Functional imaging of visual cortical layers and subplate in awake mice with optimized three-photon microscopy

Two-photon microscopy is used to image neuronal activity, but has severe limitations for studying deeper cortical layers. Here, we developed a custom three-photon microscope optimized to image a vertical column of the cerebral cortex > 1 mm in depth in awake mice with low (<20 mW) average laser power. Our measurements of physiological responses and tissue-damage thresholds define pulse parameters and safety limits for damage-free three-photon imaging. We image functional visual responses of neurons expressing GCaMP6s across all layers of the primary visual cortex (V1) and in the subplate. These recordings reveal diverse visual selectivity in deep layers: layer 5 neurons are more broadly tuned to visual stimuli, whereas mean orientation selectivity of layer 6 neurons is slightly sharper, compared to neurons in other layers. Subplate neurons, located in the white matter below cortical layer 6 and characterized here for the first time, show low visual responsivity and broad orientation selectivity.National Institutes of Health (U.S.) (grant EY007023)National Institutes of Health (U.S.) (grant NS090473)National Institutes of Health (U.S.) (grant 4-P41-EB015871)National Science Foundation (U.S.) (grant EF1451125)Picower Institute for Learning and Memory (Engineering Collaboration Grant)Massachusetts Life Sciences Initiativ

Comparison of SPECT bone scintigraphy with MRI for diagnosis of meniscal tears

BACKGROUND: Scintigraphy has been considered as competitive to MRI, but limited data are available on the accuracy of single photon emission tomography (SPECT) compared with MRI for the assessment of meniscal tears. Our objective was to assess the value of SPECT in comparison to MRI. METHODS: Between January 2003 and March 2004, sixteen patients were studied with both modalities and the accuracy rates of SPECT scan results, and MRI findings in the diagnosis of meniscal tears were compared. Arthroscopy was the gold standard. RESULTS: The respective sensitivity rate, specificity rate, and positive and negative predictive accuracies of MRI were 89%, 94%, 93%, and 79% and for SPECT those were 78%, 94%, 94%, and 88%. There was good agreement on the presence or absence of tears between two modalities (κ statistic = 0.699). CONCLUSION: SPECT and MRI are both valuable imaging techniques. SPECT is a useful alternative when MRI is unavailable or unsuitable and it is beneficial when more possible accuracy is desired (such as when MRI results are either inconclusive or conflict with other clinical data)

Structure of Protein Interaction Networks and Their Implications on Drug Design

Protein-protein interaction networks (PINs) are rich sources of information that enable the network properties of biological systems to be understood. A study of the topological and statistical properties of budding yeast and human PINs revealed that they are scale-rich and configured as highly optimized tolerance (HOT) networks that are similar to the router-level topology of the Internet. This is different from claims that such networks are scale-free and configured through simple preferential-attachment processes. Further analysis revealed that there are extensive interconnections among middle-degree nodes that form the backbone of the networks. Degree distributions of essential genes, synthetic lethal genes, synthetic sick genes, and human drug-target genes indicate that there are advantageous drug targets among nodes with middle- to low-degree nodes. Such network properties provide the rationale for combinatorial drugs that target less prominent nodes to increase synergetic efficacy and create fewer side effects

Ultrafast transient generation of spin-densitywave order in the normal state of BaFe2As2 driven by coherent lattice vibrations

The interplay among charge, spin and lattice degrees of freedom in solids gives rise to intriguing macroscopic quantum phenomena such as colossal magnetoresistance, multiferroicity and high-temperature superconductivity. Strong coupling or competition between various orders in these systems presents the key to manipulate their functional properties by means of external perturbations such as electric and magnetic fields or pressure. Ultrashort and intense optical pulses have emerged as an interesting tool to investigate elementary dynamics and control material properties by melting an existing order. Here, we employ few-cycle multi-terahertz pulses to resonantly probe the evolution of the spin-density-wave (SDW) gap of the pnictide compound BaFe2As2 following excitation with a femtosecond optical pulse. When starting in the low-temperature ground state, optical excitation results in a melting of the SDW order, followed by ultrafast recovery. In contrast, the SDW gap is induced when we excite the normal state above the transition temperature. Very surprisingly, the transient ordering quasi-adiabatically follows a coherent lattice oscillation at a frequency as high as 5.5 THz. Our results attest to a pronounced spin-phonon coupling in pnictides that supports rapid development of a macroscopic order on small vibrational displacement even without breaking the symmetry of the crystal

