female periurethral tissue (FPT) contains numerous glands which stain positive for prostate specific acid. These glands are surrounded by neuronal and vascular structures, and may have physiologic contribution to sexual function. The FPT is located adjacent to the anterior vaginal wall epithelium and surrounds the urethra passing distally from the bladder neck to the meatus. Decreased sexual function, especially lowered orgasm satisfaction, has been reported following mid-urethral sling procedures to treat stress urinary incontinence, and requires further investigation of this possible iatrogenic effect. Cadaver studies have shown the mid-urethral sling transects through the glandular, neuronal, and vascular structures of the FPT. The objectives of this study are to further histologically characterize the FPT and examine patterns of innervation in relation to its specific morphological features. Histologic and immunohistochemical investigations of glandular, vascular, and nervous structures of the FPT were examined from three fresh human female cadavers. The region of FPT examined was located in the same region of implanted mid-urethral slings.

Dissecting the Brain/Islet Axis in Metabesity.

The high prevalence of type 2 diabetes mellitus (T2DM), together with the fact that current treatments are only palliative and do not avoid major secondary complications, reveals the need for novel approaches to treat the cause of this disease. Efforts are currently underway to identify therapeutic targets implicated in either the regeneration or re-differentiation of a functional pancreatic islet β-cell mass to restore insulin levels and normoglycemia. However, T2DM is not only caused by failures in β-cells but also by dysfunctions in the central nervous system (CNS), especially in the hypothalamus and brainstem. Herein, we review the physiological contribution of hypothalamic neuronal and glial populations, particularly astrocytes, in the control of the systemic response that regulates blood glucose levels. The glucosensing capacity of hypothalamic astrocytes, together with their regulation by metabolic hormones, highlights the relevance of these cells in the control of glucose homeostasis. Moreover, the critical role of astrocytes in the response to inflammation, a process associated with obesity and T2DM, further emphasizes the importance of these cells as novel targets to stimulate the CNS in response to metabesity (over-nutrition-derived metabolic dysfunctions). We suggest that novel T2DM therapies should aim at stimulating the CNS astrocytic response, as well as recovering the functional pancreatic β-cell mass. Whether or not a common factor expressed in both cell types can be feasibly targeted is also discussed.

Circulating 11-oxygenated androgens across species

The androgen precursors, dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) are produced in high amounts by the adrenal cortex primarily in humans and a few other primates. The human adrenal also secretes 11-oxygenated androgens (11-oxyandrogens), including 11β-hydroxyandrostenedione (11OHA4), 11-ketoandrostenedione (11KA4), 11β-hydroxytestosterone (11OHT) and 11-ketotestosterone (11KT), of which 11OHT and 11KT are bioactive androgens. The 11-oxyandrogens, particularly 11KT, have been recognized as biologically important testicular androgens in teleost fishes for decades, but their physiological contribution in humans has only recently been established. Beyond fish and humans, however, the presence of 11-oxyandrogens in other species has not been investigated. This study provides a comprehensive analysis of a set of C19 steroids, including the traditional androgens and 11-oxyandrogens, across 18 animal species. As previously shown, serum DHEA and DHEAS were much higher in primates than all other species. Circulating 11-oxyandrogens, especially 11KT, were observed in notable amounts in male, but not in female trout, consistent with gonadal origin in fish. The circulating concentrations of 11-oxyandrogens ranged from 0.1 to 10 nM in pigs, guinea pigs and in all the primates studied (rhesus macaque, baboon, chimpanzee and human) but not in rats or mice, and 11OHA4 was consistently the most abundant. In contrast to fish, serum 11KT concentrations were similar in male and female primates for each species, despite significantly higher circulating testosterone in males, suggesting that 11KT production in these species is not testis-dependent and primarily originates from adrenal-derived 11-oxyandrogen precursors.

