bluuebunny/crossref_metadata_2025 huggingface dataset:
0978 Snoo: A Wellness Device To Improve Infant Sleep
Authors: Okun M , Karp H , Balasubramanian S
Published: May 2020

Introduction

One of the primary contributors to new parent sleep deprivation is infant sleep disturbances. Evidence shows that increasing sleep in infants has a positive effect on parental sleep. SNOO, a wellness device, was developed to provide sleeping babies 3 of the 5 S’s (safe swaddling, sound and swinging) in a response fashion (increasing levels of motion and white noise if babies cry) to soothe crying and improve infant sleep.

Methods

The current study compares infant sleep derived from SNOO to a reference group of a compilation of 13 peer reviewed studies of normative sleep data on sleep in traditional cribs/bassinets. Participants were 7157 babies using SNOO beginning within one week of birth and for at least 6 hours per night for 6 months. Sleep metrics calculated on a day to day basis include Longest Sleep Period: Maximum uninterrupted sleep at night (7 PM - 7 AM); Total Sleep Duration: Total time spent sleeping at night (7 PM - 7 AM); and Night Awakenings: Number of times parents attended to the baby (10 PM - 6 AM).

Results

Improvement in the longest sleep duration varied with age. Across the 6 month collection period, longest sleep period increased between 42 minutes - 2 hours 0 minutes and total sleep duration increased between 33 minutes - 1 hour 24 minutes. Babies in SNOO averaged one less waking per night compared to the reference population (1.09±.89 vs 1.89 ±1.1). The improvements in all three sleep metrics were statistically significant with p’s < 0.0005 across all ages from birth to 6 months.

Conclusion

This large-scale study suggests that infant sleep can be significantly improved by using SNOO compared to babies who slept in normal cribs or bassinets. We believe there are myriad areas of public health that may be positively impacted as a result of this significant level of improvement of infant sleep.

Support

Happiest Baby, Inc.
0979 Observational Analysis Of Juvenile Justice Sleep-wake Environment
Authors: Adornetti J P , Carlucci M , Crowley S J , Fleshman C M , Jobe S L , Wolfson A R
Published: May 2020

Introduction

Adolescence is associated with sleep regulatory changes that prompt sleep and circadian timing to shift later (delay). Poor quality, insufficient sleep, and misaligned sleep-wake schedules increase adolescents’ risk for physical and mental health consequences. Little data exists on potential sleep health risks and sleep-wake environments of juvenile justice facilities. This descriptive study examined the sleep-wake environment and daily schedules at juvenile detention and treatment centers in a Mid-Atlantic state.

Methods

Using our Sleep Justice Observational Checklist, researchers recorded number of windows in sleep and non-sleep areas, and number of beds in sleeping quarters. Illuminance was measured with a light meter during the daytime (standing, sitting, etc.) and averaged. Facility-level 24-hour schedules were obtained to determine youth’s daily routines during the observation period.

Results

In comparison to treatment centers, detention centers have earlier lights-on (MDet = 6:07 am, SDDet =:40 vs. MTreat = 6:54 am, SDTreat =:07, p = .04) and lights-off (MDet = 8:42 pm, SDDet =:36 vs. MTreat = 9:06 pm, SDTreat =:19, N.S.) times. Treatment center illuminance levels (M = 296.60 lux, SD = 150.30) were greater (brighter) compared to detention centers (M = 124.00 lux, SD = 60.40, p = .01). Per sleep area, treatment centers had more windows (MTreat = 7.84, SDTreat = 6.70 vs. MDet = 1.73, SDDet = .77, p = .02) and more beds (MTreat = 13.30, SDTreat = 14.00 vs. MDet = 1.46, SDDet = .96, p = .03) than detention centers.

Conclusion

Preliminary results indicate a variation in the sleep-wake environments and daily schedules in this sample of juvenile justice centers. Early lights-on and lights-off times can impose a higher risk for circadian misalignment in adolescents, though schedule consistency may reduce this risk. Ongoing data collection will help to further understand the sleep environment of adolescents in the juvenile justice system.

Support

Kolvenbach Research Grant, Loyola University Maryland
0980 Sleep And Activity Rhythms In Children With Duchenne Muscular Dystrophy
Authors: Hartman A G , Smagula S F , Bendixen R
Published: May 2020

Introduction

Duchenne muscular dystrophy (DMD) is a rare, progressive, neurological disorder with high rates of depression, anxiety, and attention issues. Rest-activity rhythm (RAR) disturbances are also associated with these co-morbidities in other populations. However, RAR patterns and timing have not been explored in DMD and could provide important information regarding mechanisms of sleep in which to intervene. To address this knowledge gap, we used wrist actigraphy to explore the timing of rest-activity rhythms in boys with and without DMD.

Methods

Boys aged 4-15 with DMD (n= 17) and age matched controls (n=17) wore an ActiGraph GT9X for ten consecutive days. We averaged activity counts each hour and computed Cohen’s d effect sizes and t-tests with Benjamini-Hochberg corrections. Extended cosine models were fit to derive RAR measures using custom R code.

Results

An overall delay in RAR timing was found in the DMD group due to three specific, large effect-size differences in RAR patterns. Boys with DMD were: (1) less active at 8AM and 9AM (e.g., at 9AM: d=-0.82, p=0.02, FDR=0.14); (2) more active from 10PM-midnight (e.g., at 11PM: d=1.1, p=0.003, FDR=0.07) and (3) more active at 4AM (d=0.74, p=0.04, FDR=0.14). Extended-cosine modeling showed that, while amplitude of activity was similar across groups (d=-0.29, p= 0.41), boys with DMD had later morning activity onset (d= 0.70, p= 0.05), later peak activity timing (d= 0.86, p= 0.02), and later evening activity offset (d= 0.96, p= 0.01).

