bluuebunny/crossref_metadata_2025 huggingface dataset:
CHORIOCAPILLARIS FLOW DEFICITS AS A RISK FACTOR FOR PROGRESSION OF AGE-RELATED MACULAR DEGENERATION
Authors: Corvi Federico , Tiosano Liran , Corradetti Giulia , Nittala Muneeswar Gupta , Lindenberg Sophiana , Alagorie Ahmed Roshdy , McLaughlin John Adam , Lee Thomas K. , Sadda Srinivas R.
Published: October 2020

Purpose:

To evaluate the association between choriocapillaris (CC) flow deficits and structural optical coherence tomography biomarkers and the progression of intermediate age-related macular degeneration (iAMD) to complete retinal pigment epithelial and outer retinal atrophy.

Methods:

Retrospective analysis of consecutive patients with iAMD with a minimum follow-up of 12 months. Odds ratios of intraretinal hyperreflective foci, hyporeflective drusen cores, subretinal drusenoid deposits, the presence of drusen volume ≥0.03 mm3 within a central 3-mm circle, fellow eye with late stage of AMD, and CC flow deficits at baseline and months of follow-up were estimated from logistic regression.

Results:

A total of 112 eyes with iAMD were included. Eyes that progressed were significantly more likely to show intraretinal hyperreflective foci, hyporeflective drusen cores, and drusen volume ≥0.03 mm3. The CC flow deficit was also significantly greater in eyes that developed complete retinal pigment epithelial and outer retinal atrophy. Intraretinal hyperreflective foci, hyporeflective drusen cores, drusen volume ≥0.03 mm3, and higher CC flow deficits were significantly and independently associated with the development of complete retinal pigment epithelial and outer retinal atrophy.

Conclusion:

The CC flow deficit was significantly greater in iAMD eyes that progressed to complete retinal pigment epithelial and outer retinal atrophy and remained an independent risk factor when structural optical coherence tomography biomarkers were considered. CC flow deficits may be useful for enhancing risk stratification and prognostication of patients with iAMD.
Defining catastrophic brain injury in children leading to coma and disorders of consciousness and the scope of the problem
Authors: LaRovere Kerri L. , Tasker Robert C.
Published: October 2020

Purpose of review

Severe brain injury in children resulting in coma and disorders of consciousness (DOC) is a catastrophic event for the life and function of children and their families. The present article summarizes the recently published pediatric literature on validated diagnostic assessments, potential predictors of recovery, and outcome measures used in children with catastrophic brain injury (CBI). Literature search terms included variants of consciousness, diagnostic tests, predictors of outcome, and outcome measures.

Recent findings

Developmentally appropriate diagnostic tools, outcome predictors, and outcome measures are lacking for children with CBI leading to coma and DOC. Individual case prognosis relies on serial clinical examinations and experience. Evidence regarding optimal diagnosis of the highest level of consciousness and management of children with CBI is needed. Global efforts through the ongoing Curing Coma Campaign are aimed at: developing common data elements for information capture; streamlining the classification of coma endotypes; describing trajectories with biomarkers to monitor recovery or disease progression; and devising effective treatments for adults and children.

Standardized, developmentally appropriate diagnostic and outcome assessments for CBI in children are needed. Future research should use these content standards to update our understanding of children with CBI leading to coma and DOC, and evaluate effective practices using acute adjunctive and rehabilitation therapies.
Community Health Centers Primary Care Physicians' Asthma Management Perception of Uninsured Patients
Authors: Bynum Mary
Published: October 2020

Purpose of Study:

Explore the perceptions of primary care physicians (PCPs) from community health care centers (CHCs) in Franklin County, Ohio, regarding factors that contribute to their inability to consistently provide sustainable asthma management services to their uninsured patient population.

Primary Practice Setting:

Asthmatic patients are not consistently receiving sustainable asthma management in CHCs in Ohio. Primary care physicians in CHCs play a pivotal role in closing health care gaps for asthmatic patients. To minimize the barriers that impede the efforts of PCPs to control asthma for their uninsured patients, asthma disease management programs that include case management services in CHCs in Franklin County, Ohio, are needed.

Methodology and Sample:

A convenience sample of 4 PCPs from 2 CHCs in Franklin County, Ohio, was interviewed face-to-face. Interviews, direct observation, and previously published research were the sources of data utilized for this study.

Results:

Results indicated that 75% of participants did not use standard guidelines while treating their patients. Physician time constraints and access to affordable medication were identified as some of the barriers to providing sustainable asthma management services.

Implications for Case Management:

Asthma is a complex chronic disease. Disease case managers not only are capable of coordinating health care services for a variety of patient populations but are also effective in managing complex diseases such as asthma for disadvantaged populations. Evidence-based case management models are needed to support PCPs in CHCs. Without the inclusion of asthma-specific case managers as part of the care delivery structure, CHCs may continue to provide subpar disease management services for uninsured asthmatic patients.
Pregnant Women's Reports of the Impact of COVID-19 on Pregnancy, Prenatal Care, and Infant Feeding Plans
Authors: Burgess Adriane , Breman Rachel Blankstein , Bradley Dani , Dada Sophia , Burcher Paul
Published: October 2020

Purpose:

The aim of this study is to describe how the COVID-19 (coronavirus) pandemic has affected pregnancy, prenatal maternity care practices, and infant feeding plans among pregnant persons in the United States.

