bluuebunny/crossref_metadata_2025 huggingface dataset:
Circadian Rhythm and Glaucoma: What do We Know?
Authors: Ciulla Lauren , Moorthy Meena , Mathew Sunu , Siesky Brent , Verticchio Vercellin Alice C. , Price David , Januleviciene Ingrida , Harris Alon
Published: November 2019

Purpose:

The current understanding of circadian regulation disorders and their involvement in glaucoma pathophysiology are poorly understood, yet they may have a substantial impact on the onset and progression of glaucoma. Herein, we review and summarize all the available literature on circadian rhythm disorder and glaucoma to uncover the impact on glaucoma risk, and we highlight future research and potential novel targets for glaucoma management.

Materials and Methods:

A review of the relevant literature was performed through PubMed through August 1, 2019.

Results:

Within a normal circadian rhythm, intraocular pressure (IOP) peaks at night, whereas blood pressure (BP) troughs at night. High nocturnal IOP coupled with low nocturnal systemic BP results in low ocular perfusion pressure and potential for unobserved damage to retinal tissues and the optic nerve. Circadian-related melatonin and sleep disorders also result in changes in IOP and ocular perfusion pressure that lead to the progression of glaucoma. In addition, impaired perception of light input due to glaucoma can subsequently lead to abnormal serum levels of melatonin, resulting in circadian rhythm misalignment. This disruption of the circadian rhythm also contributes to sleep and mood disorders, common in individuals with glaucoma. As regards treatment, glaucoma medications that lower nocturnal IOP without influencing nocturnal BP or diminishing circadian variation seem most effective.

Conclusions:

Glaucoma progression is influenced by multiple physiological factors regulated by the circadian rhythm. Progression of the disease may also cause physiological changes that lead to circadian-related issues. Further research is warranted on the diurnal cycle, melatonin-mediated processes, and their influence on glaucoma management.
Evaluating the impact of gabapentinoids on sleep health in patients with chronic neuropathic pain: a systematic review and meta-analysis
Authors: Kapustin Daniel , Bhatia Anuj , McParland Aidan , Trivedi Aditya , Davidson Alexandra , Brull Richard , Singh Mandeep
Published: November 2019

Chronic neuropathic pain (NP) is debilitating and impacts sleep health and quality of life. Treatment with gabapentinoids (GBs) has been shown to reduce pain, but its effects on sleep health have not been systematically evaluated. The objective of this systematic review and meta-analysis was to assess the relationship between GB therapy dose and duration on sleep quality, daytime somnolence, and intensity of pain in patients with NP. Subgroup comparisons were planned for high- vs low-dose GBs, where 300 mg per day or more of pregabalin was used to classify high-dose therapy. Trial data were segregated by duration less than 6 weeks and 6 weeks or greater. Twenty randomized controlled trials were included. Primary outcome measures included pain-related sleep interference and incidence of daytime somnolence. Secondary outcomes included daily pain scores (numerical rating scale 0-10) and patient global impression of change. Significant improvement in sleep quality was observed after 6 weeks of GB treatment when compared with placebo (standardized mean difference 0.39, 95% confidence interval 0.32-0.46 P < 0.001). Increased daytime somnolence was observed among all GB-treated groups when compared with placebo. Treated patients were also more likely to report improvement of patient global impression of change scores. Pain scores decreased significantly in patients both after 6 weeks of treatment (P < 0.001) and in trials less than 6 weeks (P = 0.017) when compared with placebo. Our data demonstrate that GBs have a positive impact on sleep health, quality of life, and pain in patients with NP syndromes. However, these benefits come at the expense of daytime somnolence.
Implications of the putamen in pain and motor deficits in complex regional pain syndrome
Authors: Azqueta-Gavaldon Monica , Youssef Andrew M. , Storz Claudia , Lemme Jordan , Schulte-Göcking Heike , Becerra Lino , Azad Shahnaz C. , Reiners Anselm , Ertl-Wagner Birgit , Borsook David , Upadhyay Jaymin , Kraft Eduard
Published: November 2019

Complex regional pain syndrome (CRPS) develops after-limb injury, with persistent pain and deficits in movement frequently co-occurring. The striatum is critical for mediating multiple mechanisms that are often aberrant in CRPS, which includes sensory and pain processing, motor function, and goal-directed behaviors associated with movement. Yet, much remains unknown with regards to the morphological and functional properties of the striatum and its subregions in this disease. Thus, we investigated 20 patients (15 female, age 58 ± 9 years, right-handed) diagnosed with chronic (6+ months of pain duration) CRPS in the right hand and 20 matched, healthy controls with anatomical and resting-state, functional magnetic resonance imaging. In addition, a comprehensive clinical and behavioral evaluation was performed, where each participant's pain, motor function, and medical history were assessed. Complex regional pain syndrome patients harbored significant abnormalities in hand coordination, dexterity, and strength. These clinical pain- and movement-related findings in CRPS patients were concomitant with bilateral decreases in gray matter density in the putamen as well as functional connectivity increases and decreases among the putamen and pre-/postcentral gyri and cerebellum, respectively. Importantly, higher levels of clinical pain and motor impairment were associated with increased putamen-pre-/postcentral gyri functional connectivity strengths. Collectively, these findings suggest that putaminal alterations, specifically the functional interactions with sensorimotor structures, may underpin clinical pain and motor impairment in chronic CRPS patients.
A Comparison of 2 Venous Puncture Sites for Peripheral Implanted Ports
Authors: Katsoulas Theodoros , Kapritsou Maria , Alexandrou Evan , Bastaki Maria , Giannakopoulou Margarita , Kiekkas Panagiotis , Stafylarakis Emmanouil , Konstantinou Evangelos A.
Published: November 2019

