A hypothalamomedullary network for physiological responses to environmental stresses.

Various environmental stressors, such as extreme temperatures (hot and cold), pathogens, predators and insufficient food, can threaten life. Remarkable progress has recently been made in understanding the central circuit mechanisms of physiological responses to such stressors. A hypothalamomedullary neural pathway from the dorsomedial hypothalamus (DMH) to the rostral medullary raphe region (rMR) regulates sympathetic outflows to effector organs for homeostasis. Thermal and infection stress inputs to the preoptic area dynamically alter the DMH → rMR transmission to elicit thermoregulatory, febrile and cardiovascular responses. Psychological stress signalling from a ventromedial prefrontal cortical area to the DMH drives sympathetic and behavioural responses for stress coping, representing a psychosomatic connection from the corticolimbic emotion circuit to the autonomic and somatic motor systems. Under starvation stress, medullary reticular neurons activated by hunger signalling from the hypothalamus suppress thermogenic drive from the rMR for energy saving and prime mastication to promote food intake. This Perspective presents a combined neural network for environmental stress responses, providing insights into the central circuit mechanism for the integrative regulation of systemic organs.

Potassium ion leakage impairs thermotolerance in Corynebacterium glutamicum.

Corynebacterium glutamicum, a gram-positive bacterium, can produce amino acids such as glutamic acid and lysine. The heat generated during cell growth and/or glutamate fermentation disturbs both the cell growth and fermentation. To overcome such a negative effect of the fermentation heat, we have tried to establish a high temperature fermentation. One of the approach is to create a thermotolerant strains, while the other is to create an optimum culture conditions able for the strain to grow at higher temperatures. In this study, we focused on the latter approach, where we examined the effect of potassium ion on cell growth at high growth temperatures of C. glutamicum. The supplementation of high concentrations of potassium chloride (300 mM) (or sorbitol, an osmolyte) mitigated the repressed cell growth induced by high temperature at 39 °C or 40 °C. The intracellular potassium concentration declines from 300 mM to ∼150 mM by increasing the growth temperature but not by supplementing potassium chloride or sorbitol. Furthermore, in vitro experiments revealed that the potassium ion leakage occurs at high temperatures, which was mitigated in the presence of high concentrations of extracellular potassium chloride. This suggested that the presence of high osmolyte in the culture medium could inhibit the potassium ion leakage induced by high temperature and subsequently support cell growth at high temperatures.

Thermal adaptation of acetic acid bacteria for practical high-temperature vinegar fermentation.

Thermotolerant microorganisms are useful for high-temperature fermentation. Several thermally adapted strains were previously obtained from Acetobacter pasteurianus in a nutrient-rich culture medium, while these adapted strains could not grow well at high temperature in the nutrient-poor practical culture medium, "rice moromi." In this study, A. pasteurianus K-1034 originally capable of performing acetic acid fermentation in rice moromi was thermally adapted by experimental evolution using a "pseudo" rice moromi culture. The adapted strains thus obtained were confirmed to grow well in such the nutrient-poor media in flask or jar-fermentor culture up to 40 or 39 °C; the mutation sites of the strains were also determined. The high-temperature fermentation ability was also shown to be comparable with a low-nutrient adapted strain previously obtained. Using the practical fermentation system, "Acetofermenter," acetic acid production was compared in the moromi culture; the results showed that the adapted strains efficiently perform practical vinegar production under high-temperature conditions.

Convenient Synthesis and Physiological Activities of Flavonoids in Coreopsis lanceolata L. Petals and Their Related Compounds.

Chalcones, flavanones, and flavonols, including 8-methoxybutin isolated from Coreopsis lanceolata L. petals, were successfully synthesized with total yields of 2⁻59% from O-methylpyrogallols using the Horner⁻Wadsworth⁻Emmons reaction as a key reaction. Aurones, including leptosidin, were also successfully synthesized with 5⁻36% total yields using the Aldol condensation reaction as a key reaction. Each chalcone, flavanone, flavonol, and aurone with the 3,4-dihydroxy groups in the B-ring showed high antioxidant activity. Additionally, each of the chalcones, flavanones, flavonols, and aurones with the 2,4-dihydroxy groups in the B-ring showed an excellent whitening ability.

