Search

Abstract A targeted injury to the mouse intervertebral disc (IVD) is often used to recapitulate the degenerative cascade of the human pathology. Since injuries can vary in magnitude and localization, it is critical to examine the effects of different injuries on IVD degeneration. We thus evaluated the degenerative progression resulting from either a partial- or full-width injury to the mouse lumbar IVD using contrast-enhanced micro-computed tomography and histological analyses. A lateral-retroperitoneal surgical approach was used to access the lumbar IVD, and the injuries to the IVD were produced by either incising one side of the annulus fibrosus or puncturing both sides of the annulus fibrosus. Female C57BL/6J mice of 3–4 months age were used in this study. They were divided into three groups to undergo partial-width, full-width, or sham injuries. The L5/6 and L6/S1 lumbar IVDs were surgically exposed, and then the L6/S1 IVDs were injured using either a surgical scalpel (partial-width) or a 33G needle (full-width), with the L5/6 serving as an internal control. These animals recovered and then euthanized at either 2-, 4-, or 8-weeks after surgery for evaluation. The IVDs were assessed for degeneration using contrast-enhanced microCT (CEµCT) and histological analysis. The high-resolution 3D CEµCT evaluation of the IVD confirmed that the respective injuries were localized within one side of the annulus fibrosus or spanned the full width of the IVD. The full-width injury caused significant deteriorations in the nucleus pulposus, annulus fibrous and at the interfaces after 2 weeks, which was sustained through the 8 weeks, while the partial width injury caused localized disruptions that remained limited to the annulus fibrosus. The use of CEµCT revealed distinct IVD degeneration profiles resulting from partial- and full-width injuries. The partial width injury may serve as an alternative model for IVD degeneration resulting from localized annulus fibrosus injuries.

The tropical Atlantic is home to multiple coupled climate variations covering a wide range of timescales and impacting societally relevant phenomena such as continental rainfall, Atlantic hurricane activity, oceanic biological productivity, and atmospheric circulation in the equatorial Pacific. The tropical Atlantic also connects the southern and northern branches of the Atlantic meridional overturning circulation and receives freshwater input from some of the world's largest rivers. To address these diverse, unique, and interconnected research challenges, a rich network of ocean observations has developed, building on the backbone of the Prediction and Research Moored Array in the Tropical Atlantic (PIRATA). This network has evolved naturally over time and out of necessity in order to address the most important outstanding scientific questions and to improve predictions of tropical Atlantic severe weather and global climate variability and change. The tropical Atlantic observing system is motivated by goals to understand and better predict phenomena such as tropical Atlantic interannual to decadal variability and climate change; multidecadal variability and its links to the meridional overturning circulation; air-sea fluxes of CO2 and their implications for the fate of anthropogenic CO2; the Amazon River plume and its interactions with biogeochemistry, vertical mixing, and hurricanes; the highly productive eastern boundary and equatorial upwelling systems; and oceanic oxygen minimum zones, their impacts on biogeochemical cycles and marine ecosystems, and their feedbacks to climate. Past success of the tropical Atlantic observing system is the result of an international commitment to sustained observations and scientific cooperation, a willingness to evolve with changing research and monitoring needs, and a desire to share data openly with the scientific community and operational centers. The observing system must continue to evolve in order to meet an expanding set of research priorities and operational challenges. This paper discusses the tropical Atlantic observing system, including emerging scientific questions that demand sustained ocean observations, the potential for further integration of the observing system, and the requirements for sustaining and enhancing the tropical Atlantic observing system.

Abstract Diabetes is associated with impaired tendon homeostasis and subsequent tendon dysfunction, but the mechanisms underlying these associations is unclear. Advanced glycation end-products (AGEs) accumulate with diabetes and have been suggested to alter tendon function. In vivo imaging in humans has suggested collagen disorganization is more frequent in individuals with diabetes, which could also impair tendon mechanical function. The purpose of this study was to examine relationships between tendon tensile mechanics in human Achilles tendon with accumulation of advanced glycation end-products and collagen disorganization. Achilles tendon specimens (n = 16) were collected from individuals undergoing lower extremity amputation or from autopsy. Tendons were tensile tested with simultaneous quantitative polarized light imaging to assess collagen organization, after which AGEs content was assessed using a fluorescence assay. Moderate to strong relationships were observed between measures of collagen organization and tendon tensile mechanics (range of correlation coefficients: 0.570–0.727), whereas no statistically significant relationships were observed between AGEs content and mechanical parameters (range of correlation coefficients: 0.020–0.210). Results suggest that the relationship between AGEs content and tendon tensile mechanics may be masked by multifactorial collagen disorganization at larger length scales (i.e., the fascicle level).