PD20-03 FEMALE PERIURETHRAL TISSUE INNERVATION STUDIES: MID-URETHRAL SLING SURGERIES MAY RESULT IN SEXUAL DYSFUNCTION

INTRODUCTION AND OBJECTIVES:The female periurethral tissue (FPT) contains numerous glands staining positive for prostate specific acid. These glands are surrounded by neuronal and vascular structures, and may have physiologic contribution to sexual function. The PFT is located adjacent to the anterior vaginal wall epithelium and surrounds the urethra passing distally from the bladder neck to the meatus. Decreased sexual function, especially lowered orgasm satisfaction has been reported following mid-urethral sling procedures to treat stress urinary incontinence, and requires further investigation of this possible iatrogenic effect. Cadaver studies have shown the mid-urethral sling transects through the glandular, neuronal, and vascular structures of the PFT. The goal of this new research is to further histologically characterize the PFT and examine patterns of innervation in relation to its specific morphological features.METHODS:Histologic and immunohistochemical investigations of glandular, vascular, an...

Genetic, Physiologic, and Behavioral Predictors of Cardiorespiratory Fitness in Specialized Military Men.

Cardiorespiratory fitness (CRF) is a crucial performance requirement of specialized military occupations. Age and physical activity are established predictors of CRF, but it is not clear how these predictors combine with each other and/or with genetic predisposition. The goal of this study was to derive inclusive explanatory models of CRF in US Navy Explosive Ordnance Disposal (EOD) operators, synthesizing conventional (e.g., age, body composition, and physical activity) and novel influences (e.g., genetic variance). In this cross-sectional study, 40 male, active duty EOD operators completed a graded exercise test to assess maximal oxygen consumption and ventilatory threshold (VT) using the Bruce protocol. Aerobic performance was further quantified via time of test termination and time at which VT was achieved. Body composition was determined via dual x-ray absorptiometry, and physical activity was assessed by self-report. Genetic variants underlying human stress systems (5HTTLPR, BclI, -2 C/G, and COMT) were assayed. Descriptive analyses were conducted to summarize subject characteristics. Hypotheses were tested with linear regression models. Specifically, separate univariate regression models first determined associations between each of the independent and dependent variables. This protocol was approved by the Naval Health Research Center Institutional Review Board (NHRC.2015.0013). In univariate regression models, age, body composition, physical activity, and 5HTTLPR consistently predicted CRF and/or aerobic performance (R2 range 0.07-0.55). Multivariate regression models routinely outperformed the univariate models, explaining 36-62% of variance. This study signifies a shift toward inclusive explanatory models of CRF and aerobic performance, accounting for combined roles of genetic, physiologic, and behavioral influences. Although we were able to quantify combined effects, we were unable to evaluate interaction effects (e.g., gene-gene, gene-behavior) due to limited statistical power. Other limitations are that this specialized military population may not readily generalize to broader populations, and the current sample was all male. Considering these limitations, we aim to replicate this study in various populations, both male and female. Despite its limitations, this study reflects a shift toward more comprehensive predictive models of CRF, explaining the unique and shared contributions of genetic predisposition, physiology, and behavior. These findings have implications for assessment, selection, and training of specialized military members, and may also impact mission success and survivability. Future studies are needed to better characterize additive, interactive, and mediated effects.

