bluuebunny/crossref_metadata_2025 huggingface dataset:
Modulation of Morpho-Physiological Responses in Populus deltoides by Elevated Carbon Dioxide and Temperature
Authors: Yadav Santosh Kumar , Singh Hukum , Nautiyal Raman , Ginwal Harish Singh , Ansari Shamim Akhtar , Barthwal Santan
Published: December 2019

Rising atmospheric carbon dioxide (CO2) and temperature alter gene-expression arrays commensurate with physio-morphological changes, resulting in issues of adaptation, growth patterns, and productivity of terrestrial vegetation. An experiment was conducted to investigate the adaptive response of Populus deltoides clone G48 to the combined effect of elevated CO2 and temperature inside open-top chambers. The elevated CO2 and temperature acted as environmental cues to help express upregulated/downregulated genes involved in important metabolic pathways. As a result, P. deltoides exposed to the elevated CO2 and temperature developed adaptation to undo the effect by enhancing gaseous exchange, transpiration, and carbon assimilation and partitioning as observed on 180 days after treatment. The elevated conditions significantly enhanced stomatal density and size on adaxial/abaxial leaf surfaces, chlorophyll b that augmented photosynthesis, stomatal conductance, transpiration, and internal CO2, but decreased instantaneous and intrinsic water-use efficiency. These stimulated biomass accumulation in root, stem, and leaves. Hence, the elevated conditions of CO2 and temperature operate at the gene-expression level that acts pleiotropically for reinforcement of photosynthetic apparatus, morphological amendment for accelerated gaseous exchange, and finally growth and biomass improvement, supporting adaptive plasticity of clonal planting stock of the species to future climatic change and global warming.
Plant Water Stress and Soil Depletion in Variable-Density, Red Alder/Western Hemlock Coastal Oregon Plantations
Authors: Cole Elizabeth C , Newton Michael
Published: December 2019

Riparian ecosystems provide critical habitat and functions while being some of the most productive areas in forests. Both conifers and hardwoods contribute to maintenance of habitat and function. To determine the impact of water stress on growth of red alder (Alnus rubra Bong.) and western hemlock (Tsuga heterophylla [Raf.] Sarg.), we installed Nelder type 1a combined with replacement series plots on three Oregon Coast Range sites. Densities ranged from 988 to 85,400 trees/hectare, with ratios (hemlock:alder) of 100:0, 75:25, 50:50, 25:75, and 0:100. In the first 4 years after planting, alder used water in the growing season at greater depths earlier than western hemlock. Higher densities resulted in greater water stress later in the growing season in weeded areas (maintained by herbicide applications), but stress was similar across densities in unweeded areas. Water stress at early ages was correlated with decreased size 14 or 24 years after planting for both species, but these correlations were confounded with other effects of density. Increasing water availability in areas with low summer precipitation could enhance growth of red alder and western hemlock, even in highly productive riparian areas.
Attitudes Toward Aging: A Glance Back at Research Developments Over the Past 75 Years
Authors: Chu Li , Lay Jennifer C , Tsang Vivian Hiu Ling , Fung Helene H
Published: December 2019

With global aging, it is crucial to understand how older adults and the process of aging are viewed by members of society. These attitudes can often influence how older adults are treated. Since the Journal of Gerontology was founded, we have gained increasing insights into attitudes toward aging, with several notable research developments, including clearer conceptualization of different types of aging attitudes (e.g., life-domain-specific attitudes and self-perceptions of aging), a wider variety of measurements, better understanding of how different social determinants shape aging attitudes, and more sophisticated investigations of cultural variance and invariance in aging attitudes. In this article, we highlight these major shifts in the field of aging attitudes in the past 75 years, discuss the contributions of these developments, and point to potential future directions.
Quantum chemical elucidation on corrosion inhibition efficiency of Schiff base: DFT investigations supported by weight loss and SEM techniques
Authors: Al-Amiery Ahmed , Salman Taghried A , Alazawi Khalida F , Shaker Lina M , Kadhum Abdul Amir H , Takriff Mohd S
Published: December 2019

The corrosion inhibition of Schiff base, namely 2-((2-hydroxy-5-methoxybenzylidene)amino)pyridine (HMAP), for mild steel (MS) in a 1 M hydrochloric acid environment was investigated by means of weight loss and scanning electron microscopy techniques. Quantum chemical calculation based on density functional theory (DFT) was carried out on HMAP. Results illustrated that HMAP is a superior inhibitor for the corrosion of MS in 1.0M hydrochloric acid environment, and inhibition efficiency is higher than 90.0% at 0.5 g/L HMAP. Inhibition performance increases with regard to concentration increase and inhibition performance decreases when raising temperature. Adsorption of the inhibitor on the MS surface followed Langmuir adsorption isotherm and the value of the free energy of adsorption; ΔGads indicated that the adsorption of HMAP was a physisorption/chemisorption process. The DFT refers to perfect correlation with methodological inhibition performance.
Privacy-preserving model learning on a blockchain network-of-networks
Authors: Kuo Tsung-Ting , Kim Jihoon , Gabriel Rodney A
Published: December 2019

Objective

To facilitate clinical/genomic/biomedical research, constructing generalizable predictive models using cross-institutional methods while protecting privacy is imperative. However, state-of-the-art methods assume a “flattened” topology, while real-world research networks may consist of “network-of-networks” which can imply practical issues including training on small data for rare diseases/conditions, prioritizing locally trained models, and maintaining models for each level of the hierarchy. In this study, we focus on developing a hierarchical approach to inherit the benefits of the privacy-preserving methods, retain the advantages of adopting blockchain, and address practical concerns on a research network-of-networks.