The use of peripheral implanted ports to administer parenteral nutrition in a number of patient cohorts is increasingly seen as a safe alternative to chest ports with equivalence in long-term outcomes. Two insertion sites on the upper arm were compared using the zone insertion method (ZIM), which was developed as an approach to optimize and reduce catheter-related exit site complications. The ZIM divides the medial upper arm into 3 main colors, red, green, and yellow, which are based on musculoskeletal, skin, and vessel characteristics. The optimal exit site is considered to be the green zone, the middle third of the upper arm. Thirty-five patients were allocated to vein puncture at the yellow/green zone (group A) and 35 patients at the yellow zone near the axilla (group B). All devices were implanted in the distal green zone. Successful peripheral port implantation was 91.4% (n = 35) for group A and 100.0% (n = 35) for group B (P = .07). No procedural or postprocedural complications were observed.
Thalidomide and Lenalidomide for Refractory Systemic/Cutaneous Lupus Erythematosus Treatment
Authors: Yuki Emily Figueiredo Neves , Silva Clovis A. , Aikawa Nadia E. , Romiti Ricardo , Heise Carlos Otto , Bonfa Eloisa , Pasoto Sandra Gofinet
Published: November 2019

Background

Thalidomide has shown exceptional results in systemic/cutaneous lupus erythematosus(SLE/CLE). Recently, lenalidomide has been also prescribed for SLE/CLE treatment. Literature regarding efficacy/adverse events for these drugs is scarce with a single systematic review and meta-analysis focused solely on thalidomide for refractory cutaneous lupus subtypes.

Objective

We, therefore, addressed in this narrative review the efficacy/adverse effects of thalidomide and lenalidomide for SLE and CLE. In addition, we provide a specialist approach for clinical practice based on the available evidence.

Results

Efficacy of thalidomide for refractory cutaneous lupus treatment was demonstrated by several studies, mostly retrospective with small sample size(≤20). The frequency of peripheral polyneuropathy is controversial varying from 15-80% with no consistent data regarding cumulative dose and length of use. Drug withdrawn results in clinical partial/complete reversibility for most cases (70%). For lenalidomide, seven studies (small sample sizes) reported its efficacy for SLE/CLE with complete/partial response in all patients with a mean time to response of 3 months. Flare rate varied from 25-75% occurring 0.5-10 months after drug withdrawn. There were no reports of polyneuropathy/worsening of previous thalidomide-induced neuropathy, but most of them did not perform nerve conduction studies. Teratogenicity risk exist for both drugs and strict precautions are required.

Conclusions

Thalidomide is very efficacious as an induction therapy for patients with severe/refractory cutaneous lupus with high risk of scarring, but its longstanding use should be avoided due to neurotoxicity. Lenalidomide is a promising drug for skin lupus treatment, particularly regarding the apparent lower frequency of nerve side effects.
FDG PET/CT and Ultrasound Evaluation of Breast Implant–Associated Anaplastic Large Cell Lymphoma
Authors: Pandika Veska , Covington Matthew F.
Published: November 2019

Breast implant–associated anaplastic large cell lymphoma (BIA-ALCL) is a rare malignancy with isolated case reports of FDG uptake on FDG PET/CT. We present 4 cases of pathology-confirmed BIA-ALCL to illustrate varying presentations and imaging features of this disease process. Breast implant–associated anaplastic large cell lymphoma presents most commonly approximately 10 years after implantation of textured silicone or saline breast implants. Patients may present with breast enlargement, peri-implant effusion, a palpable breast or axillary mass, lymphadenopathy, breast skin erythema, or pain. Diagnosis of BIA-ALCL may be confirmed by sampling of peri-implant fluid or biopsy of peri-implant masses or regional lymph nodes.
Pulmonary Vein Varix Mimicking Prostate Cancer Metastasis on 68Ga–Prostate Specific Membrane Antigen-11 PET/CT
Authors: Sgard Brian , Montravers Françoise , Fourquet Aloÿse , de la Taille Alexandre , Gauthé Mathieu
Published: November 2019

The use of PET/CT with prostate-specific membrane antigen radioligands for staging prostate cancer patients presenting a biochemical recurrence is increasing. As a consequence, the number of reports of diagnostic pitfall of this imaging modality is also increasing. A 75-year-old man referred for a second episode of biochemical recurrence of prostate cancer presented an isolated intense prostate-specific membrane antigen-11 uptake from a right lung abnormality. This abnormality was suggestive of pulmonary vein varix on contrast-enhanced lung CT. The uptake remained stable 1 month after starting androgen deprivation therapy, which confirmed the diagnostic of pulmonary vein varix.
Pharmacokinetic Analysis of [18F]FAZA Dynamic PET Imaging Acquisitions for Highlighting Sacrum Tumor Profiles
Authors: Provost Claire , Mammar Hamid , Belly-Poinsignon Anne , Madar Olivier , Champion Laurence
Published: November 2019