On the analysis of rapidly sampled fMRI data

Recent advances in parallel imaging and simultaneous multi-slice techniques have permitted whole-brain fMRI acquisitions at sub-second sampling intervals, without significantly sacrificing the spatial coverage and resolution. Apart from probing brain function at finer temporal scales, faster sampling rates may potentially lead to enhanced functional sensitivity, owing possibly to both cleaner neural representations (due to less aliased physiological noise) and additional statistical benefits (due to more degrees of freedom for a fixed scan duration). Accompanying these intriguing aspects of fast acquisitions, however, confusion has also arisen regarding (1) how to preprocess/analyze these fast fMRI data, and (2) what exactly is the extent of benefits with fast acquisitions, i.e., how fast is fast enough for a specific research aim? The first question is motivated by the altered spectral distribution and noise characteristics at short sampling intervals, while the second question seeks to reconcile the complicated trade-offs between the functional contrast-to-noise ratio and the effective degrees of freedom. Although there have been recent efforts to empirically approach different aspects of these two questions, in this work we discuss, from a theoretical perspective accompanied by some illustrative, proof-of-concept experimental in vivo human fMRI data, a few considerations that are rarely mentioned, yet are important for both preprocessing and optimizing statistical inferences for studies that employ acquisitions with sub-second sampling intervals. Several summary recommendations include concerns regarding advisability of relying on low-pass filtering to de-noise physiological contributions, employment of statistical models with sufficient complexity to account for the substantially increased serial correlation, and cautions regarding using rapid sampling to enhance functional sensitivity given that different analysis models may associate with distinct trade-offs between contrast-to-noise ratios and the effective degrees of freedom. As an example, we demonstrate that as TR shortens, the intrinsic differences in how noise is accommodated in general linear models and Pearson correlation analyses (assuming Gaussian distributed stochastic signals and noise) can result in quite different outcomes, either gaining or losing statistical power.

Conditional deletion of Des1 in the mouse retina does not impair the visual cycle in cones.

Cone photoreceptors are essential for vision under moderate to high illuminance and allow color discrimination. Their fast dark adaptation rate and resistance to saturation are believed to depend in part on an intraretinal visual cycle that supplies 11-cis-retinaldehyde to cone opsins. Candidate enzymes of this pathway have been reported, but their physiologic contribution to cone photoresponses remains unknown. Here, we evaluate the role of a candidate retinol isomerase of this pathway, sphingolipid δ4 desaturase 1 (Des1). Single-cell RNA sequencing analysis revealed Des1 expression not only in Müller glia but also throughout the retina and in the retinal pigment epithelium. We assessed cone functional dependence on Müller cell–expressed Des1 through a conditional knockout approach. Floxed Des1 mice, on a guanine nucleotide-binding protein subunit α transducin 1 knockout (Gnat1−/−) background to allow isolated recording of cone-driven photoresponses, were bred with platelet-derived growth factor receptor α (Pdgfrα)-Cre mice to delete Des1 in Müller cells. Conditional knockout of Des1 expression, as shown by tissue-selective Des1 gene recombination and reduced Des1 catalytic activity, caused no gross changes in the retinal structure and had no effect on cone sensitivity or dark adaptation but did slightly accelerate the rate of cone phototransduction termination. These results indicate that Des1 expression in Müller cells is not required for cone visual pigment regeneration in the mouse.—Kiser, P. D., Kolesnikov, A.V., Kiser, J. Z., Dong, Z., Chaurasia, B., Wang, L., Summers, S. A., Hoang, T., Blackshaw, S., Peachey, N. S., Kefalov, V. J., Palczewski, K. Conditional deletion of Des1 in the mouse retina does not impair the visual cycle in cones.

Development and applications of fluorescent probes for the detection of Fe(II) ion

Iron is the most abundant transition metal in our body and plays various pivotal roles in our lives including oxygen transport, energy production, and metabolic reactions. At the same time, an excess amount of iron may cause cellular damages through undesired oxidative reactions. We have developed several fluorescent probes, which can detect Fe(II) ion selectively with fluorescence enhancement, to understand both the physiological and pathological contributions of iron in living systems. These fluorescent probes worked in an aqueous buffer, living cells, and histochemical samples (Chem. Sci. 2013, 4, 1250; Chem. Sci. 2017, 8, 4858; Free Radic. Res. 2014, 48, 990; Sci. Rep. 2017, 7, 10621) I will present the recent progress of the development of organelle-targeted fluorescent probes for mitochondria, lysosome, and plasma-membrane (Metallomics, 2018, 10, 794; Metallomics, 2018, in press; ACS Chem. Biol., 2018, 13, 1853). Besides, our recent approach to discover iron-regulating drug by high-throughput screening with a highly sensitive fluorescent probe will be presented.