Materials and Methods

We propose a framework to combine level-wise model learning, blockchain-based model dissemination, and a novel hierarchical consensus algorithm for model ensemble. We developed an example implementation HierarchicalChain (hierarchical privacy-preserving modeling on blockchain), evaluated it on 3 healthcare/genomic datasets, as well as compared its predictive correctness, learning iteration, and execution time with a state-of-the-art method designed for flattened network topology.

Results

HierarchicalChain improves the predictive correctness for small training datasets and provides comparable correctness results with the competing method with higher learning iteration and similar per-iteration execution time, inherits the benefits of the privacy-preserving learning and advantages of blockchain technology, and immutable records models for each level.

Discussion

HierarchicalChain is independent of the core privacy-preserving learning method, as well as of the underlying blockchain platform. Further studies are warranted for various types of network topology, complex data, and privacy concerns.

Conclusion

We demonstrated the potential of utilizing the information from the hierarchical network-of-networks topology to improve prediction.
LncRNA DLGAP1-AS2 modulates glioma development by up-regulating YAP1 expression
Authors: Miao Wei , Li Ning , Gu Bin , Yi Guoqing , Su Zheng , Cheng Huilin
Published: December 2019

LncRNA DLGAP1 antisense RNA 2 (DLGAP1-AS2) is one kind cytoplasmic long non-coding RNA; however, there is rarely little information about its function in physiological process. Here, we demonstrated that LncRNA DLGAP1-AS2 was up-regulated in glioma and was quite correlated with poor prognosis of glioma patients. Depletion of DLGAP1-AS2 in glioma cells could inhibit cell proliferation and cell migration, and induce cell apoptosis, resulting in the suppression of the progression of glioma consequently. Furthermore, knockdown of DLGAP1-AS2 inhibited the growth of xenograft glioma tumour in vivo as well. Finally, we verified Yes Associated Protein 1 (YAP1) was the downstream target of DLGAP1-AS2 and DLGAP1-AS2 modulated glioma cell proliferation, migration and apoptosis via regulating YAP1. Our study revealed novel mechanism about how did lncRNA DLGAP1-AS2 execute function in glioma and thus provided potential therapeutic interventions for the treatment of glioma.
Assessment of the Systems Approach for the Phytosanitary Treatment of Wood Infested With Wood-Boring Insects
Authors: Macquarrie Chris J K , Gray Meghan , Lavallée Robert , Noseworthy Meghan K , Savard Marc , Humble Leland M
Published: December 2019

Addressing the risk from pests present in wood and wood products destined for international trade is an essential step towards minimizing the movement, introduction and establishment of invasive species. One method of managing the pest risk associated with wood commodities is the use of a systems approach that incorporates multiple independent measures applied along a production pathway. However, quantifying the reduction of risk can be difficult because the approach requires raw material infested with the pest of interest at a sufficient density to be able to quantify changes in pest abundance. We tested a systems approach for the production of sawn wood using green ash, Fraxinus pennsylvanica Marshall (Lamiales: Oleaceae), infested with emerald ash borer, Agrilus planipennis Fairmaire (Coleoptera: Buprestidae), by quantifying the change in pest density during the milling process and the precise effect of heat treatment on insects in situ. Greater than 90% of emerald ash borer were removed at the first step of the milling process (debarking) and >99% were removed before the production of green sawn wood. No insects survived kilning or heat treatment. All life stages of emerald ash borer were killed at 56°C and above. Heat, however, had no sublethal effect on emerald ash borer performance. These results show that the application of a systems approach to mitigate emerald ash borer in heat-treated, sawn wood is effective. Moreover, the model-system approach developed in this study can be a template for investigating the effect of systems approaches for other phloem-feeding insects.
Special issue on logics and artificial intelligence
Authors: Falomir Zoe , Costa Vicent , Plaza Enric , Gibert Karina
Published: December 2019

There is a significant range of ongoing challenges in artificial intelligence (AI) dealing with reasoning, planning, learning, perception and cognition, among others. In this scenario, many-valued logics emerge as one of the topics in many of the solutions to some of those AI problems. This special issue presents a brief introduction to the relation between logics and AI and collects recent research works on logic-based approaches in AI.
Knowledge, Attitudes, and Practices of Pediatric Long-term Care Facility Staff Regarding Infection Control for Acute Respiratory Infections and Influenza Vaccination
Authors: Saiman Lisa , Wilmont Sibyl , Hill-Ricciuti Alexandra , Jain Meaghan , Collins Emily , Ton Adrienne , Neu Natalie , Prill Mila M , Garg Shikha , Larson Elaine , Stone Nimalie D , Gerber Susan I , Kim Lindsay
Published: December 2019

We surveyed clinical staff and on-site teachers working at pediatric long-term care facilities regarding prevention and control of acute respiratory infections and influenza in staff and residents. We uncovered knowledge gaps, particularly among teachers and clinical staff working <5 years at sites, thereby elucidating areas for targeted staff education.
Constructing the bundle sheath towards enhanced photosynthesis
Authors: Singh Pallavi , Reeves Gregory
Published: December 2019

