LplA1-dependent utilization of host lipoyl peptides enables Listeria cytosolic growth and virulence

The bacterial pathogen Listeria monocytogenes replicates within the cytosol of mammalian cells. Mechanisms by which the bacterium exploits the host cytosolic environment for essential nutrients are poorly defined. L. monocytogenes is a lipoate auxotroph and must scavenge this critical cofactor, using lipoate ligases to facilitate attachment of the lipoyl moiety to metabolic enzyme complexes. Although the L. monocytogenes genome encodes two putative lipoate ligases, LplA1 and LplA2, intracellular replication and virulence require only LplA1. Here we show that LplA1 enables utilization of host-derived lipoyl peptides by L. monocytogenes . LplA1 is dispensable for growth in the presence of free lipoate, but necessary for growth on low concentrations of mammalian lipoyl peptides. Furthermore, we demonstrate that the intracellular growth defect of the δ lplA1 mutant is rescued by addition of exogenous lipoic acid to host cells, suggesting that L. monocytogenes dependence on LplA1 is dictated by limiting concentrations of available host lipoyl substrates. Thus, the ability of L. monocytogenes and other intracellular pathogens to efficiently use host lipoyl peptides as a source of lipoate may be a requisite adaptation for life within the mammalian cell.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72528/1/MMI+5956+Supp.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/72528/2/j.1365-2958.2007.05956.x.pd

The impact of a residential camp on grandchildren raised by grandparents: Grandparents’ perspectives

This research aimed to investigate grandparents’ perspectives on the impact of Leadership and Respite Camps, designed for children being raised by their grandparents, on their grandchildren. In-depth interviews were conducted with 34 grandparents whose grandchildren had participated in 1 of 3 camps held between September 2018 and January 2019, in Perth and the south-west of Western Australia. Findings highlighted how grandcarers’ perceived the camps created unique opportunities for grandchildren to share their experiences in a safe and supportive environment. Grandparents reported significant psychosocial benefits to their grandchild, including feeling they fitted in with their peers and were not alone in experiencing a difficult childhood and adolescence; gaining perspective on their situation and developing a new appreciation for their grandparents; being able to emotionally ‘unblock’ traumatic memories through the sharing of experiences in a safe and supportive camp environment; developing resilience, confidence and self-esteem through participation in challenging activities; and making new friendships. This research provides strong evidence that Leadership and Respite Camps designed for grandchildren being raised by their grandparents deliver significant psychosocial benefits to grandchildren, and offers a solid foundation to advocate for regular camps to address the needs of grandparent-led families

Peptidoglycan hydrolysis is required for assembly and activity of the transenvelope secretion complex during sporulation inBacillus subtilis

Sporulating Bacillus subtilis cells assemble a transenvelope secretion complex that connects the mother cell and developing spore. The forespore protein SpoIIQ and the mother-cell protein SpoIIIAH interact across the double membrane septum and are thought to assemble into a channel that serves as the basement layer of this specialized secretion system. SpoIIQ is absolutely required to recruit SpoIIIAH to the sporulation septum on the mother-cell side, however the mechanism by which SpoIIQ is localized has been unclear. Here, we show that SpoIIQ localization requires its partner protein SpoIIIAH and degradation of the septal peptidoglycan (PG) by the two cell wall hydrolases SpoIID and SpoIIP. Our data suggest that PG degradation enables a second mother-cell-produced protein to interact with SpoIIQ. Cells in which both mother-cell anchoring mechanisms have been disabled have a synergistic sporulation defect suggesting that both localization factors function in the secretion complex. Finally, we show that septal PG degradation is critical for the assembly of an active complex. Altogether, these results suggest that the specialized secretion system that links the mother cell and forespore has a complexity approaching those found in Gram-negative bacteria and reveal that the sporulating cell must overcome similar challenges in assembling a transenvelope complex

Responsiveness and interpretation of a quality of life questionnaire specific to upper gastrointestinal disorders.