A patient enrolled in a clinical trial (NCT02802969) with suspicion of chordoma underwent an [18F]FAZA PET/CT, a radiolabeled nitroimidazole analog of hypoxia PET imaging. The patient's images showed a different tumor profile compared to those observed in other hypoxic or nonhypoxic chordoma patients. The motivation for using [18F]FAZA pharmacokinetic imaging was to compare this profile with histologically confirmed cases of chordoma. Through visual imaging and quantification of blood and tumor time-activity curves, we excluded the hypothesis that it was a chordoma, diagnosing a paraganglioma.
A palaeolimnological perspective to understand regime-shift dynamics in two Yangtze-basin lakes
Authors: Xu Min , Wang Rong , Dong Xuhui , Yang Xiangdong
Published: November 2019

Natural and human disturbances have caused widespread regime shifts in shallow lakes of the lower Yangtze basin (LYB, China) resulting in a severe decline of ecosystem services. Improved understanding of the relationship between environmental forcing and ecosystem response, and the mechanisms behind regime shifts has significant implications for management. However, the patterns of these regime shifts and the underlying internal mechanisms are less known. In this study, two typical lakes (Chaohu and Zhangdu) from the LYB were selected to determine the trajectories of ecological regime shifts, both of which transitioned from vegetation- to plankton-dominated states several decades ago. Ecological trajectories since the 1900s in both lakes were reconstructed using palaeolimnological proxies, mainly diatom assemblages. Although results show that regime shifts occurred in both lakes in the 1970s and the 1950s, respectively, their inherent mechanisms were different. In Lake Zhangdu, altered hydrological conditions pushed the ecosystem across an ecological threshold, providing an example of a driver-mediated regime shift. In Lake Chaohu, ongoing nutrient loading influenced ecosystem processes and drove the lake to an alternative stable state, potentially presenting an example of a critical transition after a loss of resilience. This research indicates that palaeolimnological perspectives can provide insights into regime shift changes, as well as important information regarding which restoration methods should be tailored to individual lakes.
Model genotype–phenotype mappings and the algorithmic structure of evolution
Authors: Nichol Daniel , Robertson-Tessi Mark , Anderson Alexander R. A. , Jeavons Peter
Published: November 2019

Cancers are complex dynamic systems that undergo evolution and selection. Personalized medicine approaches in the clinic increasingly rely on predictions of tumour response to one or more therapies; these predictions are complicated by the inevitable evolution of the tumour. Despite enormous amounts of data on the mutational status of cancers and numerous therapies developed in recent decades to target these mutations, many of these treatments fail after a time due to the development of resistance in the tumour. The emergence of these resistant phenotypes is not easily predicted from genomic data, since the relationship between genotypes and phenotypes, termed the genotype–phenotype (GP) mapping, is neither injective nor functional. We present a review of models of this mapping within a generalized evolutionary framework that takes into account the relation between genotype, phenotype, environment and fitness. Different modelling approaches are described and compared, and many evolutionary results are shown to be conserved across studies despite using different underlying model systems. In addition, several areas for future work that remain understudied are identified, including plasticity and bet-hedging. The GP-mapping provides a pathway for understanding the potential routes of evolution taken by cancers, which will be necessary knowledge for improving personalized therapies.
Target counting with Presburger constraints and its application in sensor networks
Authors: Linker Sven , Sevegnani Michele
Published: November 2019

One of the applications popularized by the emergence of wireless sensor networks is target counting: the computational task of determining the total number of targets located in an area by aggregating the individual counts of each sensor. The complexity of this task lies in the fact that sensing ranges may overlap, and therefore, targets may be overcounted as, in this setting, they are assumed to be indistinguishable from each other. In the literature, this problem has been proven to be unsolvable, hence the existence of several estimation algorithms. However, the main limitation currently affecting these algorithms is that no
assurance
regarding the precision of a solution can be given. We present a novel algorithm for target counting based on exhaustive enumeration of target distributions using linear Presburger constraints. We improve on current approaches since the estimated counts obtained by our algorithm are by construction guaranteed to be consistent with the counts of each sensor. We further extend our algorithm to allow for weighted topologies and sensing errors for applicability in real-world deployments. We evaluate our approach through an extensive collection of synthetic and real-life configurations.
Areal parameter estimates from multiple datasets
Authors: Kennett B. L. N.
Published: November 2019

A wide range of methods exist for interpolation between spatially distributed points drawn from a single population. Yet often multiple datasets are available with differing distribution, character and reliability. A simple scheme is introduced to allow the fusion of multiple datasets. Each dataset is assigned an
a priori
spatial influence zone around each point and a relative weight based on its physical character. The composite result at a specific location is a weighted combination of the spatial terms for all the available data points that make a significant contribution. The combination of multiple datasets is illustrated with the construction of a unified Moho surface in part of southern Australia from results exploiting a variety of different styles of analysis.
Eikenella exigua sp. nov., isolated from brain abscess and blood
Authors: Stormo Kristin A. , Nygaard Randi M. , Bruvold Torbjørn S. , Dimmen Grete , Lindemann Paul Christoffer , Jordal Stina , Kommedal Øyvind
Published: November 2019