This article comments on:

van Rooijen R, Schulze S, Petzsch P, Westhoff P. 2020. Targeted misexpression of NAC052, acting in H3K4 demethylation, alters leaf morphological and anatomical traits in Arabidopsis thaliana. Journal of Experimental Botany 71, 1434–1448.
Deamination hotspots among APOBEC3 family members are defined by both target site sequence context and ssDNA secondary structure
Authors: McDaniel Yumeng Z , Wang Dake , Love Robin P , Adolph Madison B , Mohammadzadeh Nazanin , Chelico Linda , Mansky Louis M
Published: December 2019

The human apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3 (APOBEC3, A3) family member proteins can deaminate cytosines in single-strand (ss) DNA, which restricts human immunodeficiency virus type 1 (HIV-1), retrotransposons, and other viruses such as hepatitis B virus, but can cause a mutator phenotype in many cancers. While structural information exists for several A3 proteins, the precise details regarding deamination target selection are not fully understood. Here, we report the first parallel, comparative analysis of site selection of A3 deamination using six of the seven purified A3 member enzymes, oligonucleotides having 5′TC3′ or 5′CT3′ dinucleotide target sites, and different flanking bases within diverse DNA secondary structures. A3A, A3F and A3H were observed to have strong preferences toward the TC target flanked by A or T, while all examined A3 proteins did not show a preference for a TC target flanked by a G. We observed that the TC target was strongly preferred in ssDNA regions rather than dsDNA, loop or bulge regions, with flanking bases influencing the degree of preference. CT was also shown to be a potential deamination target. Taken together, our observations provide new insights into A3 enzyme target site selection and how A3 mutagenesis impacts mutation rates.
Constitutional mismatch repair deficiency–associated brain tumors: report from the European C4CMMRD consortium
Authors: Guerrini-Rousseau Léa , Varlet Pascale , Colas Chrystelle , Andreiuolo Felipe , Bourdeaut Franck , Dahan Karin , Devalck Christine , Faure-Conter Cécile , Genuardi Maurizio , Goldberg Yael , Kuhlen Michaela , Moalla Salma , Opocher Enrico , Perez-Alonso Vanessa , Sehested Astrid , Slavc Irene , Unger Sheila , Wimmer Katharina , Grill Jacques , Brugières Laurence
Published: December 2019

Background

Malignant brain tumors (BT) are among the cancers most frequently associated with constitutional mismatch repair deficiency (CMMRD), a rare childhood cancer predisposition syndrome resulting from biallelic germline mutations in mismatch repair genes. This study analyzed data from the European “Care for CMMRD” (C4CMMRD) database to describe their clinical characteristics, treatments, and outcome with the aim of improving its diagnosis/treatment.

Methods

Retrospective analysis of data on patients with CMMRD and malignant BT from the C4CMMRD database up to July 2017.

Results

Among the 87 registered patients, 49 developed 56 malignant BTs: 50 high-grade gliomas (HGG) (with giant multinucleated cells in 16/21 histologically reviewed tumors) and 6 embryonal tumors. The median age at first BT was 9.2 years [1.1–40.6], with nine patients older than 18. Twenty-seven patients developed multiple malignancies (including16 before the BT). Most patients received standard treatment, and eight patients immunotherapy for relapsed HGG. The 3- and 5-year overall survival (OS) rates were 30% (95% CI: 19–45) and 22% (95% CI: 12–37) after the first BT, with worse prognosis for HGG (3-year OS = 20.5%). Six patients were alive (median follow-up 2.5 years) and 43 dead (38 deaths, 88%, were BT-related). Other CMMRD-specific features were café-au-lait macules (40/41), multiple BTs (5/15), developmental brain anomalies (11/15), and consanguinity (20/38 families).

Conclusions

Several characteristics could help suspecting CMMRD in pediatric malignant BTs: giant cells on histology, previous malignancies, parental consanguinity, café-au-lait macules, multiple BTs, and developmental brain anomalies. The prognosis of CMMRD-associated BT treated with standard therapies is poor requiring new therapeutic up-front approaches.
Sequelae of Lassa Fever: Postviral Cerebellar Ataxia
Authors: Ezeomah Chiomah , Adoga Adeyi , Ihekweazu Chikwe , Paessler Slobodan , Cisneros Irma , Tomori Oyewale , Walker David
Published: December 2019

Lassa fever is a zoonotic disease endemic in some West African countries. It is exported to countries in America, Asia, and Europe. Antivirals against Lassa fever are important to provide a cure in patients with the disease and provide protection against it. In addition, due to the potential utilization of Lassa virus as a bioterrorism agent, vaccines against the disease can be utilized as a counterterrorism measure. Developing antiviral compounds and vaccines against the disease requires understanding of the pathogenesis of Lassa fever and its disease course, including the signs, symptoms, complications, and sequelae. An important sequela of Lassa fever is ataxia. A few cases of postviral ataxia following Lassa fever have been described in the literature. This review focuses on highlighting these cases, the gaps in scientific knowledge where further research is needed, and possible ways of diagnosing postviral ataxia after Lassa fever in resource-limited settings.
Exposure of the V1 Segment of the Vertebral Artery: Stepwise Cadaveric Surgical Simulation
Authors: Tayebi Meybodi Ali , Borba Moreira Leandro , Gandhi Sirin , Catapano Joshua C , Preul Mark C , Lawton Michael T
Published: December 2019

BACKGROUND

Surgical exposure of the V1 segment of the vertebral artery (V1-VA) at the lower neck may be necessary to address intravascular (atherosclerotic) and extravascular (external compression by neoplastic or degenerative) pathologies. The adjacent anatomy at the lower cervical region is complex and relatively unfamiliar to neurosurgeons compared to that of upper cervical levels. High-quality cadaveric images simulating the surgical approach to V1-VA are important for learning the relevant anatomy.

