Contribution of lactobacillus casei to the recovery from chemically induced skeletal muscle damage under chronic stress

Background: Regeneration of damaged skeletal muscle requires sufficient supply of nutrients. Fully functional intestine and colon assure sufficient supply of nutrients. Gut commensal bacteria are known to support intestinal function. Previously lactobacillus treatment of elite athletes was shown to be effective in attenuating fatigue and impaired performance. We hypothesized that Lactobacillus casei (L.casei) administration may facilitate recovery of damaged skeletal muscle when the gut function is suppressed under chronic stress in which muscle regeneration is compromised. Objective: To investigate contribution of L.casei under chronic stress to the recovery of damaged skeletal muscle in young and older adult mice. Methods: L.casei was given orally at a dose of 10-8 /day for 7days to 10 weeks old (young) and 45-55 weeks old (older adult) male C57BL/6J mice. Vehicle control mice received an equivalent volume of water for 7 days. On the eighth day, cardiotoxin (CTX) was injected to gatrocnemius muscle to induce muscle damage. Both groups were assigned 2 hours repeated-restraint stress everyday (chronic stress). On days 3, 5, 7, 10, 14 and 20 after CTX injection, mice were sacrificed. Excised gastrocnemius muscle was subjected to weight measurement and immunohistochemical analyses. Results: There were significant differences in both the recovery of muscle weight and the regeneration process of gastrocnemius muscle examined immunohistochemically between control and L.casei treated young and older adult groups. Especially, the expression of developmental MHC (dMHC), a marker of premature regeneration, was positive up to 3 days in older adult groups. The delay in the recovery of muscle weight was obvious in older adult mice regardless of the treatment. However, while the expression of dMHC was prolonged up to day 7 in the vehicle control, dMHC expression was notable only up to day 3 or day 5 in the L.casei treated. Therefore, in older adult mice L.casei treatment under chronic stress may have facilitated the maturation process of regenerating skeletal muscle. Conclusion: Our results suggests that L.casei favor under chronic stress favors the recovery of skeletal muscle from muscle damage. The maintenance of gut function by L. casei treatment may have facilitated the maturation process of regenerating skeletal muscle

Gibberellin DELLA signaling targets the retromer complex to redirect protein trafficking to the plasma membrane

The plant hormone gibberellic acid (GA) is a crucial regulator of growth and development. The main paradigm of GA signaling puts forward transcriptional regulation via the degradation of DELLA transcriptional repressors. GA has also been shown to regulate tropic responses by modulation of the plasma membrane incidence of PIN auxin transporters by an unclear mechanism. Here we uncovered the cellular and molecular mechanisms by which GA redirects protein trafficking and thus regulates cell surface functionality. Photoconvertible reporters revealed that GA balances the protein traffic between the vacuole degradation route and recycling back to the cell surface. Low GA levels promote vacuolar delivery and degradation of multiple cargos, including PIN proteins, whereas high GA levels promote their recycling to the plasma membrane. This GA effect requires components of the retromer complex, such as Sorting Nexin 1 (SNX1) and its interacting, microtubule (MT)-associated protein, the Cytoplasmic Linker-Associated Protein (CLASP1). Accordingly, GA regulates the subcellular distribution of SNX1 and CLASP1, and the intact MT cytoskeleton is essential for the GA effect on trafficking. This GA cellular action occurs through DELLA proteins that regulate the MT and retromer presumably via their interaction partners Prefoldins (PFDs). Our study identified a branching of the GA signaling pathway at the level of DELLA proteins, which, in parallel to regulating transcription, also target by a nontranscriptional mechanism the retromer complex acting at the intersection of the degradation and recycling trafficking routes. By this mechanism, GA can redirect receptors and transporters to the cell surface, thus coregulating multiple processes, including PIN-dependent auxin fluxes during tropic responses

Bundling of collagen fibrils influences osteocyte network formation during bone modeling

Osteocytes form a cellular network by gap junctions between their cell processes. This network is important since intercellular communication via the network is essential for bone metabolism. However, the factors that influence the formation of this osteocyte network remain unknown. As the early stage of osteocyte network formation occurs on the bone surface, we observed a newly formed trabecular bone surface by orthogonal focused ion beam-scanning electron microscopy. The embedding late osteoblast processes tended to avoid bundled collagen fibrils and elongate into sparse collagen fibrils. Then, we examined whether the inhibition of bundling of collagen fibrils using a potent lysyl oxidase inhibitor, beta-aminopropionitrile (BAPN) changed the cellular network of the chick calvaria. The osteocyte shape of the control group was spindle-shape, while that of the BAPN group was sphere-shaped. In addition, the osteocyte processes of the control group were elongated vertically to the long axis of the cell body, whereas the osteocyte processes of the BAPN group were elongated radially. Therefore, it was suggested that the bundling of collagen fibrils influences normal osteocyte network formation during bone modeling

Perspectives on enteral tube feeding in Japan

[Introduction] The purpose of this study was to investigate the differences in the preference of enteral tube feeding between elderly inhabitants of Mugi town, Tokushima Prefecture, Japan, and their parents in various physical conditions. [Methods] This population-based questionnaire survey studied 300 randomly selected participants aged 65–80 years. Respondents were to consider a situation where eating was difficult, and were questioned on their desire for tube feeding, using a visual analogue scale (VAS) ranging from “do not want tube feeding (0)” to “want tube feeding (100).” [Results] Valid responses of 103 (34.4%) participants were analyzed. Under conditions of being “healthy,” “bedridden,” “with dementia,” and “bedridden and with dementia,” the median (IQR) of the VAS values for the desire for tube feeding were 31.8 (3.3 to 83.8), 19.3 (2.4 to 52.3), 5.2 (0.7 to 18.9), 4.0 (0.3 to 15.2) for respondents and 55.2 (11.6 to 92.2), 48.7 (5.5 to 85.5), 9.0 (1.2 to 46.8), 5.1 (0.1 to 36.5) for parents, respectively. The VAS values for the parents were significantly higher (p=0.001, 0.002, 0.001, and 0.01, respectively for the four conditions described) for the same items. [Conclusion] Surrogate decisions made by family members often differ from what the patients would have desired

