Optical coherence tomography angiography (OCTA) is a noninvasive method of 3D imaging of the retinal and choroidal circulations. However, vascular depth discrimination is limited by superficial ...vessels projecting flow signal artifact onto deeper layers. The projection-resolved (PR) OCTA algorithm improves depth resolution by removing projection artifact while retaining in-situ flow signal from real blood vessels in deeper layers. This novel technology allowed us to study the normal retinal vasculature in vivo with better depth resolution than previously possible. Our investigation in normal human volunteers revealed the presence of 2 to 4 distinct vascular plexuses in the retina, depending on location relative to the optic disc and fovea. The vascular pattern in these retinal plexuses and interconnecting layers are consistent with previous histologic studies. Based on these data, we propose an improved system of nomenclature and segmentation boundaries for detailed 3-dimensional retinal vascular anatomy by OCTA. This could serve as a basis for future investigation of both normal retinal anatomy, as well as vascular malformations, nonperfusion, and neovascularization.
Variations of fresh meat quality exist because the quality traits are affected by various intrinsic and extrinsic factors. Because the meat quality is basically dependent on muscle fiber ...characteristics, numerous studies have reported the relationship between quality traits and fiber characteristics. Despite intensive research, the relationship is yet to be fully established, however, the present knowledge suggests several potential ways to manipulate muscle fiber characteristics to improve meat quality. The present paper reviews the definition of fresh meat quality, meat quality traits and variations of meat quality. Also, this review presents recent knowledge underlying the relationship between fresh meat quality traits and muscle fiber characteristics. Finally, the present work proposes several potential factors including breed, genotype, sex, hormone, growth performance, diet, muscle location, exercise and ambient temperature that can be used to manipulate muscle fiber characteristics and subsequently meat quality in animals.
•Fresh meat qualities are affected by various intrinsic and extrinsic factors.•The meat quality is basically dependent on muscle fiber characteristics.•The meat quality can be improved by manipulation of muscle fiber characteristics.•Muscle fiber characteristics can be controlled by various potential factors.
Mammals detect temperature with specialized neurons in the peripheral nervous system. Four TRPV-class channels have been implicated in sensing heat, and one TRPM-class channel in sensing cold. The ...combined range of temperatures that activate these channels covers a majority of the relevant physiological spectrum sensed by most mammals, with a significant gap in the noxious cold range. Here, we describe the characterization of ANKTM1, a cold-activated channel with a lower activation temperature compared to the cold and menthol receptor, TRPM8. ANKTM1 is a distant family member of TRP channels with very little amino acid similarity to TRPM8. It is found in a subset of nociceptive sensory neurons where it is coexpressed with TRPV1/VR1 (the capsaicin/heat receptor) but not TRPM8. Consistent with the expression of ANKTM1, we identify noxious cold-sensitive sensory neurons that also respond to capsaicin but not to menthol.
Adjuvant chemotherapy and chemoradiotherapy are some of the standards of care for gastric cancer (GC). The Adjuvant chemoRadioTherapy In Stomach Tumors (ARTIST) 2 trial compares two adjuvant ...chemotherapy regimens and chemoradiotherapy in patients with D2-resected, stage II or III, node-positive GC.
The ARTIST 2 compared, in a 1:1:1 ratio, three adjuvant regimens: oral S-1 (40-60 mg twice daily 4 weeks on/2 weeks off) for 1 year, S-1 (2 weeks on/1 week off) plus oxaliplatin 130 mg/m2 every 3 weeks (SOX) for 6 months, and SOX plus chemoradiotherapy 45 Gy (SOXRT). Randomization was stratified according to surgery type (total or subtotal gastrectomy), pathologic stage (II or III), and Lauren histologic classification (diffuse or intestinal/mixed). The primary endpoint was disease-free survival (DFS) at 3 years; a reduction of 33% in the hazard ratio (HR) for DFS with SOX or SOXRT, when compared with S-1, was considered clinically meaningful. The trial is registered at clinicaltrials.gov (NCT0176146).