BACKGROUND AND AIMS: The Patient Assessment of Upper Gastrointestinal Disorders-Quality of Life (PAGI-QOL) has been developed and validated to assess quality of life in gastroesophageal reflux disease, dyspepsia, and gastroparesis. The aim of this work was to assess responsiveness of the PAGI-QOL to clinical changes and provide guidance for the interpretation of score changes. METHODS: The analysis was based on 2 observational multicenter, longitudinal, 8-week observation studies, one in the United States and one in 5 European countries. The Overall Treatment Effect scale completed by patients and clinicians at 8 weeks was used to define groups of improved, worsened, and stable patients. Responsiveness was assessed by describing the change in PAGI-QOL scores for each of these groups, comparing these changes over time, and calculating effect sizes and standardized response means. These data were used to define the minimal clinically important difference. RESULTS: A total of 1736 patients with upper gastrointestinal disorders were analyzed. High sensitivity to change over time was demonstrated, with effect sizes and standardized response means in improved patients for the PAGI-QOL total score ranging from 0.79-1.41. A change of 0.4 for the PAGI-QOL total score might be considered as the minimal clinically important difference when comparing pretreatment and post-treatment PAGI-QOL total scores. CONCLUSIONS: The PAGI-QOL questionnaire is a responsive and clinically relevant instrument for assessing quality of life in patients with upper gastrointestinal disorders

GOES ABI Detection of Thin Cirrus over Land

This study develops a new thin cirrus detection algorithm applicable to overland scenes. The methodology builds from a previously developed overwater algorithm, which makes use of the Geostationary Operational Environmental Satellite 16 (GOES-16) Advanced Baseline Imager (ABI) channel 4 radiance (1.378-μm “cirrus” band). Calibration of this algorithm is based on coincident Cloud–Aerosol Lidar with Orthogonal Polarization (CALIOP) cloud profiles. Emphasis is placed on rejection of false detections that are more common in overland scenes. Clear-sky false alarm rates over land are examined as a function of precipitable water vapor (PWV), showing that nearly all pixels having a PWV of <0.4 cm produce false alarms. Enforcing an above-cloud PWV minimum threshold of ∼1 cm ensures that most low-/midlevel clouds are not misclassified as cirrus by the algorithm. Pixel-filtering based on the total column PWV and the PWV for a layer between the top of the atmosphere (TOA) and a predetermined altitude H removes significant land surface and low-/midlevel cloud false alarms from the overall sample while preserving over 80% of valid cirrus pixels. Additionally, the use of an aggressive PWV layer threshold preferentially removes noncirrus pixels such that the remaining sample is composed of nearly 70% cirrus pixels, at the cost of a much-reduced overall sample size. This study shows that lower-tropospheric clouds are a much more significant source of uncertainty in cirrus detection than the land surface. © 2022 American Meteorological Society.6 month embargo; online publication: 21 September 2022This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Cross-cultural development and validation of a patient self-administered questionnaire to assess quality of life in upper gastrointestinal disorders: the PAGI-QOL.

OBJECTIVE: Summarize the Patient Assessment of Upper GastroIntestinal Disorders-Quality of Life (PAGI-QOL) development and provide results on its reliability and validity from the international psychometric validation in dyspepsia, GastroEsophageal Reflux Disease (GERD), and gastroparesis. METHODS: Subjects completed the pilot PAGI-QOL at baseline and 8 weeks; and a subsample also at 2 weeks. Other assessments were: Patient Assessment of Upper Gastrointestinal Disorders-Symptom Severity Index, SF-36, number of disability days. RESULTS: 1736 patients completed the PAGI-QOL at baseline. The questionnaire was reduced, producing a 30-item final version covering five domains: Daily Activities, Clothing, Diet and Food Habits, Relationship (REL), and Psychological Well-Being and Distress. Internal consistency was excellent (Cronbach's alpha range: 0.83-0.96). Test-retest reproducibility was good: intraclass correlations coefficients were over 0.70 except for the REL scale (0.61). Concurrent validity between the PAGI-QOL total score and all SF-36 subscale scores was good with moderate (0.52) to strong (0.72) correlations. PAGI-QOL scores showed excellent discriminant properties: patients who had spent some days in bed, had missed some days at work, and were kept from usual activities had much lower PAGI-QOL scores than those who did not (p &lt; 0.0001). CONCLUSION: The PAGI-QOL is a valid and reliable instrument assessing quality of life in patients with dyspepsia, GERD, or gastroparesis