Study Design:

Cross-sectional descriptive study using an app-based survey.

Methods:

A link to the survey was sent via email to users of the Ovia Pregnancy app on May 20, 2020 and was open for 1 week. Participants were asked to complete the survey as it applied to their pregnancy, breastfeeding, and maternity care received during the COVID-19 pandemic, beginning approximately February 2020 through the time of the survey. There were 258 respondents who completed the survey.

Results:

The majority (96.4%; n = 251) of pregnant women felt they received safe prenatal care during this time period. Slightly less 86.3% (n = 215) felt they received adequate prenatal care during this time period. 14.2% (n = 33) reported changing or considering changing the location where they planned to give birth due to COVID-19. Of those who reported they had begun purchasing items for their baby, 52.7% reported that the COVID-19 pandemic has affected their ability to get items they need for their baby.

Clinical Implications:

Although it is imperative to implement policies that reduce risk of transmission of COVID-19 to pregnant women and health care providers, it is necessary for health care providers and policy makers to listen to the collective voices of women during pregnancy about how COVID-19 has affected their birth and infant feeding plans and their perception of changes in prenatal care.
Philtral Ridge Projection in Repaired Unilateral Cleft Lip: Three-Dimensional Anthropometry
Authors: Ganske Ingrid M. , Langa Olivia C. , Mulliken John B.
Published: October 2020

Background:

Cleft surgeons try to construct a philtral ridge during primary repair of a cleft lip, but rarely document the results. The authors used three-dimensional photogrammetry to measure projection of philtral ridges after closure of the common forms of unilateral labial cleft.

Methods:

This is a retrospective study of patients with unilateral complete, incomplete (moderate and severe), and microform cleft lip repaired by one surgeon from 2000 to 2013. Cleft type determined the technique for building a philtral ridge. The relative elevation of the ridge on the cleft versus noncleft side was measured on three-dimensional childhood photographs at two locations along the philtrum: just above the Cupid’s bow and at the midlabial level.

Results:

Thirty-four patients were evaluated at a mean age of 9.25 years. All cleft types exhibited greater projection at the philtral midlabial level compared with the Cupid’s bow level. The authors found a trend toward a more prominent cleft side philtral ridge in microforms. In incomplete cleft lips, there was slightly greater philtral ridge projection in severe forms repaired after a preliminary nasolabial adhesion compared with those repaired in a single stage. There was similar projection of the cleft side ridge in two-stage complete and single-stage repaired incomplete lips.

Conclusions:

It is possible to construct a philtral ridge that is as prominent as the noncleft side in all types of unilateral cleft lip. Increased muscle thickness may explain the slightly increased philtral ridge projection in patients with an incomplete cleft repaired in two stages compared to one-stage closure.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Medication Errors in Anesthesiology: Is It Time to Train by Example? Vignettes Can Assess Error Awareness, Assessment of Harm, Disclosure, and Reporting Practices
Authors: Duffy Caoimhe C. , Bass Gary A. , Duncan James , Lyons Barry , O’Dea Angela
Published: October 2020

Background

Perioperative medication errors (MEs) are complex, multifactorial, and a significant source of in-hospital patient morbidity. Anesthesiologists’ awareness of error and the potential for harm is not well understood, nor is their attitude to reporting and disclosure. Anesthesiologists are not routinely exposed to medication safety training.

Methods

Ten clinical vignettes, describing an ME or a near miss, were developed using eDelphi consensus. An online survey instrument presented these vignettes to anesthesiologists along with a series of questions assessing error awareness, potential harm severity, the likelihood of reporting, and the likelihood of open disclosure to the patient. The study also explored the influence of prior medication safety training.

Results

Eighty-nine anesthesiologists from 14 hospitals across Ireland (53.9% were residents, and 46.1% were attendings) completed the survey. Just 35.6% of anesthesiologists recalled having had medication safety training, more commonly among residents than attendings, although this failed to reach significance (P < 0.081). Medication error awareness varied with the vignette presented. Harm severity assessment was positively associated with error awareness. The likelihood of patient disclosure and incident reporting was both low and independent of harm severity assessment.

Conclusions

Perioperative ME awareness and assessment of potential harm by anesthesiologists is variable. Self-reported rates of incident reporting and error disclosure fall short of the standards that might apply in an environment focused on candor and safety. An extensive education program is required to raise awareness of error and embed appropriate reporting and disclosure behaviors. Vignettes, designed by consensus, may be valuable in the delivery of such a curriculum.
Unresolved issues in the identification and treatment of carbapenem-resistant Gram-negative organisms
Authors: Kois Abigail K. , Nicolau David P. , Kuti Joseph L.
Published: October 2020

Purpose of review

Carbapenem-resistant organisms (CROs), including Pseudomonas aeruginosa, Acinetobacter baumannii and Enterobacterales, are a threat worldwide. This review will cover mechanisms of resistance within CROs and challenges with identification and treatment of these organisms while pointing out unresolved issues and ongoing challenges.