We herein describe the first novel species within the genusEikenellasince it was established in 1972 by the reclassification of‘Bacteroides corrodens’ toEikenella corrodens. From a polymicrobial brain abscess, we encountered anEikenellaisolate, PXXT, that could not validly be namedE. corrodens. The isolate grew on blood agar with small, translucent, pitting colonies after 3 days of anaerobic incubation. By reviewing previously collected invasive isolates, we found an additionalEikenellastrain, EI-02, from a blood culture exhibiting the same properties as PXXT. Phylogenetic analyses based on both whole genome and individual house-keeping genes confirmed that the two strains allocate in a phylogenetic cluster separate fromE. corrodens. Using specific amplification and sequencing of theEikenella nusGgene, we further detected the novelEikenellaspecies in six historic brain abscesses previously reported to containE. corrodensbased on 16S metagenomics. Out of 24Eikenellawhole-genome projects available in GenBank, eight cluster together with PXXTand EI-02. These isolates were recovered from brain abscess (n=2), blood (n=1), bone/soft tissue (n=3), parotid gland (n=1) and unknown (n=1). It remains to be investigated whether the new species can cause endocarditis. The average nucleotide identity value between strain PXXTand theE. corrodenstype strain ATCC 23834Twas 92.1 % and the corresponding genome-to-genome distance value was 47.1 %, both supporting the classification of PXXTas a novel species. For this species we propose the nameEikenella exigua. The type strain ofE. exiguais PXXT(DSM 109756T, NCTC 14318T).
Discriminating Progressive Supranuclear Palsy from Parkinson’s Disease using wearable technology and machine learning
Authors: De Vos Maarten , Prince John , Buchanan Tim , FitzGerald James J. , Antoniades Chrystalina A.
Published: November 2019

Background

Progressive supranuclear palsy (PSP), a neurodegenerative conditions may be difficult to discriminate clinically from idiopathic Parkinson’s disease (PD). It is critical that we are able to do this accurately and as early as possible in order that future disease modifying therapies for PSP may be deployed at a stage when they are likely to have maximal benefit. Analysis of gait and related tasks is one possible means of discrimination.

Research Question

Here we investigate a wearable sensor array coupled with machine learning approaches as a means of disease classification.

Methods

21 participants with PSP, 20 with PD, and 39 healthy control (HC) subjects performed a two minute walk, static sway test, and timed up-and-go task, while wearing an array of six inertial measurement units. The data were analysed to determine what features discriminated PSP from PD and PSP from HC. Two machine learning algorithms were applied, Logistic Regression (LR) and Random Forest (RF).

Results

17 features were identified in the combined dataset that contained independent information. The RF classifier outperformed the LR classifier, and allowed discrimination of PSP from PD with 86% sensitivity and 90% specificity, and PSP from HC with 90% sensitivity and 97% specificity. Using data from the single lumbar sensor only resulted in only a modest reduction in classification accuracy, which could be restored using 3 sensors (lumbar, right arm and foot). However for maximum specificity the full six sensor array was needed.

Significance

A wearable sensor array coupled with machine learning methods can accurately discriminate PSP from PD. Choice of array complexity depends on context; for diagnostic purposes a high specificity is needed suggesting the more complete array is advantageous, while for subsequent disease tracking a simpler system may suffice.
Findings of a feasibility study of pre-operative pulmonary rehabilitation to reduce post-operative pulmonary complications in people with chronic obstructive pulmonary disease scheduled for major abdominal surgery
Authors: Marlow Lucy L , Lee Angeline HY , Hedley Emma , Grocott Michael P , Steiner Michael C , Young J. Duncan , Rahman Najib M , Snowden Christopher P , Pattinson Kyle T S
Published: November 2019

Background

Patients with chronic obstructive pulmonary disease (COPD) are at increased risk of complications and death following surgery. Pulmonary complications are particularly prominent. Pulmonary rehabilitation is a course of physical exercise and education that helps people with COPD manage their condition. Although proven to improve health outcomes in patients with stable COPD, it has never been formally tested as a pre-surgical intervention in patients scheduled for non-cardiothoracic surgery. If a beneficial effect were to be demonstrated, pulmonary rehabilitation for pre-surgical patients with COPD might be rapidly implemented across the National Health Service, as pulmonary rehabilitation courses are already well established across much of the United Kingdom (UK).

Methods

We performed a feasibility study to test study procedures and barriers to identification and recruitment to a randomised controlled trial testing whether pulmonary rehabilitation, delivered before major abdominal surgery in a population of people with COPD, would reduce the incidence of post-operative pulmonary complications. This study was run in two UK centres (Oxford and Newcastle upon Tyne).

Results

We determined that a full randomised controlled trial would not be feasible, due to failure to identify and recruit participants. We identified an unmet need to identify more effectively patients with COPD earlier in the surgical pathway. Service evaluations suggested that barriers to identification and recruitment would likely be the same across other UK hospitals.

Conclusions

Although pulmonary rehabilitation is a potentially beneficial intervention to prevent post-operative pulmonary complications, a randomised controlled trial is unlikely to recruit sufficient participants to answer our study question conclusively at the present time, when spirometry is not automatically conducted in all patients planned for surgery. As pulmonary rehabilitation is a recommended treatment for all people with COPD, alternative study methods combined with earlier identification of candidate patients in the surgical pathway should be considered.