A total of 546 patients were recruited between February 2013 and January 2018 with 182, 181, and 183 patients in the S-1, SOX, and SOXRT arms, respectively. Median follow-up period was 47 months, with 178 DFS events observed. Estimated 3-year DFS rates were 64.8%, 74.3%, and 72.8% in the S-1, SOX, and SOXRT arms, respectively. HR for DFS in the control arm (S-1) was shorter than that in the SOX and SOXRT arms: S-1 versus SOX, 0.692 (P = 0.042) and S-1 versus SOXRT, 0.724 (P = 0.074). No difference in DFS was found between SOX and SOXRT (HR 0.971; P = 0.879). Adverse events were as anticipated in each arm, and were generally well-tolerated and manageable.
In patients with curatively D2-resected, stage II/III, node-positive GC, adjuvant SOX or SOXRT was effective in prolonging DFS, when compared with S-1 monotherapy. The addition of radiotherapy to SOX did not significantly reduce the rate of recurrence after D2 gastrectomy.
•In patients with curatively D2-resected, stage II/III, node-positive GC, adjuvant SOX or SOXRT was effective in prolonging DFS, when compared with S-1 monotherapy.•The addition of radiotherapy to chemotherapy did not significantly reduce the rate of recurrence after D2 gastrectomy.•DFS between patients treated with adjuvant chemotherapy and chemoradiotherapy was similar across all subgroups, including Lauren classification.
To assess telomerase as a cancer therapeutic target and determine adaptive mechanisms to telomerase inhibition, we modeled telomerase reactivation and subsequent extinction in T cell lymphomas ...arising in Atm−/− mice engineered with an inducible telomerase reverse transcriptase allele. Telomerase reactivation in the setting of telomere dysfunction enabled full malignant progression with alleviation of telomere dysfunction-induced checkpoints. These cancers possessed copy number alterations targeting key loci in human T cell lymphomagenesis. Upon telomerase extinction, tumor growth eventually slowed with reinstatement of telomere dysfunction-induced checkpoints, yet growth subsequently resumed as tumors acquired alternative lengthening of telomeres (ALT) and aberrant transcriptional networks centering on mitochondrial biology and oxidative defense. ALT+ tumors acquired amplification/overexpression of PGC-1β, a master regulator of mitochondrial biogenesis and function, and they showed marked sensitivity to PGC-1β or SOD2 knockdown. Genetic modeling of telomerase extinction reveals vulnerabilities that motivate coincidental inhibition of mitochondrial maintenance and oxidative defense mechanisms to enhance antitelomerase cancer therapy.
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► Telomerase reactivation following genomic instability promotes invasiveness ► Telomerase inhibition leads to cell death and eventual ALT-dependent resistance ► ALT+ cells upregulate PGC axis to rescue mitochondrial dysfunction and reactive oxygen species (ROS) ► Mitochondria/ROS fitness can be targeted to enhance antitelomerase therapy
Decreasing telomerase activity initially slows tumor growth in a mouse model of lymphoma, but eventually growth resumes as resistant cells emerge. These cells display aberrant mitochondrial function and are sensitive to PGC-1β inhibition, offering a new target for enhancing the effectiveness of antitelomerase therapy.
A membrane contactor is a device that achieves gas/liquid or liquid/liquid mass transfer without dispersion of one phase within another. This is accomplished by passing the fluids on opposite sides ...of a microporous membrane. By careful control of the pressure difference between the fluids, one of the fluids is immobilized in the pores of the membrane so that the fluid/fluid interface is located at the mouth of each pore. This approach offers a number of important advantages over conventional dispersed phase contactors, including absence of emulsions, no flooding at high flow rates, no unloading at low flow rates, no density difference between fluids required, and surprisingly high interfacial area. Indeed, membrane contactors typically offer 30 times more area than what is achievable in gas absorbers and 500 times what is obtainable in liquid/liquid extraction columns, leading to remarkably low
HTU values.
Although a number of membrane module geometries are possible, hollow fiber modules have received the most attention. In general, tube side mass transfer coefficients can be predicted with reasonable accuracy; on the other hand, shell side coefficients are more difficult to determine, and several research groups are currently addressing this problem.
Membrane contactor technology has been demonstrated in a range of liquid/liquid and gas/liquid applications in fermentation, pharmaceuticals, wastewater treatment, chiral separations, semiconductor manufacturing, carbonation of beverages, metal ion extraction, protein extraction, VOC removal from waste gas, and osmotic distillation. This paper provides a general review of hollow fiber membrane contactors, including operating principles, relevant mathematics, and applications.
