Transposon Mutagenesis Identification of Polymicrobial Interaction Mechanisms Between Prokaryotic and Eukaryotic Microorganisms

Antibiotic resistance occurs when bacteria change in response to selective pressures induced by antibiotics, which has become a major concern worldwide and one of the biggest threats to global health. Antibiotic resistance can occur naturally, but the misuse and overuse of antibiotics is accelerating the process. One way to combat this process is to understand the different relationships between microbes, also known as polymicrobial interactions. Bacteria can interact with one another synergistically or antagonistically and understanding the mechanisms behind these interactions can lead to the discovery of new therapeutics or targets to fight and kill pathogenic microbes. The rarely pathogenic Gram-negative bacterium, Alcaligenes faecalis, has previously been shown in our lab as playing an important role in potentially fighting antibiotic and antifungal resistance due to its competitiveness during polymicrobial interaction. Our research has found that A. faecalis kills Bacillus cereus, Staphylococcus aureus, and Candida albicans. This is a unique characteristic as these targets encompass both prokaryotic (bacteria) and eukaryotic (fungi) microbes. These three species are known to cause numerous infections in humans and have increased cases of antibiotic and antifungal resistance. In the present study, we investigated the genetic elements A. faecalis utilizes to inhibit growth when interacting with B. cereus, S. aureus, and C. albicans. Transposon mutagenesis was performed to create a genetic library of A. faecalis loss-of-function mutants. These strains were then screened against all three microorganisms to determine which mutants no longer inhibited growth. The mutants that lacked zones-of-inhibition were sequenced to determine the gene that had been interrupted. BLAST analysis of these sequences identified a MFS transporter, a 2FE-2S iron sulfur binding protein, a mechanosensitive ion channel, and a glucose-6-phosphate isomerase as instrumental in this inhibitory mechanism. Results from this research study can be used to further study polymicrobial interactions and potentially discover new therapeutics to combat antimicrobial resistance

The survival advantage of pancreas after kidney transplant

Patient survival after pancreas after kidney transplant (PAK) has been reported to be inferior to patient survival after simultaneous pancreas–kidney transplant (SPK). The authors examine national data to further explore allograft (kidney and pancreas) and patient survival after PAK. Kaplan–Meier and Cox proportional hazard models were used to analyze Organ Procurement and Transplantation Network data from 1995 to 2010. The analysis compared PAK and SPK candidates and recipients. Kaplan–Meier analysis results showed that PAK after either a living or a deceased donor kidney transplant is associated with increased kidney graft survival compared with recipients with type 1 diabetes who received only a kidney. The best kidney allograft survival was for patients who received a living donor kidney followed by PAK. Receiving a living donor kidney was associated with increased pancreas allograft survival compared with receiving a deceased donor kidney. PAK transplant recipients who receive both organs have a survival advantage compared with uremic candidates who receive neither (SPK waitlist). Compared with uremic diabetic waitlist patients, SPK and PAK recipients showed similar overall patient survival. Successful PAK offers a survival advantage compared with receiving neither a kidney nor a pancreas transplant. These data also suggest that receiving a pancreas (after kidney) transplant may have a protective effect on the kidney allograft

A cyclic peptide inhibitor of HIF-1 heterodimerization that inhibits hypoxia signaling in cancer cells

Hypoxia inducible factor-1 (HIF-1) is a heterodimeric transcription factor that acts as the master regulator of cellular response to reduced oxygen levels, thus playing a key role in the adaptation, survival and progression of tumors. Here we report cyclo-CLLFVY, identified from a library of 3.2 million cyclic hexapeptides using a genetically encoded high-throughput screening platform, as an inhibitor of the HIF-1α/HIF-1β protein-protein interaction in vitro and in cells. The identified compound inhibits HIF-1 dimerization and transcription activity by binding to the PAS-B domain of HIF-1α, reducing HIF-1-mediated hypoxia response signaling in a variety of cell lines, without affecting the function of the closely related HIF-2 isoform. The reported cyclic peptide demonstrates the utility of our high-throughput screening platform for the identification of protein-protein interaction inhibitors, and forms the starting point for the development of HIF-1 targeted cancer therapeutics