Conclusion

A significant delay in activity was evident in the DMD group compared with controls. Although the mechanism causing this shift is currently unknown, delayed chronotypes have been linked to poor health outcomes like depression and anxiety in other populations. Further research should explore the causes and consequences of the RAR timing delays we observed and inform future care.

Support

Foundation to Eradicate Duchenne, PI: Bendixen, 1/1/2017-12/31/2019.
0997 The Sleep Disturbance Scale For Children In Youth With Tourette’S Disorder
Authors: Montalbano G E , Rozenman M , Peris T , Tan P , Piacentini J , Ricketts E
Published: May 2020

Introduction

Sleep disturbance is common in youth with Persistent Tic Disorders (PTDs), including Tourette’s Disorder. However, studies elucidating the nature of sleep problems in PTDs are limited. The present study examines the types of sleep disturbance present in youth with PTDs relative to healthy controls, and investigates the relationship between sleep disturbance and tic severity.

Methods

Participants were 56 youth ages 8 to 17 (M=11.9, SD=2.86), including individuals with PTDs (n=27), and healthy controls (n=29). An interviewer evaluated psychiatric diagnosis using the Anxiety Disorders Interview Schedule, and tic severity using the Yale Global Tic Severity Scale (YGTSS). Parents rated sleep using the Sleep Disturbance Scale for Children (SDSC), and tic severity using the Parent Tic Questionnaire (PTQ). Independent-samples t-tests and bivariate correlations were performed.

Results

Higher SDSC Total scores, t(30)=-3.74, p=.001) were found in youth with PTDs relative to healthy controls. Youth with PTDs endorsed elevated sleep disturbance with respect to: Disorders of Initiating and Maintaining Sleep, t(35)=-2.43, p=.02), Sleep-Wake Transition Disorders, t(37)=-3.04, p=.004), and Disorders of Excessive Somnolence, t(33)=-2.36, p=.02). No significant group differenceswere shown for Sleep Breathing Disorders, Disorders of Arousal, and Sleep Hyperhydrosis. There was a positive association between SDSC Total scores and YGTSS Total (p=.01, r=.56) and YGTSS Impairment scores (p= .03, r=.33). Finally, there was a positive relationship between SDSC Total and PTQ Total scores (p=.01, r=.61).

Conclusion

Findings suggest youth with PTDs are more likely to experience sleep disturbance than healthy children, particularly difficulties with sleep initiation and maintenance, abnormal movements during sleep, and daytime sleepiness. Further, there is a relationship between sleep disturbance and tic severity. Findings highlight the need for sleep screening and targeted sleep intervention in youth with PTDs.

Support

N/A
Average daily gain divergence in beef steers is associated with altered plasma metabolome and whole blood immune-related gene expression
Authors: Ogunade Ibukun M , McCoun Megan
Published: May 2020

We evaluated the plasma amine/phenol- and carbonyl-metabolome and whole-blood immune gene expression profiles in beef steers with divergent average daily gain (ADG). Forty-eight Angus crossbred beef steers (21 days postweaning; 210 ± 8.5 kg of body weight) were fed the same total mixed ration ad libitum for 42 days with free access to water. After 42 days of feeding, the steers were divided into two groups of lowest (LF: n = 8) and highest ADG (HF: n = 8). Blood samples were taken from all steers. The blood samples from LF and HF steers were used for further analysis. A subsample of the whole blood was immediately transferred into RNA-protect tubes for RNA extraction and messenger RNA expressions of 84 genes involved in innate and adaptive immune responses. Another subsample of the whole blood was immediately centrifuged to harvest the plasma for subsequent metabolome analysis. The average daily dry matter intake of the steers in LF and HF was 6.08 kg ± 0.57 and 6.04 kg ± 0.42, respectively, and was similar between the two groups (P = 0.72). The ADG (1.09 kg ± 0.13) of LF was lower (P = 0.01) than that of HF (1.63 kg ± 0.20). The expressions of 10 immune-related genes were upregulated (FC ≥ 1.2; P ≤ 0.05) in HF steers; these genes were involved in viral pathogen recognition and eradication, defense against intracellular and extracellular pathogens and parasites, and immune response homeostasis. A total number of 42 carbonyl-containing metabolites and 229 amine/phenol-containing metabolites were identified in the plasma samples of both groups. No alteration in carbonyl-metabolome was detected. Ten metabolites with immunomodulatory, anti-inflammatory, and reactive oxygen-scavenging properties were greater (FDR ≤ 0.05) in HF steers, whereas eight metabolites including arginine, phenylalanine, guanidoacetic acid, and aspartyl-threonine were greater in LF steers. This study demonstrated that beef steers with divergent ADG had altered plasma amine/phenol metabolome and immune-related gene expressions in the blood. Notably, plasma metabolites and immune-related genes of great health benefits were greater in steers with high ADG.
Symptoms and Critical Illness Among Obstetric Patients With Coronavirus Disease 2019 (COVID-19) Infection
Authors: Andrikopoulou Maria , Madden Nigel , Wen Timothy , Aubey Janice J. , Aziz Aleha , Baptiste Caitlin D. , Breslin Noelle , D'Alton Mary E. , Fuchs Karin M. , Goffman Dena , Gyamfi-Bannerman Cynthia , Matseoane-Peterssen Dara N. , Miller Russell S. , Sheen Jean-Ju , Simpson Lynn L. , Sutton Desmond , Zork Noelia , Friedman Alexander M.
Published: May 2020

OBJECTIVE:

To characterize symptoms and disease severity among pregnant women with coronavirus disease 2019 (COVID-19) infection, along with laboratory findings, imaging, and clinical outcomes.