Recent findings

The treatment of CROs has expanded through newer therapeutic options. Guided utilization through genotypic and phenotypic testing is necessary in order for these drugs to target the appropriate mechanisms of resistance and select optimal antibiotic therapy.

Identification methods and treatment options need to be precisely understood in order to limit the spread and maximize outcomes of CRO infections.
Prevalence and Predictors of Urinary Incontinence at 1 Year Postpartum
Authors: Giugale Lauren E. , Moalli Pamela A. , Canavan Timothy P. , Meyn Leslie A. , Oliphant Sallie S.
Published: October 2020

Objectives

Postpartum urinary incontinence estimates range from 13% to 47%. Clinical factors associated with incontinence 1 year after first delivery are varied. We assessed the prevalence of and factors associated with urinary incontinence in primiparous women at 12 months postpartum.

Methods

Ancillary analysis of 99 nulliparous women from a prospective cohort study that assessed participants during the first and third trimesters and 12 months postpartum. Our primary outcome was urinary incontinence 12 months postpartum. Women were asked “How often do you experience urine leakage?” and considered to have urinary incontinence if a response other than “never” was reported. We collected vaginal swabs for assessment of matrix metalloproteinase-9 activity, a measure of tissue remodeling. Bivariable and logistic regression analyses were used to compare women with and without postpartum urinary incontinence.

Results

Of 99 primiparous women, 55% (n = 54) reported urinary incontinence at 12 months postpartum. Logistic regression demonstrated that urinary incontinence during pregnancy (odds ratio, 34.3; 95% confidence interval, 7.9–149.2) and a decrease in matrix metalloproteinase 9 activity between the first and third trimesters (odds ratio, 19.34; 95% confidence interval, 3.47–107.84) were associated with postpartum urinary incontinence. The sensitivity and specificity of urinary incontinence during pregnancy for predicting postpartum urinary incontinence were 87% and 67%, respectively. The positive and negative predictive values were 76% and 81%, respectively.

Conclusions

Urinary incontinence affected 55% of primiparous women at 12 months postpartum. Urinary incontinence during pregnancy was strongly associated with postpartum incontinence. Importantly, vaginal tissue protease activity during pregnancy represents a possible mechanism for and biomarker of postpartum urinary incontinence.
A Retrospective Study of Ultrasound Accuracy for the Diagnosis of Chronic Inflammatory Demyelinating Polyneuropathy
Authors: Crump Nicholas H. , Cartwright Michael S.
Published: October 2020

Introduction:

Ultrasound is emerging as a useful tool for the evaluation of immune-mediated neuropathies because it can provide high-resolution anatomic information to complement electrodiagnostic data. Nerve enlargements are commonly found in chronic inflammatory demyelinating polyneuropathy (CIDP), and their presence likely useful in diagnosis, particularly if multifocal.

Methods:

In this study, the authors undertook a retrospective chart review to identify ultrasound findings in patients with CIDP previously studied in a single busy neurodiagnostic laboratory.

Results:

Of the 50 cases identified from 2000 to 2017, individuals with a confirmed diagnosis of CIDP (21 cases) were more likely to have multiple sites of enlargement, as well as more pronounced nerve enlargement, than patients who were subsequently found to have an alternate cause of neuropathy (22 cases). The presence of any moderately enlarged nerve segment predicted definite CIDP with sensitivity of 81% and specificity 77%.

Conclusion:

This study demonstrates that ultrasound can be of diagnostic utility in patients with suspected CIDP, even when conducted in a nonstandardized real-world setting.
Neurological Prognostication Using Raw EEG Patterns and Spectrograms of Frontal EEG in Cardiac Arrest Patients
Authors: Choi Wook Jin , Lee Jae Hoon , Kim Sang Ho
Published: October 2020

Purpose:

We investigated which raw EEG and spectrogram patterns in frontal EEG predict poor neurological outcomes in patients with hypoxic ischemic encephalopathy after cardiac arrest.

Methods:

This multicenter, prospective, observational study included 52 patients with anoxic brain injury after cardiac arrest. Raw EEGs and spectrograms (color density spectral arrays) measured with hardwired frontal EEG monitoring were used to predict poor prognosis. Neurological variables upon admission, raw EEG patterns, including highly malignant and malignant EEG patterns, and changes in frequency and amplitude from color density spectral arrays were investigated.

Results:

All patients exhibiting highly malignant EEG patterns died, and malignant EEG patterns were significant predictors of poor prognosis as the area under the receiver operating characteristic curve was 0.83 to 0.86. Irregular high-voltage waves in the high-frequency beta band in continuous background EEGs were associated with poor prognosis (P = 0.022). Malignant EEG patterns including high-voltage and high-frequency beta waves were significantly stronger predictors of poor prognosis than the absence of ventricular fibrillation and pupil reflex, delayed length of anoxic time, and lower Glasgow coma scale score (odds ratio, 9; P = 0.035). Compared with prognostication using malignant EEG patterns alone, the area under the receiver operating characteristic curve of results incorporating high-voltage and high-frequency beta waves was 0.84 (vs. 0.83) at day 1, 0.88 (vs. 0.85) at day 2, 0.92 (vs. 0.86) at day 3, and 0.99 (vs. 0.86) at day 4.