Undiagnosed dementia in primary care: A record linkage study

BackgroundThe number of people living with dementia is greater than the number with a diagnosis of dementia recorded in primary care. This suggests that a significant number are living with dementia that is undiagnosed. Little is known about this group and there is little quantitative evidence regarding the consequences of diagnosis for people with dementia.ObjectivesThe aims of this study were to (1) describe the population meeting the criteria for dementia but without diagnosis, (2) identify predictors of being diagnosed and (3) estimate the effect of diagnosis on mortality, move to residential care, social participation and well-being.DesignA record linkage study of a subsample of participants (n = 598) from the Cognitive Function and Ageing Study II (CFAS II) (n = 7796), an existing cohort study of the population of England aged ≥ 65 years, with standardised validated assessment of dementia and consent to access medical records.Data sourcesData on dementia diagnoses from each participant’s primary care record and covariate and outcome data from CFAS II.SettingA population-representative cohort of people aged ≥ 65 years from three regions of England between 2008 and 2011.ParticipantsA total of 598 CFAS II participants, which included all those with dementia who consented to medical record linkage (n = 449) and a stratified sample without dementia (n = 149).Main outcome measuresThe main outcome was presence of a diagnosis of dementia in each participant’s primary care record at the time of their CFAS II assessment(s). Other outcomes were date of death, cognitive performance scores, move to residential care, hospital stays and social participation.ResultsAmong people with dementia, the proportion with a diagnosis in primary care was 34% in 2008–11 and 44% in 2011–13. In both periods, a further 21% had a record of a concern or a referral but no diagnosis. The likelihood of having a recorded diagnosis increased with severity of impairment in memory and orientation, but not with other cognitive impairment. In multivariable analysis, those aged ≥ 90 years and those age

Flexible and Mindful Self-Tracking: Design Implications from Paper Bullet Journals

Digital self-tracking technologies offer many potential benefits over self-tracking with paper notebooks. However, they are often too rigid to support people’s practical and emotional needs in everyday settings. To inform the design of more flexible self-tracking tools, we examine bullet journaling: an analogue and customisable approach for logging and reflecting on everyday life. Analysing a corpus of paper bullet journal photos and related conversations on Instagram, we found that individuals extended and adapted bullet journaling systems to their changing practical and emotional needs through: (1) creating and combining personally meaningful visualisations of different types of trackers, such as habit, mood, and symptom trackers; (2) engaging in mindful reflective thinking through design practices and self-reflective strategies; and (3) posting photos of paper journals online to become part of a selftracking culture of sharing and learning. We outline two interrelated design directions for flexible and mindful selftracking: digitally extending analogue self-tracking and supporting digital self-tracking as a mindful design practice

Broadened Allocation of Pancreas Transplants Across Compatible ABO Blood Types

Background Current Organ Procurement and Transplantation Network (OPTN) policy restricts certain blood type-compatible simultaneous pancreas and kidney (SPK) transplants. Using the Kidney Pancreas Simulated Allocation Model, we examined the effects of 5 alternative allocation sequences that allowed all clinically compatible ABO transplants. Methods The study cohort included kidney (KI), SPK, and pancreas alone (PA) candidates waiting for transplant for at least 1 day between January 1, 2010, and December 31, 2010 (full cohort), and kidneys and pancreata recovered for transplant during the same period. Additionally, because the waiting list has shrunk since 2010, the study population was reduced by random sampling to match the volume of the 2015 waiting list (reduced cohort). Results Compared with the current allocation sequence, R4 and R5 both showed an increase in SPK transplants, a nearly corresponding decrease in KI transplants, and virtually no change in PA transplants. Life-years from transplant and median years of benefit also increased. The distribution of transplants by blood type changed, with more ABO:A, B, and AB transplants performed, and fewer ABO:O across all transplant types (KI, SPK, PA), with the relative percent changes largest for SPK. Discussion Broadened ABO compatibility allowances primarily benefitted SPK ABO:A and AB candidates. ABO:O candidates saw potentially reduced access to transplant. The simulation results suggest that modifying the current allocation sequence to incorporate broadened ABO compatibility can result in an increase in annual SPK transplants

