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Insects are well known for their ability to keep track of their heading direction based on a combination of skylight cues and visual landmarks. This allows them to navigate back to their nest, disperse throughout unfamiliar environments, as well as migrate over large distances between their breeding and non-breeding habitats. The monarch butterfly (Danaus plexippus), for instance, is known for its annual southward migration from North America to certain trees in Central Mexico. To maintain a constant flight route, these butterflies use a time-compensated sun compass, which is processed in a region in the brain, termed the central complex. However, to successfully complete their journey, the butterflies' brain must generate a multitude of orientation strategies, allowing them to dynamically switch from sun-compass orientation to a tactic behavior toward a certain target. To study whether monarch butterflies exhibit different orientation modes and if they can switch between them, we observed the orientation behavior of tethered flying butterflies in a flight simulator while presenting different visual cues to them. We found that the butterflies' behavior depended on the presented visual stimulus. Thus, while a dark stripe was used for flight stabilization, a bright stripe was fixated by the butterflies in their frontal visual field. If we replaced a bright stripe with a simulated sun stimulus, the butterflies switched their behavior and exhibited compass orientation. Taken together, our data show that monarch butterflies rely on and switch between different orientation modes, allowing the animal to adjust orientation to its actual behavioral demands., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2022. Published by The Company of Biologists Ltd.)

For navigation, animals use a robust internal compass. Compass navigation is crucial for long-distance migrating animals like monarch butterflies, which use the sun to navigate over 4,000 km to their overwintering sites every fall. Sun-compass neurons of the central complex have only been recorded in immobile butterflies, and experimental evidence for encoding the animal's heading in these neurons is still missing. Although the activity of central-complex neurons exhibits a locomotor-dependent modulation in many insects, the function of such modulations remains unexplored. Here, we developed tetrode recordings from tethered flying monarch butterflies to reveal how flight modulates heading representation. We found that, during flight, heading-direction neurons change their tuning, transforming the central-complex network to function as a global compass. This compass is characterized by the dominance of processing steering feedback and allows for robust heading representation even under unreliable visual scenarios, an ideal strategy for maintaining a migratory heading over enormous distances., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Monarch butterflies ( Danaus plexippus ) are prominent for their annual long-distance migration from North America to their overwintering area in Central Mexico. To find their way on this long journey, they use a sun compass as their main orientation reference but will also adjust their migratory direction with respect to mountain ranges. This indicates that the migratory butterflies also attend to the panorama to guide their travels. Although the compass has been studied in detail in migrating butterflies, little is known about the orientation abilities of non-migrating butterflies. Here, we investigated whether non-migrating butterflies - which stay in a more restricted area to feed and breed - also use a similar compass system to guide their flights. Performing behavioral experiments on tethered flying butterflies in an indoor LED flight simulator, we found that the monarchs fly along straight tracks with respect to a simulated sun. When a panoramic skyline was presented as the only orientation cue, the butterflies maintained their flight direction only during short sequences, suggesting that they potentially use it for flight stabilization. We further found that when we presented the two cues together, the butterflies incorporate both cues in their compass. Taken together, we show here that non-migrating monarch butterflies can combine multiple visual cues for robust orientation, an ability that may also aid them during their migration., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2020. Published by The Company of Biologists Ltd.)

Noradrenergic A2 neurons in nucleus tractus solitarius (NTS) respond to stressors such as hypoxia. We hypothesize that tyrosine hydroxylase (TH) knockdown in NTS reduces cardiovascular responses to chronic intermittent hypoxia (CIH), a model of the arterial hypoxemia observed during sleep apnea in humans. Adult male Sprague-Dawley rats were implanted with radiotelemetry transmitters and adeno-associated viral constructs with green fluorescent protein (GFP) reporter having either short hairpin RNA (shRNA) for TH or scrambled virus (scRNA) were injected into caudal NTS. Virus-injected rats were exposed to 7 days of CIH (alternating periods of 10% O2 and of 21% O2 from 8 AM to 4 PM; from 4 PM to 8 AM rats were exposed to 21% O2). CIH increased mean arterial pressure (MAP) and heart rate (HR) during the day in both the scRNA (n = 14, P < 0.001 MAP and HR) and shRNA (n = 13, P < 0.001 MAP and HR) groups. During the night, MAP and HR remained elevated in the scRNA rats (P < 0.001 MAP and HR) but not in the shRNA group. TH immunoreactivity and protein were reduced in the shRNA group. FosB/ΔFosB immunoreactivity was decreased in paraventricular nucleus (PVN) of shRNA group (P < 0.001). However, the shRNA group did not show any change in the FosB/ΔFosB immunoreactivity in the rostral ventrolateral medulla. Exposure to CIH increased MAP which persisted beyond the period of exposure to CIH. Knockdown of TH in the NTS reduced this CIH-induced persistent increase in MAP and reduced the transcriptional activation of PVN. This indicates that NTS A2 neurons play a role in the cardiovascular responses to CIH.

Chronic intermittent hypoxia (CIH) is a model of arterial hypoxemia that accompanies sleep apnea and increases resting arterial pressure (AP). We examined the effects of 7 days of exposure to CIH on arterial baroreflex control of renal sympathetic nerve activity (RSNA) and heart rate (HR) in rats. Sprague-Dawley rats (15±2 weeks old) were exposed to CIH (9% oxygen for 3 min every 10 min, 8 h per day) for 7 days (n=16) while control rats (n=18) were maintained in normoxia. Baroreflex regulation of RSNA and HR were estimated in Inactin anesthetized and artificially ventilated rats during infusions of phenylephrine and nitroprusside to manipulate AP. After exposure to CIH, resting mean AP was higher in CIH than that in control group (115±7 vs. 105±7, P<0.001). Resting HR did not differ between the two groups. Exposure to CIH shifted the AP-RSNA relationship rightward (approximately 10 mm Hg, P<0.01). CIH did not alter maximum gain of the baroreflex control of RSNA (-2.6±0.6 vs. -2.5±0.6 arbitrary units (a.u.)/mm Hg) and HR (-1.8±0.6 vs. -1.8±0.7 bpm/mm Hg, CIH vs. control). In addition, cardiac spontaneous baroreflex sensitivity in conscious rats (n=8) also did not change during exposure to CIH. These results indicate that resetting of the sympathetic baroreflex control, rather than an impairment of its sensitivity, is associated with an onset of hypertension induced by CIH., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: The goal of the current report was to demonstrate the long-term efficacy of outpatient subcutaneous (sc) interferon alpha (IFN-alpha) and sc interleukin 2 (IL-2)-based combination regimens in patients with metastatic renal cell carcinoma., Methods: In three consecutive clinical trials, 443 patients received combined sc IFN-alpha and sc IL-2 (n = 97 patients); combined sc IFN-alpha, sc IL-2, and intravenous (iv) 5-fluorouracil (5-FU) (n = 260 patients); or combined sc IFN-alpha, sc IL-2, and iv 5-FU with oral 13cis-retinoic acid (n = 86 patients)., Results: The median overall survival was 21+ months. The 2-year, 5-year, and 13-year survival rates were calculated at 45.26%, 15.96%, and 8.96%, respectively. The median time to disease progression was 6 months. The 2-year, 5-year, and 13-year progression free survival rates were 17.84%, 9.54%, and 9.20%, respectively., Conclusions: The current data suggest that combined outpatient sc IFN-alpha and sc IL-2, according to the Atzpodien regimen, achieves long-term survival benefits in a subset of patients with metastatic renal cell carcinoma, both with and without 13-cis-retinoic acid and/or 5-fluorouracil., (Copyright 2002 American Cancer Society.)