Summary
Animals exhibit innate and learned preferences for temperature and humidity—conditions critical for their survival and reproduction. Leveraging a whole-brain electron microscopy volume
,
we studied the adult
Drosophila melanogaster
circuitry associated with antennal thermo- and hygrosensory neurons. We have identified two new target glomeruli in the antennal lobe, in addition to the five known ones, and the ventroposterior projection neurons (VP PNs) that relay thermo- and hygrosensory information to higher brain centers, including the mushroom body and lateral horn, seats of learned and innate behavior. We present the first connectome of a thermo- and hygrosensory neuropil, the lateral accessory calyx (lACA), by reconstructing neurons downstream of heating- and cooling-responsive VP PNs. A few mushroom body-intrinsic neurons solely receive thermosensory input from the lACA, while most receive additional olfactory and thermo- and/or hygrosensory PN inputs. Furthermore, several classes of lACA-associated neurons form a local network with outputs to other brain neuropils, suggesting that the lACA serves as a hub for thermo- and hygrosensory circuitry. For example, DN1a neurons link thermosensory PNs in the lACA to the circadian clock via the accessory medulla. Finally, we survey strongly connected downstream partners of VP PNs across the protocerebrum; these include a descending neuron targeted by dry-responsive VP PNs, meaning that just two synapses might separate hygrosensory inputs from motor circuits. These data provide a comprehensive first- and second-order layer analysis of
Drosophila
thermo- and hygrosensory systems and an initial survey of third-order neurons that could directly modulate behavior.
One hundred thirty patients with an observed follow-up of more than 10 years after radical prostatectomy were restaged with regard to local extent of the tumor in relation to the prostate capsule. Of 112 patients with surgically staged negative pelvic lymph nodes, 62 had a tumor-free prostate capsule, 24 had capsular invasion without penetration, and 26 had tumors extending through the capsule of the prostate. Observed overall and disease-free 10-year-survival rates were 79% and 69.4%, respectively, in patients with absence of capsular involvement and 70.8% and 66.7%, respectively, in patients with capsular invasion alone. In patients with capsular penetration, however, the survival rates significantly decreased to 57.7% (P = 0.018) and to 38.5 (P = 0.017), respectively. The overall progression rate was found to be significantly higher in patients with tumors extending through the prostatic capsule (46.2%), as compared to those with absence of capsular involvement (21%; P = 0.014) as well as to those with capsular invasion alone without penetration (25%; P = 0.034). Thus, in contrast to capsular invasion alone, capsular penetration means a poor prognostic indicator, which accounts for a reduced survival expectancy and a higher progression rate following radical prostatectomy. Therefore, tumors with capsular invasion and those with capsular penetration should not be grouped together in the same tumor stage as done in the 1987 edition of the TNM tumor classification system.
Triple drug immunochemotherapy resulted in a significant clinical effect comparable to an aggressive intravenous interleukin-2 treatment regimen but without significant toxicity.
Triple drug immunochemotherapy resulted in a significant clinical effect comparable to an aggressive intravenous interleukin-2 treatment regimen but without significant toxicity.
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