OBJECTIVE

To provide a brief stepwise depiction of the exposure of the V1-VA using a cadaveric surgical simulation.

METHODS

A cadaveric surgical simulation was performed on the left side to expose the V1-VA using the retrojugular and interjugular carotid approaches. The important adjacent anatomic structures en route to the V1-VA were identified.

RESULTS

A stepwise photographic demonstration of the surgical exposure of the V1-VA is provided.

CONCLUSION

Exposure of the V1-VA can be challenging and requires a clear anatomic understanding of the relevant anatomy. The present work attempts to facilitate this objective.
A cooperative study assessing reproductive performance in sows fed diets supplemented with organic or inorganic sources of trace minerals
Authors: Tsai Tsung , Apgar Gary A , Estienne Mark J , Wilson Mark , Maxwell Charles V
Published: December 2019

Sows from three university research facilities (n = 245) were stratified by parity and initial body weight (BW), and within outcome groups, randomly assigned to fortified corn- and soybean meal-based control or organic trace mineral-supplemented, gestation (3,339 kcal/kg ME; 0.62% standradized ileal digestible [SID] lysine), and lactation (3,374 kcal/kg ME; 0.97% SID lysine) diets. Control gestation and lactation diets were supplemented with inorganic trace minerals (120 ppm Zn from ZnO, 30 ppm Cu from CuSO4, and 50 ppm Mn from MnSO4), and the experimental diets contained the same total level of minerals but complexed organic trace minerals replaced 50% of the inorganic trace minerals. Sows were fed to condition during gestation and on an ad libitum basis during lactation. Sow BW (breeding, d 110 of gestation, 48 h post-farrowing, and weaning) and feed consumed were recorded. During gestation, control sows tended to gain less weight (60.4 vs. 64.6 kg, P = 0.06) and consumed less feed (263.5 vs. 264.8 kg, P = 0.05), and had poorer Gain:Feed (G:F) (0.27 vs. 0.29, P = 0.04) than sows fed the organic trace minerals. Sow average daily feed intake (ADFI) during lactation was similar (P = 0.28) between groups (4.93 vs. 4.74 kg for control and treated sows, respectively). Number of pigs born alive (11.4 vs. 10.9, P = 0.24) and weaned (10.2 vs. 9.8, P = 0.18), and pig pre-weaning average daily gain (ADG) (0.27 vs. 0.27 kg/d, P = 0.77) and mortality (13.1 vs. 12.9%, P = 0.92) were similar for control and treated sows, respectively. Results of the current study demonstrate that sows fed diets supplemented with organic trace minerals displayed similar reproductive performance, but improved weight gain and G:F during gestation compared with sows fed inorganic trace minerals.
A case study of a theory-based method for identifying and reporting core functions and forms of evidence-based interventions
Authors: Kirk M Alexis , Haines Emily R , Rokoske Franziska S , Powell Byron J , Weinberger Morris , Hanson Laura C , Birken Sarah A
Published: December 2019

Adaptation of existing evidence-based interventions (EBIs) to improve their fit in new contexts is common. A critical first step in adaptation is to identify core functions (purposes) and forms (activities) of EBIs. Core functions should not be adapted as they are what account for the efficacy of EBIs. Despite their importance, core functions are rarely identified by EBI developers; methods for identifying them post hoc are lacking.

We present a case study of theory-based methods for identifying core functions and forms post hoc. We developed these methods as the first step in a larger effort to adapt an existing EBI to improve the timeliness of referrals to hospice to a new patient population and care setting. Our methods were rooted in the Planned Adaptation Model (PAM). Through our case study, we developed six steps for identifying core functions and forms, as well as accompanying tools and methods. Our case study further operationalized PAM in several ways. Where PAM offered guiding tenets for identifying core functions and forms (review existing EBI materials, conduct primary data collection, and identify the theory of change), we produced specific tools (interview guides and codebooks) and methods (sampling approaches and analytic methods). Our case study extended PAM with the addition of two steps in the process of identifying core functions and forms: (a) identifying the usual care pathway, including barriers to the outcome of interest encountered in usual care, and (b) mapping EBI core functions onto an extant theory. Identifying core functions and forms is a critical first step in the adaptation process to ensure adaptations do not inadvertently compromise the efficacy or effectiveness of the EBI by compromising core functions. Our case study presents step-by-step methods that could be used by researchers or practitioners to identify core functions and forms post hoc.
Epipremnum aureum Keratopathy: Case Report and Review of the Literature
Authors: Cohen Adam K. , Theotoka Despoina , Galor Anat
Published: December 2019

Objectives:

To report a novel case of Epipremnum aureum toxicity masquerading as bilateral infectious keratitis and review the literature on ocular manifestations of Epipremnum exposure.

Methods:

Case report and literature review.