METHODS:

Pregnant women with COVID-19 infection were identified at two affiliated hospitals in New York City from March 13 to April 19, 2020, for this case series study. Women were diagnosed with COVID-19 infection based on either universal testing on admission or testing because of COVID-19–related symptoms. Disease was classified as either 1) asymptomatic or mild or 2) moderate or severe based on dyspnea, tachypnea, or hypoxia. Clinical and demographic risk factors for moderate or severe disease were analyzed and calculated as odds ratios (ORs) with 95% CIs. Laboratory findings and associated symptoms were compared between those with mild or asymptomatic and moderate or severe disease. The clinical courses and associated complications of women hospitalized with moderate and severe disease are described.

RESULTS:

Of 158 pregnant women with COVID-19 infection, 124 (78%) had mild or asymptomatic disease and 34 (22%) had moderate or severe disease. Of 15 hospitalized women with moderate or severe disease, 10 received respiratory support with supplemental oxygen and one required intubation. Women with moderate or severe disease had a higher likelihood of having an underlying medical comorbidity (50% vs 27%, OR 2.76, 95% CI 1.26−6.02). Asthma was more common among those with moderate or severe disease (24% vs 8%, OR 3.51, 95% CI 1.26−9.75). Women with moderate or severe disease were significantly more likely to have leukopenia and elevated aspartate transaminase and ferritin. Women with moderate or severe disease were at significantly higher risk for cough and chest pain and pressure. Nine women received ICU or step-down–level care, including four for 9 days or longer. Two women underwent preterm delivery because their clinical status deteriorated.

CONCLUSION:

One in five pregnant women who contracted COVID-19 infection developed moderate or severe disease, including a small proportion with prolonged critical illness who received ICU or step-down–level care.
IDIOPATHIC PENETRATION OF CILIA INTO THE POSTERIOR SEGMENT PRESENTING AS SECTORAL SCLERITIS WITH PROGRESSIVE INTRAOCULAR INFLAMMATION
Authors: Saraf Steven S. , Leveque Thellea K. , Kim Joon-Bom , Nash Robert W. , Pepple Kathryn L. , Olmos de Koo Lisa C.
Published: May 2020

Purpose:

To report two cases of idiopathic intraocular cilia presenting as sectoral scleritis with progressive intraocular inflammation.

Methods:

Both patients were treated with intravitreal antibiotics and underwent pars plana vitrectomy where the cilia were removed and identified on histopathology.

Results:

One patient developed a retinal detachment while being treated for presumed endophthalmitis. The intraocular cilium was discovered during pars plana vitrectomy. In the second case, the cilium was detected on dilated fundus exam and was believed to be the cause of the patient's scleritis and vitritis. Therapeutic vitrectomy was performed. In both cases, the cilia were positively identified on histopathology.

Conclusion:

Idiopathic intraocular penetration of cilia should be considered in the differential diagnosis of sectoral scleritis with progressive intraocular inflammation.
Magnetic Resonance Imaging for Glaucoma Evaluation
Authors: Gracitelli Carolina P.B. , Gerente Vanessa M. , Furlanetto Rafael L. , Amaro Edson , Paranhos Augusto
Published: May 2020

The damage caused by glaucoma has been extensively evaluated at the level of the retina and optic nerve head. Many advances have been shown in this field in the last decades. Recent studies have also proved degenerative changes in the brain involving the intracranial optic nerve, lateral geniculate nucleus, and visual cortex. Moreover, these brain abnormalities are also correlated with clinical, optic nerve head, and visual field findings. In this review, we critically evaluate the existing literature studying the use of magnetic resonance imaging in glaucoma, and we discuss issues related to how magnetic resonance imaging results should be incorporated into our clinical practice.
Outcomes of Circumferential Trabeculotomy and Converted 180-Degree Traditional Trabeculotomy in Patients With Neonatal-onset Primary Congenital Glaucoma
Authors: Aktas Zeynep , Ucgul Ahmet Y. , Atalay Hatice T.
Published: May 2020

Précis:

The present study demonstrates that the surgical success rate of circumferential trabeculotomy is 64.7% according to target intraocular pressure (IOP) ≤21 mm Hg and ≥30% reduction from baseline in patients with neonatal-onset primary congenital glaucoma (PCG), with an average follow-up of 35.1 months.

Purpose:

The aim of the study was to evaluate the surgical success rate and applicability of circumferential trabeculotomy compared with converted traditional trabeculotomy in patients with neonatal-onset PCG in Turkey.

Patients and Methods:

A retrospective study enrolled 42 eyes of 42 patients with an average age of 34.0±6.7 (14 to 59) days at the time of the surgery, who underwent 5/0 prolene suture-assisted circumferential trabeculotomy or rigid probe-assisted traditional trabeculotomy for the treatment of neonatal-onset PCG. IOP at baseline, 1st, 2nd, 3rd, 6th, 9th, 12th, 24th, and 36th months of follow-up, need of glaucoma eye drop, need of further glaucoma surgery, cup to disc ratio, axial length, corneal diameters, and presence of corneal clouding were recorded. Surgical success was defined as IOP <21 mm Hg and ≥30% reduction from baseline without any further glaucoma surgery.