Conclusions:

Frontal EEG monitoring is useful for predicting poor neurological outcomes. Brain function monitoring using both raw EEG patterns and color density spectral arrays is more helpful for predicting poor prognosis than raw EEG alone.
Mathematical modelling evolutionarily stable behavior of zooplankton with state constraints
Authors: Kuzenkov O. , Ryabova E. , Garcia A. , Kostromina O.
Published: October 2020

The purpose of this work is to create mathematical base and software for solving the problem of finding an evolutionarily stable strategy of zooplankton diel vertical migrations and explaining the observed effects in aquatic ecosystems using this software (in particular, in the northeastern part of the Black Sea). An essential feature of this study is the inclusion in the mathematical model of state constraints on the strategy of behavior, which reflect the vertical limited zone of zooplankton habitat. The presence of state constraints creates the main mathematical difficulties for solving the optimal control problem used in the analysis of the model.

The general methodological basis for defining evolutionarily stable behavior is the Darwinian principle “survival of the fittest”. However, it remains a problem to construct a mathematical expression for the fitness function of hereditary elements. The efforts of the authors were aimed at creating a software package that allows predicting the evolutionarily stable behavior of zooplankton based on the actual universal extreme principle. The created software package includes, as a main component, a computational module for solving the set optimal control problem with state constraints.
PyEcoLib: a python library for simulatingE. colistochastic size dynamics
Authors: Blanco Camilo , Nieto Cesar , Vargas Cesar , Pedraza Juan
Published: October 2020

Recent studies describe bacterial division as a jump process triggered when it reaches a fixed number of stochastic discrete events at a rate depending on the cell-size. This theoretical approach enabled the computation of stochastic cell-size transient dynamics with arbitrary precision, with the possibility of being coupled to other continuous processes as gene expression. Here we synthesize most of this theory in the tool PyEcoLib, a python-based library to estimate bacterial cell size stochastic dynamics including continuous growth and division events. In this library, we include examples predicting statistical properties seen in experiments.
Sexually divergent cortical control of affective-autonomic integration
Authors: Wallace Tyler , Schaeuble Derek , Pace Sebastian A. , Schackmuth Morgan K. , Hentges Shane T. , Chicco Adam J. , Myers Brent
Published: October 2020

Depression and cardiovascular disease reduce quality of life and increase mortality risk. These conditions commonly co-occur with sex-based differences in incidence and severity. However, the biological mechanisms linking the disorders are poorly understood. In the current study, we hypothesized that the infralimbic (IL) prefrontal cortex integrates mood-related behaviors with the cardiovascular burden of chronic stress. In a rodent model, we utilized optogenetics during behavior andin vivophysiological monitoring to examine how the IL regulates affect, social motivation, neuroendocrine-autonomic stress reactivity, and the cardiac consequences of chronic stress. Our results indicate that IL glutamate neurons increase socio-motivational behaviors specifically in males. IL activation also reduced endocrine and cardiovascular stress responses in males, while increasing reactivity in females. Moreover, prior IL stimulation protected males from subsequent chronic stress-induced sympatho-vagal imbalance and cardiac hypertrophy. Our findings suggest that cortical regulation of behavior, physiological stress responses, and cardiovascular outcomes fundamentally differ between sexes.
Bone Marrow-Derived Cells Contribute to the Maintenance of Thymic Stroma including Thymic Epithelial Cells
Authors: Chakrabarti Shami , Hoque Mohammed , Jamil Nawshin Zara , Singh Varan J , Meer Neelab , Pezzano Mark T.
Published: October 2020

In paradox to critical functions for T-cell selection and self-tolerance, the thymus undergoes profound age-associated atrophy and loss of T-cell function, which are further enhanced by cancer therapies. Identification of thymic epithelial progenitor populations capable of forming functional thymic tissue will be critical in understanding thymic epithelial cell (TEC) ontogeny and designing strategies to reverse involution. We identified a new population of progenitor cells, present in both thymus and bone marrow (BM), that co-express the hematopoietic marker CD45 and the definitive thymic epithelial marker EpCAM and maintains the capacity to form functional thymic tissue. Confocal analysis and qRT-PCR of sorted cells from both BM and thymus confirmed co-expression of CD45 and EpCAM. Grafting of C57BL/6 fetal thymi under the kidney capsule of H2BGFP transgenic mice revealed that peripheral CD45+ EpCAM+ GFP-expressing cells migrate into the developing thymus and contribute to both TECs and FSP1-expressing stroma. Sorted BM-derived CD45+EpCAM+ cells contribute to reaggregate thymic organ cultures (RTOCs) and differentiate into keratin and FoxN1 expressing TECs, demonstrating that BM cells can contribute to the maintenance of TEC microenvironments previously thought to be derived solely from endoderm. BM-derived CD45+EpCAM+ cells represent a new source of progenitor cells that contribute to thymic homeostasis. Future studies will characterize the contribution of BM-derived CD45+EpCAM+ TEC progenitors to distinct functional TEC microenvironments in both the steady-state thymus and under conditions of demand. Cell therapies utilizing this population may prove useful for counteracting thymic involution in cancer patients.
Division stochasticity can be transmitted to protein expression through chromosome replication
Authors: Nieto Acuña César Augusto , Vargas García César Augusto , Singh Abhyudai , Pedraza Juan Manuel
Published: October 2020

