The receptor guanylyl cyclase Npr2 is essential for sensory axon bifurcation within the spinal cord

Sensory axonal projections into the spinal cord display a highly stereotyped pattern of T- or Y-shaped axon bifurcation at the dorsal root entry zone (DREZ). Here, we provide evidence that embryonic mice with an inactive receptor guanylyl cyclase Npr2 or deficient for cyclic guanosine monophosphate-dependent protein kinase I (cGKI) lack the bifurcation of sensory axons at the DREZ, i.e., the ingrowing axon either turns rostrally or caudally. This bifurcation error is maintained to mature stages. In contrast, interstitial branching of collaterals from primary stem axons remains unaffected, indicating that bifurcation and interstitial branching are processes regulated by a distinct molecular mechanism. At a functional level, the distorted axonal branching at the DREZ is accompanied by reduced synaptic input, as revealed by patch clamp recordings of neurons in the superficial layers of the spinal cord. Hence, our data demonstrate that Npr2 and cGKI are essential constituents of the signaling pathway underlying axonal bifurcation at the DREZ and neuronal connectivity in the dorsal spinal cord

Domain wall QCD with physical quark masses

We present results for several light hadronic quantities ($f_\pi$, $f_K$, $B_K$, $m_{ud}$, $m_s$, $t_0^{1/2}$, $w_0$) obtained from simulations of 2+1 flavor domain wall lattice QCD with large physical volumes and nearly-physical pion masses at two lattice spacings. We perform a short, O(3)%, extrapolation in pion mass to the physical values by combining our new data in a simultaneous chiral/continuum `global fit' with a number of other ensembles with heavier pion masses. We use the physical values of $m_\pi$, $m_K$ and $m_\Omega$ to determine the two quark masses and the scale - all other quantities are outputs from our simulations. We obtain results with sub-percent statistical errors and negligible chiral and finite-volume systematics for these light hadronic quantities, including: $f_\pi$ = 130.2(9) MeV; $f_K$ = 155.5(8) MeV; the average up/down quark mass and strange quark mass in the $\bar {\rm MS}$ scheme at 3 GeV, 2.997(49) and 81.64(1.17) MeV respectively; and the neutral kaon mixing parameter, $B_K$, in the RGI scheme, 0.750(15) and the $\bar{\rm MS}$ scheme at 3 GeV, 0.530(11).Comment: 131 pages, 30 figures. Updated to match published versio

Fermionic R-Operator and Algebraic Structure of 1D Hubbard Model: Its application to quantum transfer matrix

The algebraic structure of the 1D Hubbard model is studied by means of the fermionic R-operator approach. This approach treats the fermion models directly in the framework of the quantum inverse scattering method. Compared with the graded approach, this approach has several advantages. First, the global properties of the Hamiltonian are naturally reflected in the algebraic properties of the fermionic R-operator. We want to note that this operator is a local operator acting on fermion Fock spaces. In particular, SO(4) symmetry and the invariance under the partial particle hole transformation are discussed. Second, we can construct a genuinely fermionic quantum transfer transfer matrix (QTM) in terms of the fermionic R-operator. Using the algebraic Bethe Ansatz for the Hubbard model, we diagonalize the fermionic QTM and discuss its properties.Comment: 22 pages, no figure

Impact of actin filament stabilization on adult hippocampal and olfactory bulb neurogenesis

Rearrangement of the actin cytoskeleton is essential for dynamic cellular processes. Decreased actin turnover and rigidity of cytoskeletal structures have been associated with aging and cell death. Gelsolin is a Ca(2+)-activated actin-severing protein that is widely expressed throughout the adult mammalian brain. Here, we used gelsolin-deficient (Gsn(-/-)) mice as a model system for actin filament stabilization. In Gsn(-/-) mice, emigration of newly generated cells from the subventricular zone into the olfactory bulb was slowed. In vitro, gelsolin deficiency did not affect proliferation or neuronal differentiation of adult neural progenitors cells (NPCs) but resulted in retarded migration. Surprisingly, hippocampal neurogenesis was robustly induced by gelsolin deficiency. The ability of NPCs to intrinsically sense excitatory activity and thereby implement coupling between network activity and neurogenesis has recently been established. Depolarization-induced [Ca(2+)](i) increases and exocytotic neurotransmitter release were enhanced in Gsn(-/-) synaptosomes. Importantly, treatment of Gsn(-/-) synaptosomes with mycotoxin cytochalasin D, which, like gelsolin, produces actin disassembly, decreased enhanced Ca(2+) influx and subsequent exocytotic norepinephrine release to wild-type levels. Similarly, depolarization-induced glutamate release from Gsn(-/-) brain slices was increased. Furthermore, increased hippocampal neurogenesis in Gsn(-/-) mice was associated with a special microenvironment characterized by enhanced density of perfused vessels, increased regional cerebral blood flow, and increased endothelial nitric oxide synthase (NOS-III) expression in hippocampus. Together, reduced filamentous actin turnover in presynaptic terminals causes increased Ca(2+) influx and, subsequently, elevated exocytotic neurotransmitter release acting on neural progenitors. Increased neurogenesis in Gsn(-/-) hippocampus is associated with a special vascular niche for neurogenesis

Early diagnosis is associated with improved clinical outcomes in benign esophageal perforation: an individual patient data meta‑analysis

