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Objectives:To assess whether smoking is a risk factor for developing rheumatoid arthritis (RA).Design:Meta-analysis.Method:Data sources were observational studies that examined the association between smoking history and the risk of developing RA identified through Medline and EMBASE (from 1966 to December 2006), relevant books and a reference search. Two authors independently extracted the following: authors’ names, publication year, sample size, participant characteristics, odds ratios (OR) or relative risks, adjustment factors, study design and area where the study was conducted. Data syntheses were based upon random effects model. Summarised syntheses effects were expressed by OR.Results:Sixteen studies were selected from among 433 articles. For men, summary OR for ever, current and past smokers were 1.89 (95% CI 1.56 to 2.28), 1.87 (1.49 to 2.34) and 1.76 (1.33 to 2.31), respectively. For rheumatoid factor-positive (RF+) RA, summary OR for ever, current and past smokers were 3.02 (2.35 to 3.88), 3.91 (2.78 to 5.50) and 2.46 (1.74 to 3.47), respectively. Summary OR for 20 or more pack-years of smoking was 2.31 (1.55 to 3.41). For women, summary OR for ever, current and past smokers were 1.27 (1.12 to 1.44), 1.31 (1.12 to 1.54) and 1.22 (1.06 to 1.40), respectively. For RF+ RA, summary OR for ever, current and past smokers were 1.34 (0.99 to 1.80), 1.29 (0.94 to 1.77) and 1.21 (0.83 to 1.77). Summary OR for 20 or more pack-years of smoking was 1.75 (1.52 to 2.02).Conclusion:Smoking is a risk factor for RA, especially RF+ RA men and heavy smokers.

The analysis of the urine contents can be informative of physiological homoeostasis, and it has been speculated that the levels of urinary d-serine (d-ser) could inform about neurological and renal disorders. By analysing the levels of urinary d-ser using a d-ser dehydratase (DSD) enzyme, Ito et al. (Biosci. Rep.(2021) 41, BSR20210260) have described abundant levels of l-erythro-β-hydroxyasparagine (l-β-EHAsn), a non-proteogenic amino acid which is also a newly described substrate for DSD. The data presented support the endogenous production l-β-EHAsn, with its concentration significantly correlating with the concentration of creatinine in urine. Taken together, these results could raise speculations that l-β-EHAsn might have unexplored important biological roles. It has been demonstrated that l-β-EHAsn also inhibits serine racemase with Ki values (40 μM) similar to its concentration in urine (50 μM). Given that serine racemase is the enzyme involved in the synthesis of d-ser, and l-β-EHAsn is also a substrate for DSD, further investigations could verify if this amino acid would be involved in the metabolic regulation of pathways involving d-ser.

AbstractObjectivesTo compare the discriminative capabilities for the manifestation of sarcopenia or physical frailty between serum creatinine- and cystatin C-derived indices among community-dwelling older adults. DesignCross-sectional study. SettingPrimary Care and Community. ParticipantsWe utilized a subset of data from the Frail Elderly in the Sasayama-Tamba Area (FESTA) study, which was initiated in 2015 to gather comprehensive information on various health-related parameters among community-dwelling older individuals (age ≥65 years). MeasurementsFive serum creatinine–cystatin C based indices including the Sarcopenia Index, the serum creatinine/cystatin C ratio, the disparity between serum cystatin-C-based and creatinine-based estimated GFR, the total body muscle mass index (TBMM), and the prediction equation for skeletal muscle mass index (pSMI) were employed. Sarcopenia and physical frailty were identified based on the Asian Working Group for Sarcopenia criteria and the revised Japanese version of the Cardiovascular Health Study criteria, respectively. The receiver operating characteristic (ROC) and logistic regression analyses were performed to assess the discriminative abilities of these tools. ResultsIn the analysis of 954 participants, 52 (5.5%) were identified with sarcopenia and 35 (3.7%) with physical frailty. Regarding sarcopenia discrimination, TBMM and pSMI both exhibited area under the curve (AUC) values exceeding 0.8 for both men and women. Concerning the identification of physical frailty, AUC values ranged from 0.61 to 0.77 for males and 0.50 to 0.69 for females. In the multivariate logistic regression analyses, only TBMM and pSMI consistently displayed associations with sarcopenia, irrespective of sex (P<0.001, respectively). On the other hand, no consistent associations were observed between the indices and physical frailty. ConclusionsThis study provides a robust association of a serum creatinine- and cystatin C-derived indices, especially TBMM and pSMI, with sarcopenia among community-dwelling older adults. Conversely, the application of these indices for the screening of physical frailty has its constraints, necessitating further investigation.