Results:

Seventeen eyes underwent circumferential trabeculotomy and 25 eyes with a failure in completing circumferential trabeculotomy underwent traditional trabeculotomy. The applicability rate of circumferential trabeculotomy was 40.4%. The mean preoperative IOP value was 33.2±7.6 mm Hg. The average follow-up time was 35.1±21.7 (12 to 95) months. Surgical success rates of circumferential trabeculotomy at the first, second, and third year of follow-up were 70.6%, 64.7%, and 64.7%, respectively. Surgical success rates of traditional trabeculotomy at the first, second, and third year of follow-up were 60%, 48%, and 44%, respectively.

Conclusions:

Circumferential trabeculotomy seems to be a safer and more successful procedure than traditional trabeculotomy for the treatment of neonatal-onset PCG. Unlike the traditional procedure, the IOP-lowering effect of circumferential trabeculotomy could be maintained up to ~36 months.
Novel Magnetic Resonance Late Gadolinium Enhancement With Fixed Short Inversion Time in Ischemic Myocardial Scars
Authors: Polacin Malgorzata , Gastl Mareike , Kapos Ioannis , Eberhard Matthias , Weber Lucas , Gotschy Alexander , von Spiczak Jochen , Kozerke Sebastian , Alkadhi Hatem , Manka Robert
Published: May 2020

Aims

Late gadolinium enhancement (LGE) visualizes scar tissue after myocardial infarction. However, in clinically used LGE sequences, subendocardial infarcts can be missed due to low contrast between blood pool and subendocardium. The purpose of his study was to compare scar visibility in a novel 3-dimensional (3D) single breath-hold inversion recovery sequence with fixed, short inversion time (TI = 100 milliseconds) (short LGE) and standard 3D LGE imaging with individually adjusted TI (LGE).

Methods

Short LGE and LGE (both sequences with the same settings: spatial resolution, 1.2 × 1.2 mm2; slice thickness, 8 mm; field of view, 350 × 350 mm2; single breath-hold) were acquired in 64 patients with previous MI (13 female; mean age, 57 ± 19 years) at 1.5 T. Inversion time was set to 100 milliseconds in short LGE and adjusted individually in LGE according to the Look-Locker sequence. Two independent readers evaluated 1088 segments (17-segment model), identified infarcted segments, and categorized scar visibility (5 = excellent, 1 = poor scar visibility) and scar transmurality (4 = transmural, 0 = no scar) using a 5-point Likert scale. Signal intensity ratios between short LGE and LGE for scar and blood pool, for scar and remote myocardium, and for remote myocardium and blood pool were calculated.

Results

Short LGE showed 197 infarcted segments out of 1088 (18.1%); LGE revealed 191 segments (17.6%). Short LGE with dark scar and bright blood pool demonstrated better overall scar visibility, especially in subendocardially infarcted segments compared with LGE (4.2 vs 3.0, 5 = excellent visibility;P= 0.01). Signal intensity ratios for short LGE relative to LGE were 1.42 for scar/blood pool, 0.8 for scar/remote myocardium, and 0.22 for remote myocardium/blood.

Overall transmurality was not rated higher in short LGE compared with LGE (P= 0.8). More fibrous tissue and total fibrous percentage (P= 0.04) were measured in short LGE compared with LGE, whereas myocardial mass was not significantly different (P= 0.5). Acquisition time was similar between short LGE and LGE (26 ± 4 seconds vs 25 ± 9 seconds,P= 0.7).

Conclusions

Short LGE is a fast, single breath-hold 3D LGE sequence with no need for myocardial nulling due to fixed inversion time with improved scar visibility, especially in subendocardial infarcts.
Sodium-glucose co-transporter 2 inhibitors and diabetic retinopathy: insights into preservation of sight and looking beyond
Authors: Lahoti Sejal , Nashawi Mouhamed , Sheikh Omar , Massop David , Mir Mahnoor , Chilton Robert
Published: May 2020

Sodium-glucose co-transporter 2 Inhibitors (SGLT2i) were initially developed as therapeutic options for patients with type 2 diabetes mellitus (T2DM). Recently, randomized clinical trials have investigated their effects in cardiorenal protection through major adverse cardiovascular event reduction and reductions in diabetic nephropathy. While multiple mechanisms are proposed for this protection, microvascular protection is the primary component of their efficacy. While not primarily emphasized in clinical trials, evidence in other studies suggests that SGLT2i may confer retinoprotective effects via some of the same mechanisms in the aforementioned cardiorenal trials. Diabetic patients are susceptible to vision loss with chronic hyperglycemia promoting inflammation, edema, and retinal pathological changes. Targeting these pathways via SGLT2i may represent opportunities for providers to decrease retinopathy in high-risk T2DM patients, reduce disease progression, and lower drug burden in diabetic retinopathy patients. Further comprehensive clinical trials investigating these associations are needed to establish the potential retinoprotective effects of SGLT2i.
Sphingomonas suaedae sp. nov., a chitin-degrading strain isolated from rhizosphere soil of Suaeda salsa
Authors: Zhang Hui , Xu Lian , Zhang Jin-Xin , Sun Ji-Quan
Published: May 2020