Development and applications of Fe(II)-selective fluorescent probes

Iron is the most abundant transition metal in our body and plays various pivotal roles in our lives including oxygen transport, energy production, and metabolic reactions. At the same time, an excess amount of iron may cause cellular damages through undesired oxidative reactions due to the high redox activity of Fe ion. We have developed the several fluorescent probes which can detect Fe(II) ion selectively with fluorescence enhancement to understand both the physiological and pathological contributions of Fe ion in living systems. These fluorescent probes worked in an aqueous buffer, living cells, and histochemical-stained samples (Chem Sci. 2013;4:1250, Chem Sci. 2017;8:4858, Free Radic Res. 2014;48:990, Sci Rep. 2017;7:10621). We established a color series of Fe(II)-selective fluorescent probes from blue to deep-red, which were applied to organelle-targeted fluorescent probes for mitochondria, lysosome, and endoplasmic reticulum. Herein, I would like to focus on fluorescence imaging study about the alteration of labile Fe(II) level in each organelle during ferroptosis, iron-dependent cell death, by using the various organelle-targeted fluorescent probes of Fe(II).

Extracellular vesicles and its advances in female reproduction

Intercellular communication is an essential mechanism for development and maintenance of multicellular organisms. Extracellular vesicles (EVs) were recently described as new players in the intercellular communication. EVs are double-membrane vesicles secreted by cells and are classified according to their biosynthesis, protein markers and morphology. These extracellular vesicles contain bioactive materials such as miRNA, mRNA, protein and lipids. These characteristics permit their involvement in different biological processes. Reproductive physiology is complex and involves constant communication between cells. Different laboratories have described the presence of EVs secreted by ovarian follicular cells, oviductal cells, in vitro produced embryos and by the endometrium, suggesting that EVs are involved in the development of gametes and embryos, in animals and humans. Therefore, is important to understand physiological mechanisms and contributions of EVs in female reproduction in order to develop new tools to improve in vivo reproductive events and assisted reproductive techniques (ARTs). This review will provide the current knowledge related to EVs in female reproductive tissues and their role in ARTs.

Murine HSCs contribute actively to native hematopoiesis but with reduced differentiation capacity upon aging.

A hallmark of adult hematopoiesis is the continuous replacement of blood cells with limited lifespans. While active hematopoietic stem cell (HSC) contribution to multilineage hematopoiesis is the foundation of clinical HSC transplantation, recent reports have questioned the physiological contribution of HSCs to normal/steady-state adult hematopoiesis. Here, we use inducible lineage tracing from genetically marked adult HSCs and reveal robust HSC-derived multilineage hematopoiesis. This commences via defined progenitor cells, but varies substantially in between different hematopoietic lineages. By contrast, adult HSC contribution to hematopoietic cells with proposed fetal origins is neglible. Finally, we establish that the HSC contribution to multilineage hematopoiesis declines with increasing age. Therefore, while HSCs are active contributors to native adult hematopoiesis, it appears that the numerical increase of HSCs is a physiologically relevant compensatory mechanism to account for their reduced differentiation capacity with age.

Effect of Physiological noise on Thoraco-Lumbar spinal cord fMRI in 3T Magnetic field