The active site residues in GH1 β-glycosidases are compartmentalized into 3 functional regions, involved in catalysis or binding of glycone and aglycone motifs from substrate. However, it still remains unclear how residues outside the active site modulate the enzymatic activity. To tackle this question, we solved the crystal structure of the GH1 β-glycosidase from Spodoptera frugiperda (Sfβgly) to systematically map its residue contact network and correlate effects of mutations within and outside the active site. External mutations neighbouring the functional residues involved in catalysis and glycone-binding are deleterious, whereas mutations neighbouring the aglycone-binding site are less detrimental or even beneficial. The large dataset of new and previously characterized Sfβgly mutants supports that external perturbations are coherently transmitted to active site residues possibly through contacts and specifically disturb functional regions they interact to, reproducing the effects observed for direct mutations of functional residues. This allowed us to suggest that positions related to the aglycone-binding site are preferential targets for introduction of mutations aiming to further improve the hydrolytic activity of β-glycosidases.

ZFP521 was previously identified as a putative gene involved in induction of B-cell lymphomagenesis. However, the contribution of ZFP521 to lymphomagenesis has not been confirmed. In this study, we sought to elucidate the role of ZFP521 in B-cell lymphomagenesis. To this end, we used a retroviral insertion method to show that ZFP521 was a target of mutagenesis in pre-B-lymphoblastic lymphoma cells. The pre-B-cell receptor (pre-BCR) signaling molecules BLNK , BTK and BANK1 were positively regulated by the ZFP521 gene, leading to enhancement of the pre-BCR signaling pathway. In addition, c-myc and c-jun were upregulated following activation of ZFP521 . Stimulation of pre-BCR signaling using anti-Vpreb antibodies caused aberrant upregulation of c-myc and c-jun and of Ccnd3 , which encodes cyclin D3, thereby inducing the growth of pre-B cells. Stimulation with Vpreb affected the growth of pre-B cells, and addition of interleukin (IL)-7 receptor exerted competitive effects on pre-B-cell growth. Knockdown of BTK and BANK1 , targets of ZFP521 , suppressed the effects of Vpreb stimulation on cell growth. Furthermore, in human lymphoblastic lymphoma, analogous to pre-B-cell lymphoma in mice, the expression of ZNF521 , the homolog of ZFP521 in humans, was upregulated. In conclusion, our data showed that the ZFP521 gene comprehensively induced pre-B-cell lymphomagenesis by modulating the pre-B-cell receptor signaling pathway.

Many individuals with obstructive airway disease (OAD), including chronic obstructive pulmonary disease (COPD) and asthma, remain undiagnosed, despite the potential for reducing disease burden through early detection and treatment. OCEAN aimed to determine the prevalence of, and characteristics associated with, impaired lung function in a Japanese population, with the goal of improving strategies for early OAD detection. OCEAN was an observational, cross-sectional study in sequentially recruited Japanese individuals ≥40 years of age undergoing routine health examinations. Participants completed screening questionnaires and spirometry testing. Airflow limitation was defined as forced expiratory volume in 1 second/forced vital capacity (FEV /FVC) <0.7 by pre-bronchodilator spirometry. Preserved ratio impaired spirometry (PRISm) was defined as FEV /FVC ≥0.7 and FEV <80% predicted. The primary endpoint was prevalence of spirometry-based airflow limitation and PRISm. The characteristics of study participants were reported as secondary endpoints. Overall, 2518 individuals were included; 79% were <60 years of age (mean 52.0 years). Airflow limitation and PRISm were observed in 52 (2.1%) and 420 (16.7%) participants, respectively. FEV in the PRISm group was between that in the no airflow limitation/PRISm and airflow limitation groups, FVC was similar in the PRISm and airflow limitation groups. The PRISm group had higher mean body mass index and a higher proportion of comorbid metabolic disease compared with the airflow limitation group. The prevalence of airflow limitation and PRISm was highest among current smokers (3.9% and 21.3%, respectively) versus former or never smokers. A significant proportion of Japanese individuals <60 years of age attending their annual health examination had impaired lung function (airflow limitation and PRISm); prevalence was highest among current smokers. These findings support screening of current or former smokers ≥40 years of age using patient-reported questionnaires to inform the need for spirometry to confirm an OAD diagnosis.