Trial registration

ISRCTN 29696295, http://www.isrctn.com/ISRCTN29696295, registered 31st August 2017
An enhancer:involucrin regulatory module impacts human skin barrier adaptation out-of-Africa and modifies atopic dermatitis risk
Authors: Mathyer Mary Elizabeth , Brettmann Erin A. , Schmidt Alina D. , Goodwin Zane A. , Quiggle Ashley M. , Oh Inez Y. , Tycksen Eric , Zhou Lisa , Estrada Yeriel D. , Wong X.F. Colin C. , Denil Simon L.I.J. , Matkovich Scot A. , Shemer Avner , Common John E. A. , Guttman-Yassky Emma , de Guzman Strong Cristina
Published: November 2019

The genetic modules that contribute to human evolution are poorly understood. We identified positive selection for two independent involucrin (IVL) haplotypes in European (CEU) and Asian (JPT/CHB) populations for skin epidermis. CEUIVLassociated with increasedIVLand a known epidermal-specific enhancer underwent a recent selective sweep out-of-Africa correlating with increased northern latitude. CRISPR/Cas9 deletion of the mouse enhancer revealed enhancer-mediatedcisregulation forIvlexpression with human population-specific enhancer reporter assays confirming the additive effect. Furthermore,IVLenhancer eQTLs associated with decreasedIVLtogether with filaggrin loss-of-function variants are enriched in atopic dermatitis cases vs. controls. Together, our enhancer-IVLcis regulatory module findings reveal an emerging paradigm for recently evolved traits to impact skin disease risk in contemporary populations.
Molecular identification of the Trypanosoma (Herpetosoma) lewisi clade in black rats (Rattus rattus) from Australia
Authors: Egan Siobhon L. , Taylor Casey L. , Austen Jill M. , Banks Peter B. , Ahlstrom Liisa A. , Ryan Una M. , Irwin Peter J. , Oskam Charlotte L.
Published: November 2019

Invasive rodent species are known hosts for a diverse range of infectious microorganisms and have long been associated with the spread of disease globally. The present study describes molecular evidence for the presence of a Trypanosoma sp. from black rats (Rattus rattus) in northern Sydney, Australia. Sequences of the 18S ribosomal RNA (rRNA) locus were obtained in two out of eleven (18%) blood samples with subsequent phylogenetic analysis confirming the identity within the Trypanosoma lewisi clade.
Comparison of the Gut Microbiota Composition Between Captive and Wild Roe Deer
Authors: Liu Jinyue , Liang Xue , Liu Yanhua
Published: November 2019

In this paper, 16S-rRNA gene Illumina HiSeq sequencing was used to analyze the structural diversity of captive and wild roe deer gut flora. The results show that the microbial diversity in the feces of wild roe deer is higher than in that of captive roe deer. Both roe deer have similar flora at the phylum level, but the main genus has significant differences. The microbial group that plays an important role in captive roe deer is Bacteroidetes; in wild roe deer it is Firmicutes. This difference is mainly due to the differences in living environment, diet, and physiological functions of the two groups. In conclusion, our study makes people have a better understanding of the intestinal flora of roe deer. By comparing the intestinal microbial structure differences between captive and wild roe deer, it provides theoretical basis for people to raise captive roe deer and provides reference for the protection of wild roe deer.

IMPORTANCE

Many studies have shown that large and complex microbes in the gut of humans and non-human animals, intestinal microbes are thought to co-evolve with the host, help the host acquire nutrients, regulate immunity and to help maintain host homeostasis. The roe deer (Capreolus spp.) is a ruminant. Wild roe deer are listed on the List of Terrestrial Wild Animals Protected by the State or Have Important Economic and Scientific Values, wild roe deer is also a Chinese national protected animal under second class protection. However, current research on the gut microbiota of roe deer has not been reported.
Primary cilia are present on endothelial cells of the hyaloid vasculature but are not required for the development of the blood-retinal barrier
Authors: Pollock Lana M. , Perkins Brian , Anand-Apte Bela
Published: November 2019

Endothelial cilia are found in a variety of tissues including the cranial vasculature of zebrafish embryos. Recently, endothelial cells in the developing mouse retina were reported to also possess primary cilia that are potentially involved in vascular remodeling. Fish carrying mutations in intraflagellar transport (ift) genes have disrupted cilia and have been reported to have an increased rate of spontaneous intracranial hemorrhage (ICH), potentially due to disruption of the sonic hedgehog (shh) signaling pathway. However, it remains unknown whether the endothelial cells forming the retinal microvasculature in zebrafish also possess cilia, and whether endothelial cilia are necessary for development and maintenance of the blood-retinal barrier (BRB). In the present study, we found that the endothelial cells lining the zebrafish hyaloid vasculature possess primary cilia during development. To determine whether endothelial cilia are necessary for BRB integrity,ift57, ift88, andift172mutants, which lack cilia, were crossed with the double-transgenic zebrafish strainTg(l-fabp:DBP-EGFP;flk1:mCherry). This strain expresses a vitamin D-binding protein (DBP) fused to enhanced green fluorescent protein (EGFP) as a tracer in the blood plasma, while the endothelial cells forming the vasculature are tagged by mCherry. The Ift mutant fish develop a functional BRB, indicating that endothelial cilia are not necessary for early BRB integrity. Additionally, although treatment of zebrafish larvae with shh inhibitor cyclopamine results in BRB breakdown, the Ift mutant fish were not sensitized to cyclopamine-induced BRB breakdown.
SPOP Promotes Ubiquitination and Degradation of MyD88 to Suppress the Innate Immune Response
Authors: Li Qinghe , Wang Fei , Wang Qiao , Zheng Maiqing , Liu Ranran , Cui Huanxian , Wen Jie , Zhao Guiping
Published: November 2019