The lateral parabrachial nucleus, but not the thalamus, mediates thermosensory pathways for behavioural thermoregulation.

Thermoregulatory behaviour, such as migration to a comfortable thermal environment, is a representative innate animal behaviour and facilitates effective autonomic regulation of body temperature with a reduced cost of resources. Here we determine the central thermosensory ascending pathway that transmits information on environmental temperature from cutaneous thermoreceptors to elicit thermoregulatory behaviour. To examine the contribution of the spinothalamocortical pathway, which is known to mediate thermosensory transmission for perception of skin temperature, we lesioned thalamic regions mediating this pathway in rats. Thalamic-lesioned rats showed compromised electroencephalographic responses in the primary somatosensory cortex to changes in skin temperature, indicating functional ablation of the spinothalamocortical pathway. However, these lesioned rats subjected to a two-floor innocuous thermal plate preference test displayed intact heat- and cold-avoidance thermoregulatory behaviours. We then examined the involvement of the lateral parabrachial nucleus (LPB), which mediates cutaneous thermosensory signaling to the thermoregulatory center for autonomic thermoregulation. Inactivation of neurons in the LPB eliminated both heat- and cold-avoidance thermoregulatory behaviours and ablated heat defense. These results demonstrate that the LPB, but not the thalamus, mediates the cutaneous thermosensory neural signaling required for behavioural thermoregulation, contributing to understanding of the central circuit that generates thermal comfort and discomfort underlying thermoregulatory behaviours.

Psychological stress activates a dorsomedial hypothalamus-medullary raphe circuit driving brown adipose tissue thermogenesis and hyperthermia.

Psychological stress-induced hyperthermia (PSH) is a fundamental autonomic stress response observed in many mammalian species. Here we show a hypothalamomedullary, glutamatergic neural pathway for psychological stress signaling that drives the sympathetic thermogenesis in brown adipose tissue (BAT) that contributes to PSH. Using in vivo drug nanoinjections into rat brain and thermotelemetry, we demonstrate that the rostral medullary raphe region (rMR) and dorsomedial hypothalamus (DMH) mediate a psychosocial stress-induced thermogenesis in BAT and PSH. Functional neuroanatomy indicates that the DMH functions as a hub for stress signaling, with monosynaptic projections to the rMR for sympathetic outputs and to the paraventricular hypothalamic nucleus for neuroendocrine outputs. Optogenetic experiments showed that the DMH-rMR monosynaptic pathway drives BAT thermogenesis and cardiovascular responses. These findings make an important contribution to our understanding of the central autonomic circuitries linking stress coping with energy homeostasis-potentially underlying the etiology of psychogenic fever, a major psychosomatic symptom.

Electrophysiological and anatomical differences of the slow pathway between the fast-slow form and slow-slow form of atrioventricular nodal reentrant tachycardia.

AIMS: This study aimed to clarify whether electrophysiological and anatomical properties of the slow pathway (SP) could be different between the fast-slow form (F/S) and the slow-slow form (S/S) atrioventricular nodal reentrant tachycardia (AVNRT). METHODS AND RESULTS: Nine patients with F/S and 15 patients with S/S of atypical AVNRT were studied. The patients with S/S were divided into two groups; those with the anterograde SP being eliminated (S/S aSP-E) or preserved (S/S aSP-P) during catheter ablation. HA (CS-His) was determined as the difference of the shortest HA interval between the His bundle region and the coronary sinus (CS) region. The ratio of the amplitudes of atrial and ventricular potential (A/V ratio) of the successful ablation site of the SP was also evaluated. Effective refractory period of the retrograde SP was shorter and HA intervals during both tachycardia and ventricular pacing were longer in F/S than in S/S. HA (CS-His) did not differ between F/S and S/S (-4.3 ± 20.2 vs.-4.4 ± 18.4 ms, NS). The A/V ratio was significantly greater in the S/S aSP-P group compared with the both groups of F/S and S/S aSP-E (0.83 ± 0.29 vs. 0.38 ± 0.09 and 0.26 ± 0.15 ms, P < 0.01). CONCLUSION: Properties of the retrograde SP differ between F/S and S/S of AVNRT. Fast-slow form may utilize the same pathway for the retrograde conduction as the anterograde SP in S/S.