Stochastic fluctuations (noise) are a fundamental characteristic of protein production. Some sources of this stochasticity are still under debate. In this work, we explore how these fluctuations can originate from the stochasticity on division events. To do that, we consider the classical gene expression model with chromosome replication following the known Helmstetter & Cooper model. This model predicts intervals of the cell cycle where bacteria can have more than one copy of a particular gene. Considering the transcription rate as proportional to the number of chromosomes and division based on a continuous rate model, we explore how stochasticity in division or equivalently in cell size, could be transmitted to gene expression. Our simulations suggest that division can be an important source of such fluctuations only if chromosomes are replicating, otherwise, this noise is not well transmitted. This effect happens even if replication is deterministic. This work can be helpful for understanding cell cycle dynamics and their interplay with phenotypic variability.
Bacterial glycocalyx integrity drives multicellular swarm biofilm dynamism
Authors: Saïdi Fares , Jolivet Nicolas Y. , Lemon David J. , Nakamura Arnaldo , Garza Anthony G. , Veyrier Frédéric J. , Islam Salim T.
Published: October 2020

Bacterial surface exopolysaccharide (EPS) layers are key determinants of biofilm establishment and maintenance, leading to the formation of higher-order 3D structures conferring numerous survival benefits to a cell community. In addition to a specific EPS glycocalyx, we recently revealed that the social δ-proteobacteriumMyxococcus xanthussecretes a novel biosurfactant polysaccharide (BPS), with both EPS and BPS polymers required for type IV pilus (T4P)-dependent swarm expansion via spatio-specific biofilm expression profiles. Thus the synergy between EPS and BPS secretion somehow modulates the multicellular lifecycle ofM. xanthus. Herein, we demonstrate that BPS secretion functionally-activates the EPS glycocalyx via its destabilization, fundamentally altering the characteristics of the cell surface. This impacts motility behaviours at the single-cell level as well as the aggregative capacity of cells in groups via EPS fibril formation and T4P assembly. These changes modulate structuration of swarm biofilms via cell layering, likely contributing to the formation of internal swarm polysaccharide architecture. Together, these data reveal the manner by which the interplay between two secreted polymers induces single-cell changes that modulate swarm biofilm communities.
RIG-I has a role in immunity againstHaemonchus contortus, a gastrointestinal parasite inOvis aries- a novel report
Authors: Banerjee Samiddha , Pal Aruna , Pal Abantika , Mandal Subhas Chandra , Chatterjee Paresh Nath , Chatterjee Jayanta Kumar
Published: October 2020

RIG-I is associated to the DExD/H box RNA Helicases. It is a Pattern Recognition Receptor (PRR), playing a crucial role in the system and is a germ line encoded host sensor to perceive Pathogen Associated Molecular Patterns or PAMPs. So far reports were available for the role of RIG-I in antiviral immunity. This is the first report we have documented the role of RIG-I in parasitic immunity.Haemonchus contortusis a deadly parasite affecting sheep industry which has a tremendous economic importance and the parasite reported to be prevalent in the hot and humid agroclimatic region. We had characterized RIG-I gene in sheep (Ovis aries) and identified the important domains or binding site withHaemonchus contortusthroughin silicostudies. Differential mRNA expression analysis revealed upregulation of RIG-I gene in abomassum of infected sheep compared to that of healthy sheep, further confirming the findings. Thus it is evident that in infected sheep, expression of RIG-I is triggered for binding to more pathogen (Haemonchus contortus). Genetic similar studies with human and other livestock species were conducted to reveal that sheep may be efficiently used a model organism for studying the role of RIG-I in antiparasitic immunity of human.
Characterization of sequence specific binding of LARP6 to the 5’ stem-loop of type I collagen mRNAs and implications for rational design of antifibrotic drugs
Authors: Stefanovic Lela , Gordon Blaine H. , Silvers Robert , Stefanovic Branko
Published: October 2020

