Transcriptional reprogramming post-peripheral nerve injury: A systematic review.

Neuropathic pain is characterised by periodic or continuous hyperalgesia, numbness, or allodynia, and results from insults to the somatosensory nervous system. Peripheral nerve injury induces transcriptional reprogramming in peripheral sensory neurons, contributing to increased spinal nociceptive input and the development of neuropathic pain. Effective treatment for neuropathic pain remains an unmet medical need as current therapeutics offer limited effectiveness and have undesirable effects. Understanding transcriptional changes in peripheral nerve injury-induced neuropathy might offer a path for novel analgesics. Our literature search identified 65 papers exploring transcriptomic changes post-peripheral nerve injury, many of which were conducted in animal models. We scrutinize their transcriptional changes data and conduct gene ontology enrichment analysis to reveal their common functional profile. Focusing on genes involved in 'sensory perception of pain' (GO:0019233), we identified transcriptional changes for different ion channels, receptors, and neurotransmitters, shedding light on its role in nociception. Examining peripheral sensory neurons subtype-specific transcriptional reprograming and regeneration-associated genes, we delved into downstream regulation of hypersensitivity. Identifying the temporal program of transcription regulatory mechanisms might help develop better therapeutics to target them effectively and selectively, thus preventing the development of neuropathic pain without affecting other physiological functions.

Two-layer elastic models for single-yeast compressibility with flat microlevers.

Unicellular organisms such as yeast can survive in very different environments, thanks to a polysaccharide wall that reinforces their extracellular membrane. This wall is not a static structure, as it is expected to be dynamically remodeled according to growth stage, division cycle, environmental osmotic pressure and ageing. It is therefore of great interest to study the mechanics of these organisms, but they are more difficult to study than other mammalian cells, in particular because of their small size (radius of a few microns) and their lack of an adhesion machinery. Using flat cantilevers, we perform compression experiments on single yeast cells (S. cerevisiae) on poly-L-lysine-coated grooved glass plates, in the limit of small deformation using an atomic force microscope (AFM). Thanks to a careful decomposition of force-displacement curves, we extract local scaling exponents that highlight the non-stationary characteristic of the yeast behavior upon compression. Our multi-scale nonlinear analysis of the AFM force-displacement curves provides evidence for non-stationary scaling laws. We propose to model these phenomena based on a two-component elastic system, where each layer follows a different scaling law..

Inhibition of the membrane repair protein annexin-A2 prevents tumor invasion and metastasis.

Cancer cells are exposed to major compressive and shearing forces during invasion and metastasis, leading to extensive plasma membrane damage. To survive this mechanical stress, they need to repair membrane injury efficiently. Targeting the membrane repair machinery is thus potentially a new way to prevent invasion and metastasis. We show here that annexin-A2 (ANXA2) is required for membrane repair in invasive breast and pancreatic cancer cells. Mechanistically, we show by fluorescence and electron microscopy that cells fail to reseal shear-stress damaged membrane when ANXA2 is silenced or the protein is inhibited with neutralizing antibody. Silencing of ANXA2 has no effect on proliferation in vitro, and may even accelerate migration in wound healing assays, but reduces tumor cell dissemination in both mice and zebrafish. We expect that inhibiting membrane repair will be particularly effective in aggressive, poor prognosis tumors because they rely on the membrane repair machinery to survive membrane damage during tumor invasion and metastasis. This could be achieved either with anti-ANXA2 antibodies, which have been shown to inhibit metastasis of breast and pancreatic cancer cells, or with small molecule drugs.

Thirty-seven-year Population-based Study of Colorectal Cancer Rates in Renal Transplant Recipients in Ireland.