Results:

A 70-year-old man with a history of photorefractive keratectomy presented with a 3-day history of bilateral eye pain. The patient reported exposure to plant debris while performing yard work and also water exposure while cleaning his coral fish tanks. Clinical examination revealed bilateral epitheliopathy progressing to frank epithelial defects with underlying stromal necrosis 6 days after exposure. Empiric topical antibiotic drops were initiated, but multiple cultures, corneal biopsy, and confocal microscopy were all negative for an infectious agent. Over a 2-week period, the epithelial defects worsened and a suspicion for a toxic etiology was raised. The patient later recalled rubbing his eyes after exposure to Epipremnum aureum (Golden Pothos/Devils Ivy) sap. He was thus treated conservatively with artificial tears, topical corticosteroids, and amniotic membrane. After 3 months, the epithelial defects resolved, but with corneal scarring, prominently in the left eye and underwent penetrating keratoplasty. Five years after presentation, best-corrected visual acuity with hard contact lenses was 20/25 in the right eye and 20/20 in the left eye.

Conclusion:

Epipremnum aureum toxicity is a rare cause of keratitis. It can mimic acanthamoeba keratitis or anesthetic abuse and should be considered in cases of culture negative nonhealing corneal ulcerations. Eliciting a history of plant sap exposure can facilitate appropriate supportive care for this toxic keratitis.
Prevalence of Ocular Surface Disease and Corneal Irregularity and Outcomes in Patients Using Therapeutic Scleral Lenses at a Tertiary Care Center
Authors: Scanzera Angelica C. , Bontu Sneha , Joslin Charlotte E. , McMahon Timothy , Rosenblatt Mark , Shorter Ellen
Published: December 2019

Objectives:

To describe indications for scleral contact lens (ScCL) evaluation, previous treatments, and outcomes of patients prescribed ScCL at a tertiary referral center.

Methods:

This retrospective study reviewed 133 patients evaluated for ScCL between January 1, 2010, and December 31, 2015, at the University of Illinois at Chicago (UIC) Contact Lens Service. Patient demographics, ocular history, indications for evaluation, previous treatments, presence of punctate epithelial erosions, number of lenses ordered, follow-up visits, best-corrected visual acuity before ScCL, and visual acuity with ScCL were evaluated. Patients were categorized based on primary indication for ScCL evaluation as ocular surface disease (OSD) or corneal irregularity (CI). The primary outcome was visual acuity.

Results:

Visual acuity improved from logarithm of the minimal angle of resolution 0.3±0.4 at presentation to 0.1±0.2 with ScCL in all eyes (n=223, P=0.0001), and from 0.3±0.5 to 0.1±0.2 (n=164, P=0.001) in the OSD group and 0.5±0.4 to 0.2±0.2 (n=59, P=0.0001) in the CI group. Seventy percent of patients were evaluated for bilateral ScCL evaluation. Indication for ScCL evaluation was OSD in 71% (n=95) of patients, with 20% having a secondary diagnosis of CI. Corneal irregularity was the primary diagnosis in 29% of patients (n=38), with 50% having a secondary diagnosis of OSD.

Conclusions:

Ocular surface disease was common in this tertiary referral patient population and was a primary or secondary indication for ScCL evaluation in 85.7% (n=114) of patients evaluated for ScCL. Scleral contact lenses improved visual outcomes in patients with both primary diagnoses of CI and OSD.
Use of molecular HIV surveillance data and predictive modeling to prioritize persons for transmission-reduction interventions
Authors: Xia Qiang , Wertheim Joel O. , Braunstein Sarah L. , Misra Kavita , Udeagu Chi-Chi , Torian Lucia V.
Published: December 2019

Background:

To develop a predictive model to prioritize persons with a transmissible HIV viral load for transmission-reduction interventions.

Methods:

New York City (NYC) HIV molecular surveillance data from 2010 to 2013 were used to build a model to predict the probability that the partial pol gene of the virus of a person with a transmissible HIV viral load (>1500 copies/ml) would be genetically similar to that of a person with a new HIV infection (diagnosis at stage 0 or 1 according to the revised Centers for Disease Control and Prevention classification system). Data from 2013 to 2016 were then used to validate the model and compare it with five other selection strategies that can be used to prioritize persons for transmission-reduction interventions.

Results:

A total of 10 609 persons living with HIV (PLWH) were included in the development dataset, and 8257 were included in the validation dataset. Among the six selection strategies, the predictive model had the highest area under the receiver operating characteristic curve (AUC) [0.86, 95% confidence interval (CI) 0.84--0.88], followed by the ‘Young MSM’ (0.79, 95% CI 0.77--0.82), ‘MSM with high viral loads’ (0.74, 95% CI 0.72--0.76), ‘Random sample of MSM’ (0.73, 95% CI 0.71--0.76), ‘Persons with high viral loads’ (0.56, 95% CI 0.54--0.59), and ‘Random sample’ (0.50, 95% CI 0.48--0.53) strategies.

Conclusions:

Jurisdictions should consider applying predictive modeling to prioritize persons with a transmissible viral load for transmission-reduction interventions and to evaluate its feasibility and effectiveness.
Custom-Made Three-Dimensional Models for Craniosynostosis
Authors: Bowen Luke , Benech Rodolfo , Shafi Ahad , Gallo Pasquale , Kandasamy Jothy , Kaliaperumal Chandrasekaran , Campbell Duncan F.
Published: December 2019

The use of computer-aided design and computer-aided manufacturing in oral and maxillofacial surgery is an ever-growing field.

The availability of 3D models, cutting guides, and customised surgical instruments gives surgeons the opportunity to modify and improve their surgical procedures.