Introduction: Functional MRI methods have been used to study sensorimotor processing in the brain and the Spinal cord. However, these techniques confront unwanted contributions to the measured signal from physiological fluctuations. For the spinal cord imaging, most of the challenges are consequences of cardiac and respiratory movement artifacts that are considered as significant sources of noise. Spinal cord in Thoraco-Lumbar is close to lungs and diaphragms that influence cerebrospinal fluid-filled spaces and cause changes in thesusceptibility due to the change in the amount of air in the lung. In this study, we investigatedthe effect of each source of physiological noise and contribution of them to the outcome ofthe analysis of the BOLD signal in human spinal cord during a sensory stimulation of the foot. Materials and Methods: Fifteen young healthy male volunteers participated in the study. Sixty pressure pain stimuli delivered on L5 dermatome between the two malleoli. All of functional data were collected using a 3T Siemens Prisma scanner with 31 axial slices T2*-weighted ZOOMit (TR = 3000 ms; TE = 30 ms; FA = 90°; FoV = 160 × 160 mm; matrix size = 64 × 64). Respiratory and cardiac signals were recorded during the imaging session using the data acquired from theimplemented physiological monitoring unit. The Spinal Cord Toolbox and FSL were used forimage processing and analysis. Generated respiration and cardiac regressors were includedin the GLM for the quantification of the effect of each of them on the task-analyses results. The sum of activated voxels of the clusters in the spinal cord and in all the image was calculated. Results: Comparison of sum of activated voxels. A one-way within subject’s ANOVA was applied toevaluate the effect of physiological functions on spinal cord fMRI in three noise correction inthe GLM. There was a statistically significant effect of physiological noise correctiononnumber of activated voxels in Image, F (3, 42) = 3.00689, p = .040817, η2 =0.17, and thisvalues in spinal cord was F(3, 42) = 21.314, p =.00001, , η2 =0.6. Bonferroni post hoc testsillustrate that cardiac noise correction had an effective role on increase activated voxels (mean = 23.46±9.46) compared to other noise correction methods. Conclusion: The effect of the Heart-beat and Respiration movements has a significant role in thephysiological noise and concurrency between movements with task and correction of thismovements can remove the real effect of stimulation. Cardiac effect and changes in thecorrected results are higher than other physiological noise sources. In spite of previous work,displacement of the spinal cord and effect of this noise in the fMRI results are significant andcannot be ignored.

Leptin and Aldosterone.

The prominence of obesity in the clinical population as well as the strong association of cardiovascular risk factors with obesity has prompted the investigation of the adipose tissue and its physiological contribution to cardiovascular health. A notable finding in these investigations was the discovery of the adipocyte-derived hormone leptin. Leptin is secreted from the adipose tissue, increases in linear fashion in the circulation with increased body mass and is implicated in the development of cardiovascular disease in obesity, notably via pro-hypertensive mechanisms. Leptin stimulates the activation of the sympathetic nervous system in male patients and mice, which has been implicated as the pro-hypertensive pathway for leptin in obesity. However, obese premenopausal females do not exhibit increased sympathetic activation in response to hyperleptinemia in obesity, indicating a sex-discrepancy in mechanisms of obesity-associated hypertension. Our lab recently demonstrated that leptin also induces the adrenal production of aldosterone in a direct fashion and that this pathway leads to the hyperaldosteronemia that is characteristic of obesity. We have also published data that indicate that the implications of leptin-induced aldosterone are of particular impact in obese females. Leptin-mediated hypertension and endothelial dysfunction, a significant predictor of hypertension clinically, require activation of the mineralocorticoid receptor in female mice. The clinical potential of this pathway remains under investigation; however, existing data indicate that a sex discrepancy exists in mechanisms of leptin-mediated hypertension between males and females and that leptin-stimulated aldosterone plays a significant role in females.

Characterizing contrast origins and noise contribution in spin-echo EPI BOLD at 3 T

