BackgroundNeuropathic pain (NP) is a common occurrence following spinal cord injury (SCI). Identification of specific molecular pathways that are involved in pain syndromes has become a major priority in current SCI research. We have investigated the role of a cation-dependent chloride transporter, Cl-regulatory protein Na+-K+-Cl- 1 (NKCC1), phosphorylation profile of NKCC1 and its specific involvement in neuropathic pain following contusion SCI (cSCI) using a rat model. Administration of the NKCC1 inhibitor bumetanide (BU) increases the mean hindpaw withdrawal latency time (WLT), thermal hyperalgesia (TH) following cSCI. These results demonstrate implication of NKCC1 co-transporter and BUin SCI-induced neuropathic pain. The with-no-lysine (K)–1 (WNK1) kinase has been shown to be an important regulator of NKCC1 phosphorylation in many systems, including nocioception. Mutations in a neuronal-specific exon of WNK1 (HSN2) was identified in patients that have hereditary sensory neuropathy type II (HSANII) also implicates WNK1 in nocioception, such that these patients have loss of perception to pain, touch and heat. In our ongoing research we proposed two studies utilizing our contusion SCI (cSCI) NP model of rat.PurposeStudy 1 aimed at NKCC1 expression and activity is up-regulated following cSCI in the early edema and chronic neuropathic pain phases. Study 2 aimed at identifying the expression profile of alternatively spliced WNK1 isoforms in animals exhibiting thermal hyperalgesia (TH) following cSCI.MethodsAdult male Sprague Dawley rats (275–300 g) following laminectomy received cSCI at T9 with the NYU impactor-device II by dropping 10 g weight from the height of 12.5 mm. Control rats obtained laminectomy but no impaction. Following injury, functional recovery was assessed by BBB locomotor scores on day 1, 7, 14, 21, 35, and 42 and development of thermal hyperalgesia on day 21, 28, 35, and 42 day of injury by monitoring hind paw withdraw latency time (WLT) in seconds compared with the baseline data before injury.ResultsIncreased NKCC1 may explain observed increase in magnetic resonance imaging (MRI) T2, exhibiting NKCC1 localization in neurons. This data supports NKCC1’s role in the pathogenesis of acute and chronic phases of injury, namely spinal cord edema and chronic phase neuropathic pain. NKCC1 dependent chloride influx requires the phosphorylation at specific residues. Probing for the HSN2 exon of WNK1 reveals two key findings: i) the HSN2 exon is found in alternatively spliced neuronal isoforms found at 250 kDa and 230 kDa; ii) the 250 kDa isoform is found only in tissue that is injured.ConclusionsThis data implicates the NKCC1/WNK1/WNK1HSN2 involvement in post-injury response that contributes to the development of neuropathic pain. Targeting this system may have therapeutic benefit.
Sharks are critical apex predators, which underpin the trophic structure and functionality of marine ecosystems, yet many shark species globally have suffered major declines in recent decades due to human activities. Subsequently, a quarter of the world's sharks and rays are recognized by the International Union for the Conservation of Nature (IUCN) as threatened or at risk of extinc-
The white shark (Carcharodon carcharias) is one of the world's largest apex predators found throughout the world's temperate and subtropical marine environments. However, the species has suffered significant declines in recent decades and effective conservation programs require a sound knowledge of white shark biology and ecology. In particular, information on white shark diet across life stages and the species' range is needed to identify critical trophic interactions supporting shark populations and to predict the resilience of white sharks to environmental changes. In this study, we reassess the diet and trophic ecology of white sharks via the genetic analyses of cloacal swabs from 214 juvenile and subadult sharks from eastern Australia. Our findings are largely consistent with those of previous studies based on visual analyses of gut contents but highlight the unprecedented taxonomic resolution of prey items offered by genomic assessments of shark cloacal swabs. Diets consisted primarily of ray‐finned fishes, with Mugiliformes, Carangiformes, Perciformes, and Scombriformes being dominant prey taxa, but with elasmobranchs, marine mammals, and birds also being common dietary constituents. Statistical analyses revealed a significant effect of sex and sampling location on diet composition, indicating biological and spatial variability in diets and predatory behavior. Overall, these findings support the notion that juvenile and subadult white sharks are opportunistic predators, which may provide some level of resilience to shifts in marine resources. However, frequently consumed ray‐finned fishes, many of which are commercially targeted, may be key to supporting white shark populations in eastern Australia. This study represents the most comprehensive analysis of juvenile and subadult white shark diets performed to date and provides added confidence in the genomic analysis of cloacal swabs for dietary assessments of predatory species. These results are expected to help inform management geared toward conserving this important marine predator across the world's oceans.
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