A Gram-stain-negative, aerobic, chitin-degrading, motile bacterial strain with a single polar flagellum, designated XS-10T, was isolated from saline soil sampled from the rhizosphere of Suaeda salsa, Tumd Right Banner, Inner Mongolia, PR China. Strain XS-10T grew at 10–40 °C (optimum, 35 °C), pH 5.0–9.0 (optimum, pH 8.0) and 0–12.5% NaCl (optimum 2.0 %). The phylogenetic analysis based on both the 16S rRNA gene and the phylogenomic tree revealed that strain XS-10T formed a clade with

Sphingomonas turrisvirgatae

MCT13T and

Sphingomonas koreensis

JSS-26T, sharing 98.4 and 97.5 % 16S rRNA gene similarities to

S. koreensis

JSS-26T and

S. turrisvirgatae

MCT13T, respectively. Spermidine and Q-10 were the major polyamine and the major respiratory quinone, respectively. The major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, sphingoglycolipid, two unidentified lipids and an unidentified aminophospholipid. The major fatty acids were summed feature 8 (C18 : 1
 ω7c and/or C18 : 1
 ω6c), C16 : 0 and C17 : 1
 ω6c. The genome of strain XS-10T consisted of a 4 154 291 bp chromosome with a DNA G+C content of 65.5 mol%. The average nucleotide identity, average amino acid identity and digital DNA–DNA hybridization values of strain XS-10T with

S. turrisvirgatae

MCT13T and

S. koreensis

JSS-26T were 77.8 and 78.6 %, 75.9 and 76.3 %, and 22.0 and 22.9 %, respectively. Based on the phylogenetic, phenotypic, and genotypic characteristics, strain XS-10T is considered to represent a novel species of the genus

Sphingomonas

, for which the name Sphingomonas suaedae sp. nov. is proposed. The type strain is XS-10T (=CGMCC 1.17078T=JCM 33850T).
Pseudomonas aeruginosa biofilm formation on endotracheal tubes requires multiple two-component systems
Authors: Badal Divakar , Jayarani Abhijith Vimal , Kollaran Mohammed Ameen , Kumar Aloke , Singh Varsha
Published: May 2020

Introduction.Indwelling medical devices such as endotracheal tubes (ETTs), urinary catheters, vascular access devices, tracheostomies and feeding tubes are often associated with hospital-acquired infections. Bacterial biofilm formed on the ETTs in intubated patients is a significant risk factor associated with ventilator-associated pneumonia.Pseudomonas aeruginosais one of the four frequently encountered bacteria responsible for causing pneumonia, and the biofilm formation on ETTs. However, understanding of biofilm formation on ETT and interventions to prevent biofilm remains lagging. The ability to sense and adapt to external cues contributes to their success. Thus, the biofilm formation is likely to be influenced by the two-component systems (TCSs) that are composed of a membrane-associated sensor kinase and an intracellular response regulator.

Aim.This study aims to establish anin vitromethod to analyse theP. aeruginosabiofilm formation on ETTs, and identify the TCSs that contribute to this process.

Methodology.In total, 112P. aeruginosaPA14 TCS mutants were tested for their ability to form biofilm on ETTs, their effect on quorum sensing (QS) and motility.

Results.Out of 112 TCS mutants studied, 56 had altered biofilm biomass on ETTs. Although the biofilm formation on ETTs is QS-dependent, none of the 56 loci controlled quorum signal. Of these, 18 novel TCSs specific to ETT biofilm were identified, namely, AauS, AgtS, ColR, CopS, CprR, NasT, KdpD, ParS, PmrB, PprA, PvrS, RcsC, PA14_11120, PA14_32580, PA14_45880, PA14_49420, PA14_52240, PA14_70790. The set of 56 included the GacS network, TCS proteins involved in fimbriae synthesis, TCS proteins involved in antimicrobial peptide resistance, and surface-sensing. Additionally, several of the TCS-encoding genes involved in biofilm formation on ETTs were found to be linked to flagellum-dependent swimming motility.

Conclusions.Our study established anin vitromethod for studyingP. aeruginosabiofilm formation on the ETT surfaces. We also identified novel ETT-specific TCSs that could serve as targets to prevent biofilm formation on indwelling devices frequently used in clinical settings.
Prenatal psychosocial stress-induced behavioral and neuroendocrine abnormalities are associated with sex-specific alterations in synaptic transmission and differentially modulated by maternal environment
Authors: Zoubovsky Sandra P. , Williams Michael T. , Hoseus Sarah , Tumukuntala Shivani , Riesenberg Amy , Schulkin Jay , Vorhees Charles V. , Campbell Kenneth , Lim Hee-Woong , Muglia Louis J.
Published: May 2020

Prenatal stress (PS) is associated with increased vulnerability to affective disorders. Transplacental glucocorticoid passage and stress-induced maternal environment alterations are recognized as potential routes of transmission that can fundamentally alter neurodevelopment. However, molecular mechanisms underlying aberrant emotional outcomes or the individual contributions intrauterine stress versus maternal environment play in shaping these mechanisms remain unknown. Here, we report anxiogenic behaviors, anhedonia, and female hypothalamic-pituitary-adrenal axis hyperactivity as a consequence of psychosocial PS in mice. Sex-specific placental responses to stress and evidence of fetal amygdala programming precede these abnormalities. In adult offspring, we observe amygdalar transcriptional changes demonstrating sex-specific dysfunction in synaptic transmission and neurotransmitter systems. We find these abnormalities are primarily driven by in-utero stress exposure. Importantly, maternal care changes postnatally reverse anxiety-related behaviors and partially rescue gene alterations associated with neurotransmission. Our data demonstrate the influence maternal environment exerts in shaping offspring emotional development despite deleterious effects of intrauterine stress.
Inclusion of dimethyl sulfoxide- dissolved protease inhibitor cocktail in the lysis buffer cuts down the number of proteins resolved by two dimensional gel electrophoresis
Authors: Mahesh P.P , Mundayoor Sathish
Published: May 2020

