Search

Energy reserves, primarily stored in the insect's fat body, are essential for physiological processes such as reproduction and cocoon formation. However, whether these processes are mutually constraining is unknown. Here, we showed that cocoon-free silkworms accumulate amino acid constituents of silk proteins in the hemolymph and maintain lipid and sugar reserves in the pupal fat body by repressing the expression of sericin and fibroin genes in the middle and posterior silk glands, respectively, via butterfly pierisin-1A catalytic domain expression. This, in turn, upregulates insulin/insulin-like signaling and target of rapamycin (IIS/TOR) signaling, which enhances vitellogenesis and accelerates ovarian development, thus contributing to increased fecundity. The impacts of semi-starvation on fecundity and egg hatchability were also less pronounced in cocoon-free silkworms compared with wildtype silkworms. These data uncover the resource allocation trade-off between cocoon formation and fecundity and demonstrate that nutritional signaling plays a role in regulating silkworm reproduction., Competing Interests: The authors declare no competing interests., (© 2024 The Authors.)

Transient receptor potential melastatin 8 (TRPM8) is a cold-sensing cation channel; however, its role in the transferal of information on peripheral cold sensation to the brain remains unclear. Therefore, we herein investigated cold avoidance behaviors and the neuronal activation of the hypothalamus and cerebral cortex in TRPM8 knockout (KO) mice to innocuous and nocuous cold stimuli. An innocuous cold stimulation at 15 °C decreased the duration of sleeping and increased that of rearing, climbing, and eating in WT mice, but it did not alter the duration of these behaviors in TRPM8 KO animals. The innocuous cold stimulation also increased the frequency of rearing, climbing, walking, and eating in WT mice, but it did not change that of these behaviors in TRPM8 KO animals. In contrast, a nocuous cold stimulation at 9 °C decreased the duration of sleeping and increased that of rearing and climbing in both WT and TRPM8 KO mice. The nocuous cold stimulation increased the frequency of rearing, climbing, and walking in WT and TRPM8 KO mice. Quantitative Fos immunohistochemistry showed that both innocuous and nocuous cold stimulations increased the number of Fos-positive neurons in temperature- and metabolism-associated hypothalamic regions in WT mice, but not in TRPM8 KO animals. The number of Fos-positive neurons was markedly increased in the primary motor and somatosensory cortices in WT and TRPM8 KO mice following the nocuous cold stimulation, but only increased in WT mice after the innocuous cold stimulation. Collectively, the present results indicate that TRPM8 plays a crucial role in activating autonomic hypothalamic neuronal circuits under innocuous and nocuous cold stimuli., (Copyright © 2022. Published by Elsevier Inc.)

Transient receptor potential melastatin 8 (TRPM8) functions in the sensing of noxious and innocuous colds; however, its significance in pathogen-induced thermoregulation remains unclear. In the present study, we investigated the role of TRPM8 in the regulation of endotoxin-induced body temperature control. The peripheral administration of low-dose lipopolysaccharide (LPS) at 50 ​μg/kg generated fever in wild-type (WT) mice, whereas it caused hypothermia in TRPM8 knockout (KO) animals. LPS-induced sickness responses such as decrease in body weight, and food and water intake were not different between WT and TRPM8 KO mice. TRPM8 KO mice exhibited more severe hypothermia and lower locomotor activity following the peripheral administration of high-dose LPS at 5 ​mg/kg compared with WT ones. An intracerebroventricular (i.c.v.) injection of either LPS at 3.6 ​μg/kg or interleukin-1β at 400 ​ng/kg elicited hypothermia in TRPM8 KO mice, in contrast to fever in WT animals. The peripheral administration of zymosan at 3 ​mg/kg also induced hypothermia in contrast to fever in WT mice. An i.c.v. injection of prostaglandin E 2 at 16 or 160 ​nmol/kg induced normal fever in both WT and TRPM8 KO mice. Infrared thermography showed significant decline of the interscapular skin temperature that estimates temperature of the brown adipose tissue, regardless of no alteration of its temperature in WT animals. Fos immunohistochemistry showed stronger Fos activation of hypothalamic thermoregulation-associated nuclei in TRPM8 KO mice compared with WT animals following the peripheral administration of low-dose LPS. Therefore, the present study indicates that TRPM8 is necessary for switching between fever and hypothermia during endotoxin-induced inflammation., Competing Interests: The authors declare that there is no conflict of interest that may be perceived as prejudicing the impartiality of the research reported., (© 2021 The Authors.)

Background: The aim of our study was to examine the association of heart rate (HR) with the onset of congestive heart failure (CHF), and to compare the predictive value of HR with that of the serum level of human atrial natriuretic peptide (hANP) and the cardiothoracic ratio (CTR)., Methods: Thirty-eight patients on chronic hemodialysis (HD) aged 68 ± 11 years (61% men, 41% with diabetes) who had normal cardiac function were enrolled in this study. Among them, 6 patients had suffered CHF. Baseline characteristics and HR, hANP and CTR were compared between the 2 groups., Results: At baseline, the monthly mean pre-HR (before HD), CTR and hANP values were higher in CHF patients compared with non-CHF patients. In the CHF group, the monthly mean pre-HR increased progressively beginning 10 months before the onset of CHF, which was earlier than the increments of hANP and CTR. A significant difference between the CHF and non-CHF groups was observed earlier for monthly mean pre-HR (4 months before CHF) and ANP (4 months before CHF) than for CTR (2 months before CHF)., Conclusions: The increment of monthly mean pre-HR may reflect the early phase of cardiac overload, and is of equal significance to hANP. Further large-scale prospective studies are required to confirm these results.

The synthesis and antimicrobial activity of novel carbacephem antibiotics which have amido moiety of (S)-aminothiazolylglycyl side chain are described. Among them, the compound having 5-hydroxy-4-pyridon-2-carboxyl group (KT-4697) showed exceptionally strong activity against Pseudomonas aeruginosa as well as Gram-negative bacteria. A cephalosporin with this acyl group namely KT-4788 with methylpyridiniumthiomethyl group at C-3 was found to be the most active against Gram-positive and Gram-negative strains including P. aeruginosa.

A series of new carbacephem compounds which have substituted aminothiazolylglycyl side chain have been prepared starting from corresponding carbacephems with aminothiazolylmethoxyimino group. Among them, the compound having 3,4-dihydroxybenzoyl group showed very sharp activity against Pseudomonas aeruginosa. Moreover, the optical resolution of alpha carbon of aminothiazolylglycyl moiety was carried out through preparation of optically active side chain and the (S)-isomer (KT-4380) was found to be the most active against Pseudomonas sp. as well as other Gram-negative strains.