Background Time of diagnosis (TOD) of benign esophageal perforation is regarded as an important risk factor for clinical outcome, although convincing evidence is lacking. The aim of this study is to assess whether time between onset of perforation and diagnosis is associated with clinical outcome in patients with iatrogenic esophageal perforation (IEP) and Boerhaave’s syndrome (BS). Methods We searched MEDLINE, Embase and Cochrane library through June 2018 to identify studies. Authors were invited to share individual patient data and a meta-analysis was performed (PROSPERO: CRD42018093473). Patients were subdivided in early (≤ 24 h) and late (> 24 h) TOD and compared with mixed effects multivariable analysis while adjusting age, gender, location of perforation, initial treatment and center. Primary outcome was overall mortality. Secondary outcomes were length of hospital stay, re-interventions and ICU admission. Results Our meta-analysis included IPD of 25 studies including 576 patients with IEP and 384 with BS. In IEP, early TOD was not associated with overall mortality (8% vs. 13%, OR 2.1, 95% CI 0.8–5.1), but was associated with a 23% decrease in ICU admissions (46% vs. 69%, OR 3.0, 95% CI 1.2–7.2), a 22% decrease in re-interventions (23% vs. 45%, OR 2.8, 95% CI 1.2–6.7) and a 36% decrease in length of hospital stay (14 vs. 22 days, p < 0.001), compared with late TOD. In BS, no associations between TOD and outcomes were found. When combining IEP and BS, early TOD was associated with a 6% decrease in overall mortality (10% vs. 16%, OR 2.1, 95% CI 1.1–3.9), a 19% decrease in re-interventions (26% vs. 45%, OR 1.9, 95% CI 1.1–3.2) and a 35% decrease in mean length of hospital stay (16 vs. 22 days, p = 0.001), compared with late TOD. Conclusions This individual patient data meta-analysis confirms the general opinion that an early (≤ 24 h) compared to a late diagnosis (> 24 h) in benign esophageal perforations, particularly in IEP, is associated with improved clinical outcome.publishedVersio

Stage-based treatment for thymoma in due consideration of thymectomy: a single-center experience and comparison with the literature

BACKGROUND: Thymomas represent an uncommon and heterogeneous group of intrathoracic malignancies which require different treatments corresponding to their individual tumor stage. The objective of this study was to review the efficacy of our applied stage-based treatment for thymoma in due consideration of thymectomy. METHODS: This is a single-center, institutional review board-approved retrospective study of 50 consecutive patients with thymoma treated at our division within 10 years. RESULTS: There were 29 women (58 %) and 21 men (42 %), mean age 58.3 years. Twenty nine (58 %) had clinical symptoms and 14 (28 %) had myasthenia gravis. Forty-five patients (90 %) underwent thymectomy and complete resection was done in 42 cases (93.3 %). Histologic results were 6 subtype A, 5 AB, 8 B1, 12 B2, 12 B3, and 7 C. The Masaoka staging system revealed 20 stage I, 18 stage II, 6 stage III, and 6 stage IV. Two patients had neoadjuvant therapy and 25 received postoperative treatment. Five (11.1 %) had tumor recurrence, treated with re-resection. The 5-year disease-free survival was 91.5 %. Two patients died of tumor progression and three died of other causes (10 %). The 5-year overall survival was 82.3 % and the median survival time was 92.1 months. The 5-year survival rate after thymectomy was 87.2 % and the median survival was 92.1 months. CONCLUSIONS: Complete resection still remains the mainstay in the treatment of non-metastatic thymoma and should be performed whenever feasible. Close multidisciplinary teamwork is mandatory to optimize the neurologic outcome and to prolong postoperative survival

Tenacidad a la fractura de compuestos cermets 3Al2O3*2SiO2/Ag manufacturados por molienda de alta energía

La fabricación de materiales compuestos de matriz cerámica reforzados con partículas metálicas han propiciado la formación de nuevos materiales conocidos como compuestos CERMETS, materiales que debido a sus elementos precursores poseen propiedades distintas a las de los materiales convencionales. En este trabajo se establece la ruta de fabricación de materiales compuestos cermets base 3Al2O3*2SiO2 reforzados con partículas metálicas de Ag a partir de la formación de la composición química en peso de polvos de 3Al2O3*2SiO2 / 1% Ag en busca de un aumento en la tenacidad a la fractura con respecto al cerámico base. La composición química de polvos es sometida a un proceso de mezcla molienda de alta energía en seco en un molino tipo planetario por 2 horas a 200 rpm. Los polvos posteriormente son conformados en muestras cilíndricas de 20 mm de diámetro y 3 mm de espesor mediante la aplicación de carga uniaxial en frío de 200 MPa. Las muestras son sinterizadas a 1500°C y 1600°C por una y dos horas en un horno de resistencia eléctrica en atmósfera controlada de gas nitrógeno. Los compuestos fabricados son analizados microestructuralmente por microscopia óptica y electrónica de barrido. Se determina la densidad y las propiedades mecánicas de dureza y tenacidad a la fractura, las dos últimas por el método de indentación. Los resultados muestran la viabilidad de fabricación de materiales compuestos cermets así como los cambios en la densidad, la dureza y la tenacidad a la fractura, con respecto al cerámico 3Al2O3*2SiO2 sin refuerzo metálico