Two dimensional gel electrophoresis (2DE) resolves a mixture of proteins based on both isoelectric point and molecular weight of the individual proteins. Even when we followed a standard protocol for 2DE we got lesser number of proteins focused especially in the basic region of the IPG strip. Since the common troubleshooting measures did not solve the problem we replaced the protease inhibitor cocktail in the lysis buffer with PMSF which resulted in an ideal protein map following 2DE. We also found that the presence of the cocktail results in skewing of the mass spectra of a purified protein which eventually resulted in incorrect identification of the protein by MASCOT search. Later we found that dimethyl sulfoxide, the solvent of protease inhibitor cocktail also resulted in focusing of lesser number of proteins. Addition of 1% dimethyl sulfoxide to bovine serum albumin resulted in lesser sequence coverage for the protein by LC-MS/MS. Also, dimethyl sulfoxide was found to decrease the intensity value of the dominant peptide in a fraction when MALDI-TOF-TOF was done. Even though we do not provide a reason behind our observations, we guess dimethyl sulfoxide might have changed the charge distribution of peptides or proteins resulting in the peculiar observations we had.
Comparative physiology of five tropical montane songbirds reveals differential seasonal acclimatisation and cold adaption
Authors: Jones Samuel E.I. , Suanjak Martin , Tobias Joseph A. , Freeman Robin , Portugal Steven J.
Published: May 2020

The physiology of tropical birds is poorly understood, particularly in how it relates to local climate and changes between seasons. This is particularly true of tropical montane species, which may have sensitive thermal tolerances to local microclimates. We studied metabolic rates (using open flow respirometry), body mass and haemoglobin concentrations of five sedentary Mesoamerican songbirds between the summer and winter at two elevations (1550 m and 1950 m, respectively). We asked whether there were uniform seasonal shifts in physiological traits across species, and whether higher elevation species displayed evidence for cold tolerance. Seasonal shifts in metabolic rates differed between the three species for which data were collected. Basal metabolic rates in one species – black-headed nightingalethrushesCatharus mexicanus– were up-regulated in summer (~19% increase of winter metabolism), however two other species displayed no seasonal regulation. No species exhibited shifts in haemoglobin concentrations across season or across elevation, whereas body mass in two species was significantly higher in the summer. One species restricted to higher elevations – ruddy-capped nightingale-thrushesC. frantzii– displayed physiological traits indicative of cold-tolerance. Although only summer data were available for this species (C. frantzii), metabolic rates were constant across temperatures tested (5-34°C) and haemoglobin concentrations were significantly higher compared to the other four species. Our results suggest that seasonal acclimatisation in physiological traits is variable between species and appear unrelated to changes in local climate. As such, the distinct physiological traits observed in ruddy-capped nightingale-thrushes likely relate to historic isolation and conserved physiological traits rather than contemporary climatic adaption.
Explication of CB1receptor contributions to the hypothermic effects of Δ9-tetrahydrocannabinol (THC) when delivered by vapor inhalation or parenteral injection in rats
Authors: Nguyen Jacques D. , Creehan K. M. , Grant Yanabel , Vandewater Sophia A. , Kerr Tony M. , Taffe Michael A.
Published: May 2020

The use of Δ9-tetrahydrocannabinol (THC) by inhalation using e-cigarette technology grows increasingly popular for medical and recreational purposes. This has led to development of e-cigarette based techniques to study the delivery of THC by inhalation in laboratory rodents. Inhaled THC reliably produces hypothermic and antinociceptive effects in rats, similar to effects of parenteral injection of THC. This study was conducted to determine the extent to which the hypothermic response depends on interactions with the CB1receptor, using pharmacological antagonist (SR141716, AM-251) approaches. Groups of rats were implanted with radiotelemetry devices capable of reporting activity and body temperature, which were assessed after THC inhalation or injection. SR141716 (4 mg/kg, i.p.) blocked or attenuated antinociceptive effects of acute THC inhalation in male and female rats. SR141716 was unable to block the initial hypothermia caused by THC inhalation, but temperature was restored to normal more quickly. Alterations in antagonist pre-treatment time, dose and the use of a rat strain with less sensitivity to THC-induced hypothermia did not change this pattern. Pre-treatment with SR141716 (4 mg/kg, i.p.) blocked hypothermia induced by i.v. THC and reversed hypothermia when administered 45 or 90 minutes after THC (i.p.). SR141716 and AM-251 (4 mg/kg, i.p.) sped recovery from, but did not block, hypothermia caused by vapor THC in female rats made tolerant by prior repeated THC vapor inhalation. The CB2antagonist AM-630, had no effect. These results suggest that hypothermia consequent to THC inhalation is induced by other mechanisms in addition to CB1receptor activation.
Pairing two growth-based, high-throughput selections to fine tune conformational dynamics in oxygenase engineering
Authors: Maxel Sarah , Zhang Linyue , King Edward , Aspacio Derek , Acosta Ana Paula , Luo Ray , Li Han
Published: May 2020

