Publications by authors named "Cornwall G"

The Morris Water Maze (MWM) is the most commonly used assay for evaluating learning and memory in laboratory mice. Despite its widespread use, contemporary reviews have highlighted substantial methodological variation in experimental protocols and that the associated testing procedures are acutely (each trial) and chronically (testing across days) stressful; stress impairs attention, memory consolidation and the retrieval of learned information. Moreover, the interpretation of behavior within the MWM is often difficult because of wall hugging, non-spatial swim strategies, floating, and jumping off the escape platform.

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The mouse epididymis is a long tubule connecting the testis to the vas deferens. Its primary functions are to mature spermatozoa into motile and fertile cells and to protect them from pathogens that ascend the male tract. We previously demonstrated that a functional extracellular amyloid matrix surrounds spermatozoa in the epididymal lumen and has host defense functions, properties not unlike that of an extracellular biofilm that encloses and protects a bacterial community.

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There is considerable evidence showing that highly ordered aggregate structures known as amyloids carry out essential biological roles in species ranging from bacteria to humans. Indeed, many antimicrobial peptides/proteins form amyloids to carry out their host defense functions and many amyloids are antimicrobial. The similarity of host defense amyloids from bacterial biofilms to the mammalian epididymal amyloid matrix implies highly conserved host defense structures/functions.

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Article Synopsis
  • Limb-Girdle Muscular Dystrophy Type-2B/2R is linked to mutations in the dysferlin gene, particularly two specific missense mutations in the C2A domain.
  • These mutations disrupt dysferlin's function in cell membrane repair, likely due to their tendency to form amyloid structures that trigger an inflammatory response.
  • The study indicates that inflammation and muscle dysfunction in this condition may result from the pathological effects of these C2A mutations and other similar mutations affecting the protein's hydrophobic core.
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The epididymal lumen is an immunologically distinct environment. It maintains tolerance for the naturally antigenic spermatozoa to allow their maturation into functional cells while simultaneously defending against pathogens that can ascend the male tract and cause infertility. We previously demonstrated that a nonpathological amyloid matrix that includes several cystatin-related epididymal spermatogenic (CRES) subgroup family members is distributed throughout the mouse epididymal lumen but its function was unknown.

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Study Design: Experimental in-vivo animal study.

Objective: The aim of this study was to evaluate an Artificial Intelligence (AI)-enabled ultrasound imaging system's ability to detect, segment, classify, and display neural and other structures during trans-psoas spine surgery.

Summary Of Background Data: Current methodologies for intraoperatively localizing and visualizing neural structures within the psoas are limited and can impact the safety of lateral lumbar interbody fusion (LLIF).

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Article Synopsis
  • Research indicates that amyloids have important biological functions, particularly in the mouse epididymis, where specific cystatins form an amyloid matrix.
  • The study investigates how these amyloids assemble, focusing on cross-seeding between different cystatin members to enhance amyloid formation.
  • Findings reveal that CRES3 can create stable amyloid structures that not only help in forming additional CRES amyloids but also interact with other amyloid precursors like Aβ, suggesting a conserved mechanism for regulating amyloid assembly across different proteins.
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Spine surgery (lumbar, cervical, deformity, and entire spine) has increased in volume and improved in outcomes over the past 50 years because of innovations in surgical techniques and introduction of new technologies to improve patient care. Innovation is described as a process to add value or create change in an enterprise's economic or social potential. This mini review will assess two of three assessments of innovation in spine surgery: scientific publications and patents issued.

