Long-term retention of self-fertilization in a fish clade

Among vertebrate animals, only the mangrove rivulus (Kryptolebias marmoratus) was known to self-fertilize. Here, we use microsatellite analyses to document a high selfing rate (97%) in a related nominal species, Kryptolebias ocellatus, which likewise is androdioecious (populations consist of males and hermaphrodites). In contrast, we find no evidence of self-fertilization in Kryptolebias caudomarginatus (an androdioecious species closely related to the marmoratus-ocellatus clade) or in Kryptolebias brasiliensis (a dioecious outgroup). These findings indicate that the initiation of self-fertilization predated the origin of the marmoratus-ocellatus clade. From mitochondrial DNA sequences and microsatellite data, we document a substantial genetic distance between Kryptolebias marmoratus and K. ocellatus, implying that the selfing capacity has persisted in these fishes for at least several hundred thousand years.     

Galanin and galanin receptors in epilepsy

The shift in the balance between the inhibition and the excitation in favor of the latter is a major mechanism of the evolvement of epileptic seizures. On the neurotransmitter level two major players contribute to such misbalance: an inhibitory transmitter gamma-aminobutyric acid, and an excitatory amino acid glutamate. Neuropeptides are powerful modulators of classical neurotransmitters, and thus represent an intriguing tool for restoring the balance between the inhibition and the excitation, through either blocking or activating peptide receptors depending on whether a peptide is pro- or anticonvulsant. Galanin, a 29-amino acid residues neuropeptide which inhibits glutamate release in the hippocampus, is a likely member of the anticonvulsant peptide family. During the past decade growing evidence has been suggesting that galanin is in fact a powerful inhibitor of seizure activity. This review summarizes the state of research of galanin in epilepsy, beginning with the first simple experiments which showed that central injection of galanin agonists inhibited seizures, and that seizures themselves affected galanin signaling in the hippocampus; exploring the impact of active manipulation with the expression of galanin and galanin receptors on seizures, using transgenic animals, antisense and peptide-expressing vector approaches; and concluding with the recent advances in pharmacology, which led to the synthesis of non-peptide galanin receptor agonists with anticonvulsant properties. We also address recently established functions of galanin in seizure-associated neuronal degeneration and neuronal plasticity.     

Transient and steady state estimation of human oxygen uptake based on noninvasive portable sensor measurements

The main motivation of this study is to establish an ambulatory cardio-respiratory analysis system for the monitoring and evaluation of exercise and regular daily physical activity. We explored the estimation of oxygen uptake by using noninvasive portable sensors. These sensors are easy to use but may suffer from malfunctions under free living environments. A promising solution is to combine sensors with different measuring mechanisms to improve both reliability and accuracy of the estimation results. For this purpose, we selected a wireless heart rate sensor and a tri-axial accelerometer to form a complementary sensor platform. We analyzed the relationship between oxygen uptake measured by gas analysis and data collected from the simple portable sensors using multivariable nonlinear modeling approaches. It was observed that the resulting nonlinear multivariable model could not only achieve a better estimate compared with single input single output models, but also had greater potential to improve reliability.     

Polymorphisms in the glucocorticoid receptor co-chaperone FKBP5 predict persistent musculoskeletal pain after traumatic stress exposure

Individual vulnerability factors influencing the function of the hypothalamic-pituitary-adrenal axis may contribute to the risk of the development of persistent musculoskeletal pain after traumatic stress exposure. The objective of the study was to evaluate the association between polymorphisms in the gene encoding FK506 binding protein 51, FKBP5, a glucocorticoid receptor co-chaperone, and musculoskeletal pain severity 6 weeks after 2 common trauma exposures. The study included data from 2 prospective emergency department-based cohorts: a discovery cohort (n = 949) of European Americans experiencing motor vehicle collision and a replication cohort of adult European American women experiencing sexual assault (n = 53). DNA was collected from trauma survivors at the time of initial assessment. Overall pain and neck pain 6 weeks after trauma exposure were assessed using a 0–10 numeric rating scale. After adjustment for multiple comparisons, 6 FKBP5 polymorphisms showed significant association (minimum P < 0.0001) with both overall and neck pain in the discovery cohort. The association of rs3800373, rs9380526, rs9394314, rs2817032, and rs2817040 with neck pain and/or overall pain 6 weeks after trauma was replicated in the sexual assault cohort, showing the same direction of the effect in each case. The results of this study indicate that genetic variants in FKBP5 influence the severity of musculoskeletal pain symptoms experienced during the weeks after motor vehicle collision and sexual assault. These results suggest that glucocorticoid pathways influence the development of persistent posttraumatic pain, and that such pathways may be a target of pharmacologic interventions aimed at improving recovery after trauma.     