Cyclohexanone monooxygenases (CHMO) consume molecular oxygen and NADPH to catalyze the valuable oxidation of cyclic ketones. However, CHMO usage is restricted by poor thermostability and stringent specificity for NADPH. Efforts to engineer CHMO have been limited by the sensitivity of the enzyme to perturbations in conformational dynamics and long-range interactions that cannot be predicted. We demonstrate a pair of aerobic, high-throughput growth selection platforms inEscherichia colifor oxygenase evolution, based on NADPH or NADH redox balance. We utilize the NADPH-dependent selection in the directed evolution of thermostable CHMO and discover the variant CHMO GV (A245G-A288V) with a 2.7-fold improvement in residual activity compared to the wild type after 40 °C incubation. Addition of a previously reported mutation resulted in A245G-A288V-T415C which has further improved thermostability at 45 °C. We apply the NADH-dependent selection to alter the cofactor specificity of CHMO to accept NADH, a less expensive cofactor than NADPH. We identified the variant CHMO DTNP (S208D-K326T-K349N-L143P) with a 21-fold cofactor specificity switch from NADPH to NADH compared to the wild type. Molecular modeling indicates that CHMO GV experiences more favorable residue packing and backbone torsions, and CHMO DTNP activity is driven by cooperative fine-tuning of cofactor contacts. Our introduced tools for oxygenase evolution enable the rapid engineering of properties critical to industrial scalability.
AmpliconDesign – An interactive web server for the design of high-throughput targeted DNA methylation assays
Authors: Schönung Maximilian , Hess Jana , Bawidamann Pascal , Stäble Sina , Hey Joschka , Langstein Jens , Assenov Yassen , Weichenhan Dieter , Lutsik Pavlo , Lipka Daniel B.
Published: May 2020

Targeted analysis of DNA methylation patterns based on bisulfite-treated genomic DNA (BT-DNA) is considered as a gold-standard for epigenetic biomarker development. Existing software tools facilitate primer design, primer quality control or visualization of primer localization. However, high-throughput design of primers for BT-DNA amplification is hampered by limits in throughput and functionality of existing tools, requiring users to repeatedly perform specific tasks manually. Consequently, the design of PCR primers for BT-DNA remains a tedious and time-consuming process. To bridge this gap, we developedAmpliconDesign, a webserver providing a scalable and user-friendly platform for the design and analysis of targeted DNA methylation studies based on BT-DNA, e.g. deep amplicon bisulfite sequencing (ampBS-seq), EpiTYPER MassArray, or pyrosequencing. Core functionality of the web server includes high-throughput primer design and binding site validation based onin silicobisulfite-converted DNA sequences, prediction of fragmentation patterns for EpiTYPER MassArray, an interactive quality control as well as a streamlined analysis workflow for ampBS-seq.

Availability and Implementation

TheAmpliconDesignwebserver is freely available online at:https://amplicondesign.dkfz.de/.AmpliconDesignhas been implemented using the RShinyframework (Changet al., 2018). The source code is publicly available under the GNU General Public License v3.0 (https://github.com/MaxSchoenung/AmpliconDesign).

Contact

Daniel B. Lipka (d.lipka@dkfz.de) & Maximilian Schönung (m.schoenung@dkfz.de)
Dramatic differences in male and female mortality trends for selected European cohorts over ∼20 years
Authors: Clark Jeremy S.C. , Rydzewska Kamila , Podsiadło Konrad , van de Wetering Thierry , Ciechanowicz Andrzej
Published: May 2020

Longevity is of considerable interest. Collation of recent data after World War II by the Human Mortality Database allowed analyses, previously unattainable, of modal death-ages for sufficient numbers of selected European cohorts. The aim was to track modes and medians/means (≥60 years old (y)) of all-cause mortality for both sexes. The only highest-quality, large-number Lexis data available were analyzed: from nine countries: Denmark, Finland, France, Iceland, Italy, Netherlands, Norway, Sweden and Switzerland; raw-data modes (and medians/means ≥60y, plus thin-plate-spline averages), were analyzed, plus pooled data. Here we show that for cohorts 1880-∼1900 dramatic sex differences existed between death-age changes with all countries except Iceland showing male modal negative trends lasting ∼10-20 years and medians in all countries near-constant or negative lasting ∼10-20 years; whereas females from most countries showed fairly constant positive trends (except Finnish modes and Norwegian medians). For cohorts ∼1900-1919 male and female modal trends were positive (except Dutch and Icelandic cohorts and Finnish females). The net results were that male mortality modes for Danish, Icelandic, Italian, Dutch, Swedish and Norwegian 1919 cohorts were roughly the same as for 1880 cohorts, whereas female death-age modes increased. Results clarify previously knowledge concerning sex differences during this period. Despite improved environment in late adulthood over this period, this did not translate into increased male longevity and earlier events might have sealed their fate, especially in Denmark, Italy, Netherlands, Norway, aand Sweden (and, later, Iceland).
Modeling the transmission and vaccination strategy for porcine reproductive and respiratory syndrome virus
Authors: Galvis Jason A. , Prada Joaquin M. , Corzo Cesar A. , Machado Gustavo
Published: May 2020