BACKGROUND: Renal transplantation is associated with an increased risk of neoplasia, including colorectal cancer (CRC). Advances in surgical techniques and immunosuppressive medications have resulted in increased survival rates of both patients and grafts, but the incidence of CRC in the Irish renal transplant population is currently unknown. The aim of this study is to review the incidence of CRC in the Irish renal transplant population and compare it to the general population. METHODS: A retrospective review of a prospectively maintained database of all renal transplant recipients in Ireland between January 1980 and July 2017 was performed. RESULTS: Thirty-three out of 4230 transplant recipients (men = 20, women = 13) developed CRC subsequent to transplantation and were eligible for inclusion in the series. The mean age at transplantation was 51.5 years, with patients developing CRC on average 10.9 years post-transplantation; 6.1% (n = 2/33) had stage IV disease at diagnosis. The majority of patients (87.8%) had a pathologic T stage of T3/T4 and 45.5% had involvement of locoregional lymph nodes (N1/N2); 42.4% also had a mucinous component at histopathologic assessment. The incidence of CRC was higher in the transplant population compared to the general population. CONCLUSION: This is the first population-based assessment of CRC development in the Irish renal transplant population. Our data suggest that Irish transplant recipients have an increased risk of being diagnosed with a more advanced tumor than the general population, with most being diagnosed almost a decade after transplantation. This highlights the need for increased awareness among patients and clinicians and the potential need for coordinated lifelong surveillance of this patient population to ensure early detection and treatment.

Probing the kinetics of lipid membrane formation and the interaction of a nontoxic and a toxic amyloid with plasmon waveguide resonance.

The kinetics of formation of solid-supported lipid model membranes were investigated using a home-made plasmon waveguide resonance (PWR) sensor possessing enhanced properties relative to classic surface plasmon resonance sensors. Additionally, the kinetics of interaction of two amyloid peptides with zwitterionic and anionic membranes and their effect on lipid organization were followed.

Controlled-release panel traps for the Mediterranean fruit fly (Diptera: Tephritidae).

Solid, controlled-release dispensers containing 2 g of the synthetic attractant trimedlure now are used in Jackson traps to detect the Mediterranean fruit fly, Ceratitis capitata (Wiedemann). Panel traps consisting of trimedlure mixed in a sticky substance and spread on the surfaces of a plastic panel are used to delineate the limits of discovered insect infestations in California. We describe the development of controlled-release, polymeric panels that prolong release of trimedlure and a highly attractive analog, ceralure. Attractants were incorporated in a polyethylene matrix to form panels and in a polymer coating on cardboard panels that then were evaluated by biological and chemical assay. In addition, commercial polymer matrix panels were evaluated. Field bioassay tests conducted in Hilo, HI, using released flies and in Guatemala in a natural population showed that the polyethylene matrix panel became brittle and cracked during field exposure and that release rates of the attractants were relatively low. The coated cardboard panels were stable under field conditions and yielded high fly captures for up to 6 wk. Farma Tech commercial panels containing 12.3 and 23.4 g of trimedlure remained highly attractive throughout a 134-d test in Hawaii and appear to be a long-lasting alternative to panels coated with trimedlure in Stikem. The cost of the relatively high dose of trimedlure is offset by the prolonged active life of the panel. Commercial panels from AgriSense (10 g trimedlure and 10 g ceralure) released the attractants at a slower rate and were less attractive.

Stress incontinence in women. A practical method of evaluation.

Stress incontinence in women may have many etiologies, of which the two primary ones are detrusor overactivity (urge incontinence), which is treated medically, and anatomic (pure) stress incontinence, which is treated surgically. At the Ben Taub Gynecologic Urology Clinic, Baylor College of Medicine, 307 women were studied. Evaluations included history and physical examination, Q-tip test, catheterization for culture and residual volume, and CO2 gas urethroscopy with single-channel cystometrics. Twenty-nine percent of the patients were found to have pure anatomic stress incontinence, 33% to have urge incontinence and 38% to have combined urge and anatomic stress incontinence; 57% had irritative symptoms regardless of the etiologies. Cystocele was present in 92% of stress, 49% of urge and 83% of combined cases. Patients with anatomic stress incontinence tended to have larger cystoceles and greater Q-tip angles; however, a significant percentage of patients with urge incontinence also had cystoceles and abnormal Q-tip angles. Treatment must therefore be individualized on the basis of anatomic and physiologic findings. Of the patients, 40% were treated surgically, and 69% received some form of medical treatment, including antispasmodics, estrogen, Kegel's exercises, urethral dilatation and bladder drills; 9% were given a trial of medical therapy followed by surgical therapy. This practical approach to evaluating women with stress incontinence is easily used in the practitioner's office.