In this work, we characterize contrast origins and noise contributions of spin echo (SE) EPI BOLD signal at 3 T. SE BOLD is a fMRI method of choice for imaging brain regions affected by susceptibility artifacts at lower fields, but its sensitivity remains a limiting factor for whole-brain imaging. To resolve this, the signal and noise contributions as well as TE dependence of SE EPI are characterized in this study. By integrating a two-compartment BOLD model with a physiological-thermal noise model, a new SE-BOLD signal model was introduced. The new SE-BOLD model was fit into SE-EPI fMRI data acquired during hypercapnic manipulations at various TEs, using typical fMRI voxel dimensions (3.4 × 3.4 × 5 mm3). Our model predicts intra- and extravascular signal and noise contributions consistent with our understanding of the SE-EPI contrast mechanism. The intravascular BOLD contribution is shown to dominate at TEs lower than tissue T2, but the physiological noise contributions in SE-EPI signal is also shown to be lower than that of gradient-echo (GE). Furthermore, SE-EPI contrast-to-noise ratio (CNR) is not maximized at tissue T2 as is typically assumed. To summarize, a new SE-BOLD model was proposed to characterize SE-BOLD contrast and physiological noise contribution at 3 T. Results suggests that SE-BOLD sensitivity can be improved by using shorter TEs, making it a more attractive choice for fMRI, especially in regions with susceptibility artifacts. Such optimizations could also help extend the application of SE BOLD to WM fMRI studies.

Improvement of Flutter-Kick Performance in Novice Surface Combat Swimmers With Increased Hip Strength.

To examine strength, range of motion, anthropometric, and physiological contributions to novice surface-combat-swimming (sCS) performance and establish differences from freestyle-swimming (FS) performance to further understand the transition of FS to sCS performance. A total of 13 competitive swimmers (7 male and 6 female; 27.7 [2.3]y; 176.2 [2.6]cm; 75.4 [3.9]kg) completed 8 testing sessions consisting of the following: physiological land-based measurements for maximal anaerobic and aerobic capacity and upper- and lower-extremity strength and range of motion, an sCS anaerobic capacity swim test measuring peak and mean force and fatigue index, 2 aerobic capacity tests measuring maximal aerobic capacity for both FS and sCS, and four 500-m performance swims for time, 1 FS, and 3 sCS. Separate multiple linear-regression analysis was used to analyze predictors of both sCS and FS performance models. FS performance was predicted by the final FS maximal oxygen uptake with an R2 of 42.03% (F1,10 = 7.25; P = .0226), whereas sCS performance was predicted by isometric hip-extension peak strength with an R2 of 41.46% (F1,11 = 7.79; P = .0176). Results demonstrate that different physiological characteristics predict performance, suggesting that an altered strategy is used for novice sCS than FS. It is suggested that this may be due to the added constraints as mandated by mission requirements including boots, weighted gear, and clandestine requirements with hips lowered beneath the surface. Further research should examine the kinematics of the sCS flutter kick to improve performance by developing training strategies specific for the task.

Clinical and Genetic Heterogeneity of CARD14 Mutations in Psoriatic Skin Disease

The CARD: BCL10: MALT1 (CBM) complex is an essential signaling node for maintaining both innate and adaptive immune responses. CBM complex components have gained considerable interest due to the dramatic effects of associated mutations in causing severe lymphomas, immunodeficiencies, carcinomas and inflammatory disease. While MALT1 and BCL10 are ubiquitous proteins, the CARD-containing proteins differ in their tissue expression. CARD14 is primarily expressed in keratinocytes. The CARD14-BCL10-MALT1 complex is activated by upstream pathogen-associated molecular pattern-recognition in vitro, highlighting a potentially crucial role in innate immune defense at the epidermal barrier. Recent findings have demonstrated how CARD14 orchestrates activation of the NF-κB and MAPK signaling pathways via recruitment of BCL10 and MALT1, leading to the upregulation of pro-inflammatory genes encoding IL-36γ, IL-8, Ccl20 and anti-microbial peptides. Following the identification of CARD14 gain-of function mutations as responsible for the psoriasis susceptibility locus PSORS2, the past years have witnessed a large volume of case reports and association studies describing CARD14 variants as causal or predisposing to a wide range of inflammatory skin disorders. Recent publications of mouse models also helped to better understand the physiological contribution of CARD14 to psoriasis pathogenesis. In this review, we summarize the clinical, genetic and functional aspects of human and murine CARD14 mutations and their contribution to psoriatic disease pathogenesis.