Running,jumping, hunting,and scavenging: Functional analysis of vertebral mobility and backbone properties in carnivorans

Carnivorans are well-known for their exceptional backbone mobility, which enables them to excel in fast running and long jumping, leading to them being among the most successful predators amongst terrestrial mammals. This study presents the first large-scale analysis of mobility throughout the presacral region of the vertebral column in carnivorans. The study covers representatives of 6 families, 24 genera and 34 species. We utilized a previously developed osteometry-based method to calculate available range of motion, quantifying all three directions of intervertebral mobility: sagittal bending (SB), lateral bending (LB), and axial rotation (AR). We observed a strong phylogenetic signal in the structural basis of the vertebral column (vertebral and joint formulae, length proportions of the backbone modules) and an insignificant phylogenetic signal in most characteristics of intervertebral mobility. This indicates that within the existing structure (stabilization of which occurred rather early in different phylogenetic lineages), intervertebral mobility in carnivorans is quite flexible. Our findings reveal that hyenas and canids, which use their jaws to seize prey, are characterized by a noticeably elongated cervical region and significantly higher SB and LB mobility of the cervical joints compared to other carnivorans. In representatives of other carnivoran families, the cervical region is very short, but the flexibility of the neck (both SB and LB) is significantly higher than that of short-necked odd-toed and even-toed ungulates. The lumbar region of the backbone in carnivorans is dorsomobile in the sagittal plane, being on average ~23° more mobile than in artiodactyls and ~38° more mobile than in perissodactyls. However, despite the general dorsomobility, only some representatives of Canidae, Felidae, and Viverridae are superior in lumbar flexibility to the most dorsomobile ungulates. The most dorsomobile artiodactyls are equal or even superior to carnivorans in their ability to engage in dorsal extension during galloping. In contrast, carnivorans are far superior to ungulates in their ability to engage ventral flexion. The cumulative SB in the lumbar region in carnivorans largely depends on the mode of running and hunting. Thus, adaptation to prolonged and enduring pursuit of prey in hyenas is accompanied by markedly reduced SB flexibility in the lumbar region. A more dorsostable run is also a characteristic of the Ursidae, and the peculiar maned wolf. Representatives of Felidae and Canidae have significantly more available SB mobility in the lumbar region. However, they fully engage it only occasionally at key moments of the hunt associated with the direct capture of the prey or when running in a straight line at maximum speed.     

Targeted drug delivery to tumor vasculature by a carbohydrate mimetic peptide

Although numerous carbohydrates play significant roles in mammalian cells, carbohydrate-based drug discovery has not been explored due to the technical difficulty of chemically synthesizing complex carbohydrate structures. Previously, we identified a series of carbohydrate mimetic peptides and found that a 7-mer peptide, designated I-peptide, inhibits hematogenous carbohydrate-dependent cancer cell colonization. During analysis of the endothelial surface receptor for I-peptide, we found that I-peptide bound to annexin 1 (Anxa1). Because Anxa1 is a highly specific tumor vasculature surface marker, we hypothesized that an I-peptide-like peptide could target anticancer drugs to the tumor vasculature. This study identifies IFLLWQR peptide, designated IF7, as homing to tumors. When synthetic IF7 peptide was conjugated to fluorescent Alexa 488 (A488) and injected intravenously into tumor-bearing mice, IF7-A488 targeted tumors within minutes. IF7 conjugated to the potent anticancer drug SN-38 and injected intravenously into nude mice carrying human colon HCT116 tumors efficiently suppressed tumor growth at low dosages with no apparent side effects. These results suggest that IF7 serves as an efficient drug delivery vehicle by targeting Anxa1 expressed on the surface of tumor vasculature. Given its extremely specific tumor-targeting activity, IF7 may represent a clinically relevant vehicle for anticancer drugs.