As a canonical adaptor for Toll-like receptor (TLR) family, MyD88 has crucial roles in host defence against infection of microbial pathogens and its dysregulation might induce autoimmune diseases. Here we demonstrate that the Cullin 3-based ubiquitin ligase adaptor SPOP recognizes the intermediate domain and degrades chMyD88 through the proteasome pathway. Knockdown or genetic ablation of chSPOP leads to aberrant elevation of the chMyD88 protein. Consequently, ChSPOP negatively regulates the activity of NF-κB pathway and thus the production of IL-1β and IL-8 upon LPS challenge. Furthermore, SPOP deficiency mice are more susceptible to infection of Salmonella typhimurium. Collectively, these findings demonstrate chMyD88 as a bona fide substrate of chSPOP and uncover a mechanism by which chSPOP suppresses the innate immune signaling.

Author Summary

MyD88 is a central adaptor mediating the initiate of innate immune response and production of proinflammatory cytokines that restrain pathogens and activate adaptive immunity. Although MyD88 is crucial for the host to prevent pathogenic infection, misregulation of MyD88 abundance might lead to autoimmune diseases. Thus, degradation of MyD88 is a canonical mechanism to terminate cytokines production. Here we characterized a novel E3 ligase SPOP that target MyD88 for degradation. SPOP attenuated IL1β and IL8 production through K48-linked polyubiquitination and degradation of MyD88 and thus impaired immune responses. SPOP deficient mice show more susceptibility to infection by Salmonella typhimurium. These findings demonstrate that SPOP is a negative regulator of MyD88-dependent pathway activation triggered by LPS and Salmonella typhimurium, which helps the host to maintain immune homeostasis.
Metastatic function of METTL18 in breast cancer via actin methylation and Src
Authors: Kim Han Gyung , Kim Ji Hye , Yang Woo Seok , Park Jae Gwang , Lee Yong Gyu , Hong Yo Han , Kim Eunji , Jo Minkyeong , Lee Chae Young , Kim Shi Hyung , Sung Nak Yoon , Yi Young-Su , Ratan Zubair Ahmed , Kim Sunggyu , Yoo Byong Chul , Kang Sung-Ung , Kim Young Bong , Kim Sangmin , Paik Hyun-June , Lee Jeong Eon , Nam Seok Jin , Parameswaran Narayanan , Han Jeung-Whan , Cho Jae Youl
Published: November 2019

Recently, a SET domain containing 3 (SETD3) was identified as an actin histidine methyltransferase, functioning to control replication and pathogenesis in multiple mouse models for enterovirus infection as well as the regulation of smooth muscle contractility linked to primary dystocia. Here, in this study, we report another type of actin histidine methyltransferase, METTL18, that regulates the metastatic potential of breast cancer in human. Among methyltransferases, METTL18 was highly amplified in human breast cancer. In particular, poor prognosis was associated with high expression of METTL18 in HER2-negative breast cancer patients. This gene product was also found to be a critical component of metastatic responses. Loss of METTL18 expression significantly reduced metastatic responses of breast tumor cells both in vitro and in vivo. Mechanistically, it was observed that METTL18 increased actin polymerization, upregulated complex formation with HSP90AA1 and Src, enhanced the activity of an intermediate form of Src with tyrosine phosphorylation at both Y416 and Y527, and induced cellular metastatic responses, including morphological change, migration, and invasion of MDA-MB-231 cells in vitro and in mice. Methylated actin at His73 served as a critical site for interaction with HSP90AA1 and Src to activate p85/PI3K and STAT3. Our findings suggest that METTL18 plays critical roles in metastatic responses of HER2-negative breast cancer cells via actin polymerization and the generation of an intermediate form of Src.
Exome Sequencing in Individuals with Isolated Biliary Atresia
Authors: Rajagopalan Ramakrishnan , Tsai Ellen A. , Grochowski Christopher M. , Kelly Susan M. , Loomes Kathleen M. , Spinner Nancy B. , Devoto Marcella
Published: November 2019

Biliary atresia (BA) is a severe pediatric liver disease resulting in necroinflammatory obliteration of the extrahepatic biliary tree. BA presents within the first few months of life as either an isolated finding or with additional syndromic features. The etiology of isolated BA is unknown, with evidence for infectious, environmental, and genetic risk factors described. However, to date, there are no definitive causal genes identified for isolated BA in humans, and the question of whether single gene defects play a major role remains open. We performed exome-sequencing in 100 North American patients of European descent with isolated BA (including 30 parent-child trios) and considered several experimental designs to identify potentially deleterious protein-altering variants that may be involved in the disease. In a case-only analysis, we did not identify genes with variants shared among more than two probands, and burden tests of rare variants using a case-case control design did not yield significant results. In the trio analysis of 30 simplex families (patient and parent trios), we identified 66de novovariants in 66 genes including a nonsense variant, p.(Cys30Ter), in the geneSTIP1. STIP1is a co-chaperone for the heat-shock protein,HSP90AA1, and has been shown to have diverse functions in yeast, flies and mammals, including stress-response.