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Article Synopsis
  • The study investigates the assembly of functional amyloids in the epididymal lumen, focusing on a cystatin-rich matrix that aids in sperm maturation and protection.
  • Researchers developed a purification protocol for a mouse protein called CRES, using advanced techniques like X-ray crystallography and NMR to observe its transition from a single protein unit to a complex amyloid structure.
  • Findings reveal that CRES monomers have a distinct structural fold and can assemble through two mechanisms, providing insights into how functional amyloids form and emphasizing their diverse assembly processes.
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Article Synopsis
  • An amyloid matrix with family 2 cystatins, notably the reproductive cystatin CRES, is essential for sperm maturation and protection in the mouse epididymal lumen.
  • Research focused on purifying CRES to study its aggregation from a single unit to amyloid under conditions mimicking those in the epididymis.
  • Unlike most amyloids, CRES forms unique antiparallel β-sheet-rich structures and its early oligomers might play a crucial role in assembling functional amyloids.
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Background: We previously demonstrated the normal mouse epididymal lumen contains a non-pathological amyloid matrix that surrounds spermatozoa and plays important roles in sperm maturation and protection.

Objective: The objective herein was to present a review of this work, including studies showing the amyloid structures of four members of the CRES (cystatin-related epididymal spermatogenic) subgroup are integral and essential components of the amyloid matrix.

Methods: We used conformation-dependent reagents that recognize the cross-β-sheet structure characteristic of amyloid, including thioflavin S (ThS), thioflavin T (ThT), anti-amyloid antibodies, and X-ray diffraction, as well as negative-stain transmission electron microscopy (TEM) to visualize amyloid structures in the epididymal lumen.

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Objectives: An increasing number of abandoned clinical trials have forestalled efforts to advance the evidence base for the treatment of mood and anxiety disorders in children and adolescents. With this in mind, we sought to present and validate a Bayesian approach for the reanalysis of summary data in abandoned clinical trials and to review and re-evaluate available pharmacokinetic, tolerability, and efficacy data from two large, randomized controlled trials of buspirone in pediatric patients with generalized anxiety disorder (GAD).

Methods: Prospective, randomized, parallel-group controlled trials of buspirone in pediatric patients with GAD as well as associated pharmacokinetic studies were identified and data were extracted.

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Article Synopsis
  • Amyloids, typically seen as harmful protein aggregates linked to diseases like Alzheimer's and diabetes, can also serve important biological functions in various systems.
  • This review focuses on the role of functional amyloids in sexual reproduction, covering aspects like gametogenesis, germline specification, sperm maturation, and fertilization.
  • The study highlights that some of these reproductive amyloids are evolutionarily conserved across different species, including humans, and discusses how changes in these functional amyloids could potentially lead to pathology.
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Objectives: The aim of this study is to identify predictors of pill placebo response and to characterize the temporal course of pill placebo response in anxious youth.

Methods: Data from placebo-treated patients (N = 76) in the Child/Adolescent Anxiety Multimodal Study (CAMS), a multisite, randomized controlled trial that examined the efficacy of cognitive-behavioral therapy, sertraline, their combination, and placebo for the treatment of separation, generalized, and social anxiety disorders, were evaluated. Multiple linear regression models identified features associated with placebo response and models were confirmed with leave-one-out cross-validation.

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Study Question: Do the CRES (cystatin-related epididymal spermatogenic) subgroup members, including CRES2, CRES3 and cystatin E2, contribute to the formation of a nonpathological, functional amyloid matrix in the mouse epididymal lumen?

Summary Answer: CRES2, CRES3 and cystatin E2 self-assemble with different aggregation properties into amyloids in vitro, are part of a common amyloid matrix in the mouse epididymal lumen and are present in extracellular vesicles.

What Is Known Already: Although previously thought only to be pathological, accumulating evidence has established that amyloids, which are highly ordered protein aggregates, can also carry out functional roles in the absence of pathology. We previously demonstrated that nonpathological amyloids are present in the epididymis; specifically, that the reproductive cystatin CRES forms amyloid and is present in the mouse epididymal lumen in a film-like amyloid matrix that is intimately associated with spermatozoa.

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Background: Expandable cages are gaining popularity in anterior reconstruction of the thoracolumbar spine following corpectomy as they can provide adjustable distraction and deformity correction. Rectangular, rather than circular, endcaps provide increased resistance to subsidence by spanning the apophyseal ring; however their impact on construct stability is not known. The objective of this study was to investigate the contribution of expandable corpectomy cage endcap shape (round vs.