Here, we discuss the use of computer-aided design-computer-aided manufacturing to improve the management of a case of nonsyndromic metopic synostosis through the construction of: A cutting guide for the cranium, custom-made orbital protectors, a 3D model of the predicted postoperative meninges to allow off the table bone recontouring, and a template frontal bar to allow more specific recontouring of the frontal bar.
IRSp53 shapes the plasma membrane and controls polarized transport at the nascent lumen during epithelial morphogenesis
Authors: Bisi Sara , Rizvi Syed Abrar , Marchesi Stefano , Carra Davide , Beznoussenko Galina V. , Ferrara Ines , Deflorian Gianluca , Mironov Alexander , Bertalot Giovanni , Pisati Federica , Oldani Amanda , Cattaneo Angela , Pece Salvatore , Viale Giuseppe , Bachi Angela , Tripodo Claudio , Scita Giorgio , Disanza Andrea
Published: December 2019

Establishment of apical–basal cell polarity is necessary for generation of luminal and tubular structures during epithelial morphogenesis. Molecules acting at the membrane/ actin interface are expected to be crucial in governing these processes. Here, we show that the I-BAR-containing IRSp53 protein is restricted to the luminal side of epithelial cells of various glandular organs, and is specifically enriched in renal tubules in human, mice, and zebrafish. Using three-dimensional cultures of renal MDCK and intestinal Caco-2 cysts, we show that IRSp53 is recruited early after the first cell division along the forming apical lumen, and is essential for formation of a single lumen and for positioning of the polarity determinants aPKC and podocalyxin. Molecularly, IRSp53 directly binds to and controls localization of the inactive form of the small GTPase RAB35, a tethering factor for apical determinants. The interaction of IRSp53 with the actin capping protein EPS8 is critical for restricting IRSp53 localization. Correlative light and electron microscopy shows that IRSp53 loss perturbs the shape and continuity of the opposing apical membrane during the initial phase of lumenogenesis, which leads to preservation of multiple cytoplasmic bridges that interrupt the continuity of the nascent lumen. At the organism level, genetic removal of IRSp53 results in abnormal renal tubulogenesis, with defects in tubular polarity and architectural organization in both IRSp53 zebrafish mutant lines and IRSp53-KO murine models. Thus, IRSp53 acts as a platform for spatiotemporal regulation of assembly of the multi-protein complexes that shape the luminal membrane during the early steps of epithelial lumen morphogenesis.
Transferring structural knowledge across cognitive maps in humans and models
Authors: Mark Shirley , Moran Rani , Parr Thomas , Kennerley Steve , Behrens Tim
Published: December 2019

Relations between task elements often follow hidden underlying structural forms such as periodicities or hierarchies, whose inferences fosters performance. However, transferring structural knowledge to novel environments requires flexible representations that are generalizable over particularities of the current environment, such as its stimuli and size. We suggest that humans represent structural forms as abstract basis sets and that in novel tasks, the structural form is inferred and the relevant basis set is transferred. Using a computational model, we show that such representation allows inference of the underlying structural form, important task states, effective behavioural policies and the existence of unobserved state-trajectories. In two experiments, participants learned three abstract graphs during two successive days. We tested how structural knowledge acquired on Day-1 affected Day-2 performance. In line with our model, participants who had a correct structural prior were able to infer the existence of unobserved state-trajectories and appropriate behavioural policies.
Whole genome sequences of 23 species from the Drosophila montium species group (Diptera: Drosophilidae): A resource for testing evolutionary hypotheses
Authors: Bronski Michael J. , Martinez Ciera C. , Weld Holli A. , Eisen Michael B.
Published: December 2019

Large groups of species with well-defined phylogenies are excellent systems for testing evolutionary hypotheses. In this paper, we describe the creation of a comparative genomic resource consisting of 23 genomes from the species-rich Drosophila montium species group, 22 of which are presented here for the first time. The montium group is uniquely positioned for comparative studies. Within the montium clade, evolutionary distances are such that large numbers of sequences can be accurately aligned while also recovering strong signals of divergence; and the distance between the montium group and D. melanogaster is short enough so that orthologous sequence can be readily identified. All genomes were assembled from a single, small-insert library using MaSuRCA, before going through an extensive post-assembly pipeline. Estimated genome sizes within the montium group range from 155 Mb to 223 Mb (mean=196 Mb). The absence of long-distance information during the assembly process resulted in fragmented assemblies, with the scaffold NG50s varying widely based on repeat content and sample heterozygosity (min=18 kb, max=390 kb, mean=74 kb). The total scaffold length for most assemblies is also shorter than the estimated genome size, typically by 5 - 15 %. However, subsequent analysis showed that our assemblies are highly complete. Despite large differences in contiguity, all assemblies contain at least 96 % of known single-copy Dipteran genes (BUSCOs, n=2,799). Similarly, by aligning our assemblies to the D. melanogaster genome and remapping coordinates for a large set of transcriptional enhancers (n=3,457), we showed that each montium assembly contains orthologs for at least 91 % of D. melanogaster enhancers. Importantly, the genic and enhancer contents of our assemblies are comparable to that of far more contiguous Drosophila assemblies. The alignment of our own D. serrata assembly to a previously published PacBio D. serrata assembly also showed that our longest scaffolds (up to 1 Mb) are free of large-scale misassemblies. Our genome assemblies are a valuable resource that can be used to further resolve the montium group phylogeny; study the evolution of protein-coding genes and cis-regulatory sequences; and determine the genetic basis of ecological and behavioral adaptations.
Fibrillar Aβ triggers microglial proteome alterations and dysfunction in Alzheimer mouse models
Authors: Monasor Laura Sebastian , Müller Stephan A. , Colombo Alessio , König Jasmin , Roth Stefan , Liesz Arthur , Berghofer Anna , Saito Takashi , Saido Takaomi C. , Herms Jochen , Willem Michael , Haass Christian , Lichtenthaler Stefan F. , Tahirovic Sabina
Published: December 2019