Past infections and low ACPA in RA

Background : Rheumatoid arthritis (RA), an autoimmune disease of unknown etiology, is believed to occur as the result of actions of genetic and environmental factors. In this study, we examined the relation of past histories about infectious diseases with the levels anti-citrullinated protein autoantibodies (ACPA) in RA. Methods : Results of a questionnaire about histories of infectious diseases were obtained from 85 patients with RA, and were analyzed. Results : Significantly lower level of ACPA was detected in patients with the history of tonsillitis, otitis media or urinary cystitis than in those without it. There was no difference in the level of ACPA in RA patients between with and without cold / influenza, rubella, chickenpox, herpes labialis or herpes zoster. When RA patients were divided into two groups, high-level and low-level ACPA, multiple logistic regression analysis revealed that the history of otitis media was a significantly independent factor for the low level of ACPA. There was no significant relation between the level of rheumatoid factor and histories of infectious diseases. Conclusion : This study clarified that the past history of otitis media is associated with the low level of ACPA in RA

CRP in PMR and RS3PE syndrome

Polymyalgia rheumatica (PMR) and remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome are common inflammatory rheumatic diseases in the elderly. In this study, we investigate predictive factors which correspond to subsequent disease control of PMR and RS3PE syndrome. Twenty four patients, which contained 18 PMR and 6 RS3PE syndrome, were treated with initial dosages of 10-20 mg per day oral prednisolone, and the dosage of prednisolone was then tapered. Significantly higher initial CRP was observed in patients with poor disease control than in those with good disease control afterwards. The number of patients with negative CRP after 4 weeks was significantly more in patients with good disease control after 1 year than in those with poor disease control. Patients were shown to be in good disease control status after 1 year when CRP after 4 weeks became negative even if they had initial high CRP. Our study clarify that to make CRP negative after 4 weeks is associated with subsequent suppression of the disease activity and with decreased dosages of corticosteroids

Characteristics of medical students who would like to be a generalist physician and contribute to remote area medicine

We administered a questionnaire to 5th grade medical students to examine the effect of communitybased clinical practice on their attitudes to remote areamedicine and their course after the graduation.Data from 192 students were obtained. The intensity of students’ attitudes was estimated by using visual analogue scale. The intensities of the interest and a sense of fulfillment in remotearea medicine were significantly increased after the practice. A significantly lower level of the intensity to becomea generalist than that to becomea specialist was seen inthe students with low intensity in a sense of fulfillment. The percentages of the students who answered that they can work for 5 years or more in remote area were significantly lower in students with low intensity of a sense of fulfillment than in those with high intensity. A significantly higher percentage in students who worked at a familiar prefecture to them after the graduation was seen in female than in male. This study shows that the community-based practice is meaningful in increasing motivation which desire to work in remote area medicine, and that themotivation may affect their course after the graduation

Virological characteristics of the SARS-CoV-2 Omicron BA.2.75 variant

SARS-CoV-2オミクロンBA.2.75株（通称ケンタウロス）のウイルス学的性状の解明. 京都大学プレスリリース. 2022-10-12.The SARS-CoV-2 Omicron BA.2.75 variant emerged in May 2022. BA.2.75 is a BA.2 descendant but is phylogenetically distinct from BA.5, the currently predominant BA.2 descendant. Here, we show that BA.2.75 has a greater effective reproduction number and different immunogenicity profile than BA.5. We determined the sensitivity of BA.2.75 to vaccinee and convalescent sera as well as a panel of clinically available antiviral drugs and antibodies. Antiviral drugs largely retained potency but antibody sensitivity varied depending on several key BA.2.75-specific substitutions. The BA.2.75 spike exhibited a profoundly higher affinity for its human receptor, ACE2. Additionally, the fusogenicity, growth efficiency in human alveolar epithelial cells, and intrinsic pathogenicity in hamsters of BA.2.75 were greater than those of BA.2. Our multilevel investigations suggest that BA.2.75 acquired virological properties independent of BA.5, and the potential risk of BA.2.75 to global health is greater than that of BA.5

Convergent evolution of SARS-CoV-2 Omicron subvariants leading to the emergence of BQ.1.1 variant

In late 2022, various Omicron subvariants emerged and cocirculated worldwide. These variants convergently acquired amino acid substitutions at critical residues in the spike protein, including residues R346, K444, L452, N460, and F486. Here, we characterize the convergent evolution of Omicron subvariants and the properties of one recent lineage of concern, BQ.1.1. Our phylogenetic analysis suggests that these five substitutions are recurrently acquired, particularly in younger Omicron lineages. Epidemic dynamics modelling suggests that the five substitutions increase viral fitness, and a large proportion of the fitness variation within Omicron lineages can be explained by these substitutions. Compared to BA.5, BQ.1.1 evades breakthrough BA.2 and BA.5 infection sera more efficiently, as demonstrated by neutralization assays. The pathogenicity of BQ.1.1 in hamsters is lower than that of BA.5. Our multiscale investigations illuminate the evolutionary rules governing the convergent evolution for known Omicron lineages as of 2022