Many aspects of the porcine reproductive and respiratory syndrome virus (PRRSV) between-farm transmission dynamics have been investigated, but uncertainty remains about the significance of farm type and different transmission routes on PRRSV spread. We developed a stochastic epidemiological model calibrated on weekly PRRSV outbreaks accounting for the population dynamics in different pig production phases, breeding herds, gilt development units, nurseries, and finisher farms, of three hog producer companies. Our model accounted for indirect contacts by the close distance between farms (local transmission), between-farm animal movements (pig flow), and reinfection of sow farms (re-break). The fitted model was used to examine the effectiveness of vaccination strategies and complementary interventions such as enhanced PRRSV detection and vaccination delays and forecast the spatial distribution of PRRSV outbreak. The results of our analysis indicated that for sow farms, 59% of the simulated infections were related to local transmission (e.g. airborne, feed deliveries, shared equipment) whereas 36% and 5% were related to animal movements and re-break, respectively. For nursery farms, 80% of infections were related to animal movements and 20% to local transmission; while at finisher farms it was split between local transmission and animal movements. Assuming that the current vaccines are 1% effective in mitigating between-farm PRRSV transmission, weaned pigs vaccination would reduce the incidence of PRRSV outbreaks by 2%, indeed under any scenario vaccination alone was insufficient for completely controlling PRRSV spread. Our results also showed that intensifying PRRSV detection and/or vaccination pigs at placement increased the effectiveness of all simulated vaccination strategies. Our model reproduced the incidence and PRRSV spatial distribution; therefore, this model could also be used to map current and future farms at-risk. Finally, this model could be a useful tool for veterinarians, allowing them to identify the effect of transmission routes and different vaccination interventions to control PRRSV spread.
A screen of FDA-approved drugs identifies inhibitors of Protein Tyrosine Phosphatase 4A3 (PTP4A3 or PRL-3)
Authors: Rivas Dylan R. , Dela Cerna Mark Vincent C. , Smith Caroline N. , Patty Blaine G. , Lee Donghan , Blackburn Jessica S.
Published: May 2020

Protein tyrosine phosphatase 4A3 (PTP4A3 or PRL-3) is highly expressed in a variety of cancers, where it promotes tumor cell migration and metastasis leading to poor prognosis. Despite its clinical significance, there are currently no viable options to target PRL-3in vivo. Here, we screened 1,443 FDA-approved drugs for their ability to inhibit the activity of the PRL phosphatase family. We identified five specific inhibitors for PRL-3 as well as one selective inhibitor of PRL-2. Additionally, we found nine drugs that broadly and significantly suppressed PRL activity. Two of these broad PRL inhibitors, Salirasib and Candesartan blocked PRL-3-induced migration in human embryonic kidney (HEK) cells with no negative impact on cell viability. Both drugs prevented migration of PRL-3 expressing human colorectal cancer cells to a similar degree as the research-grade PRL inhibitor, Thienopyridone, and are selective towards PRLs over other phosphatases.In silicomodeling revealed that Salirasib binds a putative allosteric site near the WPD loop of PRL-3, while Candesartan binds a potentially novel targetable site adjacent to the CX5R motif. Inhibitor binding at either of these sites is predicted to trap PRL-3 in a closed conformation, preventing substrate binding and inhibiting function.
Mapping the architecture of regulatory variation provides insights into the evolution of complex traits
Authors: Lupo Offir , Krieger Gat , Jonas Felix , Barkai Naama
Published: May 2020

Background

Organisms evolve complex traits by recruiting existing programs to new contexts, referred as co-option. Within a species, single upstream regulators can trigger full differentiation programs. Distinguishing whether co-option of differentiation programs results from variation in single regulator, or in multiple genes, is key for understanding how complex traits evolve. As an experimentally accessible model for studying this question we turned to budding yeast, where a differentiation program (filamentous) is activated inS. cerevisiaeonly upon starvation, but used by the related speciesS. paradoxusalso in rich conditions.

Results

To define expression variations associated with species-specific activation of the filamentous program, we profiled the transcriptome ofS. cerevisiae, S.paradoxusand their hybrid along two cell cycles at 5-minutes resolution. As expected in cases of co-option, expression of oscillating genes varies between the species in synchrony with their growth phenotypes and was dominated by upstreamtrans-variations. Focusing on regulators of filamentous growth, we identified gene-linked variations (cis) in multiple genes across regulatory layers, which propagated to affect expression of target genes, as well as binding specificities of downstream transcription factor. Unexpectedly, variations in regulators essential forS. cerevisiaefilamentation were individually too weak to explain activation of this program inS. paradoxus.

Conclusions

Our study reveals the complex architecture of regulatory variation associated with species-specific use of a differentiation program. Based on these results, we suggest a new model in which evolutionary co-option of complex traits is stabilized in a distributed manner through multiple weak-effect variations accumulating throughout the regulatory network.
Hypoxia-induced SETX links replication stress with the unfolded protein response
Authors: Ramachandran Shaliny , Ma Tiffany , Ng Natalie , Foskolou Iosifina P. , Hwang Ming-Shih , Victori Pedro , Cheng Wei-Chen , Buffa Francesca M. , Leszczynska Katarzyna B. , Gromak Natalia , Hammond Ester M.
Published: May 2020

The levels of hypoxia associated with resistance to radiotherapy significantly impact cancer patient prognosis. These levels of hypoxia initiate a unique transcriptional response with the rapid activation of numerous transcription factors in a background of global repression of transcription. Here, we show that the biological response to radiobiological hypoxia includes the induction of the DNA/RNA helicase SETX. In the absence of hypoxia-induced SETX, R-loop levels increase, DNA damage accumulates, and DNA replication rates decrease. SETX plays a key role in protecting cells from DNA damage induced during transcription in hypoxia. Importantly, we show that the mechanism of SETX induction is reliant on the PERK/ATF4 arm of the unfolded protein response. These data not only highlight the unique cellular response to radiobiological hypoxia, which includes both a replication stress dependent DNA damage response and an unfolded protein response but uncover a novel link between these two distinct pathways.