Conclusion

Our results do not support the hypothesis that a simple genetic model is responsible for the majority of cases of isolated BA. Our finding of ade novomutation in a candidate gene for BA (STIP1) linked to evolutionarily conserved stress responses suggests further exploration of how genetic susceptibility and environmental exposure interact to cause BA is warranted.
Temperature sensitive SMA-causing point mutations lead to SMN instability, locomotor defects, and premature lethality inDrosophila
Authors: Raimer Amanda C. , Singh Suhana S. , Edula Maina R. , Paris-Davila Tamara , Vandadi Vasudha , Spring Ashlyn M. , Gregory Matera A.
Published: November 2019

Spinal muscular atrophy (SMA) is the leading genetic cause of death in young children, arising from homozygous deletion or mutation of theSMN1gene. SMN protein expressed from a paralogous gene,SMN2, is the primary genetic modifier of SMA; small changes in overall SMN levels cause dramatic changes in disease severity. Thus, deeper insight into mechanisms that regulate SMN protein stability should lead to better therapeutic outcomes. Here, we show that SMA patient-derived missense mutations in theDrosophilaSMN Tudor domain exhibit a pronounced temperature sensitivity that affects organismal viability, larval locomotor function, and adult longevity. These disease-related phenotypes are domain-specific and result from decreased SMN stability at elevated temperature. This system was utilized to manipulate SMN levels during various stages ofDrosophiladevelopment. Due to a large maternal contribution of mRNA and protein,Smnis not expressed zygotically during embryogenesis. Interestingly, we find that only baseline levels of SMN are required during larval stages, whereas high levels of protein are required during pupation. This previously uncharacterized period of elevated SMN expression, during which the majority of adult tissues are formed and differentiated, could be an important and translationally relevant developmental stage in which to study SMN function. Altogether, these findings illustrate a novelin vivorole for the SMN Tudor domain in maintaining SMN homeostasis and highlight the necessity for high SMN levels at critical developmental timepoints that is conserved fromDrosophilato humans.
‘Synergistic-cidal’ effect of amoxicillin conjugated silver nanoparticles againstEscherichia coli
Authors: Kirthi Arivarasan Vishnu , Karthik Loganathan , Venkatesan Jayachandran , Chaskar Atul Changdev
Published: November 2019

We are reporting the synergistic effects of amoxicillin coated silver nanoparticles, and sodium cholate is used as the stabilizer. Following, the synthesis of AgNPs physicochemical characterization was carried out using UV spectroscopy, XRD, FTIR, FESEM, AFM and NC-AFM analysis. The confirmation of AgNPs was confirmed UV spectral peak at 426 nm, the morphology of the nanoparticles was found to be spherical, oval with an average size of 35.50 nm. The cytotoxic effect was carried out using MTT assay with IC50 of 50.78 µg/mL and the antibacterial effect was observed as zone of inhibition of 12 mm for E.coli. The drug release was determined as 69%, which contributes to the therapeutic efficacy of water soluble based nanoparticles/nanomedicines for biomedical applications.
Network-based hierarchical population structure analysis for large genomic data sets
Authors: Greenbaum Gili , Rubin Amir , Templeton Alan R. , Rosenberg Noah A.
Published: November 2019

Analysis of population structure in natural populations using genetic data is a common practice in ecological and evolutionary studies. With large genomic data sets of populations now appearing more frequently across the taxonomic spectrum, it is becoming increasingly possible to reveal many hierarchical levels of structure, including fine-scale genetic clusters. To analyze these data sets, methods need to be appropriately suited to the challenges of extracting multilevel structure from whole-genome data. Here, we present a network-based approach for constructing population structure representations from genetic data. The use of community-detection algorithms from network theory generates a natural hierarchical perspective on the representation that the method produces. The method is computationally efficient, and it requires relatively few assumptions regarding the biological processes that underlie the data. We show the approach by analyzing population structure in the model plant speciesArabidopsis thalianaand in human populations. These examples illustrate how network-based approaches for population structure analysis are well-suited to extracting valuable ecological and evolutionary information in the era of large genomic data sets.
Sustainability in the wine sector
Authors: Mastroberardino Piero , Calabrese Giuseppe , Cortese Flora , Petracca Miriam
Published: November 2019

Purpose

The purpose of this paper is to analyse the level of awareness of the topic of sustainability among Italian consumers in the wine sector and their perception – that is, what does it mean to consumers – of this issue.

Design/methodology/approach

This paper develops a quali-quantitative study on a random sample of Vivino reviews analysed through content analysis.

Findings

Awareness of topic of sustainability among Italian wine consumers is currently low, although it is increasing. It is not among the main factors that influence the choice of wine among Italian consumers, who are still mainly attracted by organoleptic properties and characteristics linked to the terroir concept.

Research limitations/implications

The research utilises a random sample, and the analysis is limited to the perception of consumers using online word of mouth (WOM).

Practical implications

To develop a long-term perspective on sustainability in the wine sector, it is necessary to have the courage to make a distinction between sustainability and short-term commercial performance. In addition, a cultural change in wine consumers is necessary and requires a willingness to pay a premium price for sustainable products.