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The zona pellucida (ZP) surrounding the oocyte is an extracellular fibrillar matrix that plays critical roles during fertilization including species-specific gamete recognition and protection from polyspermy. The mouse ZP is composed of three proteins, ZP1, ZP2, and ZP3, all of which have a ZP polymerization domain that directs protein fibril formation and assembly into the three-dimensional ZP matrix. Egg coats surrounding oocytes in nonmammalian vertebrates and in invertebrates are also fibrillar matrices and are composed of ZP domain-containing proteins suggesting the basic structure and function of the ZP/egg coat is highly conserved.

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The epididymal lumen is a complex microenvironment in which spermatozoa acquire motility and fertility. Spermatozoa are synthetically inactive and therefore the maturation process requires their interaction with proteins that are synthesized and secreted in a highly regionalized manner by the epididymal epithelium. In addition to the integration of epididymal secretory proteins, posttranslational modifications of existing sperm proteins are important for sperm maturation and acquisition of fertilizing potential.

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Study Design: In vitro cadaveric biomechanical study of lateral interbody cages and supplemental fixation in a degenerative spondylolisthesis (DS) model.

Objective: To investigate changes in shear and flexion-extension stability of lateral interbody fusion constructs.

Summary Of Background Data: Instability associated with DS may increase postoperative treatment complications.

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The acrosomal matrix (AM) is an insoluble structure within the sperm acrosome that serves as a scaffold controlling the release of AM-associated proteins during the sperm acrosome reaction. The AM also interacts with the zona pellucida (ZP) that surrounds the oocyte, suggesting a remarkable stability that allows its survival despite being surrounded by proteolytic and hydrolytic enzymes released during the acrosome reaction. To date, the mechanism responsible for the stability of the AM is not known.

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Hereditary cystatin C amyloid angiopathy is an autosomal dominant disorder in which a variant form of cystatin C (L68Q) readily forms amyloid deposits in cerebral arteries in affected individuals resulting in early death. L68Q protein deposits in human cystatin C amyloid angiopathy patients have also been found in tissues outside of the brain including the testis, suggesting possible effects on fertility. Heterozygous transgenic mice (L68Q) that express the human L68Q variant of cystatin C under the control of the mouse cystatin C promoter were unable to generate offspring, suggesting the presence of L68Q cystatin C amyloid affected sperm function.

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Background Context: Stand-alone interbody cages with integrated screws potentially provide a biomechanically stable solution for anterior lumbar interbody fusion (ALIF) that alleviates the need for additional exposure for supplemental fixation, thereby reducing the chance of additional complications and morbidity.

Purpose: To compare the stability of a stand-alone anterior interbody fusion system with integrated fixation screws against traditional supplemental fixation methods and to evaluate the difference between three and four fixation screws in the stand-alone cage.

Study Design: In vitro cadaveric biomechanical study.

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Cystatin-related epididymal spermatogenic protein (CRES, also CST8) is expressed in both the testis and epididymis and found associated with spermatozoa. It appears as nonglycosylated (14 and 12 kDa) and glycosylated isoforms (19 and 17 kDa). The role of CRES remains enigmatic and is dependent on localization of its isoforms, which is the objective of this study.

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Object: In the surgical treatment of spinal deformities, the importance of restoring lumbar lordosis is well recognized. Smith-Petersen osteotomies (SPOs) yield approximately 10° of lordosis per level, whereas pedicle subtraction osteotomies result in as much as 30° increased lumbar lordosis. Recently, selective release of the anterior longitudinal ligament (ALL) and placement of lordotic interbody grafts using the minimally invasive lateral retroperitoneal transpsoas approach (XLIF) has been performed as an attempt to increase lumbar lordosis while avoiding the morbidity of osteotomy.

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A critical step during fertilization is the sperm acrosome reaction in which the acrosome releases its contents allowing the spermatozoa to penetrate the egg investments. The sperm acrosomal contents are composed of both soluble material and an insoluble material called the acrosomal matrix (AM). The AM is thought to provide a stable structure from which associated proteins are differentially released during fertilization.

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