Abstract Introduction Diabetes has long been implicated as a major risk factor for intervertebral disc (IVD) degeneration, interfering with molecular signaling and matrix biochemistry, which ultimately aggravates the progression of the disease. Glucose content has been previously shown to influence structural and compositional changes in engineered discs in vitro, impeding fiber formation and mechanical stability. Methods In this study, we investigated the impact of diabetic hyperglycemia on young IVDs by assessing biochemical composition, collagen fiber architecture, and mechanical behavior of discs harvested from 3‐ to 4‐month‐old db/db mouse caudal spines. Results We found that discs taken from diabetic mice with elevated blood glucose levels demonstrated an increase in total glycosaminoglycan and collagen content, but comparable advanced glycation end products (AGE) levels to wild‐type discs. Diabetic discs also contained ill‐defined boundaries between the nucleus pulposus and annulus fibrosus, with the latter showing a disorganized and unaligned collagen fiber network at this same boundary. Conclusions These compositional and structural changes had a detrimental effect on function, as the diabetic discs were twice as stiff as their wild‐type counterparts and demonstrated a significant resistance to deformation. These results indicate that diabetes may predispose the young disc to DDD later in life by altering patterns of extracellular matrix deposition, fiber formation, and motion segment mechanics independently of AGE accumulation.

Type 2 diabetes mellitus (T2D) is an increasingly prevalent disease with numerous comorbidities including many in the spine. T2D is strongly linked with vertebral fractures, intervertebral disc (IVD) degeneration, and severe chronic spinal pain. Yet the causative mechanism for these musculoskeletal impairments remains unclear. The chronic hyperglycemic state in T2D promotes the formation of advanced glycation end-products (AGEs) in tissues, and the accumulation of AGEs may play a role in musculoskeletal complications by modifying the extracellular matrix, impairing cellular homeostasis, and perpetuating an inflammatory cascade via its receptor (RAGE). The AGE and RAGE associated alterations in extracellular matrix composition and morphological features of the vertebral bodies and IVDs are likely contributors to the incidence and severity of spinal pathologies in T2D. This review will broadly examine the effects of AGEs on tissues in the spine in the context of T2D, with an emphasis on the changes in the vertebrae and the IVD. Along with the clinical and epidemiological findings, we will provide an overview of preclinical rodent models of T2D that exhibit deficits in the IVD and vertebral bone. Elucidating the role of AGEs and RAGE will be crucial for understanding the disease mechanisms and translation therapies of musculoskeletal pathologies in T2D.

Abstract Mouse models are often used for studies of intervertebral disc (IVD) homeostasis and degeneration, yet the relatively small size of the IVD poses challenges for noninvasive, longitudinal imaging modalities. The recently developed contrast‐enhanced microCT (CEμCT) using Ioversol has been successful in detecting degenerative changes in the murine IVD ex vivo at the micrometer scale. Further leveraging the superior biocompatibility of Ioversol as a contrast agent, we demonstrate the in vivo use of this CEμCT technique to examine IVDs at multiple spinal sites. Ioversol was administered via tail vein injection (TVI) in growing and adult male FVB/NJ mice (n = 5 /group). The animals were anesthetized and underwent in vivo micro‐computed tomographic (microCT) at the coccygeal (CC5/CC6), lumbar (L5/6), and thoracic (T12/T13) IVDs. TVI of Ioversol was well‐tolerated by all animals. As Ioversol filtered through the kidneys and accumulated in the bladder, the attenuations of the mouse bladder and kidneys increased due to the high molecular weight of Ioversol, confirming that the Ioversol is biological available. Average IVD attenuations increased 3%‐15% following TVI (ANOVA; P

Leader identity theory posits that, in addition to being positional, leadership is also a malleable state of mind. This means that even employees holding positions of authority within their organization may be nudged to identify more strongly with their leader role on some days versus others. The leadership literature, however, is silent about predictors that may prime leader identity day-to-day. We draw from leader identity theory and research on expressive writing to propose that leader identity can be activated daily via positive leader self-reflection (e.g., reflecting and writing about qualities that make one a good leader) in ways that are beneficial for the leader both at work and at home. We tested our theoretical expectations in two field experiments. In the first study, as expected, we find that leaders reported higher activated leader identity and more goal progress on intervention (vs. control) days. In turn, activated leader identity and goal progress enhanced leader well-being measured in the evening at home. Surprisingly, and contrary to expectations, the well-being enhancing effects of positive leader self-reflection were weaker for leaders who were higher (vs. lower) in identity fusion with their followers. In the second study, we demonstrate the malleable nature of leader identity by showing not only that positive leader self-reflection activates leader identity, but also that negative leader self-reflection diminishes its activation. [ABSTRACT FROM AUTHOR]

Marine ascidians are an abundant source of new bioactive metabolites. The current investigation aimed at characterizing anti-mycobacterial compounds from Indonesian marine ascidian Polycarpa sp. After extracting ethanol, Ascidian Polycarpa sp. was segregated with EtOAc and H2O. Ethyl acetate extract was purified using preparative HPLC. Identification and characterization of compounds using spectroscopic analysis. Anti-mycobacterial activity testing using the disc diffusion method on Mycobacterium smegmatis. This study showed that the ethyl acetate extract of ascidian Polycarpa sp produced two known compounds polycarpine (1) and palycarpaurine A (2). Compounds 1 and 2 exhibited activity against Mycobacterium smegmatis at 50 μg/disc, with 12- and 10-mm inhibition zones, respectively. This study suggests that polycarpine (1) and palycarpaurine A (2) have potential compounds for antimycobacterium. [ABSTRACT FROM AUTHOR]