Inositol Acylation of Phosphatidylinositol Mannosides: A Rapid Mass Response to Membrane Fluidization in Mycobacteria

Mycobacteria share an unusually complex, multilayered cell envelope, which contributes to adaptation to changing environments. The plasma membrane is the deepest layer of the cell envelope and acts as the final permeability barrier against outside molecules. There is an obvious need to maintain the plasma membrane integrity, but the adaptive responses of the plasma membrane to stress exposure remain poorly understood. Using chemical treatment and heat stress to fluidize the membrane, we show here that phosphatidylinositol (PI)-anchored plasma membrane glycolipids known as PI mannosides (PIMs) are rapidly remodeled upon membrane fluidization in Mycobacterium smegmatis. Without membrane stress, PIMs are predominantly in a triacylated form: two acyl chains of the PI moiety plus one acyl chain modified at one of the mannose residues. Upon membrane fluidization, we determined the fourth fatty acid is added to the inositol moiety of PIMs, making them tetra-acylated variants. Additionally, we show that PIM inositol acylation is a rapid response independent of de novo protein synthesis, representing one of the fastest mass conversions of lipid molecules found in nature. Strikingly, we found that M. smegmatis is more resistant to the bactericidal effect of a cationic detergent after benzyl alcohol pre-exposure. We further demonstrate that fluidization-induced PIM inositol acylation is conserved in pathogens such as Mycobacterium tuberculosis and Mycobacterium abscessus. Our results demonstrate that mycobacteria possess a mechanism to sense plasma membrane fluidity change. We suggest that inositol acylation of PIMs is a novel membrane stress response that enables mycobacterial cells to resist membrane fluidization

Safety and Efficacy of the Surgical Management of Hemodialysis Patients with Gastric Cancer

This retrospective study evaluated the short- and long-term outcomes after surgical management for gastric cancer in hemodialysis patients compared to non-dialysis patients. Twelve hemodialysis patients were compared with a propensity score-matched cohort of 39 gastric cancer patients who had not undergone hemodialysis. Short- and long-term outcomes along with scores estimating physiological ability and surgical stress were evaluated in both groups. The incidence of postoperative morbidity according to the Clavien-Dindo classification was higher in the hemodialysis gastric cancer group than in the non-dialysis gastric cancer group. The 5-year overall survival rate in the non-dialysis group was 69.2% after surgical resection for gastric cancer and 22.2% in the hemodialysis group. Patients with preoperative risk scores≥0.48 had significantly poorer survival outcomes compared to those with preoperative risk scores<0.48 (5-year survival rate, 83.3% vs. 39.4%, respectively). Our analyses suggest that hemodialysis patients undergoing surgery for gastric cancer have a significantly poorer postoperative prognosis and an elevated risk of postoperative complications

Relation between psychosocial variables and the glycemic control of patients with type 2 diabetes: A cross-sectional and prospective study

<p>Abstract</p> <p>Background</p> <p>This cross-sectional and prospective study used a variety of psychological inventories to evaluate the relationship between psychosocial factors and the glycemic control of patients with type 2 diabetes.</p> <p>Methods</p> <p>Participants were 304 patients with type 2 diabetes who were treated as outpatients at diabetes clinics. All participants were assessed for HbA_1cand completed the following self-report psychological inventories: 1) Diabetes Treatment Satisfaction Questionnaire (DTSQ), 2) Problem Areas in Diabetes Survey (PAID), 3) Well-being Questionnaire 12 (W-BQ12), 4) Self-Esteem Scale (SES), 5) Social Support Scale, and 6) Self-Efficacy Scale. HbA_1cwas again measured one year later. The relationships between the psychosocial variables obtained by analysis of the psychological inventories and baseline or one-year follow-up HbA_1cwere determined.</p> <p>Results</p> <p>Baseline HbA_1cwas significantly correlated with age, diet treatment regimen, number of microvascular complication of diabetes, and the total scores of DTSQ, W-BQ12, PAID, SES and the Self-Efficacy Scale. Hierarchical stepwise multiple regression revealed that significant predictors of baseline HbA_1cwere total DTSQ and PAID scores, along with age, diet treatment regimen, and number of microvascular complication of diabetes after adjustment for demographic, clinical and other psychosocial variables. Two hundred and ninety patients (95.4% of 304) were followed and assessed one year after baseline. Hierarchical stepwise multiple regression analysis showed the significant predictors of follow-up HbA_1cto be total DTSQ and PAID scores, along with age and diet treatment regimen. However, the correlation between baseline and follow-up HbA_1cwas so high that the only other variable to retain significance was diet treatment regimen once baseline HbA_1cwas included in the regression of follow-up HbA_1c.</p> <p>Conclusion</p> <p>The DTSQ and the PAID predicted both current and future HbA_1cto a similar and significant degree in patients with type 2 diabetes.</p