Choreographic Process and Performance

“Nerves” (choreographed by Kendra Fox) is an original dance composition created for five dancers that explores musicality, partnering and the artistry of each dancer. Created for an open space, the work can be performed on a stage or in a site-specific location. The piece formed as an investigation of space, shape and time, and was propelled forward to performance with the support of the Baroni Family Dance Entrepreneurship Grant. “Nerves” was first showcased at the American College Dance Association’s regional festival at Boston University in February 2018 as a culmination and synthesis of movement principles and concepts in choreographic form. Through continued investigation and exploration of physicality and relationships between the dancers, the piece has taken on its’ current form. The newest version of the work will be performed under a new title at the Spring 2018 Contemporary Dance Ensemble with PSU Choirs Collaborative Showcase

Acceleration of hippocampal atrophy rates in asymptomatic amyloidosis.

Increased rates of brain atrophy measured from serial magnetic resonance imaging precede symptom onset in Alzheimer's disease and may be useful outcome measures for prodromal clinical trials. Appropriate trial design requires a detailed understanding of the relationships between β-amyloid load and accumulation, and rate of brain change at this stage of the disease. Fifty-two healthy individuals (72.3 ± 6.9 years) from Australian Imaging, Biomarkers and Lifestyle Study of Aging had serial (0, 18 m, 36 m) magnetic resonance imaging, (0, 18 m) Pittsburgh compound B positron emission tomography, and clinical assessments. We calculated rates of whole brain and hippocampal atrophy, ventricular enlargement, amyloid accumulation, and cognitive decline. Over 3 years, rates of whole brain atrophy (p < 0.001), left and right hippocampal atrophy (p = 0.001, p = 0.023), and ventricular expansion (p < 0.001) were associated with baseline β-amyloid load. Whole brain atrophy rates were also independently associated with β-amyloid accumulation over the first 18 months (p = 0.003). Acceleration of left hippocampal atrophy rate was associated with baseline β-amyloid load across the cohort (p < 0.02). We provide evidence that rates of atrophy are associated with both baseline β-amyloid load and accumulation, and that there is presymptomatic, amyloid-mediated acceleration of hippocampal atrophy. Clinical trials using rate of hippocampal atrophy as an outcome measure should not assume linear decline in the presymptomatic phase

Narratives of self and identity in women's prisons: stigma and the struggle for self-definition in penal regimes

A concern with questions of selfhood and identity has been central to penal practices in women's prisons, and to the sociology of women's imprisonment. Studies of women's prisons have remained preoccupied with women prisoners’ social identities, and their apparent tendency to adapt to imprisonment through relationships. This article explores the narratives of women in two English prisons to demonstrate the importance of the self as a site of meaning for prisoners and the central place of identity in micro-level power negotiations in prisons

The Grizzly, September 11, 2008

Republican National Convention Rallies Supporters • Studies Show Half of College Students Contemplate Suicide • Start of New Now on View Art Film Festival • Science, Strife and Speculation of Hurricane Season \u2708 • UC Senior Implements First Ever Bike Share Program • Cinematic Guild Brings Creative Filmography to Campus • Introducing Cassandra Aguilar • The Grizzly Catches Up with Dean Nolan • Celebrating Herencia Latina Fall Events • Molly Maguire\u27s: A Bit O\u27 Irish Spirit • UC Women\u27s Soccer Fights for Another Strong Season • Football\u27s New Motto: No Interceptions, No Exceptionshttps://digitalcommons.ursinus.edu/grizzlynews/1767/thumbnail.jp