Microglial dysfunction is a key pathological feature of Alzheimeŕs disease (AD), but little is known about proteome-wide changes in microglia during the course of AD pathogenesis and their functional consequences. Here, we performed an in-depth and time-resolved proteomic characterization of microglia in two mouse models of amyloid β (Aβ) pathology, the overexpression APPPS1 and the knock-in APP-NL-G-F (APP-KI) model. We identified a large panel of Microglial Aβ Response Proteins (MARPs) that reflect a heterogeneity of microglial alterations during early, middle and advanced stages of Aβ deposition. Although both mouse models display severe microglial alterations at late stages of amyloid pathology, MARP signatures occur earlier in the APPPS1 mice. Strikingly, the kinetic differences in proteomic profiles correlated with the presence of fibrillar Aβ, rather than dystrophic neurites, suggesting that fibrillar Aβ aggregates are the main drivers of the AD-associated microglial phenotype and the observed functional decline. The identified microglial proteomic fingerprints of AD provide a valuable resource for functional studies of novel molecular targets and potential biomarkers for monitoring AD progression or therapeutic efficacy.
Sensory neurons contacting the cerebrospinal fluid require the Reissner fiber to detect spinal curvature in vivo
Authors: Orts-Del’Immagine Adeline , Cantaut-Belarif Yasmine , Thouvenin Olivier , Roussel Julian , Baskaran Asha , Langui Dominique , Koëth Fanny , Bivas Paul , Lejeune François-Xavier , Bardet Pierre-Luc , Wyart Claire
Published: December 2019

Recent evidence indicate active roles for the cerebrospinal fluid (CSF) on body axis development and morphogenesis of the spine implying CSF-contacting neurons (CSF-cNs) in the spinal cord. CSF-cNs project a ciliated apical extension into the central canal that is enriched in the channel PKD2L1 and enables the detection of spinal curvature in a directional manner. Dorsolateral CSF-cNs ipsilaterally respond to lateral bending while ventral CSF-cNs respond to longitudinal bending. Historically, the implication of the Reissner fiber (RF), a long extracellular thread in the CSF, to CSF-cN sensory functions has remained a subject of debate. Here, we reveal using electron microscopy in zebrafish larvae that the RF is in close vicinity with cilia and microvilli of ventral and dorsolateral CSF-cNs. We investigate in vivo the role of cilia and the Reissner fiber in the mechanosensory functions of CSF-cNs by combining calcium imaging with patch-clamp recordings. We show that disruption of cilia motility affects CSF-cN sensory responses to passive and active curvature of the spinal cord without affecting the Pkd2l1 channel activity. Since ciliary defects alter the formation of the Reissner fiber, we investigated whether the Reissner fiber contributes to CSF-cN mechanosensitivity in vivo. Using a hypomorphic mutation in the scospondin gene that forbids the aggregation of SCO-spondin into a fiber, we demonstrate in vivo that the Reissner fiber per se is critical for CSF-cN mechanosensory function. Our study uncovers that neurons contacting the cerebrospinal fluid functionally interact with the Reissner fiber to detect spinal curvature in the vertebrate spinal cord.

Abstract Figure

eToC

The role of the Reissner fiber, a long extracellular thread running in the cerebrospinal fluid (CSF), has been since its discovery in 1860 a subject of debate. Orts-Del’Immagine et al. report that the Reissner fiber plays a critical role in the detection of spinal curvature by sensory neurons contacting the CSF.

Highlights

Since its discovery, the role of the Reissner fiber has long been a subject of debate

Mechanoreception in CSF-contacting neurons (CSF-cNs) in vivo requires the Reissner fiber

CSF-cN apical extension is in close vicinity of the Reissner fiber

CSF-cNs and the Reissner fiber form in vivo a sensory organ detecting spinal curvature
Gene regulatory effects of a large chromosomal inversion in highland maize
Authors: Crow Taylor , Ta James , Nojoomi Saghi , Aguilar-Rangel M. Rocío , Rodríguez Jorge Vladimir Torres , Gates Daniel , Rellan-Alvarez Ruben , Sawers Ruairidh , Runcie Daniel
Published: December 2019

Chromosomal inversions play an important role in local adaptation. Inversions can capture multiple locally adaptive functional variants in a linked block by repressing recombination. However, this recombination suppression makes it difficult to identify the genetic mechanisms that underlie an inversion’s role in adaption. In this study, we explore how large-scale transcriptomic data can be used to dissect the functional importance of a 13 Mb inversion locus (Inv4m) found almost exclusively in highland populations of maize (Zea mays ssp. mays). Inv4m introgressed into highland maize from the wild relative Zea mays ssp. mexicana, also present in the highlands of Mexico, and is thought to be important for the adaptation of these populations to cultivation in highland environments. First, using a large publicly available association mapping panel, we confirmed that Inv4m is associated with locally adaptive agronomic phenotypes, but only in highland fields. Second, we created two families segregating for standard and inverted haplotypess of Inv4m in a isogenic B73 background, and measured gene expression variation association with Inv4m across 9 tissues in two experimental conditions. With these data, we quantified both the global transcriptomic effects of the highland Inv4m haplotype, and the local cis-regulatory variation present within the locus. We found diverse physiological effects of Inv4m, and speculate that the genetic basis of its effects on adaptive traits is distributed across many separate functional variants.