Excessive synthesis of type I collagen characterizes fibrotic diseases. Binding of LARP6 to the 5’ stem-loop (5’SL) of collagen mRNAs regulates their translation and the high rate of biosynthesis in fibrosis. LARP6 needs two domains to form stable complex with 5’SL RNA, the La-domain and the juxtaposed RRM domain (jointly called the La-module). We describe that the La-domain of LARP6 is necessary and sufficient for recognition of 5’SL in sequence specific manner. The three amino acid motif, RNK, located in the flexible loop which connects the second α-helix to the β-sheet of the La domain is critical for binding. Mutation of any of these three amino acids abolishes the binding of La-domain to 5’SL. The major site of crosslinking of LARP6 to 5’SL RNA was mapped to this motif. The RNK motif is not found in other LARPs, which can not bind 5’SL. Presence of RRM increases the stability of complex between La-domain and 5’SL RNA and RRM domain does not make extensive contacts with 5’SL RNA. We propose a model in which the initial recognition of 5’SL by LARP6 is mediated by the RNK epitope and further stabilized by the RRM domain. This discovery suggests that the interaction between LARP6 and collagen mRNAs can be blocked by small molecules that target the RNK epitope and will help rational design of the LARP6 binding inhibitors as specific antifibrotic drugs.
Th2 Cytokine Modulates Herpesvirus Reactivation in a Cell Type Specific Manner
Authors: Wang Guoxun , Zarek Christina , Chang Tyron , Tao Lili , Lowe Alexandria , Reese Tiffany A.
Published: October 2020

Gammaherpesviruses, such as Epstein-Barr virus (EBV), Kaposi’s sarcoma associated virus (KSHV), and murine γ-herpesvirus 68 (MHV68), establish latent infection in B cells, macrophages, and non-lymphoid cells, and can induce both lymphoid and non-lymphoid cancers. Research on these viruses has relied heavily on immortalized B cell and endothelial cell lines. Therefore, we know very little about the cell type specific regulation of virus infection. We have previously shown that treatment of MHV68-infected macrophages with the cytokine interleukin-4 (IL-4) or challenge of MHV68-infected mice with an IL-4-inducing parasite leads to virus reactivation. However, we do not know if all latent reservoirs of the virus, including B cells, reactivate the virus in response to IL-4. Here we used anin vivoapproach to address the question of whether all latently infected cell types reactivate MHV68 in response to a particular stimulus. We found that IL-4 receptor expression on macrophages was required for IL-4 to induce virus reactivation, but that it was dispensable on B cells. We further demonstrated that the transcription factor, STAT6, which is downstream of the IL-4 receptor and binds a viral promoter in macrophages, did not bind to the viral promoter in B cells. These data suggest that stimuli that promote herpesvirus reactivation may only affect latent virus in particular cell types, but not in others.

Importance

Herpesviruses establish life-long quiescent infections in specific cells in the body, and only reactivate to produce infectious virus when precise signals induce them to do so. The signals that induce herpesvirus reactivation are often studied only in one particular cell type infected with the virus. However, herpesviruses establish latency in multiple cell types in their hosts. Using murine gammaherpesvirus-68 (MHV68) and conditional knockout mice, we examined the cell type specificity of a particular reactivation signal, interleukin-4 (IL-4). We found that IL-4 only induced herpesvirus reactivation from macrophages, but not from B cells. This work indicates that regulation of virus latency and reactivation is cell type specific. This has important implications for therapies aimed at either promoting or inhibiting reactivation for the control or elimination of chronic viral infections.
Torsin ATPases influence chromatin interaction of the Torsin regulator LAP1
Authors: Luithle Naemi , de Bos Jelmi uit , Hovius Ruud , Maslennikova Daria , Lewis Renard , Ungricht Rosemarie , Fierz Beat , Kutay Ulrike
Published: October 2020

The inner nuclear membrane is functionalized by diverse transmembrane proteins that associate with nuclear lamins and/or chromatin. When cells enter mitosis, membrane-chromatin contacts must be broken to allow for proper chromosome segregation; yet how this occurs remains ill-understood. Unexpectedly, we observed that an imbalance in the levels of the lamina-associated polypeptide 1 (LAP1), an activator of ER-resident Torsin AAA+-ATPases, causes a failure in membrane removal from mitotic chromatin, accompanied by chromosome segregation errors and changes in post-mitotic nuclear morphology. These defects are dependent on a hitherto unknown chromatin-binding region of LAP1 that we have delineated. LAP1-induced NE abnormalities are efficiently suppressed by expression of wild-type but not ATPase-deficient Torsins. Furthermore, a dominant-negative Torsin induces chromosome segregation defects in a LAP1-dependent manner. These results indicate that association of LAP1 with chromatin in the nucleus can be modulated by Torsins in the perinuclear space, shedding new light on the LAP1-Torsin interplay.
VARIOUS METHODS OF CHILLING AND HIGH-VOLTAGE ELECTRICAL STIMULATION APPLIED IN SUSTAINABLE BEEF PRODUCTION SYSTEMS
Authors: Banach Joanna K. , Żywica Ryszard , Matusevičius Paulius
Published: October 2020

Entrepreneurs implementing the concept of sustainable development of meat production are highly interested in combining various red meat chilling systems with quality-improving techniques. Therefore, we analyzed the impact of high-voltage electrical stimulation (HVES) and selected chilling methods on changes in quality characteristics and weight loss of beef. We also studied energy consumption based on the heat balance of chilling chambers during the fast chilling of varying amounts of raw material.