The statistical coupling analysis of 768 β-glucosidases from the GH1 family revealed 23 positions in which the amino acid frequencies are coupled. The roles of these covariant positions in terms of the properties of β-glucosidases were investigated by alanine-screening mutagenesis using the fall armyworm Spodoptera frugiperda β-glycosidase (Sfβgly) as a model. The effects of the mutations on the Sfβgly kinetic parameters (kcat/Km) for the hydrolysis of three different p-nitrophenyl β-glycosides and structural comparisons of several β-glucosidases showed that eleven covariant positions (54, 98, 143, 188, 195, 196, 203, 398, 451, 452 and 460 in Sfβgly numbering) form a layer surrounding the active site of the β-glucosidases, which modulates their catalytic activity and substrate specificity via direct contact with the active site residues. Moreover, the influence of the mutations on the transition temperature (Tm) of Sfβgly indicated that nine of the coupled positions (49, 62, 143, 188, 223, 278, 309, 452 and 460 in Sfβgly numbering) are related to thermal stability. In addition to being preferentially occupied by prolines, structural comparisons indicated that these positions are concentrated at loop segments of the β-glucosidases. Therefore, due to these common biochemical and structural properties, these nine covariant positions, even without physical contacts among them, seem to jointly modulate the thermal stability of β-glucosidases.

The growth and yield of 13 red and green leaf lettuce (Lactuca sativa L.) cultivars were evaluated under two types of white LED irradiation. There was a difference in growth under the two types white LEDs, specifically in the fresh total weight, fresh leaf weight and dry weight in all cultivars. In addition, the main stem elongation was confirmed for red and green lettuce cultivars under all treatments, but some cultivars promoted the growth of the main stem and the others were inhibited by treatment with far-red light applied at the end of the day (EOD-FR). Furthermore, the EOD-FR treatment affected the characteristic reactions due to white LED light quality in each of the cultivars. These results showed that it is necessary to investigate the selection of white LEDs with and without EOD-FR treatment for each lettuce cultivar.

Fluid chemistry and microbial community patterns in chimney habitats were investigated in two hydrothermal fields located at the Central Indian Ridge. Endmember hydrothermal fluid of the Solitaire field, located ~3 km away from the spreading center, was characterized by moderately high temperature (307°C), Cl depletion (489 mm), mildly acidic pH (≥4.40), and low metal concentrations (Fe ≤ 105 μm and Mn = 78 μm). Chloride depletion indicates that the subseafloor source fluid had undergone phase separation at temperatures higher than ~390°C while the metal depletion was likely attributable to fluid alteration occurring at a venting temperature of around 307°C. These different temperature conditions suggested from fluid chemistry might be associated with an off‐spreading center location of the field that allows subseafloor fluid cooling prior to seafloor discharge. The microbial community in the chimney habitat seemed comparable to previously known patterns in typical basalt‐hosted hydrothermal systems. Endmember hydrothermal fluid of the Dodo field, standing on center of the spreading axis, was characterized by high H2 concentration of 2.7 mm. The H2 enrichment was likely attributable to fresh basalt–fluid interaction, as suggested by the nondeformed sheet lava flow expansion around the vents. Thermodynamic calculation of the reducing pyrite–pyrrhotite–magnetite (PPM) redox buffer indeed reproduced the H2 enrichment. The quantitative cultivation test revealed that the microbial community associated with the hydrothermal fluid hosted abundant populations of (hyper)thermophilic hydrogenotrophic chemolithoautotrophs such as methanogens. The function of subseafloor hydrogenotrophic methanogenic populations dwelling around the H2‐enriched hydrothermal fluid flows was also inferred from the 13C‐ and D‐depleted signature of CH4 in the collected fluids. It was observed that the hydrothermal activity of the Dodo field had ceased until 2013.

The active site residues in GH1 [beta]-glycosidases are compartmentalized into 3 functional regions, involved in catalysis or binding of glycone and aglycone motifs from substrate. However, it still remains unclear how residues outside the active site modulate the enzymatic activity. To tackle this question, we solved the crystal structure of the GH1 [beta]-glycosidase from Spodoptera frugiperda (Sf[beta]gly) to systematically map its residue contact network and correlate effects of mutations within and outside the active site. External mutations neighbouring the functional residues involved in catalysis and glycone-binding are deleterious, whereas mutations neighbouring the aglycone-binding site are less detrimental or even beneficial. The large dataset of new and previously characterized Sf[beta]gly mutants supports that external perturbations are coherently transmitted to active site residues possibly through contacts and specifically disturb functional regions they interact to, reproducing the effects observed for direct mutations of functional residues. This allowed us to suggest that positions related to the aglycone-binding site are preferential targets for introduction of mutations aiming to further improve the hydrolytic activity of [beta]-glycosidases.