Psoriasis is a chronic inflammatory skin disease characterized by the infiltration of T cell and other immune cells to the skin in response to injury or autoantigens. Conventional, as well as ...unconventional, γδ T cells are recruited to the dermis and epidermis by CCL20 and other chemokines. Together with its receptor CCR6, CCL20 plays a critical role in the development of psoriasiform dermatitis in mouse models. We screened a panel of CCL20 variants designed to form dimers stabilized by intermolecular disulfide bonds. A single-atom substitution yielded a CCL20 variant (CCL20 S64C) that acted as a partial agonist for the chemokine receptor CCR6. CCL20 S64C bound CCR6 and induced intracellular calcium release, consistent with G-protein activation, but exhibited minimal chemotactic activity. Instead, CCL20 S64C inhibited CCR6-mediated T cell migration with nominal impact on other chemokine receptor signaling. When given in an IL-23–dependent mouse model for psoriasis, CCL20 S64C prevented psoriatic inflammation and the up-regulation of IL-17A and IL-22. Our results validate CCR6 as a tractable therapeutic target for psoriasis and demonstrate the value of CCL20 S64C as a lead compound.
We present the analysis of OGLE-2016-BLG-0613, for which the lensing light curve appears to be that of a typical binary-lens event with two caustic spikes but with a discontinuous feature on the ...trough between the spikes. We find that the discontinuous feature was produced by a planetary companion to the binary lens. We find four degenerate triple-lens solution classes, each composed of a pair of solutions according to the well-known wide/close planetary degeneracy. One of these solution classes is excluded due to its relatively poor fit. For the remaining three pairs of solutions, the most-likely primary mass is about , while the planet is a super Jupiter. In all cases, the system lies in the Galactic disk, about halfway toward the Galactic bulge. However, in one of these three solution classes, the secondary of the binary system is a low-mass brown dwarf, with relative mass ratios (1:0.03:0.003), while in the two others the masses of the binary components are comparable. These two possibilities can be distinguished in about 2024 when the measured lens-source relative proper motion will permit separate resolution of the lens and source.
Background: CC chemokine receptor-7 (CCR7), which plays a critical role in the migration of activated dendritic cells to regional lymph nodes via afferent lymphatic vessels, is also expressed by ...human breast and melanoma cell lines. Because neoplastic cells also enter lymphatic vessels before metastasis to the lymph nodes, we investigated whether CCR7 expression enhances metastasis of B16 murine melanoma cells to regional lymph nodes. Methods: B16 cells were transduced with a retroviral vector containing CCR7 complementary DNA (CCR7-B16 cells) or with vector alone (pLNCX2-B16 control cells). The functional assay for CCR7 protein was Ca2+ flux stimulated by the chemokine CCL21, a CCR7-specific ligand produced by lymphatic endothelial cells. B16 tumor cells were injected into the footpad of mice. Tumor cell metastasis to draining lymph nodes was assessed by measuring messenger RNA (mRNA) for tyrosinase-related protein-1 (TRP), a melanocyte-specific enzyme, with real-time, quantitative reverse transcription–coupled polymerase chain reaction. All statistical tests were two-sided. Results: One week after injection into the footpad, 701-fold (95% confidence interval CI = 64- to 1336-fold) more TRP mRNA was detected in draining lymph nodes from CCR7-B16 cell-injected mice than in those from control cell-injected mice. Three weeks after footpad injection, 58% (11 of 19) of the draining lymph nodes from CCR7-B16 cell-injected mice and 5% (one of 19) of those from control mice showed gross metastases (P<.001). CCR7-B16 cells isolated from lymph node metastases retained functional CCR7 expression. Lymph node metastasis of CCR7-B16 cells was blocked by neutralizing anti-CCL21 antibodies (metastasis in none of five lymph nodes) but not by control immunoglobulin G (three of five). Enhanced metastasis of CCR7-B16 cells was specific for a lymphatic route because both CCR7-B16 and control cells co-injected intravenously metastasized to the lung at the same frequency. Conclusion: Expression of a single chemokine receptor gene, CCR7, increased B16 cell metastasis to draining lymph nodes, suggesting that cancer cells may co-opt normal mechanisms of lymph node homing during metastasis.
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