The HVES and the fast chilling method yielded positive economic (meat weight loss), technological (high quality, hot-boning), energetic (lower electricity consumption), and organizational effects (increased chilling speed, reducing of storage surfaces and expenditures for staff wages) compared to the slow and accelerated methods. Reaching the desired final temperature with an increased amount of chilled meat enabled a few-fold reduction in the total heat collected from the chambers and in meat weight loss. This allows recommending the above actions to be undertaken by entrepreneurs in the pursuit of sustainable meat production.
The Potential Applications of Site-Directed Mutagenesis for Crop Improvement: A review
Authors: Bezie Yilkal , Tilahun Tadesse , Atnaf Mulugeta , Taye Mengistie
Published: October 2020

The search for technologies for crop improvement has been a continuous practice to address the food insecurity to the growing human population with an ever decreasing arable land and dynamic climate change around the world. Considering the potential technologies for crop improvement could close the rooms of poverty in developing countries in particular and around the globe at large. This review aimed to assess the site-directed mutation creation methods and to show the potential tools for future crop improvement programs. Site-directed mutagenesis was found to be an efficient process to create targeted mutation on cereal crops, horticultural crops, oilseed crops, and others. Agronomic traits such as yield, quality, and stress tolerance have been improved using site-directed mutagenesis. Besides, selectable marker elimination was also reported from transgenic crops by targeted mutation. Most of the reports on site-directed mutagenesis is focusing on cereal crops (58.339%) followed by horticultural crops (22.92%). Among the four mutagenic tools that have been reported, the CRISPR/Ca9 technology was found to be frequently used (66.67%) followed by TALENs. This tool is potential since it is efficient in creating targeted mutagenesis and less likely off-target effect, so it is repeatedly used in different research works. TALENs were used usually to knockout genes with bad traits. Moreover, the mutation created by mutagenic tools found to be efficient, and the mutated traits proved as it was heritable to generations. Hence, site-directed mutagenesis by the CRISPR/Cas9 system is advisable for agricultural development thereby ensuring food sustainability around the world.
Could network structures generated with simple rules imposed on a cubic lattice reproduce the structural descriptors of globular proteins?
Authors: Okan Osman Burak , Turgut Deniz , Atilgan Canan , Atilgan Ali Rana , Ozisik Rahmi
Published: October 2020

A direct way to spot structural features that are universally shared among proteins is to find proper analogues from simpler condensed matter systems. In most cases, sphere-packing arguments provide a straightforward route for structural comparison, as they successfully characterize a wide array of materials such as close packed crystals, dense liquids, and structural glasses. In the current study, the feasibility of creating ensembles of artificial structures that can automatically reproduce a large number of geometrical and topological descriptors of globular proteins is investigated. Towards this aim, a simple cubic (SC) arrangement is shown to provide the best background lattice after a careful analysis of the residue packing trends from 210 proteins. It is shown that a minimalistic set of ground rules imposed on this lattice is sufficient to generate structures that can mimic real proteins. In the proposed method, 210 such structures are generated by randomly removing residues (beads) from clusters that have a SC lattice arrangement until a predetermined residue concentration is achieved. All generated structures are checked for residue connectivity such that a path exists between any two residues. Two additional sets are prepared from the initial structures via random relaxation and a reverse Monte Carlo simulated annealing (RMC-SA) algorithm, which targets the average radial distribution function (RDF) of 210 globular proteins. The initial and relaxed structures are compared to real proteins via RDF, bond orientational order parameters, and several descriptors of network topology. Based on these features, results indicate that the structures generated with 40% occupancy via the proposed method closely resemble real residue networks. The broad correspondence established this way indicates a non-superficial link between the residue networks and the defect laden cubic crystalline order. The presented approach of identifying a minimalistic set of operations performed on a target lattice such that each resulting cluster possess structural characteristics largely indistinguishable from that of a coarse-grained globular protein opens up new venues in structural characterization, native state recognition, and rational design of proteins.
The Effects of Social Stress on Memory: If, How and When
Authors: McManus Elizabeth , Talmi Deborah , Haroon Hamied , Muhlert Nils
Published: October 2020

Physical stress, such as from the cold-pressor test, has been robustly associated with altered memory retrieval, but it is not yet clear whether the same happens following psychosocial stress. Studies using psychosocial stressors report mixed effects on memory, leading to uncertainty about the common cognitive impact of both forms of stress. The current study uses a stepped replication design, with four near-identical experiments, each differing by a single critical factor. In three experiments we induced psychosocial stress after participants encoded word stimuli, then assessed retrieval after a prolonged delay. These experiments found no group level influence of postencoding stress on recognition of neutral words or cued recall of word-pairs, but a small effect on recollection of semantically-related words. There was, however, some indication of positive relationships within the stress group between measures of stress (cortisol in experiment 1 and self-reported-anxiety in experiment 3) and recollection of single word stimuli. In the fourth experiment, we found that psychosocial stress immediately before retrieval did not influence word recognition. Overall, our findings demonstrate that psychosocial stress has a typically modest impact on memory, lower than previously claimed, but that individual differences in stress responsivity, particularly for tasks that tap recollection, may help to explain variability in previous findings.
Case report: 16-yr life history and genomic evolution of an ER+ HER2− breast cancer
Authors: Xu Bing , Amallraja Anu , Swaminathan Padmapriya , Elsey Rachel , Davis Christel , Theel Stephanie , Viet Sarah , Petersen Jason , Krie Amy , Davies Gareth , Williams Casey B. , Ehli Erik , Meißner Tobias
Published: October 2020