Originality/value

Research on the awareness and perception of Italian wine consumers diffused by online WOM through communities such as Vivino has not yet been carried out.
Culture and Native American economic development
Authors: Lofthouse Jordan Karl
Published: November 2019

Purpose

The purpose of this paper is to explore how culture affects economic development on Native American reservations by examining how culture directs the attention of entrepreneurs and interacts with formal governance institutions.

Design/methodology/approach

This paper combines theoretical insights from economic sociology, market process economics and institutional economics as a basis to evaluate entrepreneurship and economic development on Native American reservations. Culture, as a web of social meanings, shapes what opportunities entrepreneurs are alert to, influences how they perceive transaction costs and determines whether institutions achieve their intended ends. Historical and contemporary case studies are used to build analytical narratives to corroborate the theoretical approach.

Findings

The federal government has imposed many formal institutions on reservations, which have disrupted traditional governance and property rights structures. If formal institutions do not comport with the underlying culture, those institutions do not facilitate positive entrepreneurship and economic growth. Despite the barriers, entrepreneurs across several reservations have leveraged their cultural and social ties to create robust informal economies. In some cases, imposed institutions have fostered rent-seeking and have given rise to a culture of rent-seeking.

Research limitations/implications

This paper looks at Native American entrepreneurship and institutions in the broadest sense. However, there is a large amount of diversity within the cultural and governance structures of Native American communities. Future research could examine specific tribes or reservations in more detail.

Practical implications

This paper elucidates cultural and institutional barriers to productive entrepreneurship on Native American lands. Policymakers must understand these root causes if they are to facilitate economic growth.

Originality/value

This paper’s combination of theoretical perspectives helps explain the widespread economic development issues on Native American lands.
Knowledge, attitude and practice levels regarding malaria among people living in the malaria endemic area of Myanmar
Authors: Aung Pyae Linn , Pumpaibool Tepanata , Soe Than Naing , Kyaw Myat Phone
Published: November 2019

Purpose

Malaria still remains a significant public health problem in Myanmar and it has a complex epidemiology. Evidence-based community awareness raising interventions are also particularly needed. This cross-sectional study was organized to explore the basic characteristics associated with knowledge, attitude and practice (KAP) regarding malaria among people living in the most malaria-endemic villages of the Banmauk Township, Sagaing Region, Myanmar. The paper aims to discuss these issues.

Design/methodology/approach

The Banmauk, one of the most malaria-endemic townships, was selected purposively in order to represent the survey results for people living in malaria hotspots. During the peak malaria season (July 2018), 250 household leaders were invited to be interviewed with structured questionnaires. In addition to descriptive data, the associations were determined byχ2-test and correlation.

Findings

Overall KAP indicated considerably low percentages of good levels, especially in practice, only 21.6 percent showed good practice, 38.4 percent had good knowledge and 56.8 percent had good attitude. Age (p=0.022) and annual family income (p<0.001) were significantly associated with the knowledge level, whereas having fever attacks among family members in the last two weeks (p=0.023) showed statistical association with attitude at ap-value <0.05. Surprisingly, there were no associated variables with malaria practice. In addition, there were negative correlations between knowledge with attitude and knowledge with practice; however, the results were not significant.

Originality/value

The overall KAP regarding malaria was at relatively poor levels among people living in malaria transmission areas. Therefore, new approaches to improve malaria KAP are promptly needed in this community.
Do health care companies of India fulfil government’s new orientation towards CSR activities
Authors: Yadav Shashi Lata , Vishwanath Babitha , Patnaik Debasis
Published: November 2019

Purpose

Corporate social responsibility (CSR) in India includes education, environment, healthcare and rural development. In post-liberalized India, the healthcare sector (services and facilities) has grown in leaps and bounds over last two decades. The purpose of this paper is to reveal and explain the CSR profile of select healthcare companies of India and reveal gaps and scope of healthcare activities with a special consideration towards maternal health.

Design/methodology/approach

Primary data are collected from seven listed companies of Goa state which were willing to participate in the study. In total, 67 companies constituting the Healthcare Sector Index of Standard & Poor of the Bombay Stock Exchange are considered as secondary source. Data of 59 companies that come within the threshold of Companies Act, 2013, are studied. CSR guidelines (with a turnover of Rs 10bn or a market capitalization of Rs 5bn or a net profit of Rs 50m) are taken as an initial frame of reference.

Findings

In total, 89.83 per cent of these companies have initiatives related to health care. Structured companies (contribute to the company’s overall mission and goals) with CSR policy have committee size varying from three to five directors with an independent director. During 2016–2017, they were mandated to spend Rs 4.2613bn out of which only 74.59 per cent was spent. Geographical spread of CSR initiatives is skewed, with majority of companies focussing on the states of Maharashtra and Gujarat, whereas the states of Odisha and North-Eastern being neglected. The focus areas of CSR are education, healthcare and rural development. The variation of MMR in different states of India is an indicator for corporate as to which state needs more attention. The corporate sector in India needs to focus on SDG3 target of MMR and move towards a newer dimension and direction.

Originality/value

The originality of this paper lies in the recognition of the initiative of Government of India of weaning out CSR activities outside the purview of business sense and towards instilling a social sense in company behaviour. This is a dimensional and directional change in the evolution of CSR practices in companies and countries. To this end, 59 healthcare sector companies under the threshold of Companies Act 2013 were studied and results were outlined.