Inhibition or knock out of Inducible nitric oxide synthase result in resistance to bleomycin-induced lung injury

BACKGROUND: In the present study, by comparing the responses in wild-type mice (WT) and mice lacking (KO) the inducible (or type 2) nitric oxide synthase (iNOS), we investigated the role played by iNOS in the development of on the lung injury caused by bleomycin administration. When compared to bleomycin-treated iNOSWT mice, iNOSKO mice, which had received bleomycin, exhibited a reduced degree of the (i) lost of body weight, (ii) mortality rate, (iii) infiltration of the lung with polymorphonuclear neutrophils (MPO activity), (iv) edema formation, (v) histological evidence of lung injury, (vi) lung collagen deposition and (vii) lung Transforming Growth Factor beta1 (TGF-β1) expression. METHODS: Mice subjected to intratracheal administration of bleomycin developed a significant lung injury. Immunohistochemical analysis for nitrotyrosine revealed a positive staining in lungs from bleomycin-treated iNOSWT mice. RESULTS: The intensity and degree of nitrotyrosine staining was markedly reduced in tissue section from bleomycin-iNOSKO mice. Treatment of iNOSWT mice with of GW274150, a novel, potent and selective inhibitor of iNOS activity (5 mg/kg i.p.) also significantly attenuated all of the above indicators of lung damage and inflammation. CONCLUSION: Taken together, our results clearly demonstrate that iNOS plays an important role in the lung injury induced by bleomycin in the mice

Postoperative outcomes in oesophagectomy with trainee involvement

BACKGROUND: The complexity of oesophageal surgery and the significant risk of morbidity necessitates that oesophagectomy is predominantly performed by a consultant surgeon, or a senior trainee under their supervision. The aim of this study was to determine the impact of trainee involvement in oesophagectomy on postoperative outcomes in an international multicentre setting. METHODS: Data from the multicentre Oesophago-Gastric Anastomosis Study Group (OGAA) cohort study were analysed, which comprised prospectively collected data from patients undergoing oesophagectomy for oesophageal cancer between April 2018 and December 2018. Procedures were grouped by the level of trainee involvement, and univariable and multivariable analyses were performed to compare patient outcomes across groups. RESULTS: Of 2232 oesophagectomies from 137 centres in 41 countries, trainees were involved in 29.1 per cent of them (n = 650), performing only the abdominal phase in 230, only the chest and/or neck phases in 130, and all phases in 315 procedures. For procedures with a chest anastomosis, those with trainee involvement had similar 90-day mortality, complication and reoperation rates to consultant-performed oesophagectomies (P = 0.451, P = 0.318, and P = 0.382, respectively), while anastomotic leak rates were significantly lower in the trainee groups (P = 0.030). Procedures with a neck anastomosis had equivalent complication, anastomotic leak, and reoperation rates (P = 0.150, P = 0.430, and P = 0.632, respectively) in trainee-involved versus consultant-performed oesophagectomies, with significantly lower 90-day mortality in the trainee groups (P = 0.005). CONCLUSION: Trainee involvement was not found to be associated with significantly inferior postoperative outcomes for selected patients undergoing oesophagectomy. The results support continued supervised trainee involvement in oesophageal cancer surgery

Measurements of photo-nuclear jet production in Pb plus Pb collisions with ATLAS

Ultra-peripheral heavy ion collisions provide a unique opportunity to study the parton distributions in the colliding nuclei via the measurement of photo-nuclear jet production. An analysis of jet production in ultra-peripheral Pb+Pb collisions at √sNN = 5.02 TeV performed using data collected with the ATLAS detector in 2015 is described. The data set corresponds to a total Pb+Pb integrated luminosity of 0.38 nb−1. The ultra-peripheral collisions are selected using a combination of forward neutron and rapidity gap requirements. The cross-sections, not unfolded for detector response, are compared to results from Pythia Monte Carlo simulations re-weighted to match a photon spectrum obtained from the STARlight model. Qualitative agreement between data and these simulations is observed over a broad kinematic range suggesting that using these collisions to measure nuclear parton distributions is experimentally realisable