Metastatic breast cancer is one of the leading causes of cancer-related death in women. Limited studies have been done on the genomic evolution between primary and metastatic breast cancer. We reconstructed the genomic evolution through the 16-yr history of an ER+ HER2− breast cancer patient to investigate molecular mechanisms of disease relapse and treatment resistance after long-term exposure to hormonal therapy. Genomic and transcriptome profiling was performed on primary breast tumor (2002), initial recurrence (2012), and liver metastasis (2015) samples. Cell-free DNA analysis was performed at 11 time points (2015–2017). Mutational analysis revealed a low mutational burden in the primary tumor that doubled at the time of progression, with driver mutations in PI3K–Akt and RAS–RAF signaling pathways. Phylogenetic analysis showed an early branching off between primary tumor and metastasis. Liquid biopsies, although initially negative, started to detect an ESR1 E380Q mutation in 2016 with increasing allele frequency until the end of 2017. Transcriptome analysis revealed 721 (193 up, 528 down) genes to be differentially expressed between primary tumor and first relapse. The most significantly down-regulated genes were TFF1 and PGR, indicating resistance to aromatase inhibitor (AI) therapy. The most up-regulated genes included PTHLH, S100P, and SOX2, promoting tumor growth and metastasis. This phylogenetic reconstruction of the life history of a single patient's cancer as well as monitoring tumor progression through liquid biopsies allowed for uncovering the molecular mechanisms leading to initial relapse, metastatic spread, and treatment resistance.
Impact of corporate governance compliance and board attributes on operating liquidity in pre- and post-corporate governance reforms
Authors: Khan Javed , Rehman Shafiq Ur
Published: October 2020

Purpose

This study aims to investigate the impact of corporate governance compliance, governance reforms and board attributes on operating liquidity of Pakistani listed non-financial firms. The study further tests how these relationships vary in the pre- and post-corporate governance reforms.

Design/methodology/approach

Fixed-effect regression model is used on 10 years panel data from 2007 to 2016 for a sample of 170 firms listed on the Pakistan Stock Exchange. Two-stage least squares model is used for addressing the endogeneity problem.

Findings

The findings reveal that governance compliance and governance reforms negatively affect operating liquidity. Among the board attributes, board meetings, directors’ remuneration, board foreign diversity and board gender diversity are significantly related to operating liquidity. Further exploration indicates that internal governance mechanisms are less effective to safeguard shareholders from expropriation during weak external governance. This suggests that strong external governance is inevitable to the effectiveness of internal governance mechanisms. Overall, the study findings support the agency theory.

Practical implications

The findings provide valid recommendations to policymakers interested in safeguarding the investors to focus on macro-level governance for making the micro-level governance effective. Further, the results provide the executives with an insight to improve the compliance level with the code of corporate governance.

Originality/value

Unlike prior studies, this study examines the impact of corporate governance compliance and novel board attributes – directors’ attendance at board meetings, number of board committees, directors’ remuneration and board foreign diversity on operating liquidity. Further, the study subdivides its sample period into pre- and post-corporate governance reforms to examine how external governance influences internal governance effectiveness.
The challenges of access to local finance for PPP infrastructure project delivery in Nigeria
Authors: Bolomope Muhammed Temitayo , Baffour Awuah Kwasi Gyau , Amidu Abdul-Rasheed , Filippova Olga
Published: October 2020

Purpose

This study explores the challenges of access to finance from local financial institutions (LFIs), i.e. local banks, for public–private partnership (PPP) infrastructure project delivery in Nigeria. The aim is to provide useful insights that could inform policy solutions to ease the local funding of PPP infrastructure projects in Nigeria and, by extension, other developing economies.

Design/methodology/approach

Adopting a qualitative research methodology, the study engaged PPP stakeholders involved in securing funds for PPP infrastructure projects in Nigeria. A total of 15 PPP stakeholders, drawn from the public and private sectors, were purposively selected and their views on the research problem obtained through recorded telephone interviews. The opinions of the research participants were subsequently analyzed and the results discussed with the outcome of the examination of relevant literature.

Findings

The study found that the significant factors affecting access to local finance for PPP infrastructure projects in Nigeria include low capital base by LFIs, weak project viability, lack of capacity to manage PPP-related activities, inconsistent government policy, poor legal framework and public perception of PPP.

Research limitations/implications

Insights from this study are useful for PPP stakeholders in mitigating the barriers that influence access to local finance for PPP infrastructure projects in Nigeria and other developing economies. This study is also useful in enhancing the current policy structure in developing countries as a way of revamping the existing infrastructure framework through LFIs.

Originality/value

This study provides clarity on the peculiar challenges impeding access to finance from LFIs for PPP infrastructure projects in Nigeria and will be useful for debt providers and policymakers in evaluating the bankability of PPP infrastructure projects in Nigeria and other developing countries.