Author Summary

Chromosomal inversions are an important type of genomic structural variant. However, mapping causal alleles within their boundaries is difficult because inversions suppress recombination between homologous chromosomes. This means that inversions, regardless of their size, are inherited as a unit. We leveraged the high-dimensional phenotype of gene expression as a tool to study the genetics of a large chromosomal inversion found in highland maize populations in Mexico - Inv4m. We grew plants carrying multiple versions of Inv4m in a common genetic background, and quantified the transcriptional reprogramming induced by alternative alleles at the locus. Inv4m has been shown in previous studies to have a large effect on flowering, but we show that the functional variation within Inv4m affects many developmental and physiological processes.

Author Contributions

T. Crow, R. Rellan-Alvarez, R. Sawers and D. Runcie conceived and designed the experiment. M. Aguilar-Rangel, J. Rodrǵuez, R. Rellan-Alvarez and R. Sawers generated the segregating families. T. Crow, J. Ta, S. Nojoomi, M. Aguilar-Rangel, J. Rodrǵuez D. Gates, D. Runcie performed the experiment. T. Crow, D. Gates, D. Runcie analyzed the data. T. Crow, D. Runcie wrote the original manuscript, and R. Rellan-Alvarez and R. Sawers provided review and editing.
Development of a highly effective African swine fever virus vaccine by deletion of the I177L gene results in sterile immunity against the current epidemic Eurasia strain
Authors: Borca Manuel V. , Medina Elizabeth Ramirez , Silva Ediane , Vuono Elizabeth , Rai Ayushi , Pruitt Sarah , Holinka Lauren G. , Salinas Lauro Velazquez , Zhu James , Gladue Douglas P.
Published: December 2019

African swine fever virus (ASFV) is the etiological agent of a contagious and often lethal disease of domestic pigs that has significant economic consequences for the swine industry. The disease is devastating the swine industry in Central Europe and East Asia, with current outbreaks caused by circulating strains of ASFV derived from the 2007 Georgia isolate (ASFV-G), a genotype II ASFV. In the absence of any available vaccines, African Swine Fever (ASF) outbreak containment relies on control and culling of infected animals. Limited cross protection studies suggest that in order to ensure a vaccine is effective it must be derived from the current outbreak strain or at the very least from an isolate with the same genotype. Here we report the discovery that deletion of a previously uncharacterized gene, I177L, from the highly virulent ASFV-G produces complete virus attenuation in swine. Animals inoculated intramuscularly with the virus lacking the I177L gene, ASFV-G-ΔI177L, in a dose range of 102to 106HAD50remained clinically normal during the 28 day observational period. All ASFV-G-ΔI177L-infected animals had low viremia titers, showed no virus shedding, developed a strong virus-specific antibody response and, importantly, they were protected when challenged with the virulent parental strain ASFV-G. ASFV-G-ΔI177L is one of the few experimental vaccine candidate virus strains reported to be able to induce protection against the ASFV Georgia isolate, and the first vaccine capable of inducing sterile immunity against the current ASFV strain responsible for recent outbreaks.

Importance

Currently there is no commercially available vaccine against African swine fever. Outbreaks of this disease are devastating the swine industry from Central Europe to East Asia, and they are being caused by circulating strains of African swine fever virus derived from the Georgia2007 isolate. Here we report the discovery of a previously uncharacterized virus gene, which when deleted completely attenuates the Georgia isolate. Importantly, animals infected with this genetically modified virus were protected from developing ASF after challenge with the virulent parental virus. Interestingly, ASFV-G-ΔI177L confers protection even at low doses (102HAD50) and remains completely attenuated when inoculated at high doses (106HAD50), demonstrating its potential as a safe vaccine candidate. At medium doses (104HAD50) sterile immunity is achieved. Therefore, ASFV-G-ΔI177L is a novel efficacious experimental ASF vaccine protecting pigs from the epidemiologically relevant ASFV Georgia isolate.
Is the replication crisis a problem for biologists? A geometric morphometric approach
Authors: Vrdoljak Juan , Sanchez Kevin Imanol , Arreola-Ramos Roberto , Diaz Huesa Emilce Guadalupe , Villagra Alejandro , Avila Luciano Javier , Morando Mariana
Published: December 2019

Replicability of findings is the key factor of scientific reliability. However, literature on this topic is scarce and apparently taboo for large scientific areas. Some authors named the failure to reproduce scientific findings ‘replication crisis’. Geometric morphometrics, a vastly used technique, is especially silent on replication crisis concern. Nevertheless, some works pointed out that sharing morphogeometric information is not a trivial fact, but need to be careful and meticulous. Here, we investigated the replicability of geometric morphometrics protocols on complex shapes and measurement error extension in three different types of taxa, as well as the potentiality of these protocols to discriminate among closely related species. We found a wide range of replication error that contributed from 19.5% to 60% of the total variation. Although, measurement error decreased with the complexity of the quantified shape, it often maintained high values. All protocols were able to discriminate between species, but more morphogeometric information does not imply better performance. We present evidence of replication crisis in life sciences and highlight the need to explore in deep different sources of variation that could lead to low replicability findings. Lastly, we enunciate some recommendations in order to improve the replicability and reliability of scientific findings.