DV200 Index for Assessing RNA Integrity in Next-Generation Sequencing

Poor quality of biological samples will result in an inaccurate analysis of next-generation sequencing (NGS). Therefore, methods to accurately evaluate sample integrity are needed. Among methods for evaluating RNA quality, the RNA integrity number equivalent (RINe) is widely used, whereas the DV200, which evaluates the percentage of fragments of >200 nucleotides, is also used as a quality assessment standard. In this study, we compared the RINe and DV200 RNA quality indexes to determine the most suitable RNA index for the NGS analysis. Seventy-one RNA samples were extracted from formalin-fixed paraffin-embedded tissue samples (n=30), fresh-frozen samples (n=25), or cell lines (n=16). After assessing RNA quality using the RINe and DV200, we prepared two kinds of stranded mRNA sequencing libraries. Finally, we calculated the correlation between each RNA quality index and the amount of library product (1(st) PCR product per input RNA). The DV200 measure showed stronger correlation with the amount of library product than the RINe (R2=0.8208 for the DV200 versus 0.6927 for the RINe). Receiver operating characteristic curve analyses revealed that the DV200 was the better marker for predicting efficient library production than the RINe using a threshold of >10 ng/ng for the amount of the 1(st) PCR product per input RNA (cutoff value for the RINe and DV200, 2.3 and 66.1%; area under the curve, 0.99 and 0.91; sensitivity, 82% and 92%; and specificity, 93% and 100%, respectively). Our results indicate that NGS libraries prepared using RNA samples with the DV200 value>66.1% exhibit greater sensitivity and specificity than those prepared with the RINe values>2.3. These findings suggest that the DV200 is superior to the RINe, especially for low-quality RNA, because it is a more consistent assessment of the amount of the 1(st) NGS library product per input

Proposal and Demonstration of Free-Space Optical Communication Using Photonic Crystal Surface-Emitting Lasers

We propose and demonstrate free-space optical (FSO) communication using photonic crystal surface-emitting lasers (PCSELs). Unlike other types of conventional semiconductor lasers, such as edge-emitting lasers (EELs) and vertical-cavity surface-emitting lasers (VCSELs), PCSELs achieve much larger area single-mode coherent lasing, and this unique feature enables high-power (>watt) and lens-free operations at the same time. To date, these advantages have been recognized to be game changing, especially in light detection and ranging (LiDAR) and laser processing applications. In this work, we show that FSO communication can also benefit from these advantages of PCSELs; more specifically, conventional transmitters that include low-power semiconductor lasers, optical lenses, and fiber-based amplifiers could be replaced with a single PCSEL. Since fiber amplifiers usually consist of bulky components and have low conversion efficiencies, PCSELs can offer more space- and power-saving solutions. Moreover, the narrow beam divergence angles directly obtained from large-area single-mode PCSELs can also eliminate the need for lens systems on the transmitter side. To experimentally verify these potential advantages, we performed FSO transmission experiments based on PCSELs and successfully transmitted 480-MHz and 864-MHz orthogonal frequency division multiplexed (OFDM) signals over 1.1 m using a 500-μm PCSEL in a lens-free transmitter configuration. We believe that PCSELs open new possibilities and choices in FSO communication

Identification of in vivo Essential Genes of Vibrio vulnificus for Establishment of Wound Infection by Signature-Tagged Mutagenesis

Vibrio vulnificus can cause severe necrotic lesions within a short time. Recently, it has been reported that the numbers of wound infection cases in healthy hosts are increasing, for which surgical procedures are essential in many instances to eliminate the pathogen owing to its rapid proliferation. However, the mechanisms by which V. vulnificus can achieve wound infection in healthy hosts have not been elucidated. Here, we advance a systematic understanding of V. vulnificus wound infection through genome-wide identification of the relevant genes. Signature-tagged mutagenesis (STM) has been developed to identify functions required for the establishment of infection including colonization, rapid proliferation, and pathogenicity. Previously, STM had been regarded to be unsuitable for negative selection to detect the virulence genes of V. vulnificus owing to the low colonization and proliferation ability of this pathogen in the intestinal tract and systemic circulation. Alternatively, we successfully identified the virulence genes by applying STM to a murine model of wound infection. We examined a total of 5418 independent transposon insertion mutants by signature-tagged transposon mutagenesis and detected 71 clones as attenuated mutants consequent to disruption of genes by the insertion of a transposon. This is the first report demonstrating that the pathogenicity of V. vulnificus during wound infection is highly dependent on its characteristics: flagellar-based motility, siderophore-mediated iron acquisition system, capsular polysaccharide, lipopolysaccharide, and rapid chromosome partitioning. In particular, these functions during the wound infection process and are indispensable for proliferation in healthy hosts. Our results may thus allow the potential development of new strategies and reagents to control the proliferation of V. vulnificus and prevent human infections