Phosphoribosylpyrophosphate synthetase as a metabolic valve advances Methylobacterium/Methylorubrum phyllosphere colonization and plant growth.

The proficiency of phyllosphere microbiomes in efficiently utilizing plant-provided nutrients is pivotal for their successful colonization of plants. The methylotrophic capabilities of Methylobacterium/Methylorubrum play a crucial role in this process. However, the precise mechanisms facilitating efficient colonization remain elusive. In the present study, we investigate the significance of methanol assimilation in shaping the success of mutualistic relationships between methylotrophs and plants. A set of strains originating from Methylorubrum extorquens AM1 are subjected to evolutionary pressures to thrive under low methanol conditions. A mutation in the phosphoribosylpyrophosphate synthetase gene is identified, which converts it into a metabolic valve. This valve redirects limited C1-carbon resources towards the synthesis of biomass by up-regulating a non-essential phosphoketolase pathway. These newly acquired bacterial traits demonstrate superior colonization capabilities, even at low abundance, leading to increased growth of inoculated plants. This function is prevalent in Methylobacterium/Methylorubrum strains. In summary, our findings offer insights that could guide the selection of Methylobacterium/Methylorubrum strains for advantageous agricultural applications.

[Herbalogical analysis of Aconiti Carmichaeli Radix].

Tianxiong has been used as a Chinese medicinal in China for thousands of years, and the earliest record can be traced back to the Shennong's Classic of Materia Medica. It is effective in dispersing wind, dissipating cold, and replenishing fire to streng-then yang. To clarify the origin of Tianxiong, the present herbalogical study reviewed the ancient and modern literature from the origin, processing, and clinical efficacy. Before the Tang Dynasty, although the description of Tianxiong was quite superficial, an apparent difference between Tianxiong and Fuzi was recognized. In the Tang and Song Dynasties, Tianxiong and Fuzi were mistakenly recognized to be prepared from a same plant since their raw materials came from artificial cultivation. Medical literature in the Ming and Qing Dynasties mostly followed the previous records, with the origin of Tianxiong remaining controversial. There were three mainstream views about the origin of Tianxiong according the ancient medical books. First, Tianxiong was a kind of Aconiti Radix(Chuanwu) without attachment of Fuzi. Second, Tianxiong was the large Fuzi. Third, Tianxiong derived from Aconiti Kusnezoffii Radix(Caowu) about 10 cm in length. By contrast, Fuzi in a large size was simply regarded as Tianxiong in modern times. The processing methods were diversified in the ancient times, and the fire-processing was continuously applied. With the deepening of the research on the efficacy and detoxification mechanism, more methods were discovered, such as processing with ginger juice, child's urine and alcohol. As for modern times, the processing of Tianxiong has not been nearly passed down. The characteristic processing of Tianxiong only handed down in Sichuan province and Lingnan area, which can be discriminated by the last step. The efficacies of Tianxiong can be directly understood from its literal name, including dispersing wind, dissipating cold, and replenishing fire to assist yang. Nowadays, Tianxiong is mostly used to strengthen yang.

Regulation of gammaherpesvirus lytic replication by endoplasmic reticulum stress-induced transcription factors ATF4 and CHOP.

The stress-induced unfolded protein response (UPR) in the endoplasmic reticulum (ER) involves various signaling cross-talks and controls cell fate. B-cell receptor (BCR) signaling, which can trigger UPR, induces gammaherpesvirus lytic replication and serves as a physiological mechanism for gammaherpesvirus reactivation in vivo However, how the UPR regulates BCR-mediated gammaherpesvirus infection is unknown. Here, we demonstrate that the ER stressors tunicamycin and thapsigargin inhibit BCR-mediated murine gammaherpesvirus 68 (MHV68) lytic replication by inducing expression of the UPR mediator Bip and blocking activation of Akt, ERK, and JNK. Both Bip and the downstream transcription factor ATF4 inhibited BCR-mediated MHV68 lytic gene expression, whereas UPR-induced C/EBP homologous protein (CHOP) was required for and promoted BCR-mediated MHV68 lytic replication by suppressing upstream Bip and ATF4 expression. Bip knockout was sufficient to rescue BCR-mediated MHV68 lytic gene expression in CHOP knockout cells, and this rescue was blocked by ectopic ATF4 expression. Furthermore, ATF4 directly inhibited promoter activity of the MHV68 lytic switch transactivator RTA. Altogether, we show that ER stress-induced CHOP inhibits Bip and ATF4 expression and that ATF4, in turn, plays a critical role in CHOP-mediated regulation of BCR-controlled MHV68 lytic replication. We conclude that ER stress-mediated UPR and BCR signaling pathways are interconnected and form a complex network to regulate the gammaherpesvirus infection cycle.